Impact of vericiguat on heart failure with reduced ejection fraction:a review

Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guanosine monophosphate(cGMP)production are the causes of HF's development.Vericiguat prescribed under the brand name Verquvo was approved by U.S.Food and Drug Administration(FDA)in January 2021.It is a novel agent and the first sGC stimulator which helps to treat patients suffering from heart failure with reduced ejection fraction(HFrEF).Objective:The mechanism of action(cGMP pathway)of vericiguat,its clinical trials,its use in the treatment of heart failure,and its possible future aspects in therapeutic recommendations are all covered in this review.It will also raise awareness amongst healthcare professionals about the pharmacokinetic and pharmacodynamic parameters,dosing,administration,and drug-related problems of this new drug.Methods:Various databases for drug review were used in this review like PubMed,Medline,Google scholar,Drug bank,U.s.FDA,Medscape,and European society of cardiology guidelines.A total of 58 articles were screened out of which 39 articles were included in this review.Results:This review discusses vericiguat's mechanism of action(cGMP pathway),clinical studies,application in the treatment of heart failure,and potential future considerations in therapeutic recommendations.It will also educate healthcare professionals about the new drug's pharmacokinetics and pharmacodynamics,dose,administration,and drug-related problems.Conclusion:After hospitalization for HFrEF,the 5-year survival rate is just 25%,and disease morbidity and death are stil significant.As adjunctive therapy for individuals with heart failure and a low ejection fraction,vericiguat has a moderate level of effectiveness.Vericiguat's efficacy as an adjunct therapy to different drugs used to cure HF has to be further investigated.Vericiguat's safety and dosage in patients who have severe renal or hepatic illness need to be studied further.

Synthesis,characterization and pharmacological evaluation of pyrazolyl urea derivatives as potential anti-inflammatory agents

p38α mitogen activated protein kinase(MAPK) inhibitors provide a novel approach for the treatment of inflammatory disorders.A series of fifteen pyrazolyl urea derivatives(3a-o) were synthesized and evaluated for their p38α MAPK inhibition and antioxidant potential.Compounds 3a-e,3g and 3h showed low micromolar range potency(IC_(50) values ranging from 0.037 ±1.56 to 0.069± 0.07μmol/L)compared to the standard inhibitor SB 203580(IC_(50) = 0.043 + 3.62μmol/L) when evaluated for p38αMAPK inhibition by an immunosorbent-based assay.Antioxidant activity was measured by a 2,2'-diphenyl-1-picryl hydrazyl radical(DPPH) free radical scavenging method and one of the compounds,3c,showed better percentage antioxidant activity(75.06%) compared to butylated hydroxy anisole(71.53%)at 1 mmol/L concentration.Compounds 3a-e,3g and 3h showed promising in vivo anti-inflammatory activity(ranging from 62.25%to 80.93%) in comparison to diclofenac sodium(81.62%).The ulcerogenic liability and lipid peroxidation activity of these compounds were observed to be less in comparison to diclofenac sodium.These compounds also potently inhibited the lipopolysaccharide(LPS)-induced TNF-αrelease in mice(ID_(50) of 3a-c = 19.98,11.32 and 9.67 mg/kg,respectively).Among the screened compounds,derivative 3c was found to be the most potent and its binding mode within the p38α MAPK is also reported.

Assessment of renewable energy:Status,challenges,COVID-19 impacts,opportunities,and sustainable energy solutions in Africa

Today’s more focus and efforts are being put by all the energy leaders towards power generation using renewable energy resources.Fortunately,these resources are becoming affordable to facilitate a swift shift towards green and clean energy.Possible strategic assets are an add-on for all the developing nations in terms of economy.The technological advancement and power market revolution resulting in an adequate reduction of renewable energy cost and affordability.This paper mainly focusing on Covid-19 impacts in the African energy sector.Also,analyzing recent developments in African renewable energy generation that holds the immense capacity for im-provisation.This paper highlighting the recommendations in response to the COVID-19 pandemic for the African renewable energy sector.This paper is a result of rigorous analysis based on major issues governing sustainable solutions for Africa.This review paper comes up with effective conclusions to address the challenges in the cur-rent pandemic situation.In Africa abundance of resources is found with huge potential for the generation of power.But still,Africa undergoing a phase of serious crises because they are not able to tap its huge capital of renewable energies.There is a subsequent need for power grid restructuring,energy storage technologies,and parallel mitigation of environmental factors with seasonal variations.Proposed review analysis bringing a better opportunity for all issues towards sustainable solutions,that will ease the renewable energy status in Africa.It is observed that there is an inevitable need to focus on having strong government policy frameworks and proper regulations.The various recommendations are required to swing towards renewable energy development.Com-bined efforts are required in luring foreign investments and to address feasible issues like setting-up targets.This paper demonstrated a smart energy system using a proposed machine learning-based framework for enhancing the PV forecasting and up-gradation in available technologies.