👤 Seyed Fazlollah Mousavi

Human studies have reported inconsistent associations between early-life exposure to per- and polyfluoroalkyl substances (PFAS), particularly during critical windows of brain development, and neurodevelopmental outcomes. To address the lack of clarity regarding how PFAS affect neurodevelopment, this study developed the first unified adverse outcome pathway (AOP) network to explore the mechanisms involved in developmental neurotoxicity (DNT). Of 343 AOPs retrieved from AOP-Wiki, 19 linear AOPs associated with DNT satisfied the inclusion criteria. To pinpoint critical nodes and relationships, the constructed DNT-AOP network was examined using topological metrics. Through a combination of qualitative weight of evidence (WoE) assessment and network topology analysis, two critical paths were identified: one based on thyroid hormone disruption and the other on the intracellular calcium (Ca Show less

Cardio-metabolic disease (CMetD) is a prevalent health issue among healthcare professionals, and suboptimal management of metabolic disorders places a burden on the healthcare system. The present study aimed to cluster the participants based on risk factors for the CMetDs using Latent Profile Analysis (LPA). This study was conducted on 500 healthcare providers, aged 18 to 75 years at Tabriz University of Medical Sciences, Tabriz, Iran. LPA was used to explore the latent risk profiles based on age, blood pressure (BP), lipid profile, insulin, body mass index (BMI), and waist circumference. The individuals were classified into three LPA-driven profiles: low (42.4%), intermediate (21.8%), and high (35.8%). The high-risk profile found in older age and higher BMI, insulin, fasting blood glucose (FBS), as well as higher levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, and triglyceride. Furthermore, in the intermediate risk profile, elevated levels of systolic/diastolic BP and waist circumference were associated with higher levels of risk. Haemoglobin and hematocrit levels were significant predictors of low and intermediate latent profiles. Higher levels of hemoglobin and hematocrit were associated with lower odds of being in low and intermediate latent profiles, compared to the high-risk profile (all LPA-derived latent profiles and the specific predictors of profiles help find control and prevention measures in CMetDs; older individuals with poorer lipid profiles, and, elevated insulin, triglyceride, FBS, BP, and BMI levels should be screened more carefully. Show less

LncRNAs, pseudogenes, and miRNAs participate a fundamental function in tumorigenesis, metabolism, and invasion of cancer cells, although their regulation of tumor glycolysis in prostate adenocarcinoma (PRAD) is thoroughly not well studied. In this study, we applied transcriptomic, proteomic, and medical information to identify glycolysis-related key genes and modules associated with PRAD. Then, the glycolysis-related lncRNA/lncRNAs/pseudogenes-miRNA-mRNA network was constructed. Analysis of DNA methylation status and expression data determined a DNA methylation-dysregulated three-DE-mRNAs signature for predicting diagnosis, ANGPTL4, GNE, and HSPA in PRAD patients and healthy control. Several lncRNAs/pseudogenes, significantly correlated with the overall survival PVT1, CA5BP1, MIRLET7BHG, SNHG12, and ZNF37BP and disease-free survival status, MALAT1, GUSBP11, MIRLET7BHG, and SNHG1, of patients with PRAD were determined. The methylation profile of DE-lncRNA/pseudogenes was significantly proper for predicting PRAD prognostic model. The transcription level of 6 DE-mRNA ANGPTL4, QSOX1, BIK, CLDN3, DDIT4, and TFF3 was correlated with cancer-related fibroblast infiltration in PRAD. The mutated form of 7 mRNAs, COL5A1, IDH1, HK2, DDIT4, GNE, and QSOX1, was associated with PRAD. In addition to the glycolysis pathway, DE-RNAs play regulatory roles on several pathways, including DNA damage, RTK, cell cycle, RAS/MAPK, TSC/mTOR and PI3K/AKT, AR hormone, and EMT. Overall, our study improves our knowledge of the relation between lncRNAs/pseudogenes and miRNA related to glycolysis and PRAD pathogenesis. Show less

Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial etiology. Several studies show that genetic factors have an important part in the incidence of SLE. The C1QTNF4 gene is involved in the regulation of the inflammatory pathways by pro-inflammatory function. In the present study, we have evaluated the association between C1QTNF4 gene p.His198Gln mutation and risk of SLE. Forty SLE patients and 40 control subjects were recruited in this case-control study. Genotyping of C1QTNF4 p.His198Gln mutation was performed using real-time polymerase chain reaction high resolution melting method. We found a significant association between this mutation (GG + GC) with the risk of SLE (odds ratio = 6.33, 95% CI = 1.28-31.11). Furthermore, we observed that in the patient group, this mutation leads to early-onset SLE (19.7 ± 4.34 years for mutation carriers compared to 27.7 ± 11.4 years for wild type carriers; P = .003). Our results suggest that this mutation (p.His198Gln) potentially has an important role in SLE risk in the Iranian population. Show less