Gastrointestinal and Hepatic Involvement in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic coronavirus disease-19 (COVID-19) that began in Wuhan city, China, in December 2019. Till 14th April, 19,39,801 people have been affected by this virus, of whom 1,20,897 died. Though respiratory symptoms are the typical manifestation of this disease, gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, loss of taste sensation, diarrhea, abdominal pain, and discomfort have been reported. The pooled prevalence of GI symptom is 17.6% (95% confidence interval, 12.3%-24.5%), as indicated in a meta-analysis. A few studies suggested that the presence of GI symptoms is associated with poorer prognosis. The virus is excreted in feces during the acute disease, and even after, the nasopharyngeal swab has become negative for viral ribonucleic acid. Fecal viral excretion may have clinical significance because of possible feco-oral transmission of the infection. Nearly, 10.5%-53% of patients with COVID-19, particularly those with severe disease, have been shown to have an elevation of hepatic enzymes though biochemical and clinical jaundice are uncommon. Knowledge about this disease in general and GI involvement, in particular, is currently evolving.

Novel SARS-CoV-2/COVID-19: Origin, pathogenesis, genes and genetic variations, immune responses and phylogenetic analysis.

In this review, we focused on the origins of the novel coronavirus (SARS-CoV-2), origin, pathogenesis, immune responses, genes and genetic variations, phylogenetic analyses, and potential therapeutic strategies to summarize approaches for developing broadly effective preventions and vaccines to cope COVID-19. Towards the end of 2019, SARS-CoV-2 has emerged in association with the SARS, later was named COVID-19 caused an environment of chaos worldwide and infected a massive number of lives. Since these epidemics or pandemics had spread to 210 countries and territories around the world and 2 international conveyances with 6,467,229 confirmed cases, including, 382,766 deaths, as of June 03, 2020 (https://www.worldometers.info/coronavirus/), hence the World Health Organization declared it as a global Public Health Emergency. There are no clinically approved vaccines or antiviral drugs available for either of new or old corona infections; thus, the development of effective therapeutic and preventive strategies that can be readily available to cope with these strains.

Differences in the expression of the renin angiotensin system and the kallikrein-kinin system during the course of myocardial infarction in male and female Wistar rats.

BACKGROUND: There is some evidence that components of the renin-angiotensin system and kallikrein-kinin system are not similarly regulated in both sexes. The aim of this work was to analyze the expression of angiotensin-converting enzyme, angiotensin-converting enzyme 2, angiotensin 1 receptor, angiotensin 2 receptor, beta-1 receptor, and beta-2 receptor during the evolution of myocardial infarction. METHODS: Thirty-six male and 36 female Wistar rats were used. Myocardial infarction was induced. Six groups of both sexes were formed, (n=6): (a) sham; (b) 48 h myocardial infarction; (c) one week myocardial infarction; (d) two weeks myocardial infarction; (e) three weeks myocardial infarction and (f) four weeks myocardial infarction. The expression was evaluated by real-time polymerase chain reaction on the penumbra of left ventricle. RESULTS: The mRNA expression of most biomarkers was lower in females than in males. During acute infarction, an increase of all protein expression was found in female and at two weeks while in the male only biomarker changes occurred at three weeks. In addition, in male biomarkers mRNA expression decreased during chronic infarction while in females it did not. CONCLUSIONS: The renin-angiotensin system and kallikrein-kinin system biomarkers expression occurs at earlier times in the female than in the male rat. In addition, during chronic myocardial infarction these biomarkers remained unchanged in females while in males they decreased.

Angiotensin receptor subtypes regulate adipose tissue renewal and remodelling.

Obesity is often associated with high systemic and local renin-angiotensin system (RAS) activity in adipose tissue. Adipose-derived mesenchymal stem/stromal cells (ADSCs), responsible for adipose tissue growth upon high-fat diet, express multiple angiotensin II receptor isoforms, including angiotensin II type 1 receptor (AT1 R), angiotensin II type 2 receptor (AT2 R), Mas and Mas-related G protein-coupled receptor D. Although AT1 R is expressed on most ADSCs, other angiotensin receptors are co-expressed on a small subpopulation of the cells, a phenomenon that results in a complex response pattern. Following AT1 R activation, the effects are transient due to rapid receptor internalisation. This short-lived effect can be prevented by heteromerisation with AT2 R, a particularly important strategy for the regulation of ADSC differentiation and secretory activity. Heteromeric AT2 R might be especially important for the generation of thermogenic beige adipocytes. This review summarises current data regarding the regulation of adipose tissue renewal and particularly ADSC adipogenic differentiation and secretory activity by RAS, with an emphasis on AT2 R and its effects. We reveal a new scheme that implicates AT2 R into the regulation of ADSC hormonal sensitivity.

Association of angiotensin receptor 2 gene polymorphisms with pregnancy induced hypertension risk.

OBJECTIVES: To investigate the association of polymorphisms and haplotypes of angiotensin receptor 2 (AT2R) gene with pregnancy induced hypertension (PIH) in Chinese Han women. METHODS: A case-control study was designed with 446 cases (gestational hypertension, GH: 124; pre-eclampsia, PE + eclampsia, E: 322) and 650 controls. rs5193, rs1403543 and rs12710567 of AT2R gene were genotyped. A logistic regression approach was applied to estimate the relationship between the polymorphisms and haplotypes of AT2Rgene with PIH risk. RESULTS: No relationship between AT2R gene polymorphisms and PIH was detected. The haplotype analysis also showed a negative result. CONCLUSIONS: rs5193, rs1403543 and rs12710567 of AT2R gene might have no effect on PIH risk among Chinese Han women.

A Novel Antithrombotic Mechanism Mediated by the Receptors of the Kallikrein/Kinin and Renin-Angiotensin Systems.

The contact activation (CAS) and kallikrein/kinin (KKS) systems regulate thrombosis risk in two ways. First, the CAS influences contact activation-induced factor XI activation and thrombin formation through the hemostatic cascade. Second, prekallikrein (PK) and bradykinin of the KKS regulate expression of three vessel wall G-protein-coupled receptors, the bradykinin B2 receptor (B2R), angiotensin receptor 2, and Mas to influence prostacyclin formation. The degree of intravascular prostacyclin formation inversely regulates intravascular thrombosis risk. A 1.5- to 2-fold increase in prostacyclin, as seen in PK deficiency, increases vessel wall Sirt1 and KLF4 to downregulate vessel wall tissue factor which alone is sufficient to lengthen induced thrombosis times. A twofold to threefold increase in prostacyclin, as seen the B2R-deficient mouse, delays thrombosis and produces a selective platelet function defect of reduced GPVI activation and platelet spreading. Regulation of CAS and KKS protein expression has a profound influence on thrombosis-generating mechanisms in the intravascular compartment.

Physiologic activities of the contact activation system.

The plasma contact activation (CAS) and kallikrein/kinin (KKS) systems consist of 4 proteins: factor XII, prekallikrein, high molecular weight kininogen, and the bradykinin B2 receptor. Murine genetic deletion of factor XII (F12(-/-)), prekallikrein (Klkb1(-/-)), high molecular weight kininogen (Kgn1(-/-)) and the bradykinin B2 receptor (Bdkrb2(-/-)) yield animals protected from thrombosis. With possible exception of F12(-/-) and Kgn1(-/-) mice, the mechanism(s) for thrombosis protection is not reduced contact activation. Bdkrb2(-/-) mice are best characterized and they are protected from thrombosis through over expression of components of the renin angiotensin system (RAS) leading to elevated prostacyclin with vascular and platelet inhibition. Alternatively, prolylcarboxypeptidase, a PK activator and degrader of angiotensin II, when deficient in the mouse leads to a prothrombotic state. Its mechanism for increased thrombosis also is mediated in part by components of the RAS. These observations suggest that thrombosis in mice of the CAS and KKS are mediated in part through the RAS and independent of reduced contact activation.