Ginsenoside Rh2 regulates triple-negative breast cancer proliferation and apoptosis via the IL-6/JAK2/STAT3 pathway.

Introduction: Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer to treat. While previous studies have demonstrated that ginsenoside Rh2 induces apoptosis in TNBC cells, the specific molecular targets and underlying mechanisms remain poorly understood. This study aims to uncover the molecular mechanisms through which ginsenoside Rh2 regulates apoptosis and proliferation in TNBC, offering new insights into its therapeutic potential.

Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.

Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.

Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.

Anti-proliferative and photodynamic activities of Senna didymobotrya (Fresen.) leaf alkaloid-rich extracts against breast cancer cells.

Background: Amongst all neoplastic diseases, breast cancer represents a major cause of death among the female population in developed and developing countries. Since alkaloid drugs are commonly used in chemotherapy to manage this disease, this study investigated the anti-proliferative effectiveness of alkaloid-rich fractions of Senna didymobotrya leaves only and with laser irradiation against MCF-7 breast cancer cells.

Method And Materials: A powdered sample of the plant leaves was extracted with 50% ethanol, filtered and their pH was adjusted with acid and base solution followed by partitioning with chloroform and ethyl acetate solvents.

Identification of promising SARS-CoV-2 main protease inhibitor through molecular docking, dynamics simulation, and ADMET analysis.

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Mechanistic insights into pachymic acid's action on triple-negative breast Cancer through TOP2A targeting.

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of human epidermal growth factor receptor 2 (HER2) expression. Traditional Chinese medicine (TCM) has demonstrated promising efficacy in treating TNBC. This study explored the mechanisms of pachymic acid (PA) on TNBC by merging network pharmacology with experimental validation.

In vivo Calcium Extrusion from Accumbal Astrocytes Reduces Anxiety-like Behaviors but Increases Compulsive-like Responses and Compulsive ethanol drinking in Mice.

The ventral striatum is crucially involved in reward processing. The present study investigates the behavioral effects of astrocyte-specific calcium extrusion virus "CalEx" on perseverative responses in the operant five-choice serial reaction time task and ethanol-conditioned place preference. Mice were injected with CalEx via the GfaABCD promoter to extrude cytosolic calcium from astrocytes within the ventral striatum.

Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.

Unlocking the therapeutic mechanism of : a comprehensive review of its antioxidant and anti-cancer properties, ethnopharmacology, and phytochemistry.

Herbal medicine are an invaluable reservoir of bioactive compounds, offering immense potential for novel drug development to address a wide range of diseases. Among these, has gained recognition for its historical medicinal applications and substantial therapeutic potential. This review explores the ethnopharmacological significance, phytochemical composition, and pharmacological properties of , with a particular focus on its anticancer activities.

Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation.

Background: Dachaihu decoction (DCHD) is a common Chinese medicine formula against sepsis-induced acute lung injury (SALI). PANoptosis is a novel type of programmed cell death. Nevertheless, The mechanisms of DCHD against SALI via anti-PANoptosis remains unknown.

The Hormetic Potential of GDF15 in Skeletal Muscle Health and Regeneration: A Comprehensive Systematic Review.

Background: Growth Differentiation Factor 15 (GDF15) has been described as influencing skeletal physiology. Nevertheless, no systematic appraisal of the effect of GDF15 on skeletal muscle tissues has been developed to the present day.

Objective: The aim of the present work was to review the evidence on the topic.

Single-cell atlas reveals multi-faced responses of losartan on tubular mitochondria in diabetic kidney disease.

Background And Objective: Mitochondria are crucial to the function of renal tubular cells, and their dynamic perturbation in many aspects is an important mechanism of diabetic kidney disease (DKD). Single-nucleus RNA sequencing (snRNA-seq) technology is a high-throughput sequencing analysis technique for RNA at the level of a single cell nucleus. Here, our DKD mouse kidney single-cell RNA sequencing conveys a more comprehensive mitochondrial profile, which helps us further understand the therapeutic response of this unique organelle family to drugs.

Identification of potent TMPRSS4 inhibitors through structural modeling and molecular dynamics simulations.

TMPRSS4, a transmembrane serine protease type II, is associated with various pathological illnesses. It has been found to activate SARS-CoV-2, enhance viral infection of human small-intestinal enterocytes and is overexpressed in different types of cancers. Therefore, this study aims to disover potential TMPRSS4 inhibitors that have better binding affinity than the approved inhibitors: 2-hydroxydiarylamide and tyroserleutide.

Role of the androgen receptor in melanoma aggressiveness.

Malignant melanoma represents the fifth most common cancer in the world and its incidence is rising. Novel therapies targeting receptor tyrosine kinases, kinases and immune checkpoints have been employed with a significant improvement of the overall survival and long-term disease containment. Nevertheless, the disease often progresses and becomes resistant to the therapies.

CD133PD-L1 cancer cells confer resistance to adoptively transferred engineered macrophage-based therapy in melanoma.

Adoptive transfer of genetically or nanoparticle-engineered macrophages represents a promising cell therapy modality for treatment of solid tumor. However, the therapeutic efficacy is suboptimal without achieving a complete tumor regression, and the underlying mechanism remains elusive. Here, we discover a subpopulation of cancer cells with upregulated CD133 and programmed death-ligand 1 in mouse melanoma, resistant to the phagocytosis by the transferred macrophages.

Development of an G Protein-Coupled Receptor Fragment Molecule Screening Approach with High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance.

Small molecules are essential for investigating the pharmacology of membrane proteins and remain the most common approach for therapeutically targeting them. However, most experimental small molecule screening methods require ligands containing radiolabels or fluorescent labels and often involve isolating proteins from their cellular environment. Additionally, most conventional screening methods are suited for identifying compounds with moderate to higher affinities ( < 1 μM) and are less effective at detecting lower affinity compounds, such as weakly binding molecular fragments.

Integrated Network Pharmacology, Machine Learning and Experimental Validation to Identify the Key Targets and Compounds of for the Treatment of Breast Cancer.

Background: TiaoShenGongJian (TSGJ) decoction, a traditional Chinese medicine for breast cancer, has unknown active compounds, targets, and mechanisms. This study identifies TSGJ's key targets and compounds for breast cancer treatment through network pharmacology, machine learning, and experimental validation.

Methods: Bioactive components and targets of TSGJ were identified from the TCMSP database, and breast cancer-related targets from GeneCards, PharmGkb, and RNA-seq datasets.

Therapeutic effects of platelet-derived extracellular vesicles on viral myocarditis correlate with biomolecular content.

Introduction: Extracellular vesicles (EVs) can potently inhibit inflammation yet there is a lack of understanding about the impact of donor characteristics on the efficacy of EVs. The goal of this study was to determine whether the sex and age of donor platelet-derived EVs (PEV) affected their ability to inhibit viral myocarditis.

Methods: PEV, isolated from men and women of all ages, was compared to PEV obtained from women under 50 years of age, which we termed premenopausal PEV (pmPEV).

Imperatorin's Effect on Myocardial Infarction Based on Network Pharmacology and Molecular Docking.

Myocardial infarction (MI), a severe cardiovascular disease, is the result of insufficient blood supply to the myocardium. Despite the improvements of conventional therapies, new approaches are needed to improve the outcome post-MI. Imperatorin is a natural compound with multiple pharmacological properties and potential cardioprotective effects.

BRAT1 - a new therapeutic target for glioblastoma.

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.

Synthesis and evaluation of nitrochromene derivatives as potential antileishmanial therapeutics through biological and computational studies.

Leishmaniasis is a parasitic disease caused by protozoan organisms belonging to the Leishmania genus, affecting many individuals worldwide, with the burden surpassing one million cases. This disease leads to considerable morbidity and mortality, predominantly within tropical and subtropical regions. The current therapeutic options for leishmaniasis are far from ideal, as they fail to achieve a level of efficacy that can be deemed universally effective.

The Development of Opioid Vaccines as A Novel Strategy for the Treatment of Opioid Use Disorder and Overdose Prevention.

Opioid use disorder (OUD) affects over 40 million people worldwide, creating significant social and economic burdens. Medication for opioid use disorder (MOUD) is often considered the primary treatment approach for OUD. MOUD, including methadone, buprenorphine, and naltrexone is effective for some, but its benefits may be limited by poor adherence to treatment recommendations.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.

Development and experimental validation of dephosphorylation-related biomarkers to assess prognosis and immunotherapeutic response in gliomas.

Background: Gliomas are common aggressive brain tumors with poor prognosis. Dephosphorylation-related biomarkers are in a void in gliomas. This study aims to construct a validated prognostic risk model for dephosphorylation, which will provide new directions for clinical treatment, prognostic assessment, and temozolomide (TMZ) resistance in glioma patients.

The Protective Effects of Citrulline on Testicular Injury Induced by Torsion and Detorsion in Adult Male Rats: An Experimental Study.

Background: Testicular torsion is a critical urological emergency that can lead to testicular ischemia and significant tissue damage. Citrulline, a supplement known for enhancing cellular metabolism and mitigating oxidative stress and inflammation, has been explored for its protective effects against testicular injury resulting from torsion and detorsion in rat models.

Methods: This study involved 42 Wistar rats, divided into six groups: Sham, torsion/detorsion (T/D), and four groups receiving varying doses of Citrulline (300, 600, 900 ) and vitamin E (20 ).