Effect of genetic profiling on surgical decisions at hereditary colorectal cancer syndromes.

Hereditary colorectal cancer syndromes, such as Lynch syndrome and familial adenomatous polyposis (FAP), present significant clinical challenges due to the heightened cancer risks associated with these genetic conditions. This review explores genetic profiling impact on surgical decisions for hereditary colorectal cancer (HCRC), assessing options, timing, and outcomes. Genotypes of different HCRCs are discussed, revealing a connection between genetic profiles, disease severity, and outcomes. For Lynch syndrome, mutations in the MLH1, MSH2, MSH6, and PMS2 genes guide the choice of surgery. Subtotal colectomy is recommended for patients with mutations in MLH1 and MSH2, while segmental colectomy is preferred for those with MSH6 and PMS2 mutations. In cases of metachronous colon cancer after segmental colectomy, subtotal colectomy with ileorectal anastomosis is advised for all mutations. Surgical strategies for primary rectal cancer include anterior resection or abdominoperineal resection (APR), irrespective of the specific mutation. For rectal cancer occurring after a previous segmental colectomy, proctocolectomy with ileal pouch-anal anastomosis (IPAA) or APR with a permanent ileostomy is recommended. In FAP, surgical decisions are based on genotype-phenotype correlations. The risk of desmoid tumors post-surgery supports a single-stage approach, particularly for certain APC gene variants. Juvenile Polyposis Syndrome (JPS) surgical decisions involve genetic testing, polyp characteristics with attention to vascular lesions in SMAD4 mutation carriers. However, genetic profiling does not directly dictate the specific surgical approach for JPS. In conclusion this review highlights the critical role of personalized surgical plans based on genetic profiles to optimize patient outcomes and reduce cancer risk. Further research is needed to refine these strategies and enhance clinical guidelines.

MicroRNAs as biomarkers for early diagnosis, targeting and prognosis of prostate cancer.

Globally, prostate cancer (PC) is leading cause of cancer-related mortality in men worldwide. Despite significant advances in the treatment and management of this disease, the cure rates for PC remains low, largely due to late detection. PC detection is mostly reliant on prostate-specific antigen (PSA) and digital rectal examination (DRE); however, due to the low positive predictive value of current diagnostics, there is an urgent need to identify new accurate biomarkers. Recent studies support the biological role of microRNAs (miRNAs) in the initiation and progression of PC, as well as their potential as novel biomarkers for patients' diagnosis, prognosis, and disease relapse. In the advanced stages, cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant part of circulating vesicles and cause detectable changes in the plasma vesicular miRNA profile. Recent computational model for the identification of miRNA biomarkers discussed. In addition, accumulating evidence indicates that miRNAs can be utilized to target PC cells. In this article, the current understanding of the role of microRNAs and exosomes in the pathogenesis and their significance in PC prognosis, early diagnosis, chemoresistance, and treatment are reviewed.

Cardiovascular manifestations in COVID-19 patients: A systematic review and meta-analysis.

Since December 2019, the COVID-19 pandemic has affected the global population, and one of the major causes of mortality in infected patients is cardiovascular diseases (CVDs).For this systematic review and meta-analysis, we systematically searched Google Scholar, Scopus, PubMed, Web of Science, and Cochrane databases for all articles published by April 2, 2020. Observational studies (cohort and cross-sectional designs) were included in this meta-analysis if they reported at least one of the related cardiovascular symptoms or laboratory findings in COVID-19 patients. Furthermore, we did not use any language, age, diagnostic COVID-19 criteria, and hospitalization criteria restrictions. The following keywords alone or in combination with OR and AND operators were used for searching the literature: "Wuhan coronavirus", "COVID-19", "coronavirus disease 2019", "SARS-CoV-2", "2019 novel coronavirus" "cardiovascular disease", "CVD", "hypertension", "systolic pressure", "dyspnea", "hemoptysis", and "arrhythmia". Study characteristics, exposure history, laboratory findings, clinical manifestations, and comorbidities were extracted from the retrieved articles. Sixteen studies were selected which involved 4754 patients, including 2103 female and 2639 male patients. Among clinical cardiac manifestations, chest pain and arrhythmia were found to have the highest incidence proportion. In addition, elevated lactate dehydrogenase (LDH) and D-dimer levels were the most common cardiovascular laboratory findings. Finally, hypertension, chronic heart failure, and coronary heart disease were the most frequently reported comorbidities. The findings suggest that COVID-19 can cause various cardiovascular symptoms and laboratory findings. It is also worth noting that cardiovascular comorbidities like hypertension have a notable prevalence among COVID-19 patients.

PD-1 and cancer: molecular mechanisms and polymorphisms.

The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers. In particular, PD-1 over-expression influences tumor-specific T cell immunity in a cancer microenvironment. Blocking the PD-1/PD-1 ligand (PD-L1) pathway could potentially augment endogenous antitumor responses. Along these lines, the use of PD-1/PD-L1 inhibitors has been applied in clinical trials against diverse forms of cancer. It was believed that antibodies targeting PD-1/PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity by blocking inhibitory receptor-ligand interactions. However, in all cases, the host genetic status (as well as that of the tumor) is likely to have an impact on the expected outcomes. Various investigations have evaluated the association between PD-1 polymorphisms and the risk of various types of cancer. Frequently studied PD-1 polymorphisms, PD-1.1 (rs36084323), PD-1.3 (rs11568821), PD-1.5 (rs2227981), PD-1.9 (rs2227982), and PD-1 rs7421861, and their associations in the risk of susceptibility to different types of cancer are mentioned in this review, as are studies highlighting the significance of conducting genetic association studies in different ethnic populations.

Association of endothelial nitric oxide synthase gene variants (-786 T>C, intron 4 b/a VNTR and 894 G>T) with idiopathic recurrent pregnancy loss: A case-control study with haplotype and in silico analysis.

OBJECTIVE(S): Many lines of evidence suggest that reduced production of nitric oxide (NO) due to single nucleotide polymorphisms in endothelial nitric oxide synthase (eNOS) gene may affect the implantation and maintenance of pregnancy. Accordingly, our objective was to investigate whether the eNOS polymorphisms (-786 T>C, intron 4 b/a VNTR and 894 G>T) and haplotypes may be associated with increased susceptibility to recurrent pregnancy loss (RPL). STUDY DESIGN: A total of 130 women with a history of two or more unexplained consecutive first trimester miscarriages and 110 ethnically matched women with at least two normal pregnancies and no history of pregnancy loss were included in the study as cases and controls, respectively. To identify the genotypes, we used polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods In addition, an in silico analysis was conducted to predict the possible effects of the eNOS 894 G>T polymorphism on the structure and function of eNOS mRNA and protein using prediction servers. RESULTS: Our findings revealed that the prevalence of eNOS -786 T>C polymorphism, eNOS -786C allele and TC+CC genotype in cases were significantly higher than those in healthy controls (p<0.05). Also, the combination genotypes -786TT/4b4a and -786TT/894GG were significantly associated with reduced risk of RPL. We also found that the C-4a-G haplotype of the eNOS gene studied polymorphisms was significantly associated with a predisposition to RPL (odds ratio, 3.219; 95% confidence interval, 1.649-6.282; p=0.0003). The in silico analysis showed that the eNOS 894 G>T polymorphism couldn't affects eNOS mRNA and protein significantly. CONCLUSION: Our findings provide evidence to support the hypothesis that eNOS -786 T>C polymorphism and the -786C-4a-894G haplotype are associated with the high risk of RPL.