Investigating the expression level of miR-17-3p, miR-101-3p, miR-335-3p, and miR-296-3p in the peripheral blood of patients with acute myocardial infarction.

The role of inflammation has been proven in acute myocardial infarction (AMI) pathogenesis. Due to the effect of NLRP3 gene expression in the inflammation process of MI, we aimed to explore the expression changes and diagnostic power of four inflammation-related miRNAs including miR-17-3p, miR-101-3p, miR-335-3p, miR-296-3p and their potential target, NLRP3, in ST-segment elevation myocardial infarction (STEMI), and non-STEMI (NSTEMI) patients as two major classes of AMI. The expression level of these genes were evaluated in 300 participants equally divided into three groups of STEMI, NSTEMI, and control using quantitative real-time PCR. The expression level of NLRP3 was upregulated in STEMI and NSTEMI patients compared to control subjects. Besides, the expression levels of miR-17-3p, miR-101-3p, and miR-296-3p were significantly downregulated in STEMI and NSTEMI patients compared to controls. The increased expression of NLRP3 had a very strong inverse correlation with miR-17-3p in patients with STEMI and with miR-101-3p in the STEMI and NSTEMI patients. ROC curve analysis showed that the expression level of miR-17-3p had the highest diagnostic power for discrimination between STEMI patients and controls. Remarkably, the combination of all markers resulted in a higher AUC. In summary, there is a significant association between the expression levels of miR-17-3p, miR-101-3p, miR-335-3p, miR-296-3p, and NLRP3 and the incidence of AMI. Although the miR-17-3p expression level has the highest diagnostic power to distinguish between STEMI patients and control subjects, the combination of these miRNAs and NLRP3 could serve as a novel potential diagnostic biomarker of STEMI.

Evaluation of circulating levels of miR-135a and miR-193 in patients with sepsis.

BACKGROUND: Sepsis is a life-threatening condition where early diagnosis and prognostic awareness provide guidance for selecting the appropriate treatment strategies. A wide variety of biomarker-based studies in clinical medicine provide new insights into personalized medicine for sepsis patients. MiRNAs are endogenous non-coding RNA molecules that have been acting as great potential diagnostic, prognostic and therapeutic biomarkers in various diseases. METHODS AND RESULTS: In the present study, the expression levels of two selected miRNAs, including miR-135a and miR-193, were evaluated for their prognostic potential in patients with sepsis. The circulating levels of miRNAs were quantified by quantitative PCR (qPCR) in patients with sepsis (n = 100) and age- and sex-matched healthy controls (n = 100). Statistical findings confirmed the valuable prognostic potential of miR-135a in patients with sepsis, while no significant difference was found between the miR-193 expression level in the patients with sepsis and the controls. CONCLUSIONS: Circulating levels of miRNA-135a can serve a the prognostic biomarker for patients with sepsis. These findings highlight the importance of miRNAs as signatures in the personalized managements of sepsis.

Prognostic potential of circulating cell free mitochondrial DNA levels in COVID-19 patients.

BACKGROUND: In viral infections, mitochondria act as one of the main hubs of the pathogenesis. Recent findings present new insights into the potential role of circulating cell-free mitochondrial DNA (ccf-mtDNA) in COVID-19 pathogenesis by the induction of immune response and aggressive cytokine storm in SARS-CoV-2 infection. METHODS AND RESULTS: The levels of ccf-mtDNA were investigated in 102 hospitalized patients with COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong association between the levels of ccf-mtDNA and and mortality, ICU admission, and intubation. Also, our findings highlighted the pivotal role of comorbidities as a risk factor for COVID-19 mortality and severity. CONCLUSION: Higher levels of ccf-mtDNA can serve as a potential early indicator for progress and poor prognosis of COVID-19.

Reverse expression pattern of sirtuin-1 and histone deacetylase-9 in coronary artery disease.

BACKGROUND: SIRT1 and HDAC 9 genes are related to inflammation and may contribute to the pathogenesis of coronary artery disease (CAD). We aimed to evaluate the expression level, methylation profile and polymorphisms of these genes in CAD patients. METHODS: In this study, 50 CAD patients and 50 healthy individuals were recruited. The expression level change was evaluated using the TaqMan Real-Time PCR method. The methylation of genes promoter and genotyping of polymorphisms were evaluated by the HRM. RESULTS: The expression level of SIRT1 was reduced while the HDAC9 expression level showed a significant elevation (p < .001). The SIRT1 gene promoter was hypomethylated and the HDAC9 gene promoter was hypermethylated in CAD patients. Also, CG + GG genotype in SIRT1 and both genotypes in the HDAC9 gene were associated with expression change. CONCLUSIONS: SIRT1 and HDAC9 genes, expression changes can be suggested as a potential biomarker for CAD detection.

Association between leukocyte telomere length and COVID-19 severity.

Background: Inter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases. Result: In this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity. Conclusions: These findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1186/s43042-023-00415-z.

Associations between short-term exposure to fine particulate matter and acute myocardial infarction: A case-crossover study.

BACKGROUND: Previous studies evaluated the impact of particle matters (PM) on the risk of acute myocardial infarction (AMI) based on local registries. HYPOTHESIS: This study aimed to evaluate possible short term effect of air pollutants on occurrence of AMI based on a specific case report sheet that was designed for this purpose. METHODS: AMI was documented among 982 patients who referred to the emergency departments in Tehran, Iran, between July 2017 to March 2019. For each patient, case period was defined as 24 hour period preceding the time of emergency admission and referent periods were defined as the corresponding time in 1, 2, and 3 weeks before the admission. The associations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2 .5 ) and particulate matter with an aerodynamic diameter ≤10 µm (PM10 ) with AMI were analyzed using conditional logistic regression in a case-crossover design. RESULT: Increase in PM2.5 and PM10 was significantly associated with the occurrence of AMI with and without adjustment for the temperature and humidity. In the adjusted model each 10 µg/m3 increase of PM10 and PM2.5 in case periods was significantly associated with increase myocardial infarction events (95% CI = 1.041-1.099, OR = 1.069 and 95% CI = 1.073-1.196, and OR = 1.133, respectively). Subgroup analysis showed that increase in PM10 did not increase AMI events in diabetic subgroup, but in all other subgroups PM10 and PM2 .5 concentration showed positive associations with increased AMI events. CONCLUSION: Acute exposure to ambient air pollution was associated with increased risk of AMI irrespective of temperature and humidity.

Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity.

Within the past several decades, the emergence and spread of infectious diseases with pandemic potential have endangered human lives. Coronavirus disease 2019 (COVID-19) outbreak represents an unprecedented threat for all health systems worldwide. The clinical spectrum of COVID-19 is highly heterogeneous, ranging from asymptomatic and mild upper respiratory tract illness to severe interstitial pneumonia with respiratory failure and even death. Highly age-dependent patterns of immune response potentially explain the higher rates of the severe forms of COVID-19 in elderly patients. However, genetic and epigenetic architecture can influence multiple biological processes during the lifespan, therefore as far as our knowledge shows, vulnerability to viral infection concerning telomere length and epigenetic signature is not a new idea. This review aims is to summarize the current understanding of the role of telomere length and epigenetic mechanisms on the severity of COVID-19. The current knowledge highlights the significant association between the shorter telomere length and the higher risk of developing severe COVID-19. Differential DNA methylation patterns and miRNA expression profiles imply that these hallmarks can play a pivotal role in COVID- 19 pathogenesis. Understanding the causes of inter-individual variations in COVID-19 outcomes could provide clues to the development of the personalized therapeutic intervention.

Variation in the expression level of MALAT1, MIAT and XIST lncRNAs in coronary artery disease patients with and without type 2 diabetes mellitus.

Background: The MALAT1, MIAT, and XIST long noncoding RNAs (lncRNAs) participate in the pathogenesis of complex diseases and also serve as diagnostic markers. The study aimed to assess their expressions in CAD patients with or without T2DM against diabetic and non-diabetic controls.Methods: The expression levels of three lncRNAs in 50 CAD patients (with or without diabetes) and 50 non-CAD subjects (with or without diabetes) were evaluated by using the TaqMan Assay method.Results: MALAT1 and MIAT were upregulated in CAD patients (p Value= .0008 and .0078, respectively). The expression level of XIST was significantly elevated diabetic compared to non-diabetic CAD patients (p Value= .0003). MALAT1 gene had the highest diagnostic power for discrimination of CAD patients from controls (AUC= 0.682, p Value=.001).Conclusions: The current study supports the participation of lncRNAs in the pathogenesis of CAD and T2DM and highlights their potential as diagnostic biomarkers.

Roles of mitochondrial DNA in dynamics of the immune response to COVID-19.

Mitochondria dynamics have a pivotal role in many aspects of immune function. Viral infections affect mitochondrial dynamics and trigger the release of mitochondrial DNA (mtDNA) in host cells. Released mtDNA guides the immune response towards an inflammatory response against pathogens. In addition, circulating cell-free mtDNA (ccf-mtDNA) is considered an invaluable indicator for the prognosis and severity of infectious diseases. This study provides an overview of the role of mtDNA in the dynamics of the immune response to COVID-19. We focused on the possible roles of mtDNA in inducing the signaling pathways, and the inflammasome activation and regulation in SARS-CoV-2. Targeting mtDNA-related pathways can provide critical insights into therapeutic strategies for COVID-19.

The Association Between Hematologic Indices With TIMI Flow In STEMI Patients Who Undergo primary percutaneous coronary intervention.

BACKGROUND: The Primary Percutaneous Coronary Intervention (PPCI) is the preferred therapeutic strategy for patients who experienced ST-Elevation Myocardial Infarction (STEMI). OBJECTIVE: We aimed to evaluate the association of hematological indices, including hemoglobin level, platelets, White Blood Cells (WBCs) count, and MPV before PPCI with the TIMI grade flow after PPCI. METHODS: STEMI patients who experienced PPCI were included in the present retrospective crosssectional study. Then participants were divided into three groups based on their post-procedural TIMI flow grades. Demographic data and hematologic indices of patients before PPCI were collected and their association with the TIMI grade flow after PPCI was evaluated. To compare the quantitative and qualitative variables, chi-square and t-tests were performed, respectively. RESULTS: We found that elevated levels of hemoglobin and decreased levels of MPV had a significant association with an advanced grade of TIMI flow. Interestingly, in the normal range, there was a significant association between higher platelet count and TIMI-flow grade 1. Besides, TIMI flow grades 2 and 3 had a significant association with low and moderate platelets count, respectively. CONCLUSION: In conclusion, evaluating MPV, platelets, and hemoglobin levels before PPCI as easy and accessible parameters may be able to identify high-risk STEMI patients undergoing PPCI.

The association between QTc, QTd, TPE, and fragmented QRS before and after PPCI with hospital mortality in STEMI patients.

INTRODUCTION: ST-elevation myocardial infarction (STEMI) is known to be associated with significant arrhythmia and consequent mortality. QT prolongation is a risk factor for arrhythmia in STEMI patients who underwent primary percutaneous coronary intervention (PPCI). The aim of this investigation was to evaluate the association of corrected QT interval (QTc), QT dispersion (QTd), T-wave peak to end (TPE), and fragmented QRS with mortality in these patients. METHODS: Eligible patients with the characteristic symptoms of STEMI who underwent PPCI were included. QTc, QTd, TPE, and fragmented QRS were measured before and after the PPCI. These predictors were compared between patients who died during hospitalization and discharged patients. RESULTS: After coronary angiography, 10 patients (4%) died during the hospitalization after PPCI. Comparing the non-survivers and discharged patients in terms of arrhythmia predictors showed that the mean QT dispersion and TPE before intervention were significantly higher in the non-survivors. Also, the number of patients who experienced fragmented QRS both before and after the intervention was significantly higher in the non-survivors. CONCLUSION: These data suggested that evaluating such arrhythmia predictors, especially before PPCI, could be used as a predictor of mortality in STEMI patients who underwent PPCI.

MicroRNA-copy number variations in coronary artery disease patients with or without type 2 diabetes mellitus.

BACKGROUND: An important cause of Coronary Artery Disease (CAD) is Type 2 Diabetes Mellitus (T2DM). The aim of this study was the evaluation of copy number variations (CNVs) of hsa-miR-93, hsa-miR-122, hsa-miR-192 in CAD patients with or without T2DM. METHODS: CNVs of three micro-RNAs in 50 CAD patients and 50 non-CAD subjects both with and without diabetes were evaluated by real-time PCR and compared in three comparison groups namely 1, 2 and 3 (including comparison between CAD and non-CAD, diabetic CAD and non-diabetic CAD and between diabetic CAD and diabetic non-CAD subjects, respectively). RESULTS: There were significant differences in CNVs of hsa-miR-93 between cases and controls in comparison groups 1 and 3 (p = .0310 and .0232, respectively), for hsa-miR-122 in all comparison groups, and for hsa-miR-192 in comparison group 3 (p = .0181). CONCLUSION: We showed the association of these microRNA-CNVs with CAD, T2DM or both simultaneously.

Methylation of the PKD1 Promoter Inversely Correlates with its Expression in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), a multisystem disorder, is the most prevalent type of hereditary kidney disease. Here, we aimed to evaluate methylation of the PKD1 gene (PKD1) promoter and its correlation with PKD1 expression in peripheral blood. METHODS: In this case-control study methylation of the PKD1 promoter was evaluated using methylation-sensitive high-resolution melt (MS-HRM) analysis. PKD1 expression was assessed by quantitative real-time PCR. The correlation was evaluated using the Pearson correlation test. RESULTS: Twenty subjects from both the patient and control groups (n= 40 for each) were methylated at the PKD1 promoter to various levels (18.9% in patients and 62.5% in controls). This difference was statistically significant (p< 0.0001). PKD1 expression in blood samples was significantly greater in ADPKD patients than in controls (p= 0.0081). Significant correlation was seen between PKD1 expression and its promoter methylation status in peripheral blood (r case= -0.5300, p= 0.0162, and r control = -0.6265, p= 0.0031). CONCLUSION: Methylation of the PKD1 promoter in ADPKD patients was inversely correlated with PKD1 expression.

c.376G>A mutation in WFS1 gene causes Wolfram syndrome without deafness.

Wolfram syndrome is one of the rare autosomal recessive, progressive, neurodegenerative disorders, characterized by diabetes mellitus and optic atrophy. Several other features are observed in patients including deafness, ataxia, and peripheral neuropathy. A gene called WFS1 is identified on chromosome 4p, responsible for Wolfram syndrome. We investigated a family consisted of parents and 8 children, which 5 of them have been diagnosed for Wolfram syndrome. WFS1 gene in all family members was sequenced for causative mutations. A mutation (c.376G>A, p.A126T) was found in all affected members in homozygous state and in both parents in heterozygous state. The bioinformatics analysis showed the deleterious effects of this nucleotide change on the structure and function of the protein product. As all of the patients in the family showed the homozygote mutation, and parents were both heterozygote, this mutation is probably the cause of the disease. We identified this mutation in homozygous state for the first time as Wolfram syndrome causation. We also showed that this mutation probably doesn't cause deafness in affected individuals.

Association of CLU and TLR2 gene polymorphisms with late-onset Alzheimer disease in a northwestern Iranian population.

BACKGROUND/AIM: A number of genetic variants from different genes have been reported to be related to late-onset Alzheimer disease (LOAD) susceptibility. From these genes, polymorphisms in CLU and TLR2 have been replicated in several studies. In this study we examined the association of rs11136000 in CLU and the TLR2 -196 to -174 del polymorphism with the risk of LOAD in a northwestern Iranian population. MATERIALS AND METHODS: We conducted a case-control study with a dataset of 160 LOAD patients and 163 healthy controls. To examine polymorphisms of CLU and TLR2 in LOAD we used the PCR/RFLP method and genotype frequencies were statistically determined. RESULTS: There was no association between CLU polymorphism and the risk of LOAD, but for deletion in TLR2 we found significant differences between LOAD and the control group (P > 0.001, OR = 0.55). CONCLUSION: This result suggests that the TLR2 -196 to -174 del polymorphism is an additional risk factor for LOAD. Allelic frequencies of CLU may have no effect on risk of LOAD.