Evaluation of Cardiovascular Diseases Risk in the Iranian Population

Background: Cardiovascular diseases (CVDs) are among the leading causes of death and morbidity around the world. Risk score assessment can assist in anticipating a person's CVD risk over the next five years. Objectives: This study aimed to investigate the risk of CVDs in the general Iranian population. Methods: This study was conducted in September 2020, and 5324 participants aged 35 to 74 years were registered from 95 metro stations throughout Tehran. Participants' demographics (ie, age, gender, current smoking and exercise habits, and family history of hypertension, CVDs, and diabetes) were collected by in-person interviews, and their body mass index (BMI) and systolic blood pressure (SBP) were measured. The five-year risk of CVDs was estimated and categorized into low (< 10%), some risk (10 - 20%), moderate (21 - 30%), increased (31 - 40%), and high (> 40%) groups, and its association with the participants’ demographics was evaluated by SPSS version 21. Results: The mean age of 5324 participants was 45.3 ± 14.8 years, and 64% were male. The frequency of CVD risk scores was as follows: low (54%), some risk (17.5%), moderate (15.4%), increased (5.7%), and high (3.5%), which were significantly associated with gender (P < 0.001), smoking status (P = 0.048), exercise (P = 0.014), and family history of diseases (all P < 0.001). Age (β = 0.774, P < 0.001) increased the odds of CVD, while other variables had small or no effects on CVD. Conclusions: This study found a high prevalence of high-risk CVD in the Iranian population, emphasizing the importance of risk score assessment, which should include not only basic non-laboratory risk assessment scores, but also exercise and a positive family history of associated diseases.

Collagen VI-Related Myopathies: Genetic and Clinical Findings

Introduction: Collagen VI-related disorders are a group of heterogeneous muscular diseases due to mutations within the COL6A1, COL6A2, and COL6A3 genes, encoding collagen VI as an essential component of the extracellular matrix. Here, we reported four patients affected by collagen VI-related disorders with genetic variants in COL6A genes. Case Presentation: After a comprehensive clinical examination, four unrelated patients with muscular dystrophy were referred for genetic counseling. Whole-exome sequencing followed by Insilco analysis was done for one affected individual from each family. The analysis of genomic data revealed four different mutations within the COL6A1, COL6A2, and COL6A3 genes in the affected individuals. Conclusions: According to the previous reports, limb-girdle muscular dystrophy is inherited as autosomal dominant, and congenital myosclerosis phenotype is inherited in an autosomal recessive manner. Carrier testing and prenatal testing are possible if pathogenic variants are recognized in an affected family member.

Diagnostic Potential of miR-30a and miR-200c in Invasive Breast Ductal Carcinoma

Background: Breast cancer is one of the most common cancers worldwide and is responsible for the death of many people. It is mainly found in women; however, it is rarely observed in men. Nowadays, extensive research has been conducted on the detection, diagnosis, and prognosis of biomarkers of this type of cancer, as well as other types. MicroRNAs play a major role in regulating the onset and progression of breast cancer. To date, many significant increases and decreases in microRNAs levels have been reported during various cancers, and also tumor inhibitory roles have been reported for these small non-coding RNA molecules. Methods: In this study, miR-30a and miR-200c were studied to find new expression patterns in breast cancer patients. For this purpose, a quantitative polymerase chain reaction was used to analyze the relationships between expression levels of miR-30a and miR-200c and several clinical and pathological features of the disease, such as tumor stage, HER2 gene expression, and lymphatic metastasis. Results: Our results showed that the expression of miR-200c and miR-30a in tumor samples was significantly lower than in normal samples (P < 0.01). Also, at higher stages of the disease, the expression of both miRNAs was remarkably reduced (P < 0.01). We also found that the expression of two miRNAs in patients with HER2 gene expression and metastasis in lymphatic regions was significantly lower than in HER2-negative and non-metastatic patients (P < 0.05 and P < 0.01, respectively). Conclusions: We identified the relationship between miR-200c and miR-30a and breast cancer. These findings indicate that these microRNAs can be considered biomarkers in breast cancer.

Orofacial Closure Defects: Forty-Five Genes Associated Cleft Lip and Palate

Context: Cleft lip and palate (CLP) is the most common congenital malformations in the face and neck. Given that the inheritance of this disease is multifactorial and both genetic and environmental factors play crucial roles in its creation, studying these factors may be a step toward reducing the prevalence of the disease in future generations. Method: For this study, we looked through several national and international databases, consisting of Scientific Information Database, IranDoc, ScienceDirect, Google Scholar, PubMed, and Scopus. Based on our search method, we found 800 published articles, of which 750 were obtained from the international databases, and the remaining 50 were extracted from the national databases. After data refining, 600 articles with eligible criteria remained for data extraction, and data related to embryological origin, classification and etiology, genes and environmental factors, and complications caused by CLP were collected. Results: The CLP etiology was multifactorial and involved both genetic and environmental risk factors. The primary purpose of this review was to give the reader an overview of studies on multifactorial causes of this congenital disability. The functions of genes are very different, indicating a high level of vulnerability in the cranial and facial growth pathways. Conclusions: These findings have advanced our understanding of genes associated with CLP and genetic polymorphisms involved in orofacial closure defects. The findings can create new clinical and molecular research opportunities.

Application of Genome-Editing Technologies for Off-the-Shelf T Cell-Based Cancer Immunotherapy

: Genetically, engineered T-cell therapy is a personalized treatment that has demonstrated considerable therapeutic potential for solid tumors and hematopoietic cancers. However, endogenous T-cell receptors (TCRs) on the surface of engineered T cells hamper their application in the allogeneic settings by inducing graft-versus-host disease, where endogenous TCRs on the surface of engineered T cells respond to the recipient’s tissues. Since the cause of this allogeneic response is the TCR complex on the surface of the engineered T cells, preventing the expression of TCR components on the surface of these cells is a promising strategy to address this challenge. This review discusses the production of allogeneic chimeric antigen receptor T cells using genome-editing methods.

The Integration Pattern of Human Papillomavirus in the Host Genome as a Promising Guide for Precise Radiation Therapy in Cervical Cancer

Context: Cervical cancer (CC) is one of the most common cancers among women worldwide. Infection with high-risk human papillomavirus (HPV) is the leading risk factor for this cancer. Currently, concurrent chemotherapy and radiotherapy are the standard of care for patients with locally advanced CC. However, the response to radiotherapy varies widely among patients, underscoring the need to identify biomarkers to predict patients’ treatment outcomes. Evidence Acquisition: In order to find relevant articles, we performed a systematic search using ISI Web of Science, Scopus, PubMed, and Embase, with a combination of the keywords “human papillomaviruses”, “cervical cancer”, “radiotherapy”, “biomarkers”, “viral integration”, and “episome”. All types of studies, including observational or retrospective studies, clinical trials, congress abstracts, and case reports or case series, were examined to find relevant data. No time limitation was considered for the studies. Results: The integration of HPV DNA into the host genome is considered to be a critical step in HPV carcinogenesis. The HPV integration pattern has been investigated as a potent prognostic factor for the tailored treatment of CC. Conclusions: It is indicated that the integration state of the HPV genome in host DNA is a potential prognostic or predictive biomarker for CC response to radiotherapy.

Molecular Pathways in Low and High-grade Non-muscle Invasive Bladder Cancer as Revealed by Several OMICs Data Analyses

Background: Bladder cancer is one of the most prevalent cancers, accounting for 2.1% of cancer mortalities worldwide. Bladder cancer is categorized into non-muscle invasive and muscle-invasive bladder cancers. Non-muscle invasive bladder cancer (NMIBC) is the most common and widely heterogeneous type with different outcomes. Objectives: This study was designed to categorize NMIBC tumor grade based on microarray data analysis. Methods: We performed microarray data analysis using GSE7476, GSE13507, and GSE37815 in patients diagnosed with NMIBC. Differentially expressed genes (DEGs) were identified based on low-grade and high-grade NMIBC. Protein-protein interaction (PPI) network analysis was carried out, and hub genes and underlying molecular pathways were identified. Results: We observed low-grade Hub genes, including GAS6, TGFB3, TPM1, COL5A1, COL1A2, SERPING1, ACTA2, TPM2, SDC1, and A2M involved in a variety of gene ontology (GO) biological processes, while high-grade genes were involved in cell cycle and cell division. The most relevant pathways suggested for low-grade NMIBC were extracellular matrix organization, platelet degranulation, and muscle contraction. Conclusions: The identification of gene hubs and underlying pathways in several low and high-grade NMIBC samples may offer better treatment management and prognostication based on molecular profiling.