Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis DOI Creative Commons

Cheng-Fei Bi,

Jia Liu, Xiao Hu

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Sepsis is defined as a life-threatening organ dysfunction caused by dysregulated host response to infection. It characterized high morbidity and mortality one of the major diseases that seriously hang over global human health. Autophagy crucial regulator in complicated pathophysiological processes sepsis. The activation autophagy known be great significance for protecting sepsis induced dysfunction. Recent research has demonstrated N6-methyladenosine (m6A) methylation well-known post-transcriptional RNA modification controls epigenetic gene expression well number biological In addition, m6A affects stability, export, splicing translation transcripts involved autophagic process. Although it been suggested regulates metabolic more frequently seen progression pathogenesis, underlying molecular mechanisms m6A-modified have not thoroughly elucidated. present article fills this gap providing an review its potential role development novel therapeutics.

Language: Английский

High-dose Vitamin C injection ameliorates against sepsis induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats DOI Creative Commons
Yanan Cui, Na Tian,

Yan-Hai Luo

et al.

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: April 19, 2024

Aims: This study aimed to evaluate the effects of VC on SIMI in rats. Methods: In this study, survival rate high dose for was evaluated within 7 days. Rats were randomly assigned three groups: Sham group, CLP and (500 mg/kg i.v.) group. The animals each group treated with drugs 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes HE used detect cardiac function. IL-1β, IL-6, IL-10 TNF-α) serum measured using ELISA kits. Western blot proteins related apoptosis, inflammation, autophagy, MAPK, NF-κB PI3K/Akt/mTOR signaling pathways. Results: High improved staining showed that high-dose relieved rats a time-dependent manner. And compared decreased expressions pro-apoptotic proteins, while increased expression anti-apoptotic protein. phosphorylation levels Erk1/2, P38, JNK, IKK α/β protein Beclin-1 LC3-II/LC3-I ratio, whereas P62 Finally, attenuated PI3K, AKT mTOR Significance: Our results has good protective effect after continuous treatment, which may be mediated by inhibiting apoptosis inflammatory, promoting autophagy through regulating PI3K/AKT/mTOR pathway.

Language: Английский

Citations

4
Experimental Study on Myocardial Protective Effect of Xuebijing Injection on Extracorporeal Membrane Oxygenation Perfused Isolated Heart: Based on Autophagy and NLRP3 Inflammatory Pathway DOI

Shijie Yin,

Chunhua Wang, Yue Xiao

et al.

Transplantation Proceedings, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Quantitative analysis of drug–drug interactions among active components of Xuebijing in inhibiting LPS-induced TLR4 signaling and NO production DOI Creative Commons
Tianshu Zhang, Hongyuan Li, Cong Lin

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 1, 2025

Despite the long history of Traditional Chinese Medicine (TCM) in disease treatment, underlying "Jun–Chen–Zuo–Shi" principle remains largely unexplored. To address this gap, it is essential to elucidate interactions between active substances TCM through quantitative molecular and cellular pharmacology. The Chou–Talalay method particularly effective for investigating drug combinations, making highly relevant formulas. This study employed explore drug–drug Xuebijing (XBJ), a formula used treating sepsis. aim was by main XBJ: danshensu salvianolic acid B (from Radix Salviae Miltiorrhizae), senkyunolide A Rhizoma Chuanxiong), ligustilide Angelicae Sinensis), safflower yellow hydroxysafflor Flos Carthami), paeoniflorin Paeoniae Rubra). We quantitatively analyzed their TLR4 antagonistic activities combination index (CI) quantify interactions, revealing synergism (CI < 1), additive effects = antagonism > 1). results show these agents inhibit nitric oxide (NO) production, with some combinations demonstrating synergistic at certain concentrations, while others present effects. Understanding provides scientific foundation optimizing formulations, enhancing quality control, efficacy, safety.

Language: Английский

Citations

0
Integrated Metabolomics and Network Pharmacology Reveal the Mechanisms of Xuebijing in Counteracting Sepsis-induced Myocardial Dysfunction DOI

Yan Hu,

Yang Xu, Jian Gao

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119729 - 119729

Published: April 1, 2025

Language: Английский

Citations

0
Role of copper ion overload triggered by CD44 endocytosis on STAT3-mediated cuproptosis in septic myocardial injury DOI
Meng Zhang,

Donglin Fu,

Qiuhong Zhang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Abstract Sepsis-induced myocardial injury (SIMI) is a severe complication in sepsis patients, contributing to high mortality rates. The pathogenesis remains unclear, but emerging evidence suggests copper ion overload may trigger cell death via "cuproptosis." This study investigates the role of CD44, glycoprotein involved inflammation and metal uptake, copper-induced SIMI. Using an LPS-induced H9C2 cardiomyocyte model, we found CD44 expression upregulated SIMI, correlating with increased levels oxidative stress. inhibition reduced mitigated damage, confirming its copper-mediated injury. Furthermore, facilitated uptake into mitochondria, inducing dysfunction STAT3 pathway activation. overexpression exacerbated injury, highlighting critical role. These findings suggest CD44-mediated activation contributes positioning as potential therapeutic strategy for sepsis-induced damage.

Language: Английский

Citations

0
A Direct Relationship Between ‘Blood Stasis’ and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment DOI Creative Commons
Douglas B. Kell, Etheresia Pretorius, Huihui Zhao

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 712 - 712

Published: May 12, 2025

‘Blood stasis’ (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it known as Xue Yu (血瘀). Similar concepts exist Korean (‘Eohyul’) and Japanese Kampo medicine (Oketsu). Blood stasis considered to underpin large variety of inflammatory diseases, though an exact equivalent Western systems yet be described. Some time ago we discovered that blood can clot into anomalous amyloid form, creating what have referred fibrinaloid microclots. These microclots occur great many chronic, diseases are comparatively resistant fibrinolysis, thus the ability block microcapillaries hence lower oxygen transfer tissues, with multiple pathological consequences. We here develop idea precisely relate to, largely mechanistically responsible for, traditional (a term also used by Virchow). First, associated all stasis. Secondly, blocking red cell transport, provide simple mechanistic explanation for physical slowing down (‘stasis’) flow. Thirdly, herbal formulae proposed treat these especially Fu Zhu its derivatives, anticoagulatory anti-inflammatory, consistent they actually helping levels microclots, plausibly part catalysis polymerization fibrinogen form. rehearse some actions constituent herbs specific bioactive molecules contain. Consequently, such formulations (and their components), which little science medicine, would seem offer opportunity novel, safe, useful treatments chronic display including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, even ischemic stroke.

Language: Английский

Citations

0
ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway DOI Creative Commons
Zhen Peng, Xiaolong Lv, Xintong Wang

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 29, 2023

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported ACT001, modified compound parthenolide, improved survival sepsis mice. In this work, used cecal ligation puncture (CLP) model induce SIC. Transthoracic echocardiography HE staining assays were adopted evaluate influence ACT001 on sepsis-induced cardiac dysfunction. Our results showed significantly heart function reduced Coagulation accelerates damage We found decreased blood clotting FeCl 3 -induced carotid artery thrombosis experiment. also production neutrophil extracellular traps (NETs). RNA-sequencing tissues revealed downregulated expression pro-inflammatory cytokines JAK-STAT signaling pathway. These confirmed with real-time PCR ELISA. summary, rescued mice from septic shock protecting cardiovascular system. This was partially mediated inhibiting cytokine down-regulating signaling.

Language: Английский

Citations

4
METTL14 Promotes Lipopolysaccharide-Induced Myocardial Damage via m6A-Dependent Stabilization of TRPM7 mRNA DOI Open Access

Xinzhu Wu,

Pan Huang,

Yanmin Xiao

et al.

International Heart Journal, Journal Year: 2024, Volume and Issue: 65(6), P. 1118 - 1127

Published: Nov. 29, 2024

Sepsis-induced myocardial injury (SIMI) is a vital pathological component of severe sepsis and septic shock. As prevalent internal mRNA modification in eukaryotic cells, N6-methyladenosine (m6A) implicated immune disorders. Methyltransferase-like 14 (METTL14), core subunit the methyltransferase complex that catalyzes messenger RNA m6A modification, involved regulation human cardiomyocyte cell line (AC16) injury. This study aimed to explore role mechanism METTL14 lipopolysaccharide (LPS) -induced injury.Cell viability apoptosis were analyzed via 3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT), flow cytometry, TdT-mediated dUTP nick-end labeling (TUNEL) assay. The Tumor necrosis factor alpha (TNF-α) Interleukin-1beta (IL-1β) levels Enzyme linked immunosorbent assay (ELISA). Caspase-3 activity, reactive oxygen species malondialdehyde level, glutathione level assessed using special kits. transient receptor potential melastatin 7 (TRPM7) determined Real-time quantitative polymerase chain reaction (RT-qPCR). Meanwhile, protein TRPM7, METTL14, phospho-p65 (p-p65), total p65 (p65), p-IκBα, IκBα (IκBα) examined western blot assay.LPS treatment repressed AC16 induced apoptosis, inflammatory response, oxidative stress, ferroptosis vitro. TRPM7 upregulated LPS-treated cells. At molecular could increase stability methylation. Moreover, deficiency abolish LPS-triggered regulation.METTL14 knockdown reversed LPS-caused damage mainly by regulating mRNA, providing novel therapeutic target for cardiomyopathy treatment.

Language: Английский

Citations

1
Xuebijing Injection Alleviate Sepsis-induced Myocardial Damage by Inhibiting Apoptosis via PI3K/AKT/Foxo3a and MAPK Signaling Pathways DOI Creative Commons

An-Bu Liu,

Na Tian, Ke Feng

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 12, 2024

Abstract Background Xuebijing injections (XBJ) originate from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It is composed of five herbal extracts; Carthami flos, Paeoniae radix rubra, Chuanxiong rhizoma, Salviae miltiorrhizae, and Angelicae Sinensis radix. The China Food Drug Administration approved XBJ as a TCM preparation for adjuvant treatment sepsis. However, mechanisms underlying effects on sepsis-induced myocardial damage (SIMD) have yet to be fully elucidated. This study explores potential therapeutic mechanism SIMD. Methods In this study, rats were randomly assigned three groups: Sham group, cecal ligation puncture (CLP) group. Echocardiography, enzymes hematoxylin-eosin (H&E) used detect cardiac function. IL-1β, IL-6 IL-10, TNF-α, SOD MDA in serum measured using ELISA kits. AutoDockTools Vina was utilized molecular docking analyze binding with PI3K, AKT, Foxo3a, ERK1/2, P38 JNK protein. Western blotting conducted levels p-PI3K, p-AKT, p-Foxo3a, p-ERK1/2, p-P38, P38, p-JNK, JNK, Bax, Bcl-2, Cleaved-Caspase 3, Survivin proteins tissue. Immunofluorescence staining examine activity Immunohistochemical detection Bcl-2 3 expression. Results results echocardiography, enzyme H&E test showed that could effectively improve injury caused by CLP increase time. decreased IL-6, TNF-α levels, but increased IL-10 level CLP-induced SIMD ELISA. Molecular analysis indicated there strong stable affinity PI3K/AKT/Foxo3a MAPK signaling pathways. led downregulation p-P38 p-JNK while upregulating protein (p < 0.05). Conclusion may alleviate suppressing cell apoptosis inflammation possibly via

Language: Английский

Citations

0
Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis DOI Creative Commons

Cheng-Fei Bi,

Jia Liu, Xiao Hu

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Sepsis is defined as a life-threatening organ dysfunction caused by dysregulated host response to infection. It characterized high morbidity and mortality one of the major diseases that seriously hang over global human health. Autophagy crucial regulator in complicated pathophysiological processes sepsis. The activation autophagy known be great significance for protecting sepsis induced dysfunction. Recent research has demonstrated N6-methyladenosine (m6A) methylation well-known post-transcriptional RNA modification controls epigenetic gene expression well number biological In addition, m6A affects stability, export, splicing translation transcripts involved autophagic process. Although it been suggested regulates metabolic more frequently seen progression pathogenesis, underlying molecular mechanisms m6A-modified have not thoroughly elucidated. present article fills this gap providing an review its potential role development novel therapeutics.

Language: Английский

Citations

0