Identification of potential therapeutic phytocompounds targeting the G-glycoprotein of Nipah Virus: an in-silico study.

Public health is seriously threatened by the highly pathogenic zoonotic Nipah virus (NIV). Since no effective medicines or vaccines exist, it is imperative to investigate potential therapeutic molecules against NIV. In this research, we concentrated on the G-glycoprotein of NIV as a potential therapeutic target.

SGK3 promotes estrogen receptor-positive breast cancer proliferation by activating STAT3/ZMIZ2 pathway to stabilise β-catenin.

Background And Purpose: Breast cancer is a leading threat to women's health, with approximately 70% of cases being estrogen receptor-positive. SGK3 is regulated by estrogen and is positively associated with estrogen receptor expression, although its molecular role remains unclear.

Experimental Approach: Proteomics was used to identify SGK3's downstream targets.

PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.

DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.

The GLP-1 Agonist Semaglutide Ameliorates Cognitive Regression in P301S Tauopathy Mice Model via Autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization.

Tau hyper-phosphorylation has been recognized as an essential contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies. In the last decade, tau hyper-phosphorylation has gained considerable concern in AD therapeutic development. Tauopathies are manifested with a broad spectrum of symptoms, from dementia to cognitive decline and motor impairments.

Investigating Pb2 CAP-binding domain inhibitors from marine bacteria for targeting the influenza A H5N1.

The ongoing increase in the prevalence and mutation rate of the influenza virus remains a critical global health issue. A promising strategy for antiviral drug development involves targeting the RNA-dependent RNA polymerase, specifically the PB2-cap binding domain of Influenza A H5N1. This study employs an in-silico approach to inhibit this domain, crucial for viral replication, using potential inhibitors derived from marine bacterial compounds.

Deciphering the interplay between SETD2 mediated H3K36me3 and RNA N6-methyladenosine in clear cell renal cell carcinoma (ccRCC).

RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of followed by mutations in epigenetic regulators , , and . Mutations in , a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming.

Restoring cefepime activity against multidrug-resistant KPC-producing by combination with boronic acid inhibitors, MB076 and S02030.

Foremost in the design of new β-lactamase inhibitors (BLIs) are the boronic acid transition state inhibitors (BATSIs). Two highly potent BATSIs being developed are S02030 and MB076 strategically designed to be active against cephalosporinases and carbapenemases, especially KPC. When combined with cefepime, S02030 and MB076 demonstrated potent antimicrobial activity against laboratory and clinical strains of expressing a variety of class A and class C β-lactamases, including and .

Comparative dissection of transcriptional landscapes of human iPSC-NK differentiation and NK cell development.

Clinical and preclinical research has demonstrated that iPSC-derived NK (iNK) cells have a high therapeutic potential, yet poor understanding of the detailed process of their differentiation and their counterpart cell development has hindered therapeutic iNK cell production and engineering. Here we dissect the crucial differentiation of both fetal liver NK cells and iNK cells to enable the rational design of advanced iNK production protocols. We use a comparative analysis of single-cell RNA-seq (scRNA-seq) to pinpoint key factors lacking in the induced setting which we hypothesized would hinder iNK differentiation and/ or functionality.

EpigenPlot: An interactive web platform for DNA methylation-based biomarker and drug target discovery in colorectal cancer.

Background And Purpose: Genome-wide methylation studies have significantly advanced our understanding of colorectal adenocarcinoma progression and biomarker discovery. Aberrant DNA methylation plays a crucial role in gene expression regulation during cancer transformation, highlighting the need to identify differentially methylated regions (DMRs) as potential diagnostic and therapeutic markers. However, an integrated resource to explore and validate methylation alterations across colorectal cancer stages has been lacking.

Increasing cellular NAD protects hepatocytes against palmitate-induced lipotoxicity by preventing PARP-1 inhibition and the mTORC1-p300 pathway activation.

Hepatic lipotoxicity, resulting from excessive lipid accumulation in hepatocytes, plays a central role in the pathogenesis of various metabolic liver diseases. Despite recent progress, the precise mechanisms remain incompletely understood. Employing excessive exposure to palmitate in hepatocytes as our primary experimental model and mice studies, we aimed to uncover the mechanisms behind hepatic lipotoxicity, thereby developing potential treatments.

Analysis of the potential biological mechanisms of geniposide on renal fibrosis by network pharmacology and experimental verification.

Background: Renal fibrosis is crucial in the progression of chronic kidney disease (CKD) to end-stage renal failure. Geniposide, an iridoid glycoside, has shown therapeutic potential in acute kidney injury, diabetic nephropathy, and atherosclerosis. The aim of this study was to investigate the role of geniposide in renal fibrosis and its underlying mechanisms.

Mechanisms of wogonoside in the treatment of atherosclerosis based on network pharmacology, molecular docking, and experimental validation.

Background: Atherosclerosis serves as the fundamental pathology for a variety of cardiovascular disorders, with its pathogenesis being closely tied to the complex interplay among lipid metabolism, oxidative stress, and inflammation. Wogonoside is a natural flavonoid extracted from Scutellaria baicalensis with a variety of biological activities, including anti-inflammatory, hypolipidemic, and cardiac function improvement properties. Despite these known effects, the specific role of wogonoside in the context of atherosclerosis remains to be elucidated.

Piezoelectric biosensor with dissipation monitoring enables the analysis of bacterial lytic agent activity.

Antibiotic-resistant strains of Staphylococcus aureus pose a significant threat in healthcare, demanding urgent therapeutic solutions. Combining bacteriophages with conventional antibiotics, an innovative approach termed phage-antibiotic synergy, presents a promising treatment avenue. However, to enable new treatment strategies, there is a pressing need for methods to assess their efficacy reliably and rapidly.

The potential of alphapinene as a therapeutic agent for maternal hypoxia-induced cognitive impairments: a study on HO-1 and Nrf2 gene expression in rats.

This research seeks to address the gap in past studies by examining the role of the Nrf2 (nuclear factor erythroid 2-related factor 2) and HO-1 (heme oxygenase-1) signaling pathways in hypoxia and the potential effects of alpha-pinene on these factors. Wistar rats were divided into 7 experimental groups (n = 7): 1) control, 2 and 3) groups receiving alpha-pinene 5 and 10 mg/kg (i.p.

Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.

Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC.

Isovitexin targets SIRT3 to prevent steroid-induced osteonecrosis of the femoral head by modulating mitophagy-mediated ferroptosis.

The death of osteoblasts induced by glucocorticoid (GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head (SIONFH). Improving bone formation driven by osteoblasts has shown promising outcomes in the prognosis of SIONFH. Isovitexin has demonstrated antioxidant properties, but its therapeutic effects on GC-induced oxidative stress and SIONFH remain unexplored.

Ribes diacanthum Pall modulates bile acid homeostasis and oxidative stress in cholestatic mice by activating the SIRT1/FXR and Keap1/Nrf2 signaling pathways.

Ethnopharmacological Relevance: Cholestatic liver injury (CLI) is a pathophysiological syndrome characterized by the accumulation of bile acids (BAs), which leads to significant hepatic dysfunction. This condition is frequently associated with disturbances in BAs homeostasis and the induction of oxidative stress. Ribes diacanthum Pall (RDP), a conventional folk medicinal plant, has been employed in Mongolia, the Inner Mongolia region of China, and other areas for the remediation of hepatic disorders.

Development and characterization of in vitro inducible immortalization of a murine microglia cell line for high throughput studies.

There are few in vitro models available to study microglial physiology in a homeostatic context. Recent approaches include the human induced pluripotent stem cell model, but these can be challenging for large-scale assays and may lead to batch variability. To advance our understanding of microglial biology while enabling scalability for high-throughput assays, we developed an inducible immortalized murine microglial cell line using a tetracycline expression system.

Icaritin alleviates motor impairment and osteoporosis in Parkinson's disease mice via the ER-PI3K/Akt pathway.

This study investigates the role of flavonoid Icaritin (ICT) in estrogen-deficient ovariectomized (OVX) female mice by activating the Estrogen receptor (ER)/ Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, potentially delaying Parkinson's disease (PD) progression post-castration. Seventy-five 8-week-old C57BL/6J female mice underwent ovariectomy, followed by MPTP (20 mg/kg) injection for 7 days. ICT (20 mg/kg) was administered for 14 days, and motor function was assessed using various behavioral tests.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.

Anti-osteosarcoma activity of Corynoline via Src/JNK signaling-mediated cell cycle arrest and mitochondrial apoptosis.

Corynoline (COR) is an isoquinoline alkaloid derived from the traditional Chinese medicine Corydalis bungeana Turcz, known for its analgesic, antibacterial, neuroprotective, and osteoporosis-alleviating properties. However, its potential molecular effects against osteosarcoma (OS) remain unclear, warranting further investigation. This study demonstrated that COR inhibits OS cell proliferation and promotes apoptosis in a dose-dependent manner.

Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries.

Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL's viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now.

An Investigation of the Anticancer Mechanism of L. Extract Against Colorectal Cancer by Integrating a Network Pharmacological Analysis and Experimental Validation.

L. has exhibited various pharmacological effects, yet its anticancer activities against colorectal cancer (CRC) and underlying molecular mechanisms remain unclear. This study investigated the anticancer properties of an ethanol extract of L.

Changes in Lysine Methylation Contribute to the Cytotoxicity of Curcumin in Colon Cancer Cells.

Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells.