SHOCK最新文献

{"title":"Correcting the Carotid Flow Time with the Formula of Bazett: mind the units.","authors":"Jon-Emile S Kenny","doi":"10.1097/SHK.0000000000002487","DOIUrl":"10.1097/SHK.0000000000002487","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Analysis of Endothelial Markers to predict Sepsis in the Emergency Department.","authors":"Noa Galtung, Vanessa Stein, Monika Prpic, Burak Boyraz, Jannis Ulke, Stephan Kurz, Jens Dernedde, Eva Diehl-Wiesenecker, Wolfgang Bauer, Kai Kappert","doi":"10.1097/SHK.0000000000002482","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002482","url":null,"abstract":"<p><strong>Background: </strong>Acute infections and sepsis are a leading cause of death. These patients are primarily encountered at the emergency department (ED), where early assessment for sepsis is necessary to improve outcome. In sepsis, the inflammatory response causes several characteristic pathophysiological changes, including a dysregulated and generalized activation of the endothelium. This study aimed to analyse endothelial markers released to the blood as diagnostic biomarkers for acute infection and sepsis in the ED, as smaller studies have previously shown promising results in other settings.</p><p><strong>Methods: </strong>Serum samples from n = 312 adult patients with suspected acute infections at presentation to the ED were utilized. Patients' courses of disease and outcomes were assessed by clinical adjudication. E-Selectin, P-Selectin, ICAM-1, and VCAM-1 were measured by ELISAs. The accuracy of each marker for predicting bacterial infection, sepsis, and in-hospital mortality, was evaluated.</p><p><strong>Results: </strong>For sepsis, E-Selectin and ICAM-1 both showed an AUROC of 0.62, lower than procalcitonin with 0.77 (both p < 0.01) and lactate with 0.73 (p = 0.030 and 0.046, respectively), but similar to CRP with 0.60 (p = 0.758 and 0.876, respectively). For 28-day in-hospital mortality among patients with infection, ICAM-1 performed best with an AUROC of 0.75.</p><p><strong>Conclusions: </strong>Despite promising results in small studies and specific cohorts, particularly in intensive care units, this large-scale evaluation of four endothelial biomarkers highlights their limited diagnostic utility in a broader inclusion set-up design at the earliest possible time-point of evaluation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole transcription analysis identified the regulation of hypoxia-inducible factors in monocytes with immune suppression: implications for clinical outcomes.","authors":"Zhao Shuai, Li Hui, Luo Wei, Hu Zhaolan, Wang Yulu, Liu Tao, Zhang Yanling, Dai RuPing","doi":"10.1097/SHK.0000000000002479","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002479","url":null,"abstract":"<p><strong>Aims: </strong>Sepsis progression is marked by a complex immune response, where the involvement of hypoxia-inducible factors (HIF) plays an uncertain role. The study aims to elucidate the involvement of HIF-1α in monocyte function during sepsis and its potential as a prognostic indicator.</p><p><strong>Methods and results: </strong>Transcriptomic data from healthy individuals and septic patients in datasets GSE54514, GSE167363, and GSE46955 were analyzed. Additionally, human monocytes were employed to elucidate how HIF regulates immune responses in the context of sepsis. Septic non-survivors exhibited sustained upregulation of HIF-1α expression alongside compromised inflammatory response and antigen presentation, with downregulation of NF-κB and HLADRB1 genes associated with poor sepsis prognosis. Conversely, septic survivors displayed an increased proportion of classical monocytes and enhanced inflammation and expression of antigen presentation-related genes. During the recovery phase of sepsis, monocytes continued to demonstrate elevated HIF-1α expression. In cultured THP1 cells and septic CD14+ monocytes, HIF hindered inflammatory responses and antigen presentation, while also suppressing the proportion of classical monocytes after LPS stimulation. Mechanistically, HIF significantly attenuated LPS-induced immune responses in monocytes by inhibiting the phosphorylation of IKK.</p><p><strong>Conclusions: </strong>HIF in monocytes acts as a suppressor of immune-inflammatory responses and antigen presentation, and may serve as a negative molecular marker for sepsis development.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYELOID-DERIVED TLR4-TRIF SIGNALING PATHWAY MEDIATES OXIDATIVE STRESS IN LPS/D-GALN-INDUCED ACUTE LIVER FAILURE.","authors":"Jing Li, Li Jiang, Kai Zhao, Yiting Tang, Xiangning Yuan, Yunfei Xu","doi":"10.1097/SHK.0000000000002438","DOIUrl":"10.1097/SHK.0000000000002438","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Acute liver failure (ALF) is a severe clinical syndrome characterized by massive hepatocyte death in a short time due to viruses, drugs, alcohol, or other factors. Oxidative stress is an important pathogenic mechanism of ALF. LPS-induced internalization of toll-like receptor 4 (TLR4) and the subsequent activation of the toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) signaling pathway widely mediate inflammatory responses in a series of diseases. However, whether the TLR4-TRIF signaling pathway contributes to ALF by mediating oxidative stress processes remains unclear. Methods: An ALF mouse model was induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN). TLR4-TRIF systemic knockout mice and TLR4 conditional knockout mice were used to determine the role of the TLR4-TRIF signaling pathway in ALF. The effects of TLR4 or TRIF deficiency on oxidative stress were investigated. In addition, we examined the protective role of the clodronate liposomes (macrophage scavengers) and the antioxidant N-acetylcysteine (NAC) in ALF. Results: TLR4 or TRIF deficiency significantly alleviated LPS/D-GalN-induced lethality, hepatic dysfunction, and hepatic pathologic injury, which was dependent on myeloid-derived TLR4. Hence, macrophage clearance exhibits a similar protective effect. Mechanically, TLR4 or TRIF deficiency was observed to inhibit oxidative stress by increasing glutathione, while decreasing malondialdehyde, 8-hydroxy-2-deoxyguanosine, and γ-H2AX. Therefore, the pharmacologic antioxidant NAC exhibited significant hepato-protective effects. Conclusions: Targeting myeloid-derived TLR4-TRIF signaling pathway or antioxidant therapy may be a potential therapeutic direction to treat ALF.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE USE OF POLOXAMER 188 IN BURN INJURY TREATMENT: A SYSTEMATIC LITERATURE REVIEW.","authors":"Kevin T Mutore, Roopa Koduri, Nagham Alatrash, Vanessa Nomellini","doi":"10.1097/SHK.0000000000002439","DOIUrl":"10.1097/SHK.0000000000002439","url":null,"abstract":"<p><strong>Abstract: </strong>Although there have been numerous advancements in burn wound management, burn injuries are still a major cause of morbidity and mortality in the United States, and novel therapeutics are still needed to improve outcomes. Poloxamer 188 (P188) is a synthetic copolymer with Food and Drug Administration (FDA) approval that has many biological applications. This study aimed to review the literature on P188 in burn injuries and its effects based on burn mechanisms. We employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to complete this systematic literature review. We searched the databases of Google Scholar, PubMed, and SCOPUS using the keywords burn, p188, poloxamer 188, and pluronic F68 in combination. Two reviewers independently screened the articles for inclusion. Articles that were not in English, were book chapters or conference proceedings, or did not evaluate P188 in the setting of burn injuries were excluded. We included a total of 33 full-text articles with both in vivo and in vitro preclinical studies. P188 was found to be beneficial in animal and cell studies evaluating electrical and thermal burn injuries. P188 was also found to be useful in burn wound management. Although its utility may be limited in radiation injuries, P188 may be helpful in delaying the initial damage caused by radiation burns. P188 therefore has the potential to be used as a therapy in both burn wound management and in the treatment of systemic injuries sustained through burns. Future studies should aim to assess the efficacy of P188 in clinical models of burn injury.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FACTORS INFLUENCING LATE PROGNOSIS IN PATIENTS WITH ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION TREATED WITH DIRECT PERCUTANEOUS CORONARY INTERVENTION.","authors":"Yonghong Li, Guangke Cao","doi":"10.1097/SHK.0000000000002432","DOIUrl":"10.1097/SHK.0000000000002432","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: To investigate factors influencing the late prognosis of patients with acute ST-segment elevation myocardial infarction treated by direct percutaneous coronary intervention. Methods: We retrospectively analyzed 349 ST-segment elevation myocardial infarction patients treated with direct percutaneous coronary intervention. Patients were categorized based on catheter laboratory activation time (CLAT) (≤15 or >15 min), time of arrival (working hours or out-of-hours), and mode of arrival (emergency medical services transportation or self-presentation). The primary endpoint was the 2-year major adverse cardiovascular events (MACEs), defined as all-cause death, nonfatal myocardial infarction, and target vessel revascularization. Results: Patients with CLAT ≤15 min showed significant differences in oxygen saturation, FMC-to-device time, symptom-to-device time, symptom-to-FMC time, presentation mode, presentation duration, and MACEs (all P < 0.005). Self-presentation (odds ratio = 0.593, 95% confidence interval = 0.413-0.759) and out-of-hours presentation (odds ratio = 0.612, 95% confidence interval = 0.433-0.813) were risk factors for CLAT >15 min. The working-hours group showed significant differences in FMC-to-device time, activation-to-arrival time at the catheter laboratory, and the number of cases with activation time ≤15 min (all P < 0.005). The emergency medical services and self-presentation groups differed significantly in age, blood pressure, FMC-to-device time, and electrocardiography-to-CLAT (all P < 0.005). Conclusion: Reducing CLAT to 15 min significantly lowers the 2-year MACE rate. Self-presentation and out-of-hours presentation are risk factors for delayed catheter laboratory activation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RENIN AND ANGIOTENSIN (1-7) OFFER PREDICTIVE VALUE IN PEDIATRIC SEPSIS: FINDINGS FROM PROSPECTIVE OBSERVATIONAL COHORTS.","authors":"Dandan Pi, Lijun Zheng, Caixia Gao, Changxue Xiao, Zhicai Yu, Yueqiang Fu, Jing Li, Chengzhi Chen, Chengjun Liu, Zhen Zou, Feng Xu","doi":"10.1097/SHK.0000000000002417","DOIUrl":"10.1097/SHK.0000000000002417","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Pediatric sepsis is a common and complex syndrome characterized by a dysregulated immune response to infection. Aberrations in the renin-angiotensin system (RAS) are factors in several infections of adults. However, the precise impact of RAS dysregulation in pediatric sepsis remains unclear. Methods: Serum samples were collected from a derivation cohort (58 patients with sepsis, 14 critically ill control subjects, and 37 healthy controls) and validation cohort (50 patients with sepsis, 37 critically ill control subjects, and 46 healthy controls). Serum RAS levels on day of pediatric intensive care unit admission were determined and compared with survival status and organ dysfunction. Results: In the derivation cohort, the serum renin concentration was significantly higher in patients with sepsis (3,678 ± 4,746) than that in healthy controls (635.6 ± 199.8) ( P < 0.0001). Meanwhile, the serum angiotensin (1-7) was significantly lower in patients with sepsis (89.7 ± 59.7) compared to that in healthy controls (131.4 ± 66.4) ( P < 0.01). These trends were confirmed in a validation cohort. Nonsurvivors had higher levels of renin (8,207 ± 7,903) compared to survivors (2,433 ± 3,193) ( P = 0.0001) and lower levels of angiotensin (1-7) (60.9 ± 51.1) compared to survivors (104.0 ± 85.1) ( P < 0.05). A combination of renin, angiotensin (1-7) and procalcitonin achieved a model for diagnosis with an area under the receiver operating curve of 0.87 (95% CI: 0.81-0.92). Conclusion: Circulating renin and angiotensin (1-7) have predictive value in pediatric sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME.","authors":"Colin J Sallee, Aline B Maddux, Joseph A Hippensteel, Daniela Markovic, Kaori Oshima, Andreas Schwingshackl, Peter M Mourani, Eric P Schmidt, Anil Sapru","doi":"10.1097/SHK.0000000000002421","DOIUrl":"10.1097/SHK.0000000000002421","url":null,"abstract":"<p><strong>Abstract: </strong>Introduction: Sepsis-induced degradation of endothelial glycocalyx heparan sulfate (HS) contributes to the pulmonary microvascular endothelial injury characteristic of acute respiratory distress syndrome (ARDS) pathogenesis. Our objectives were to (1) examine relationships between plasma indices of HS degradation and protein biomarkers of endothelial injury and (2) identify patient subgroups characterized by distinct profiles of HS degradation in children with ARDS. Methods: We analyzed prospectively collected plasma (2018-2020) from a cohort of invasively mechanically ventilated children (aged >1 month to <18 years) with ARDS. Mass spectrometry characterized and quantified patterns of HS disaccharide sulfation. Protein biomarkers reflective of endothelial injury (e.g., angiopoietin-2, vascular cell adhesion molecule-1, soluble thrombomodulin) were measured with a multiplex immunoassay. Pearson correlation coefficients were used to construct a biomarker correlation network. Centrality metrics detected influential biomarkers (i.e., network hubs). K-means clustering identified unique patient subgroups based on HS disaccharide profiles. Results: We evaluated 36 patients with pediatric ARDS. HS disaccharide sulfation patterns, 6S, NS, and NS2S, positively correlated with all biomarkers of endothelial injury (all P < 0.05) and were classified as network hubs. We identified three patient subgroups, with cluster 3 (n = 5) demonstrating elevated levels of 6S and N-sulfated HS disaccharides. In cluster 3, 60% of children were female and nonpulmonary sepsis accounted for 60% of cases. Relative to cluster 1 (n = 12), cluster 3 was associated with higher oxygen saturation index (P = 0.029) and fewer 28-day ventilator-free days (P = 0.016). Conclusions: Circulating highly sulfated HS fragments may represent emerging mechanistic biomarkers of endothelial injury and disease severity in pediatric ARDS.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLINICAL OUTCOMES OF PATIENTS WITH CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION: THE GULF-CARDIOGENIC SHOCK REGISTRY.","authors":"Amin Daoulah, Mohammed Alshehri, Prashanth Panduranga, Hatem M Aloui, Nooraldaem Yousif, Abdulrahman Arabi, Wael Almahmeed, Mohammed A Qutub, Ahmed Elmahrouk, Amr A Arafat, Omar Kanbr, Adnan Fathey Hussien, Mubarak Abdulhadi Aldossari, Abdulmohsen H Al Mefarrej, Tarique Shahzad Chachar, Haitham Amin, Gladsy Selva Livingston, Abeer Said Mohamed Al Rawahi, Jassim Alswuaidi, Shahrukh Hashmani, Mohammed Al Jarallah, Mohamed Ajaz Ghani, Badr Alzahrani, Maryam Jameel Naser, Wael Qenawi, Taher Hassan, Abdullah Alenezi, Ahmad S Hersi, Waleed Alharbi, Sultan Al Obaikan, Salman Saad Almalki, Sulafa Almukhtar Mohammed Ballool, Husam A Noor, Manar Khalid AlSuwaidi, Harvey Antony, Marwa Abd Elghany Albasiouny Alkholy, Khaled Alkhodari, Hassan Khan, Ali Alshehri, Ahmed A Ghonim, Seraj Abualnaja, Mokhtar Abdirahman Kahin, Rajesh Rajan, Khaled Almerri, Faisal Omar M Al Nasser, Ahmed Alhaydhal, Mohammed Awad Ashour, Omer A Elamin, Ahmed Jamjoom, Sary Mahmoud Wedinly, Youssef Elmahrouk, Ziad Dahdouh, Ethan M Ross, Said Al Maashani, Abdulwali Abohasan, Wael Tawfik, Mohammed Balghith, Abdelmaksoud Elganady, Ibrahim A M Abdulhabeeb, Rasha Mohammed Borini, Ayman Basardah, Abdulrahman M Alqahtani, Alaa Aldossari, Abdullah Omair Alsuayri, Mushira Khan, Amir Lotfi","doi":"10.1097/SHK.0000000000002433","DOIUrl":"10.1097/SHK.0000000000002433","url":null,"abstract":"<p><strong>Abstract: </strong>Background: There is a paucity of data regarding acute myocardial infarction (MI) complicated by cardiogenic shock (AMI-CS) in the Gulf region. This study addressed this knowledge gap by examining patients experiencing AMI-CS in the Gulf region and analyzing hospital and short-term follow-up mortality. Methods: The Gulf-Cardiogenic Shock registry included 1,513 patients with AMI-CS diagnosed between January 2020 and December 2022. Results: The incidence of AMI-CS was 4.1% (1,513/37,379). The median age was 60 years. The most common presentation was ST-elevation MI (73.83%). In-hospital mortality was 45.5%. Majority of patients were in SCAI (Society for Cardiovascular Angiography and Interventions shock classification) stage D and E (68.94%). Factors associated with hospital mortality were previous coronary artery bypass graft (odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.321-4.693), cerebrovascular accident (OR: 1.621; 95% CI: 1.032-2.547), chronic kidney disease (OR: 1.572; 95% CI: 1.158-2.136), non-ST-elevation MI (OR: 1.744; 95% CI: 1.058-2.873), cardiac arrest (OR: 5.702; 95% CI: 3.640-8.933), SCAI stage D and E (OR: 19.146; 95% CI: 9.902-37.017), prolonged QRS (OR: 10.012; 95% CI: 1.006-1.019), right ventricular dysfunction (OR: 1.679; 95% CI: 1.267-2.226), and ventricular septal rupture (OR: 6.008; 95% CI: 2.256-15.998). Forty percent had invasive hemodynamic monitoring, 90.02% underwent revascularization, and 45.80% received mechanical circulatory support (41.31% had intra-aortic balloon pump and 14.21% had extracorporeal membrane oxygenation/Impella devices). Survival at 12 months was 51.49% (95% CI: 46.44%-56.29%). Conclusions: The study highlighted the significant burden of AMI-CS in this region, with high in-hospital mortality. The study identified several key risk factors associated with increased hospital mortality. Despite the utilization of invasive hemodynamic monitoring, revascularization, and mechanical circulatory support in a substantial proportion of patients, the 12-month survival rate remained relatively low.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSDMD KNOCKOUT ALLEVIATES SEPSIS-ASSOCIATED SKELETAL MUSCLE ATROPHY BY INHIBITING IL18/AMPK SIGNALING.","authors":"Yongsheng Zhang, Tonghan Li, Yukun Liu, Chuntao Wang, Dongfang Wang, Ligang Xu, Hong Zhao, Xiangjun Bai, Zhanfei Li, Yuchang Wang","doi":"10.1097/SHK.0000000000002430","DOIUrl":"10.1097/SHK.0000000000002430","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial muscle weakness and degeneration, ultimately contributing to an adverse prognosis. Studies have shown that programmed cell death is an important factor in the progression of muscle loss in sepsis. However, the precise role and mechanism of pyroptosis in skeletal muscle atrophy are not yet fully comprehended. Therefore, we aimed to examine the role and mechanism of action of the pyroptosis effector protein GSDMD in recognized cellular and mouse models of sepsis. Methods: The levels of GSDMD and N-GSDMD in skeletal muscle were evaluated 2, 4, and 8 days after cecal ligation and puncture. Sepsis was produced in mice that lacked the Gsdmd gene (Gsdmd knockout) and in mice with the normal Gsdmd gene (wild-type) using a procedure called cecal ligation and puncture. The degree of muscular atrophy in the gastrocnemius and tibialis anterior muscles was assessed 72 h after surgery in the septic mouse model. In addition, the architecture of skeletal muscles, protein expression, and markers associated with pathways leading to muscle atrophy were examined in mice from various groups 72 h after surgery. The in vitro investigations entailed the use of siRNA to suppress Gsdmd expression in C2C12 cells, followed by stimulation of these cells with lipopolysaccharide to evaluate the impact of Gsdmd downregulation on muscle atrophy and the related signaling cascades. Results: This study has demonstrated that the GSDMD protein, known as the \"executive\" protein of pyroptosis, plays a crucial role in the advancement of skeletal muscle atrophy in septic mice. The expression of N-GSDMD in the skeletal muscle of septic mice was markedly higher compared with the control group. The Gsdmd knockout mice exhibited notable enhancements in survival, muscle strength, and body weight compared with the septic mice. Deletion of the Gsdmd gene reduced muscular wasting in the gastrocnemius and tibialis anterior muscles caused by sepsis. Studies conducted in living organisms ( in vivo ) and in laboratory conditions ( in vitro ) have shown that the absence of the Gsdmd gene decreases indicators of muscle loss associated with sepsis by blocking the IL18/AMPK signaling pathway. Conclusion: The results of this study demonstrate that the lack of Gsdmd has a beneficial effect on septic skeletal muscle atrophy by reducing the activation of IL18/AMPK and inhibiting the ubiquitin-proteasome system and autophagy pathways. Therefore, our research provides vital insights into the role of pyroptosis in sepsis-related skeletal muscle wasting, which could potentially lead to the development of therapeutic and interventional approaches for preventing septic skeletal muscle atrophy.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}