A mechanism study of tripartite motif 10 modulating septic cardiomyopathy DOI Open Access
Zhimei Yang, Jie Su

CytoJournal, Год журнала: 2024, Номер 21, С. 73 - 73

Опубликована: Дек. 26, 2024

Septic cardiomyopathy (SCM), as a complication of the septic process, severely affects myocardial function patients, but its pathogenesis remains unclear. The article aims to explore mechanism tripartite motif 10 (TRIM10) in rats with SCM and provide animal experimental basis for treatment prevention SCM. An rat model was constructed by intraperitoneal injection lipopolysaccharide (LPS). Sh-NC sh-TRIM10 groups were injected sh-NC tail vein 3 consecutive days before modeling. expression TRIM10 detected Western blot reverse transcription-polymerase chain reaction analyses. Hematoxylin-eosin staining performed observe pathological changes myocardium. Cardiomyocyte apoptosis flow cytometry. Serum levels cardiac troponin I, myohemoglobin, creatine kinase-MB, interleukin-18 (IL-18), interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase, glutathione peroxidase (GSH-Px) enzyme-linked immunosorbent assay. Apoptosis-related proteins toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) pathway-related explored increased LPS group (P < 0.0001). Myocardial tissue injury improved after reduction compared that group. Knockdown decreased MDA 0.01), IL-18 0.0001), IL-1β TNF-α 0.0001) contents SOD 0.001) GSH-Px those reduced H9C2 cells After interference, p-P65/P65 TLR4 decreased. knockdown can reduce inflammation, oxidative stress, has protective effect on cardiomyocytes, which may be attributed regulation TLR4/NF-κB pathway.

Язык: Английский

NLRP3 Inflammasome Targeting Offers a Novel Therapeutic Paradigm for Sepsis-Induced Myocardial Injury DOI Creative Commons

Yuzi Jin,

Joshua S. Fleishman,

Yudong Ma

и другие.

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 1025 - 1041

Опубликована: Фев. 1, 2025

Cardiac or myocardial dysfunction induced by sepsis, known as sepsis-induced cardiomyopathy injury (SIMI), is a common complication of sepsis and associated with poor outcomes. However, the pathogenesis molecular mechanisms underlying SIMI remain poorly understood, requiring further investigations. Emerging evidence has shown that NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasomes contribute to SIMI. Compounds inhibit NLRP3-associated pyroptosis may exert therapeutic effects against In this review, we first outlined principal elements NLRP3 signaling cascade summarized recent studies highlighting how activation contributes We selective small-molecule modulators function inhibitors delineated their action attenuate Finally, discuss major limitations current paradigm propose possible strategies overcome them. This review highlights pharmacological inhibition promising strategy.

Язык: Английский

Процитировано

1
Stachyose ameliorates myocardial ischemia–reperfusion injury by inhibiting cardiomyocyte ferroptosis and macrophage pyroptosis DOI

Ao-Yuan Zhang,

Jia‐Bao Su,

Heting Sun

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113334 - 113334

Опубликована: Окт. 8, 2024

Язык: Английский

Процитировано

6
Identifying key palmitoylation-associated genes in endometriosis through genomic data analysis DOI Creative Commons
Jinyan Kai,

Jiaqi Su,

Y. Nancy You

и другие.

BMC Women s Health, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 5, 2025

Palmitoylation, a post-translational lipid modification, has garnered increasing attention for its role in inflammatory processes and tumorigenesis. Emerging evidence suggests potential association between palmitoylation responses the pathogenesis of endometriosis. However, precise mechanistic interplay remains elusive, necessitating further investigation. This study integrated transcriptomic analysis Mendelian randomization (MR) to identify causal gene set implicated Differentially expressed genes (DEGs) were first identified training dataset using limma package R. Weighted co-expression network (WGCNA) was subsequently performed, leveraging Single Sample Gene Set Enrichment Analysis (ssGSEA)-derived scores palmitoylation-related (PRGs) as phenotypic traits key modular genes. The intersection these with DEGs yielded refined set. Machine learning algorithms then applied optimize selection, followed by external validation, immune infiltration analysis, RNA construction, exploration targeted drug candidates. Through rigorous screening process, VRK1, GALNT12, RMI1 emerged associated palmitoylation, exhibiting significant downregulation endometriosis samples (P < 0.05), indicative protective role. Immune revealed strong correlations M2 macrophages well resting Natural Killer (NK) cells. Additionally, investigations into profiling provided novel insights, laying groundwork future high-quality validation studies. employed comprehensive analytical framework palmitoylation-associated integration immunoinfiltration offers valuable insights advancing clinical diagnostics, disease monitoring, therapeutic development

Язык: Английский

Процитировано

0
Palmitoylation in cardiovascular diseases: Molecular mechanism and therapeutic potential DOI
Rongli Wang,

Yi He,

Yan Wang

и другие.

IJC Heart & Vasculature, Год журнала: 2025, Номер 58, С. 101675 - 101675

Опубликована: Апрель 6, 2025

Язык: Английский

Процитировано

0
Exploring the role of palmitoylation in sepsis: mechanistic insights and future perspectives DOI Creative Commons
Susu Cao, Wenyan Xiao,

Sinong Pan

и другие.

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Июнь 3, 2025

The palmitoylation system is intricate, multidimensional, and plays a crucial role in various inflammatory immune-related disorders. Palmitoylation controls protein stability, cargo sorting, signal transmission, as well cell differentiation death. Notably, growing body of studies has highlighted its participation processes, either directly or indirectly, indicating broad complex involvement the development sepsis. Understanding mechanisms underlying essential for advancing research on We began this review with brief summary related to sepsis progression. Second, we went over recent palmitoylation. Third, compiled described palmitoylation-related alterations vital molecules biological processes involved Lastly, outlined promising features proposed hopeful outlook future

Язык: Английский

Процитировано

0
High-Throughput Screening of an FDA-Approved Compound Library Reveals a Novel GAS6 Receptor Agonist for Therapeutic Intervention in Septic Myocardial and microvascular Injury via Modulation of Danger-Associated Molecular Patterns DOI Creative Commons

Haowen Zhuang,

Chun Guang Li, Lingjun Wang

и другие.

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(15), С. 6222 - 6240

Опубликована: Ноя. 11, 2024

PGAM5 and VDAC1 have both been reported to regulate mitophagy. However, the mechanisms by which they sepsis-induced inflammatory microvascular injury remain unverified. In previous studies, we established role of this regulatory axis in various phenotypic processes, including mitophagy, mitochondrial biogenesis, unfolded protein response, dynamics, while further confirming interactive proteins within axis. validation elucidation these phenotypes primarily focused on ischemic heart diseases such as myocardial failure. Sepsis-related is currently recognized a significant cardiac impairment, although there are cardioprotective nutritional agents available for supportive therapy, fundamental research validating upstream targets still lacking. Based our research, explored mitophagy dysfunction mediated its coronary injury. We also confirmed material basis metabolic pathway regulation targeting PGAM5- mechanism with relevant drugs. Our findings suggest that PGAM5-mediated may be crucial factor leading injury, interacting VDAC1-mediated membrane dysfunction. Animal experiments revealed cardiac-specific knockout could reverse LPS-induced damage, restoring ejection function functionality. vitro studies PGAM5-VDAC1 interaction can normalize normal morphology structure mitochondria maintaining energy metabolism levels respiratory chain function. Further pharmacological indicated active ingredients traditional Chinese medicine-Puerarin (TCM, GAS6 Receptor Agonist) target inhibit necrotic apoptosis cardiomyocytes, potentially reversing pathway-related TCM emerge prospective therapeutic agent

Язык: Английский

Процитировано

2
Regulation of pattern-recognition receptor signaling by palmitoylation DOI Creative Commons

Xiaocui Li,

Xiaofang Hu,

Hongjuan You

и другие.

iScience, Год журнала: 2024, Номер 28(2), С. 111667 - 111667

Опубликована: Дек. 20, 2024

Язык: Английский

Процитировано

2
A mechanism study of tripartite motif 10 modulating septic cardiomyopathy DOI Open Access
Zhimei Yang, Jie Su

CytoJournal, Год журнала: 2024, Номер 21, С. 73 - 73

Опубликована: Дек. 26, 2024

Septic cardiomyopathy (SCM), as a complication of the septic process, severely affects myocardial function patients, but its pathogenesis remains unclear. The article aims to explore mechanism tripartite motif 10 (TRIM10) in rats with SCM and provide animal experimental basis for treatment prevention SCM. An rat model was constructed by intraperitoneal injection lipopolysaccharide (LPS). Sh-NC sh-TRIM10 groups were injected sh-NC tail vein 3 consecutive days before modeling. expression TRIM10 detected Western blot reverse transcription-polymerase chain reaction analyses. Hematoxylin-eosin staining performed observe pathological changes myocardium. Cardiomyocyte apoptosis flow cytometry. Serum levels cardiac troponin I, myohemoglobin, creatine kinase-MB, interleukin-18 (IL-18), interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase, glutathione peroxidase (GSH-Px) enzyme-linked immunosorbent assay. Apoptosis-related proteins toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) pathway-related explored increased LPS group (P < 0.0001). Myocardial tissue injury improved after reduction compared that group. Knockdown decreased MDA 0.01), IL-18 0.0001), IL-1β TNF-α 0.0001) contents SOD 0.001) GSH-Px those reduced H9C2 cells After interference, p-P65/P65 TLR4 decreased. knockdown can reduce inflammation, oxidative stress, has protective effect on cardiomyocytes, which may be attributed regulation TLR4/NF-κB pathway.

Язык: Английский

Процитировано

0