Angiotensin-converting enzyme I/D gene polymorphism and risk of type 2 diabetes mellitus in Iranian individuals.

This study aimed to examine the relationship between type 2 diabetes mellitus (T2DM) and renin-angiotensin system gene polymorphisms in the Iranian population. Additionally, we performed a straightforward meta-analysis of the present articles to better understand this role. A total of 100 Iranian individuals, 50 patients with T2DM, and 50 age-matched healthy individuals were included in this study. DNA was extracted using the salting-out approach, polymerase chain reaction was used to amplify the angiotensin-converting enzyme (ACE) gene, electrophoresis techniques were used, and genotyping was performed. We also searched PubMed, Web of Science, Scopus, and Google Scholar databases for papers published in 2023. We found a significantly higher frequency of I/D genotype in the patient group than in the control group, and the risk of T2DM was 10 times higher in individuals with the I/D genotype (OR, 10 [95% CI, 3.7 to 27]; p < 0.0001) and also 2.85 time higher in individuals with the D allele OR, 2.85 [95% CI, 1.55 to 5.24]; p < 0.001). The ACE polymorphism alleles D and I/D genotypes may increase the risk of developing T2DM in an Iranian population.

Impact of a 50bp insertion/deletion polymorphism of the superoxide dismutase-1 on oxidative stress status and risk of keratoconus.

Keratoconus (KC) is characterized by the predominant primary ectatic disease, affecting the cornea, necessitating corneal transplants in some cases. While some loci associated with KC risk have been identified, the understanding of the disease remains limited. Superoxide dismutase (SOD) enzymes play a crucial role in countering the reactive oxygen species and providing protection against oxidative stress (OS). Accordingly, the objective of this study was to investigate a potential association of a 50 nucleotide base pairs (bp) insertion/deletion (I/D) within the SOD1 promoter, and the located 1684 bp upstream of the SOD1 ATG, with KC in the Iranian population. Additionally, an assessment was conducted on SOD activity and the total antioxidant capacity (TAC), as determined by the ferric reducing-antioxidant power assay, along with malondialdehyde (MDA) levels. In this case-control study, genomic DNA was extracted from the blood cells of KC (n = 402) and healthy (n = 331) individuals. The genotype of this gene was determined using the PCR technique. Furthermore, the amount of SOD enzyme activity and the MDA and TAC levels were measured in the serum of the study groups. The (I/I) genotype was present in 84.23%, the (I/D) genotype in 15.06%, and the (D/D) genotype in 0.69% of both groups. A statistically significant relationship was seen between different genotypes and TAC, MDA, and SOD1 activity indices (P < 0.05). Individuals with the D/D genotype exhibited a decrease in total antioxidant capacity, an increase in the amount of MDA, and a decrease in SOD1 enzyme activity (P < 0.05). Moreover, the logistic regression analysis of KC development indicated that elevated levels of MDA increased the risk of KC incidence in the patient group compared to the healthy group, while a higher activity of SOD1 and greater values of TAC decreased the KC risk. The removal of the 50 bp fragment reduced SOD1 activity and elevated OS levels, thereby impacting the oxidant-antioxidant balance. This could potentially play a significant role in individuals afflicted by KC.

Crosstalk between autophagy and insulin resistance: evidence from different tissues.

Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in CAD patients with and without opium addiction. This case-control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Carnosol Attenuates LPS-Induced Inflammation of Cardiomyoblasts by Inhibiting NF-κB: A Mechanistic in Vitro and in Silico Study.

Carnosol possesses several beneficial pharmacological properties. However, its role in lipopolysaccharide (LPS) induced inflammation and cardiomyocyte cell line (H9C2) has never been investigated. Therefore, the effect of carnosol and an NF-κB inhibitor BAY 11-7082 was examined, and the underlying role of the NF-κB-dependent inflammatory pathway was analyzed as the target enzyme. Cell viability, inflammatory cytokines levels (tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and prostaglandin E 2 (PGE2)), and related gene expression (TNF-α, IL-1ß, IL-6, and cyclooxygenase-2 (COX-2)) were analyzed by ELISA and real-time PCR. In addition, docking studies analyzed carnosol's molecular interactions and binding modes to NF-κB and IKK. We report that LPS caused the reduction of cell viability while enhancing both cytokines protein and mRNA levels (P < 0.001, for all cases). However, the BAY 11-7082 pretreatment of the cells and carnosol increased cell viability and reduced cytokine protein and mRNA levels (P < 0.001 vs. LPS, for all cases). Furthermore, our in silico analyses also supported the modulation of NF-κB and IKK by carnosol. This evidence highlights the defensive effects of carnosol against sepsis-induced myocardial dysfunction and, contextually, paved the rationale for the next in vitro and in vivo studies aimed to precisely describe its mechanism(s) of action.

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in patients with CAD with and without opium addiction. This case-control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Iron Chelator or Iron Supplement Consumption in COVID-19? The Role of Iron with Severity Infection.

Iron is a trace element that is used to replicate the virus and has a role in the vital functions of the body and the host's innate immune system. The mechanism of iron in COVID-19 severity is still not well understood. The aim of this study was to evaluate the association of the iron with COVID-19 severity. A case-control study was performed on 147 patients with a positive PCR test result and 39 normal individuals admitted to the Persian Gulf Martyrs Hospital in Bushehr, Iran. The iron profiles and related tests were measured along with hematological analytes. Hemoglobin (Hb), Fe, and saturated transferrin decreased in all the groups compared to the controls, but ferritin increased in the patient groups. After adjusting for age and sex, we found that increased ferritin levels augmented the odds ratio (OR) of the disease in the moderate (OR = 2.95, P = 0.007), severe (OR = 6.1, P < 0.001), and critical groups (OR = 8.34, P < 0.001). The decreased levels of Fe reduced the OR of the disease in the mild (OR = 0.96, P < 0.001), moderate (OR = 0.96, P < 0.001), severe (OR = 0.95, P < 0.001), and critical (OR = 0.98, P = 0.001) groups. Fe (AUC = 85.95, cutoff < 75.5 µg/dL, P < 0.001) and ferritin (AUC = 84.45, cutoff > 157.5 ng/dL, P < 0.001) have higher AUC for disease prognosis, but only ferritin (AUC = 74.89, cutoff > 261.5 ng/dL, P < 0.001) has higher AUC for disease severity assays. It could be concluded that the use of iron chelators to reduce iron intake can be considered a therapeutic goal. In addition, measuring Fe and ferritin is beneficial for the diagnosis of the disease and determining its severity.

Association of C677T (rs1081133) and A1298C (rs1801131) Methylenetetrahydrofolate Reductase Variants with Breast Cancer Susceptibility Among Asians: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis were conducted to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with breast cancer (BC) in Asians. Systematic searches were conducted in PubMed, EMBASE, Web of Science, and Scopus by May 2020. Inter-study heterogeneity was also assessed with a Q test, along with I2 statistics. Random-effects models were applied to pooled crude ORs with corresponding 95% CIs for the genetic models. A total of 1097 identified results, along with 36 qualified studies were included: for MTHFR C677T polymorphism, a total of 36 studies was comprised of 11,261 cases and 13,318 controls and for MTHFR A1298C polymorphism, a number of 19 studies contained 7424 cases and 8204 controls. Likewise, for C677T polymorphism, an increased risk of BC was seen for the allelic (OR 1.21, 95% CI 1.09-1.33, P < 0.01, I2 = 78.9%), dominant (OR 1.17, 95% CI 1.05-1.30, P < 0.01, I2 = 71.8%), recessive (OR 1.43, 95% CI 1.23-1.67, P < 0.01, I2 = 55.8%), and homozygous models (OR 1.48, 95% CI 1.25-1.75, P < 0.01, I2 59.9%) among BC patients compared to controls. Also, in terms of A1298C polymorphism, an association was found between the allelic (OR 1.15, 95% CI 1.04-1.28, P < 0.01, I2 70.4%) and homozygous models (OR 1.38, 95% CI 1.15-1.66, P < 0.01, I2 44.2%) with the risk of BC. In conclusion, findings revealed that MTHFR C677T variant might be a factor that predisposes BC in Asians. Furthermore, it was found that A1298C variant acts as a BC risk factor, particularly in a Western Asia population.

A Systematic Review and Meta-analysis on Blood Lead Level in Opium Addicts: an Emerging Health Threat.

This meta-analysis was conducted aiming to summarize the results obtained from the previous studies so that the effect of opium on blood lead levels (BLLs) can be investigated. Scopus, Embase, PubMed, and Web of Science (ISI) were systematically searched up to June 2020. Heterogeneity of the included studies was evaluated using Cochrane's Q test and the I2 statistic. A random-effects model was used to pool the weighted mean differences (WMDs) and their 95% confidence intervals (CIs). Out of a total of 2372 citations, eleven articles with 916 participants (487 opium addicts and 429 controls) were included in the study. The meta-analysis results showed that there were higher lead levels (WMD = 14.59 µg/dL, 95% CI = 11.59 to 17.92, Z = 8.60, P < 0.001) in opium addicts than in the control group. The degree of heterogeneity observed (P < 0.001, I2 = 98.1%) might be mainly the result of the type of sampling and of consumption. Moreover, the findings of meta-regression analyses indicated that publication year (ß = 1.23, P = 0.287), total sample size (ß = 0.05, P = 0.728), and quality scores (ß = - 2.91, P = 0.546) had no effects on lead levels in opium addicts. In the sensitivity analysis, it was found that the pooled WMDs remained stable after excluding one by one study. Oral opium consumption increased the amount of lead in the bloodstream, and the measurement of lead levels in opium addicts' blood may be regarded as a useful test to diagnosis and prognosis of disorders that may lead poisoning causes.

Effects of Cigarette Smoke and Opium on the Expression of CD9, CD36, and CD68 at mRNA and Protein Levels in Human Macrophage Cell Line THP-1.

Cigarette smoking and opium use are risk factors for coronary artery disease (CAD). It has been known that scavenger receptors such as CD36 and CD68 play critical roles in the pathogenesis of CAD. CD9, as a member of the tetraspanin, has been shown to interact with scavenger receptors. The aim of this study was to investigate the effects of these risk factors on expression levels of CD9, CD36, and CD68 on the THP-1 cell line. The THP-1 cell line treated with cigarette smoke extract (CSE( and opium, both individually and combinatory, in 24 h incubation. The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by flow cytometry and quantitative reverse transcription-Polymerase Chain Reaction (qRT-PCR) techniques, respectively. CD36 and CD68 mRNA and protein expression levels were significantly increased in the cells treated with cigarette smoke extract compared to the control (p<0.001 in mRNA expression levels and p=0.016 and p=0.012 in protein expression levels, respectively). The CSE increased the level of CD9 protein expression compared to the control group (p=0.041) on the human macrophage cell line THP-1. No significant differences were observed in the CD9, CD36, and CD68 gene expression and at the protein levels between opium-treated THP-1 cells and controls. In conclusion, cigarettes by increasing the levels of CD36, CD68, and CD9 can be a risk factor in the development of many inflammatory diseases, including cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and lung carcinoma.

CD36 gene polymorphism rs1761667 (G > A) is associated with hypertension and coronary artery disease in an Iranian population.

BACKGROUND: CD36 is associated with regulation of lipid metabolism, atherosclerosis, and blood pressure. Moreover, its variation may be involved in the development of hypertension and/or coronary artery disease (CAD). The present study was conducted to investigate the possible association of CD36 rs1761667 (G > A) polymorphism with hypertension and/or CAD in the southeastern of Iran. METHODS: The present observational study was composed of 238 subjects who were admitted for coronary angiography, and divided into four groups: 1) hypertensive without CAD (H-Tens, n = 52); 2) hypertensive with CAD (CAD + H-Tens, n = 57); 3) CAD without hypertension (CAD, n = 65); and 4) non-hypertensive without CAD as the control group (Ctrl, n = 64). The CD36 rs1761667 polymorphism was genotyped with PCR-RFLP method. Association between CD36 rs1761667 genotypes and the risk of CAD and hypertension was assessed using multinomial regression by adjusting for age, sex, creatinine, fasting blood sugar (FBS), systolic blood pressure (SBP) and diastolic blood pressure (DBP). RESULTS: In the present study, minor allele (A) frequency was 0.36. The genotype, but not allele frequency of the CD36 rs1761667 was significantly different between the four study groups (p = 0.003). Furthermore, using a recessive inheritance model CD36 rs1761667 polymorphism was significantly associated with an increased risk of CAD with hypertension (OR = 5.677; 95% CI = 1.053-30.601; p = 0.043). However, using the dominant model of CD36 rs1761667 had a protective effect on H-Tens and CAD patients. CONCLUSION: The present findings revealed an association between CD36 rs1761667 polymorphism and susceptibility to hypertension and/or CAD in a southeastern Iranian population.

Evaluation of serum arsenic and its effects on antioxidant alterations in relapsing-remitting multiple sclerosis patients.

BACKGROUND: Environmental factors that are involved in the development of autoimmune diseases include bacteria, viruses, and xenobiotics such as chemicals, drugs, and metals. Regarding the metals, a number of studies have demonstrated that oxidative stress is one of the well-directed pathways of arsenic-induced tissue damages. This study was designed to explore the serum concentrations of arsenic and its correlation with markers associated with oxidative stress in relapsing-remitting MS (RRMS) patients. METHODS: This case-controlled study comprised 50 patients with RRMS and 50 healthy subjects. Serum arsenic levels, total antioxidant potential, malondialdehyde (MDA), and lactate levels were measured. RESULTS: The arsenic value, MDA, and lactate levels were elevated meaningfully while FRAP level significantly was decreased in RRMS patients with respect to healthy subjects (P <0.05). Furthermore, arsenic serum levels were positively correlated with serum concentrations of MDA and lactate. In contrast, serum levels were negatively correlated to FRAP values in RRMS patients. CONCLUSION: Taken together, the association between arsenic level and oxidative stress parameters supports the hypothesis that high serum arsenic levels may play a critical role in the pathogenesis of MS progression.

Evaluation of lithium serum level in multiple sclerosis patients: A neuroprotective element.

INTRODUCTION: It has been claimed that continuous and high production of nitric oxide (NO) and its metabolites may be involved in the pathogenesis of several neurological disorders such as multiple sclerosis. A number of studies have demonstrated that lithium regulates NO levels in disorders of the central nervous system. The aim of this study was to investigate whether NO as a marker of disease activity is correlated with lithium deficiency in relapsing remitting multiple sclerosis (RR-MS). METHODS: This case-controlled study comprised 44 patients with RR-MS and 43 healthy subjects matched by age, gender, smoking status, and body mass index. The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in serum. In addition serum lithium levels were measured using atomic absorption spectrometry method. The mean serum NO concentrations in the groups RR-MS and the control were 18.5 ± 3.1µM and 15.5 ± 2.9µM, respectively. Data analysis showed a statistically significant difference between subjects with RR-MS and the control group (p < 0.05). Furthermore, serum lithium concentrations in RR-MS (0.57 ± 0.2) were remarkably lower in RR-MS patients than the controls (2.29 ± 0.7) (p < 0.05). CONCLUSION: The present findings suggest that lithium deficiency may upregulates NO production in RR-MS. Further studies with larger samples are needed to confirm the effects of lithium treatment on NO pathway and its association with synaptic plasticity in RR-MS patients.

Characteristics of 26 kDa antigen of H. Pylori by Monoclonal Antibody.

Alkylhydroperoxide reductase (AhpC, the 26 kDa antigen) is one of the abundant antioxidant enzymes in Helicobacter pylori and seems to have a good potential for use in development of immunoassays to detect H. pylori infection in clinical specimens. This study aimed to investigate some properties of this antigen by the produced monoclonal antibodies. Five established hybridoma cell lines secreting monoclonal antibodies (MAbs) against 26 kDa antigen of H. pylori were cultivated and MAbs were purified by affinity chromatography. Subsequently, MAbs were conjugated with biotin, and different combinations of capture and tracer antibodies used in sandwich ELISA. Immunoblotting of bacterial extracts were performed to estimate aggregation status of the antigen. Release of antigen from the cultivated bacteria on solid media was examined by sandwich ELISA, and also, existence of interference in fecal extract was investigated by immunoblotting and sandwich ELISA. Our findings showed that the MAbs against 26 kDa antigen of H. pylori could recognize three bands of nearly 25 kDa, 50 kDa, and 75 kDa in immunoblotting. This study also indicated presence of more antigens in the culture medium around the bacteria than the bacterial extract itself. The results of sandwich ELISA and immunoblotting on fecal extracts suggest the presence of interfering agents that prevent detection of antigen by antibody in ELISA but not in immunoblotting. In this study the oligomerization of the 26 kDa antigen, presence of interfering agents in stool matrix, and release of antigen to outside of bacteria, were demonstrated.