Estrogen receptor subtype mediated anti-inflammation and vasorelaxation via genomic and nongenomic actions in septic mice DOI Creative Commons
Luyun Zhang, Hanxing Wan, Mengting Zhang

et al.

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

Published: May 17, 2023

Sepsis is a life-threatening disease with high mortality worldwide. Septic females have lower severity and than the males, suggesting estrogen exerts protective action, but nothing known about role of vascular endothelial receptor subtypes in this process. In present study, we aimed to study receptors on mesenteric arterioles normal sepsis mice elucidate underlying mechanisms. was induced by intraperitoneal injection LPS. The changes expression release serum cell supernatant proinflammatory cytokines, including TNF-α, IL-1β IL-6, were measured qPCR ELISA, functions multiple organs analyzed. functional activities mouse determined Mulvany-style wire myograph. phospholipase C (PLC) inositol 1,4,5-trisphosphate (IP3R) cells examined Western blot their characterized Ca2+ imaging. female had higher survival rate male mice, pretreatment E2 for 5 days significantly improved inhibited cytokines septic mice. ameliorated pulmonary, intestinal, hepatic renal organ injuries mice; ER via PLC/IP3R/Ca2+ pathway. E2/ER immediately endothelial-derived hyperpolarization (EDH)-mediated vasorelaxation pathway, which more impaired could rescue acetylcholine (ACh)-induced EDH-mediated through mediates anti-inflammation genomic nongenomic actions sepsis. Mechanistically, activation reduces induces leading amelioration sepsis-induced injury rate.

Language: Английский

Pyroptosis-related non-coding RNAs emerging players in atherosclerosis pathology DOI
Weam M. A. Khojali,

Nasrin E. Khalifa,

Farhan Alshammari

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 255, P. 155219 - 155219

Published: Feb. 16, 2024

Language: Английский

Citations

2
Xijiao Dihuang Decoction Protects Against Murine Sepsis-Induced Cardiac Inflammation and Apoptosis via Suppressing TLR4/NF-κB and Activating PI3K/AKT Pathway DOI Creative Commons
Wei Li,

Mingrui Lin,

Jiapeng Li

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 853 - 863

Published: Feb. 1, 2024

Background: Xijiao Dihuang decoction (XJDHT), a traditional Chinese medicine, is widely used to treat patients with sepsis.However, the mechanisms underlying effects of XJDHT on cardiac dysfunction have yet be fully elucidated.The present study evaluated potential utility in protecting against sepsis-induced and myocardial injury.Methods: The mice were randomly divided into 3 groups administered Lipopolysaccharide (LPS,10 mg/kg) or equivalent saline solution (control) treated (10 g/kg/day) by gavage for 72 hours.XJDHT was dissolved 0.9% sodium chloride at 200 μL per mouse.Transthoracic echocardiography, RNA-seq, TUNEL assays hematoxylin eosin (H&E) staining tissues performed.Results: Treatment significantly enhanced function attenuated pathological change, infiltration inflammatory cells, levels TNF-α, IL-1β expression TLR4 NF-κB sepsis.RNA sequencing Kyoto Encyclopedia Genes Genomes pathway analyses identified 531 differentially expressed genes multiple enriched signaling pathways including PI3K/AKT pathway.Further, apoptosis decreased Bax protein while increasing Bcl-2, PI3K, p-AKT sepsis.Conclusion: In summary, improves murine model sepsis attenuating inflammation via suppressing TLR4/NF-κB activating pathway.

Language: Английский

Citations

2
The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice DOI
Ruiyu Wang, Minggui Wang,

Han-zhang Tang

et al.

Journal of Cardiovascular Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: March 25, 2024

Abstract: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication high morbidity mortality rates. The current study aimed to investigate the effects potential mechanisms of natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced injury septic mice. We found that RUS effectively alleviated pathological damage, normalized cardiac function, increased survival RNA sequencing (RNA-seq) demonstrated administration significantly inhibited activation NOD-like receptor signaling pathway tissues Subsequent experiments further confirmed suppressed inflammation pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged LPS, we observed could protect these cells LPS-induced cytotoxicity by suppressing pyroptosis. Notably, both vivo vitro findings indicated NLRP3 upregulation stimulated LPS. As expected, knockdown blocked cells. Furthermore, cardioprotective on under LPS stimulation abolished novel agonist BMS-986299. Taken together, our results suggest can alleviate sepsis, at least part NLRP3-mediated pyroptosis, highlighting this molecule as promising candidate for SIMD therapy.

Language: Английский

Citations

2
GSDMD knockout alleviates sepsis-associated skeletal muscle atrophy by inhibiting IL18/AMPK signaling DOI
Yongsheng Zhang,

Tonghan Li,

Yukun Liu

et al.

Shock, Journal Year: 2024, Volume and Issue: 62(4), P. 565 - 573

Published: Sept. 3, 2024

ABSTRACT Background: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial weakness and degeneration, ultimately contributing an adverse prognosis. Studies have shown that programmed cell death is important factor in the progression of loss sepsis. However, precise role mechanism pyroptosis atrophy are not yet fully comprehended. Therefore, we aimed examine action effector protein GSDMD recognized cellular mouse models Methods: The levels N-GSDMD were evaluated 2, 4, 8 days after cecal ligation puncture. was produced mice lacked Gsdmd gene (Gsdmd knockout) with normal (wild-type) using a procedure called degree muscular gastrocnemius tibialis anterior muscles assessed 72 h surgery septic model. In addition, architecture muscles, expression, markers associated pathways leading examined from various groups surgery. vitro investigations entailed use siRNA suppress expression C2C12 cells, followed stimulation these cells lipopolysaccharide evaluate impact downregulation on related signaling cascades. Results: This study has demonstrated protein, known as “executive” pyroptosis, plays crucial advancement mice. markedly higher compared control group. knockout exhibited notable enhancements survival, strength, body weight Deletion reduced wasting caused conducted living organisms ( vivo ) laboratory conditions absence decreases indicators sepsis blocking IL18/AMPK pathway. Conclusion: results this demonstrate lack beneficial effect reducing activation inhibiting ubiquitin-proteasome system autophagy pathways. our research provides vital insights into sepsis-related wasting, which could potentially lead development therapeutic interventional approaches for preventing atrophy.

Language: Английский

Citations

2
Estrogen receptor subtype mediated anti-inflammation and vasorelaxation via genomic and nongenomic actions in septic mice DOI Creative Commons
Luyun Zhang, Hanxing Wan, Mengting Zhang

et al.

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

Published: May 17, 2023

Sepsis is a life-threatening disease with high mortality worldwide. Septic females have lower severity and than the males, suggesting estrogen exerts protective action, but nothing known about role of vascular endothelial receptor subtypes in this process. In present study, we aimed to study receptors on mesenteric arterioles normal sepsis mice elucidate underlying mechanisms. was induced by intraperitoneal injection LPS. The changes expression release serum cell supernatant proinflammatory cytokines, including TNF-α, IL-1β IL-6, were measured qPCR ELISA, functions multiple organs analyzed. functional activities mouse determined Mulvany-style wire myograph. phospholipase C (PLC) inositol 1,4,5-trisphosphate (IP3R) cells examined Western blot their characterized Ca2+ imaging. female had higher survival rate male mice, pretreatment E2 for 5 days significantly improved inhibited cytokines septic mice. ameliorated pulmonary, intestinal, hepatic renal organ injuries mice; ER via PLC/IP3R/Ca2+ pathway. E2/ER immediately endothelial-derived hyperpolarization (EDH)-mediated vasorelaxation pathway, which more impaired could rescue acetylcholine (ACh)-induced EDH-mediated through mediates anti-inflammation genomic nongenomic actions sepsis. Mechanistically, activation reduces induces leading amelioration sepsis-induced injury rate.

Language: Английский

Citations

6