Structure-Guided Identification and Evaluation of Epalrestat and Ranirestat-Like Compounds Against Aldose Reductase: Therapeutic Management of Diabetic Neuropathy.

Aldose reductase (ALDR) is a critical protein involved in the pathogenesis of diabetic complications such as retinopathy, neuropathy, and nephropathy. Due to the activation of inflammatory and cytotoxic pathways under hyperglycemic conditions, ALDR has become an important target for therapeutic development. Currently, available drugs such as epalrestat and ranirestat are suboptimal due to factors such as toxicity and low solubility.

Targeting programmed death ligand 1 for anticancer therapy using computational drug repurposing and molecular simulations.

Discovering new drug candidates for complex diseases like cancer is a significant challenge in modern drug discovery. Drug repurposing provides a cost-effective and time-efficient strategy to identify existing drugs for novel therapeutic targets. Here, we exploited an integrated in-silico approach to identify repurposed drugs that could inhibit programmed death-ligand 1 (PD-L1).

Advancing vaccine-based immunotherapy in glioblastoma treatment.

Glioblastomas (GBMs) originate from glial cells and are characterized by aggressive growth and poor prognosis. Despite advances in surgical resection, complete elimination remains challenging, often leading to recurrence that is resistant to standard therapies. Immunotherapy and conventional treatments show promise in enhancing therapeutic outcomes across various cancers.

Evidence based molecular pathways, available drug targets, pre- clinical animal models and future disease modifying treatments of huntington's disease.

Huntington's disease is an autosomal dominant neurodegenerative disorder of variable progression. Its major features are motor dysfunction, cognitive decline, and psychiatric disturbances. The onset of HD in a patient occurs because of a polyglutamine-expanding mutation within the HTT gene, which leads to the formation of mutant huntingtin protein that aggregates and disrupts neuronal function.

Non-coding RNAs in cancer therapy-induced cardiotoxicity: Unlocking precision biomarkers for early detection.

Anti-cancer therapy poses significant risks for cardiovascular diseases, including hypertension, thromboembolic ischemia, arrhythmias, dyslipidemia, hyperglycemia, obesity, and high cholesterol. Cardiotoxicity is a leading cause of increased mortality among cancer patients, with many anti-cancer drugs contributing to this issue. Emerging research highlights the role of non-coding RNAs (ncRNAs) in regulating drug-induced cardiotoxicity by influencing genetic, epigenetic, transcriptional, and translational processes.

An in silico Approach for Identification of Novel Natural Selective ALR2 Inhibitors from Cynomorium songaricum for Treating Diabetic Complications.

Introduction: Aldose reductase-2 (ALR2) is a key enzyme in the polyol pathway whose overexpression is implicated in several diabetic complications, including neuropathy, nephropathy, retinopathy, and atherosclerotic plaque formation. Under hyperglycemic conditions, the intracellular accumulation of sorbitol and the depletion of NADPH lead to osmotic imbalance and oxidative stress, driven by the formation of reactive oxygen species and advanced glycation end products. Although various ALR2 inhibitors have been developed, their clinical application has been hampered by nonselective inhibition of both ALR2 and the homologous enzyme ALR1.

Structure-guided discovery of microtubule affinity-regulating kinase 4 inhibitory potential of Harmane: towards therapeutic targeting of Alzheimer's disease.

Microtubule affinity-regulating kinase (MARK), particularly MARK4, are involved in the pathological phosphorylation of tau, contributing to neurodegenerative diseases and conditions such as cancer, inflammation, and atherosclerosis. The β-carboline family, specifically Harmane, exhibits broad biological activity, including neuroprotective effects. We investigated the inhibitory potential of Harmane against MARK4 using both computational and experimental approaches.

Identification of potential inhibitors of interleukin-2-inducible T-cell kinase: insights from docking, molecular dynamics, MMPBSA and free energy landscape studies.

Interleukin-2-inducible T-cell kinase (ITK) is an essential enzyme that plays a key role in both the activation and differentiation of T-cells. As a member of the Tec family of non-receptor tyrosine kinases, ITK is predominantly expressed in T cells, exerting a critical influence on T-cell receptor signaling and downstream pathways. Moreover, ITK regulates cytokine production, notably interleukin-2 (IL-2), and the differentiation of Th2 cells.

Breaking Barriers: Synergistic Interactions Between Pt Single Atoms and Nitrogen-Rich g-CN for Maximized Photocatalytic Hydrogen Production.

Designing an active catalyst and an in situ route for the decoration of single atoms (SA) on graphitic carbon nitride (CN) toward efficient photocatalytic H evolution reaction has been a wide area of focus. However, ultralow loading of SAs and miniaturizing of the catalyst with excess nitrogen for maximized photocatalytic H production from water remains challenging. Herein, a simple novel method is demonstrated to fasten ultralow concentration of Pt atom (0.

Identification of high-affinity inhibitors for epoxide hydrolase 2 from repurposed drugs in Parkinson's disease therapeutics.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that leads to bradykinesia and rest tremors. While the molecular mechanisms underlying PD are not fully understood, rising evidence shows neuroinflammation as a key factor in dopaminergic neuron damage. The soluble epoxide hydrolase (sEH) has appeared as a key player in neuroinflammation associated with PD which represents itself as a promising drug target.

Exploring bioactive phytoconstituents as USP21 inhibitors for therapeutic development against cancer.

Ubiquitin-specific protease 21 (USP21) is a member of the ubiquitin-specific protease subfamily of deubiquitinating enzymes implicated in tumorigenesis and could be a target for anticancer therapy. Remarkably, it has been reported that overexpression and increased activity of USP21 are observed in various types of cancer, which explains the need for its novel small-molecule inhibitors. Plant-based compounds have emerged as promising candidates for therapeutic development due to their diverse biological activities and potential to modulate key molecular targets in disease pathways.

Unveiling Promising PARP12 Inhibitors through Virtual Screening for Cancer Therapy.

Background: Poly (ADP-ribose) polymerase 12 (PARP12) plays a crucial role in DNA damage response (DDR) through DNA repair, maintaining genomic stability. Mutations in PARP12 contribute to genomic instability, leading to cancer progression. Targeting PARP12 mutants with small molecule inhibitors offers a promising therapeutic strategy.

The stereo-divergent functionalization of alkynes: a comprehensive review.

Alkynes are central in crafting pharmaceuticals, agrochemicals, and materials owing to their reactivity and linear geometry. This review unveils cutting-edge advancements in the stereo-divergent functionalization of alkynes, transforming them into invaluable tools for synthesizing stereochemically defined alkenes and alkanes. The review highlights ground-breaking methodologies that achieve exceptional - and -selectivity using innovative catalysts like cobalt, nickel, and palladium through hydrogenation, hydroboration, and hydrosilylation.

Correction: Exploring the role of epidermal growth factor receptor variant III in meningeal tumors.

[This corrects the article DOI: 10.1371/journal.pone.

Mechanistic insights into the inhibition of microtubule affinity-regulating kinase 4 by Syringic acid: A computational and experimental study.

Microtubule affinity regulating kinase 4 (MARK4) is a vital protein kinase that serves as a dual target in cancer and neurodegenerative diseases. It is implicated in the development of tauopathies and also linked to the pathogenesis of several cancer types, implying its importance. Syringic acid is a naturally occurring phenolic molecule that has shown significant efficacies in cancer and neurodegenerative diseases by modulating several key pathways.

Seven Hub Genes Associated with Huntington's Disease and Diagnostic and Therapeutic Potentials Identified by Computational Biology.

Huntington's disease (HD) is characterized by progressive motor dysfunction and cognitive decline. Early diagnosis and new therapeutic targets are essential for effective interventions. We performed integrative analyses of mRNA profiles from three microarrays and one RNA-seq dataset from the Gene Expression Omnibus database.

Therapeutic Targeting of Interleukin-2-Inducible T-Cell Kinase (ITK) for Cancer and Immunological Disorders: Potential Next-Generation ITK Inhibitors.

Interleukin-2-inducible T-cell kinase (ITK) is a critical tyrosine kinase enzyme that is involved in the activation and differentiation of T cells. ITK is mainly found in T cells, which plays an essential role in controlling T-cell receptor signaling and downstream pathways. ITK regulates the synthesis of cytokines, particularly interleukin-2 (IL-2), and the development of Th2 cells.

Ultrafast broadband spectroscopy of widely spread excitonic features in WSe nanosheets.

The performance of an optoelectronic device is largely dependent on the light harvesting properties of the active material as well as the dynamic behaviour of the photoexcited charge carriers upon absorption of light. Recently, atomically thin two-dimensional transition metal dichalcogenides (2D TMDCs) have garnered attention as highly prospective materials for advanced ultrathin solar cells and other optoelectronic applications, owing to their strong interaction with electromagnetic radiation, substantial optical conductivity, and impressive charge carrier mobility. WSe is one such extremely promising solar energy material.

Phytochemicals Withanolide N and Dryobalanolide as Potential Bioactive Leads for Developing Anticancer Drugs Targeting Tyrosine-Protein Kinase Mer.

There is a growing interest in harnessing natural compounds and bioactive phytochemicals to accelerate drug discovery and development, including in the treatment of human cancers. Receptor tyrosine kinases (RTKs) are critical regulators of many fundamental cellular processes and have been implicated in cancer pathogenesis as well as targets for anticancer drug development. The members of TAM, Tyro3, Axl, and MERTK subfamily RTKs, especially Mer, affect immune homeostasis in the tumor microenvironment.

Remodeling of tumour microenvironment: strategies to overcome therapeutic resistance and innovate immunoengineering in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) stands as the most complex and daunting subtype of breast cancer affecting women globally. Regrettably, treatment options for TNBC remain limited due to its clinical complexity. However, immunotherapy has emerged as a promising avenue, showing success in developing effective therapies for advanced cases and improving patient outcomes.

Hybrid of Deep Feature Extraction and Machine Learning Ensembles for Imbalanced Skin Cancer Datasets.

Skin cancer remains one of the most common and deadly forms of cancer, necessitating accurate and early diagnosis to improve patient outcomes. In order to improve classification performance on unbalanced datasets, this study proposes a distinctive approach for classifying skin cancer that utilises both machine learning (ML) and deep learning (DL) methods. We extract features from three different DL models (DenseNet201, Xception, Mobilenet) and concatenate them to create an extensive feature set.

Distinctive roles of aquaporins and novel therapeutic opportunities against cancer.

Aquaporins (AQPs) are integral membrane proteins responsible for facilitating the transmembrane transport of water and small solutes. Their involvement in diverse physiological functions extends to pathological conditions, including cancer, positioning them as promising targets for anticancer therapy. Tumor cells, particularly those with high metastatic potential, exhibit elevated AQP expression, reinforcing their critical role in tumor biology.

Identification of high-affinity Monoamine oxidase B inhibitors for depression and Parkinson's disease treatment: bioinformatic approach of drug repurposing.

Depression and Parkinson's disease (PD) are devastating psychiatric and neurological disorders that require the development of novel therapeutic interventions. Drug repurposing targeting predefined pharmacological targets is a widely use approach in modern drug discovery. Monoamine oxidase B (MAO-B) is a critical protein implicated in Depression and PD.

compounds: A new avenue for ALR-2 inhibition in diabetes mellitus.

Diabetes mellitus (DM) is a prominent contributor to morbidity and mortality in developed nations, primarily attributable to vascular complications such as atherothrombosis occurring in the coronary arteries. Aldose reductase (ALR2), the main enzyme in the polyol pathway, catalyzes the conversion of glucose to sorbitol, leading to a significant buildup of reactive oxygen species in different tissues. It is therefore a prime candidate for therapeutic targeting, and extensive study is currently underway to discover novel natural compounds that can inhibit it.