Abstract-There is increasing evidence that all-trans retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension. Key Words:hypertension, essential Ⅲ angiotensin-converting enzyme Ⅲ renin-angiotensin system Ⅲ rats I t is well-recognized that essential hypertension is a genetically complex metabolic and cardiovascular disorder controlled by both genetic and environmental factors. 1 The ideal aim of modern antihypertensive therapy is not only a reduction of blood pressure but also the prevention or amelioration of its complications, such as myocardial remodeling at the molecular genetic level. 2,3 Research advances on the key transcription factors and nuclear hormone receptors provide insight into the development of novel transcriptionmodulating antihypertensive drugs, among which is all-trans retinoic acid (atRA), a biologically active metabolite of vitamin A. 2 atRA modulates gene transcription and exerts its other effects by binding the retinoic acid receptor (RAR) and retinoid X receptor (RXR) 4,5 and interfering with some key transcription factors such as the activated protein-1. 6,7 Studies have demonstrated that atRA influences the activities of genes responsible for the pathogenesis of hypertension and its complications. 2,3,6,8 Dechow et al 6 reported that atRA reduced blood pressure in the renal damage model. Spontaneously hypertensive rats (SHR) are recognized as genetically hypertensive rats, which resemble, in many aspects, humans with essential hypertension. 9 Chronic atRA treatment prevented medial thickening of intramyocardial and intrarenal arteries and ventricular fibrosis in SHR. 3 However, whether atRA reduces arterial pressure and attenuates myocardial damage in SHR deserves further study.atRA has been shown to regulate the gene expression of components of renin-angiotensin system (RAS), including renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and its type 1 (AT 1 ) receptor. 6,7,10 RAS is critically inv...

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Chronic atRA treatment activates gene and protein expression of APJ and apelin and reduces blood pressure in SHR, suggesting that atRA may regulate the balance between apelin-APJ and angiotensin II-AT(1) signaling and have potential clinical value in the prevention and treatment of human hypertension.

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GSK126 inhibits cell migration and angiogenesis in solid tumor cell lines through down-regulation of VEGF-A expression. Thus, it may be considered as a novel anticancer drug candidate for solid tumor.

ObjectivesAs of 13 January 2021, there have been 3 113 963 confirmed cases of SARS-CoV-2 and 74 619 deaths across the African continent. Despite relatively lower numbers of cases initially, many African countries are now experiencing an exponential increase in case numbers. Estimates of the progression of disease and potential impact of different interventions are needed to inform policymaking decisions. Herein, we model the possible trajectory of SARS-CoV-2 in 52 African countries under different intervention scenarios.DesignWe developed a compartmental model of SARS-CoV-2 transmission to estimate the COVID-19 case burden for all African countries while considering four scenarios: no intervention, moderate lockdown, hard lockdown and hard lockdown with continued restrictions once lockdown is lifted. We further analysed the potential impact of COVID-19 on vulnerable populations affected by HIV/AIDS and tuberculosis (TB).ResultsIn the absence of an intervention, the most populous countries had the highest peaks in active projected number of infections with Nigeria having an estimated 645 081 severe infections. The scenario with a hard lockdown and continued post-lockdown interventions to reduce transmission was the most efficacious strategy for delaying the time to the peak and reducing the number of cases. In South Africa, projected peak severe infections increase from 162 977 to 2 03 261, when vulnerable populations with HIV/AIDS and TB are included in the analysis.ConclusionThe COVID-19 pandemic is rapidly spreading across the African continent. Estimates of the potential impact of interventions and burden of disease are essential for policymakers to make evidence-based decisions on the distribution of limited resources and to balance the economic costs of interventions with the potential for saving lives.

INPH patients present hyperdynamic flow with increased velocity and volume both in systole and diastole phase. Degree of rising in diastole phase exceeds that of systole phase. The resulting reversal of netflow direction may play a key role in the occurrence of ventriculomegaly in iNPH patients.

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