Yoda1 Inhibits TGFβ-Induced Cardiac Fibroblast Activation via a BRD4-Dependent Pathway.

Fibrosis represents a pivotal pathological process in numerous diseases, characterized by excessive deposition of extracellular matrix (ECM) that disrupts normal tissue architecture and function. In the heart, cardiac fibrosis significantly impairs both structural integrity and functional capacity, contributing to the progression of heart failure. Central to this process are cardiac fibroblasts (CFs), which, upon activation, differentiate into contractile myofibroblasts, driving pathological ECM accumulation.

Induced Mitophagy Promotes Cell Cycle Re-Entry in Adult Cardiomyocytes.

: The limited regenerative capacity of adult mammalian cardiomyocytes (CMs) poses a significant challenge for cardiac repair following myocardial infarction. In contrast to adult mammals, CMs in zebrafish and newt hearts retain a lifelong capacity for proliferation and cardiac regeneration. Likewise, neonatal mice exhibit a brief postnatal period, during which CMs retain the ability to proliferate and contribute to myocardial repair, which markedly diminishes within the first week of life.

Marine Fungi-Derived Compounds as Promising KRas Localization Blockers: Structural Insights Into PDE6δ Inhibition.

Cancer, often driven by genetic mutations like KRas activation, is a leading global cause of mortality. This study identified potential inhibitors of PDE6δ, a key chaperone required for KRas membrane localization, from marine fungi-derived compounds. Through molecular docking, molecular dynamics (MD) simulations, MMGBSA free energy calculations, and free energy landscape (FEL) analyses, three promising compounds were identified: CMNPD29003, CMNPD9449, and CMNPD30443.

Nanostructured solid lipid for Paclitaxel and Kaempferol co-delivery as a novel synergistic approach for breast cancer.

This study focuses on the development and evaluation of solid lipid nanoparticles (SLNs) as an efficient carrier for the co-delivery of paclitaxel (PTX) and kaempferol (KMF) in breast cancer treatment. PTX, a BCS (Biopharmaceutics Classification System)-IV class drug, was combined with KMF, a flavonoid extracted and isolated from bee pollen, to enhance therapeutic efficacy. The optimal synergistic ratio of PTX and KMF was incorporated into SLNs using a hot homogenization technique, resulting in PTX-KMF-SLNs with a stable core-shell structure, narrow size distribution (166.

Surrogate matrix approach to quantify endogenous progesterone in a fasting bioequivalence study of soft gelatin capsules in postmenopausal women.

In the present study, endogenous progesterone in plasma was quantified using a validated LC-MS/MS method. This bioanalytical technique was successfully applied to a bioequivalence study in postmenopausal female volunteers. The assay achieved a lower limit of quantification (LLOQ) of 20 pg/mL for endogenous progesterone.

Anticancer efficacy of dual-loaded SLNs with Doxorubicin (DOX) and Pterostilbene (PTS): formulation, characterization, and evaluation for breast cancer.

Aims: This study aimed to develop optimized doxorubicin (DOX) and pterostilbene (PTS) co-loaded solid lipid nanoparticles (SLNs) for synergistic triple-negative breast cancer (TNBC) therapy, enhancing drug stability, tumor targeting, and therapeutic efficacy.

Materials & Methods: Calibration curves for DOX and PTS were validated. Synergy was assessed in MDA-MB-231 cells via Combination Index (CI) and Loewe-HSA models.

Encapsulation of lysozyme in hybrid vesicles to protect from thermal challenges.

This study explores the formation of hybrid vesicles (HVs) through the co-assembly of dipalmitoyl phosphatidylcholine (DPPC) and the triblock copolymer F127. Our findings demonstrate that HVs offer enhanced stability compared to pure copolymer micelles and phospholipid vesicles. To evaluate their functional properties, we encapsulated the thermolabile protein lysozyme within the HVs.

Structural Dynamics and Network Pharmacology for the Discovery of Inhibitors Targeting DYRK1 A in Neurological Disorders.

Neurological disorders, including Down syndrome, Alzheimer's disease, and autism spectrum disorders, involve intricate disruptions in brain function and development. DYRK1A (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) has become an essential target in these diseases because it helps neurons grow, differentiate, and change shape. Overexpression of DYRK1A is connected to problems with neurodevelopment, memory loss, and tauopathies, which makes it an essential target for therapy.

Rubia cordifolia Linn.: Isolation, molecular docking and BRAC1/PKD1 gene targeting for polycystic ovary syndrome in rats.

Polycystic Ovarian Syndrome (PCOS) is a disorder of endocrine system characterized by irregular menstrual cycles, high androgen levels, and polycystic ovaries. The aim of this study is to evaluate pharmacological activity of Rubia cordifolia (RC) in treating letrozole-induced PCOS in rats that exhibit metabolic and endocrinal criteria of PCOS patients. The plant RC was collected, characterized and prepared an extract, to obtained the phenolic and flavonoid content, which was confirmed by GC-MS.

HuR inhibition reduces post-ischemic cardiac remodeling by dampening myocyte-dependent inflammatory gene expression and the innate immune response.

The RNA-binding protein human antigen R (HuR) has been shown to reduce cardiac remodeling following both myocardial infarction and cardiac pressure overload, but the full extent of the HuR-dependent mechanisms within cells of the myocardium has yet to be elucidated. Wild-type mice were subjected to 30 min of cardiac ischemia (via LAD occlusion) and treated with a novel small molecule inhibitor of HuR at the time of reperfusion, followed by direct in vivo assessment of cardiac structure and function. Direct assessment of HuR-dependent mechanisms was done in vitro using neonatal rat ventricular myocytes (NRVMs) and bone marrow-derived macrophages (BMDMs).

5-Fluorouracil- and Sesamol-Loaded Transliposomal Gel for Skin Cancer: , and Dermatokinetic Evaluation.

This study explores a novel approach to managing skin conditions through a combination therapy utilizing a phospholipid-enriched edge activator-based nanoformulation. 5-Fluorouracil (5-FU)- and sesamol (SES)-loaded transliposomes (FS-TL) were developed using a thin film hydration method and optimized using Box-Behnken Design. FS-TL characterization indicated a vesicle size of 165.

QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite.

The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydroxyapatite nanoparticles to mimic and compensate for synthetic estrogens and biomineralization. Hypothesizing this bimodal approach, hydroxyapatite nanoparticles (HAPNPs) were synthesized using the chemical-precipitation method followed by drug loading (DZHAPNPs) via sorption.

Cell-free supernatant of (RAMULAB51) from coconut inflorescence sap (Neera) enhances glucose uptake and PPAR-γ in 3T3-L1 adipocytes and inhibits α-glucosidase and α-amylase.

Introduction: Lactic acid bacteria are prized for their probiotic benefits and gut health improvements. This study assessed five LAB isolates from Neera, with RAMULAB51 (, GenBank ON171686.1) standing out for its high hydrophobicity, auto-aggregation, antimicrobial activity, and enzyme inhibition.

Optimisation and evaluation of long circulating Ru-SLNs carrier for targeting melanoma cells.

The aim of study was to prepared and evaluated rutin-loaded solid-lipid-nanoparticles (Ru-SLNs) gel for treatment of melanoma cells. SLNs were prepared by ultrasonication method through optimisation and evaluated their mean-diameter, PDI, zeta-potential, morphology, entrapment-efficiency, drug-loading, interaction by FTIR, in vitro skin permeation, stability, antioxidant/MTT assay and fluorescence microscopic. Further developed Ru-SLNs was incorporated into gel and characterised their physicochemical properties, drug contents, in vitro diffusion, ex vivo permeation and retention studies in human cadaver skin.

Synthesis, characterization, and bioactivity of Cu(II), Fe(II), Co(II), Ni(II), and Mn(II) complexes with benzilmonoximethiocarbohydrazide-O-methoxybenzaldehyde: experimental and computational insights.

In this study, a novel ligand, benzilmonoximethiocarbohydrazide-O-methoxybenzaldehyde (HBMToMB), was synthesized and subsequently complexed with Cu(II), Fe(II), Co(II), Ni(II), and Mn(II) ions. The metal complexes were comprehensively characterized using techniques such as NMR, IR, Mass Spectrometry, UV-Vis, elemental analysis (CHNS), and magnetic susceptibility measurements. The complexes exhibited superior antibacterial and antifungal activity compared to the free ligand.

Development, Analysis, and Determination of Pharmacokinetic Properties of a Solid SMEDDS of Voriconazole for Enhanced Antifungal Therapy.

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole.

Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulations Reveal the Mechanisms of in Diabetic Nephropathy Treatment: An In Silico Study.

Diabetic nephropathy (DN) is a serious diabetes-related complication leading to kidney damage. (CT), traditionally used in managing diabetes and kidney disorders, has shown potential in treating DN, although its active compounds and mechanisms are not fully understood. This study aims to identify CT's bioactive compounds and explore their therapeutic mechanisms in DN.

Paliperidone-loaded nose to brain targeted NLCS: optimisation, evaluation, histopathology and pharmacokinetic estimation for schizophernia.

Study was to develop a nanostructured-lipid-careers (NLCs) of paliperidone (PLP) for nose-to-brain targeting. NLCs was prepared by sonication, high-shear homogenisation method, and characterised their mean diameter, PDI, zeta-potential, morphology (by SEM, TEM and AFM), entrapment efficiency, drug loading, release, interaction study (by FTIR), and stability. Further, permeation and ciliotoxicity performed in sheep nasal mucosa, and biodistribution/pharmacokinetic was performed in rats for schizophernia.

(Forssk.) - A comprehensive insight of its ethnopharmacology, phytochemistry, and pharmacological activities.

Otostegia fruticosa (Forssk.) is a shrub of the Lamiaceae family with a wide geographic distribution in Saudi Arabia, Western and Eastern Africa, Ethiopia, and the Middle East. The current study provides an overview of recent developments in the knowledge of 's ethnobotanical, pharmacological, and phytochemical properties.

Comprehensive Computational Screening and Analysis of Natural Compounds Reveals Promising Estrogen Receptor Alpha Inhibitors for Breast Cancer Therapy.

Breast cancer remains a leading cause of death among women, with estrogen receptor alpha (ERα) overexpression playing a pivotal role in tumor growth and progression. This study aimed to identify novel ERα inhibitors from a library of 561 natural compounds using computational techniques, including virtual screening, molecular docking, and molecular dynamics simulations. Four promising candidates - Protopine, Sanguinarine, Pseudocoptisine, and Stylopine - were selected based on their high binding affinities and interactions with key ERα residues.

Forecasting the Pharmacological Mechanisms of and in Diabetic Retinopathy Treatment: A Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Study.

(1) Background: Diabetic retinopathy (DR) is a major complication of diabetes, marked by abnormal angiogenesis, microaneurysms, and retinal hemorrhages. Traditional Ayurvedic medicine advocates multi-target strategies for DR management. However, the mechanisms by which (SX) and (PZ) exert therapeutic effects are not well understood; (2) Methods: To investigate these mechanisms, we employed network pharmacology and molecular docking techniques.

Understanding the stability and dynamics of influenza a H5N1 polymerase PB2 CAP-Binding domain in complex with natural compounds for antiviral drug discovery.

Influenza A virus, particularly the H5N1 strain, poses a significant threat to public health due to its ability to cause severe respiratory illness and its high mortality rate. Traditional antiviral drugs targeting influenza A virus have faced challenges such as drug resistance and limited efficacy. Therefore, new antiviral compounds are needed to be discovered and developed.

(Ylang-Ylang) Essential Oil Containing Nanoemulgel for the Topical Treatment of Scalp Psoriasis and Dandruff.

This research aimed to evaluate the efficacy of a nanoemulgel (NE) containing (Ylang-Ylang) oil for managing scalp psoriasis and dandruff through various assessments. The study involved phytochemical screening, characterization, stability testing, in vivo performance evaluation, dermatokinetic analysis, central composite rotatable design (CCRD) optimization, in vitro release profiling, and antioxidant and antimicrobial activity assessment of the NE. The NE exhibited excellent stability and maintained physical parameters over a three-month period.

Optimisation and evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model.

Aim: The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from seed oil) loaded liposome based lotion for enhancement of skin permeation and retention.

Method: Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design.

Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.

Unlabelled: During heart failure, gene and protein expression profiles undergo extensive compensatory and pathological remodeling. We previously observed that fast skeletal myosin binding protein-C (fMyBP-C) is upregulated in diseased mouse hearts. While fMyBP-C shares significant homology with its cardiac paralog, cardiac myosin binding protein-C (cMyBP-C), there are key differences that may affect cardiac function.