Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity DOI
Bingjie Hao,

Shumeng Lin,

Haipeng Liu

и другие.

Autophagy, Год журнала: 2024, Номер unknown, С. 1 - 17

Опубликована: Дек. 22, 2024

Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer traditional Chinese medicine, isscreened and validated to target CD274 induces itsmacroautophagic/autophagic degradation. Moreover, we demonstrate thatCD274 directly interacts with MAP1LC3B (microtubule associatedprotein 1 light chain 3 beta). Intriguingly, baicalein potentiatesCD274-LC3 interaction facilitate autophagic-lysosomal degradationof CD274. Importantly, targeted degradation via baicaleininhibits tumor by boosting T-cell-mediated antitumorimmunity. Thus, elucidate critical role autophagy-lysosomalpathway mediating degradation, conceptually demonstratethat design molecular "glue" that tethers CD274-LC3interaction is an appealing strategy develop inhibitors incancer therapy.

Язык: Английский

The active ingredients and mechanism of Zuoqing San in the treatment of sigmoid ulcerative colitis by retention enema DOI
Ming Li, Heng Deng, Shuqing Xu

и другие.

Journal of Complementary and Integrative Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Abstract Objectives This investigation aimed to evaluate the efficacy, key active ingredients, and mechanisms of Zuoqing San (ZQS), a traditional Chinese medicine formula, in managing sigmoid ulcerative colitis (SUC). Methods A cohort 126 participants was recruited treated with ZQS at daily dosage 100 mL for 12 weeks. The primary endpoint percentage subjects achieving favorable treatment outcomes. Liquid chromatography-mass spectrometry employed identify principal ingredients ZQS. Network pharmacology utilized predict central targets its ingredients. Protein-protein interaction networks, Gene Ontology enrichment analyses, Kyoto Encyclopedia Genes Genomes pathway analyses were conducted identified core targets. Finally, molecular dynamics simulations performed. Results Following weeks therapy, withdrawal rate 7.93 %, outcomes observed 31.03 % 4 weeks, 66.37 8 (Odds Ratio: 1.54, 95 Confidence Interval: 0.41–1.83), 68.10 1.86, CI: 0.32–1.27). comprises 31 chemical constituents. Key within protein-protein network included TNF, AKT1, IL6, IL1β, PTGS2, TP53, JUN, MMP9, CASP3, HIF1A, BCL1. Pathway analysis indicated primarily impacts NF-kB, IL-17 signaling pathways. Molecular simulation results showed oxymatrine, cynarin had higher affinity TNF respectively. Conclusions research elucidates components potential multicomponent–multitarget–multipathway pharmacological mechanisms, demonstrating promising therapeutic SUC management.

Язык: Английский

Процитировано

0

Aromatic Molecular Compatibility Attenuates Influenza Virus-Induced Acute Lung Injury via the Lung–Gut Axis and Lipid Droplet Modulation DOI Creative Commons
Yi Li, Jiakang Jiao,

Haoyi Qiao

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 468 - 468

Опубликована: Март 26, 2025

Background: Acute lung injury (ALI) is a major cause of death in patients with various viral pneumonias. Our team previously identified four volatile compounds from aromatic Chinese medicines. Based on molecular compatibility theory, we defined their combination as (AC), though its therapeutic effects and underlying mechanisms remain unclear. Methods: This study used influenza A virus (IAV) A/PR/8/34 to construct cell mouse models ALI explore AC’s protective against infection. The effect AC was verified by evaluating the antiviral efficacy models, including improvements colon inflammation, oxidative stress, suppression NLRP3 inflammasome. In addition, 16S rDNA lipid metabolomics were analyze potential AC. Results: vitro vivo studies demonstrated that increased survival IAV-infected cells mice, inhibited replication expression proinflammatory factors tissues, ameliorated barrier damage colonic tissues. ROS inflammasome improved inflammatory infiltration into Finally, effectively regulated intestinal flora disorders metabolism model significantly reduced cholesterol triglyceride expression, thus abnormal accumulation droplets (LDs) after IAV Conclusions: this study, could treat IAV-induced ALIs through multiple pathways, anti-inflammatory pathways modulation LDs.

Язык: Английский

Процитировано

0

Innovative Application of Medicinal Insects: Employing UHPLC-MS, Bioinformatics, In Silico Studies and In Vitro Experiments to Elucidate the Multi-Target Hemostatic Mechanism of Glenea cantor (Coleoptera: Cerambycidae) Charcoal-Based Medicine DOI Creative Commons

B. Zhong,

Wei Zhang, Liangshan Ming

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 479 - 479

Опубликована: Март 27, 2025

Background: Longhorn beetles, a widely recognized group of Chinese traditional medicinal insects, are characterized by their notable hemostatic properties. However, the comprehensive understanding potential has been hindered limitations current research methodologies. Methods: This study focuses on species Glenea cantor (Fabricius), which can produce several generations per year, and introduces novel method using microwave carbonization techniques. By employing an in vitro coagulation test, UHPLC-MS, network pharmacology, molecular docking, dynamics simulation, efficacy mechanism action charcoal medicine (GC-CM) were thoroughly studied. Results: In tests showed that GC-CM significantly reduced activated partial thromboplastin time (APTT) prothrombin (PT), indicating its ability to enhance cascade preliminarily confirming (p < 0.01 vs. blank control group). The analysis revealed comprises 453 components, including 137 bioactive components with high human utilization. After predictions via databases such as SwissTargetPrediction deduplication, 215 targets linked specificity identified. These regulate signaling pathways platelet activation, complement cascades, cGMP-PKG. Molecular docking demonstrated strong affinities between key SRC PIK3R1 compounds 2′,6′-dihydroxy 4′-methoxydihydrochalcone, 1-monolinoleoyl-rac-glycerol (binding energy −5 kcal/mol). simulations show good binding capacity core Conclusions: aim this was elucidate material basis GC-CM, offering model for exploring other insect-based resources.

Язык: Английский

Процитировано

0

Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity DOI
Bingjie Hao,

Shumeng Lin,

Haipeng Liu

и другие.

Autophagy, Год журнала: 2024, Номер unknown, С. 1 - 17

Опубликована: Дек. 22, 2024

Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer traditional Chinese medicine, isscreened and validated to target CD274 induces itsmacroautophagic/autophagic degradation. Moreover, we demonstrate thatCD274 directly interacts with MAP1LC3B (microtubule associatedprotein 1 light chain 3 beta). Intriguingly, baicalein potentiatesCD274-LC3 interaction facilitate autophagic-lysosomal degradationof CD274. Importantly, targeted degradation via baicaleininhibits tumor by boosting T-cell-mediated antitumorimmunity. Thus, elucidate critical role autophagy-lysosomalpathway mediating degradation, conceptually demonstratethat design molecular "glue" that tethers CD274-LC3interaction is an appealing strategy develop inhibitors incancer therapy.

Язык: Английский

Процитировано

0