Selective inhibition of histone deacetylase 3 (HDAC3) prevents vincristine-induced peripheral neuropathy via macrophage polarization.

Neuroinflammation is vital in vincristine-induced peripheral neuropathy (VIPN). Locally infiltrated macrophages polarize to pro-inflammatory M1-type, release inflammatory cytokines, and contribute to neuropathic pain. Histone deacetylase 3 (HDAC3) regulates macrophage polarization.

Anthraimidazoledione-based charge transfer probe for solvent-guided selective detection of S and AcO: A colorimetric strategy for analysis of fecal contamination in toilet water.

In this work, we report the design and synthesis of an anthraimidazoledione-based colorimetric probe (compound 1) and investigated their self-assembly properties in the aqueous medium. The compound showed strong intramolecular charge transfer (ICT) characteristics and formation of thermoresponsive, pH-tuneable nanoaggregates in water medium. The probe exhibited a rapid colorimetric response to basic anions, such as CN, F, HPO, and AcO in acetonitrile.

Intensity of Nest Defense of White-Winged Choughs () in Urban Versus Natural Habitats.

Nesting birds face significant risks of predation, prompting parents to invest in nest defense. However, not all environments are the same, and parental investment may vary across different environments. Urbanization often leads to habitat changes and an increase in generalist nest predators, potentially driving a higher risk of reproductive failure for birds.

Design and development of chromene-3-carboxylate derivatives as antidiabetic agents: Exploring the antidiabetic potential via dual inhibition of angiotensin II type 1 receptor and neprilysin enzyme.

Diabetes mellitus, particularly type II diabetes mellitus, is a metabolic condition that has a substantial impact on the health of individuals. The implication of diabetes with increased risk of cardiovascular diseases (CVD) and, consequently, myocardial infarction is well established. However, developing new antidiabetic drugs with an established efficacy on cardiovascular health is an underdeveloped area of research.

Recent advances in designing synthetic plant regulatory modules.

Introducing novel functions in plants through synthetic multigene circuits requires strict transcriptional regulation. Currently, the use of natural regulatory modules in synthetic circuits is hindered by our limited knowledge of complex plant regulatory mechanisms, the paucity of characterized promoters, and the possibility of crosstalk with endogenous circuits. Synthetic regulatory modules can overcome these limitations.

Thermal and desalination performance enhancement of single slope solar still using phase change material.

The study that is being presented focused on the numerical analysis of the melting regime for various phase change materials (PCMs) in order to select an optimal material that would enhance the desalination efficiency of single-slope solar stills. While choosing the PCMs, the following factors were considered, availability, economic viability, environmental friendliness, and thermophysical properties. The study utilised ANSYS Fluent 18.

The interplay of tuberculosis and COVID-19: Insights into global health challenges.

Tuberculosis (TB), an ancient disease, has plagued humankind for centuries, and the coronavirus disease 2019 (COVID-19) pandemic has worsened the crisis. This article discusses various intersecting aspects of TB and COVID-19, including transmission, co-infection, progression, and resurgence, which underline the necessity of a coordinated response. The respiratory transmission routes shared by both diseases, coupled with overlapping symptoms, complicate their diagnosis.

SARM1: The Checkpoint of Axonal Degeneration in the Nervous System Disorders.

Axons are metabolically active neuronal segments with well-controlled axonal degeneration and regeneration. External stress or injury displaces this equilibrium toward degeneration leading to axonal dysfunction observed in the pathology of several diseases. The demand and supply matrix of energy at the synapses are maintained by the axonal transport.

A predictive chromatin architecture nexus regulates transcription and DNA damage repair.

Genomes are blueprints of life essential for an organism's survival, propagation, and evolutionary adaptation. Eukaryotic genomes comprise of DNA, core histones, and several other nonhistone proteins, packaged into chromatin in the tiny confines of nucleus. Chromatin structural organization restricts transcription factors to access DNA, permitting binding only after specific chromatin remodeling events.

Recent Advances in Nanotherapeutics and Theranostics for Squamous Cell Carcinoma: A Comprehensive Review.

Recent advancements in nanotherapeutics have revolutionized cancer treatment through the integration of diagnostic and therapeutic modalities, known as theranostics. This critical review examines the current landscape of nanotherapeutics for various cancers, such as bladder and head and neck squamous cell carcinoma, highlighting current advancements in nanotherapeutics and challenges. Key approaches discussed include biomimetic smart nanocarriers, polymeric smart nanocarriers, inorganic-based smart nanocarriers, and nanorobots.

Recent advancements in the therapeutic approaches for Alzheimer's disease treatment: current and future perspective.

Alzheimer's disease (AD) is a complex, incurable neurological condition characterized by cognitive decline, cholinergic neuron reduction, and neuronal loss. Its exact pathology remains uncertain, but multiple treatment hypotheses have emerged. The current treatments, single or combined, alleviate only symptoms and struggle to manage AD due to its multifaceted pathology.

CLOCK gene 3'UTR and exon 9 polymorphisms show a strong association with essential hypertension in a North Indian population.

Background: Hypertension (HTN) is a medical condition characterized by persistent systolic and diastolic blood pressures of ≥ 140 mmHg and ≥ 90 mmHg, respectively. With more than 1200 million adult patients aged 30-79 years worldwide according to the latest WHO data, HTN is a major health risk factor; more importantly, 46% of patients are unaware of this condition. Essential hypertension (EH), also known as primary hypertension, is the predominant subtype and has a complex etiology that involves both genetic and non-genetic factors.

Structure-based virtual screening of FDA-approved drugs to discover potential inhibitors of phosphoinositide kinase, PIKfyve.

The phosphoinositide kinase, PIKfyve is a lipid kinase that plays a vital role in membrane trafficking, endosomal transport, retroviral budding, and toll-like receptor signaling. Thus, it has emerged as a potential therapeutic target for several diseases, including, cancer, viral infections, and autoimmune diseases. However, a limited number of PIKfyve inhibitors have been reported so far.

Structure-Based Virtual Screening and Biological Characterization of Novel BACE-1 and Amyloid-β Aggregation Inhibitors.

Alzheimer's disease (AD) is a complex neurodegenerative disorder having limited treatment options. The beta-site APP cleaving enzyme 1 (BACE-1) is a key target for therapeutic intervention in Alzheimer's disease. To discover new scaffolds for BACE-1 inhibitors, a ChemBridge DIVERSet library of 20,000 small molecules was employed to structure-based virtual screening.

Medicinal chemistry-based perspectives on thiophene and its derivatives: exploring structural insights to discover plausible druggable leads.

Thiophene is a privileged pharmacophore in medicinal chemistry owing to its diversified biological attributes. The thiophene moiety has been ranked 4th in the US FDA drug approval of small drug molecules, with around 7 drug approvals over the last decade. The present review covers USFDA-approved drugs possessing a thiophene ring system.

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.

Sulfotransferase-mediated phase II drug metabolism prediction of substrates and sites using accessibility and reactivity-based algorithms.

Sulphotransferases (SULTs) are a major phase II metabolic enzyme class contributing ~20 % to the Phase II metabolism of FDA-approved drugs. Ignoring the potential for SULT-mediated metabolism leaves a strong potential for drug-drug interactions, often causing late-stage drug discovery failures or black-boxed warnings on FDA labels. The existing models use only accessibility descriptors and machine learning (ML) methods for class and site of sulfonation (SOS) predictions for SULT.

Rapid paper-based optical sensing of ester hydrolysis.

We have developed an easily scalable chromogenic probe for the dual-mode sensing of Nuclear polyhedrosis viruses (SpobNPV) in aqueous media. The mechanistic investigations establish that the imidazole-mediated hydrolysis of acyl ester linkage in which water (general base) acts as a nucleophile induces a pronounced change in the emission colour from blue to cyan. To the best of our knowledge, this is the first attempt at quantifying OBs of SpobNPV using a small molecule-based optical probe with a detection limit of 2.

Promoter characterization of relZ-bifunctional (pp)pGpp synthetase in mycobacteria.

The second messenger guanosine 3',5'-bis(diphosphate)/guanosine tetraphosphate (ppGpp) and guanosine 3'-diphosphate 5'-triphosphate/guanosine pentaphosphate (pppGpp) ((p)ppGpp) has been shown to be crucial for the survival of mycobacteria under hostile conditions. Unexpectedly, deletion of primary (p)ppGpp synthetase-Rel did not completely diminish (p)ppGpp levels leading to the discovery of novel bifunctional enzyme-RelZ, which displayed guanosine 5'-monophosphate,3'-diphosphate (pGpp), ppGpp, and pppGpp ((pp)pGpp) synthesis and RNAseHII activity. What conditions does it express itself under, and does it work in concert with Rel? The regulation of its transcription and whether the Rel enzyme plays a role in such regulation remain unclear.

Artificially designed synthetic promoter for a high level of salt induction using a cis-engineering approach.

This work aimed to design a synthetic salt-inducible promoter using a cis-engineering approach. The designed promoter (PS) comprises a minimal promoter sequence for basal-level expression and upstream cis-regulatory elements (CREs) from promoters of salinity-stress-induced genes. The copy number, spacer lengths, and locations of CREs were manually determined based on their occurrence within native promoters.

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.

Insulin Analogs and the Mode of Insulin Delivery: Recent Advances and Challenges.

Diabetes is a medical condition associated with impaired glucose regulation caused either due to insufficient insulin production or resistance to insulin (Type 2 diabetes, gestational diabetes) or the absence of insulin through the selective killing of beta cells in the pancreas (Type 1 diabetes). Irregular insulin production leads to various health complications. To prevent such complications, patients must adhere to medical recommendations before availing of any advanced insulin therapy(ies), considered productive for the treatment.

Isomeric Benzenediol-Linked Organophosphonates as a Handy Reusable Emitting Platform: Diversity in Polyamine Vapor Detection.

This work introduces metal/column-free facile quantitative access to conformationally twisted catechol-linked organophosphonate () as a blue-emitting solid that could reversibly detect only 1,3-diaminopropane (DAP) and 1,2-ethylenediamine (EDA) vapors, belonging to industrially and pharmaceutically abundant crucial diamines. In , two adjacent hydroxy groups in a benzene ring facilitate selective diamine-dihydroxy (amine-phenol type) interactions in the solid phase, leading to a quenched emission with selectively smaller aliphatic PAs, that is, DAP and EDA. The disparity was noticed with an isomeric resorcinol-linked emitter (), detecting various polyamine vapors with superior sensitivity.

Tuning sensing efficacy of anthraimidazoledione-based charge transfer dyes: nitro group positioning impact.

Anthraimidazoledione-based optical sensors have been designed by varying the position of the nitro functional group. All three positional isomers showed highly colored, photostable optical signals owing to intramolecular charge transfer interactions. Despite having the same anion-binding site (imidazole unit), the selectivity and sensitivity of the compounds depend on the positioning of the nitro group.