Novel therapeutic targets for cardiorenal syndrome.

Cardiorenal syndrome (CRS) is an interdependent dysfunction of the heart and kidneys, where failure in one organ precipitates failure in the other. The pathophysiology involves sustained renin-angiotensin-aldosterone-system (RAAS) activation, mitochondrial dysfunction, inflammation, fibrosis, oxidative stress and tissue remodeling, culminating in organ dysfunction. Existing therapies targeting the RAAS, diuretics and other agents have limitations, including diuretic resistance and compensatory sodium reabsorption.

LncRNA MALAT1 as a potential diagnostic and therapeutic target in kidney diseases.

Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript1 (MALAT1) has emerged as a crucial biomarker and therapeutic target for kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), lupus nephritis (LN), and renal cell carcinoma (RCC). LncRNAs are non-coding RNAs that have more than 200 nucleotides that play a crucial role in gene regulation at the post-translational stage, transcriptional, and epigenetic levels. LncRNA MALAT1 regulates gene expression and modulates cellular functions such as proliferation, inflammation, apoptosis, and fibrosis, which are key pathophysiology of kidney diseases.

Novel dysregulated long non-coding RNAs in the acute kidney injury-to-chronic kidney diseases transition unraveled by transcriptomic analysis.

Acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition involves a complex pathomechanism, including inflammation, apoptosis, and fibrosis where long non-coding RNAs (lncRNAs) play a crucial role in their regulation. However, to date, only a few lncRNAs have been discovered to be involved in the AKI-to-CKD transition. Therefore, this study aims to investigate the dysregulated lncRNAs in the AKI-to-CKD transition in vitro and in vivo.

ULK1 as a therapeutic target in kidney diseases: Current perspective.

Introduction: Globally, ~850 million people are affected by different kidney diseases. The pathogenesis of kidney diseases is intricate, where autophagy is crucial for maintaining kidney homeostasis. Iteliminates damaged organelles, thus reducing renal lesions and allowing tissue regeneration.

A perspective on the development of small molecular neprilysin inhibitors (NEPi) with emphasis on cardiorenal disease.

Neprilysin is a cell surface metallo-endopeptidase, commonly identified as neutral endopeptidase (NEP), that plays a crucial role in the cleavage of peptides, for example, natriuretic peptides, angiotensin II, enkephalins, endothelin, bradykinin, substance P, glucagon-like peptide and amyloid beta. In the case of heart failure, a significant upsurge in NEP activity and expression enhances the degradation of natriuretic peptides. Therefore, NEP inhibitors have gained attention in the field of cardiology.

Apelinergic system in acute kidney injury: Mechanistic insights and therapeutic potential.

Acute kidney injury (AKI) has emerged as a global health crisis, surpassing mortality rates associated with several cancers and heart failure. The lack of effective therapies, coupled with challenges in diagnosis and the high cost of kidney transplantation, underscores the urgent need to explore novel therapeutic targets and strategies for AKI. Understanding the intricate pathophysiology of AKI is paramount in this endeavor.

Acyl-CoA Synthetase Long-Chain Isoenzymes in Kidney Diseases: Mechanistic Insights and Therapeutic Implications.

Long-chain acyl-CoA synthetases (ACSLs) are pivotal enzymes in fatty acid metabolism, essential for maintaining cellular homeostasis and energy production. Recent research has uncovered their significant involvement in the pathophysiology of various kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), and renal cell carcinoma (RCC). While ACSL1, ACSL3, ACSL4, and ACSL5 have been extensively studied for their roles in processes such as ferroptosis, lipid peroxidation, renal fibrosis, epithelial-mesenchymal transition, and tumor progression, the role of ACSL6 in kidney diseases remain largely unexplored.

Wnt/beta-catenin modulation: A promising frontier in chronic kidney disease management.

Background: Being amongst the leading factors of death and distress, chronic kidney disease (CKD) has affected around 850 million people globally. The Wnt/β-catenin axis is vital for maintaining kidney homeostasis, from nephron generation to overall management. The β-catenin growth factor is typically not expressed in the adult kidney; however, its expression is found to increase under stress and injury conditions.

Targeting polo-like kinase 1 to treat kidney diseases.

Globally, ∼850 million individuals suffer from some form of kidney disease. This staggering figure underscores the importance of continued research and innovation in the field of nephrology to develop effective treatments and improve overall global kidney health. In current research, the polo-like kinase (Plk) family has emerged as a group of highly conserved enzyme kinases vital for proper cell cycle regulation.

Natriuretic peptide system in hypertension: Current understandings of its regulation, targeted therapies and future challenges.

The natriuretic peptide system (NPS) is the key driving force of the heart's endocrine function. Recent developments in NPS-targeted therapies have been found promising and effective against cardiovascular diseases, including hypertension. Notably, after discovering crosstalk between NPS and the renin-angiotensin-aldosterone system (RAAS), various combinations such as neprilysin/angiotensin II receptor type 1 AT receptor inhibitors and neprilysin/renin inhibitors have been preclinically and clinically tested against various cardiac complications.

A structure-based pharmacophore modelling approach to identify and design new neprilysin (NEP) inhibitors: An in silico-based investigation.

Neutral endopeptidase or neprilysin (NEP) cleaves the natriuretic peptides, bradykinin, endothelin, angiotensin II, amyloid β protein, substance P, etc., thus modulating their effects on heart, kidney, and other organs. NEP has a proven role in hypertension, heart disease, renal disease, Alzheimer's, diabetes, and some cancers.

Network pharmacology combined with molecular docking and dynamics to assess the synergism of esculetin and phloretin against acute kidney injury-diabetes comorbidity.

Acute kidney injury (AKI) is a global health concern with high incidence and mortality, where diabetes further worsens the condition. The available treatment options are not uniformly effective against the complex pathogenesis of AKI-diabetes comorbidity. Hence, combination therapies based on the multicomponent, multitarget approach can tackle more than one pathomechanism and can aid in AKI-diabetes comorbidity management.

Immunosuppressants against acute kidney injury: what to prefer or to avoid?

Background: Acute kidney injury (AKI) is a critical global health issue associated with high mortality rates, particularly in patients undergoing renal transplants and major surgeries. These individuals often receive immunosuppressants to dampen immune responses, but the impact of these drugs on AKI remains unclear.

Objective: This review aims to provide a detailed understanding of the effects of different classes of immunosuppressants against AKI, elucidating their role in either exacerbating or mitigating the occurrence or progression of AKI.

Significance of LncRNAs in AKI-to-CKD transition: A therapeutic and diagnostic viewpoint.

Acute kidney injury to chronic kidney disease (AKI-to-CKD) transition is a complex intermingling of characteristics of both AKI and CKD. Pathophysiologically, the transition lasts seven days after the AKI episode and thereafter silently progresses towards CKD. Growing reports confirm that the AKI-to-CKD transition is heavily regulated by epigenetic modifiers.

Renoprotective effect of esculetin against ischemic acute kidney injury-diabetic comorbidity.

Mitophagy maintains cellular homeostasis by eliminating damaged mitochondria. Accumulated damaged mitochondria can lead to oxidative stress and cell death. Induction of the PINK1/Parkin-mediated mitophagy is reported to be renoprotective in acute kidney injury (AKI).

Molecular insights into P2X signalling cascades in acute kidney injury.

Acute kidney injury (AKI) is a critical health issue with high mortality and morbidity rates in hospitalized individuals. The complex pathophysiology and underlying health conditions further complicate AKI management. Growing evidence suggests the pivotal role of ion channels in AKI progression, through promoting tubular cell death and altering immune cell functions.

Phloretin: a comprehensive review of its potential against diabetes and associated complications.

Objectives: Phloretin is ubiquitous in apples (Malus domestica) and other fruits and has potential antidiabetic properties. Considering the preclinical potential of phloretin, its transition to clinical observations has unintentionally been neglected, particularly within the diabetic population. Furthermore, a comprehensive understanding of its pharmacokinetics remains elusive.

Targeting DNA methylation in diabetic kidney disease: A new perspective.

Diabetic kidney disease (DKD) is a leading diabetic complication causing significant mortality among people around the globe. People with poor glycemic control accompanied by hyperinsulinemia, dyslipidemia, hypertension, and obesity develop diabetic complications. These diabetic patients develop epigenetic changes and suffer from diabetic kidney complications even after subsequent glucose control, the phenomenon that is recognized as metabolic memory.

Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis.

Calcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney's filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations.

ER stress modulated Klotho restoration: A prophylactic therapeutic strategy against acute kidney injury-diabetes comorbidity.

Klotho is a renoprotective factor that is at the forefront of research as a potential therapeutic agent and biomarker of acute kidney injury (AKI). Endoplasmic reticulum (ER) stress and Klotho downregulation are the critical hallmarks of AKI progression. Importantly, the crosstalk between ER and Klotho is still elusive in AKI under diabetic condition.

Phloretin as an add-on therapy to losartan attenuates diabetes-induced AKI in rats: A potential therapeutic approach targeting TLR4-induced inflammation.

Aim: Targeting Toll-like receptor 4 (TLR4) and Angiotensin II type 1 receptor (AT1R) could provide renoprotection during acute kidney injury (AKI) mainly by regulating inflammation, oxidative stress, mitochondrial dysfunction, and apoptosis. Phloretin (TLR4 inhibitor) as an add-on therapy to losartan (AT1R inhibitor) could provide more therapeutic benefits against AKI under diabetic condition. We aimed to study the effect of phloretin as an add-on therapy to losartan against AKI under diabetic condition.

Metabolic reprogramming: Unveiling the therapeutic potential of targeted therapies against kidney disease.

As a high-metabolic-rate organ, the kidney exhibits metabolic reprogramming (MR) in various disease states. Given the >800 million cases of kidney disease worldwide in 2022, understanding the specific bioenergetic pathways involved and developing targeted interventions are vital needs. The reprogramming of metabolic pathways (glucose metabolism, amino acid metabolism, etc.

Epigenetic regulation of mitochondrial-endoplasmic reticulum dynamics in kidney diseases.

Kidney diseases are serious health problems affecting >800 million individuals worldwide. The high number of affected individuals and the severe consequences of kidney dysfunction demand an intensified effort toward more effective prevention and treatment. The pathophysiology of kidney diseases is complex and comprises diverse organelle dysfunctions including mitochondria and endoplasmic reticulum (ER).

Nutraceuticals and network pharmacology approach for acute kidney injury: A review from the drug discovery aspect.

Acute kidney injury (AKI) has become a global health issue, with ∼12 million reports yearly, resulting in a persistent increase in morbidity and mortality rates. AKI pathophysiology is multifactorial involving oxidative stress, mitochondrial dysfunction, epigenetic modifications, inflammation, and eventually, cell death. Hence, therapies able to target multiple pathomechanisms can aid in AKI management.