Exploring the bioactive constituents from spices targeting N-methyl-d-aspartate receptors: An in silico and in vitro approach to identify druggable leads against neurological disability.

N-methyl-d-aspartate (NMDA) receptors are validated druggable targets for the treatment of Alzheimer's and other associated neurological conditions, particularly in individuals with disabilities. Considering the excitotoxicity associated with NMDA receptors, which leads to neuronal damage, cognitive impairment, and limitations of current therapeutic regimens, better therapeutic candidates are required. One of the validated drug discovery approaches is computer-assisted drug discovery, supplemented by molecular docking, mechanics, and dynamics.

Metallic and lipid nanoparticles against multidrug resistant candida: advances and translational hurdles.

Introduction: Among the many ongoing difficulties, Candida infections present significant clinical hurdles due to the rapid development of resistance, recurrent episodes, and the limited effectiveness of conventional therapies. In recent decades, metallic nanoparticles (MNPs) and lipid nanoparticles (LNPs) have shown a specific impact ( > 84% Candida biofilm inhibition in pre-clinical models) by addressing the critical challenges of mitigating drug side effects and multidrug resistance (MDR).

Areas Covered: This paper provides an in-depth overview of synthesis, fabrication, mechanistic insights, preclinical and clinical practices for MNPs and LNPs, discussing and highlighting their therapeutic efficacy against resistant Candida species over traditional methods.

Hesperidin mitigates lead-induced neurotoxicity via TFEB-dependent restoration of mitochondrial function, oxidative balance, and neuroinflammation in rats.

Lead (Pb) neurotoxicity remains a global concern, causing irreversible cognitive and motor impairments through mechanisms like mitochondrial dysfunction, oxidative stress and inflammation. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy that also coordinates mitochondrial function, has emerged as a novel target in neuroprotection. This study evaluated the neuroprotective potential of hesperidin (natural flavonoid) against Pb-induced neurotoxicity, with a focus on the role of TFEB.

Deploying the drug repurposing approach for the identification of selective monoamine oxidase-B inhibitors against neurological disabilities: an in Silico and in vitro approach.

Monoamine oxidase-B (MAO-B) plays a regulatory role in controlling the activity of monoamine neurotransmitters, especially dopamine. Its overexpression leads to a decreased concentration of dopamine in the brain, converts MPTP to MPP + (a potential toxin for dopaminergic neurons), and increases hydrogen peroxide and ROS levels in gliosis, leading to neurodegeneration. Thus, MAO-B becomes a key target enzyme for neurological disabilities such as PD and AD.

Revolutionizing Drug Delivery: The Promise of Self-emulsifying Systems in Overcoming Bioavailability Challenges.

Introduction: The oral route is a preferred method for drug administration; however, lipophilic drugs often suffer from poor water solubility, significantly limiting their therapeutic effectiveness. Traditional approaches like complexation, micronization, and solid dispersion have been explored, but each comes with inherent limitations.

Methods: Self-Emulsifying Drug Delivery Systems (SEDDS) have emerged as a promising strategy to address solubility challenges.

Nanotherapeutics Mediated Intranasal Delivery for Therapeutic Effect on Parkinson's Disease: Balancing Advancements and Challenges.

Managing Parkinson's Disease (PD) presents formidable challenges due to the impermeability of the Blood-Brain Barrier (BBB), which severely restricts effective drug delivery. Traditional treatment modalities often prove inadequate, prompting the exploration of intranasal drug delivery as a novel and promising alternative. This innovative approach provides direct access to the central nervous system while bypassing the Blood-Brain Barrier (BBB).

Employing a drug repurposing strategy to identify B-cell lymphoma-2 (BCL-2) inhibitors with anticancer potential: An in silico and in vitro based study.

BCL-2 (B-cell lymphoma-2) is a key protein overexpressed in numerous cancers. Further, its association with cancer cell survival, prognosis, and ability to evade apoptosis makes it an important drug target in cancer chemotherapy. Venetoclax (ABP199) is the only FDA-approved BCL-2 inhibitor for chronic lymphocytic leukemia (CLL).

Quantum Dots in Neurotheranostics for the Treatment of Alzheimer's Disease.

Age-related neurodegeneration is one of the primary causes associated with the pathogenesis of Alzheimer's disease (AD). Currently, there are 5.8 million cases of AD worldwide.

Design and synthesis of tetrazole tethered quinazoline derivatives via azide-isocyanide cross-coupling reaction: Exploring the utility as anticancer agents via the SRC kinase inhibition in breast cancer.

Kinases, particularly non-receptor tyrosine kinases (nRTK), are vital growth factors that determine the fate of numerous cancers, including breast cancer (BC). One such nRTK is c-Src, which plays a profound role in BC, is associated with BC development and metastasis, and induces resistance to cancer therapeutics. Considering the critical role of c-Src in BC outcome, we herein rationally designed and developed the tetrazole tethered quinazoline derivatives, considering the pharmacophoric feature of the catalytic domain of c-Src.

Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?

The ubiquitin-proteasome system (UPS) plays a critical role in protein homeostasis within eukaryotic cells. This review article examines the UPS's role in neuronal morphology and neurodegeneration through systematic analysis of current research. In neurodegenerative disorders (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), UPS dysfunction contributes significantly to pathogenesis through accumulation of ubiquitinated misfolded proteins, disruption of cellular proteostasis, impaired substrate ubiquitination, and proteasomal deterioration.

Transforming advancing autosomal dominant polycystic kidney disease care: investigating new horizons in treatment and research.

A hereditary disorder called autosomal dominant polycystic kidney disease (ADPKD) results from changes in the PKD1 and PKD2 genes. The most typical indication of ADPKD is the progressive growth of many kidney cysts, which ultimately results in end-stage kidney disease (ESKD) and necessitates renal replacement treatment. Numerous therapies have been developed to treat ADPKD.

Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer's mice model.

Alzheimer's disease (AD) is responsible for more than 80% of cases of dementia in senior individuals globally. In the current study, the role of modulation of the FGF1/PI3K/Akt pathway in the protective effect of tozasertib was evaluated. Experimental dementia was induced in mice by injecting streptozotocin (STZ) intracerebroventricularly.

Recent progress in the development of HSP90 inhibitors: structure-activity relationship and biological evaluation studies.

In cellular biology, Heat Shock Protein 90 (Hsp90) plays a pivotal role in coordinating several processes essential or cellular survival, cell signaling and other processes. This analysis explores the complex structure, biological significance, and regulatory mechanisms clarifying its essential function in preserving cellular homeostasis and its relevance in a range of illnesses, such as cancer, neurological conditions, infectious diseases, cardiovascular conditions, and autoimmune diseases. Hsp90 is a prominent target for cancer treatment.

Target-Specific Potency and Drug-Ability Profile of Flavonoids Against Lung Cancer: An Integrative Multi-Omics Approach for Lead Identification.

Since lung cancer accounts for approximately 20% of cancer-related fatalities globally, it is one of the most common and deadly cancers, necessitating the discovery of innovative, potent, and less toxic treatment agents as imperative. Opportunistically, phytoflavonoids (PFs), a specific class of phytochemicals, display promising anticancer activity through their multimodal apoptosis-inducing properties. Based on existing evidence, the present study employs an integrative multi-omics approach to assess the target-specific binding efficacy and drug-ability outlines of PFs against lung cancer.

Targeting Cdc42: Novel Approaches in Cardiovascular Disorders.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, and need novel molecular targets for improved diagnosis and treatment. There are some potential new molecular targets for CVD treatment, including miRNAs, C-reactive protein, interleukins, fibrinogen, monocyte chemotactic protein-1, etc. One of the newer targets can be cell division control protein 42 homolog (Cdc42), a small GTPase of the Rho family, which has a significant role in cardiovascular physiology and pathology.

A perspective on the synthetic methodologies and biological attributes of thiazole-hydrazone compounds: a medicinal chemistry-based investigation.

Thiazole-hydrazone compounds serve as an essential bis-heterocyclic scaffold in drug discovery, combining the features of a thiazole ring and a hydrazone linkage. This combination offers enhanced biological activity and versatility due to the distinct characteristics of each component. The thiazole ring provides electron density through its sulfur and nitrogen atoms, contributing to lipophilicity and improved membrane permeability, which enhances the drug's ability to reach intracellular targets.

The Dual Role of Conjugated Linoleic Acid in Obesity and Metabolic Disorders.

Conjugated Linoleic Acid (cis-9, trans-11, CLA)/(trans-10, cis-12, CLA) has been extensively studied for its role in obesity control and metabolic diseases. This review explores the molecular characteristics of CLA, its metabolic pathways, and its inconsistent effects on lipid metabolism, adipogenesis, energy expenditure, and inflammation. Preclinical and clinical studies suggest that CLA may promote fat oxidation and modulate adipocyte function; however, inconsistent findings highlight dose-dependent outcomes and individual variability in response.

Exploration of Imatinib involved in amyloidogenesis as a common foundation for type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD).

Diabetes patients have reduced basal cognitive abilities like learning, memory, and perceptual quickness, as well as a 65 percent higher risk of acquiring AD. AD and diabetes share a number of risk factors, including elevated cholesterol, Aβ deposition, degeneration, inflammation, oxidative stress, cardiovascular diseases, dysmetabolism syndrome, τ-protein phosphorylation, glycogen synthesis kinase 3, apoptosis and apolipoprotein E4. This study explores the potential inhibitory effects of imatinib at doses of 1 and 5 mg/kg, with a particular emphasis on the role of c-Abl in amyloidogenesis, a common mechanism that underlies T2DM and AD.

PERK activation mediates neuroprotection against chronic unpredictable stress-induced neurobehavioral changes via the TFEB pathway.

Chronic unpredictable stress (CUS) is a significant contributor to neurobehavioral changes, via disrupted cellular homeostasis, corticosterone and altered neurotransmitter dynamics. The PERK (Protein Kinase RNA-like Endoplasmic Reticulum Kinase)-TFEB (Transcription factor EB) pathway integrates stress responses with autophagy and lysosomal biogenesis to maintain cellular resilience, influencing oxidative stress, neuroinflammation and neurodegeneration. Hence, this study was intended to explore the possible involvement of PERK-TFEB pathway in mediating the neuroprotective effects of SB202190 (a PERK activator) in mitigating neurobehavioral changes induced by CUS.

Hippocampal Neurogenesis: Bridging Stress, Cognitive Decline, and Therapeutic Strategies for Neural Health.

The hippocampus plays a critical role in spatial and contextual learning, and its age-related decline significantly contributes to cognitive impairment. Adult hippocampal neurogenesis (AHN), the continuous production of new neurons in the dentate gyrus, provides a unique form of structural plasticity essential for lifelong learning and memory. AHN is notably altered in various neurodegenerative and mental health disorders characterized by cognitive deficits, suggesting its crucial involvement in maintaining neuronal populations and endogenous regenerative capacity.

Piceatannol attenuates chronic unpredictable stress-induced neurobehavioral deficits in mice via SIRT1-mediated modulation of neuroinflammation, oxidative stress, and neurotransmitter imbalance.

Exposure to chronic unpredictable stress (CUS) serves as the major contributor for the neurobehavioral changes. The current study explores the possible involvement of the SIRT1 pathway in mediating the neuroprotective properties of piceatannol in CUS induced neurobehavioral changes. Molecular docking studies showed binding interactions of piceatannol with SIRT1, suggesting that it may modulate SIRT1 activity.

Small Interfering RNA (siRNA) for Cardiorenal Disease: Mechanistic Insights from Preclinical and Clinical Studies.

Small Interfering RNA (siRNA) is a class of double-stranded, noncoding RNA that silences pathogenic mRNA through the process of RNA interference (RNAi). Its medical application is extensive, particularly in targeting genes associated with cardiorenal diseases, including atherosclerosis, chronic kidney disease, hypertension and cardiac failure. The pathophysiology of cardiorenal syndrome is intricate, involving a network of neurohormonal, metabolic, hemodynamic, and inflammatory interactions.

Parkinson's disease: exploring the systemic immune mechanisms through molecular investigations.

Parkinson's disease (PD) is a neurodegenerative disorder that is mainly caused by the degeneration of dopaminergic neurons of the substantia nigra. Although the pathological feature involves α-synuclein aggregation, recent findings suggest that systemic immune dysregulation is a key process in initiating and advancing the disease. This article seeks to untangle the complex molecular mechanisms that contribute to the immune response in PD, with specific emphasis on innate and adaptive immune processes.

Drug repurposing for renin inhibition: identifying panobinostat for hypertension management.

Renin, an aspartyl protease enzyme, is a crucial part of the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure. However, numerous renin inhibitors, including Aliskiren, Zankiren, Enalkiren, Fasidotril, and Remikiren, are in the clinical arena of managing hypertension, but they are associated with numerous drawbacks. The important one includes modest efficacy in contrast to other antihypertensive agents, which reduces their use as monotherapy; secondly, the related side effects, including hyperkalemia and renal impairment.

Pyrazole in drug development: a medicinal-chemistry based analysis of USFDA-approved drugs in last decade.

Among the diversity of existing heterocycles, nitrogen-containing heterocycles, i.e., azaheterocycles, are the most popular entity in drug discovery.