Angiotensin Converting Enzyme 2 (ACE2) and COVID-19: An overview of its structure, physiologic role and its involvement in SARS-COV2 infection and therapy

Coronavirus disease of 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a great global and national public health concern. Structural studies suggested that the SARS-CoV2 binds through its spike-protein to target cells by interacting with the angiotensin-converting enzyme 2 (ACE2) receptor which is widely expressed in the heart, kidneys, lungs, gut and testes cells. This article reviews the structural and physiologic roles of the human ACE2 and its correlation with the SARS-CoV2 infection and therapy. Evidence has been provided that the amino acids 318-510 of the viral spike protein represent the receptor-binding domain (RBD) which binds to ACE2, especially by means of the critical amino acids at positions 479 and 487, then allowing virus tropism and propagation. ACE2 play a crucial role in the down regulation of the renin-angiotensin-aldosterone system (RAAS). The RAAS ACE-Angiotensin II-AT1R regulatory axis promotes detrimental effects on the host, such as vasoconstriction, generation of reactive oxygen species, inflammation and matrix remodeling. However, the ACE2-Ang 1-7-MasR axis counterbalances the activation of the classical RAS system which inhibits cell growth, inflammation and fibrosis. The ACE2 has a protective effect against organ damage, lung injury and underlying chronic diseases such as hypertension, diabetes, and cardiovascular diseases wich are linked with poor prognosis of healing in patients with COVID-19. On account of the protective effects of ACE2, the design and development of drugs enhancing its activity may become one of the most promising strategies for the therapy of COVID-19 in the future

Glioblastomes : les facteurs pronostics cliniques et génétiques

Glioblastoma (GBM) is the most malignant and most aggressive brain tumor with a median survival of one year despit progress in diagnosis and therapy. It’s high-grade malignancy, called astrocytoma grade IV. It’s characterized by a rapidly progressive clinical deterioration and molecullares alterations in distincts genetics pathways. The diagnosis is established by nuclear imaging magnetic raisonnance and confirmation is made by pathological study based on the WHO criteria. Therapeutic strategy based on surgery, radiotherapy and chemotherapy. Age and neurological status as assessed by the Karnofski index and mutation of the IDH are the most important factors associated with prognosis. The aim is to highlight the value of molecular analysis in the identification of histopathological subtypes, clinical and genetic factors that predict prognosis.Les glioblastomes (GBM) sont les tumeurs cérébrales primitives les plus malignes et les plus agressives, avec une survie médiane d’un an en dépits du progrès des moyens diagnostics et thérapeutiques. Ils sont de haut grade de malignité, appelé astrocytome grade IV. Ils sont caractérisés par un tableau clinique rapidement progressif et des altérations molécullaires évoluant dans des voies génétiques distinctes. Le diagnostic est établi par l’imagerie par raisonnance magnétique nucléaire et la confirmation se fait par l’étude anatomo-pathologique en se basant sur les critères de l’OMS. La stratégie thérapeutique repose sur la chirurgie, la radiothérapie et la chimiothérapie. L’âge et le statu neurologique, évalué par l’indice de Karnofski et la mutation de l’IDH sont les facteurs les plus associés au pronostic. Le but est de  mettre en évidence l’intérêt de l’analyse moléculaire dans l’identification des sous types histopathologiques et des facteurs cliniques et génétiques qui permettent de prédire le pronostic

Phytochemical compounds and Pharmacological Activities of Garlic (Allium sativum L.): A Review

Garlic (Allium sativum L.) is a species of monocotyledonous perennial vegetable plant whose bulbs, with a strong odor and taste, are often used as a condiment in cooking and a traditional remedy for various diseases. Garlic possesses more than 100 biologically useful secondary metabolites, including alliin, alliinase, allicin, S-allyl cysteine (SAC), diallyldisulfide (DADS), diallyltrisulfide (DATS) and methyl allyl trisulfide. The γ-glutamyl-S-alk(en)yl-L-cysteines are the major sulfur compounds present in garlic. Fundamental studies have shown that garlic and its bioactive constituents have antioxidant, anti-diabetic, anti-obesity, neuroprotective, anti-inflammatory, antibacterial, antifungal, immunomodulatory, cardiovascular protective, anticancer, renal protective, digestive system protective, hepatoprotective and wound healing properties.This review examines the phytochemical composition, and pharmacological activities of A. sativum extracts as well as its main active constituent, allicin to cure many diseases, highlighting and discussing the relevant mechanisms of actions for many of their therapeutic effects

Density reconstruction from biased tracers and its application to primordial non-Gaussianity

Large-scale Fourier modes of the cosmic density field are of great value for learning about cosmology because of their well-understood relationship to fluctuations in the early universe. However, cosmic variance generally limits the statistical precision that can be achieved when constraining model parameters using these modes as measured in galaxy surveys, and moreover, these modes are sometimes inaccessible due to observational systematics or foregrounds. For some applications, both limitations can be circumvented by reconstructing large-scale modes using the correlations they induce between smaller-scale modes of an observed tracer (such as galaxy positions). In this paper, we further develop a formalism for this reconstruction, using a quadratic estimator similar to the one used for lensing of the cosmic microwave background. We incorporate nonlinearities from gravity, nonlinear biasing, and local-type primordial non-Gaussianity, and verify that the estimator gives the expected results when applied to N-body simulations. We then carry out forecasts for several upcoming surveys, demonstrating that, when reconstructed modes are included alongside directly-observed tracer density modes, constraints on local primordial non-Gaussianity are generically tightened by tens of percents compared to standard single-tracer analyses. In certain cases, these improvements arise from cosmic variance cancellation, with reconstructed modes taking the place of modes of a separate tracer, thus enabling an effective "multitracer" approach with single-tracer observations.Comment: 30 pages plus 14 pages appendices, 19 figure

COVID-19 severityin patients with diabetes and cardiovascular diseases: A Short Review

A novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been become a global health hazard and declared as a pandemic disease by WHO. Patients with Covid-19 and pre-existing medical conditions like cardiovascular diseases, diabetes mellitus and hypertension have an increased risk of severe disease and death. Furthermore, the increased expression of Angiotensin -converting enzyme 2 (ACE-2) in patients with diabetes or cardiovascular diseases could increase the risk of severe infection with SARS-CoV-2

Mutational analysis of the RB1 gene in Moroccan patients with retinoblastoma

PURPOSE: Retinoblastoma (RB), the most common intraocular tumor occurring in infancy and early childhood, is most often related to mutations in the RB1 gene. In this study, we screened the RB1 germline mutations in 41 unrelated Moroccan patients with retinoblastoma, 25 heritable cases, and 16 sporadic unilateral cases. METHODS: After complete ophthalmic examinations were performed and consent obtained, DNA was extracted from peripheral blood, and screening of RB1 mutations was performed with PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene. RESULTS: We identified ten germline mutations in 10/41 (24.39%) unrelated patients, among which three had not been previously reported. The mutation detection rate was 40% (10/25) in the heritable cases and 0% (0/16) in the sporadic unilateral cases. Of these mutations, six were nonsense, and three were frameshifts, all associated with severe phenotypes resulting in bilateral and multifocal tumors. One splice site mutation was found in a familial case associated with a low expressivity phenotype resulting in unilateral and unifocal tumors. Moreover, eight intronic variants were identified, three of which were novel. CONCLUSIONS: This first report of RB1 gene screening in Moroccan patients with retinoblastoma shows a comparable mutational spectrum to those reported previously, which has evident importance for managing patients with retinoblastoma and their families

Association of Spermatogenic Failure with the b2/b3 Partial AZFc Deletion

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3)

Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants

The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts