Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.

PURPOSE: Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications. METHODS: In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods. RESULTS: Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]. CONCLUSION: The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

The study of HMOX1 DNA methylation and gene expression and the diagnostic potential of miR-153-3p in preeclampsia.

Background: The objective was to elucidate the potential epigenetic regulatory mechanism in HMOX1 expression in preeclampsia. Materials & methods: HMOX1 promoter DNA methylation was evaluated in the placental tissue and blood of preeclamptic and normotensive pregnant women. HMOX1 and miR-153-3p gene expression were assessed in placental tissue and peripheral blood mononuclear cells (PBMCs). Related microarray datasets in the Gene Expression Omnibus database were also analyzed. Results: In placental tissue, despite HMOX1 expression downregulation, there was no significant change in HMOX1 methylation. In PBMCs, there was no significant alteration in HMOX1 expression, while hypomethylation was observed in blood. The miR-153-3p expression increased in the placental tissue and in the PBMCs of preeclampsia. Conclusion: DNA methylation does not affect HMOX1 expression, while miR-153-3p might be a biomarker for preeclampsia.

The influence of Nrf2 gene promoter methylation on gene expression and oxidative stress parameters in preeclampsia.

BACKGROUND AND AIMS: Preeclampsia (PE) is a serious medical condition that usually causes high blood pressure and affects multiple organs. Considering the adverse effect of oxidative stress on the process of PE in pregnant women and regarding the role of the Nrf2 gene in placental oxidative pathways, this study was conducted to investigate the DNA methylation status of Nrf2 in PE and healthy pregnant women. MATERIALS AND METHODS: The present case-control study consisted of 70 PE and 70 healthy pregnant women. Blood and placenta samples were taken from all subjects, and the percentage of the Nrf2 gene methylation in the samples was assessed by the Methyl Light PCR method. Also, the Nrf2 gene expression was evaluated by real-time PCR. The total antioxidant capacity (TAC) and total oxidative status (TOS) were measured by the colorimetric method. RESULTS: In PE women, there was a significant increase in blood pressure, term of pregnancy, and BMI. In addition, there were enhanced Nrf2 DNA methylation percentage in placenta tissue and increased TOS levels in placenta tissue and blood compared to healthy pregnant women (P < 0.05). Also, in the PE group, there was a significant decrease in Nrf2 gene expression and TAC level in placenta tissue compared to the control group (P < 0.05). CONCLUSION: The Nrf2 gene undergoes epigenetic modifications of DNA hypermethylation in the PE placenta. Decreased expression of this gene and the changes in the level of oxidative parameters (TAC, TOS) confirm it.

Interplay of miRNAs and lncRNAs in STAT3 signaling pathway in colorectal cancer progression.

In recent decades, colorectal cancer (CRC) has turned into one of the most widespread malignancies, and the incidence of this malignancy is expected to increase. Despite considerable improvements in therapeutic approaches, the prognosis, and the management of CRC face many problems. Likely, the main limitation in the successful treatment of CRC is the lack of appropriate clinical therapeutic targets. As an effective target, the signal transducer and activator of transcription 3 (STAT3) are regulated by a wide range of genes and involved in cellular processes, including cell growth, migration, invasion, immunosuppression, and angiogenesis. Aberrant regulation of STAT3 signaling leads to cellular dysfunction, diseases, and malignancies, including CRC. Consequently, targeting this signaling pathway is considered one of the therapeutic strategies used in CRC treatment. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are non-coding RNA molecules with partial or no protein-coding activity that participate in gene regulation at epigenetic, transcriptional, and post-transcriptional levels and regulate multiple signaling pathways, including STAT3 signaling (especially JAK/STAT). Therefore, these regulatory molecules are suggested to be very promising targets to present new insights into overcoming the limitations of conventional therapeutic strategies. Therefore, the current review study aimed to summarize the therapeutic and diagnostic significance of miRNAs and lncRNAs and their therapeutic and diagnostic significance related to the expression and activity of STAT3 in CRC.

Variants and Haplotypes of SIRT1 (rs7895833, rs7069102, and rs2273773) are Associated with the Risk of Preeclampsia and Affect the Trace Elements and Antioxidant Enzymes Levels.

Preeclampsia is the most common and serious complication of pregnancy. Variants of Sirtuin-1 (SIRT1) as a key player in the regulation of oxidant/antioxidant signaling pathways might be involved in the pathogenesis of preeclampsia. In the present case-control study 300 women with and without preeclampsia were studied for SIRT1 variants (rs7895833, rs7069102, and rs2273773) and haplotypes. Also, the relationship of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and Zn, Cu, and Se levels to the polymorphisms were investigated. The SIRT1 rs7895833 A > G, rs7069102 C > G, and the rs2273773 C > T polymorphisms were associated with the risk of preeclampsia. We found the haplotypes G (rs7895833) C (rs7069102) C (rs2273773), GCC, and ACC compared to the AGT decreased the risk of preeclampsia. The risk haplotype of AGT was associated with higher GPx activity compared to the GCC haplotype. A significantly higher level of Cu and lower levels of Zn and Se in patients with preeclampsia compared to controls were detected. Also, a significantly lower SOD and higher GPx activity in preeclamptic patients compared to controls were found. The three risk genotypes of AA (rs7895833), GG (rs7069102), and TT (rs2273773) significantly decreased the Zn level and SOD activity, and the TT genotype (rs2273773) increased the Cu level in all studied women. The presence of rs7069102 polymorphism was associated with enhanced systolic blood pressure. For the first time, we indicated three SIRT1 polymorphisms and the AGT haplotype are risk factors for preeclampsia development. Also, SIRT1 variants and haplotypes affect the levels of antioxidant enzymes and their cofactors, complicating the pregnancy outcome.

The GPx-1 Gene Variants (rs1050450) in Obesity: Association with the Risk of Obesity and the GPx Activity in Females.

Background: This study aimed to investigate the GPx-1 gene polymorphism (rs1050450), the level of oxidative stress and antioxidant parameters, and the lipid profile in an obese Kurdish population in Sulaimani, Iraq. Methods: In a case-control study,134 obese subjects and 131 normal BMI healthy individuals participated. The GPx-1 gene polymorphism was assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The levels of biochemical and oxidative parameters were determined using photometric methods. Results: The results showed that the fasting blood sugar (FBS), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in obese subjects compared to the control group. Obese individuals had significantly lower levels of high-density lipoprotein cholesterol (HDL-C) than the controls. The GPx-1 activity and total antioxidant capacity (TAC) levels were significantly elevated in the obese group compared to the control group (P=0.006, and P<0.001, respectively). No significant difference was detected in genotype and allele frequencies of GPx-1 (rs1050450) between obese and normal BMI groups. However, the presence of the GPx-1 TT genotype enhanced the risk of obesity in females by 1.93-fold (95% CI 1.04-3.58, P=0.036). In the total population, the GPx activity increased in the presence of TT compared to CC+CT and CT genotypes. Conclusion: The study indicated that obesity is linked to significantly higher levels of FBS, TG, LDL-C, TAC, and GPx activity and lower level of HDL-C. Also, we found the GPx-1 gene polymorphism was associated with the risk of obesity in females and increased the GPx activity.

Aberrant Methylation of the SOD1 GENE, its Expression and Enzyme Activity in the Placenta of Patients with Preeclampsia.

Background: Oxidative stress is involved in the pathogenesis of preeclampsia (PE). Dysregulation of SOD1 may be involved in the pathogenesis of PE. We examined and compared the methylation level of the promoter region (PMR) of the SOD1, gene expression, and enzyme activity of superoxide dismutase (SOD) in both placenta and maternal blood in PE women. Methods: A total of 140 blood samples and 40 placental tissue samples from PE and healthy pregnant controls were studied. The PMR of the SOD1 (Methylight PCR method), the expression (Real-time PCR), and its enzyme activity were investigated and compared in two groups. Results: The PMR of the SOD1 gene in the placental tissue of the patients was significantly increased compared to the control group (P= 0.008); this result was accompanied by a decrease in the expression of the gene and a decrease in the activity of the SOD enzyme. Meanwhile, the PMR of the SOD1 gene did not significantly change in the blood samples of the patients (P= 0.95), while a significant decrease in the expression of SOD1 (without a significant change in the SOD activity) was observed. Conclusion: The results showed significant changes in the PMR of the SOD1 gene and gene expression in placenta tissue. The results highlight the role of the placenta in complications during pregnancy and also revealed epigenetics as an important regulatory pathway in the pathogenesis of preeclampsia.

CD44 Suppression Improved the Chemosensitivity of HT-29 Colorectal Cancer Cells to 5-Fluorouracil and Inhibited Cell Migration.

Purpose: CD44 plays a pivotal role through tumorigenesis by regulating cancer cell metastasis, stemness, and chemosensitivity and is considered a promising therapeutic target for human cancers, including colorectal cancer (CRC). Therefore, the present research aimed to examine the simultaneous therapeutic effect of CD44 silencing and 5-fluorouracil (5-FU) on in vitro tumorigenesis of CRC cells. Methods: CD44 expression was initially evaluated in TCGA datasets and CRC tissues. Furthermore, functional analysis was performed on HT-29 CRC cells overexpressing CD44. The cells were transfected with CD44 siRNA and then treated with 5-FU. Consequently, to explore the combination therapy effect on cell viability, migration, apoptosis, and chromatin fragmentation, we performed MTT assay, scratch assay, Annexin V/PI staining and DAPI staining assays, respectively. The spheroid and colony formation assays were further employed to investigate stemness features. The gene expression at protein and mRNA levels were explored using western blotting and qPCR. Results: Our findings illustrated that CD44 was significantly overexpressed in CRC tissues compared to normal samples. The suppression of CD44 considerably promoted the chemosensitivity of HT-29 cells to 5-FU by apoptosis induction. Also, the combination therapy led to overexpression of apoptotic genes, including P53, caspase-3, and caspase-9, as well as downregulation of AKT1 expression. Furthermore, CD44 suppression, separately or combined with 5-FU, hindered stemness properties in HT-29 cells via downregulation of Sox2 and Nanog expression. Besides, the combination therapy remarkably downregulated MMPs and suppressed CRC cell migration. Conclusion: Considering its involvement in chemosensitivity to 5-FU, CD44 could be suggested as a potential target for improving the efficiency of CRC chemotherapy.

Tobacco smoking and blood parameters in the kurdish population of Iran.

OBJECTIVE: This study investigates the relationship between smoking and blood parameters in the Iranian Kurdish population. METHOD: The current study was conducted based on the recruitment phase of the Ravansar Non-Communicable Disease (RaNCD) cohort study. RESULTS: Current smokers had higher levels of RBC count, HCT, HGB, MCV, MCH, MCHC, WBC count, and GR%, than in other groups significantly. Passive smokers had higher levels of PLT count and PCT statistically. The increasing exposure time of smoking positively affected WBC count, GR%, PLT count, PCT, and RDW in female passive smokers. In addition, heavy smokers, as well as participants with a higher duration time of smoking, had the same results for significantly lower levels of lymphocyte and monocyte and a higher level of RBC indices. CONCLUSION: According to the present study, along with the current smokers, the intensity of smoking, as well as the duration time of the smoke, could have a positive correlation with blood parameters. Furthermore, passive smokers and specifically secondhand female smokers were more vulnerable to smoke.

Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran.

PURPOSE: We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. METHOD AND RESULTS: Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4-4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2-0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 (AGTR1) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14-0.68, P = 0.002). CONCLUSIONS: Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.

Codelivery of resveratrol melatonin utilizing pH responsive sericin based nanocarriers inhibits the proliferation of breast cancer cell line at the different pH.

Protein-based nanocarriers have demonstrated good potential for cancer drug delivery. Silk sericin nano-particle is arguably one of the best in this field. In this study, we developed a surface charge reversal sericin-based nanocarrier to co-deliver resveratrol and melatonin (MR-SNC) to MCF-7 breast cancer cells as combination therapy. MR-SNC was fabricated with various sericin concentrations via flash-nanoprecipitation as a simple and reproducible method without complicated equipment. The nanoparticles were subsequently characterized for their size, charge, morphology and shape by dynamic light scattering (DLS) and scanning electron microscope (SEM). Nanocarriers chemical and conformational analysis were done by fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) respectively. In vitro drug release was determined at different pH values (7.45, 6.5 and 6). The cellular uptake and cytotoxicity were studies using breast cancer MCF-7 cells. MR-SNC fabricated with the lowest sericin concentration (0.1%), showed a desirable 127 nm size, with a net negative charge at physiological pH. Sericin structure was preserved entirely in the form of nano-particles. Among the three pH values we applied, the maximum in vitro drug release was at pH 6, 6.5, and 7.4, respectively. This pH dependency showed the charge reversal property of our smart nanocarrier via changing the surface charge from negative to positive in mildly acidic pH, destructing the electrostatic interactions between sericin surface amino acids. Cell viability studies demonstrated the significant toxicity of MR-SNC in MCF-7 cells at all pH values after 48 h, suggesting a synergistic effect of combination therapy with the two antioxidants. The efficient cellular uptake of MR-SNC, DNA fragmentation and chromatin condensation was found at pH 6. Nutshell, our result indicated proficient release of the entrapped drug combination from MR-SNC in an acidic environment leading to cell apoptosis. This work introduces a smart pH-responsive nano-platform for anti-breast cancer drug delivery.

Contribution of NOS3AS Variants to Susceptibility to Essential Hypertension: A Study in Kermanshah Province, Western Iran.

Hypertension (HTN) is a global health challenge and increase the risk of cardiovascular disease. Hypertension has a multifactorial course of evolution, with both genetic and environmental factors playing an important role. To date, a number of genes and pathways have been proposed to be associated with HTN, among which is Nitric Oxide pathway. NO levels can be regulated by reactive oxygen species (ROS), superoxide and post-transcriptional mechanisms, including sense-anti sense interactions. NOS3AS gene encodes an antisense RNA (sONE) which is complementary to NOS3 transcript in 662 nucleotides and may regulate NOS3 in a post-transcriptional manner. In this study, we sought to define the role of NOS3AS in the pathophysiology of essential HTN. A total of 131 cases with hypertension and 115 controls were enrolled in the study. Peripheral blood was drawn from all study participants after signing the informed consent form. Three variants (rs71539868, rs12666075 and rs7830) were investigated by Tetra-ARMS PCR method. The results were then statistically analyzed. We found statistically significant association between rs7830 TT genotype, rs12666075 GT and TT genotypes with susceptibility to HTN. We failed to observe association between rs71539868 and susceptibility to HTN. The present study showed a strong association between NOS3AS variants and susceptibility to hypertension in the population of Kermanshah province. Our results may shed more light on the mechanisms of disease development and may also help to better identify genetic predispositions and individuals at risk.

The influence of LPL S447X variants and obesity on lipid profile, oxidative stress, and the risk of T2DM: A case-control study.

Aims: The present study aimed to investigate the association between lipoprotein lipase (LPL) S447X polymorphism and type 2 diabetes mellitus (T2DM), obesity, lipid profile, and oxidative stress parameters in a population from the Kurdistan region of Iraq. Method: We studied 250 adults (51% female and 49% male) aged 45-65 years in four groups, obese and normal body mass index (BMI) diabetic patients versus healthy normal BMI and obese individuals as controls. Lipid profile and oxidative stress parameters were analyzed by colorimetric assay. The LPL S447X genotypes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Results: We found that the obese diabetic group had higher levels of triglycerides (TG), cholesterol, and low-density lipoprotein-cholesterol, and lower level of high-density lipoprotein-cholesterol than other groups. Obese diabetic patients had higher anthropometric indices than nonobese diabetic patients, obese and normal BMI controls. The levels of TG and total oxidative status (TOS) were significantly lower and higher, respectively, in normal BMI controls than in obese controls. Obese diabetic patients had a lower level of total antioxidant capacity than nondiabetic obese controls. The level of TOS was lower in nondiabetic controls compared to the patient groups. Obese diabetic patients had the highest TOS and malondialdehyde levels. The LPL SX genotype was associated with decreased the risk of T2DM by 79% (odds ratio [OR] = 0.21; 95% confidence interval [CI]: 0.05-0.81, p = 0.03). Also, the presence of this genotype reduced the risk of obesity by 39% (OR = 0.61; 95% CI: 0.07-4.90, p = 0.6). In all individuals, the presence of the SX genotype was associated with significantly lower levels of fasting blood sugar (FBS) and TOS. Conclusion: We report the influence of obesity on lipid profile in diabetic and nondiabetic individuals and the effect of LPL SX genotype on decreased risk of T2DM and reduced levels of FBS and TOS.

Association Between Vitamin D Binding Protein Gene Polymorphism (rs7041), Vitamin D Receptor, and 25-Hydroxyvitamin D Serum Levels With Prostate Cancer in Kurdish Population in West of Iran.

Prostate cancer (PCa) pathology has been linked to vitamin D, vitamin D receptors (VDRs), and vitamin D binding proteins (VDBPs). We sought to investigate the association between VDR rs2228570 and rs1544410 as well as VDBP rs7041 polymorphisms and serum 25-hydroxyvitamin D (25(OH)-vitamin D) levels in PCa patients. Blood samples were collected from 111 PCa patients and 150 age-matched healthy volunteers. The VDR rs2228570 T/C, rs1544410 G/A, and VDBP rs7041 T/G genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 25(OH)-vitamin D and PSA (Total and Free) serum levels were measured. The frequencies of VDBP genotypes T/G vs. T/T (56.5% vs. 44.5%, p = 0.01) according to the dominant model T/G + G/G vs. T/T (84.3% vs. 71.5%, p = 0.01) were significantly higher in PCa patients when compared to control group and considerably increased the risk of disease by 2.29, 1.44, and 2.13 folds respectively. Interestingly, the results demonstrated that PCa patients with the dominant model (T/G + G/G vs. T/T) of VDBP had significantly lower serum levels of vitamin D and higher serum levels of total and free PSA in comparison to the controls. Furthermore, when compared to controls, PCa patients with the dominant model T allele (T/G + G/G vs. TT) of VDBP had significantly higher vitamin D, total PSA, and free PSA concentrations. Serum levels of 25(OH)-vitamin D and rs7041 T/G polymorphism of the VDBP gene could be potential risk factors for PCa.

Pregnancy, Preeclampsia, and COVID-19: Susceptibility and Mechanisms: A Review Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through angiotensin converting enzyme 2 (ACE2), which expression of its gene increases during pregnancy that is resulted in an enhanced level of the ACE2 enzyme. It might enhance the risk of SARS-CoV-2 infection and its complications in the pregnant women. Although, pregnancy hypertensive disorders and severe infection with SARS-CoV-2 are correlated with high comorbidity, these two entities should be discriminated from each other. Also, there is a concern about the risk of preeclampsia and consequently severe coronavirus disease 2019 (COVID-19) development in the pregnant women. So, to answer these questions, in the present review the literature was surveyed. It seems there is higher severity of COVID-19 among pregnant women than non-pregnant women and more adverse pregnancy outcomes among pregnant women infected with SARS-CoV-2. In addition, an association between COVID-19 with preeclampsia and the role of preeclampsia and gestational hypertension as risk factors for SARS-CoV-2 infection and its complications is suggested. However, infection of the placenta and the SARS-CoV-2 vertical transmission is rare. Various mechanisms could explain the role of COVID-19 in the risk of preeclampsia and association between preeclampsia and COVID-19. Suggested mechanisms are included decreased ACE2 activity and imbalance between Ang II and Ang-(1-7) in preeclampsia, association of both of severe forms of COVID-19 and pregnancy hypertensive disorders with comorbidity, and interaction between immune system, inflammatory cytokines and the renin angiotensin aldosterone system and its contribution to the hypertension pathogenesis. It is concluded that preeclampsia and gestational hypertension might be risk factors for SARS-CoV-2 infection and its complications.

New inflammatory biomarkers (lymphocyte and monocyte percentage to high-density lipoprotein cholesterol ratio and lymphocyte to monocyte percentage ratio) and their association with some cardiometabolic diseases : Results from a large Kurdish cohort study in Iran.

BACKGROUND: The incidence of metabolic heart diseases has increased significantly in Middle Eastern countries such as Iran. The present study aimed to investigate the association between monocyte percentage to high-density cholesterol ratio (MHR), lymphocyte percentage to high-density cholesterol ratio (LHR), and lymphocyte to monocyte percentage ratio (LMR) and cardiometabolic diseases in a Kurdish population in the west of Iran. METHODS: This study recruited 9803 individuals, 4728 (48.2%) were male and 5084 (51.8%) were female from Ravansar, Iran. All biomarkers were analyzed by the standard methods. RESULTS: The prevalence of cardiometabolic diseases was higher in overweight/obese participants and increased with age. MHR and LHR increased significantly in cardiometabolic individuals compared with healthy controls. Individuals in the fourth quartiles of LHR and MHR had higher odds ratio (ORs) for metabolic syndrome (MetS) and diabetes mellitus (DM) than the first quartiles. The LMR had a statistical association with non-alcoholic fatty liver disease (NAFLD) ORs and FLI. Besides, all these associations were stronger for females, and increased physical activity decreased inflammatory biomarkers. CONCLUSION: The present study showed MHR and LHR had significant associations with ORs of MetS and DM. Also, MHR and LHR had a significant positive correlation with cardiometabolic risk factors. The LMR only had a statistical association with NAFLD and fatty liver index (FLI). Besides, the strong correlation between inflammatory biomarkers and cardiometabolic risk factors in females might be relevant to higher fat accumulation and metabolic inflammation background, and lower physical activity.

Demographics, clinical characteristics, and outcomes of 27,256 hospitalized COVID-19 patients in Kermanshah Province, Iran: a retrospective one-year cohort study.

BACKGROUND: Since the first official report of SARS-CoV-2 infection in Iran on 19 February 2020, our country has been one of the worst affected countries by the COVID-19 epidemic in the Middle East. In addition to demographic and clinical characteristics, the number of hospitalized cases and deaths is an important factor for evidence-based decision-making and disease control and preparing the healthcare system to face the future challenges of COVID-19. Therefore, this cohort study was conducted to determine the demographics, clinical characteristics, and outcomes of hospitalized COVID-19 patients in Kermanshah Province, west of Iran. METHODS: This multicenter retrospective cohort study included all suspected, probable, and confirmed cases of COVID-19 hospitalized in Kermanshah Province, Iran during the first year of the COVID-19 pandemic. Demographics, clinical characteristics, outcomes and other additional information of hospitalized patients were collected from the COVID-19 database of the Medical Care Monitoring Center (MCMC) of Kermanshah Province. RESULTS: Kermanshah Province experienced three waves of COVID-19 infection considering the hospitalization and mortality rates between February 20, 2020 and February 19, 2021. A total of 27,256 patients were included in the study: 5203 (19.09%) subjects were suspected, 9136(33.52%) were probable, and 12,917 (47.39%) were confirmed COVID-19 cases. The mean age of the patients was 53.34 ± 22.74 years and 14,648 (53.74%) were male. The median length of hospital stay among COVID-19 survivors and non-survivors patients were 4 (interquartile range [IQR] 1-6) and 4 (IQR 1-8) days, respectively. Among patients with COVID-19, 2646 (9.71%) died during hospitalization. A multivariable logistic regression revealed that odds of death among patients ≥ 85 years was significantly greater than among patients < 15 years (adjusted odds ratio [aOR] 4.79, 95% confidence interval [CI] = 3.43-6.71, p≤ 0.001). Patients with one (aOR 1.38, 95% CI 1.21-1.59, p = 0.04), two (aOR 1.56, 95% CI 1.27-1.92, p = 0.001) or more (aOR 1.50, 95% CI 1.04-2.17, p = 0.03) comorbidities had higher odds of in-hospital death compared to those without comorbidities. The male sex (aOR 1.20, 95% CI 1.07- 1.35, p = 0.002), ICU admission (aOR 4.35, 95% CI 3.80-4.97, p < 0.001), intubation (aOR 11.09, 95% CI 9.58-12.84, p < 0.001), respiratory distress (aOR 1.40, 95% CI 1.22-1.61, p < 0.001), loss of consciousness (aOR 1.81, 95% CI 1.45-2.25, p < 0.001), anorexia (aOR 1.36, 95% CI 1.09-1.70, p = 0.006) and peripheral oxygen saturation (SpO2) < 93(aOR 2.72, 95% CI 2.34-3.16, p < 0.001) on admission were associated with increased risk of death in patients with SARS-CoV-2 infection. Having cough (aOR 0.82, 95% CI 0.72-0.93, p = 0.003) and headache (aOR 0.70, 95% CI 0.50-0.97, p = 0.03) decreased the odds of death. CONCLUSION: The mortality rate of the patients admitted to the general wards and ICU can be a guide for allocating resources and making appropriate plans to provide better medical interventions during the COVID-19 pandemic. Several risk factors are associated with the in-hospital mortality of COVID-19, including advanced age, male sex, ICU admission, intubation, having comorbidity, SpO2 < 93, respiratory distress, loss of consciousness, headache, anorexia, and cough. These risk factors could help clinicians identify patients at high risk for death.

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, diabetic neuropathy, diabetic retinopathy, and obesity.

INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. METHODS: In a case-control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.

Nrf2 rs6721961 and Oxidative Stress in Preeclampsia: Association with the Risk of Preeclampsia and Early-Onset Preeclampsia.

Preeclampsia as a multifactor hypertensive disorder of pregnancy is associated with enhanced placental oxidative stress. The Keap1-Nrf2 pathway protects cells against oxidative stress. We examined the possible association between the Nrf2 variants in relation to oxidative stress parameters with the risk of preeclampsia. We studied 150 preeclampsia women and 150 women with a normal pregnancy to find the frequency of Nrf2 rs6721961 genotypes using the PCR-RFLP method. Also, an association between the Nrf2 genotypes with the levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) was analyzed. Significantly lower TAC and higher MDA levels were found in preeclampsia patients compared to controls (P<0.0001). For the first time, we report an association between the Nrf2 rs6721961 polymorphism and preeclampsia risk. The present study indicated that the GT genotype and the T allele of the Nrf2 rs6721961 increased the risk of preeclampsia by 2.81 and 2.39 times, respectively. Also, the Nrf2 TT genotype was associated with a 3.9-fold increased risk of early-onset preeclampsia. We detected a positive association between the levels of body mass index, MDA, and the Nrf2 polymorphism with the risk of preeclampsia and a negative correlation between the level of TAC with the preeclampsia risk. Also, an association between the rs6721961 TT genotype with higher serum MDA levels was found. Our study suggests oxidative stress is involved in the pathogenesis of preeclampsia and the Nrf2 rs6721961 polymorphism through alteration in the levels of oxidative stress parameters might increase the risk of preeclampsia and early-onset preeclampsia.

COVID-19 and psoriasis: biologic treatment and challenges.

BACKGROUND: There is concern about susceptibility of psoriatic patients on biologics to coronavirus disease 2019 (COVID-19) and its clinical course. PURPOSE: The aims of present review were to determine whether the biologic treatment of psoriasis increases the risk of SARS-CoV-2 infection and if biologics affect the clinical course of COVID-19 in these patients. METHODS: We searched database of MEDLINE (PubMed) for key term of psoriasis biologic and COVID-19 until June 9, 2020 and all published 14 papers and an experience from Iran (10509 cases) related to the psoriatic patients on biologics and COVID-19 along with relevant papers were summarized. In spite of limitation in some reports, due to some of strengths that will be discussed, all papers were included in this review. RESULTS: According to 8769 medical reports around 0.3% of psoriatic patients had COVID-19 and the rate of hospitalization was 0.1%. No death due to COVID-19 was reported among 10509 patients. Reports indicated psoriatic patients on biologics were not more susceptible to COVID-19 and the severe clinical course of disease. CONCLUSION: While there is not definitive controlled trial data, the available evidence suggests that patients with psoriasis without COVID-19 can continue the biologic therapy for psoriasis.