Search results for “regulation

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75 articles
Human Psychology Open Access

Honour and Shame as Moral-Emotional Identity Regulation in Diaspora: An Interpretative Phenomenological Analysis of Young British South Asian Women

Apr 2026 DOI 10.14302/issn.2644-1101.jhp-26-6100
Asif-Malik AmanCorresponding author

Honour and shame are central moral constructs within many South Asian communities, yet their psychological internalisation in diasporic contexts remains underexamined. This qualitative study explored how young British South Asian women (aged 18–25; N = 6) understand and negotiate honour in relation to gender, religion, and identity. Semi-structured interviews were analysed using Interpretative Phenomenological Analysis. Six interrelated themes illustrated honour as a gendered and relational system sustained through anticipatory shame, behavioural surveillance, and sexual double standards. Participants described internalised self-monitoring, bicultural identity tension, and strategic resistance through selective compliance and religious reinterpretation. We propose that honour and shame in minority diaspora contexts function as a moral-emotional identity-regulation system characterised by anticipatory shame, relational accountability, and boundary maintenance under racialisation. This conceptualisation advances acculturation and bicultural identity frameworks by arguing that moral emotion, particularly anticipatory shame, functions as a primary mechanism of cultural internalisation, rather than merely an outcome of value endorsement. The findings further illuminate how moral surveillance shapes identity negotiation and psychological wellbeing, with implications for culturally responsive community and clinical practice.

Some Regulation Mechanisms of Candidate Genes for Human Cardiovascular Diseases

Mar 2021 DOI 10.14302/issn.2329-9487.jhc-21-3742
Sisay TesfayeCorresponding author Associate Professor

Cardiovascular disease is actually a major cause of mortality, illness and hospitalization worldwide. Several risk factors have been identified that are strongly associated with the development of cardiovascular disease. Public prevention strategies have relied predominately on managing environmental factors that contribute to cardiovascular disease, such as obesity, smoking and lack of exercise. The understanding of the role of genetics in cardiovascular disease development has become much more important to link genetics with the onset of disease and response to therapy. This seeks to examine how genes can predispose individuals to cardiovascular disease and how this knowledge might be applied to more comprehensive preventive strategies in the future. In addition, the review explores possibilities for genetics in cardiovascular disease treatment, particularly through the use of identified driver genes and gene therapy. To fully understand the biological implications of these associations, there is a need to relate them to the exquisite, multilayered regulation of protein expression and regulatory elements, mutation, microRNAs and epigenetics. Understanding how the information contained in the DNA relates to the operation of these regulatory layers will allow us not only to better predict the development of cardiovascular disease but also to develop more effective therapies.

Quercetin Attenuates Manganese-Induced Neurotoxicity in Mice Hippocampus by Regulation of Oxidative Stress and Tumour Necrosis factor Alpha Expression 

Dec 2020 DOI 10.14302/issn.2577-2279.ijha-20-3634
Oloruntoba Adekeye AdeshinaCorresponding author Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria

The hippocampus is involved in learning and memory processes, an integral component of cognitive function. The aim of this study is to assess the efficacy of quercetin on manganese-induced neurotoxicity in the hippocampus of the adult mice. In this study, 40 adult mice of average weight of 18 –29g were randomly distributed into five groups of eight each. The brain was harvested and the region of the hippocampus was grossed for histological and immunohistochemical analysis. The results revealed a significant increased level of oxidative stress markers of manganese treated mice when compared with the normal control and quercetin treated animals (p<0.05). Immunohistochemical analysis also showed a decrease expression of Tumour necrosis factor alpha (TNFα) with quercetin treated animals when compared with manganese treated animals indicating its neuroprotective function. In addition, quercetin treated animals all had an improved working spatial memory in Y-maze test. The histological results also revealed a degeneration of pyramidal cells with a characteristic pyknotic activities at the granular layer of the hippocampus leading to neuronal integrity damage following chronic exposure to manganese but normal architectural design was however maintained with quercetin. Conclusively, exposure to manganese in excess may have adverse effect on extensive neuronal degeneration that could affect the learning, memory and possibly spatial navigation ability of miceand quercetin attenuates this induced neurotoxicity via inhibition of oxidative stress and reduction of TNF expression.

Ophthalmic Science Open Access

Resveratrol Prevents Cataract Formation by Inhibiting Pro-inflammatory Mediator-induced Dysregulation of Lens Calcium

Apr 2020 DOI 10.14302/issn.2470-0436.jos-20-3303
Manikandan R.Corresponding author Department of Zoology, University of Madras, Guindy Campus, Chennai-600025 

The effect of resveratrol, a free radical scavenger, during cataract development was evaluated in the Wistar rat pup model. This study investigated the possible free radical scavenging potential of resveratrol at 40 mg/ kg body wt dose in selenite-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 µm mol/ kg body wt) in 8 to 10 day old rat pups lead to severe oxidative stress in the tissues evidenced by decreased antioxidants and increased lipid peroxidase, nitric oxide, superoxide anion, hydroxyl radical generation, inducible nitric oxide synthase (iNOS) as well as nuclear factor kappa B (NF-kB) expression levels that probably led to cataract formation. Selenite exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca2+ ATPase but not Na+/ K+ ATPase or Mg2+ ATPase. However, both pre- and co-treatments with resveratrol, but not post-treatment, led to an increase in antioxidant levels with a concomitant reduction in oxidative stress and also rescued the selenite-mediated increase in lens Ca2+ and inhibition of Ca2+ ATPase activity in the eye lens. The results of this study demonstrate antioxidants decrease and increase in free radical generation triggered by selenite causes the inactivation of lens Ca2+ ATPase leading to a rise in intracellular Ca2+ level. Resveratol treatment was able to prevent selenite-induced oxidative stress and in turn the inhibition of lens opacification. Thus, resveratrol has the potential to function as an anti-cataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca2+ in the eye lens.

Research Status and Application Prospect of Epigenetic Regulation of BDNF Gene Expression in Chronic Pain 

Jun 2019 DOI 10.14302/issn.2688-5328.ijp-19-2731
Wei XiangCorresponding author Hospital of Suzhou University, Suzhou, China

The rise of epigenetics provides a new idea for studying the regulation of chronic pain-related genes and synaptic plasticity. External environmental stimuli can regulate BDNF genes through different epigenetic modifications. The epigenetic changes of the BDNF gene can affect the expression of its mRNA and protein and participate in the development of chronic pain. By reviewing the literature, this paper reviews the mechanism of epigenetic regulation of brain-derived neurotrophic factor (BDNF) in chronic pain, which provides some new directions and targets for the treatment of chronic pain.

Regulation of Expression of Reactive Oxygen Intermediates During Plasmodium Infection to Reduce Immunopathology Provides a Possible Antioxidant Adjuvant to Enhance Anti-Malarial Drug Therapy

Aug 2017 DOI 10.14302/issn.2690-4721.ijcm-17-1676
W. Taylor-Robinson AndrewCorresponding author School of Health, Medical & Applied Sciences, Central Queensland University, Brisbane, QLD 4000, Australia

Malaria is a mosquito-transmitted infectious disease caused by intracellular protozoan parasites of the genus Plasmodium. In the absence of prompt and appropriate treatment contraction of primary infection by a human being often represents a medical emergency since it may progress rapidly to life-threatening complications. Exposure to parasites activates the immune system resulting in, among other effects, the release of reactive oxygen intermediates (ROI). This has the potential to induce oxidative damage, thereby causing cellular destruction, and hence to have a severe effect on vital organs of the body. Overexpression of ROI leads to immunosuppression and is a causal factor in the development of malaria-related disease symptoms. However, the body possesses various defence mechanisms, notably including the production of antioxidants, which are capable of reducing the cellular effects of ROI. Antioxidants are either sourced exogenously from the diet or synthesized through different intracellular mechanisms. Antioxidants that include glutathione peroxidase, catalase, EDTA and vitamin C suppress the initial production of ROI. Others such as uric acid, superoxide dismutase and vitamin E may also inhibit potentially damaging products of ROI metabolism. Current anti-malarial drugs often have damaging side-effects, as exemplified by memory impairment following treatment for cerebral malaria. Recent studies have explored the potential use of antioxidants alone or in combination with anti-malarials as a therapeutic means to negate Plasmodium-induced oxidative stress and its associated metabolic complications. It is indicated that when utilized in an adjuvant capacity antioxidants of natural and synthetic origin may improve anti-malarial therapy by causing less damage to the host during malaria infection.

Low Energy Intake Impairs Glucose Regulation and Stamina in Japanese Young Women

Dec 2016 DOI 10.14302/issn.2379-7835.ijn-16-1360
Kaneko MichiyoCorresponding author Department of Home Economics, Kobe Women’s University 2-1 Aoyama, Higashisuma, Suma-ku, Kobe, Hyogo Prefecture 654-8585, Japan

Energy intake has been decreasing these ten years in Japan, and low energy intake is remarkable especially among young women. We attempted to show the dietary habits and physiological function including glucose tolerance and stamina for endurance-running in contemporary young Japanese women who take insufficient energy. 85 healthy women aged 20.5±1.1 years were enrolled in the present study. Subjects were categorized in two groups; Group I (n=70) with higher energy intake, and Group II (n=15) with lower energy intake than the basal metabolic rate (BMR). Actual energy intake in Group I was 1598.8±282.1 kcal/day, and it was 1019.9±127.1 kcal/day in Group II (p<0.01). Standard 75-g oral glucose-tolerance test was performed, and the capillary glucose value was measured at the fingertip. In Group I, glucose values at fasting, 30, 60 and 120 min were 75.0±9.1, 132.1±25.2, 120.5±27.4, 105.3±19.5 mg/dl, and those in Group II were 78.9±7.7, 155.8±26.6, 142.2±26.6, 112.3±16.0 mg/dl, respectively. The values of Group II at 30 and 60 min showed significantly high (p< 0.01). Stamina and the intake of protein in Group II were significantly lower than those in Group I (p<0.05), and muscle mass and grip strength were less in Group II than in Group I, though there was no significant difference. We indicated with these results that low skeletal muscle was considered to be responsible for the impairment of glucose regulation in Group II. This study showed that young women with low energy intake should take sufficient energy and build skeletal muscle to prevent the impairment of glucose regulation.

GR-RNF43 Regulation in Colorectal Cancer

Mar 2016 DOI 10.14302/issn.2326-0793.jpgr-16-941
Chan ChristinaCorresponding author Cell and Molecular Biology Program, Michigan State University, 567 Wilson Road, Rm 2240A, East Lansing, Michigan 48824, USA

In contrast to approaches that compare pair-wise control (i.e. normal) to treated (i.e. disease) samples, we compared colorectal cancer samples not only to a set of control samples but also against a wide range of samples and conditions to collect the differentially expressed genes and identify target genes. We identified specific genes for colorectal cancer and showed that they are significantly associated with colorectal cancer in the literature. Analysis of independent datasets revealed a significantly distinct expression pattern for glucocorticoid receptor (GR) and ring finger protein 43 (RNF43) in colorectal cancer samples. GR was downregulated whereas RNF43 was upregulated in colorectal cancer with respect to various conditions in different datasets. In HCT116 colorectal cancer cell line, knock-down of GR levels with siRNA resulted in increased RNF43 levels, suggesting that GR might be a negative regulator of RNF43. Our study suggests that the downregulation of GR might be involved in the upregulation of RNF43 in colorectal cancer.

New Regulations for Foods Offered to School Children in Chile: Barriers to Implementation

Jun 2015 DOI 10.14302/issn.2379-7835.ijn-14-615
Prochownik KatherineCorresponding author The Johns Hopkins University Baltimore, Maryland

Objective: To prevent childhood obesity, the Chilean government has recently implemented food regulation laws that apply to schools. This paper reviews the literature regarding the challenges in successfully integrating policies to regulate foods offered in schools. In addition, to understand some of the potential implementation barriers, a survey was conducted to evaluate how well food regulation laws were understood and implemented in Chilean schools. Methodology: A narrative literature review was conducted regarding food regulation policies in Chilean schools and potential barriers to implementation. This informed a subsequent descriptive, qualitative survey which was conducted in the Valparaíso region of Chile to examine knowledge, practices, and potential barriers to implementation of the new regulations. Twelve randomly-selected school food kiosk owners completed a survey and structured interview. Visual observations were also performed at each food kiosk. Content analysis identified trends in food items sold and determined the depth of understanding kiosk owners have of a specific new food law, "La Composición Nutricional de los Alimentos y Su Publicidad (20.606)." Key Results: 7 articles in Spanish and 10 in English were reviewed. The literature review revealed that unhealthful food options are readily available to Chilean students in school kiosks. The results of the survey and interview indicated that the school kiosk owners surveyed have a general understanding of the food law. 10 out of 12, however, were unsure of the law's exact contents. Unhealthful food options, inconsistent with regulation 20.606 were observed in all 12 visited kiosks. Conclusion: Evidence from a literature review and the survey findings confirm that unhealthful foods persist in Chilean schools, despite government food regulations. Although the majority of the school kiosk owners acknowledge law 20.606, most lack an understanding of its exact contents and their role in promoting healthier foods in schools. Further education of vendors and school administrators is needed to enhance compliance with the new Chilean food regulations.

The Role of FIP-2 (Optineurin) in Regulation of the Chemokines and Kinases

Jan 2014 DOI 10.14302/issn.2326-0793.jpgr-13-355
Tarassishin LeonidCorresponding author Department of Microbiology and Immunology

FIP-2 is a multifunctional protein which is involved in various cellular processes. Using different approaches we investigated its regulatory activity. The microarray analysis has shown that FIP-2 substantially altered the expression of 75 genes (35+/40-) from different functional groups with maximal presentation in “Signal transduction” and “Transcription regulation”. Real time RT-PCR indicated significant elevation in the transcription of chemokines, particularly IL-8 (CXCL8). Production of IL-8 in HEK293 cells dramatically increased with FIP-2 overexpression. We also demonstrated that FIP-2 induced activation of IL-8 promoter activity through NF-kB binding site. Additionally, we showed that FIP-2 could interact with PAK3 and increase its kinase activity. Overall, we demonstrated the role of FIP-2 in the regulation of chemokines (IL-8, MPIF-1, MCP-1) and kinases (PAK3, ALK).

Intravascular Laser Irradiation of Blood (ILIB) on Sleep Quality Improvement: A Randomized Placebo-Controlled Clinical Trial

May 2026 DOI 10.14302/issn.2574-4518.jsdr-25-5773
Peres de Sousa LucasCorresponding author

Introduction Sleep quality is a fundamental determinant of human health and well-being. Modified Intravascular Laser Irradiation of Blood (ILIB), a non-invasive therapeutic modality, has emerged as a potential intervention for sleep-related disturbances. Proposed mechanisms include reduced blood viscosity and platelet aggregation, activation of superoxide dismutase, increased oxygen bioavailability, enhanced microcirculation, elevated serotonin levels, and decreased cortisol concentrations—physiological processes intricately involved in sleep regulation, mood modulation, and the stress response. Objective To evaluate the effects of Modified Intravascular Laser Irradiation of Blood (ILIB) on sleep quality in individuals with self-reported sleep disturbances. Methods A randomized, placebo-controlled clinical trial was conducted with participants who reported poor sleep quality. Subjects were randomly assigned to one of two groups: the intervention group received ILIB using a 660 nm red laser, while the control group received a placebo treatment (light emission with sub-therapeutic power, <1 mW). Both groups underwent the same treatment schedule. Sleep quality was assessed at baseline and after six treatment sessions using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Results Participants in the ILIB group showed statistically significant improvements in the primary outcome of global sleep quality. PSQI scores decreased from 10.24 at baseline to 6.47 post-treatment. ESS scores showed a non-significant change from 10.44 to 10.12. These results suggest enhanced overall sleep quality and reduced sleep latency, although the observed reduction in daytime sleepiness did not reach statistical significance. Conclusion Modified Intravascular Laser Irradiation of Blood appears to be a promising non-invasive approach for improving sleep quality. The clinical outcomes observed are comparable to those reported in both pharmacological and behavioral sleep interventions, particularly in terms of PSQI improvements. These preliminary findings support the need for further research to clarifyunderlying mechanisms, optimize treatment parameters (e.g., dosimetry and duration), and expand outcome assessments to include biomarkers and polysomnographic data.

Diabetic Mouse Delayed Wound Model Following Treatment with the NerveStim™ Neuropathy System

Apr 2026 DOI 10.14302/issn.2640-6403.jtrr-26-6077
Kalmeta MargaretCorresponding author

Delayed wound healing in diabetes is characterized by impaired angiogenesis, persistent inflammation, extracellular matrix dysregulation, and peripheral neuropathy. A preclinical study was conducted using a diabetic mouse delayed wound model to evaluate the surrounding tissue of a wound, (its periwound) and its tissue responses following treatment with the NerveStim™ Neuropathy System, a combination topical gel and neuromuscular electrical stimulation platform. Periwound tissue was harvested at Day 14 and analyzed using NanoString gene expression profiling. Treated animals demonstrated visibly increased periwound tissue thickness compared to untreated controls. Differential expression analysis identified 76 significantly upregulated and 17 downregulated genes. Upregulated pathways included angiogenesis (Vegfa, Fgf2, Pdgfb, Nos3), neurotrophic signaling (Ngf, Bdnf, Scn9a, Trpv1), macrophage polarization (Arg1, Mrc1, Il10), and extracellular matrix remodeling (Col1a1, Col3a1, Mmp9, Timp1). Downregulation of select pro-inflammatory mediators (Nos2, Mif) was observed. These coordinated transcriptional changes are consistent with activation of reparative immune, neurovascular, and matrix remodeling pathways in diabetic periwound tissue.

A Review and Update on the Biochemical Basis of Conscious Breathing (Pranayama)

Mar 2026
Aulesa CarlosCorresponding author

Breathing has long been recognised as a vital process in Eastern traditions such as YOGA and Ayurvedic medicine, where Pranayama is regarded as a transformative practice that harmonises body and mind. While the East developed sophisticated systems of breath regulation for health and self-awareness, the West largely overlooked their significance until the late 19th and early 20th centuries. A group of pioneering physicians, sometimes referred to as "the pulmonauts", including Christian Bohr, Konstantin Buteyko, and Peter M Litchfield, explored the physiological foundations of respiration. They emphasised the benefits of slow, nasal breathing and its relationship to both physical and emotional well- being. In the 21st century, contemporary researchers and practitioners such as James Nestor, J. Patrick McKeown and Anders Olsson have expanded this understanding through the fields of biochemistry, physiology, and biomechanics. Their work has clarified the mechanisms underlying conscious breathing and refined ancient pranayama techniques. Integrating insights from both Eastern and Western traditions reveals that breathing is a central factor in maintaining homeostasis and emotional balance.

Lineage-Specific Disruption of Hematopoiesis by Oxaliplatin: Mechanisms of Erythropoietin Resistance and Immune Suppression

Feb 2026 DOI 10.14302/issn.2372-6601.jhor-25-5944
Y. Berezin MikhailCorresponding author

Background Oxaliplatin, a widely used chemotherapeutic agent, is associated with hematologic toxicities such as anemia, leukopenia, and thrombocytopenia. Despite their clinical relevance, the molecular mechanisms underlying lineage-specific bone marrow suppression remain poorly understood. Methods We administered oxaliplatin to mice over eight weeks and performed RNA-sequencing (RNA integrity >8) on bone marrow alongside peripheral blood analysis and cytokine profiling. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. For that, we applied a thematic Gene Ontology (thematicGO) enrichment method that groups GO terms into biologically meaningful categories, such as hematopoietic lineage disruption, cell cycle arrest, and cytokine signaling. Results Oxaliplatin induced broad transcriptional suppression of erythropoiesis and lymphopoiesis, with 3,691 DEGs identified (FDR<0.05, |FC|>1.5). Upregulation of Cdkn1a and downregulation of E2f2 suggest G1/S cell cycle arrest, correlating with repression of key erythroid maturation genes (e.g., Spta1, Slc4a1, Alas2) and hemoglobin subunits (Hba-a1/2, Hbb-bs/t). Despite a ~3000-fold increase in renal Epo expression, bone marrow Epor was reduced, indicating erythropoietin resistance. B and T cell markers were also significantly downregulated, signifying a collapse in adaptive immunity. Notably, neutrophil populations were largely spared. Cytokine analysis in plasma revealed a pro-inflammatory shift with elevated TNF-α and reduced TGF-β, potentially exacerbating hematopoietic dysfunction. Conclusions Oxaliplatin induces a lineage-dependent suppression of hematopoiesis, driven by coordinated cell cycle arrest, metabolic stress, and disrupted cytokine signaling. RNA-seq analysis enabled integration of transcriptomic findings into coherent biological themes. These findings provide mechanistic insights into oxaliplatin’s hematologic toxicity linking bone marrow failure (potentially reversible) via interconnected inflammatory and metabolic pathways and may inform therapeutic strategies to minimize or restore myelosuppression in cancer patients.

Women's Mental Health Open Access

Exploring the Mechanism of Complex Lemon-Angelica Sinensis-Boswellia Essential Oil on Anxiety Disorders with Melasma Through Network Pharmacology and Experimental Validation

Dec 2025
Liu LipingCorresponding author

The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.

Embryology Open Access

Molecular Control of Human Embryonic Development: A Comprehensive Study

Nov 2025 DOI 10.14302/issn.3070-5657.je-24-5327
Khanday ShifanCorresponding author

Human embryonic development is a highly coordinated and complex process that transforms a single fertilized cell into a fully formed human organism. This process is governed by intricate molecular mechanisms involving genetic regulation, signal transduction pathways, and intercellular communication. This study explores key molecular pathways controlling human embryonic development, focusing on the roles of morphogens, transcription factors, signaling molecules, and epigenetic modifications. By reviewing the most recent literature and experimental studies, we aim to highlight the molecular orchestration that directs cell fate decisions, tissue patterning, and organogenesis in humans.

Review on Frequency Neurofeedback on Autism Spectrum Disorder: Overview, Efficacy and Research Direction

Nov 2025
Ryan AlexanderCorresponding author

Frequency neurofeedback (FNF) is a biofeedback method that targets frequencies between 1 and 50 Hz. The efficacy of FNF with autism has been labeled ‘probably efficacious’ in literature reviews in the last decade, despite new research pointing towards a higher standard. The aim of this review was to analyze key features of these studies, with a goal of determining the efficacy standard of FNF on autism and establishing a research direction. Electronic databases and literature reviews were used to collect a total of ten randomized and/or matched controlled trials. FNF reaches a Level 4 efficacy standard, with an impact on a broad range of factors including core autistic traits, social communication, emotional regulation, cognitive flexibility, executive function, behaviors of concern, attention, metabolic or thermal activity, and EEG e.g. decreased absolute power, mu rhythm, coherence and hyperconnectivity. Current evidence generalizes to male children, up to 18 years, with a low-average or higher intellectual functioning, with autism as the only diagnosis. A meta-analysis suggests a large superior effect when compared to wait list controls. Current research does not meet the higher efficacy standards outlined by Arns et al. (2020). Small samples plague most studies, and the maintenance of improvements post-training are yet to be assessed adequately. Eight recommendations are made.

Applying Cultural Humility During an International Collaboration Seeking to Optimize A Peaceful Coexistence Intervention in The Kingdom of Bahrain: Lessons Learned

Oct 2025 DOI 10.14302/issn.2641-4538.jphi-25-5661
Rashwan NaglaaCorresponding author

The World Health Organization emphasizes the importance of international collaboration to save lives and improve health at national and global levels. However, significant challenges face those engaged in international collaborations such as language barriers, cultural differences, different rules and regulations, and limited resources. This paper discusses the use of cultural humility theory to support an international collaboration between stakeholders from different countries with diverse cultural backgrounds working together to optimize a novel middle and high school curriculum intended to promote peaceful coexistence in the Kingdom of Bahrain. We use the attributes of cultural humility as a framework to reflect on lessons learned while navigating cultural differences, conclude by recommending the use of this framework during international collaborations, and provide practical examples about how to operationalize the attributes of cultural humility to inform international collaborations attempting to promote global public health.

Intersecting Epidemics: Intimate Partner Violence, Stress, and Diabetes Among South Asian Women in the United States

Feb 2025 DOI 10.14302/issn.2641-4538.jphi-25-5420
Nagaraj NitashaCorresponding author

South Asian women in the United States face disproportionate health challenges, including higher rates of intimate partner violence as well as higher rates of Type 2 diabetes and gestational diabetes compared to other racial and ethnic groups. This cross-sectional study examines the association between intimate partner violence (psychological, physical, and sexual) and the diagnosis of gestational diabetes and type 2 diabetes. A web-based survey recruited 2,634 South Asian women in the U.S., collecting data on socio-demographics, intimate partner violence experiences, stress levels, and diabetes diagnosis. Logistic regression models adjusted for significant sociodemographic factors revealed that women with a history of intimate partner violence were 5.82 significantly more likely to report a type 2 diabetes diagnosis and 3.91 more likely to report a gestational diabetes diagnosis. Furthermore, stress as measured by the perceived stress scale, was also higher among women with intimate partner violence, potentially moderating the relationship between intimate partner violence and adverse health outcomes through cortisol dysregulation. Despite high levels of educational attainment and employment, the prevalence of intimate partner violence was alarmingly high (66.7%), highlighting its pervasive impact on socioeconomic strata. These findings underscore the urgent need for culturally tailored interventions addressing intimate partner violence and its health consequences within South Asian communities. Further research is warranted to elucidate causal pathways and inform integrated public health strategies to mitigate disparities in chronic disease and intimate partner violence-related health outcomes.

Acute Hypomagnesemia-Induced Cerebellar Down-Beat Nystagmus Syndrome Due to Benign Paroxysmal Positional Vertigo: A Case Report

Jul 2024 DOI 10.14302/issn.2470-5020.jnrt-24-5148
Marcelli VincenzoCorresponding author

Magnesium is essential for the proper functioning of all human cells and is involved in the regulation of neurotransmitter function and neurological function. Acute and chronic hypomagnesemia cause severe neurological symptoms such as neuromuscular irritability, myoclonus, stridor, dysphagia, mainly postural tremor and movement disorders along with vertical downbeat nystagmus. Here we report a case of cerebellar downbeat nystagmus syndrome induced by acute hypomagnesemia (HICS) due to very frequent vomiting in a 75-year-old woman with benign paroxysmal positional vertigo (BPPV). The clinical condition improved with daily intravenous and then oral magnesium supplementation. To our knowledge, this is the first described case of HICS induced by acute hypomagnesemia due to vomiting triggered by a benign peripheral pathology such as BPPV which was then successfully treated once the central syndrome was resolved.

Parents and Siblings as Role Models in Dealing With Digital Screen Media. Findings from A Media Fasting Intervention

Jun 2024 DOI 10.14302/issn.2381-862X.jwrh-24-5099
Schwarz SilkeCorresponding author

Parents' and siblings’ role model motivation and function could play an important role in positively influencing both their own media behavior and that of family members. To investigate whether parents and siblings consciously take on this role model function, their intentions were being evaluated with a standardized questionnaire before a 6-week media fasting intervention. 135 pairs of parents and 178 pairs of children were included. A major component of the parents' media fasting intention to media fast was to be a role model for their children. This was particularly related to the idea that media fasting has something cleansing about it, as well as the hope of becoming more attentive and calm as a family. These parents seem to want to strengthen family cohesion and climate and protect their children from excessive media consumption. Children who want to be role models for their parents also intend to have a positive influence within the family and want to be role models for their siblings. Regression analyses revealed several predictors of the parents' intent for role model function: the hope of becoming more attentive and calm as a family, the view that media fasting has something cleansing about it, and the perception that it is good for one's children to use less digital screen media, and, inversely, age (R2 =.35). The best predictors of the corresponding intention among the children were the desire to be a role model for their siblings, for the family to do more together again and, as for the parents, a younger age (R2=.57). The intentions of both groups are different, but the possibility of using less media is perceived as sensible. The role model function appears to be a relevant motivating and influencing factor regarding the conscious use of digital screen media and regulation of screen time. This should be taken into account when developing interventions.

Measuring Quality Change in the Market for Anti-Ulcer Drugs

Apr 2024 DOI 10.14302/issn.2574-4526.jddd-24-4996
Haider RehanCorresponding author

The General Accounting Office released a study in August 1992 of twenty-nine sampled prescription drugs that reported an average increase in the price of approximately 138 percent between 1985 and 1991 (GAO 1992, 4, Table 1) Those and other published price indexes are increasingly being used in the public policy arena to focus the debate on the potential regulation of pharmaceutical prices and the coverage of health insurance. In an industry where products are multidimensional and the rate of technological progress is brisk, misinterpretation of unadjusted indices of drug prices can easily arise. This can lead to erroneous conclusions regarding appropriate policies for the pharmaceutical industry. Researchers have addressed numerous general theoretical issues concerning the construction and interpretation of price indices 1. Two issues of particular interest for pharmaceutical markets are the new goods problem, which deals with the introduction of generic drugs into a drug price index, and the quality problem, which recognizes that newer versions of drugs with the same basic Chemical action may be superior in certain dimensions to drugs already on the market. Specific to pharmaceutical markets, 2 have also argued that the sampling procedure used by the Bureau of Labor Statistics to calculate pharmaceutical price indices is flawed. Each of those problems deserves careful analysis. This study focuses on the issue of product quality measurement and quality change.

Evolutionary Science Open Access

Rbm45 Phylogenetics, Protein Domain Conservation, and Gene Architecture in Clade Metazoa

Mar 2024 DOI 10.14302/issn.2689-4602.jes-24-4982
O. Henderson JeffreyCorresponding author

Mammalian Rbm45 is predominately expressed in neuronal tissue and is integral in brain development and neuronal differentiation under physiological conditions. Dysregulation of Rbm45 has been strongly associated with neurodegenerative disorders in humans and can drive hepatocellular carcinoma through reprogramming lipid metabolism. Intriguingly, Rbm45 is an ancient protein, evolutionarily conserved throughout metazoans, including in sponges which lack a nervous system. Curiously, the evolution of Rbm45 gene structure and protein domain conservation across kingdom Animalia is largely unknown. We performed phylogenetic analysis of Rbm45 nucleotide and amino acid sequences from 36 species representing 9 phyla: Porifera, Cnidaria, Priapulida, Mollusca, Brachiopoda, Arthropoda, Echinodermata, Hemichordata, and Chordata. While the tree from Rbm45 nucleotide sequence data resulted in clades Protostomia and Deuterostomia showing paraphyly, the phylogeny derived from Rbm45 amino acid sequence largely recapitulated known monophyletic relationships among metazoans. Human RBM45 protein structure includes three RNA-binding domains (RBD), a homo-oligomerization association (HOA) domain, a nuclear localization sequence (NLS), and a nuclear export sequence (NES). Multiple sequence alignment across the same 36 taxa used for phylogenetic analysis revealed conservation of all three RBDs, the HOA, and NLS; in contrast the NES was only detected in clade Craniata and not in clades Ambulacraria and Protostomia. Rbm45 gene structure analysis revealed increasing gene complexity concomitant with increasing evolutionary complexity. Rbm45 from non-bilaterian taxa had from 2 to 4 large exons, while bilaterian taxa had between 6 to17 small exons. These findings demonstrate that Rbm45 is an ancient, highly conserved gene among metazoans suggesting a function in a breadth of neural/sensory systems.

Cervical Cancer Open Access

Cervical Cancer with The Active And Stable PI3K/MTOR/AKT Pathway In Azerbaijan Patients

Mar 2024 DOI 10.14302/issn.2997-2108.jcc-23-4838
S. Mardanova KonulCorresponding author

Among the reproductive cancers cervical cancer has special place, because the second most frequent cause of cancer-related death among women worldwide. The studies suggested that the PI3K/mTOR/AKT signaling pathway is associated with certain reproductive tumors. A lot of research is ongoing for understanding this pathway evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that targeted PI3K/AKT. In this a single-arm study included 34 Azerbaijan population woman with HPV-negative cervical tumors. The core genes of PAM signaling pathway were analyzed using RT-PCR method. Our preliminary results suggested that tumorgenesis of HPV-negative cervical cancer patients approximately 25% associated with dysregulation of PAM signaling pathway reason which are core genes alteration. The overall survival times in the PAM-active and PAM-stable patients were not significantly varies. However, the main factor for overall survival times were treatment strategy: both PAM-active and PAM-stable patients who received radiation therapy alone had a shorter overall survival than patients who received radiation plus chemotherapy. The patients with alteration of ATK1 and mTOR genes in PAM signaling pathway had poor prognosis then patients with PIK3CA and PTEN mutation

Scrutinizing Local Probiotic Supplements and Drinks Available in the Bangladesh Market

Jan 2024 DOI 10.14302/issn.2379-7835.ijn-23-4802
Fatema AkterCorresponding author

The host's health may benefit from the probiotic microorganisms found in many products available on the market. In addition to food, these products include dietary supplements, food for special medical purposes, medicines, cosmetics, and medical devices. These products have anywhere from one to a dozen strains of bacteria from the same or different species, and sometimes they also have strains of fungi. Since the health benefits of probiotics depend on the strain, the number of cells in a dose, and the absence of pathogenic microorganisms, it is crucial to regulate the quality of probiotics. Depending on how a product is classified, how it looks, and how many microorganisms it has, it is very important to count and identify the microorganisms correctly. We investigated nine probiotic products in this study: five commercially available probiotic supplements and four probiotic drinks. The majority of commercial products did not contain all of the labeled lactic acid bacteria, nor did they contain any possibly harmful microorganisms. To ensure that consumers in Bangladesh obtain good products, probiotic-containing product rules and regulations should be developed. Furthermore, it should be the duty of probiotics-containing product manufacturers to provide consumers with information that is accurate, reliable, and compliant with legal and scientific requirements

Deficiency of Adenosine Deaminase Type 2 (ADA2) DADA2 Masquerade as Lupus

Aug 2023
Almabadi BayanCorresponding author

DADA2 (deficiency of adenosine deaminase type 2) is an autoinflammatory autosomal recessive disease resulting from biallelic loss of function mutations in ADA2 gene. Clinical presentation and age of onset vary widely even among related patients, and variability of symptoms and severity manifestations include bone marrow failure, autoinflammation, immunodeficiency and vasculitis. Here, we report a case of young male with adult onset DADA2, who presented with fever, lower limbs skin rash, joint pain, and anemia resembling systemic lupus erythematous (SLE). DADA2 has an extremely variable clinical phenotype. It was described into three categories: inflammatory/vascular, immune dysregulation, and hematologic. However, the data is scant in describing autoimmunity phenotype in DADA2 and further studies are required to investigate the clinical correlation and presence of autoantibodies. We recommend genetic testing in cases with lupus-like disease especially if there is consanguinity between parents and family history of vasculitis.

The Adverse Effects of Underwater Sound upon Fishes and Invertebrates

Feb 2023 DOI 10.14302/issn.2643-0282.imsj-22-4314
D Hawkins AnthonyCorresponding author

Underwater sound is very important to most fishes and invertebrates. Underwater sounds from both natural and human sources can have adverse effects upon aquatic animals, and especially fishes, and invertebrates. It is important to examine the effects of sound upon them, and especially the effects of sounds derived from human sources (anthropogenic sounds). It may be possible to introduce protective regulations to reduce their effects. Fishes and invertebrates can detect underwater sounds, and they use sound to obtain key information about the environment around them. They can also make sounds themselves, especially during their spawning. Sounds travel rapidly over great distances in water and can provide detailed information to these animals on the presence of prey, predators, and related species, while the overall acoustic scene provides them with key information about their environment. Anthropogenic sounds can be very harmful, and it is therefore important to deal with them. A succession of reports and scientific papers have emphasised the risks to these animals from exposure to man-made sounds or noise and will be mentioned in this paper, which also deals with the Criteria and Metrics for assessing the effects of underwater sound on fishes and invertebrates.

Marginal SARS-CoV-2 Spike Protein Increases Interferon and Balances Cytokine Gene Expression

Oct 2022 DOI 10.14302/issn.2692-1537.ijcv-22-4296
Das SatadalCorresponding author Genetic Research Unit, Heritage Institute of Technology, Kolkata-700107

Some evidence confirms the paradoxical beneficial role of harmful antigens when used in highly diluted forms. In this experiment, we observed cytokine gene expression changes in Gallus gallus embryo after challenge with Delta SARS-CoV-2 RBD spike protein antigen, from a concentration of 10 µg/mL to a series of highly diluted forms in ethanol, along with controls. We have also studied pre-and post- experimental combined sets of higher (10 µg/mL) and significantly lower antigen concentrations (attogram level). Attogram and zeptogram level concentrations of the antigen showed consistently remarkable up-regulation of INF-α among different cytokine gene expressions. INF-β gene expressions at the zeptogram level of the antigen showed consistent changes, although not so outstanding. The pre-experimental set having attogram level antigen administered first, followed by a 10µg/mL antigen challenge, showed excellent cytokine balance. Other experimental groups, including the control sets, showed variable results at different concentrations.

RETRACTED: The Impact of Underwater Sound on Aquatic Animals – And Especially Fishes

Jul 2022 DOI 10.14302/issn.2643-0282.imsj-22-4216
Donald Hawkins AnthonyCorresponding author Kincraig, Blairs, Aberdeen, Scotland, United Kingdom.

This article has been retracted on 30 May 2023. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2643-0282.imsj-25-5851) Underwater sounds from human sources can have detrimental effects upon aquatic animals, including fishes, and currently such sounds are very common. It is important to examine such anthropogenic sounds and their effects upon aquatic animals, so that it is possible to introduce protective regulations. Fishes and other aquatic animals can detect underwater sounds and use them to obtain key information about the environment around them. Sounds travel rapidly over great distances in water and can provide detailed information on the presence of prey, predators, and related fishes, while the overall acoustic scene provides the fishes with key information about their environment. Although some of the background noise is generated by natural sources, including the precipitation of rain and snow, and wind and waves, many underwater sounds now come from anthropogenic sources, often termed “noise”. Some of these human-made sounds can kill or injure fishes and other aquatic animals, also impairing their hearing, and altering their behavior. There is a need for more work on the impact of human-made underwater noise upon the fitness of aquatic animals. This paper considers the gaps in information that must be resolved. The effects that need to be considered include death and injuries, physiological effects, and changes in behavior.

Biological Effects of High Radiofrequency Radiation on Wistar Rats: A Literature Review

Jun 2022 DOI 10.14302/issn.2641-4538.jphi-22-4197
A. Attah TimothyCorresponding author National Space Research and Development Agency (NASRDA), Obasanjo Space Centre, Umaru Musa Yar'adua expressway, P.M.B. 437, Lugbe, Abuja, Nigeria

Aim and Objective Despite the growing concerns about the relationship between exposure to radiofrequency radiation (RFR) and detrimental health effects due to the changes in biological processes of experimental animals, there is still ongoing debate on the significance of these findings in causing significant public health problems with the growing advancement in internet technology. The aim of this study is to review existing literature on the effects of high RFR on wistar rats. Method A search was conducted on Google scholar and PubMed to identify relevant peer-reviewed articles to be included into the review. Studies eligible for inclusion included free full text articles on wistar rats exposed to ≥ 2.45GHz RFR conducted in the past 5 years. Studies included in this review were written or transcribed in English language. From 286 titles, 36 eligible studies were included in the review and assessed for quality using the Strengthening the Report of Observational Studies in Epidemiology – Veterinary Extension (STROBE-Vet) quality assessment tool. Results Studies included in this review generally had good quality (>60%) based on the STROBE-Vet assessment. This review identified numerous biological changes in wistar rats exposed to high RFR including variations in biochemical, cholinergic, genetic, histopathologic, psychological, optical, and dermatological parameters. In this review, studies identified variations in protein and liver enzymes while high RFR was found to induce oxidative stress and cellular damage of exposed wistar rats compared to the unexposed groups. This was seen in the changes in protein, lipids, enzymatic and non-enzymatic antioxidants. Studies also identified changes in expression of genes and neurotransmitters with imbalance in hormones. In addition, this review identified structural changes of cells, tissues and organs indicative of apoptosis, damage and death. Exposed rats were identified to have behavioral changes indicative of anxiety and memory decline while studies identified optical and dermatologic changes in exposed rats compared to the unexposed. Conclusion With numerous biological changes identified in wistar rats exposed to high RFR, there is an increasing risk of detrimental health events giving the advancement in internet technology and limited regulations to control exposures to RFR. Therefore, studies should be conducted to identify strategies to mitigate human exposure to RFR while policies are developed and enforced to protect human health.

Nephrology Advances Open Access

Thyroid Function Abnormalities in Patients with Chronic Kidney Disease

Feb 2022 DOI 10.14302/issn.2574-4488.jna-21-4039
K Al Miraj ACorresponding author Research Assistant, Department of Vascular Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU)Dhaka, Bangladesh.

The function of the thyroid gland is one of the most important in the human body as it regulates the majority of the body's physiological actions. The thyroid produces hormones (T3 and T4) that have many actions including metabolism, development, protein synthesis, and the regulation of many other important hormones. There is a lot of interaction between the kidney and thyroid gland during the disease States thyroid hormones have a major role in regulating the glomerular filtration rate through its hormonal actions in normal physiology. But these things are altered in the disease States such as chronic kidney disease. It is a well-known fact that hypothyroidism causes decreased Glomerular filtration rate whereas hyperthyroidism causes increased Glomerular filtration rate leading to renin-angiotensin-aldosterone system activation. In our study we aim to see the prevalence of low T3 syndrome in different stages of CKD which is a state of physiological benefit in preserving the proteins lost through the Kidneys in CKD patients and since CKD is progressed in hyperthyroidism state it is a protective mechanism in restoring the CKD status. Other subclinical hypothyroidism hyperthyroidism. Autoimmune hypothyroidism. Glomerulonephritis are all part of a dynamic endocrine and nephrology sequence. Thorough knowledge of these is required for optimum treatment of thyroid in CKD patients.

Community Health Needs Assessment in Urban Communities in Kigali City In Rwanda: A Cluster-Randomized Trial

May 2021 DOI 10.14302/issn.2641-4538.jphi-21-3632
Placide MUTABAZICorresponding author Save the Children International, Nkumba University, School of postgraduate and research, P.O. Box 237 Entebbe-Uganda

Introduction Reporting of suspected or confirmed communicable diseases is paramount. Although physicians have primary responsibility for reporting, school nurses, laboratory directors, infection control practitioners, daycare center directors, health care facilities, state institutions and any other individuals providing health care services are also required to report communicable disease. Therefore, community health needs assessment in urban communities remains an essential instrument for the rapid and accurate dissemination of epidemiological information on cases and outbreaks of diseases under the national health regulations and other communicable diseases of public health importance, including emerging or re-emerging infections. Purpose of the Study Todescribe relevant medical needs of townspeople so that treatment plans can be developed accordingly. Methods The Study was a cross-sectional with qualitative approach. In-depth interviews and focus group interviews was used as research technique. Data was categorized to look for emerging themes then further distilled to identify any abstract themes that could be understood holistically. Results Urban decision-makers need to advocate the problem of human resources in public health facilities and the mutual health insurance to revise its insurance policy to allow their clients to be received even in private clinics. Dental services was wished to be available in public health centers. Study participants suggested that new useful information could be posted in private public premises rather than to be in public institutions only. Conclusion The patient waiting time, dental services in health centers, and the way of dissemination new health information, mutual health insurance and insufficient human resources are the major concerns of townspeople that they wish improvement.

Chirps Amidst Coronavirus Disease-2019 (COVID-19) Transmission and Prevention in Ethiopia in 2020

Apr 2021 DOI 10.14302/issn.2692-1537.ijcv-21-3741
Assegid SahiluCorresponding author MD, MPH, Associate Professor of Epidemiology Jimma University, Jimma, Ethiopia

Background Ethiopia confirmed its 1st case of COVID-19 on Friday 13th February 2020. The burden increased dramatically by August/2020. The conditions that led to this rise were not reviewed. Objective To exploreCOVID-19 related phenomena in Ethiopia during 2019-2020. Materials and Methods Review of journals, books, and letters to editors, e-sources, news, personal experiences, observations, and communications. Results The zoonotic source of SARS- CoV-2 (Severe Acute Respiratory Distress Syndrome- Coronavirus-2) is not confirmed. The precedent events; and exact mechanism of COVID-19 is not clear. Dynamic models were required on the time line of dynamics of COVID-19; dynamics of infectiousness of COVID-19, and mechanism of transmission of COVID-19. Incubatory carriers might have been missed. Screening based on temperature had been problematic. The time spent in the development of diagnostic test for COVID-19 might have contributed to the early spread. Uninterrupted flights to China during the epidemic by Ethiopian Airlines as well as uninterrupted domestic flights; IDP (Internally Displaced People); and others put Ethiopia (and other countries) at great risk. Demographic adjustment may not be applicable for Ethiopia due to lack of census which had to be conducted every 10 year, was conducted only in 2007. This adds to the problem of error projection. The impact of HIV (Human Immuno-Deficiency Virus Disease) and war in Ethiopia before 2000 might have had affected people who would be now old age and who would be at the most risk of death. This made the impact of COVID-19 to appear low as revealed by the lower number of COVID-related deaths in Ethiopia. There were also hesitations inconsistencies in case definitions; implementations of quarantine; and burial regulations. Conclusion Even though uninhibited foreign flight to China as well as domestic flights; inconsistencies in the implementation of regulations pertaining to COVID-19 have contributed to COVID- 19 emergence in Ethiopia, the absence of census; the demographic impact of HIV and war before 2000 might have made the impact of COVID-19 to appear low as revealed by the lower number of COVID-related deaths in Ethiopia. Recommendation Accurate and current evaluation of the impact of COVID-19 in Ethiopia may require the absence of census; demographic consequences of HIV; and war before 2000 into consideration.

A Summary of Circular RNAs in Alzheimer's Disease

Jan 2021 DOI 10.14302/issn.2470-5020.jnrt-20-3619
Chen KepingCorresponding author Professor, Jiangsu University, Zhenjiang, China

Circular RNAs (circRNAs) are recently rediscovered eukaryotic molecules that form a covalently closed-loop structure through a special type of alternative splicing known as backsplicing. These closed-loop structures are highly stable and resistant to RNase degradation, and are thereby expressed in a tissue-specific and evolutionarily conserved manner, which regulates the expression of proteins and mRNAs that are involved in the metabolic pathways associated with specific diseases. Recent evidence of the ubiquitous expression of circRNAs in cancer under physiological and pathophysiological conditions indicates that dysregulation of gene and protein expression might promote tumorigenesis and carcinogenesis, and that circRNAs have important clinical significance in the diagnosis, treatment, and prognosis of cancer and other diseases. This review provides a brief introduction to the characteristics, formation, and function of circRNAs. Some of circRNAs act as microRNA (miRNA) sponges to regulate the level of transcriptional splicing and the expression of parental genes through the circRNA-miRNA-mRNA regulation axis. We summarize recent progress in above-mentioned circRNAs associated with Alzheimer's disease (AD).

Adopting High Fat Diets for Fat Loss and Improving Brain Health.

Oct 2020 DOI 10.14302/issn.2379-7835.ijn-20-3581
Nashte VaishnaviCorresponding author Sports Nutrition, K11 Academy of Fitness Sciences, 3rd Year, BAJMC, MITWPU

With an increased intake of processed carbohydrates and refined sugars, the obesity rate has shot up in the past decade giving rise to mental and physical health problems. These individuals are also the most vulnerable to a number of other diseases including the current pandemic of Covid-19. This paper aims to address the knowledge gap that is required to promote a healthy lifestyle for mental and physical wellbeing. The paper also analyses a number of different studies conducted and helps in understanding obesity as a strong risk factor to various disorders. Despite constant recommendations from healthcare organisations to address the importance of weight regulation, the process to do so often remains uncertain to the general population. The paper analyses the effects of the ketogenic diet for fat loss as well as treating mental illnesses and aims to address the influence of high carbohydrate diets on mental illnesses.

Human Psychology Open Access

Causes and Self-regulatory Mechanisms of Frustration: A Qualitative Exploration of Rock Climbers

Sep 2020 DOI 10.14302/issn.2644-1101.jhp-20-3524
Zheng YuannanCorresponding author Department of Physical Education, Zhejiang University, Hangzhou, China

In recent years, rock climbing has become increasingly popular around the world. However, due to its challenging and competitive nature, it is common for rock climbers to encounter frustration. It leads to negative emotions, reducing participation, and withdrawal behavior, which requires effective self-regulation. Therefore, the purpose of this study was to explore the causes and self-regulatory mechanisms of frustration in rock climbing. Using qualitative methods, 15 rock climbers were interviewed, and 6 themes were identified by thematic analysis. Task comparison and social comparison are the main causes of frustration in rock climbing. The self-regulatory mechanism of task comparative frustration includes focusing on tasks and habitual reflection. The self-regulatory mechanism of social comparative frustration involves emotion regulation and changing goal orientation. It is suggested that future rock climbers, especially beginners, deal with frustration through the self-regulatory mechanisms that can help them enjoy and pursue rock climbing.

Energy Conservation Open Access

Energy Conservation Measures in Heavy Trucks Freight Transport

Jul 2020 DOI 10.14302/issn.2642-3146.jec-20-3389
Tageldin Hago Ahmed SuhailCorresponding author Faculty of Engineering, University of Khartoum, Sudan

Since the independence of South Sudan, Sudan lost 75% of its oil reserves, this led to major fuel shortages country wide, the fuel shortage raised the fuel prices and the overall transport prices. Scarcity led to black market trade of fuel specially in states away from the Capital City (Khartoum). Managing the available stock comes first before increasing the supply amount in order to solve the problem, one of the major fuel consumers to be managed is the transport sector specially the long haulage freight transport. Moving freight in Sudan is constrained by inadequate infrastructure and high costs. This paper covers specifically the long haulage freight transport between Khartoum State and Western side of the country (Darfur Region), Contributing to manage fuel consumption for trucks, taking into account trucks types used, roads, environmental impacts and mitigation measures applicable to save fuel . The results showed that the primary reason for the excessive fuel consumption is the usage of the rigid trucks (lorries) for transport specially the Hino700 series, this truck type, overload and absence of weight stations and control policies contributed significantly to deterioration of roads and transport efficiency decreasing. First step towards the solution would be in upgrading roads infrastructure assuring high quality along with enforced weight regulations and weight stations to protect roads from damages. High quality roads shall ease the usage of different truck types with different configurations. Then stablish a policy to force replacement of the low efficiency lorry truck types with high quality tractor semi-trailer combinations.

Energy Conservation Open Access

Confirming Tonality at Residences Influenced by Wind Turbines

May 2020 DOI 10.14302/issn.2642-3146.jec-20-3359
K.G. Palmer WilliamCorresponding author Independent Researcher, TRI-LEA-EM, 76 Sideroad 33-34, RR 5, Paisley, ON N0G 2N0, Canada.

For 5 years, since the start-up of an array of 140 wind turbines, residents have filed complaints with the Ontario Ministry of the Environment (the regulator), and K2 Wind (the operator). Residents complained that the turbines produce a tonal sound, and that the irritation this produced impacted their sleep, their health, and the enjoyment of their property. To confirm tonality from the wind turbines, this research examined over 200 data examples from two families. These families collected data by two independent methods, a continuously recording system, and by making selected audio recordings. The recorded data was correlated with the wind turbine operational performance, and local weather conditions. The correlated data was analyzed for tonality using international standard evaluation methods. The analysis confirmed over 84% correlation between complaints of irritating conditions, and tonality from 5 dB to over 20 dB. Finally, the results showed that the assumption of the regulator to only require assessment of compliance when the resident was downwind of the nearest wind turbine was incorrect. Most complaints arose from other wind directions. Neither was the regulator’s assumption correct that curtailing the wind turbine operation to continue operating at only partially reduced outputs would give remediation. The research concludes that tonality arises consistent with the wind turbine operation, identifying a critical need to revise the practices to prevent chronic irritation. In the original issuance of this paper, the author inadvertently erred by stating that there was a difference between the method for assessing wind turbine tonality of an expert group panel and the method now prescribed by regulations. That statement was incorrect, and the author apologizes for the error and for any confusion it may have caused. The error, miscalculations resulting from the error, where necessary conclusions drawn from erroneous calculations are corrected.

Skeletal Muscle Open Access

The Mechanism of Decline of Senescent Skeletal Muscle Satellite Cell Self-Renewal and Regenerative Proliferation: The Role of Heparan Sulfate-FGF-2--FGFR1-p38αMAPK Axis, Sprouty1, miR-1, miR-133 and miR-29a

Apr 2020 DOI 10.14302/issn.2832-4048.jsm-20-3211
Papaconstantinou JohnCorresponding author The Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston Texas 77555-0643

Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344

Nucleoside and Nucleotide Reverse Transcriptase Inhibitors Induce Aging by Inhibiting Telomerase Function

Nov 2019 DOI 10.14302/issn.2324-7339.jcrhap-19-3070
Sharma BechanCorresponding author Department of Biochemistry, Faculty of Science, University of Allahabad, Allahabad-211002, UP, India.

The telomeres existing at the end of the eukaryotic chromosome, play an important role in localization, pairing of homologous chromosomes during cell division and synapsis formation, while telomerase is involved in maintenance of the telomere length. The application of antiHIV-1 molecules particularly NRTIs have been shown to interfere with telomerase function thereby inducing aging processes. Since the application of these molecules has already indicated production of oxidative stress and toxicity in AIDS patients, their adverse impact on telomerase function may further worsen the situation. In addition, the negative influence of antiHIV-1 regimens on certain host factors involved in telomerase function may enhance aging. HAART changes the landscape of the disease by progressively decreasing the progression of HIV-1, but exerts prolonged adverse effects on the telomerase function. Though there is no exact information available on this issue, intensive efforts are needed to explore regulation of telomerase expression in HIV infected individuals and particularly those receiving antiretrovirals. 

Long Non-Coding RNAs Emerging as Potential Epigenetic Biomarkers for Tobacco and/or Alcohol-Induced Head and Neck Cancer

Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2973
Bharadwaj MausumiCorresponding author National Institute of Cancer Prevention and Research (ICMR), I-7, Sector-39, Noida-201301, India.

Head and Neck cancer (HNC) is one of the most prevalent and lethal cancer globally. The incidence of tobacco-induced HNC is gradually increasing in low and middle income countries. Among the various causative factors associated with HNCs, tobacco and alcohol play synergistic effect and are frequently associated with the risk of HNC. Tobacco-induced HNCs show distinct genetic and epigenetic alterations leading to different clinical outcomes in comparison to HPV-infected HNCs. Tobacco-induced HNCs are often associated with tumor aggressiveness, poor prognosis and low or nil prevalence of HPV infection. Apart from carcinogenic effects of these causative factors (use of tobacco products, alcohol intake and HPV or EBV infections), recent studies show that exposure to these factors alter/disrupt the regulation of non-coding RNAs including the long non-coding RNAs (lncRNAs). Altered lncRNA regulation is brought about by signalling networks that regulate cellular differentiation, apoptosis, angiogenesis and inflammatory pathways which play key functions in the genesis of different cancers including HNCs. There are numbers of studies supporting the emerging role of lncRNAs in development of HNC; however, reports connecting lncRNAs expression and addiction habits in HNC are still preliminary and sparse. Therefore, identification and characterization of lncRNAs that are differentially expressed upon exposure to risk-factors can serve as unique therapeutic targets and potential biomarker(s) for effective treatment of HNC subtypes. In this short review, we briefly reviewed the emerging role of lncRNAs in tobacco and alcohol induced HNCs.

Motorcycle-Related Head and Limbs Injuries from Road Traffic Accident at a Second Level Hospital in Cameroon

Mar 2019 DOI 10.14302/issn.2474-3585.jpmc-19-2633
ErickTandi TinyamiCorresponding author Department of Preventive Medicine, College of Medicine, Graduate School of Public Health Korea University, Seoul South Korea.

Motorcycles have been increasing used widely in various urban, suburban and villages in Cameroon with an increased in accidents resulting to injuries among the population. Head and limbs injuries are responsible for most of the cases encountered from related crashes. A prospective study on head and limbs injuries resulting from motorcycle crash were assessed among the different cases brought to the casualty and emergency department of the Kumba district hospital. Most of the injured cases were of motorcycle and other vehicle collisions 203 (47.65) and the least among motorcycle lone crash 51 (11.97). Motorcycle to motorcycle collisions accounted for 107 (25.12 %) of the cases. 65 (15.26%) were motorcycle with pedestrians related collision. Stepping up and facilitating the regulations on licenses and the use of personal protective equipment for riders, improvement of roads infrastructures with pedestrian path, expanding health facilities and equipment, and human resources for health as well as empowering the population on road safety measures will be very important for RTAs control measures of the nation.

Developing Cellular & Molecular Biomarkers for Anti-Inflammatory Activities of Probiotic Bacteria in Fermented Foods

Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2578
E. Ahmed FaridCorresponding author GEM Tox Labs, Institute for Research in Biotechnology, 2905 South Memorial Drive, Greenville, NC 27834, USA.

We present below a mechanistic cellular and molecular approaches for the development of Anti-Inflammatory biomarkersof Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses approaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory pathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary components on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.

Self Determination and Quality of Life: a Comparison of the Measurement Scales for Students with Intellectual Disabilities

Feb 2019 DOI 10.14302/issn.2643-6655.jcap-18-2570
Emanuela ZappellaCorresponding author Department of Human and Social Sciences, University of Bergamo, Italy

Self-determination is a key concept to promote greater self-awareness in the subjects with disability, to build appropriate educational or professional projects and to evaluate the already active programs. Using PRISMA checklist, I selected articles from different databases (CINAHL, Medline, Psych INFO, Cochrane Library, ERIC, Scholar. The 9 evaluation measures identified are analyzed with respect to: choice of the points of view to be collected, domains, items and data collection methods. The results show that while some scales focus on autonomy, empowerment, self-realisation and self-regulation and others focus on knowledge, skills and abilities, attitudes and beliefs. Two instruments added also: opportunities and support. With respect to the choice of the points of view to be collected: in some cases the student’s opinion is collected but in other cases their point of view is integrated or replaced with that of teachers and parents. Only one tool is designed for all children and starts from the belief that self-determination is important for all people, including those with a disability. A third element of the analysis is the possibility of answering the questions posed by the various evaluation tools. A typical form is Likert scale while in other cases open questions are used. The analysis highlights two critical issues. The variety of definitions of self-determination is inevitably reflected in the choice of domains and items and therefore self-determination is only partially investigated. Secondly the opinion and people with disabilities are sometimes completed or replaced by that of third persons as parents and teachers. Starting from the analysis of existing instruments. the article closes with a reflection on the possibility of constructing a scale that considers all the aspects of self-determination offered in the literature (at the individual and environmental level) and collects the opinion of all the subjects involved in self-determination projects. This synthesis represents a first step in the construction of a possible universal scale starting from the analysis of the literature. A comparison would then be necessary with the students with intellectual disabilities, the family members and the other actors involved to understand which domains are really meaningful to them and to build indicators that correspond to the elements that are important to them. In this way we would have a tool capable of combining the point of view of literature with that of the people directly involved.

Robust Sampling of Defective Pathways in Parkinson Disease

Jan 2019 DOI 10.14302/issn.2641-5526.jmid-18-2529
Luis Fernández-Martínez JuanCorresponding author Group of Inverse Problems, Optimization and Machine Learning. Department of Mathematics. C/ Federico García Lorca, 18. 33007 Oviedo. University of Oviedo. Spain

Discrimination of case-control status based on gene expression differences has potential to identify novel pathways relevant to neurodegenerative diseases including Parkinson’s disease (PD). In this paper we applied two different novel algorithms to predict dysregulated pathways of gene expression across several different regions of the brain in PD and controls. The Fisher’s ratio sampler uses the Fisher’s ratio of the most discriminatory genes as prior probability distribution to sample the genetic networks and their likelihood (accuracy) was established via Leave-One-Out-Cross Validation (LOOCV). The holdout sampler finds the minimum-scale signatures corresponding to different random holdouts, establishing their likelihood using the validation dataset in each holdout. Phenotype prediction problems have by genesis a very high underdetermined character. We used both approaches to sample different lists of genes that optimally discriminate PD from controls and subsequently used gene ontology to identify pathways affected by disease. Both algorithms identified common pathways of Insulin signaling, FOXA1 Transcription Factor Network, HIF-1 Signaling, p53 Signaling and Chromatin Regulation/Acetylation. This analysis provides new therapeutic targets to treat PD.

Brain Hemodynamics and Cerebrovascular Reactivity in Patients with Tension-Type Headache

Jan 2019 DOI 10.14302/issn.2470-5020.jnrt-18-2555
Ya. Abdullaiev RizvanCorresponding author Kharkiv Medical Academy of Postgraduate Education, Department of Ultrasound Diagnostics, Ukraine

Introduction: Tension-type headache (TTH) is very common, with a lifetime prevalence in the general population ranging in different studies between 30% and 78%. TTH, divided into episodic and chronic types, introduced in the manual "International Classification of Headache Disorders"(ICHD-I), is of practical importance. Infrequent episodic headaches (no more than once a month) may not require drug therapy, but, on the contrary, frequent forms may require expensive treatment. Objective: To study the state of cerebral hemodynamics and cerebrovascular reactivity in patients with Tension-type headache and evaluate the efficacy of treatment with Phenibite using Doppler ultrasound. Materials and Methods: A retrospective analysis of the results of ultrasound dopplerography of the anterior, middle and posterior cerebral arteries (ACA, MCA and PCA), Vertebral and Basal (VA, BA) arteries was performed in 188 patients with TTH. Among them are infrequent episodic TTH - 68 (36,2%) patients, frequent episodic TTH - 64 (34,0%) patients, chronic TTH - 56 (29,8%) patients. The age of the subjects was 18-45 years, among them 85 (45.2%) men and 103 (54.8%) women. The maximum systolic velocity (Vs), the end diastolic velocity (Vd), the resistance and pulsativity indexes (RI, PI) in all vessels were determined. Patients were given consent to participate in the study. Results: Infrequent episodic (IFE) TTH were recorded in 86.4% of cases, frequent episodic (FE) — in 88.9%, and chronic (Ch) TTH — in 81.6% of cases. Bilateral TTH was noted in 39.2%, frontal localization - in 35.6%, in the occipital region - in 25–7% of cases. The asymmetry of the maximum systolic blood flow velocity (Vs) in the paired arteries within 20-30% was considered a violation of cerebral hemodynamics, which was detected in 38.7% of patients. An increase in Vs was noted in all cerebral vessels, especially in patients with FE TTH and chronic Ch TTH compared with the control group. In patients with IFE TTH the average value of RcFMt was 1.24±0.03, in patients with FE TTH - 1.25±0.02, in patients with Ch TTH - 1.27±0.03. In patients with TTH, hyper-responsiveness to hypercapnic test was detected: RcCO2 was 1.43±0.05 in the group with FE TTH; 1.39±0.07 in the group of Ch TTH and 1.37±0.04 in the group of IFE TTH, which indicates a tendency for the tension of the vasodilator regulation mechanism even in clinically insignificant forms of TTH. In the study of reactivity to the O2-test, a hyporeactive response was observed in the groups with FE TTH and Ch TTH (0.38±0.04 and 0.35±0.05, respectively. The treatment with Phenibut carried out in a step-by-step manner - during the first week the drug was applied at a dose of 250 mg 2 times a day, over the next 6 weeks the dose increased to 500 mg 2 times a day, then the dose was reduced back to 250 mg 2 times a day. Among patients with FE TTH, the frequency of headache decreased from 5.7±2.3 to 3.6±2.1 days/month, and in patients with Ch TTH - from 22.8±1.7 to 17.7±1,3 days/month (P<0,05). Influence of the drug was manifested at the initially increased RcFMt and RcCO2. A decrease in initially elevated RcCO2 was noted in all (FE TTH, ChTTH, IFETTH) clinical groups. However, this decrease was not statistically significant. Conclusion: In patients with TTH, an increase in the Vs is more often recorded, their asymmetry in the middle cerebral artery. Hyperreactivity on CO2-load is typical for patients with chronic TTH, and reflects the mobilization of metabolic regulation of cerebral blood flow. Conducting FMt was the most informative method for detecting autoregulatory disorders mainly in patients with IFE TTH. FE TTH in patients is characterized by the presence of a hyperactive reaction to hypercapnic and orthostatic tests, probably due to mobilization of humoral-metabolic and neurogenic links of regulation. In the group of patients with chronic TTH prevails hyporeactivity for hyperventilation test, reflecting the depletion of vasoconstriction reserve. The use of Phenibut(Noophen® (JSC Olainfarm Latvia in the treatment of TTH is accompanied by a decrease in the frequency of pain, and of pericranial muscle tone, most pronounced in patients with FE TTH. It's effectiveness is evident in the normalization of the coefficients of cerebrovascular reactivity in a patients with chronic TTH. The minimal statistical significance was observed on the dynamics of blood flow only in the VA.

Metal Metalloproteinase 2 is Differentially Regulated by the Interplay between Glucose and Insulin

Nov 2018
Shiau Ming-YuhCorresponding author Department of Nursing, College of Nursing, Hungkuang University, Taichung, Taiwan.

Pre-adipocytes are the precursors with the potential to make new fat cells during adipose tissue expansion. Nevertheless, the pre-adipocytes behaviors, and their possible roles in energy homeostasis have long been overlooked. Our previous study implicates that interleukin-4 (IL-4) plays a positive metabolic role by promoting insulin sensitivity and inhibiting lipid accumulation. Besides, abundant evidence shows the involvement of matrix metalloproteinase-2 (MMP-2) in the process of adipose tissue expansion. The present study aimed at examining the cross talk among glucose, insulin and IL-4 on regulating MMP-2 expression and activity in 3T3-L1 pre-adipocytes. Effects of insulin and/or IL-4 on MMP-2 expression and activity were examined in pre-adipocytes under euglycemic or hyperglycemic environment by RT-PCR and gelatin zymography, respectively. Our results revealed that glucose level is a pre-requisite for pre-adipocytes responding to insulin and/or IL-4 treatment. In high glucose-containing environment, short-term acute insulin treatment (AI) and long-term chronic insulin exposure (CI) showed opposite regulation to MMP-2 expression and activity. Interestingly, the dominant MMPs regulatory role of CI under euglycemic condition was attenuated in cells exposed to high glucose concentration. Our results suggest pre-adipocytes may participate in the process of increasing adiposity, diabetic onset and diabetic complications through ECM alterations resulted from the insulin- and/or glucose- mediated changes of MMP-2 activity. The present study uncovers novel observations regarding pre-adipocytes behaviors. 

Need of Nutraceuticals / Functional Food Products for Health Benefits to World-Wide People

Oct 2018 DOI 10.14302/issn.2576-6694.jbbs-18-2408
K. Srivastava RajeshCorresponding author GIT, Gitam Institute of Technology and Management (GITAM) (Deemed to be University)

Improved economic and developed people with their lifestyle have created many challenges of health issues (obesity, osteoporosis, cancer, diabetes, allergies and dental problems), due to selection of different food habits (such as consumption of manifold junk foods). It has created number of health problem (development of many diseases) related to nutritional deficiencies food. Nowadays, people have developed the habit for shifting of synthetic food ingredients to organic foods and ingredients, obtained from natural sources. In this regards, nutraceuticals food or its food products can perform important role in controlling the diseases via fulfilling all the health benefits to many people at worldwide. Incredible dietary supplements as nutraceuticals food (involvement in nutritional, immunologic and physiological functions) can help in prevention or treatment of many diseases (mitigating of gastrointestinal (GI) tract problem), as it is synthesized from raw herbals and lots of rapidly growing industries are reported to synthesize these natural products. And around 100 million people are found to take these products (power of plant based materials) for getting health benefits. It can work as drugs as health benefit of nutraceuticals via regulation/ control for diseases. Global nutraceuticals market had been valued for US$ 165.62 billion in 2014 and it would be grow the value of US$ 278.96 billion by 2021 with compound annual growth rate of 7.3%. This proposed paper will discuss the different types of nutraceuticals food or its functional components involved in prevention or treatment of diseases.

The Use of Mirnas as Activators of Dental Implant Surfaces, A Review

Sep 2018
Di Gianfilippo RiccardoCorresponding author The University of Michigan - School of Dentistry, Department of Periodontics and Oral Medicine, 1011 North University Avenue, 48109-1078, Ann Arbor, MI – USA

MicroRNAs are short sequences of non-coding RNAs crucial in regulation of cell development, proliferation and differentiation. Some of them showed to be related with the expression of osteogenic genes. Aim of the present review was to evaluate the biological effects of titanium implant surfaces activated with miRNAs or antimiRNAs. A bibliographical electronic research was carried out on PubMed/Medline. Articles investigating the influences of miRNA functionalized surfaces on human or animal cells were included. Reports were excluded if investigating surfaces modified with molecules different from miRNAs, if miRNAs were not loaded to titanium surfaces. Five articles met the inclusion criteria. Surfaces functionalized with miRNAs showed to up-regulate the expression of osteogenic genes like RUNX2, OPN, OCN, BMP, OSX, ALP, COL1 and COL3. Investigated surfaces additionally showed more bone-like mineralized tissues, bone lacunae, osteocytes and new blood vessels. MiRNAs loaded to titanium implant surfaces stimulate the expression of genes related to osteoblasts differentiation, osteogenesis, osseointegration and reparation of mineralized tissues. Vectors used to link titanium surfaces and miRNAs did not show cytotoxicity or interference with cells’ viability.

Molecular and Cell Biological Considerations in the Initiation and Development of Sporadic Non-Hereditary Solid Cancers  

Aug 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2183
F. Niculescu VladimirCorresponding author Cell Biologist, Germany, Kirschenweg 1, 86420 Diedorf

This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.

Neoplasms Open Access

Statins and Lung Cancer: A Review of Current Literature

Mar 2018 DOI 10.14302/issn.2639-1716.jn-18-1993
W. Kurtis ChildersCorresponding author

Cardiovascular disease and lung cancer are two of the most common causes of death in the United States. The cardioprotective benefits of statin class drugs is predominantly mediated through the inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, decreasing available mevalonate, and thus limiting in vivo cholesterol biosynthesis. Mevalonate and its metabolites have significant roles in cellular membrane synthesis, which is dysregulated during tumorigenesis, and is therefore a potential source for anti-tumor effects of statins. Similarly, dysregulation of cellular signaling is a hallmark of tumorigenesis. In vitro studies of EGFR, RAS, and AKT signaling pathways in cancer cells can all be reformed back to states more indicative of normally functioning cells when treated with statins. Statins have also been shown to exert beneficial properties in the presence of chemotherapeutic medications and radiation therapies by modulating the deleterious effects of reactive oxygen species, decreasing tumor cell resistance, and minimizing damage to surrounding native tissues. There is abundant of in vitro evidence to support the beneficial effects of statins on lung cancer patients. Prospective studies to determine the value of statin therapy on lung cancer prevention could lead to a significant change in lung cancer treatment.

Acute and Chronic Wound Fluid Inversely Influence Wound Healing in an in-Vitro 3D Wound Model

Dec 2017 DOI 10.14302/issn.2640-6403.jtrr-17-1818
Manuela BesserCorresponding author University Witten/Herdecke, Centre for Biomedical Education and Research (ZBAF), Dpt. Of Translational Wound Research

If a wound progressively heals or the healing process is impaired is basically influenced by the surrounding milieu. This is reflected by the wound fluid. Its specific composition triggers the migration, proliferation and differentiation of dermal and epidermal cells which so far was not sufficiently examined in 2D cell culture models. The influence of the different wound entities was analyzed on a newly implemented three dimensional in-vitro model, which improved the transferability to the in-vivo situation. The influence of pooled wound fluids from patients suffering from acute or chronic wounds were investigated within a time period of 10 days after wound application. Histological and immunohistochemical analyses were performed addressing the impact of AWF and CWF on regeneration, such as cell proliferation, fibroblast activity and cell migration. AWF slightly stimulated fibroblast migration while CWF inhibited their activation and migration. The CXCR4- immunopositive population was continuously decreased compared to the control and AWF treatment. The expression of FAP was enhanced under AWF and medium. In keratinocytes CWF massively stimulated cell proliferation initiating on day six after injury. The presence of 10% CWF inhibited fibroblast activation and migration and induced the degradation of the collagen matrix. Keratinocytes were stimulated to proliferate, resulting in healing inhibiting hyperplasia. Transferred to human wounds, no effective wound closure would be achieved because of the de-regulation of pro-proliferative and migration-stimulating factors and a degraded extracellular matrix. This newly implemented 3D study model represents a novel appropriate in-vitro system for studying healing mechanisms and potential therapeutic applications.

Shotgun Label-Free Proteomic Analyses of the Oyster Parasite Perkinsus Marinus

Jul 2017 DOI 10.14302/issn.2326-0793.JPGR-17-1571
C. P. Figueiredo HenriqueCorresponding author AQUACEN, National Reference Laboratory for Aquatic Animal Diseases, Ministry of Agriculture, Livestock and Food Supply, Federal University of Minas Gerais, Belo Horizonte, Brazil

Perkinsus marinus is an intracellular parasitic protozoan that is responsible for serious disease epizootics in marine bivalve mollusks worldwide. Despite all available information on P. marinus genomics, more baseline data is required at the proteomic level. Our aim was to study the proteome profile of in vitro cultured P. marinus isolated from oysters Crassostrea spp. using a label-free shotgun UDMSE approach. A total of 4073 non-redundant proteins were identified across three biological replicates with stringent identification. Proteins specifically related to adaptive survival, cell recognition, antioxidants, regulation of apoptosis and others were detected. Important virulence factors of P. marinus were identified including serine protease and iron-dependent superoxide dismutase. Other proteins with involvement in several pathogens invasion strategies were rhoptries, serine-threonine kinases, and protein phosphatases. Interestingly, peptides corresponding to retroviruses polyproteins were identified in all replicates. The interactomic analysis of P. marinus proteins demonstrated extensive clusters network related to biological processes. In conclusion, we provide the first comprehensive proteomic profile of P. marinus that can be useful for further investigations on Perkinsus biology and virulence mechanisms.

Frailty and the Immune System

Jun 2017 DOI 10.14302/issn.2474-7785.jarh-17-1578
Wilson DaisyCorresponding author Institute of Ageing and Inflammation, University of Birmingham, Edgbaston, Birmingham, UK, B15 2GW

Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research. The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype. Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome. Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty. Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fast-evolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.

“That Which is Measured Improves”: A Theoretical and Empirical Review of Self-Monitoring in Self-Management and Adaptive Behavior Change

May 2017 DOI 10.14302/issn.2474-9273.jbtm-16-1180
A. Chen JessicaCorresponding author Department of Psychology, University of Washington

Current psychological treatment approaches that rely on time-intensive, face-to-face psychotherapy are not capable of meeting the demand for mental health services. Mental health interventions that promote self-regulation and self-management of symptoms will play an increasingly important role in the well-being of millions of individuals. Self-monitoring is a core assessment and intervention component of many mental health interventions and an obligatory first step in the self-regulation process. The present paper reviews prominent theories of self-regulation and describes classic studies spanning clinical, social, cognitive, and personality psychology, which identify potential mechanisms underlying self-monitoring. At the empirical level, we describe the use of self-monitoring across a range of behavioral interventions directed at mental health and physical outcomes, identify factors that influence the effects of self-monitoring, and suggest ways in which technology can be incorporated into these interventions to improve the reach of psychological interventions.

Ophthalmic Science Open Access

Transiently Raised IOP Equivalent to That Experienced During Ocular Surgery Causes Moderate Inflammation but does not Affect Retinal Function or Result in Retinal Ganglion Cell Loss in An Animal Model

May 2017 DOI 10.14302/issn.2470-0436.jos-17-1453
Zhang JieCorresponding author Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Private bag 92019, Auckland 1142, New Zealand.

Purpose: High intraocular pressure (IOP) is known to result in retinal ganglion cell (RGC) loss, both with chronically raised intraocular pressure (such as with glaucoma) and with acute raises in pressure (due to injury or acute angle closure). Because IOP is often raised during ocular surgery, the purpose of this study was to evaluate the effect of transient moderate IOP on retinal function, RGC survival and the expression of Connexin 43 (Cx43) and glial fibrillary acidic protein (GFAP), ubiquitously expressed central nervous system (CNS) proteins that are known to be elevated during the retinal inflammatory response to injury. Materials and Methods: Wistar rats were exposed to transient IOP at 40 mmHg for 5 or 30 minutes, and 60 mmHg for 5 minutes (via cannulation of the anterior chamber with a saline reservoir raised to a height corresponding to the desired IOP), mimicking potential IOP rises during surgery such as DSAEK and some laser procedures (LASIK and femtosecond laser cataract surgery). Separate groups of animals had IOP maintained at 10 mmHg for 5 or 30 minutes as cannulation controls, or 120 mmHg for 60 minutes as positive controls. Changes in the optic nerve and retina were assessed immunohistochemically for GFAP and Cx43 expression. Retinal function was assessed using electroretinography (ERG) recorded at baseline and 14 days after the IOP rise and compared with RGC counts. Results: Results showed that there was a differential GFAP labelling pattern observed in the anterior optic nerve in the 40 mmHg 30 minute and 60 mmHg 5 minute groups 4 hours after manipulation. Gap junction protein Cx43 was minimally up-regulated in the retina in the short-term. There was, however, minimal long-term effect on retinal function and no RGC loss. Conclusions: n conclusion, elevations of IOP that are short in duration such as those occurring during surgical procedures, do not cause significant changes long-term in retinal function or RGC survival. Key Messages: Cx43 and GFAP are known to be elevated during the retinal inflammatory response to injury. No previous study has explored the effect of moderate and relatively short increases in IOP on the initial inflammatory response. We observed a mild glial inflammatory response in the anterior optic nerve, but only a minimal up-regulation of Cx43. However, transient and moderate IOP rises did not induce long term disruption to RGC function or number as measured by electrophysiology and RGC counts, respectively. This is applicable to clinical practice, as it means the IOP elevations that occur during some surgical procedures are unlikely to be causing long term damage in retinal function or RGC survival.

Psychopathology of Brain Frontal Lobe Tumors : When the Neurosurgery Meets Psychiatry

May 2017 DOI 10.14302/issn.2694-1201.jsn-17-1470
Domenico ChirchigliaCorresponding author Professor of Department of Neurosurgery, University of Catanzaro

Brain tumors occur when abnormal cells form within the brain.There are two main types of tumors: malignant and benign tumors. Then, tumors can be divided into primary that start within the brain, and secondary tumors that have spread from somewhere else, known as brain metastasis tumors. Secondary brain tumors occur in approximately 15 % of cancer patients with about half of metastases coming from lung cancer. Primary brain tumors occur in around 250,000 people a year globally, making up less than 2% of whole body tumors. According to American Brain Tumor Association the most common types of primary tumors are gliomas, representing 74,6 % of all malignant tumors and meningiomas ( 36,6% ) while more affected region is frontal lobe, about 22 % . Particularly, prefrontal cortex ( PFC ), the anterior part of the frontal lobe that is highly developed in humans plays a role in the regulation of personality, emotional, and behavioral functioning, leading to serious cognitive impairments 1. These are the psychological signs of frontal lobe tumors, in addition to other functions such as the expressive language of Broca's area or those relating to voluntary movement, linked to frontal cortical motor areas. It relates to the so-called higher nervous functions, concerning the life of relationship and communication. The PFC physiology explains the psychological mechanisms of its associated functions: connections with the limbic cortex, thalamus, hypothalamus, basal ganglia and other subcortical areas.The regions of the PFC at the base of the psychophysiological mechanisms involved are basically the dorso-lateral, the ventro-medial, the orbito-frontal establishing contacts primarily with limbic structures, such as the cingulate gyrus, hippocampus, amygdala.

Dual Effects of Neuroprotection and Neurotoxicity by General Anesthetics on Neural Stem Cells: Role of Autophagy

Feb 2017 DOI 10.14302/issn.2574-4372.jesr-16-1380
Wei HuafengCorresponding author Department of Anesthesiology and Critical Care, Perelman School of Medicine,

General anesthetics (GAs) are widely used for various essential surgical or medical procedures. Recent studies implicate the GAs has dual effects of neuroprotection and neurotoxicity on neurogenesis with unclear mechanisms. This minireview summarizes recent studies on GAs mediated effects on neurogenesis and proposed mechanisms, with focus on autophagy regulation and intracellular calcium homeostasis.

Prevalence of Impulse Control Disorders among Adult Filipino Patients with Idiopathic Parkinson’s Disease seen at Jose R. Reyes Memorial Medical Center

Oct 2016 DOI 10.14302/issn.2470-5020.jnrt-16-1240
Kristoper P. de Guzman JanCorresponding author Department of Neurology, Jose R. Reyes Memorial Medical Center

Background: Impulse Control Disorders (ICDs) are characterized as pathologicalbehavioral patterns of excess impulsivity which may result as part of the non-motor complications of Parkinson’s disease (PD). These significantly affect the patient’s overall quality of life and have impact on their care givers, as well. Currently, the prevalence of ICDs among adult Filipino patients with Parkinson’s disease is unknown and less reported. Objectives: The study is intended to determine the prevalence of ICDs and its severityamong adult Filipino patients with idiopathic Parkinson’s disease seen at Jose R. Reyes Memorial Medical Center. Specifically, this study will identify risk factors and the clinical correlates to these patients. Methods: Adult Filipino patients diagnosed withidiopathic Parkinson’s diseasewhowere seen at the outpatient department from March 2015 – September 2015 are screened for the study. The Modified Hoehn and Yahr staging was utilized to determine the stage of PD. With approval from the author, the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS) was used for detecting the presence of ICDs and corresponding severity. Results: We were able to examine 66 patients (31 males and 35 females) withidiopathic Parkinson disease. Majority of the patients manifested with Tremor Dominant (50%) subtype, followed by Early Disease Onset (34.8%), and Non-Tremor Dominant (15.2%). Sixteen (16) out of 66 patients (24.2%) have ICD symptoms with the following incidence rates: hobbyism/ punding 56.25%, compulsive eating 50%, hypersexuality 18.75%, compulsive shopping 18.75, Dopamine dysregulation syndrome 18.75%, and gambling 12.5%. Overall average QUIP-RS score is 5.42. There is significant association of PD duration with occurrence of ICD symptoms; the longer the PD duration, the higher risk of having ICD symptoms (x2 20.41; p = 0.026). Patients with higher mean modified Hoehn and Yahr stage (2.66±0.94), t 2.735, df 64, p 0.008, have much higher incidence of ICD symptoms. Conclusion: Filipino patients with idiopathic Parkinson disease who are majority onlevodopa + carbidopa therapy may develop impluse control disorders (ICDs). Other contributory factors in development of ICDs include longer duration of PD and higher mean Modified Hoehn and Yahr stage.

Breastfeeding Biology Open Access

Breast Feeding and Melatonin: Implications for Improving Perinatal Health

Jul 2016 DOI 10.14302/issn.2644-0105.jbfb-16-1121
Anderson GeorgeCorresponding author CRC Scotland & London, Eccleston Square, London, UK.

The biological underpinnings that drive the plethora of breastfeeding benefits over formula-feeding is an area of intense research, given the cognitive and emotional benefits as well as the offsetting of many childhood- and adult-onset medical conditions that breast-feeding provides. In this article, we review the research on the role of melatonin in driving some of these breastfeeding benefits. Melatonin is a powerful antioxidant, anti-inflammatory and antinociceptive as well as optimizing mitochondrial function. Melatonin is produced by the placenta and, upon parturition, maternal melatonin is passed to the infant upon breastfeeding with higher levels in night-time breast milk. As such, some of the benefits of breastfeeding may be mediated by the higher levels of maternal circulating night-time melatonin, allowing for circadian and antioxidant effects, as well as promoting the immune and mitochondrial regulatory aspects of melatonin; these actions may positively modulate infant development. Herein, it is proposed that some of the benefits of breastfeeding may be mediated by melatonin's regulation of the infant's gut microbiota and immune responses. As such, melatonin is likely to contribute to the early developmental processes that affect the susceptibility to a range of adult onset conditions. Early research on animal models has shown promising results for the regulatory role of melatonin.

Fertility Biomarkers Open Access

Family with Sequence Similarity 213, Member A is Associated with the Fertility Selection Index in Holsteins

Jul 2016 DOI 10.14302/issn.2576-2818.jfb-16-1035
Sugimoto MayumiCorresponding author National Livestock Breeding Center, Nishigo, Fukushima, Japan,

Female fertility is an economically important trait in the dairy industry, and the fertility selection index has been developed as a method of including female fertility in the breeding goals of this industry. This index considers a combination of factors, including days open, number of inseminations per lactation, success after first insemination, and pregnancy within 70 d, 90 d, and 110 d after parity. Based on a genome-wide association study of the fertility selection index using 442 Holsteins, we found that the index is influenced by a variation in the thioredoxin fold region of the family with the sequence similarity 213, member A (FAM213A) protein. FAM213A is a CXXC motif-containing peroxiredoxin 2-like protein that regulates cellular redox status. A replacement of isoleucine with valine in FAM213A was associated with poor fertility in cows. The overexpression of FAM213AVal in bovine endometrial epithelial cells reduced reactive oxygen species to a lesser extent relative to the overexpression of FAM213AIle and caused a decrease in cyclooxygenase-2 expression. Downregulation of cyclooxygenase-2 led to a decline in prostaglandin E2, which is critical for implantation because it protects the conceptus from the maternal immune system. Cows with FAM213AVal showed lower levels of prostaglandin E2 than did cows with FAM213AIle, suggesting that cows with FAM213AVal are less fertile than cows with FAM213AIle because of their reduced uterine environment. Thus, the present study found that FAM213A unexpectedly modulates female fertility in cattle.

Cytoplasmic Retention of CDC6 Induces Premature Senescence in Immortalized Cells and Suppresses Tumor Formation in Mice

Jun 2016 DOI 10.14302/issn.2372-6601.jhor-16-1125
Kato Jun-yaCorresponding author Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan

Senescence is a powerful mechanism that prevents the development of tumors in vivo; however, once tumors are formed, most are refractory to senescence in response to oncogenic stress. Therefore, a novel pathway leading to senescence is required. We herein demonstrated that the cell cycle regulator CDC6 translocated from the nucleus to the cytoplasm during senescence in a leptomycin B-resistant manner. In order to evaluate the translocation of CDC6, we utilized an estrogen receptor (ER) tag to retain CDC6 in the cytoplasm. ER-tagged CDC6 was exclusively cytoplasmic, inhibited cell proliferation, and induced senescence-associated (SA) b-galactosidase activity. Furthermore, ER-CDC6 inhibited the transformation of mouse fibroblasts by the active ras oncogene in vitro, and suppressed tumor formation in NOD-SCID mice. Thus, CDC6 may play a critical role in the regulation of senescence in the cytoplasm in order to counteract tumorigenesis.

Basal Serum Cortisol Levels, Depression and Medial Temporal Lobe Atrophy in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Mar 2016 DOI 10.14302/issn.2476-1710.jdt-15-719
Dhikav VikasCorresponding author Postgraduate Institute of Medical Education & Research & Dr. Ram Manohar Lohia Hospital, New Delhi, INDIA

This clinical study explores associations among basal serum cortisol, depressive symptoms, and medial temporal lobe atrophy in patients with MCI and Alzheimer's disease. It discusses stress‑axis dysregulation as a potential contributor to neurodegeneration and outlines implications for assessment and intervention.

Ophthalmic Science Open Access

Ciliary Neurotrophic Factor Activated Signaling Pathways in Retinal Müller Cells

Mar 2016 DOI 10.14302/issn.2470-0436.jos-15-739
P. Sarthy VijayCorresponding author Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 606111.

Ciliary neurotrophic factor (CNTF) is a well-tested, neuroprotective agent that has been shown to retard photoreceptor degeneration in several animal models of retinitis pigmentosa. The molecular mechanisms underlying CNTF-mediated neuroprotection are currently not understood. CNTF could act directly on photoreceptors or it could act indirectly by stimulating Müller glial cells to produce photoreceptor neuroprotective agents. To better characterize CNTF action on Müller cells, we have studied signaling pathways activated by CNTF using an established retinal Müller cell line, rMC-1. RNA was isolated from CNTF-treated cultures, and suppressor of signal transducer and activator of transcription (SOCS3) and Glial fibrillary acidic protein (GFAP) transcript levels were assessed by quantitative real-time PCR. Immunoblotting was used to examine activation ofmitogen activated protein kinase (ERK1/2/MAPK) and phosphoinositide 3-kinase (PI3-K)/Aktpathways in response to CNTF. Additionally, the level of5' AMP-activated protein kinase (AMPK), an enzyme that plays a key role in cellular energy homeostasis levels, was determined by immunoblotting. CNTF treatment resulted strong upregulation of SOCS3 and GFAP transcripts that were blocked by expression of a dominant-negative STAT3 mutant. CNTF treatment also resulted in transient activation of ERK1/2/MAPK but not PI3K/Akt signaling pathway. There was no change in activation of AMPK. We conclude that CNTF treatment leads to stimulation of JAK-STAT and MAPK signaling pathways but not the PI3K/AKT pathway, associated with cell death, in Müller cells.

Computational STAT4 rSNP Analysis, Transcriptional Factor Binding Sites and Disease

Feb 2016 DOI 10.14302/issn.2374-9431.jbd-15-890
E. Buroker NormanCorresponding author Department of Pediatrics, University of Washington, Seattle, WA 98195, USA

Purpose Signal Transducer and Activator of Transcription 4 (STAT4) is important for signaling by interleukins (IL-12 and IL-23) and type 1 interferons and has been found to have several simple nucleotide polymorphisms (SNPs) associated with human disease. STAT4 SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to human disease. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theSTAT4 gene from 4 kb upstream of the transcriptional start site to 8.3 kb past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The STAT4 SNPs in the 70 kb intron between exon 2 and 3 are in linkage disequilibrium and have previously been found to be significantly associated with several vasculitis diseases as well as diabetes. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the STAT4 gene. These STAT4 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF STAT4 regulation. These regulatory changes were discussed with respect to changes in human health that result in disease.

Computational EPAS1 rSNP Analysis, Transcriptional Factor Binding Sites and High Altitude Sickness or Adaptation

Feb 2016 DOI 10.14302/issn.2326-0793.jpgr-15-889
E. Buroker NormanCorresponding author Department of Pediatrics, University of Washington, Seattle, WA 98195, USA

Purpose The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) gene which encodes hypoxia-inducible-factor-2 alpha (HIF2a) is a transcription factor that is involved in the response to hypoxia. EPAS1 has been found to have four (rs56721780, rs6756667, rs7589621, rs1868092) simple nucleotide polymorphisms (SNPs) associated with human disease.These SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to disease and alterations in high altitude adaptation in humans. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theEPAS1 gene from 1.6 kb upstream of the transcriptional start site to 539 bps past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The EPAS1 SNPs in the promoter, intron two and the 3’UTR regions have previously been found to be significantly associated with disease and different levels of high-altitude hypoxia among native Tibetans. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the EPAS1 genesuch as for the glucocorticoid and mineralocorticoid nuclear receptor binding sites created by the rs7589621 rSNP EPAS1-G allele. These receptors regulate carbohydrate, protein and fat metabolism. Also the minor rs7589621 rSNP EPAS1-A creates a punitive TFBS for the FOXC TF which is an important regulator of cell viability and resistance to oxidative stress. These EPAS1 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF EPAS1 regulation. The punitive changes in TFBS created by the four rSNPs could very well influence the significant cline in allele frequencies seen in Tibetans with increasing altitude or the haplotype association with high altitude polycythemia in male Han Chinese. These regulatory changes were discussed with respect to changes in human health that result in disease and sickness.

Clinical and Immunological Beneficial Effects of Phyto V7 Consumption by HIV-1 Seropositive Individuals

Dec 2015 DOI 10.14302/issn.2324-7339.jcrhap-13-264
J. R WernikCorresponding author Facultad de Medicina, UDELAR, Montevideo, Uruguay;

Phytochemicals (PHT) are a large group of biologically active plant chemicals that may have positive effects on human health such as immune system stimulation, down regulation of inflammatory responses, radical scavenging activities, cell repair function, and antibacterial and antiviral activity. In this proof of principle 6 months study, the effects of supplementing a PHT mix, Phyto V7, to HIV-1 seropositive individuals and AIDS patients were examined. Individuals with CD4+ T-cells below 350 counts/mm3were assigned to one of the following treatments: CG1 - no treatment, CG2 - only highly active antiretroviral treatment (HAART), TG1 - only Phyto V7, and TG2- both Phyto V7 and HAART. After 3 months of treatment there were approximately (-)1%, 1%, 2% and 4% increase in the mean weight of the CG1, CG2, TG1 and TG2 groups, respectively. The tendency for the body mass index (BMI) was similar. The CD4+ counts increased by 13%, 39%, 53% and 35%, respectively. Similar trends were noted after 6 months with 2%, 79%, 53% and 69% increases in the CD4+ counts, respectively. There was a significant reduction in viremia only in groups receiving HAART. Overall better results were obtained in the group of patients receiving both HAART and Phyto V7, in which the mean weight increased by 5.7% and the CD4+ T-cell counts increased by 69% after 6 months. This study indicates that providing Phyto V7 to HIV-1 seropositive individuals and AIDS patients, receiving or not receiving HAART, improves their physical wellbeing and CD4+ counts, enabling them to cope better with the viral infection.

Overexpression of Prostate Apoptosis Response Protein-4 In Colon Cancer Cells Can Inhibit Metastasis by Upregulating E-cadherin Expression

May 2015 DOI 10.14302/issn.2471-7061.jcrc-14-574
B. Irby RosalynCorresponding author Department of Medicine Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA 17033. &Denotes equal contribution

Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year. Patients with metastatic colorectal cancer have a significantly worse prognosis, a 12.9% five-year survival. This emphasizes the need for strategies to inhibit the growth and metastases of colorectal cancer. Prostate apoptosis response protein 4 (Par-4) is a pro-apoptotic protein that has been shown to mediate apoptosis in response to stimuli, such as chemotherapeutics and radiation. Recombinant Par-4 protein has been shown to reduce the occurrence of Lewis lung carcinoma metastases in-vivo; however, the mechanism by which Par-4 can inhibit metastasis has not been elucidated. In this study, human colon cancer cell lines - SW480 and SW620 - were transfected with Par-4 plasmid or anti-Par-4 shRNA, and the effect on metastasis was examined. Par-4 overexpression inhibited cell migration and invasion, while Par-4 knockdown promoted it. Moreover, the morphology of SW620 cells was altered when Par-4 levels were increased. The change was characteristic of a mesenchymal-to-epithelial transition (MET) in these cells. MET can be induced by upregulation of E-cadherin expression, and RT-PCR and Western blot analyses showed that E-cadherin mRNA and protein levels, respectively, were increased in the Par-4 overexpressing cells concomitant with a decrease in vimentin. The results of this study demonstrate the potential of Par-4 in colon cancer therapy, not only in primary tumors but also in metastatic cells.

Epigenetics and Nutrition

May 2015 DOI 10.14302/issn.2379-7835.ijn-14-603
Lundstrom KennethCorresponding author PanTherapeuitcs, Rue des Remparts 4, CH1095 Lutry, Switzerland

Epigenetic mechanisms based on DNA methylation, histone modifications and RNA interference have recently showed important association to the development of a wide variety of diseases such as cancer, cardiovascular, metabolic, skin, autoimmune diseases and neurologic disorders. In the context of preventive aspects, the importance of nutrition on epigenetic function has been revealed. Therefore, drastic changes in dietary modifications may contribute to reduced disease risk. For instance, dietary intervention has been showed to affect DNA methylation in Alzheimer’s disease patients. Moreover, maternal high-fat diet can regulate gene expression through promoter histone modifications. Most importantly, RNA interference and particularly micro-RNA mediated regulation of gene expression has been linked to disease development. Remarkably, dietary intake has been demonstrated to significantly affect various miRNAs and their regulation on gene function. In this review, the relationship between epigenetics and disease and development of drugs based on epigenetic targets is presented as well as the influence of dietary intake on epigenetic mechanisms and its effect on disease prevention and therapy will be discussed.

Hypertension in Hypoxia

Oct 2014 DOI 10.14302/issn.2329-9487.jhc-14-edt3
Guchhait PrasenjitCorresponding author UNESCO Regional Centre for Biotechnology, Delhi NCR, India.

An overview of blood pressure regulation in hypoxia addresses altitude physiology, sleep disordered breathing, and cardiopulmonary disease. It reviews pathophysiology and therapeutic implications.

Molecular Cytogenetic Investigations in a Novel Chromosomal Abnormality of t(10;15)(q22;q22) in a Pediatric Precursor-B-Acute Lymphoblastic Leukemia Patient

Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-358
Mandava SwarnaCorresponding author Cytogenetic division, SRL Ltd., Mumbai, India.

Acute lymphoblastic leukemia (ALL) is a rapid form of leukemia characterized by clonal proliferation and accumulation of immature hematopoietic stem cells of the lymphoid lineage in the bone marrow as well as peripheral blood. Chromosomal aberrations identified in childhood ALL have an important role in disease diagnosis, prognosis and management. We present the results of hematologic, immunophenotypic, cytogenetic, FISH and Multiplex RT-PCR analysis of a 6-year-old boy diagnosed with B-cell precursor Acute Lymphoblastic Leukemia (BCP- ALL). In this study, we identified a novel chromosomal translocation t(10;15)(q22;q22) by cytogenetic and FISH analysis. To the best of our knowledge, this is the first report of this novel chromosomal translocation in this subset of ALL and has not yet been reported elsewhere. This rearrangement may include certain cancer associated tumor suppressor gene(s) or genes involved in apoptosis and transcription regulation, which on loss of normal function may lead to leukaemogenesis.

Evaluating the Efficacy of Gene Silencing in Dopaminergic Neuronal Cells In-Vitro using Gold Nanorods (GNR) with Different Surface Properties Complexed to DARPP-32 siRNA.

Jan 2014 DOI 10.14302/issn.2328-0182.japst-12-183
D. Mahajan SupriyaCorresponding author Department of Medicine, Division of Allergy, Immunology, and Rheumatology,

Gold nanorods (GNRs) are plasmonic nanostructures by virtue of their size-dependent optical properties, offer a bionanotechnology platform in areas of bioimaging, drug delivery etc for disease diagnosis, prognosis, and therapy. GNRs are more sensitive to changes in local environments, and offer strong scattering and absorption efficiencies thus providing opportunities to integrate multiple imaging modes and therapeutic strategies. The hydrodynamic size of these GNR under physiological condition is <100 nm, making them ideal as intracellular delivery agents. RNA interference using small inhibitory RNA (siRNA) has become a powerful tool to downregulate mRNA levels by cellular nucleases that become activated when a sequence homology between the siRNA and a respective mRNA molecule is detected. siRNA is used to silence genes involved in the pathogenesis of various diseases and holds a promising option for the development of novel therapeutic strategies in neurological dysregulation such as that observed in drug addiction. However, a major challenge in gene therapy continues to be effective delivery of siRNA and its sustained release at targeted sites. Previously, we have shown the GNR coated with poly (diallyldimethyl ammoniumchloride) (GNR-PDDAC) electrostatically complexed to the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) siRNA forming a GNR-nanoplex that was able to effectively silence the DARPP-32 gene expression in dopaminergic neuronal (DAN) cell cultures in- vitro. The current report, explores if modification of the surface coating properties of the GNRs with different surface coatings namely, amino terminated polyethylene glycol (GNR-PEG), polyethyleneimine (GNR-PEI) and Chitosan (GNR-CIT) alters their stability, cytotoxicity and DARPP-32 gene silencing efficiency in-vitro dopaminergic neuronal (DAN) cell cultures with the goal of determining the most suitable surface coating for the GNR that would provide a GNR-nanoplex with the most stability, least cytotoxicity and most efficacious gene silencing.

Kynurenines and Vitamin B6: Link Between Diabetes and Depression.

Sep 2013 DOI 10.14302/issn.2374-9431.jbd-13-218
Oxenkrug GregoryCorresponding author Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston MA, USA.

The increased association between depression and diabetes mellitus is generally acknowledged. Recent studies suggest that depression leads to diabetes.However, the underlying molecular mechanisms for this association remain unclear.Literature and our data indicate that inflammatory and/or stress factors in depression up-regulate tryptophan (TRP) conversion into kynurenine (KYN), a substrate for nicotinamide adenine dinucleotide (NAD) biosynthesis. Deficiency of vitamin B6, a co-factor of the key enzymes of KYN – NAD pathway, shunts KYN metabolism from formation of NAD towards production of xanthurenic (XA) and kynurenic (KYNA) acids. Human and experimental studies reveal that XA, KYNA and their metabolites interfere with production, release and biological activity of insulin. We propose that inflammation- and/or stress-induced up-regulation of TRP – KYN metabolism in combination with vitamin B6 deficiency is one of the mechanisms mediating increased risk of diabetes in depression. Consequently, monitoring formation of diabetogenic KYN derivatives might help to identify subjects-at-risk for the development of diabetes. Pharmacological down-regulation of the TRP – KYN – NAD pathway and maintenance of adequate vitamin B6 status might help to prevent the development of diabetes in depression and other conditions associated with inflammation/stress–induced excessive production of KYN and vitamin B6 deficiency, e.g., obesity, cardiovascular diseases, aging, menopause, pregnancy, and hepatitis C virus infection.

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