Single-Cell RNA Sequencing, Cell Communication, and Network Pharmacology Reveal the Potential Mechanism of Buch.-Ham in Hepatocellular Carcinoma Inhibition.

Background: Hepatocellular carcinoma (HCC), a prevalent form of primary liver malignancy, arises from liver-specific hepatocytes. Buch.-Ham(Climbing senecio) is a bitter-tasting plant of the Compositae family with anti-tumor properties.

(-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter.

Background: Durazz. is one of the most popular herbs used for depression treatment, but the molecular basis for its mechanism of action has not been fully addressed. Previously, we isolated and identified two lignan glycoside derivatives that were shown to noncompetitively inhibit serotonin transporter (SERT) activity but with a relatively low inhibitory potency compared with those of conventional antidepressants.

Association of genetically proxied cancer-targeted drugs with cardiovascular diseases through Mendelian randomization analysis.

Background: Cancer-targeted therapies are progressively pivotal in oncological care. Observational studies underscore the emergence of cancer therapy-related cardiovascular toxicity (CTR-CVT), impacting patient outcomes. We aimed to investigate the causal relationship between different types of cancer-targeted therapies and cardiovascular disease (CVD) outcomes through a two-sample Mendelian randomization (MR) study.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for -Mutated NSCLC After Complete Resection.

Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA -mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation.

Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and (exon 19 deletion or L858R) mutations were enrolled in this observational study.

Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target.

Background: Hepatocellular carcinoma (HCC) continues to be a major cause of cancer-related death worldwide, primarily due to delays in diagnosis and resistance to existing treatments. Recent research has identified ATP-dependent chromatin remodeling-related genes (ACRRGs) as promising targets for therapeutic intervention across various types of cancer. This development offers potential new avenues for addressing the challenges in HCC management.

Targeting Fibroblast Activation Protein for Molecular Imaging of Fibrotic Remodeling in Pulmonary Arterial Hypertension.

The purpose of this study was to investigate the feasibility of using F-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in assessing the fibrotic remodeling of the pulmonary artery (PA) and the right ventricle (RV) in pulmonary arterial hypertension (PAH). In a rat model of monocrotaline-induced PAH, rats were euthanized at different time points for tissue analysis (fibroblast activation protein immunofluorescence and Masson's trichrome staining) after completing F-FAPI PET/CT and hemodynamic measurements. Thirty-eight PAH patients were enrolled to participate in F-FAPI PET/CT imaging, with right heart catheterization and echocardiography performed within 1 wk to assess pulmonary hemodynamics and cardiac function.

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis.

Nasopharyngeal carcinoma (NPC) presents significant treatment challenges due to its complex etiology and late-stage diagnosis. The traditional Chinese medicine Selaginella doederleinii Hieron (S. doederleinii) has shown potentiality in NPC treatment due to its multi-target, multi-pathway anti-cancer mechanisms.

Machine Learning-Based Pathomics Model Predicts ANGPT2 Expression and Prognosis in Hepatocellular Carcinoma.

Angiopoietin (ANGPT)-2 shows promise as prognostic marker and therapeutic target in hepatocellular carcinoma (HCC). However, assessing ANGPT2 expression and prognostic potential using histopathology images viewed with naked eye is challenging. Machine learning was employed to develop a pathomics model for analyzing histopathology images to predict ANGPT2 status.

YAP K236 acetylation facilitates its nucleic export and deprived the protection against cardiac hypertrophy in mice.

The subcellular localization of Yes-associated protein (YAP) is dynamically regulated by post-transcriptional modifications, critically influencing cardiac function. Despite its significance, the precise mechanism controlling YAP nuclear sequestration and its role in cardiac hypertrophy remain poorly defined. In this study, utilizing immunoprecipitation-mass spectrometry, we identified potential acetylation sites and interacting proteins of YAP.

Discovery of a Potent and Selective GSPT1 Molecular Glue Degrader for the Treatment of Castration-Resistant Prostate Cancer.

The treatment of castration-resistant prostate cancer (CRPC) remains a significant challenge, necessitating the development of new and promising therapeutic strategies. Utilizing molecular glue to degrade previously intractable cancer drivers represents an emerging and promising therapeutic approach to cancer treatment. In this study, we developed a novel CRBN-interacting molecular glue, (XYD049), which exhibits potent and selective degradation of G1 to S phase transition 1 (GSPT1), a well-known untargetable cancer driver in diverse cancer cells.

High-throughput screening of dual-target inhibitors for SARS-CoV-2 main protease and papain-like protease from Chebulae Fructus: prediction and experimental verification.

Background: The unavoidable propagation of the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has underscored the urgent requirement for efficacious therapeutic agents. The dried fruit of Retz., namely Chebulae Fructus, is widely used for treating bacterial and viral infectious diseases, which was witnessed to perform anti-SARS-CoV-2 activity in recommended Chinese patent medicine.

Multi-omics approach reveals TGF-β signaling-driven senescence in periodontium stem cells.

Introduction: The periodontal ligament (PDL), a dynamic connective tissue that anchors teeth to the alveolar bone, enables tooth retention and facilitates continuous turnover. The integrity of the periodontium is maintained by periodontal ligament stem cells (PDLSCs), whose dysfunction and senescence with age can disrupt tissue homeostasis, hinder injury repair, and lead to tooth loss, ultimately impacting overall health. Transforming growth factor-β1 (TGF-β1) is known for its regenerative properties and as a functional paracrine factor in stem cell therapy, but its precise role in modulating PDLSC activity remains controversial and poorly understood.

Diagnostic value of SAT-TB in stool and urine samples for intestinal and urinary tuberculosis.

Background: The simultaneous amplification/testing for tuberculosis (SAT-TB) targets specific 16s rRNA for detecting Mycobacterium tuberculosis in real-time.

Objective: To evaluate SAT-TB's performance in detecting intestinal and urinary TB using stool and urine samples.

Methods: Stool (94) and urine samples (69) (From 2021 to 2022), were collected from pulmonary combined with suspected intestinal or urinary tuberculosis.

NRP1 instructs IL-17-producing ILC3s to drive colitis progression.

Group 3 innate lymphoid cells (ILC3s) control tissue homeostasis and orchestrate mucosal inflammation; however, the precise mechanisms governing ILC3 activity are fully understood. Here, we identified the transmembrane protein neuropilin-1 (NRP1) as a positive regulator of interleukin (IL)-17-producing ILC3s in the intestine. NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) compared with healthy controls.

Mechanistic insights into the anti-oxidative and anti-inflammatory functions of covalent-reactive cinnamyl compounds within Cinnamomum cassia.

Background: Cinnamomum cassia Presl (Lauraceae) is widely used as a medicinal plant in the folk medicine and pharmaceutic industry, for its promising anti-inflammatory, anti-oxidative, and anti-bacterial function. However, the major bioactive components were still in debate, and their underlying molecular mechanism was not yet fully understood.

Purpose: This study aimed to identify the bioactive ingredients of C.

Characterization of Active Compounds in Sanhuang Shu'ai Decoction for the Management of Ulcerative Colitis: A UHPLC-MS Study.

Objective: The effectiveness of Sanhuang Shu'ai decoction (SSD), a traditional Chinese medicine used to treat diarrhea and colitis, especially ulcerative colitis (UC), is not well understood regarding how its chemical components work.

Methods: This research used ultra-high-performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS), network pharmacology, and molecular docking to understand the active substances and potential mechanisms of SSD in treating UC.

Results: UHPLC and MS analyses identified 710 active components in SSD extracts (ZYTQY) and 387 in SSD-containing serum (HYXQ), with 35 active compounds found in both ZYTQY and HYXQ and 67 active compounds from SSDD (SSD compound obtained directly from the database), along with 6 metabolites that may be key components in its function.

N-methyladenosine in 28S rRNA promotes oncogenic mRNA translation and tyrosine catabolism.

Aberrant N-methyladenosine (mA) modification on mRNA results in dysregulated mRNA translation and cancer progression; however, the role of mA modification on rRNA remains unclear in cancers. Here, we show that ZCCHC4 and its mediated mA modification on 28S rRNA are upregulated in various cancers and correlated with poor survival. Functionally, ZCCHC4 promotes intrahepatic cholangiocarcinoma (ICC) progression via its catalytic activity.

Red ginseng prevents niraparib-induced myelosuppression in C57BL/6 mice via inhibiting p53-mediated upregulation of p21 and p27.

Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients.

Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.

Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.

Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Bioinformatics identification based on causal association inference using multi-omics reveals the underlying mechanism of Gui-Zhi-Shao-Yao-Zhi-Mu decoction in modulating rheumatoid arthritis.

Object: Rheumatoid arthritis (RA) is a prevalent and currently incurable autoimmune disease. Existing conventional medical treatments are limited in their efficacy, prolonged disease may lead to bone destruction, joint deformity, and loss of related functions, which places a huge burden on RA patients and their families. For millennia, the use of traditional Chinese medicine (TCM), exemplified by the Gui-Zhi-Shao-Yao-Zhi-Mu decoction (GZSYZM), has been demonstrated to offer distinct therapeutic advantages in the management of RA.