Chromosomal single-strand break repair and neurological disease: Implications on transcription and emerging genomic tools.

Cells are constantly exposed to various sources of DNA damage that pose a threat to their genomic integrity. One of the most common types of DNA breaks are single-strand breaks (SSBs). Mutations in the repair proteins that are important for repairing SSBs have been reported in several neurological disorders. While several tools have been utilised to investigate SSBs in cells, it was only through recent advances in genomics that we are now beginning to understand the architecture of the non-random distribution of SSBs and their impact on key cellular processes such as transcription and epigenetic remodelling. Here, we discuss our current understanding of the genome-wide distribution of SSBs, their link to neurological disorders and summarise recent technologies to investigate SSBs at the genomic level.

The role of angiotensin-converting enzyme 2 (ACE2) genetic variations in COVID-19 infection: a literature review.

Background: The angiotensin-converting enzyme-2 (ACE2) is recognized to be the fundamental receptor of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), responsible for the worldwide Coronavirus Disease-2019 (COVID-19) epidemic. However, genetic differences between people besides racial considerations and their relation to disease susceptibility are still not fully elucidated. Main body: To uncover the role of ACE2 in COVID-19 infection, we reviewed the published studies that explore the association of COVID-19 with the functional characteristics of ACE2 and its genetic variations. Notably, emerging studies tried to determine whether the ACE2 variants and/or expression could be associated with SARS-CoV/SARS-CoV2 have conflicting results. Some researchers investigated the potential of "population-specific" ACE2 genetic variations to impact the SARS-CoV2 vulnerability and suggested no ethnicity enrichment for ACE2 polymorphisms that could influence SARS-CoV2 S-protein binding. At the same time, some studies use data mining to predict several ACE2 variants that could enhance or decline susceptibility to SARS-CoV. On the other hand, fewer studies revealed an association of ACE2 expression with COVID-19 outcome reporting higher expression levels of ACE2 in East Asians. Conclusions: ACE2 gene variants and expression may modify the deleterious consequences of SARS-CoV2 to the host cells. It is worth noting that apart from the differences in gene expression and the genetic variations of ACE2, many other environmental and/or genetic factors could modify the disease outcome, including the genes for the innate and the adaptive immune response.

Association of polymorphisms in metastasis suppressor genes NME1 and KISS1 with breast cancer development and metastasis.

BACKGROUND: NME1 and KISS1 genes are two tumor metastasis suppressor genes, mapped to chromosomes 17q21.3 and 1q32 respectively. Here, we analyzed the association of EcoR1 (rs34214448-G/T) polymorphism in NME1 gene and 9 del T (rs5780218-A/-) polymorphism in KISS1 gene with breast cancer development and metastasis. RESULTS: The study included 75 women newly diagnosed with breast cancer recruited from Oncology Center at Mansoura University Hospitals and 37 age-matched healthy female volunteers as a control group. DNA was extracted from peripheral blood samples and genotyping of rs34214448 and rs5780218 SNPs was carried out by PCR-RFLP technique. NME1 EcoR1 (rs34214448) polymorphism has a statistically significant association with breast cancer risk (P < 0.001). Most of breast cancer group (55%) had heterozygous (G/T) genotype while most of control group (95%) had homozygous wild (G/G) genotype (P < 0.0005). Also, KISS1 rs5780218 polymorphism has a statistically significant association with breast cancer risk. The wild (A/A) genotype was associated with lower risk of breast cancer (A/- + -/- vs. A/A: OR = 3.1, 95% CI = 1.15-8.36, P = 0.025). EcoR1 (rs34214448) polymorphism revealed a significant association with tumor stage and distant metastasis as patients. Carriers of the wild (G/G) genotype were more likely to present with advanced disease stages and distant metastasis. CONCLUSIONS: Both EcoR1 (rs34214448) polymorphism of NME1 gene and rs5780218 polymorphism of KISS1 gene revealed significant association with increased risk of breast cancer development. The (G/G) genotype of EcoR1 polymorphism was associated with higher risk of breast cancer metastasis.

Biomarkers in Spinal Cord Injury: Prognostic Insights and Future Potentials.

Spinal Cord Injury (SCI) is a major challenge in Neurotrauma research. Complex pathophysiological processes take place immediately after the injury and later on as the chronic injury develops. Moreover, SCI is usually accompanied by traumatic injuries because the most common modality of injury is road traffic accidents and falls. Patients develop significant permanent neurological deficits that depend on the extent and the location of the injury itself and in time they develop further neurological and body changes that may risk their mere survival. In our review, we explored the recent updates with regards to SCI biomarkers. We observed two methods that may lead to the appearance of biomarkers for SCI. First, during the first few weeks following the injury the Blood Spinal Cord Barrier (BSCB) disruption that releases several neurologic structure components from the injured tissue. These components find their way to Cerebrospinal Fluid (CSF) and the systemic circulation. Also, as the injury develops several components of the pathological process are expressed or released such as in neuroinflammation, apoptosis, reactive oxygen species, and excitotoxicity sequences. Therefore, there is a growing interest in examining any correlations between these components and the degrees or the outcomes of the injury. Additionally, some of the candidate biomarkers are theorized to track the progressive changes of SCI which offers an insight on the patients' prognoses, potential-treatments-outcomes assessment, and monitoring the progression of the complications of chronic SCI such as Pressure Ulcers and urinary dysfunction. An extensive literature review was performed covering literature, published in English, until February 2018 using the Medline/PubMed database. Experimental and human studies were included and titles, PMID, publication year, authors, biomarkers studies, the method of validation, relationship to SCI pathophysiology, and concluded correlation were reported. Potential SCI biomarkers need further validation using clinical studies. The selection of the appropriate biomarker group should be made based on the stage of the injuries, the accompanying trauma and with regards to any surgical, or medical interference that might have been done. Additionally, we suggest testing multiple biomarkers related to the several pathological changes coinciding to offer a more precise prediction of the outcome.

Uterine Sarcoma: Analysis of 13,089 Cases Based on Surveillance, Epidemiology, and End Results Database.

OBJECTIVE: The aim was to study the incidence and survival of patients with uterine sarcoma diagnosed in the period from 2000 to 2012 based on Surveillance, Epidemiology, and End Results (SEER) database. METHODS: All 18 registries of the SEER database were used to select cases. We included women aged 30 years or older diagnosed with uterine sarcoma. Histological subtypes were defined as leiomyosarcoma, carcinosarcoma, stromal sarcoma, adenosarcoma, and sarcoma not otherwise specified according to the 2003 World Health Organization classification. Using SEER*Stat software version 8.1.2. We calculated the age-adjusted incidence rates, extent of disease at time of diagnosis, and survival rates with different treatment modalities for white, black, and other races. Univariate and multivariate Cox proportional hazards analysis were done to examine factors affecting survival. RESULTS: We identified 13,089 patients diagnosed with uterine sarcoma in the period from 2000 to 2012. The age-adjusted incidence rate for patients aged 50 years or older was more than that of younger patients (6.4/10 vs 1.5/10, P < 0.0001). Also, the age-adjusted incidence rate for black women was twice that of white women (7.3/10 vs 3.5/10, P < 0.0001). Carcinosarcoma was the most commonly diagnosed subtype followed by leiomyosarcoma. Women aged 50 years or older had worse survival than those younger than 50 years (hazard ratio, 1.78; 95% confidence interval, 1.64-1.92; P < 0.001). The overall survival of patients who had surgery with radiation was better than those who had surgery alone (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P < 0.001). In women with localized disease, surgery was associated with better survival than surgery with radiation (66.4% vs 74.4%, P < 0.00001). CONCLUSIONS: Uterine sarcoma is an aggressive tumor that occurs more in old age and among women of black race. Poor survival was associated with old age, black race, and advanced disease stage. Radiotherapy in patients with localized stage does not improve the survival.