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ABSTRACT Background and Aims Mounting evidence have implicated that rs1801131 and rs1801133, located in the Methylenetetrahydrofolate reductase (MTHFR) gene, may emerge as novel biomarkers for coronary artery disease (CAD). The Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is also an appropriate predictor for revascularization strategy in patients with complex CAD. The aim of this study is to investigate the correlation between rs1801131 and rs1801133 with the severity of coronary lesions in patients with ST‑Elevation Myocardial Infarction (STEMI) and Non‑ST‑Elevation Myocardial Infarction (NSTEMI) based on the SYNTAX score. Methods This retrospective cross‐sectional study included 96 patients diagnosed with STEMI and NSTEMI from Razi University Hospital between April and September 2019. Ninety‐six patients were diagnosed with STEMI (N = 43) and NSTEMI (N = 53) were recruited from South Khorasan, Iran. The angiographical characteristics of CAD were defined by the SYNTAX score. Genomic DNA was isolated from peripheral blood and genotyped for rs1801131 and rs1801133 using the TaqMan real‐time PCR method. Results The results of the one‐way analysis of variance indicated that there is no association between rs1801131 and rs1801133 with the severity of coronary lesions in patients with STEMI (p = 0.44) and NSTEMI (p = 0.91). However, the two‐way analysis of variance comparison and post‐hoc test demonstrated that rs1801133 in the presence of rs1801131 is correlated with the SYNTAX score in NSTEMI (p = 0.03) and total patients (p = 0.03). Conclusion In conclusion, our study reveals a significant association between the MTHFR polymorphism rs1801133 and CAD severity, particularly in NSTEMI patients. While rs1801131 showed no correlation, rs1801133 may serve as a valuable genetic biomarker for assessing CAD severity. Further research with larger populations is needed to confirm these findings.

Abstract Background Acute myocardial infarction (AMI) is a leading cause of death and morbidity around the world. Although the association between thrombophilia and AMI is well-established, controversial data are present on the association between thrombophilic polymorphisms and AMI. The aim of this study was to investigate the association of three thrombophilic polymorphisms including factor V Leiden (FVL), MTHFRC677T (methylenetetrahydrofolate reductase), and Coagulation factor XIIIVal34Leu with AMI in East of Iran. Result There were no statistically significant differences between the patients and control groups in terms of the distributions of allelic and genotypic frequencies of FVL and FXIIIVal34Leu polymorphisms (P-value > 0.05). Subjects who carried CT genotype of MTHFR C677T polymorphism were at a 2.03-fold higher risk for AMI (P-value: 0.02, OR 1.76, 95% CI 1.07–2.75). Furthermore, patients with MTHFR 677CT (P-value 0.05). Conclusion Our findings showed that MTHFRC677T polymorphism could contribute to AMI susceptibility and increase creatinine levels in east Iran population. This was the first study to examine the association of these three polymorphisms with AMI in east Iran.

Trastuzumab has been applied widely in the treatment of breast cancer. The majority of initial responders display disease progression again within one year. Regardless of the high resistance rate, the molecular mechanisms affected this disease are not well understood. MicroRNAs are small, non-coding RNA molecules that involved in gene regulation. There is evidence that promotes miRNAs as potential candidates to mediate therapeutic actions by targeting genes involved in drug response. The purpose of this study is to evaluate miR-885-3p in HER2 positive breast cancer chemoresistance. Trastuzumab-resistant BT-474 cells were generated by in vitro culture of BT-474 cells continuously in the presence of trastuzumab about 9 months. The relative expression of miR-885-3p to U6 RNA was evaluated in trastuzumab-resistant and sensitive cells using Relative Real-Time PCR. The Mann-Whitney test is used to compare the differences between the two groups. The MTT assay showed that BT-474 breast cancer cells were resistant to this drug under long-term culturing with trastuzumab (p < 0.05). MiR-885-3p expression was also significantly downregulated in trastuzumab-resistant cells in comparison with the parent cells (p < 0.05).: As the relative expression of candidate microRNAs was statistically different in trastuzumab-resistant and sensitive cells, we hypothesize that miR-885-3p downregulation as a possible mechanism of trastuzumab resistance.

Background and Aim: Resistance to trastuzumab has been a critical barrier to targeted therapy of HER 2-positive (Human Epidermal Growth Factor Receptor 2) breast cancers. MicroRNAs (miRNAs) are known as decisive core regulators of drug resistance that modulate the epithelial-to-mesenchymal transition (EMT) and cancer-related immune responses. The present study aimed at examining the expression of miR-141 in trastuzumab-resistant and trastuzumab-sensitive BT-474 breast cancer cells. Materials and Methods: In this experimental study, trastuzumab-resistant BT-474 cells were generated by continuous in-vitro culture of BT-474 cells in the presence of trastuzumab for six months. The relative expression of miR-141 to U6 RNA was then evaluated in trastuzumab-resistant and trastuzumab-sensitive cells using Relative Real-Time PCR. Mann-Whitney test was used to compare the difference between the two groups. Results: There was a significant difference between the survival rates of resistant BT-474 cells and sensitive cells in the MTT test in the presence of different concentrations of trastuzumab showing that BT-474 breast cancer cells have turned resistant to this drug under long-term culture (P=0.001). Also, the expression of miR-141 in trastuzumab-resistant cells was significantly reduced by four times compared with the BT-474 parent cells (P=0.049). Conclusion: Down-regulation of miR-141 in trastuzumab-resistant BT-474 cells might be one possible mechanism for resistance against trastuzumab and an indication of the role of this microRNA in controlling the metastasis pathway.