Azim Nejatizadeh

Background: Dyslipidemia is one of the main risk factors for cardiovascular diseases worldwide. The current study aimed to determine the prevalence and correlates of dyslipidemia in Iran, in addition to factors associated with receiving treatment and attaining treatment goals. Methods: The current study used the data of a very large cross-sectional survey, Prospective Epidemiological Research Studies in IrAN (PERSIAN), including 163,770 Iranians aged 35–70 years from 18 distinct areas across Iran, between 2014 and 2020. Participants’ characteristics were recorded using validated questionnaires including biological samples, physical measurements, and self-reported information. Dyslipidemia was defined according to the Third Report of the Adult Treatment Panel. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were measured as components of dyslipidemia. We calculated participants’ 10-years cardiovascular risk using the World Health Organization risk charts to assess the eligibility for treatment and achievement of control. Multivariable logistic regression analyses were conducted to investigate the correlates of dyslipidemia, receiving treatment, and control. Results: The mean age of participants was 49.4 (±9.1) years, among whom 55% were women and 70% were urban residents. The weighted prevalence of dyslipidemia was 73.2% (95% CI: 71.5–75.0%). High TG (40.4%, 36.9%−44.4%) and high TC (36.2%, 32.9%−39.4%) comprised the most prevalent components of dyslipidemia, followed by low HDL-C (32.1%, 25.8%−38.4%), high non-HDL-C (26.6%, 24.0%−29.1%), and high LDL-C (23.4%, 21.1%−25.7%). In multivariable logistic regression analysis, younger age, tobacco consumption, low physical activity, high BMI, diabetes, and hypertension were associated with low HDL-C and high TG. Older age, alcohol consumption, low physical activity, and high BMI were associated with high TC and high LDL-C. Women had higher likelihood of having abnormal levels for all components of dyslipidemia, except for high TG. Older age, high wealth score, high BMI, and low physical activity were associated with higher utilization of statin treatment. Good lipid control in those who were treated with statin was higher in males and diabetics. Conclusion: The prevalence of dyslipidemia in Iranian population is extremely high, and certain groups are at higher risk of poor lipid control. Findings of this study highlight the necessity of developing a national guideline for management of dyslipidemia.

The online version contains supplementary material available at 10.1038/s41598-026-48710-0.

Infertility affects 50-80 million individuals globally (WHO), with male factors, particularly abnormal semen parameters, contributing to 50% of cases. Among these, impaired sperm motility (asthenozoospermia, AZ) critically compromises fertilization potential. This study aimed to identify molecular biomarkers for AZ by investigating gene and competing endogenous RNA (ceRNA) networks associated with sperm motility. The study population included 100 participants, including 50 AZ and 50 Normozoospermia (NZ, control), according to the semen criteria (WHO 2021). We integrated bioinformatics analyses, including differential gene expression profiling (Gene Expression Omnibus dataset), protein-protein interaction (PPI) networks, and miRNA-lncRNA-mRNA regulatory networks. Candidate biomarkers were experimentally validated via qRT-PCR and receiver operating characteristic (ROC) curve analyses in AZ patients. An integrated bioinformatics and experimental approach identified AKT1, hsa-miR-1286, and LINC00242 as a putative network associated with sperm motility that warrants further functional validation. QRT-PCR validation demonstrated significant downregulation of AKT1 and hsa-miR-1286, alongside upregulation of LINC00242 in AZ samples. Expression levels of AKT1 and hsa-miR-1286 showed positive correlations with sperm motility, whereas LINC00242 exhibited a strong negative correlation. ROC curve analysis further suggests preliminary diagnostic potential of these molecules. Key findings suggested that AKT1, hsa-miR-1286, and linc00242 may represent preliminary diagnostic molecules, with the hsa-miR-1286/linc00242/AKT1 relationship emerging as a putative expression associated network linked to sperm motility.

Background Cancer remains a significant global health concern, with familial cases often involving complex interactions between genetic predispositions and environmental factors. Variants of Uncertain Significance (VUS) pose challenges in genetic counseling and risk assessment, particularly in genes like MRE11, which plays a crucial role in DNA double-strand break repair and genomic stability. Methods and results This study aimed to investigate the effect of the MRE11 c.1138 C > T (p.Arg380Cys) variant in a family affected by familial cancer, focusing on its potential contribution to inherited cancer risk and the challenges it poses for genetic counseling in families with clustering of malignancies. Whole-exome sequencing was used to identify the variant, which was validated by Sanger sequencing. In silico protein modeling and bioinformatics analyses, including pathogenicity prediction tools like REVEL, SIFT, PolyPhen-2, and MutationTaster, were employed to assess the variant’s functional effects. The MRE11 c.1138 C > T (p.Arg380Cys) variant was identified in a family with a history of breast, ovarian, and colorectal cancers. Conclusions Bioinformatics analyses suggested that this variant may destabilize the MRE11 nuclease domain, potentially impairing its function in DNA repair. Pathogenicity prediction tools consistently classified the variant as deleterious, although some family members with cancer did not carry the variant, indicating a complex interplay between genetic and environmental factors. The MRE11 p.Arg380Cys variant poses challenges in clinical interpretation due to its incomplete segregation within families. This pattern may reflect reduced penetrance, epistatic interactions with other genes (within MRN complex or others), or environmental influences.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by immune dysregulation and multi-organ involvement. This study focuses on the dysregulated expression of lncRNAs SNHG15 and OTUD6B-AS1 as potential biomarkers for disease progression and diagnostics. A comprehensive bioinformatics analysis of RNA-sequencing data from PBMCs of SLE patients and healthy controls identified differentially expressed lncRNAs, miRNAs, and mRNAs. The DAVID tool was employed for functional enrichment analyses to elucidate the biological pathways and functions associated with these differentially expressed genes. Concurrently, the STRING database was used to predict protein–protein interactions, enhancing our understanding of the molecular interactions and networks involved. Additionally, the relationships between lncRNAs, miRNAs, and mRNAs were explored through the construction of a competing endogenous RNA (ceRNA) network, visualized using Cytoscape. The findings from the bioinformatics analysis were substantiated by qPCR, which validated the differential expression of the lncRNAs SNHG15 and OTUD6B-AS1 in a larger cohort of samples, affirming their potential roles as biomarkers for SLE. The findings revealed significant up-regulation of SNHG15 (fold change = 2.01, p = 0.0011) and down-regulation of OTUD6B-AS1 (fold change = 0.26, p < 0.0001) in SLE patients compared to controls. Correlation analyses linked OTUD6B-AS1 expression with hematological and inflammatory markers, while SNHG15 was associated with liver function indicators. ROC analysis demonstrated high diagnostic accuracy for both lncRNAs, particularly OTUD6B-AS1. This study establishes SNHG15 and OTUD6B-AS1 as promising biomarkers for SLE, highlighting their distinct associations with immune and organ-specific pathology. The robust diagnostic performance of OTUD6B-AS1, evidenced by its high sensitivity and specificity, suggests its utility in developing more accurate diagnostic tests for SLE. Furthermore, the correlation of these lncRNAs with disease activity markers underscores their potential role in monitoring disease progression and severity in SLE patients.

Background: This study assessed the prevalence of gastroesophageal reflux disease (GERD) in a general adult population in Iran. The association between GERD and various factors was also evaluated. Methods: We performed a cross-sectional study on 163,018 individuals aged over 35 who were enrolled in the PERSIAN cohort. GERD was defined as the occurrence of heartburn and/or regurgitation symptoms at least several days a month. Survey design analysis for pooled data was performed and multiple regression analysis was conducted to determine the independent risk factors for GERD. Results: The prevalence of GERD in our study was estimated at 21.86% (95% confidence interval:17.4%-36.4%). The mean age of the participants was 49.84 years±9.25 (35–70) and 44.75% of the participants were male. Symptoms of heartburn and regurgitation were reported in 18.65% (n: 29,170) and 6.06% (n: 9,717) of participants, respectively. In the multivariate analysis, several factors were found to be associated with a higher prevalence of GERD: female sex, age >50, current smoking, opium use, weekly consumption of fried foods, frequent consumption of hot tea, less than 6 hours of sleep per night, psychiatric disorders, usage of NSAIDs, and poor oral hygiene, were associated with a higher prevalence of GERD. Conversely, higher education levels and average physical activity were found to be less commonly associated with GERD. Conclusion: We found a relatively high prevalence of GERD (21.86%) in this population-based study in Iran. By identifying modifiable risk factors, this research offers opportunities for targeted interventions and lifestyle modifications to reduce the burden of GERD.

Background:Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern.Methods:We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer.Results:We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69–1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16–2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21–4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11–6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24–4.42) than in current smokers (OR = 1.52; 95% CI, 0.72–3.15). All observed associations were consistently higher for urothelial histology.Conclusions:Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium.Impact:The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers.See related In the Spotlight, p. 461