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According to recent epidemiological analysis, the percentage of world population infected with COVID-19 by end of December 2020 is approximately 12.56% 1 . COVID induced acute care and ICU hospitalization rates are around 9.22 (95% CI: 18.73-19.51), and 4.14 (95% CI: 4.10-4.18) per 1000 population 1 . Although therapeutic strategies such as antivirals, intravenous immunoglobulins and corticosteroids have shown modest efficacy in reducing the disease progression, they are not disease specific and only temper the immune mediated attack on the systemic tissues. Therefore, clinicians started to rely on mRNA COVID-19 vaccines, which are clinically efficacious in reducing the incidence, disease severity and systemic complications of COVID-19 infections. Nevertheless, usage of COVID-19 mRNA vaccines is also associated with cardiovascular complications such as myocarditis and pericarditis. On the other hand, COVID-19 infections itself are associated with cardiovascular complications such as myocarditis. The underlying signaling pathways for occurrence of COVID-19 and mRNA COVID-19 vaccine induced myocarditis are quite different although there is some overlap in autoimmunity and cross reactivity mechanisms. With media reports highlighting the cardiovascular complications of COVID-19 vaccines such as myocarditis, general population have become more hesitant and uncertain regarding the safety and efficacy of these mRNA vaccines. We plan to review the current literature and provide insights into their pathophysiological mechanisms for myocarditis and offer recommendations for further research studies in this regard. This will hopefully dispel some doubts and encourage more people to be vaccinated for preventing the risk of COVID-19 induced myocarditis and other associated cardiovascular complications., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Studies have demonstrated that protease-activated receptors (PARs) with four subtypes (PAR1-4) are mainly expressed in the renal epithelial, endothelial, and podocyte cells. Some endogenous and urinary proteases, namely thrombin, trypsin, urokinase, and kallikrein released during diseased conditions, are responsible for activating different subtypes of PARs. Each PAR receptor subtype is involved in kidney disease of distinct aetiology. PAR1 and PAR2 have shown differential therapeutic outcomes in rodent models of type-1 and type-2 diabetic kidney diseases due to the distinct etiological basis of each disease type, however such findings need to be confirmed in other diabetic renal injury models. PAR1 and PAR2 blockers have been observed to abolish drug-induced nephrotoxicity in rodents by suppressing tubular inflammation and fibrosis and preventing mitochondrial dysfunction. Notably, PAR2 inhibition improved autophagy and prevented fibrosis, inflammation, and remodeling in the urethral obstruction model. Only the PAR1/4 subtypes have emerged as a therapeutic target for treating experimentally induced nephrotic syndrome, where their respective antibodies attenuated the podocyte apoptosis induced upon thrombin activation. Strikingly PAR2 and PAR4 subtypes involvement has been tested in sepsis-induced acute kidney injury (AKI) and renal ischemia-reperfusion injury models. Thus, more studies are required to delineate the role of other subtypes in the sepsis-AKI model. Evidence suggests that PARs regulate oxidative, inflammatory stress, immune cell activation, fibrosis, autophagic flux, and apoptosis during kidney diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

The up-regulation of Wnt/β-catenin pathway induces cardiac function abnormalities, hypertrophy, and fibrosis in diabetic hypertensive and pressure overload models. The present study investigates the cardioprotective effects of Wnt/β-catenin inhibition on isoproterenol (ISO) induced cardiotoxicity in rats. ISO was administered at a dose of 85 mg/kg (s.c) for 2 days. Wnt/β-catenin inhibitor pyrvinium (60 μg/kg, p.o) was given 2h prior and glibenclamide at a dose of 5 mg/kg; p.o, 2 h after ISO injection. Cardiac function parameters were assessed on isolated hearts by using automated Biopac apparatus. The β-catenin transcription and expression was detected by RT-PCR technique and immunohistochemical method. Serum and cardiac tissue biochemical changes including cardiac troponin-I, CK-MB, LDH, anti-oxidant enzyme levels, inflammatory cytokines, and membrane associated Na + /K  +  ATPase and Ca 2+ ATPase and caspase-3 activity, collagen content, fibronectin protein levels were evaluated in various study groups. Histological studies were also carried out to analyze the cardiomyocyte damage, hypertrophy, fibrosis, and necrosis, while α-SMA, TGF-β expression was checked by immunostaining. ISO administration enhanced β-catenin gene expression and transcription which promoted oxidative and nitrosative stress, inflammatory cytokine release, reduced ATP levels, induced over-expression of fibrotic proteins resulting in cardiac hypertrophy, myocardial necrosis, functional and histological changes. However, antagonism of Wnt/β-catenin pathway attenuated these ISO induced pathological manifestations. Notably, the co-treatment with ATP-sensitive K + channel inhibitor partially, reduced the cardioprotective effects of Wnt/β-catenin blocker pyrvinium in ISO rats. Thus Wnt/β-catenin inhibition exhibits cardioprotective in ISO model by anti-oxidant, anti-inflammatory, anti-fibrotic properties and by possible involvement of ATP-sensitive potassium channel activation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Renal injury might originate from multiple factors like ischemia reperfusion (I/R), drug toxicity, cystic fibrosis, radio contrast agent etc. The four adenosine receptor subtypes have been identified and found to show diverse physiological and pathological roles in kidney diseases. The activation of A 1 adenosine receptor (A 1 ) protects against acute kidney injury by improving renal hemodynamic alterations, decreasing tubular necrosis and its inhibition might facilitate removal of toxin or drug metabolite in chronic kidney disease models. Furthermore, recent findings revealed that A 2A receptor subtype activation regulates macrophage phenotype in experimental models of nephritis. Interestingly the emerging role of adenosine kinase inhibitors in kidney diseases has been discussed which act by increasing adenosine availability at target sites and thereby promote A 2A receptor stimulation. In addition, the least explored adenosine receptor subtype A 3 inhibition was observed to exert anti- oxidant, immunosuppressive and anti-fibrotic effects, but more studies are required to confirm its benefits in other renal injury models. The clinical studies targeting A 1 receptor in patients with pre-existing kidney disease have yielded disappointing results, perhaps owing to the origin of unexpected neurological complications during the course of trial. Importantly, conducting well designed clinical trials and testing adenosine modulators with lesser brain penetrability could clear the way for clinical approval of these agents for patients with renal functional impairments., (Copyright © 2020 Elsevier Inc. All rights reserved.)