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Jul 2024 DOI 10.14302/issn.2575-1212.jvhc-24-5146
C SteffenCorresponding author
Dietary intake of inorganic phosphates is linked to various adverse health effects. Excessive intake of highly soluble inorganic phosphates, which are used as feed and food additives, have been found to impair parameters of kidney health. As chronic kidney disease represents one of the most frequently occurring terminal diseases especially in cats, extensive knowledge regarding the safety of these additives is important. Other minerals, such as calcium, can modulate their effects on the phosphate homeostasis and kidney health. Therefore, it is crucial to examine further factors, such as the dietary cation-anion balance (CAB), resulting from the concentrations of major minerals in a diet. In this study, eleven healthy cats were fed a control diet and two diets with added sodium monophosphate (NaH2PO4) with either a low (-10 mmol/kg dry matter) or high (+450 mmol/kg dry matter) CAB for 28 days each. The serum concentrations of phosphate and parameters of phosphate homeostasis were determined in the fasting and postprandial blood samples next to the apparent digestibility and retention of phosphate and calcium. The diet with positive CAB led to an increase of serum phosphate and the phosphatonin FGF23, apparently digested phosphate, and phosphate retention. This is further proof that source and amount of phosphates in a diet are not the only determinants of the extent of potential adverse health effects. Until the interactions between inorganic phosphates and other dietary compounds are fully understood, recommendations regarding the safe use of phosphate containing additives in pet food are precarious.
Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-346
E. Clapham ChloeCorresponding author
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
Targeting cell metabolism is a therapeutic approach which has been used for the treatment of cancers with high levels of proliferation. Inhibition of metabolic processes in cancer cells has shown synergy with current therapeutic options to reduce refractory disease and relapse. In contrast, chronic lymphocytic leukaemia (CLL) is a disease where expansion of the malignant clone results from a combination of enhanced cell survival coupled with low level proliferation. The purpose of this article is to highlight how further research is needed to determine whether targeting cell metabolism may be a viable therapeutic strategy in this disease. We discuss how lymphocyte doubling time (LDT) remains a robust prognostic indicator used in the current clinical management of CLL, and how recognition of CLL as a proliferative disease has led to a greater understanding of the importance of energy-generating processes in its pathobiology. We summarize what is currently known about normal B cell metabolism and consider whether there is evidence of the Warburg effect in CLL cells. Finally, we speculate on how CLL cells may exploit protective mechanisms such as autophagy during times of metabolic stress and how they might influence or be influenced by metabolic characteristics of the microenvironment.
Feb 2026
Xing HuiCorresponding author
Keratinocytes are pivotal in mediating cutaneous inflammation. Identifying anti-inflammatory factors within these cells holds promise for developing novel therapeutic strategies to manage skin inflammation. Transcription factor EB (TFEB) has recently emerged as a key regulator linking cellular energy metabolism to inflammatory processes, primarily through its influence on autophagy and NF-κB signaling. However, whether TFEB activation exerts anti-inflammatory effects in keratinocytes remains unclear. In vitro inflammation model was established in HaCat cells by incubation with proinflammatory mediators LPS and IL-1β. Cell viability and TFEB expression and phosphorylation were measured. The effect of TFEB activation by C1 and adenoviral TFEB overexpression on the expression of proinflammatory genes including COX-2, MCP-1 and IL-6 were detected. Also, IκBα protein level were determined. TFEB phosphorylation is increased while TFEB total protein expression is inhibited by treatment with LPS and IL-1β. Pharmacological activation of TFEB by compound C1 and TFEB overexpression suppressed the expression of COX-2, MCP-1 and TNF-α induced by LPS and IL-1β. TFEB overexpression increased basal IκBα expression and restored IκBα level under LPS treatment. TFEB knockdown reduced TFEB expression and lowered basal expression level of COX-2, MCP-1 and TNF-α. Our findings indicate that TFEB activation can mitigate inflammatory gene expression in keratinocytes triggered by LPS and IL-1β. This implicates TFEB as a significant novel modulator of cutaneous inflammation, highlighting its potential as a therapeutic target. Targeting TFEB could thus be a viable strategy for developing new treatments for chronic inflammatory skin conditions.
Aug 2025 DOI 10.14302/issn.2690-4829.jen-25-5617
Elizabeth Martínez-González MónicaCorresponding author
Redox enzymes are a type of enzyme that catalyzes redox reactions, that is, electron transfer reactions between two chemical species. Redox enzymes are essential for many biological processes, including cellular respiration, photosynthesis, energy production, and the elimination of free radicals. They are divided into two main types: oxidoreductases and electron transferases. Oxidoreductases catalyze the direct transfer of electrons between two chemical species, while electron transferases catalyze electron transfer by cofactors. Examples of redox enzymes include cytochrome c oxidase, NADH dehydrogenase, succinate dehydrogenase, and catalase. Each of these enzymes play an important role in cellular metabolism and organism homeostasis.
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.
Jan 2024 DOI 10.14302/issn.2374-9431.jbd-23-4842
Wissam Younes SamerCorresponding author
Over the past 20 years, the number of persons with diabetes has more than doubled globally. The purpose of this review article is to investigate the connection between certain vitamins and diabetes. Diabetes patients have been found to have decreased amounts of certain antioxidant vitamins including A, C, and E, presumably as a result of the requirement to control oxidative stress brought on by problems with glucose metabolism. Retinol-binding protein has regulatory and adipocytokine function. Thiamine, pyridoxine, and biotin levels are also decreased in diabetics. Studies have shown that it restricts the absorption of several nutrients, such as vitamins B9 and B12, thus diabetics must frequently replenish these vitamins. Low vitamin D levels increase the risk of developing diabetes and associated complications, such as cardiovascular disease. Although some studies indicate that vitamin K supplementation can enhance glucose metabolism, it is not known if vitamin K supplementation can prevent or repair oxidative damage. Numerous studies have demonstrated the detrimental consequences of excessive vitamin supplementation. The association between a few nutrients—specifically, vitamins A, D, C, B3, B6, B9, Zn, B12, E, B1/K, and irons—and the already mentioned pathways implicated in diabetes—as well as their potential regulatory activity—will be analyzed in the review that follows.
Mar 2022
Javier Torres-Gómez FranciscoCorresponding author
Pathology Unit. High Resolution Hospital. Utrera, Sevilla. Spain
Verruca vulgaris is a very common lesion, of viral etiology, benign clinical behavior and different types of simple treatments. Its epidemiological, morphological, histological and therapeutic study has been sufficiently reflected in the literature. We present a peculiar clinical case in which calcium deposits developed on a common wart without any alterations in its metabolism being observed in the analytical studies carried out (calcinosis cutis). A 9-year-old male patient attended the dermatology service due to an excrescent keratotic lesion of recent appearance and rapid growth. We have conducted an unsucessful bibliographic search of this relationship, possibly because these have not been communicated because it is simply a morphological finding with no clinical significance.
Mar 2022
Bereda GudisaCorresponding author
Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia
Dolutegravir suppresses this integration enzyme, so human immune virus can’t create every greater copies of itself, thus ‘’integrase inhibitor.’’ Dolutegravir is hastily absorbed pursuing oral administration. The median maximum plasma concentration is reached 1.5–2.5 hours after oral uptake with a mean half-life of 12–15 hours, rendering feasible for once-daily dosing without the need for pharmacological boosting. The terminal half-life is about 14 hours. The apparent oral clearance is about 1 liter/hour. Fifty three percent of the total oral dose of dolutegravir is excreted unchanged in the feces, thirty two percent through urine as glucuronide (eighteen percent) or alkylated product (three point five percent), and other organic conjugated products sequencing from phase II liver metabolisms. Dolutegravir’s categorized as pregnancy category B (no confirmation of pitfall in humans) means either animal-reproduction inquests have not substantiated a fetal peril but there are no restrained inquests in pregnant women or animal-reproduction inquests have reveal an adverse effect (distinctive than a de-escalate in fertility) that was not inveterate in restrained inquests in women in the first trimester (and there is no confirmation of a pitfall in later trimesters) or there is survey in animal that revealed the medication is safe in pregnant animal, but there is no fetal pitfall confirmation in pregnant women.Antiviral Pregnancy Registry (APR) revealed that as of January 2017, pregnancy outcomes and birth defects were analyzed from 142 pregnancies with reported exposure to DTG during pregnancy. There were 128 live births reported (3 terminations, 11 miscarriages, no stillbirths). Only 4 (3.0%) reported birth defects, which is similar to the expected rate of birth defects in the general population. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPIC) displayed that as of July 2017, 101 pregnancies with exposure to DTG had been identified with 84 birth outcomes. Rates of preterm delivery and “small for gestational age” were identical to outcomes reported from women on alternative regimens (standard of care in the United Kingdom of Great Britain and Northern Ireland).
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.
Oct 2021 DOI 10.14302/issn.2690-0904.ijoe-21-3966
Polyana Rocha Mendes MicheleCorresponding author
Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
The impact of the environment on the development of non-communicable chronic diseases has gained prominence in recent years. In this context, a new chemical exposure assessment strategy is needed that is capable of revealing multiple exposures, as well as reflecting the cumulative interaction between such environmental contaminants in the biological system. From this perspective, metabolomics emerges as a promising tool in this field of knowledge, since it is able to identify changes in metabolism and/or gene expression resulting from exposure to environmental factors. The aim of this study was to describe important concepts, as well as the steps that permeate the metabolomics analysis, and also to present some relevant works with the application of metabolomics in the assessment of chemical exposure. A literature review showed a significant increase in the use of metabolomics in environmental toxicology in recent years. This increase is mainly due to advances in analytical techniques and the improvement of data processing tools. However, this field of investigation remains little explored, especially with regard to the study of toxicity associated with chronic exposure to low levels of chemical agents. Thus, it is urgent that omic biomarkers can be used as a tool for decision-making, especially with a view to protecting, diagnosing and recovering human health.
Sep 2020 DOI 10.14302/issn.2576-6694.jbbs-20-3525
K. Srivastava RajeshCorresponding author
Department of Biotechnology, GITAM Institute of Technology, GITAM Deemed to be University, Gandhi Nagar Campus, Rushikonda, Visakhapatnam - 530045 (A.P.), India.
The photosynthetic potential and underlying internal metabolism of a plant are some of the most commonly affected physiological functions as a direct consequence of stresses due to salt and water resulting in hindering plant growth and productivity. Under the influence of such detrimental stresses, a drastic alteration in a plant's osmotic requirements, hormonal production, shedding of leaves, and closure of stomata, along with a lessening in the diffusion and transportation of CO2 and H2O are commonly seen. This review unfolds with a description of the basic methodology involved in the proteomic analysis of various proteins involved in stress response along with a brief idea on identifying and obtaining a genomic sequence for proteomic studies. It then dives deep into understanding the impact of abiotic stresses such as salinity, drought and high temperatures on cereal crops such as rice and sorghum as well as the internal dynamics of tolerance mechanism unfolding during stresses have also been described. Extensive literature describing the proteomic and physiological responses to primary and secondary effects of salt stress in cereal crops emphasizing on ROS production and apoptosis, the role of osmolytes as ROS scavengers during osmotic stress and vacuolar antiporters in ionic stress along with the responses during drought stress such as the accumulation of LEA proteins and ABA-based signaling has been reviewed and critically discussed. The study also sheds light on some experimental proteomic studies conducted on the seedlings, root tissues, and shoots of rice cultivars.
Mar 2020 DOI 10.14302/issn.2471-2140.jaa-20-3236
Sanikidze TamarCorresponding author
Tbilisi State Medical University, Tbilisi, Georgia
Objective Search of pathogenetic mechanisms and risk factors of atherosclerosis in the employees of the cleaning service in Tbilisi. Materials and Methods As a result of a preliminary survey and examination of 200 employes of Tbilisi cleaning service aged 25-45 years (2014-2016), 22 patients with angina, hypercholesterolemia, intimae-media thickness > 0.65 mm, were selected into I group, and 23 individuals without these disorders into II group. In the blood plasma of the selected patients the intensity of oxidative metabolism parameters, TAA and MDA were determined. The variance and correlation analysis (АNOVA) was used for conducting the comparative analysis of the levels of studied parameters. Results In the combined group (I+II) there are several reliable correlations between the Age -TCol, Age-MDA, BMI-Tg, BMI-MDA, LDLChol-HDLChol, LDLChol–TChol, HDLChol-TChol, LDLChol-MDA, LDLChol-TAA. no correlation between these parameters in individual groups (I and II) was found. That indicates that we have an imaginary correlation related to the large intergroup difference between the average values of the group indicators, that is the values of various indicators change during the development of the pathological process, but there is no causal relationship between these alterations. The reliable TAA-MDA correlation in the combined group (I+II) is related to the high anticorrelation between these parameters and the significantly higher average value of TAA in the low-risk group (II) in comparison to the high-risk group (I). Conclusion The results analysis indicates both the diagnostic value of redox status indicators and their leading role in the atherogenesis processes. In populations with a high risk of atherosclerosis, monitoring of serum TAA is recommended.
Jan 2020 DOI 10.14302/issn.2379-7835.ijn-20-3171
Ozcelik FatihCorresponding author
University of Health Sciences, Sultan 2. Abdulhamid Han Training and Research Hospital, Department of Medical Biochemistry, Istanbul, Turkey
Biogenic amines, which are responsible for the realization of many physiological conditions of our body, are compounds that can be produced by microorganisms especially in fermented foods with high protein content. They can have harmful effects on human health only when taken in high amounts with food. However, in individuals with impaired anti-toxic metabolism, which is responsible for detoxification, even lower amounts may cause toxic effects. The most common health effects are nausea, vomiting, severe headaches, hypotension, hypertension, tachycardia, various allergic reactions, abdominal pain and death in more severe cases. For these reasons, legislations on biogenic amines in foods have been established with some restrictions. Food producers have been asked to comply with these legislations. However, despite all precautions, biogenic amines in foods have not been completely removed. Further research is still needed to find effective solutions to prevent biogenic amine formation. In addition, consumers need to be made aware of this issue.
Sep 2019 DOI 10.14302/issn.2577-2279.ijha-19-3026
Awad Hegazy AbdelmonemCorresponding author
Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt
Background Hypothyroidism is a metabolic disorder affecting the functions of many tissues in the body including the testis. Testis is rich in the polyunsaturated fatty acids content and lacks strong intrinsic antioxidant system making it prone to such oxidative stress. L-carnitine (LC) regulates long chain fatty acids metabolism; and is considered a valuable antioxidant factor. Aim It was to evaluate the effect of hypothyroidism induced by propylthiouracil (PTU) on rats’ testes and the possible protective role of LC. Methods Forty-eight adult male albino rats were used in this work. The animals were divided into three groups with sixteen animals in each. Group 1 (Control): Animals were kept without medications. Group 2 (PTU-treated): was subjected to administration of PTU; while group 3 (PTU and LC) received both PTU and LC. By the end of the experiment “30 days”, blood samples were taken for hormonal assay; then animals were anaesthetized and sacrificed. Specimens were homogenized for biochemical analysis; epididymal content of each rat was obtained immediately for semen analysis. Testes’ specimens were harvested, prepared and examined by light microscope examination. Results Induced hypothyroidism was noticed to cause histopathological, morphometric and biochemical changes in rat’s testes. LC protected the testicular specimens against such changes; it also improved the seminal quality and quantity as well as testicular structure and biochemistry. Conclusion Hypothyroidism could result in hazards to the structure of testis. Fortunately co-administration of LC might reduce such hazards.
Jun 2019 DOI 10.14302/issn.2690-0904.ijoe-19-2792
Neuberger ManfredCorresponding author
Center of Public Health, Medical University of Vienna, Wien, Felbigergasse 3/2/18, Austria
In deaths and diseases attributed to tobacco smoke cardiovascular events exceed cancer and respiratory diseases. Second hand smoke promotes the development of arteriosclerosis and can trigger acute changes of endothelial function and blood coagulability. Indoor smoking bans reduced coronary syndrome and myocardial infarction 10-20% within one year and were followed by sustainable decreases of stroke and diabetes. With a smoke-free hospitality industry people recognized tobacco smoke as an air pollutant, smoking in public was denormalized and social acceptance of smoking in front of children and pregnant women decreased also in homes and cars. Combined effects with ambient air pollution are proven for active smoking and suspected for SHS. Contamination with third hand smoke (THS) persists for months in homes and cars, creating secondary pollutants that in some cases are more toxic (e.g. nitrosamines). Remnants found in air, dust, and on surfaces (carpets, wallpapers, upholstery, soft toys) were associated with their metabolites in saliva of children and in urine of nonsmokers residing in homes previously occupied by smokers. In animal experiments effects of THS were found on thrombogenesis, insulin resistance through oxidative stress, on the developing immune system, lipid metabolism and alterations in liver, lung, skin and behavior. Much less is known about health effects for bystanders from the aerosols exhaled during “vaping” of e-cigarettes, but nicotine and other toxins from e-cigarettes are certainly a hazard, which should be prevented by the use of dermal and oral nicotine products, which are safer for nicotine replacement and without risk for bystanders.
Jan 2019 DOI 10.14302/issn.2643-0282.imsj-18-2448
Santiago Freitas e Silva KleberCorresponding author
Biological Sciences Institute, Federal University of Goiás, Brazil
Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.
Nov 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2455
Habotta OlaCorresponding author
Education and Research Center for Marine Resources and Environment, Faculty of Fisheries, Kagoshima University, Japan.
In the current study, The GC-MS metabolomics approach was used to evaluate the effect of cypermethrin on the metabolic profile in liver tissue of common carp fish. Fish were exposed to low and high concentrations of cypermethrin (0.1 and 1 µg/L respectively) for 24 and 96 h with subsequent PCA analysis to illustrate the response of the metabolic system after exposure to the pyrethroid. Cypermethrin induced obvious alteration in the intermediates of TCA cycle and encouraged consumption of non-carbohydrate sources in liver at all-time points. Additionally, cypermethrin exposure reduced the level of several amino acids and induced damage to the nucleotides reflecting the effect of cypermethrin on purine metabolism. GC-MS based metabolomics approach is a new and powerful tool to understand the toxicological effects and the underlying mechanism of cypermethrin on fish.
Sep 2018 DOI 10.14302/issn.2377-2549.jndc-18-2315
Jana SnehasisCorresponding author
Trivedi Science Research Laboratory Pvt. Ltd.,Bhopal, India
Selenium is an essential micronutrient required for healthy metabolism, as well as prevention, and treatment of selenium deficiency diseases. The experiment aimed to evaluate the influence of the Trivedi Effect®-Consciousness Energy Healing Treatment on the physicochemical and thermal properties of selenium using modern analytical techniques. The selenium sample was divided into two parts, one part of the test sample was called the control sample, while the second part of the test sample received the Biofield Treatment remotely by a renowned Biofield Energy Healer, Gopal Nayak, and was called the treated sample. The particle size values were significantly decreased by 37.69% (d10), 14.36% (d50), 4.31% (d90), and 11.58% D(43), hence, the specific surface area was significantly increased by 33.64% in the treated sample compared to the control sample. The PXRD peak intensities and crystallite sizes were significantly altered ranging from 5.23% to 100% and 75% to 111.7%, respectively; whereas 7.81% significantly decreased the average crystallite size in the treated sample than the control sample. The latent heat of fusion of the treated sample was significantly increased by 12.37% compared with the control sample.The results suggested that the Trivedi Effect® might generate a new polymorphic form of selenium which would offer better solubility, bioavailability and be thermally more stable compared with the control sample. The Biofield Treated selenium would be more useful to design novel nutraceutical/pharmaceutical formulations and might offer an enhanced therapeutic response against cardiovascular disease, cancer, neuromuscular disorders, diabetes, stress, aging, male infertility, viral diseases, degenerative ailments, etc.
Nov 2017 DOI 10.14302/issn.2576-9383.jhhr-17-1816
Abu Syed Md. MosaddekCorresponding author
Background: Disorders of lipid metabolism are manifested by elevation of the plasma concentration of the various lipid and lipoprotein fractions and the result, predominantly cardiovascular diseases. Lipid research clinic’s coronary primary prevention trial has provided useful information on the reduction of plasma cholesterol level in hyperlipidemic subjects by diet and drug therapy and thus the reduction in risk of myocardial infarction and death. Conventional lipid lowering drugs are used for lowering lipid level. But in the last few years’ herbal drugs are gaining popularity in the management of hyperlipidemia. In this study we compare the hypolipidemic effect of MomordicaCharantia (MC) with atorvastatin, a commonly used hypolipidemic drug. Methods: The present experimental study was done in the pharmacology department of Dhaka Medical College during the period of July, 2011 to June, 2012. For this study a total number of 30 Norwegian rats of either sex were selected. They were divided into 5 groups each comprises of 6 rats. In the experiment group A was given normal diet with high fatty diet (1.5 ml olive oil plus 1% cholesterol) which was control group and other experimental groups (B,C,D,) were allowed to feed a high fatty diet along with fresh juice of MomordicaCharantia (in different doses) for 10 days. Another experimental group, E was given high fatty diet along with atorvastatin (0.14mg/kg/day) for 10 days. Rats were sacrificed on 11th day and blood was collected by cardiac puncture for estimation of serum lipid profile. Results: After administration of fatty diet in group A for 10 days, there was significant increased total cholesterol (TCL), low density lipoprotein (LDL) and triglyceride (TG) levels. Concomitant administration of fatty diet and fresh juice of MC (in different doses) daily for 10 days in group B,C,D reduced serum TCL, LDL and TG levels which was more significant in higher doses in comparison to atorvastatin given group E. Conclusion: The present study provides a rationale for use a new herbal medicine much needed for the reduction of serum lipid levels.MomordicaCharantia could be useful in hyperlipidemic conditions. They are as effective as a standard lipid lowering agent- atorvastatin.
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.
Jul 2017 DOI 10.14302/issn.2639-1716.jn-17-1495
J Gonzalez MichaelCorresponding author
University of Puerto Rico Medical Sciences Campus, Schools of Public Health and Pharmacy, San Juan PR.
Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic processes, via an effect on tumor cell proliferation or tumor cell loss, has not been clearly established. In the studies described in this communication, three methods were utilized to study tumor cell proliferation, i.e., H3-thymidine autoradiographic analysis, 5-bromo 2'-deoxyuridine (Brdu) flow cytometric analysis, and proliferative cell nuclear antigen (PCNA) flow cytometric analysis. Two methods were used to study tumor cell loss, i.e., a determination of the I125Urd tumor emission rate and a determination of a cell loss factor from the formulas of Steel and Begg. The tumor examined was the human breast carcinoma cell line MDA- MB231 maintained in athymic nude mouse. No significant difference in cell proliferation between carcinomas of mice fed a high corn oil diet (20% w/w) and a diet high in fish oil (19% menhaden oil, 1% corn oil). In contrast, a significant (p<0.05) increase in the rate of I125Urd emission rate and cell loss factor from the carcinomas in the fish oil fed mice compared to the corn oil fed mice was observed. In summary, the decreased tumor volume in the human breast carcinomas maintained in athymic nude mice fed a fish oil diet as compared to those fed a corn oil diet, appears to be due, at least in part, to an increased rate of carcinoma cell loss rather than a decreased rate of carcinoma cell proliferation.
Jul 2017 DOI 10.14302/issn.2379-7835.ijn-17-1636
R. Holt PeterCorresponding author
The Rockefeller University
Adipose tissue inflammation is associated with obesity comorbidities. Reducing such inflammation may ameliorate these comorbidities. n-3 fatty acids have been reported to have anti-inflammatory properties in obesity, which may modulate this inflammatory state. In the current study a 1 gram per day oral supplement of the n-3 fatty acid docosahexaenoic acid (DHA) was administered for 12 weeks to 10 grade 12 obese postmenopausal women and markers of adipose tissue and systemic inflammation measured and compared before and after supplementation. DHA administration resulted in approximately a doubling of plasma and red cell phospholipid and adipose tissue DHA content but no change in systemic markers of inflammation, such as circulating C-reactive protein (CRP) or interleukins (IL) 6, 8 and 10 (IL-6, IL-8, IL-10). DHA supplementation did not alter the adipose tissue marker of inflammation crown-like structure density nor did it affect any gene expression pathways, including anti-inflammatory, hypoxic and lipid metabolism pathways. The obese postmenopausal women studied were otherwise healthy, which leads us to suggest that in such women DHA supplementation is not an effective means for reducing adipose tissue or systemic inflammation. Further testing is warranted to determine if n-3 fatty acids may ameliorate inflammation in other, perhaps less healthy, populations of obese individuals.
Apr 2017 DOI 10.14302/issn.2572-5424.jgm-17-1482
H Baslow MorrisCorresponding author
Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research
Canavan disease (CD) is a globally occurring but rare human spongiform leukodystrophy that is associated with inborn errors affecting the activity of aspartoacylase (ASPA), an enzyme highly expressed in oligodendrocytes that hydrolyzes N-acetylaspartate (NAA). Lack of ASPA activity is associated with the inability of oligodendrocytes to build or maintain axon-enveloping myelin sheaths. The primary source of NAA in brain is neurons, cells that synthesize but cannot catabolize it. Neurons also synthesize N-acetylaspartylglutamate (NAAG) from NAA and glutamate but cannot catabolize this substance as well. For their metabolism, these substances are released to extracellular fluid and are metabolized by oligodendrocyte ASPA and astrocyte NAAG peptidase respectively. A hypothesis developed suggested that the cause of the leukodystrophy component in CD was due to release of NAAG by neurons at white matter nodes of Ranvier, its catabolism by astrocytes forming NAA and increased osmotic-hydrostatic pressure as a result of its buildup at these nodes due to the lack of ASPA activity. In this communication, we provide evidence supporting this hypothesis and comment on the cause and possible cure for human CD.
Aug 2016 DOI 10.14302/issn.2474-7785.jarh-16-1157
Arlappa NimmathotaCorresponding author
Division of Community Studies, National Institute of Nutrition (NIN), Hyderabad, Telangana, India.
Objectives: World has witnessed a considerable increase in the proportion of elderly population.Aging is associated with decreased physical activity and metabolism and thereby the changes in the nutritional requirements of older adults.The objective of this communication was to assess the nutritional status of rural elderly population in India. Methodology: A community based cross-sectional study; adopting multistage stratified random sampling procedure was carried out by the National Nutrition Monitoring Bureau (NNMB), during 2005-06 among the rural population of nine major states of India. A total of 3871 older adults were covered for anthropometry and of them, a total of 2138 older adults were covered for dietary assessment. Key Results: In general, the consumption of all the foods was below recommended daily intakes (RDI), and the in-adequacy (<70% of RDI) of intake was high with respect to leafy vegetables, milk & milk products, fats & oils and sugar & jaggery. Similarly, the in-adequacy of intakes of micronutrients such as vitamin A, iron, riboflavin and free folic acid was high among both genders. The poor intake of diet was reflected in high prevalence of chronic energy deficiency (CED) among the rural elderly in India. Conclusions: In general,the rural elderly were subsisting on inadequate diets in terms of both quantity and quality. Similarly, the prevalence of CED among elderly is a ‘‘very high’’ public health nutrition problem in India. Therefore, the Government of India should initiate appropriate nutrition intervention measures to improve the overall nutritional status and special nutrition policies to address the health and nutritional problems of the aging population.
Jul 2016 DOI 10.14302/issn.2572-5424.jgm-16-1066
Harrison SanjayCorresponding author
Northern Deanery, UK
Lactic acidosis is a condition commonly encountered in the hospital setting particularly in critically ill patients and is very often used as a diagnostic adjunct when encountering cases of ischaemia or other hypoperfusion states. Despite its use many clinicians have long forgotten the biochemical mechanisms that give rise to hyperlactataemia. One reason for this is because the basic science regarding lactate metabolism is taught in the early years of the medical undergraduate course, and unless one specialises in metabolic medicine, is unlikely to encounter it again. In this article we aim to elucidate the basic mechanisms of lactate metabolism and the accompanying acidosis, and illustrate various clinical settings that give rise to this biochemical abnormality.
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.
Feb 2016 DOI 10.14302/issn.2372-6601.jhor-15-896
Zaichick VladimirCorresponding author
Radionuclide Diagnostics Department, Medical Radiological Research Centre, Obninsk 249036, Russia.
Objectives: Adenocarcinoma of prostate is an internationally important health problem of the man, particularly in developed countries. The aim of this exploratory study was to evaluate whether significantchanges in the prostatic tissue levels of calcium (Ca), potassium (K), and magnesium (Mg) as an androgen dependent chemical element, and bromine (Br), manganese (Mn), and sodium (Na), as androgen independent elements, exist in the malignantly transformed prostate. Methodology: Prostatic tissue levels of Br, Ca, K, Mg, Mn, and Na contents were prospectively evaluated in 10 patients with adenocarcinoma and 37 healthy male inhabitants. Measurements were performed using non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for chemical element analysis. The reliability of difference in the results between normal and cancerous prostate tissues was evaluated by Student’s t-test. Key Results: Mean values ± standard error of means (M±SΕΜ) for mass fraction (mg/kg on dry mass basis) of chemical element in the normal tissue were:Br32.9±3.6, Ca 2280±178, K 11211±414, Mg 1118±76, Mn 1.24±0.07, and Na 11100±408, respectively. The contents of Br and Mn were significantly higher (approximately 4 and 6 times, respectively) while those of Ca and Mg (nearly 3 times) and K and Na (20% and 30%, respectively) were significantly lower in cancerous tissues than in normal tissues. Major Conclusions: In adenocarcinoma transformed prostate tissue the chemical element metabolism is significantly disturbed.
Jun 2015 DOI 10.14302/issn.2379-7835.ijn-14-479
Erdmann JohannesCorresponding author
Department of Nutritional Medicine, University of Applied Sciences Weihenstephan-Triesdorf, Weidenbach, Germany
Objective: Detailed reports in changes of eating habits especially in elderly subjects with successful weight loss and maintenance are virtually unknown. In this paper we have analyzed the eating habits of 104 obese patients (BMI 37.8±0.3 kg/m2, age range 65 and 84 years) who lost 11.5±0.3kg over an average follow-up period of 37.5±0.5 months. Design: Patients recorded food intake over a period of 12 days before and 12 days after changes of eating habits. Dietary counseling was based on food energy density (ED) with the aim to maintain food quantity as much as possible for adequate satiety in conjunction with a reduction of energy intake. Individual eating habits should be preserved as much as possible. Results: Average daily energy intake of solid food was reduced by 267kcal, food intake by 114g and ED by 0.10 kcal/g, respectively. Liquid calories were reduced by 79 kcal/d. Lower daily energy intake was the result of a reduction of medium and high ED food items compensated for by a greater intake of low ED food items. Changes of macronutrients comprised substantially lower carbohydrate and fat intake with minimal reduction of protein. From 28 different food groups 9 were reduced significantly (bread, butter, marmalade, cheese, meat products, fast food, fruit and chocolate) while 3 were increased (eggs, curds, ham). The relative contributions of the various food groups to daily energy intake remained fairly similar indicating that individual preferences were largely maintained. Conclusion: The data demonstrates that in elderly subjects with severe obesity an individual change of eating habits can lead to successful long-term weight loss with improvement of carbohydrate metabolism. This will contribute to increased mobility and to improved quality of life. This method which is based on the energy density of food items is a simple measure to reduce energy intake while ensuring long-term adherence.
Mar 2014 DOI 10.14302/issn.2372-6601.jhor-13-362
A. Vlahopoulos SpirosCorresponding author
Horemio Research Institute, First Department of Pediatrics, University of Athens Medical School, “Aghia Sophia” Children’s Hospital, Athens, Greece
A narrative review summarizes how fenofibrate influences cancer cell metabolism and proliferation. It reviews PPAR‑α–dependent and independent mechanisms, context‑specific effects, and implications for repurposing studies.
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.
Dec 2012 DOI 10.14302/issn.2326-0793.jpgr-12-100
Li ShitaoCorresponding author
Department of Microbiology & Immunobiology, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Defining protein-protein interactions is essential for understanding the mechanisms by which cells regulate basic functions, such as metabolism, transcription, and signal transduction. Affinity purification followed by tandem mass spectrometry (AP-MS) has application for discovery of new interactors regulating various cellular processes. Here we optimize the purification method for AP-MS and develop a simplified unbiased analytical tool, Z-score plus prey occurrence and reproducibility (ZSPORE) for data analysis. Using this pipeline we achieve a higher efficiency of AP-MS and enhanced identification of high confidence interacting proteins (HCIP) in mammalian cells. When applied to analysis of the innate immune interactome, these methods enhanced HCIP identification. In addition, we investigated the GRB2 complex, which is associated with signal transduction and cell growth. Twenty-four known GRB2 interacting proteins were identified plus 26 new GRB2 binding partners. Thus, these straightforward methods recapitulate known protein interactions, discover novel complexes, and allow mapping of protein interaction networks.