Aspirin and clopidogrel resistance; a neglected gap in stroke and cardiovascular practice in Iran: a systematic review and meta-analysis.

OBJECTIVE: Antiplatelet drugs, such as Aspirin and Clopidogrel (Plavix) are effective in the primary prevention of thromboembolic events. They are commonly used to reduce the risk of recurrence of thromboembolism. The body's hemostatic system responds differently to these drugs in different people. Resistance testing for aspirin and Clopidogrel is now recommended before starting antiplatelet therapy. METHODS: A systematic literature search was performed on May 12, 2021, using the medical search engines PubMed, Scopus, and Web of Science, and the local databases SID and Magiran. After data extraction, a meta-analysis was performed using Comprehensive Meta-Analysis (CMA2) software. The I2 statistic was used to measure heterogeneity between estimates. RESULTS: Among the 949 papers, Clopidogrel resistance was assessed in 136 patients and Aspirin resistance in 400 patients. The prevalence of Aspirin resistance was found to be 52.1% and the prevalence of Clopidogrel resistance was found to be 20.5%. CONCLUSION: It seems that in Iran, the issue of Aspirin and Clopidogrel resistance is suboptimally addressed. This pattern could also occur in other developing countries in the Middle East region.

Dysregulation of miRNA expression in patients with chronic myelogenous leukemia at diagnosis: a systematic review.

Aim: The present systematic review aimed to explore miRNAs as a potential biomarker for early diagnosis of chronic myeloid leukemia (CML). Materials & methods: A systematic search was conducted in three electronic databases, including Web of Science, Scopus and PubMed, to obtain relevant articles investigating the alteration of miRNA expression in patients with CML. Results: The authors found miRNAs whose expression changes are effective in the induction of CML disease. Among them, miR-21 and miR-155 were identified as the most common miRNAs with increased expression and miR-150 and miR-146 as the most common miRNAs with decreased expression. Conclusion: miRNAs can be used as an indicator for the early detection and treatment of CML phase.

Evaluating the frequency, prognosis and survival of RUNX1 and ASXL1 mutations in patients with acute myeloid leukaemia in northeastern Iran.

To evaluate the frequency and prognosis of runt-related transcription factor 1 (RUNX1) and additional sex combs like-1 (ASXL1) mutations in acute myeloid leukaemia (AML) patients in northeastern Iran. This cross-sectional study was performed on 40 patients with AML (including 35 patients with denovo AML and five patients with secondary AML) from February 2018 to February 2021. All patients were followed up for 36 months. We evaluated the frequency and survival rate of RUNX1 and ASXL1 mutations in AML patients. To detect mutations, peripheral blood samples and bone marrow aspiration were taken from all participants. One male patient (2.5%) had RUNX1 mutations and four cases (10%; 3 females vs. 1 male) had ASXL1 mutations. The survival rates of AML patients after 1, 3, 6, 9, 12, 24 and 36 months were 98%, 90%, 77%, 62%, 52%, 27% and 20%, respectively. There was a significant relationship between the occurrence of ASXL1 mutations and the survival of patients with AML (p = 0.027). Also, there was a significant relationship between the incidence of death and haemoglobin levels in patients with AML (p = 0.045). Thus, with an increase of one unit in patients' haemoglobin levels, the risk of death is reduced by 16.6%. Patients with AML had a high mortality rate, poor therapy outcome and low survival rate. ASXL1 and RUNX1 mutations are associated with a worse prognosis in patients with newly diagnosed AML. Also, we witnessed that the prevalence of ASXL1 to RUNX1 mutations was higher in northeastern Iran compared with other regions.

Altered expression of NEAT1 variants and P53, PTEN, and BCL-2 genes in patients with acute myeloid leukemia.

BACKGROUND: Newly discovered evidence showed that long non-coding RNAs (lncRNAs) can play crucial roles in the development of cancer therapies. Nuclear Enriched Abundant Transcripts 1 (NEAT1) is one of the lncRNAs the expression of which changes in different cancers. The role of NEAT1 in apoptosis is discussed in various malignancies. This study aimed to determine the NEAT1 expression and its correlation with P53, PTEN, and BCL-2 genes expression in acute myeloid leukemia (AML) patients. METHOD: In this study, using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression of NEAT1, P53, PTEN, and BCL-2 genes in 21 AML patients. Moreover, relative quantification analysis was performed by delta-delta CT method (2 -ΔΔCT) method. RESULTS: Our results showed that NEAT1 expression was significantly lower in AML patients compared to healthy controls (P-value < 0.05). While a significant correlation was observed between the expression levels of NEAT1 and PTEN genes in AML patients (P-value < 0.05), there was no correlation between the expression levels of NEAT1 with P53 and BCL-2 (P-value > 0.05). CONCLUSION: According to the results, increased expression of NEAT1 gene may play a role in the apoptosis of AML cells, despite the oncogenic role in most solid tumors.

High levels of Von Willebrand factor markers in COVID-19: a systematic review and meta-analysis.

The SARS-CoV-2 virus has spread to all corners of the world. Thrombosis is the cause of organ failure and subsequent death in COVID-19. The pathophysiology of thrombosis in COVID-19 needs to be further explored to shed light on its downside. For this reason, this meta-analysis of Von Willebrand Factor profile (VWF: Ag, VWF: activity, VWF: RCo), ADAMTS-13, and factor VIII levels in COVID-19 was performed. To obtain data on the status of the aforementioned hemostatic factors, a systematic literature review and meta-analysis were performed on COVID-19. After reviewing the evaluation of 348 papers, 28 papers included in the meta-analysis, which was performed using STATA. The analysis showed an increase in VWF: Ag levels in COVID-19 patients. VWF: Ac was higher in all COVID-19 patients, while it was lower in the COVID-19 ICU patients. The pooled mean of VWF: RCO in all patients with COVID-19 was 307.94%. In subgroup analysis, VWF: RCO was significantly higher in ICU patients than in all COVID-19 patients. The pooled mean of ADAMTS-13 activity was 62.47%, and 58.42% in ICU patients. The pooled mean of factor VIII level was 275.8%, which was significantly higher in ICU patients with COVID-19 than all patients with COVID-19. Levels of VWF: Ag, VWF: activity, VWF: ristocetin, and factor VIII are increased in patients with COVID-19. The elevated levels in ICU patients with COVID-19 suggest that these markers may have prognostic value in determining the severity of COVID-19. New therapeutic programs can be developed as a result.

Blockade of TGF-ßR improves the efficacy of doxorubicin by modulating the tumor cell motility and affecting the immune cells in a melanoma model.

TGF-ß contributes to drug resistance and the invasiveness of tumor cells and weakens the anti-tumor immune responses. The present study aimed at examining the efficacy of the combination of SB431542, as a specific inhibitor of TGF-ßR, and doxorubicin in controlling the melanoma tumor in mice. The impact of the combination of the doxorubicin and SB431542 on the cell growth, apoptosis, migration, and invasiveness of B16-F10 cells was examined. Besides, the B16-F10 tumor was induced in C57BL/6 mice, and the effects of the mentioned treatment on the tumor volume, survival, and the exhaustion state of T cells were evaluated. Although the combination of doxorubicin and SB431542 did not exhibit synergism in the inhibition of cell growth and apoptosis induction, it efficiently prohibited the migration and the epithelial to mesenchymal transition of B16-F10 cells, and the combination of doxorubicin and SB431542 caused an increase in mRNA levels of E-cadherin and, on the other hand, led to a decline in the expression of Vimentin. Tumor volume and the survival of tumor-bearing mice were efficiently controlled by the combination therapy. This treatment also eventuated in a decrease in the percentage of PD-L1+, TCD4+, and TCD8+ cells as indicators of exhausted T cells within the spleens of tumor-bearing mice. Blockade of TGF-ßR also propelled the RAW 264.7 cells towards an anti-tumor M1 macrophage phenotype. The inhibition of TGF-ßR demonstrated a potential to increase the efficacy of doxorubicin chemotherapy by the means of affecting cellular motility and restoring the anti-tumor immune responses.