A molecular and computational study of galbanic acid as a regulator of Sirtuin1 pathway in inhibiting lipid accumulation in HepG2 cells.

INTRODUCTION: Sirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro. METHODS: HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns. RESULTS: The semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar. CONCLUSION: Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells.

Predictive value of body mass index (BMI) and determination of optimum cut-off point in the diagnosis of endometrial hyperplasia in pre-menopausal women with abnormal uterine bleeding.

Background: The suitable BMI cut-off point in persons with endometrial cancer or hyperplasia with abnormal uterine bleeding was investigated in this study. Methods: This case-control research was conducted on 1470 women with abnormal uterine bleeding in Ayatollah Rouhani Hospital,Babol between 2010 and 2012, with 312 participants included in the study. In terms of uterine biopsy results, patients were split into six groups: simple hyperplasia without atypia, simple hyperplasia with atypia, complicated hyperplasia with atypia, complex hyperplasia without atypia, endometrial cancer, and normal persons. Results: The mean age and BMI of patients in these three groups were not significantly different (P equal to 0.081 and 0.435, respectively). The kind of disease exhibited a strong relationship with menstruation (P 0.001). The body mass index (BMI) values ​​did not have significant levels under the curve to determine the appropriate cut-off point in the diagnosis of hyperplasia plus endometrial cancer and endometrial cancer alone (P 0.380 and 0.124, respectively) and hyperplasia alone (P = 0.920). Based on logistic regression, age 50 years and older and irregular menstruation were significant with OR equal to 2.36 and 2.09 (P = 0.011) and HTN with OR equal to 0.44 (P = 0.026), respectively. Conclusion: BMI has little predictive value in the detection of endometrial cancer or hyperplasia, according to the findings, and other diagnostic and screening modalities should be utilized instead. The findings backed up the theory that old age and irregular menstruation are linked to an increased risk of endometrial cancer.

Association of S19W polymorphism in APOA5 gene and serum lipid levels in patients with type 2 diabetic nephropathy.

OBJECTIVES: Type 2 diabetic Mellitus (T2DM) is the most common systemic and endocrine disease in humans, and diabetic nephropathy is one of the most serious complications of this disorder. The polymorphisms in the apolipoprotein A5 (ApoA5) gene are strongly related to hypertriglyceridemia and are considered a predisposing factor for diabetic nephropathy. The current study proposed to examine the association of APOA5-S19W polymorphism with serum lipids levels in patients with type 2 diabetic nephropathy in Mazandaran province. METHODS: This case-control study was designed to determine the association of APOA5-S19W polymorphism with plasma lipid profile in 161 T2DM patients with nephropathy (DN+), without nephropathy (DN-), and in 58 healthy individuals. Lipid profile values were measured using Pars Azmoun commercial kits. S19W variant, one of the polymorphisms of the APOA5 gene, was determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and Taq1 restriction enzyme. RESULTS: In comparison between the three groups, DN+ had a higher mean TG than DN- and the control group (p<0.001). The incidence of the G allele in DN+ was not significant compared to groups of DN-. Comparing the relationship between the mean of biochemical variables with CC and CG genotypes showed that the mean level of TG in people with CC genotype was increased compared to people with CG genotype in diabetic patients. However, this increase was not significant (p=0.19). CONCLUSIONS: There was no association between SNP APOA5 S19W and serum lipids in diabetic patients with and without nephropathy.

The benefits of Vitamin D in the COVID-19 pandemic: biochemical and immunological mechanisms.

In December 2019, a new infectious complication called CoronaVirus Infectious Disease-19, briefly COVID-19, caused by SARS-COV-2, is identified in Wuhan, China. It spread all over the world and became a pandemic. In many individuals who had suffered SARS-COV-2 infection, cytokine storm starts through cytokine overproduction and leads to Acute Respiratory Syndrome (ARS), organ failure, and death. According to the obtained evidence, Vitamin D (VitD) enhances the ACE2/Ang(1-7)/MasR pathway activity, and it also reduces cytokine storms and the ARS risk. Therefore, VitD intake may be beneficial for patients with SARS-COV-2 infection exposed to cytokine storm but do not suffer hypotension. In the present review, we have explained the effects of VitD on the renin-angiotensin system (RAS) function and angiotensin-converting enzyme2 (ACE2) expression. Furthermore, we have reviewed the biochemical and immunological effects of VitD on immune function in the underlying diseases and its role in the COVID-19 pandemic.

Serum calprotectin can indicate current and future severity of COVID-19.

BACKGROUND: Predictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID-19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID-19. METHODS: This two-center prospective study focused on PCR-proven COVID-19 patients (n = 76) with different clinical presentations and SARS-CoV-2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL-6 and other laboratory parameters. RESULTS: Median levels of SC were significantly higher in COVID-19 patients in comparison to the control group (3760 vs. 2100 ng/ml, p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases, p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared. CONCLUSION: Calprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID-19 patients.

Investigation of Zinc Supplement Impact on the Serum Biochemical Parameters in Pulmonary Tuberculosis: A Double Blinded Placebo Control Trial.

BACKGROUND: Zinc (Zn) is nutritionally essential trace element, and thus deficiency may severely affect human health. The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. Our goal is to investigate whether Zn supplementation can increase the effects of anti-TB treatment or not. METHODS: Patients with newly diagnosed tuberculosis were divided in to 2 groups. One group (n= 37) received capsule contains 50 mg of elemental zinc (as zinc sulfate) for 6 months every other day (micronutrient group) and Group II (n= 37) received placebo. Both groups received the same anti-tuberculosis treatment recommended by the WHO. Clinical examination, BMI, chest X-ray, direct sputum examination, assessment of serum zinc levels (by atomic absorption spectrophotometry), and biochemical markers serum concentration (by using an RA1000 AutoAnalyzer) were carried out before and after 2- and 6-months anti-tuberculosis treatment. RESULTS: Plasma zinc concentrations in the micronutrient group was higher than placebo group After treatment. In the placebo group increasing in SGOT and SGPT concentrations were significantly higher than micronutrient group after 2 months of treatment (p< 0.05). The significant changes (p< 0.05) were observed on the serum levels of total protein, albumin. Alkaline phosphatase (ALP) levels, serum creatinine, uric acid and urea in groups were not significantly different. CONCLUSION: Zinc supplementation results in earlier sputum smear conversion in the micronutrient group during the first 6 weeks. Increased body weight and serum zinc and serum albumin and decrease in total protein was observed in the micronutrient group.

The Association between Serum Oxidative Stress Indexes and Pathogenesis of Parkinson's Disease in the Northwest of Iran.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder. Oxidative stress is a main modulator in the advancement of PD. This investigation aimed to evaluate the relations between serum trace elements, vitamin C, ferritin, transferrin, Nitrite Oxide (NOx) and Peroxynitrite (PrN) concentrations and clinical parameters in patients with PD. METHODS: Serum concentrations of variables were measured in 75 PD patients and 75 healthy subjects from Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran between Feb 2016 and Sep 2018. Receiver Operating Characteristic (ROC) analysis was performed to examine incremental diagnostic value of vitamin C, NOx, and PrN in the study groups. RESULTS: Mean serum NOx (35.81±5.16 vs. 11.27±3.59 mol/L, P<0.001) and PrN (15.78±4.23 vs. 9.62±4.57 mol/L, P= 0.004) were markedly higher in patient group versus healthy individuals. Significant differences were also observed in the serum levels of vitamin C (P<0.001), copper (Cu) (P<0.001), Iron (Fe) (P=0.003), and Zinc (Zn) (P<0.001) between patients with PD and healthy subjects. Nevertheless, the serum levels of Se (P=0.515), ferritin (P=0.103), and transferrin (P=0.372) were not statistically significant between the study groups. ROC analysis has revealed a diagnostic ability of serum vitamin C levels for PD with an area under ROC curve of ≥0.7 (P<0.05) and relatively high sensitivity and specificity. CONCLUSION: Serum levels of NOx and PrN are significantly higher in patients with PD. In additions, serum vitamin C levels have a diagnostic value as a biomarker. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures.

Serum lipid profile of Parkinson's disease patients: A study from the Northwest of Iran.

BACKGROUND: Parkinson's disease (PD) is defined as a long-lasting, neurological illness. Low levels of serum lipid fractions are related with a high risk of PD. Current investigation was designed to evaluate the concentration blood lipid fractions in patients suffering from PD and compared with healthy subjects. METHODS: This case-control study was conducted from February 2016 to September 2018 in Tabriz University of Medical Sciences, Tabriz, Iran. The present investigation consisted of 75 persons who had PD and 75 normal people. The blood levels of lipid fractions were measured by concentrations of total cholesterol (TC), serum triglycerides (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and total cholesterol. The results were analyzed with SPSS software using Kolmogorov-Smirnov, chi-square, and student's t-test. RESULTS: Serum level of TG was remarkably lower in patients with PD (111.92±8.75 mg/dL) compared with healthy subjects (123.64±9.97 mg/dL, P=0.008). Furthermore, we saw an important difference in the level of LDL-C (P=0.001) and TC (P=0.004) between the two groups. However, there was not any observed meaningful difference in the serum concentrations of HDL-C between the studied groups (P=0.135). CONCLUSION: Our results showed that the serum concentration of TG, LDL-C, and TC are noticeably lower in the PD suffering patients. Further investigations are needed to provide comprehensive information on the participants' cognitive layout and subsequent actions.

Mechanisms of COVID-19 Entry into the Cell: Potential Therapeutic Approaches Based on Virus Entry Inhibition in COVID-19 Patients with Underlying Diseases.

The Coronavirus disease 2019 (COVID-19) virus spread from Wuhan, China, in 2019 and is spreading rapidly around the world. COVID-19 victims are almost associated with cardiovascular disease, high blood pressure, diabetes, and other underlying diseases. Concerning the high prevalence of these disorders, widespread mortality threatens global society, and its fatality rate may increase with increasing COVID-19 prevalence in countries with older populations. Therefore, evaluating patients' clinical status with severe COVID-19 infection and their medical history can help manage treatment. Currently, one of the considered treatments is angiotensin-converting enzyme 2 (ACE2) inhibition. This study investigated virus entry mechanisms through membrane receptors, their role in the pathogenesis of COVID-19 and underlying diseases, and treatment methods based on the viral entrance inhibition. According to existing studies, inhibition of ACE2 can increase oxidative stress, inflammation, fibrosis and ultimately exacerbate underlying diseases such as cardiovascular disease, kidney disease, diabetes, and hypertension in individuals with COVID-19. The ACE2 inhibition is not suitable for patients with COVID-19 with underlying diseases, but it seems that the recombinant ACE2 solution is more appropriate for inhibiting the virus in these patients if hypotension would be monitored.

Seroprevalence of Cytomegalovirus among Women of Reproductive Age in Iran: A Systematic Review and Meta-Analysis.

BACKGROUND: Human cytomegalovirus (CMV) able to cause infection for an entire lifetime. This systematic review and meta-analysis was conducted to determine seroprevalence of CMV among women of reproductive age in Iran. METHODS: English and Persian databases such as Web of Science (WOS), PubMed, Scopus, Cochrane Library, SID, Iran doc, Iran Medex, Magiran, and Medlib were searched (from 2008 to 2017) accurately using the keywords: Cytomegalovirus, Pregnant women or Pregnancy, Epidemiology, Prevalence and Iran. RESULTS: Results of 15 studies with total samples of 5253 persons from 2008 to 2017 were combined and meta-analyzed. The pooled prevalence rate of IgG among women was estimated 90% (95% CI: 87-93%). The highest prevalence rate of IgG was in Tehran, Rasht, Mashhad and Yasoj, all 100% (95% CI: 100-100%), and the lowest prevalence was in Jahrom 0.62% (95% CI: 53-71%). The overall prevalence rate of IgM among women was estimated at 0.06% (95% CI: 0.03-0.13%). The highest prevalence rate of IgM was in Kerman 0.34% (95% CI: 0.29-0.39%) and Mashhad 0.25% (95% CI: 0.2-0.31%), and the lowest prevalence was in Yasoj 0% (95% CI: 0.00%-0.00%). CONCLUSION: The prevalence of immunity in Iran, is satisfactory. Nevertheless, to maintain and increase the level of immunity across the country, it is necessary to routinely screen the women of reproductive ages across the country.

Investigating the Relationship between Magnesium levels and Diabetes Mellitus in Pregnant Women.

Gestational diabetes mellitus (GDM) is defined as one of the three main types of diabetes mellitus (DM). It is established that GDM is associated with exceeding nutrient losses owing to glycosuria. Magnesium (Mg), as one of the essential micronutrients for fetus development, acts as the main cofactor in most enzymatic processes. The aim of this study was to measure serum and cellular levels of Mg, albumin, creatinine, and total protein to further clarify the relationship between these components and DM in pregnant women. Blood samples were obtained from 387 pregnant women. The participants were classified into four groups based on their type of diabetes, namely GDM (n=96), DM (n=44), at high-risk of DM (n=122), and healthy controls (n=125). All participants' fasting blood sugar (FBS), creatinine, albumin, Mg, and total protein in the serum levels and red blood cell Mg (RBC-Mg) were measured during 24-28 weeks of gestation. Groups were compared for possible association between DM and abortion, gravidity, and parity. The serum levels of creatinine, FBS, albumin, Mg, and RBC-Mg were statistically different among four groups (P =0.001). Significant lower levels of RBC- Mg was observed in all studied groups in comparison with controls. Given a positive correlation between DM and abortion, it seems that decreased levels of RBC-Mg and serum albumin can increase the risk of abortion in pregnant women. Our data demonstrated significant alterations in albumin, Mg, and creatinine concentrations in women with DM or those at high risk of DM during their gestational age. It seems that the measurement of these biochemical parameters might be helpful for preventing the complications, and improving pregnancy outcomes complicated with DM.

Prevalence of Human Immunodeficiency Virus in Iranian Blood Donors: A Systematic Review and Meta-Analysis.

BACKGROUND: The probability of HIV transmission through contaminated blood and blood products is eye catching. 5%-10% of blood products are contaminated with HIV. Therefore, it is essential to provide safe blood supply to prevent transmission of infectious diseases. Current systematic review and meta-analysis was conducted to evaluate the weighted prevalence of HIV in Iranian blood donors. METHODS: This study was reported according to PRISMA checklist for systematic reviews and meta- analysis. Required data were collected by using key words such as "HIV", "blood donation" OR "blood donors", "epidemiology" OR "prevalence", "blood transfusion" and "Iran", in international databases including PubMed, Scopus, Web of Science, Cochrane, Embase and national databases including Magiran, IranMedex and Scientific Information Databank. Papers were searched until December 2017. Cochran's Q test and I2 index were used to assess the heterogeneity among studies. RESULTS: A total of 49 studies including 5403170 donors entered this meta-analysis. According to analysis, the prevalence of HIV-positive patients among Iran blood donors was estimated 7.9/100000 (95% CI: 0.000052-0.000121%). The highest prevalence was related to the central region of Iran (11.3/100,000 [95% CI:0.000063-0.0002%]) and Kermanshah province (49.2/100000 [95% CI:0.000273-0.000888%]) and the lowest prevalence was related to the eastern region (1/100000 [95% CI:0.000001-0.000072%]) and Khorasan Razavi province (0.9/100000 [95% CI:0.000001-0.000139%]. CONCLUSION: The overall HIV prevalence in Iranian blood donors is low and satisfying. However, the high prevalence in some regions and provinces should be reviewed more meticulously.

R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke.

The polymorphic gene of serum paraoxonase (PON1) and its activity involved in atherosclerosis. The purpose of the study was to analyze PON1 192 Q/R polymorphism and the enzyme activities in ischemic stroke. The polymorphism as the most common polymorphism in PON1 gene coding sequence is associated with variation in the enzyme activity and vascular disease. The study included 85 stroke patients and 71 control subjects. PON1 192 polymorphism was genotyped using PCR protocol. Paraoxonase activity (Para) and arylesterase activity (Aryl) were determined spectrophotometrically using paraoxon and phenylacetate as the substrates. The QR and RR genotypes were more frequent in stroke population compared to controls, resulting in a higher frequency of the R allele in patients (0.24 vs 0.18, OR = 1.41). Patients had significantly higher Para/Aryl ratio than that of controls (P = 0.016). In stroke patients, Para/Aryl and Para/HDL ratios increased with this order: QQ < QR < RR. Hypertension significantly increased the risk of ischemic stroke by 15-fold among R-containing people, while this was significantly increased 4-fold for QQ homozygotes. Smoking increased the risk of having ischemic stroke in both QQ homozygote and QR + RR group (OR = 2.84 and OR = 2.33, respectively). In conclusion, these data highlight the importance of PON1 192 R allele and high Para/Aryl ratio in susceptibility to ischemic stroke in the population. The presence of the 192 R allele potentiates the risk of stroke especially in hypertensive people. Decreased Aryl and increased Para/Aryl, Para/HDL and Aryl/HDL ratios may be markers indicated the increased susceptibility to ischemic stroke in the population.