Association Between PGC-1Alpha Gene Polymorphisms and Type 2 Diabetes Risk: A Case-Control Study of an Iranian Population

Objective: The peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1 alpha) gene could play a role in the onset of type 2 diabetes mellitus. The aim of this study was to explore the possible associations among polymorphisms Gly482Ser, Thr394Thr and Thr528Thr of the PGC-1 alpha gene and the risk of type 2 diabetes in Kurdish-Iranians. Methods: DNA specimens from all 173 type 2 diabetes subjects and 173 normoglycemic subjects were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. Genotypic and allelic frequencies were analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostasis model assessment of insulin resistance and glycated hemoglobin levels were determined using the conventional methods. The data were analyzed using SPSS software. Results: The GA genotype of Gly482Ser was associated with a significant susceptibility for type 2 diabetes (odds ratio 5.23, p<0.000). Furthermore, the GA genotype of Thr528Thr had a higher risk for type 2 diabetes (odds ratio 2.37, p<0.002). Normoglycemic persons carrying the GA+AA genotypes of Gly482Ser variation had significantly lower high-density lipoprotein cholesterol in comparison with persons having GG genotype. In comparison with GG genotype carriers, normoglycemic subjects carrying the GA+AA genotypes of Thr394Thr variation had significantly higher fasting blood sugar, fasting serum insulin and homeostasis model assessment of insulin resistance. Normoglycemic subjects with the GA+AA genotypes of Thr528Thr variation had significantly higher levels of low-density lipoprotein cholesterol compared with subjects having the GG genotype. Type 2 diabetes subjects carrying the GA+AA genotypes of this polymorphism had significantly higher waist-hip ratio in comparison with the GG genotype carriers. We also found that haplotype 394-GG/482-GA/528-GG of PGC-1 alpha was significantly associated with higher risk of type 2 diabetes. Conclusions: Our findings revealed significant associations between PGC-1alpha Gly482Ser and Thr528Thr polymorphisms and type 2 diabetes in Kurdish-Iranians. (C) 2015 Canadian Diabetes Associatio

Cyperus spp.: A Review on Phytochemical Composition, Biological Activity, and Health-Promoting Effects

Cyperaceae are a plant family of grass-like monocots, comprising 5600 species with a cosmopolitan distribution in temperate and tropical regions. Phytochemically, Cyperus is one of the most promising health supplementing genera of the Cyperaceae family, housing ˜950 species, with Cyperus rotundus L. being the most reported species in pharmacological studies. The traditional uses of Cyperus spp. have been reported against various diseases, viz., gastrointestinal and respiratory affections, blood disorders, menstrual irregularities, and inflammatory diseases. Cyperus spp. are known to contain a plethora of bioactive compounds such as a-cyperone, a-corymbolol, a-pinene, caryophyllene oxide, cyperotundone, germacrene D, mustakone, and zierone, which impart pharmacological properties to its extract. Therefore, Cyperus sp. extracts were preclinically studied and reported to possess antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, antidepressive, antiarthritic, antiobesity, vasodilator, spasmolytic, bronchodilator, and estrogenic biofunctionalities. Nonetheless, conclusive evidence is still sparse regarding its clinical applications on human diseases. Further studies focused on toxicity data and risk assessment are needed to elucidate its safe and effective application. Moreover, detailed structure-activity studies also need time to explore the candidature of Cyperus-derived phytochemicals as upcoming drugs in pharmaceuticals.NM acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

National guidelines for cognitive assessment and rehabilitation of Iranian traumatic brain injury patients

Background: Individuals with moderate to severe traumatic brain injury (TBI) often have prolonged cognitive impairments, resulting in long-term problems with their real-life activities. Given the urgent need for evidence-based recommendations for neuropsychological management of Iranian TBI patients, the current work aimed to adapt eligible international guidelines for cognitive assessment and rehabilitation of the TBI patients in Iran. Methods: The project was led by an executive committee, under the supervision of the Iranian Ministry of Health and Medical Education (MOHME). Following a systematic literature search and selection process, four guidelines were included for adaptation. Clinical recommendations of the source guidelines were tabulated as possible clinical scenarios for 90 PICO clinical questions covering all relevant phases of care. After summing up the scenarios, our initial list of recommendations was drafted according to the Iranian patients� conditions. The final decision-making, with the contribution of a national interdisciplinary panel of 37 experts from across the country, was conducted in two rounds using online and offline survey forms (Round 1), and face-to-face and telephone meetings (Round 2). Results: A total of 63 recommendations in six sections were included in the final list of recommendations, among which 24 were considered as key recommendations. In addition, some of the recommendations were identified as fundamental, meaning that proper implementation of the other recommendations is largely dependent on their implementation. Conclusion: Iranian health policy makers and rehabilitation program managers are recommended to address some fundamental issues to provide the necessary infrastructure to set up an efficient cognitive rehabilitation service system. © 2020 Academy of Medical Sciences of I.R. Iran. All rights reserved

Alterations in Plasma Glucose and Cardiac Antioxidant Enzymes Activity in Streptozotocin-Induced Diabetic Rats: Effects of Trigonella foenum-graecum Extract and Swimming Training

Objectives: Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia. Trigonella Tomlin-gamin( (fenugreek) and swimming training have previously been reported to have hypoglycemic and antioxidant effects. We aimed to evaluate the effects of swimming training and fenugreek aqueous extract, alone and in combination, on plasma glucose and cardiac antioxidant enzymes activity of streptozotocin-induced diabetes in rats. Methods: We divided 70 male Wistar rats equally into 7 groups: diabetic control (DC), healthy control (FIC), swimming (5), fenugreek seed extract (1.74 g/kg) (Fl), fenugreek seed extract (0.87 g/kg) (F2), swimming + fenugreek seed extract (1.74 glkg) (5F1), and swimming+ fenugreek seed extract (0.87 glkg) (SF2). We used streptozotocin for the induction of diabetes. Statistical analyses were performed using the statistical program SPSS. Results: We did not detect any significant differences in body weight in the Fl, F2, S, SF1 and SF2 groups compared with the DC group (p>0.05). The results also revealed that the hypoglycemic effect of combined swimming and fenugreek was significantly stronger (p<0.05) than either of those alone. The Fl, 5, SF1 and SF2 groups showed improved superoxide dismutase activity with respect to the DC group (p<0.05). Catalase activity in the Fl, S, SF1 and SF2 groups were significantly higher than those of the DC group (p<0.05). Glutathione peroxidase activity in the S, SF1 and SF2 groups were significantly increased corn pared with the DC group (p<0.05). Conclusions: Our findings suggest that the combination of fenugreek seed extract and swimming could be useful for the treatment of hyperglycemia and cardiac oxidative stress induced by type 1 diabetes mellitus. (C) 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved

Do genetic factors predispose people to COVID-19: A review article

The pandemic of coronavirus disease 2019 (COVID-19) has become a threat to human life and society. Scientists and clinicians are struggling with the intrusive SARS-CoV-2 virus to enhance their knowledge about its pathogenesis and find an effective medicine and vaccine to combat its complications. Till now, they have learned that this SARS-CoV-2 has not infected all people exposed to this virus, and also severe respiratory illnesses have not been observed in all infected patients. Patients over 65 or with underlying diseases are more vulnerable to develop severe disease. Based on this premise, a high challengeable question is why some people are more susceptible to this virus and others are not. The present study was aimed to reviewthe current information which explains the broad spectrum of COVID-19 presentation.Herewe discussed that how genetic background, immune system, underlying disease, smokingstatus as well as age, race, and gender affect COVID-19 susceptibility

Effects of aGVHD and cGVHD according to relapse status on survival rate in patients with acute lymphocytic leukemia

Objectives: Graft-versus-host disease (GVHD) is an exaggerated and dysregulated response of the normal immune system to tissue damage that is intrinsic to transplantation. The aim of this study was to assess the effects of acute GVHD (aGVHD) and chronic GVHD (cGVHD) according to relapse status on the survival rate in patients with acute lymphocytic leukemia (ALL). Methods: Patients with ALL (n = 425) between 1991 and 2011, who underwent bone marrow transplantation and stem cell transplantation in Tehran (Iran), were recruited into a longitudinal study. All patient records were screened for the occurrence of adverse events including GVHD and relapse. Data were assessed using SPSS software with log-rank, univariate, and multivariate Cox regression analyses. Results: Five-year survival rate based on a Kaplan-Meier curve was 60.2 overall (95 confidence interval (CI): 54.32-66.08) and 66.6 (95 CI: 59.35-73.86) for individuals in their first complete remission (CR1) disease stage. A significantly higher survival rate was observed for patients who developed cGVHD in comparison with those who did not develop it, with a 2.7 fold increased risk of mortality for the latter group (P < 0.001). A significant Cox proportional hazard ratio of 2.3 was observed for mortality following adjustments for age and gender. The presence of cGVHD, reduced the risk of mortality for all individuals, which was observed to be significant for those patients without relapse (P = 0.004). Conclusion: This study is one of the largest studies (regarding the number of participants) done to date in the Middle East with quite a long duration (20 years). Findings suggest that cGVHD has a positive influence on the survival rates for ALL patients, which subsequently may assist physicians to make optimal treatment decisions. Additional research is now needed to determine the mechanisms around this increased survival and its influence on patients' survival

siRNA therapeutics in the treatment of diseases

siRNAs are a class of dsRNAs, 21-23 nucleotides in length, which are able to silence their target genes through enzymatic cleavage of target mRNA. The sequence-specific gene-silencing by siRNA can be used as a new therapeutic approach for treatment of a variety of diseases that are incurable by conventional drugs. Many efforts have been made to overcome the problems related to delivery, stability, off-target gene silencing and immunostimulatory effects of siRNA. Different studies have carried out done to improve in vitro and in vivo delivery of naked or formulated siRNAs. In this review, different aspects of using siRNA as a new class of drugs will be discussed

The Study on the Relationship Between IRS-1 Gly972Arg and IRS-2 Gly1057Asp Polymorphisms and Type 2 Diabetes in the Kurdish Ethnic Group in West Iran

An association between the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms and type 2 diabetes mellitus (T2DM) in different ethnic groups is controversial. We aimed to identify the association of these polymorphisms with T2DM in the Kurdish ethnic group of Iran. Study groups included 336 T2DM and 341 normoglycemic subjects. Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotypic and allelic frequencies were then evaluated. GR and RR genotypes of IRS-1 Gly972Arg variant gave a higher risk for T2DM (odds ratios OR = 1.76 and OR = 3.86, respectively). IRS-1 Gly972Arg polymorphism was found to be significantly associated with T2DM (OR = 1.63) for the dominant model (GG vs. GR + RR). GD genotypes of the IRS-2 Gly1057Asp variant gave a higher risk for T2DM (OR = 1.63). The dominant model analysis of the IRS-2 Gly1057Asp genotypes (GG vs. GD + DD) also showed an enhanced association with T2DM (OR = 1.69). Among several combinations, GR/GD gave the highest risk for T2DM (OR = 3.1). Other combinations were also significantly associated with T2DM, including, GR/GG (OR = 1.86), RR/GG (OR = 1.76), GG/GD (OR = 1.83), and GG/DD (OR = 2.35). HbA1c, serum triglyceride, and systolic blood pressure were higher in the control subjects with GR + RR genotypes compared with the GG genotype. Among the T2DM subjects, fasting plasma glucose was significantly lower in subjects with the GG genotype in relation to those with the GR + RR genotypes. Normoglycemic subjects carrying GD + DD genotypes of IRS-2 Gly1057Asp variation had a significantly higher fasting plasma glucose and total cholesterol, as compared with those with the GG genotype. Our findings revealed that IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms are associated with T2DM in the Kurdish ethnic group

TNF-alpha knockdown alleviates palmitate-induced insulin resistance inC2C12 skeletal muscle cells

Insulin resistance is a cardinal feature of Type 2 Diabetes (T2D), which accompanied by lipid accumulation and TNF-alpha overexpression in skeletal muscle. The role of TNF-alpha in palmitate-induced insulin resistance remained to be elucidated. Here, we assessed effects of TNF-alpha knockdown on the components of insulin signaling pathway (IRS-1 and Akt) in palmitate-induced insulin resistant C2C12 skeletal muscle cells. To reduce TNF-a expression, C2C12 cells were transduced with TNF-alpha-shRNA lentiviral particles. Afterwards, the protein expression of TNF-alpha, IRS-1, and Akt, as well as phosphorylation levels of IRS-1 and Akt were evaluated by western blot. We also measured insulin-stimulated glucose uptake in the presence and absence of palmitate. TNF-alpha protein expression in C2C12 cells significantly increased by treatment with 0.75 mM palmitate (P 0.05). Furthermore, palmitate significantly reduced insulin-dependent glucose uptake in control cells, however, it was not able to reduce insulin-stimulated glucose uptake in TNF-alpha knockdown cells in comparison with the untreated control cells (P < 0.01). These findings indicated that TNF-alpha down-regulation maintains insulin sensitivity, even in the presence of palmitate, therefore, TNF-alpha inhibition could be a good strategy for the treatment of palmitate-induced insulin resistance. (C) 2015 Elsevier Inc. All rights reserved

Shared Pathological Mechanisms Between Diabetes Mellitus and Neurodegenerative Diseases

Neurodegeneration is a term for the description of the progressive neuronal and neural structure loss, function, and their populations in the central nervous system (CNS). Recent studies have shed light on shared pathological mechanisms including inflammation, mitochondrial dysfunction, and oxidative stress between diabetes mellitus (DM) and neurodegenerative disorders. The association between these age-related chronic diseases has attracted immense attention during the past decade. Because shared mechanisms may underlie the co-occurrence of DM and neurodegeneration, deep understanding about the potential links between these conditions may be helpful for a better management of both diseases. In the present review, we attempt to provide an overview on the relationship pathways between DM and chronic neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). © 2019, Springer Nature Switzerland AG