Separation and characterization of degradation impurities of upadacitinib by liquid chromatography and high resolution mass spectrometry.

Upadacitinib is an oral Janus Kinase inhibitor used for the treatment of rheumatoid arthritis. This research focuses on the forced degradation study of upadacitinib and the characterization of its degradation impurities. Upadacitinib was subjected to various degradation conditions such as hydrolysis (acid, base, neutral), oxidation, thermal, and photolysis according to International Council for Harmonisation guidelines.

A central composite design-based targeted quercetin nanoliposomal formulation: Optimization and cytotoxic studies on MCF-7 breast cancer cell lines.

This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables.

Reconnoitring signaling pathways and exploiting innovative approaches tailoring multifaceted therapies for skin cancer.

Nowadays, skin cancer is widespread just like a varied malignant cancer which can cause serious health issues. Skin cancer, which encompasses malignant melanoma, basal cell carcinoma, and squamous cell carcinoma, is a prevalent form of cancer among humans. Due to its broad prevalence, financial burden, mortality rates, and cosmetic effects, it is a major public health issue.

Stachydrine, a pyrrole alkaloid with promising therapeutic potential against metabolic syndrome and associated organ dysfunction.

Metabolic syndrome is a multifaceted condition marked by interconnected risk factors, significantly increasing the risk of serious diseases like cardiovascular disease, type 2 diabetes, and stroke. Effective management often demands new medications due to complexity of the conditions and limitations of current treatments. Natural compounds are increasingly recognized in drug discovery due to their vast chemical diversity, commercial availability, low cost, and minimal side effects.

Prediction of molecular targets for antidepressant potential of hydroalcoholic extract of using network pharmacology approach and evaluating its efficacy in Chronic Unpredictable Mild Stress model in mice.

The prevalence of psychological disorders has surged since the 1990s, posing a significant global health burden with depressed individuals averaging six lost hours per week and contributing to over 20% of all missed workdays. Current antidepressants, while effective for some, have limited efficacy, dietary restrictions, and adverse effects, including liver damage and hypertension. Natural remedies offer promising therapeutic potential with minimal side effects.

A Molecular Dynamic Simulation, Structural Analysis, and Ex Vivo Insights into the P-glycoprotein-Mediated Interactions of Dietary Polyphenols with Cyclin-dependent Kinase Inhibitors: A Potential Strategy to Counteract Drug Efflux.

Introduction: P-glycoprotein, an ATP-dependent efflux transporter, plays a crucial role in eliminating cellular toxins and affects the intracellular concentration and bioavailability of CDK 4/6 inhibitors. Moreover, dietary flavonoids are natural bio-enhancers that can effectively inhibit the efflux function of these transporters. Therefore, this study aimed to assess the impact of dietary polyphenols on the inhibition of P-glycoprotein and the subsequent efflux of CDK inhibitors palbociclib and ribociclib.

In Silico and In Vivo Evaluation of Anti-Arthritic Effects of Bakuchiol from Psoralea corylifolia Seeds in Experimental Rat Model.

Rheumatoid arthritis is an autoimmune disease mainly affecting the joints categorized by inflammation, swelling of the synovium and decrease in the joint movement. Bakuchiol, a meroterpene class of natural product present in Psoralea corylifolia known to possess anti-inflammatory effects by a variety of mechanisms. However, its effects in rheumatoid arthritis still remain unclear.

Exploring the role of miRNA in diabetic neuropathy: from diagnostics to therapeutics.

Diabetic neuropathy (DN) is one of the major microvascular complications of diabetes mellitus affecting 50% of the diabetic population marred by various unmet clinical needs. There is a need to explore newer pathological mechanisms for designing futuristic regimens for the management of DN. There is a need for post-transcriptional regulation of gene expression by non-coding RNAs (ncRNAs) to finetune different cellular mechanisms with significant biological relevance.

Manifesting the Dasatinib-gallic acid co-amorphous system to augment anticancer potential: Physicochemical characterization, in silico molecular simulation, ex vivo permeability, and in vitro efficacy.

Dasatinib (DAB) has been explored for repurposing in the treatment of breast cancer (BC) due to its known effectiveness in treating leukemia, in addition to its role as a tyrosine kinase inhibitor. Gallic acid (GA) was chosen as a co-former due to its anticancer potential in BC, as demonstrated in several previous studies. DAB is a low-solubility drug, which is a significant hurdle for its oral bioavailability.

Structure-aided function assignment to the transcriptomic conopeptide Am931.

Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of Conus peptides.

Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier.

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % of all cases. It affects millions of people worldwide. AD poses a substantial economic burden on societies and healthcare systems.

Quality by design (QbD) based approach for development of itraconazole-loaded transferosomes for skin cancer: and cell line studies.

Objective: Itraconazole (ITZ), a widely used systemic antifungal drug, has been ingeniously repurposed for its antitumor effects. In the present work, we have prepared and optimized the ITZ-loaded transferosomes by Quality by Design (QbD) approach and repurposed them for skin cancer.

Methods: The transferosomal formulation was optimized by employing a QbD approach with the design of experiment.

Simvastatin exerts neuroprotective effects post-stroke by ameliorating endoplasmic reticulum stress and regulating autophagy/apoptosis balance through pAMPK/LC3B/ LAMP2 axis.

Statins have evident neuroprotective role in acute ischemic stroke(AIS). The pleiotropic effect by which statin exerts neuroprotective effects, needs to be explored for considering it as one of the future adjunctive therapies in AIS. Endoplasmic reticulum(ER) assists cellular survival by reducing protein aggregates during ischemic conditions.

Faecalibacterium prausnitzii, FOS and GOS loaded synbiotic reverses treatment-resistant depression in rats: Restoration of gut-brain crosstalk.

Alterations in commensal gut microbiota, such as butyrate-producing bacteria and its metabolites, have been linked to stress-related brain disorders, including depression. Herein, we investigated the effect of Faecalibacterium prausnitzii (ATCC-27766) administered along with fructooligosaccharides (FOS) and galactooligosaccharides (GOS) in a rat model of treatment-resistant depression (TRD). The behavioral changes related to anxiety-, anhedonia- and despair-like phenotypes were recorded employing elevated plus maze, sucrose-preference test, and forced-swim test, respectively.

Zein: Potential biopolymer in inflammatory bowel diseases.

Effectively managing inflammatory bowel disease (IBD) poses difficulties due to its persistent nature and unpredictable episodes of exacerbation. There is encouraging evidence that personalized medication delivery systems can improve therapy efficacy while reducing the negative effects of standard medicines. Zein, a protein produced from corn, has garnered interest as a possible means of delivering drugs for the treatment of IBD.

Synthesis of γ-Spirolactams via Rh(III)-Catalyzed C-H Activation/Directing Group Migration/Dearomatization/Spiroannulation of Indoles with 1,3-Enynes.

1,3-Enynes are valuable coupling partners in transition-metal-catalyzed C-H functionalizations. Certainly, aliphatic-substituted 1,3-enynes have been thoroughly investigated in C-H functionalizations, whereas aromatic-substituted 1,3-enynes remain underexplored. Herein, we report the realization of this goal, where we achieve an atom-economical protocol for the synthesis of γ-spirolactams via Rh(III)-catalyzed C-H functionalization of -carbamoylindoles with 1,3-enynes.

Photodynamic therapy of cancer using graphene nanomaterials.

Introduction: High incidence and fatality rates of cancer remain a global challenge. The success of conventional treatment modalities is being questioned on account of adverse effects. Photodynamic therapy (PDT) is a potential alternative.

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action.

The crucial role of VPS35 and SHH in Parkinson's disease: Understanding the mechanisms behind the neurodegenerative disorder.

Parkinson's disease (PD) is indeed a complex neurodegenerative disorder recognized by the progressive depletion of dopaminergic neurons in the brain, particularly in the substantia nigra region, leading to motor impairments and other symptoms. But at the molecular level, the study about PD still lacks. As the number of cases worldwide continues to increase, it is critical to focus on the cellular and molecular mechanisms of the disease's presentation and neurodegeneration to develop novel therapeutic approaches.

Indole-3 Carbinol and Diindolylmethane Mitigated β-Amyloid-Induced Neurotoxicity and Acetylcholinesterase Enzyme Activity: In Silico, In Vitro, and Network Pharmacology Study.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by beta-amyloid (Aβ) deposition and increased acetylcholinesterase (AchE) enzyme activities. Indole 3 carbinol (I3C) and diindolylmethane (DIM) are reported to have neuroprotective activities against various neurological diseases, including ischemic stroke, Parkinson's disease, neonatal asphyxia, depression, stress, neuroinflammation, and excitotoxicity, except for AD. In the present study, we have investigated the anti-AD effects of I3C and DIM.

Additive Manufacturing of SmartEx QD 100 Designed Oral Three-Dimensional Printlets Containing Isoniazid for Immediate Gastric Release by Selective Laser Sintering.

The selection of appropriate materials and compatibility of selected materials with drugs and formulations are limiting steps in three-dimensional printing technology. In this study, SmartEx QD 100 (SM QD 100) was introduced as a novel, coprocessed, unexplored excipient that can be used in SLS-mediated 3D printing. The current study aimed to evaluate the feasibility of fabricating SM QD 100 containing INH-embedded SLS-mediated immediate gastric release tablets.

Nuciferine inhibits TLR4/NF-κB/MAPK signaling axis and alleviates adjuvant-induced arthritis in rats.

Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats.

Scaffold overlay of flavonoid-inspired molecules: Discovery of 2,3-diaryl-pyridopyrimidin-4-imine/ones as dual hTopo-II and tubulin targeting anticancer agents.

Almost half of all medicines approved by the U.S. Food and Drug Administration have been found to be developed based on inspiration from natural products (NPs).