Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis DOI Creative Commons
Na‐Na Zhu,

Tianlun Li,

Yili Bai

и другие.

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Апрель 15, 2024

Abstract Background Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, major pathological contributor. Central to the development of fibrosis myocardial inflammation. This study focuses on Natriuretic Peptide (ANP) and its role in mitigating aiming elucidate specific mechanisms by which ANP exerts effects, an emphasis fibroblast dynamics. Methods results The involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang + ANP, only. administration 1 µg/kg/min was given groups, while both groups received 0.1 intravenously for duration 14 days. Cardiac fibroblasts were used vitro validation proposed mechanisms. observed that rats showed increase blood pressure decrease body weight, more pronounced group. Diastolic dysfunction, characteristic group, alleviated ANP. Additionally, significantly reduced II-induced myofibroblast proliferation, collagen overexpression, macrophage infiltration, elevated expression Interleukin 6 (IL-6) Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling Furthermore, studies along PI3K inhibitor LY294002, effectively pathway activation TN-C, collagen-I, collagen-III, induced II. Conclusions demonstrates ANP’s potential inhibiting inflammation reducing fibrosis. Notably, effect countering seems be mediated through suppression PI3K/Akt-Tenascin-C pathway. These insights enhance our understanding AF pathogenesis position as therapeutic agent treating

Язык: Английский

Pulsatile Flow Increases METTL14-induced m6A modification and attenuates septic cardiomyopathy: an experimental study DOI Creative Commons
Shenyu Zhu, Kai Wang, Zhexuan Yu

и другие.

International Journal of Surgery, Год журнала: 2024, Номер unknown

Опубликована: Март 28, 2024

Introduction: Septic cardiomyopathy is a sepsis-mediated cardiovascular complication with severe microcirculatory malperfusion. Emerging evidence has highlighted the protective effects of pulsatile flow in case disturbance, yet underlying mechanisms are still elusive. The objective this study was to investigate N6-methyladenosine (m 6 A) modification alleviation septic associated extracorporeal membrane oxygenation (ECMO)-generated flow. Methods: Rat model established and supported under ECMO either or non-pulsatile Peripheral perfusion index (PPI) cardiac function parameters were measured using ultrasonography. Dot blot assay applied examine m A level, while qRT-PCR, Western blot, immunofluorescence, immunohistochemistry used measure expressions related genes. RNA immunoprecipitation performed validate interaction between molecules. Results: ECMO-generated significantly elevates PPI, improves myocardial function, protects endothelium, prolongs survival rat models cardiomyopathy. mediates METTL14-mediated zonula occludens- (ZO-) 1 mRNA which stabilizes ZO-1 depending on presence YTHDF2. suppresses PI3K-Akt signaling pathway, downstream molecule Foxo1, negative transcription factor METTL14, binds METTL14 promoter inhibits METTL14-induced modification. Conclusion: increases attenuates progression cardiomyopathy, suggesting that pulsatility might be new therapeutic strategy by alleviating disturbance.

Язык: Английский

Процитировано

6
Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk DOI

Chunmeng Jin,

Xiaobo Tao,

Wendi Zhang

и другие.

Archives of Toxicology, Год журнала: 2024, Номер 98(9), С. 2907 - 2918

Опубликована: Май 29, 2024

Язык: Английский

Процитировано

5
Paroxetine alleviates dendritic cell and T lymphocyte activation via GRK2-mediated PI3K–AKT signaling in rheumatoid arthritis DOI Creative Commons
Tingting Liu, Chao Jin, Jing Sun

и другие.

Chinese Medical Journal, Год журнала: 2024, Номер unknown

Опубликована: Июнь 14, 2024

Abstract Background: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In present work, we explored how paroxetine, a GRK2 inhibitor, modulates differentiation and activation immune rheumatoid arthritis (RA). Methods: The blood samples healthy individuals RA patients were collected between July 2021 March 2022 from First Affiliated Hospital Anhui Medical University. C57BL/6 mice used to induce collagen-induced (CIA) model. Flow cytometry analysis was characterize function dendritic (DCs)/T cells. Co-immunoprecipitation explore specific molecular mechanism. Results: RA, high expression peripheral lymphocytes, accompanied by increases phosphatidylinositol 3 (PI3K), protein B (AKT), mammalian target rapamycin (mTOR). animal model, decrease regulatory T (T regs ), an increase cluster 8 positive (CD8 + ) cells, maturation DCs observed. Paroxetine, when vitro CIA mice, restrained CD8 induced proportion . Paroxetine inhibited secretion pro-inflammatory cytokines, C-C motif chemokine 7 Simultaneously, paroxetine upregulated programmed death ligand 1, anti-inflammatory cytokines. Additionally, PI3K–AKT–mTOR metabolic pathway both This associated reduction mitochondrial membrane potential changes utilization glucose lipids, particularly DCs. reversed PI3K–AKT 740 Y-P (a PI3K agonist) through inhibiting interaction Conclusion: exerts immunosuppressive effect targeting GRK2, which subsequently inhibits metabolism-related cell RA.

Язык: Английский

Процитировано

5
Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment DOI Creative Commons
Yunfeng Wu, Jiajia Li,

Linfeng Shu

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 29, 2024

The tumor microenvironment (TME) plays an important role in dynamically regulating the progress of cancer and influencing therapeutic results. Targeting is a promising treatment method recent years. importance immune regulation by ultrasound combined with microbubbles now widely recognized. Ultrasound work together to induce antigen release cell through mechanical or thermal effects, promoting presentation T cells’ recognition killing cells, improve immunosuppression microenvironment, which will be breakthrough improving traditional problems such as checkpoint blocking (ICB) himeric receptor (CAR)-T therapy. In order effect TME targeted therapy, it necessary develop optimize application system microbubble for organs diseases. Therefore, combination field continue focus on developing more effective strategies regulate mechanisms, so activate anti-tumor immunity and/or efficacy immune-targeted drugs, At present, potential value therapy has great potential, been confirmed experimental research breast cancer, colon pancreatic prostate provides new alternative idea clinical treatment. This article reviews tumors their microenvironment.

Язык: Английский

Процитировано

4
Ba-Qi-Rougan formula alleviates hepatic fibrosis by suppressing hepatic stellate cell activation via the MSMP/CCR2/PI3K pathway DOI Creative Commons

Yan Xue,

Wanchun Zhu,

Fengjie Qiao

и другие.

Journal of Ethnopharmacology, Год журнала: 2024, Номер 329, С. 118169 - 118169

Опубликована: Апрель 16, 2024

The Ba-Qi-Rougan formula (BQRGF) is a traditional and effective compound prescription from Traditional Chinese Medicine (TCM) utilized in treating hepatic fibrosis (HF).

Язык: Английский

Процитировано

4
Immune response gene 1 deficiency aggravates high fat diet-induced nonalcoholic fatty liver disease via promotion of redox-sensitive AKT suppression DOI Creative Commons
Xue Zhang,

Ying Zhi,

Xinyan Zan

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(4), С. 166656 - 166656

Опубликована: Янв. 25, 2023

Язык: Английский

Процитировано

11
Identification of shared gene signatures and molecular mechanisms between chronic kidney disease and ulcerative colitis DOI Creative Commons
Liang Zhou, Xinrong Hu,

Ruoni Lin

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 13, 2023

There is a complex interaction between chronic kidney disease (CKD) and ulcerative colitis (UC), but the pathophysiological mechanisms underlying coexistence of CKD UC are unclear. This study aimed to investigate key molecules pathways that may mediate co-occurrence through quantitative bioinformatics analysis based on public RNA-sequencing database. The discovery datasets (GSE66494) (GSE4183), as well validation (GSE115857) (GSE10616), were downloaded from Gene Expression Omnibus (GEO) After identifying differentially expressed genes (DEGs) with GEO2R online tool, Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses for DEGs performed. Next, protein-protein network was constructed Search Tool Retrieval Interacting (STRING) visualized by Cytoscape. modules identified plug-in MCODE hub screened using CytoHubba. Then, correlation immune cell infiltration analyzed, receiver operating characteristic curves used assess predictive value genes. Finally, immunostaining human specimens validate relevant findings. A total 462 common selected further analyses. GO KEGG indicated these primarily enriched in immune- inflammation-related pathways. Among them, PI3K-Akt signaling ranked top both cohorts, signal molecule phosphorylated Akt (p-Akt) shown be significantly overexpressed kidneys colons, elevated CKD-UC comorbidity specimens. Moreover, nine candidate genes, including CXCL8, CCL2, CD44, ICAM1, IL1A, CXCR2, PTPRC, ITGAX, CSF3, identified, which ICAM1 validated gene. Besides, revealed neutrophils, macrophages, CD4+ T memory cells accumulated diseases, remarkably associated neutrophil infiltration. Furthermore, intercellular adhesion molecule1 (ICAM1)-mediated upregulated colon biopsies patients, increased patients diagnosed UC. had critical diagnostic marker Our elucidated response, pathway, ICAM1-mediated might pathogenesis UC, potential biomarker therapeutic target two diseases.

Язык: Английский

Процитировано

11
Calenduloside E ameliorates non-alcoholic fatty liver disease via modulating a pyroptosis-dependent pathway. DOI
Yifei Le,

Jianan Guo,

Zhijun Liu

и другие.

Journal of Ethnopharmacology, Год журнала: 2023, Номер 319, С. 117239 - 117239

Опубликована: Сен. 28, 2023

Язык: Английский

Процитировано

11
Yunweiling alleviates functional constipation: integrating network pharmacology and experimental study DOI Creative Commons
Peng Zhang, Wei Li,

Weiwen Zheng

и другие.

Animal Models and Experimental Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Abstract Background This study investigated the impacts and mechanisms of yunweiling in management Functional Constipation (FC) using network pharmacology experimental research. Methods Using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), Genecard, Online Mendelian Inheritance Man (OMIM) databases, a potential gene target for treating FC was found. A pharmacological built viewed Cytoscape. protein interaction map created with STRING ‘clusterProfiler’ helped uncover its mechanism. Molecular docking done AutoDock Vina. In constipation mouse model, Western blot used to assess yunweiling's effectiveness. Results To investigate therapeutic effects on FC, we employed loperamide‐induced model. Successful model establishment confirmed by first black stool time, reduced output, impaired gastrointestinal motility. Yunweiling treatment, especially at high medium doses, significantly alleviated symptoms reducing increasing enhancing HE staining revealed ability restore colon tissue structure. modulated expression key proteins TP53, P‐AKT, P‐PI3K, RET, Rai, implicating involvement PI3K‐Akt signaling pathway. Comparative analysis showed be more effective than individual components (shionone, β‐sitosterol, daucosterol) improving constipation. The combination TP53 inhibitors further enhanced effects, suggesting synergistic Conclusions integration investigations indicated effectiveness managing offering essential theoretical support clinical application.

Язык: Английский

Процитировано

0
Kinsenoside attenuates ER stress and inhibits inflammatory responses through IL-10/STAT/SOCS3 pathway in chronic pain relief DOI
Wei Wang,

Yingzhuo Ding,

Chunxia Yu

и другие.

Neuropharmacology, Год журнала: 2025, Номер unknown, С. 110463 - 110463

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0