Fabrication and characterization of teriflunomide-loaded chondroitin sulfate hybridized zein nanoparticles for the management of triple negative breast cancer.

The objective of this work was to explore the Teriflunomide (TFM) -loaded chondroitin sulfate hybridized zein nanoparticles (TZCNPs) for the treatment of triple-negative breast cancer (TNBC). The particle size, PDI and %EE of optimized TZCNPs was found 208.7 ± 7.

Doxorubicin-induced phosphorylation of lamin A/C enhances DNMT1 and activates cardiomyocyte death via suppressing GATA-4 and Bcl-xL in rat heart.

Cardiotoxic effect of Doxorubicin (Dox) limits its clinical application. Previously, we reported that Dox induces phosphorylation of lamin A/C (pS22 lamin A/C), increased nuclear size, damage to the nuclear membrane, and cell death. However, the activation of signalling pathway during this event remains elusive, and it is unclear whether increased phospho-lamin A/C activates the cell death pathway in heart.

Multipotent Effect of Clozapine on Lipopolysaccharide-Induced Acetylcholinesterase, Cyclooxygenase-2,5-Lipoxygenase, and Caspase-3: In Vivo and Molecular Modeling Studies.

Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer's disease (AD) is the most common cause of dementia, and the inhibition of acetylcholinesterase (AChE) is a key approach in treating AD. Meanwhile, Caspase-3 catalyzes early events in apoptosis, contributing to neurodegeneration and subsequently AD.

Computer-aided drug design approaches for the identification of potent inhibitors targeting elongation factor G of Mycobacterium tuberculosis.

Elongation factor G (EF-G) is essential for protein synthesis in Mycobacterium tuberculosis (Mtb), positioning it as a promising target for anti-tubercular drug development. This study employs Structure-Based Drug Design (SBDD) to identify potential small molecule inhibitors that specifically target EF-G. Initially, binding hotspots on EF-G were pinpointed, and the binding modes of various compounds were analyzed.

Role of Nanotechnology in Ischemic Stroke: Advancements in Targeted Therapies and Diagnostics for Enhanced Clinical Outcomes.

Each year, the number of cases of strokes and deaths due to this is increasing around the world. This could be due to work stress, lifestyles, unhealthy food habits, and several other reasons. Currently, there are several traditional methods like thrombolysis and mechanical thrombectomy for managing strokes.

Analytical quality by design guided white analytical chemistry driven green in the development of LC-ICP-MS method for arsenic speciation analysis in HEK-293 cells.

An analytical quality by design-guided LC-ICP-MS method for simultaneous arsenic speciation analysis in HEK-293 cells was optimized and validated. Initially, critical method variables (CMVs) were identified to achieve the targeted critical quality attribute (CQA) of the analytical target profile (ATP). Based on knowledge and risk assessments, formic acid (X), citric acid (X), and pH (X) were studied for their effect on method responses such as resolutions (Y1, Y2) and retention time of As(V), As(III) and DMA (Y3, Y4, and Y5) using central composite design (CCD).

Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.

Introduction: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration.

High-throughput sequencing: a breakthrough in molecular diagnosis for precision medicine.

High-resolution insights into the nucleotide arrangement within an organism's genome are pivotal for deciphering its genetic composition, function, and evolutionary trajectory. Over the years, nucleic acid sequencing has been instrumental in driving significant advancements in genomics and molecular biology. The advent of high-throughput or next-generation sequencing (NGS) technologies has revolutionized whole genome sequencing, revealing novel and intriguing features of genomes, such as single nucleotide polymorphisms and lethal mutations in both coding and non-coding regions.

Opto-Laser-Responsive Smart NanoGel with Mild Hyperthermia, Vascularization, and Anti-Inflammatory Potential for Boosting Hard-to-Heal Wounds in a Diabetic Mice Model.

It is well known that impaired wound healing associated with diabetes mellitus has led to a challenging problem as well as a global economic healthcare burden. Conventional wound care therapies like films, gauze, and bandages fail to cure diabetic wounds, thereby demanding a synergistic and promising wound care therapy. This investigation aimed to develop a novel, greener synthesis of a laser-responsive silver nanocolloid (LR-SNC) prepared using hyaluronic acid as a bioreductant.

Anti-inflammatory activity, stability, bioavailability and toxicity studies on seabuckthorn polyphenol enriched fraction and its phospholipid complex (Phytosomes) preparation.

A standardized polyphenol-enriched fraction (IPHRFPPEF) was formulated into a phospholipid complex (IPHRFPPEF-PC) to enhance oral bioavailability and evaluate stability, toxicity, and in vivo anti-inflammatory activity in Sprague Dawley rats. IPHRFPPEF was prepared from crude extract using XAD-HP7/Diaion-HP20 resin column chromatography and analyzed via HPLC and NMR. Total phenolic and flavonoid contents were quantified, with IPHRFPPEF showing higher values than the crude fraction.

Impact of Oxidative Stress and Neuroinflammation on Sarco/Endoplasmic Reticulum Ca-ATPase 2b Downregulation and Endoplasmic Reticulum Stress in Temporal Lobe Epilepsy.

Epilepsy is one of the most common neurological disorders. Calcium dysregulation and neuroinflammation are essential and common mechanisms in epileptogenesis. Sarco/endoplasmic reticulum (ER) Ca-ATPase 2b (SERCA2b), a crucial calcium regulatory pump, plays pathological roles in various calcium dysregulation-related diseases.

Multi-Targeting Phytochemicals for Alzheimer's Disease.

Alzheimer's disease (AD) is a type of neurodegenerative illness in which β-amyloid (Aβ) and tau protein accumulate in neurons in the form of tangles. The pathophysiological pathway of AD consists of Aβ-amyloid peptides, tau proteins, and oxidative stress in neurons and increased neuro-inflammatory response. Food and Drug Administration in the United States has authorized various drugs for the effective treatment of AD, which include galantamine, rivastigmine, donepezil, memantine, sodium oligomannate, lecanemab, and aducanumab.

Optimizing etodolac and quercetin loaded MSNs using taguchi design: an approach for enhancing drug loading efficiency.

The application of mesoporous silica nanoparticles (MSN) as a drug carrier system got immense attention in the past few years due to their exceptional high drug loading efficiency. However, the process of drug loading is quite challenging compared to other lipid-based drug delivery systems. Hence, the MSNs using different catalysts were synthesized, and their mesoporous material characteristic was confirmed by the type IV adsorption-desorption isotherm using BET analyzer.

Modulation of copper-induced neurotoxicity by monoisoamyl 2,3-dimercaptosuccinic acid loaded nanoparticles through inhibition of mitophagy and reduction of oxidative stress in SH-SY5Y cells.

Copper (Cu) dysregulation, often stemming from ATP7B gene mutations, exacerbates neurological disorders like Huntington's, Alzheimer's, and Parkinson's diseases. Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) shows promise in mitigating Cu induced neurotoxicity by chelating intracellular Cu ions, reducing oxidative stress, and restoring antioxidant enzyme function. However, challenges such as poor bioavailability hinder its therapeutic efficacy.

Optimizing Linezolid: Transforming It into a Selective MAO-B Inhibitor via a Toxicity-to-Activity Optimization Approach.

Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.

Antigen Specificity: A Fluctuating Aspect in the Development of Clinical Antibodies?

Development of antibodies for clinical use is a complex process involving numerous aspects, with antigen specificity being the most important. Initially, polyclonal antibodies, that can recognize multiple specific and nonspecific antigens (polyreactive), were developed and were very effective in the treatments. Later on, the polyspecificity/polyreactivity of these polyclonal antibodies (binding to multiple antigens) raised concerns about therapeutic efficacy because of their nonspecific interactions and challenges, such as development of immune complexes, batch-to-batch variability.

Marine-derived bioactive compounds for neuropathic pain: pharmacology and therapeutic potential.

Neuropathic pain, a challenging condition often associated with diabetes, trauma, or chemotherapy, impairs patients' quality of life. Current treatments often provide inconsistent relief and notable adverse effects, highlighting the urgent need for safer and more effective alternatives. This review investigates marine-derived bioactive compounds as potential novel therapies for neuropathic pain management.

Biomarker Detection and Therapy of Parkinson's and Alzheimer's disease using upconversion based approach: A Comprehensive Review.

Neurodegenerative diseases (NDs) are debilitating disorders characterized by the progressive and selective loss of function or structure in the brain and spinal cord. Both chronic and acute forms of these diseases are associated with significant morbidity and mortality, as they involve the degeneration of neurons in various brain regions. Misfolding and aggregation of amyloid proteins into oligomer and β-sheet rich fibrils share as common hallmark and lead to neurotoxicity.

Direct Printing of an Electrochemical Device and Its Interface with Paper for Uric Acid Detection in Human Sweat.

Using a laser-scribed (direct printing) technique, we have fabricated an enzymeless, mediatorless, and paper-interfaced electrochemical device (P-LSG) for uric acid detection on a flexible polyimide sheet. Various paper substrates were investigated, and it was found that Whatman filter paper-1 is promising to obtain the best electrochemical signals at the small volume of electrolyte, i.e.

Therapeutic Role of Scutellarein in Neurological Disorders.

Scutellarein, a flavone found in the perennial herb Scutellaria baicalensis, has a wide range of pharmacological actions, such as antioxidant, anti-inflammatory, and neuroprotective. Increasing evidence has emphasized the developing significance of scutellarein in several neurological illnesses, such as Alzheimer's and Parkinson's disease, cerebral ischemia, and neuroblastoma. This review is centered on the molecular processes that underlie the neuroprotective properties of scutellarein in various neurological disorders, as indicated by recent pre-clinical research.

Innovative Approaches in Regulatory Affairs: Leveraging Artificial Intelligence and Machine Learning for Efficient Compliance and Decision-Making.

Artificial Intelligence (AI) and AI-driven technologies are transforming industries across the board, with the pharmaceutical sector emerging as a frontrunner beneficiary. This article explores the growing impact of AI and Machine Learning (ML) within pharmaceutical Regulatory Affairs, particularly in dossier preparation, compilation, documentation, submission, review, and regulatory compliance. By automating time-intensive tasks, these technologies streamline workflows, accelerate result generation, and shorten the product approval timeline.

Aerobic exercise and metformin attenuate the cognitive impairment in an experimental model of type 2 diabetes mellitus: focus on neuroinflammation and adult hippocampal neurogenesis.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that increases the prevalence of cognitive impairment in the geriatric population. Aerobic exercise is an excellent non-pharmacological therapeutic strategy to prevent Alzheimer's disease, the most common form of dementia. The exact molecular mechanism of aerobic exercise (Exe) as an intervention to counter cognitive decline is far from clear.

Recent advancements in the quest of benzazoles as anti-Mycobacterium tuberculosis agents.

Tuberculosis (TB) remains a global health challenge, claiming numerous lives each year, despite recent advancements in drug discovery and treatment strategies. Current TB treatment typically involves long-duration chemotherapy regimens that are often accompanied by adverse effects. The introduction of new anti-TB drugs, such as Bedaquiline, Delamanid, and Pretomanid, offers hope for more effective treatment, although challenges persist keeping the quest to find new anti-TB chemotypes an incessant exercise of medicinal chemists.

Nano-structured polyaniline in biocatalysis: Manifesting simultaneous competence of polyaniline nanofibers and nanotubes as immobilization matrices for laccase mediated synthesis of drug intermediates.

Customized nano-biocatalysts of laccase have been made using nano-structured polyaniline viz. nano-fibers and nano-tubes, as immobilization supports and a simultaneous comparison between them has been made. Laccases are poly-phenol oxidases having tremendous utility concerning wider areas of application especially in the field of organic and drug syntheses.

Enhanced Anti-inflammatory Effect of Puerarin through Optimized Release and Bioavailability via PDLG-Loaded Nanoparticles.

Puerarin (PU), a bioactive constituent reported to possess therapeutic effectiveness, but it suffers a drawback of poor bioavailability. In the present study, the PU nanoparticles (PU-NPs) were prepared using solvent-diffusion-evaporation method and optimized using Box-Behnken design (BBD), a response surface methodology for obtaining the optimal material ratio of PU-NPs. Further, PU and PU-NPs were evaluated to assess their cytotoxic effect and in vitro efficiency of inflammatory responses using lipopolysaccharide-sensitive macrophage cell line (RAW264.