SHOCK最新文献

{"title":"INHIBITING SIRT2 ATTENUATES SEPSIS-INDUCED ACUTE KIDNEY INJURY VIA FOXO1 ACETYLATION-MEDIATED AUTOPHAGY ACTIVATION.","authors":"Binmei Yu, Lijun Weng, Jiaxin Li, Tingjie Wang, Weihuang Qiu, Yuying Li, Menglu Shi, Bo Lin, Xianzhong Lin, Zhongqing Chen, Zhenhua Zeng, Youguang Gao","doi":"10.1097/SHK.0000000000002505","DOIUrl":"10.1097/SHK.0000000000002505","url":null,"abstract":"<p><strong>Abstract: </strong>Sepsis-associated acute kidney injury (SAKI), a common complication in intensive care units (ICUs), is linked to high morbidity and mortality. Sirtuin 2 (SIRT2), an NAD + -dependent deacetylase, has been shown to have distinct effects on autophagy regulation compared to other sirtuins, but its role in SAKI remains unclear. This study explored the potential of SIRT2 as a therapeutic target for SAKI. We found that inhibition of SIRT2 with the antagonist AGK2 improved the survival of septic mice. SIRT2 inhibition reduced kidney injury, as indicated by lower levels of KIM-1, NGAL, serum creatinine, blood urea nitrogen, and proinflammatory cytokines following cecal ligation and puncture. Pretreatment with AGK2 in septic mice increased autophagosome and autolysosome formation in renal tubular epithelial cells and upregulated LC3 II expression in the renal cortex. Consistent with in vivo findings, SIRT2 gene silencing promoted autophagy in LPS-treated HK-2 cells, whereas SIRT2 overexpression inhibited it. Mechanistically, SIRT2 inhibition increased FOXO1 acetylation, inducing its nuclear-to-cytoplasmic translocation, which promoted kidney autophagy and alleviated SAKI. Our study suggests SIRT2 as a potential target for SAKI therapy.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"255-266"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACUTE KIDNEY INJURY FOLLOWING ACUTE CHOLANGITIS: A RISK MULTIPLIER FOR ADVERSE OUTCOMES AND HEALTHCARE UTILIZATION.","authors":"Lili Tang, Weiwei Wan, Jie Zhang, Hongtao Zhang, Yuhao Wang, Xiaoyue Li","doi":"10.1097/SHK.0000000000002462","DOIUrl":"10.1097/SHK.0000000000002462","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Acute kidney injury (AKI) is a common, fatal complication of acute cholangitis (AC). The link between AC and AKI is poorly understood. Aims: To delineate the incidence trends, clinical outcomes and healthcare utilization of inpatients with AKI following AC and to explore the risk factors for AKI following AC. Methods: This population-based retrospective study used the National Inpatient Sample database from 2010 to 2018 to compare the demographics, complications, in-hospital mortality and healthcare utilization between AC patients with and without AKI. Predictors of AKI and the prognostic impact of AKI on in-hospital outcomes were defined using multivariate logistic regression. Results: The overall incidence of AKI was 24.06% among AC patients. Its trend generally increased annually. AKI was associated with more complications, greater invasive therapy requirements, longer hospital stays, costlier total hospital charges, and higher in-hospital mortality. The risk factors for AKI following AC were advanced age, Black race, multiple comorbidities, large hospitals, teaching hospitals, urban hospitals, hospitals in the southern and western United States, choledocholithiasis/cholelithiasis, surgery, percutaneous transhepatic biliary drainage, deficiency anemia, congestive heart failure, coagulopathy, diabetes, hypertension, chronic liver disease, obesity, chronic kidney disease excluding end-stage renal disease, weight loss, acute pancreatitis, and severe sepsis. Female sex, private insurance, elective admission, and endoscopic retrograde cholangiopancreatography were protective factors against AKI in AC patients. Conclusion: AKI often follows AC and is strongly associated with poor prognosis and increased healthcare utilization. Healthcare professionals should make more efforts to identify patients with AC at risk of AKI and start management promptly to limit adverse outcomes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"226-232"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005149","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":"ZBTB16 DRIVES VASCULAR CALCIFICATION THROUGH ACCELERATING VSMCS OSTEOBLASTIC TRANSITION IN CHRONIC KIDNEY DISEASE VIA WNT/Β-CATENIN PATHWAY.","authors":"Yan Shen, Huaxing Huang, Lianglan Shen, Wubin Yao, Rong Wang, Meizi Kang, Jiashan Huang, Yan Xie, Hongli Yang","doi":"10.1097/SHK.0000000000002488","DOIUrl":"10.1097/SHK.0000000000002488","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic kidney disease (CKD)-related vascular calcification (VC) is a common degenerative phenomenon of the vessel wall and its pathological basis is the phenotypic transformation of vascular smooth muscle cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have been reported to be expressed in the aortic tissues in a rat model of VC. This work is conducted to reveal the functions of ZBTB16 on VC in CKD and to probe its involved reaction mechanisms. In vivo CKD rat models were established by adenine and VSMC calcification were stimulated with high phosphate (Pi) in vitro . Renal function indexes were estimated with relevant assay kits. Renal tissues were histologically examined with hematoxylin and eosin staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR and western blot were used to detect ZBTB16 expression. Western blot, immunohistochemistry, and immunofluorescence staining were used to detect osteogenic markers and smooth muscle cell markers. Western blot was used to measure the expressions of proteins implicated in Wnt/β-catenin pathway. In the blood samples of CKD patients with VC, aortic tissues of CKD rats, and Pi-treated VSMCs, ZBTB16 expression was significantly increased. ZBTB16 knockdown reduced renal dysfunction, calcium deposition and inhibited VSMCs osteoblast differentiation both in vitro and in vivo . Moreover, silencing with ZBTB16 inactivated Wingless-related integration site (Wnt)/β-catenin pathway. LiCl (Wnt/β-catenin agonist) reversed the protective effects of ZBTB16 knockdown on the calcification and osteoblastic transformation in vitro . Together, ZBTB16 silencing may downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"312-319"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507132","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":"FIBRINOGEN-LIKE PROTEIN 2 PROTECTS THE AGGRAVATION OF HYPERTRIGLYCERIDEMIA ON THE SEVERITY OF HYPERTRIGLYCERIDEMIA ACUTE PANCREATITIS BY REGULATING MACROPHAGES.","authors":"Xiuli Dong, Haibo Xu, Baiqi He, Meijuan Zhang, Wanqi Miu, Zhiming Huang, Chengshui Chen","doi":"10.1097/SHK.0000000000002503","DOIUrl":"10.1097/SHK.0000000000002503","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. Methods: Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay. Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163. Results: The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. Conclusion: FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"327-337"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627410","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":"EUGENOL RESTRAINS ANGIOTENSIN II-INDUCED DEATH, INFLAMMATION AND FERROPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS BY TARGETING STAT3/HMGB2 AXIS.","authors":"Birun Huang, Haiyan Chen, Xiulan Zhang","doi":"10.1097/SHK.0000000000002498","DOIUrl":"10.1097/SHK.0000000000002498","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Eugenol has been found to inhibit a variety of disease processes, including abdominal aortic aneurysm (AAA) formation. However, the specific role and the underlying molecular mechanism of Eugenol in AAA progression need to be further revealed. Methods: Vascular smooth muscle cells (VSMCs) were pretreated with Eugenol, followed by treated with Angiotensin II (Ang-II). VSMCs were transfected with HMGB2 siRNA or overexpression vector and treated with Ang-II to confirm the effect of HMGB2 on AAA progression. Cell proliferation and death were determined using cell counting kit 8 assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry. Inflammatory factors were examined by ELISA. Fe 2+ , glutathione, and malondialdehyde levels were tested to evaluate cell ferroptosis. The protein levels of ferroptosis-related markers, high mobility group box 2 (HMGB2), and STAT3 were measured using western blot. Human AAA tissues and normal abdominal aortic tissues were collected to detect HMGB2 mRNA expression by quantitative real-time PCR. The interaction between HMGB2 and STAT3 was confirmed by chromatin immunoprecipitation assay and dual-luciferase reporter assay. Results: Eugenol enhanced VSMCs proliferation, while restrained Ang-II-induced death, inflammation, and ferroptosis. HMGB2 was upregulated in AAA tissues and Ang-II-induced VSMCs, and Eugenol significantly decreased HMGB2 expression. HMGB2 knockdown reduced Ang-II-induced VSMCs death, inflammation, and ferroptosis, Besides, HMGB2 overexpression abolished the effect of Eugenol on Ang-II-induced VSMCs injury. Transcription factor STAT3 bound to HMGB2 promoter region to increase its expression. In addition, Eugenol decreased STAT3 expression to regulate HMGB2. Conclusion: Eugenol could slow down the development of AAA, which might be achieved by regulating STAT3/HMGB2 axis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"320-326"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507120","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":"METTL14/IGF2BP2-MEDIATED M6A MODIFICATION OF STEAP1 AGGRAVATES ACUTE LUNG INJURY INDUCED BY SEPSIS.","authors":"Junhua Lai, Shaochi Yu, Xia Li, Qiuxing Wei, Jian Qin","doi":"10.1097/SHK.0000000000002456","DOIUrl":"10.1097/SHK.0000000000002456","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Acute lung injury (ALI) is a severe complication of sepsis, characterized by inflammation, edema, and injury to alveolar cells, leading to high mortality rates. Septic ALI is a complex disease involving multiple factors and signaling pathways. STEAP family member 1 (STEAP1) has been reported to be upregulated in a sepsis-induced ALI model. However, the role of STEAP1 in the regulation of septic ALI is not yet fully understood. Methods: The study stimulated human pulmonary microvascular endothelial cells (HPMECs) using lipopolysaccharides (LPS) to establish an in vitro ALI model. The study used quantitative real-time polymerase chain reaction to measure mRNA expression, and western blotting assay or immunohistochemistry assay to analyze protein expression. Cell Counting Kit-8 assay was performed to assess cell viability. Flow cytometry was conducted to analyze cell apoptosis. Tube formation assay was used to analyze the tube formation rate of human umbilical vein endothelial cells. Enzyme-linked immunosorbent assays were used to measure the levels of interleukin 1beta and tumor necrosis factor alpha. The levels of Fe 2+ and reactive oxygen species were determined using colorimetric and fluorometric assays, respectively. The glutathione level was also determined using a colorimetric assay. m6A RNA immunoprecipitation assay, dual-luciferase reporter assay, and RNA immunoprecipitation assay were performed to identify the association of STEAP1 with methyltransferase 14, N6-adenosine-methyltransferase noncatalytic subunit (METTL14) and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2). The transcript half-life of STEAP1 was analyzed by actinomycin D assay. Finally, a rat model of polymicrobial sepsis was established to analyze the effects of STEAP1 knockdown on lung injury in vivo . Results: We found that the mRNA expression levels of STEAP1 and METTL14 were upregulated in the blood of ALI patients induced by sepsis compared to healthy volunteers. LPS treatment increased the protein levels of STEAP1 and METTL14 in HPMECs. STEAP1 depletion attenuated LPS-induced promoting effects on HPMECs' apoptosis, inflammatory response, and ferroptosis, as well as LPS-induced inhibitory effect on tube formation. We also found that METTL14 and IGF2BP2 stabilized STEAP1 mRNA expression through the m6A methylation modification process. Moreover, METTL14 silencing attenuated LPS-induced effects by decreasing STEAP1 expression in HPMECs, and STEAP1 silencing ameliorated cecal ligation and puncture-induced lung injury of mice. Conclusion: METTL14/IGF2BP2-mediated m6A modification of STEAP1 aggravated ALI induced by sepsis. These findings suggest potential therapeutic targets for the treatment of this disease.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"217-225"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081393","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":"COMPREHENSIVE CHARACTERIZATION OF CYTOKINES IN PATIENTS UNDER EXTRACORPOREAL MEMBRANE OXYGENATION: EVIDENCE FROM INTEGRATED BULK AND SINGLE-CELL RNA SEQUENCING DATA USING MULTIPLE MACHINE LEARNING APPROACHES.","authors":"Zhen Chen, Jianhai Lu, Genglong Liu, Changzhi Liu, Shumin Wu, Lina Xian, Xingliang Zhou, Liuer Zuo, Yongpeng Su","doi":"10.1097/SHK.0000000000002425","DOIUrl":"10.1097/SHK.0000000000002425","url":null,"abstract":"<p><strong>Abstract: </strong>Background : Extracorporeal membrane oxygenation (ECMO) is an effective technique for providing short-term mechanical support to the heart, lungs, or both. During ECMO treatment, the inflammatory response, particularly involving cytokines, plays a crucial role in pathophysiology. However, the potential effects of cytokines on patients receiving ECMO are not comprehensively understood. Methods : We acquired three ECMO support datasets, namely two bulk and one single-cell RNA sequencing (RNA-seq), from the Gene Expression Omnibus (GEO) combined with hospital cohorts to investigate the expression pattern and potential biological processes of cytokine-related genes (CRGs) in patients under ECMO. Subsequently, machine learning approaches, including support vector machine (SVM), random forest (RF), modified Lasso penalized regression, extreme gradient boosting (XGBoost), and artificial neural network (ANN), were applied to identify hub CRGs, thus developing a prediction model called CRG classifier. The predictive and prognostic performance of the model was comprehensively evaluated in GEO and hospital cohorts. Finally, we mechanistically analyzed the relationship between hub cytokines, immune cells, and pivotal molecular pathways. Results : Analyzing bulk and single-cell RNA-seq data revealed that most CRGs were significantly differentially expressed; the enrichment scores of cytokine and cytokine-cytokine receptor (CCR) interaction were significantly higher during ECMO. Based on multiple machine learning algorithms, nine key CRGs (CCL2, CCL4, IFNG, IL1R2, IL20RB, IL31RA, IL4, IL7, and IL7R) were used to develop the CRG classifier. The CRG classifier exhibited excellent prognostic values (AUC > 0.85), serving as an independent risk factor. It performed better in predicting mortality and yielded a larger net benefit than other clinical features in GEO and hospital cohorts. Additionally, IL1R2, CCL4, and IL7R were predominantly expressed in monocytes, NK cells, and T cells, respectively. Their expression was significantly positively correlated with the relative abundance of corresponding immune cells. Gene set variation analysis (GSVA) revealed that para-inflammation, complement and coagulation cascades, and IL6/JAK/STAT3 signaling were significantly enriched in the subgroup that died after receiving ECMO. Spearman correlation analyses and Mantel tests revealed that the expression of hub cytokines (IL1R2, CCL4, and IL7R) and pivotal molecular pathways scores (complement and coagulation cascades, IL6/JAK/STAT3 signaling, and para-inflammation) were closely related. Conclusion : A predictive model (CRG classifier) comprising nine CRGs based on multiple machine learning algorithms was constructed, potentially assisting clinicians in guiding individualized ECMO treatment. Additionally, elucidating the underlying mechanistic pathways of cytokines during ECMO will provide new insights into its treatment.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"267-281"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TARGETING S100A9-TLR2 AXIS CONTROLS MACROPHAGE NLRP3 INFLAMMASOME ACTIVATION IN FATTY LIVER ISCHEMIA REPERFUSION INJURY.","authors":"Mingwei Sheng, Weihua Liu, Yingli Cao, Shixuan Wang, Yuanbang Lin, Wenli Yu","doi":"10.1097/SHK.0000000000002470","DOIUrl":"10.1097/SHK.0000000000002470","url":null,"abstract":"<p><strong>Abstract: </strong>Liver ischemia reperfusion (IR) injury significantly impacts clinical outcomes by increasing the risk of hepatic dysfunction after liver surgery. Fatty livers are more susceptible to IR stress. Recent studies have demonstrated that S100A9 plays a crucial role in both IR injury and the progression of liver steatosis. Nevertheless, the precise mechanisms underlying these effects remain unclear. In our study, transcriptome analysis of fatty livers subjected to IR insult in mice identified S100A9 as an important mediator. Employing loss-of-function approaches, we investigated the immune regulatory function of S100A9 and its downstream signaling in fatty liver IR injury. As expected, S100A9 emerged as one of the most significantly upregulated genes during the reperfusion stage in fatty livers. Genetic knockdown of S100A9 markedly ameliorated liver pathological damage, evidenced by reduced macrophage/neutrophil infiltration as well as the decreased expression of proinflammatory factors. Transcriptome/functional studies revealed that S100A9 triggered liver inflammatory response via regulating toll-like receptor 2 (TLR2)/activating transcription factor 4 (ATF4) signaling. Additionally, TLR2 expression was notably increased in macrophages from ischemic fatty livers. In vitro , recombinant S100A9-stimulated macrophages exhibited the elevated production of proinflammatory factors and TLR2/ATF4 pathway activation. Intriguingly, S100A9 facilitated ATF4 nuclear translocation and enhanced NEK7/NLRP3 inflammasome activation in macrophages. In conclusion, our study identified S100A9 as a key regulator responsible for macrophage NLRP3 inflammasome activation and subsequent inflammatory injury in fatty liver IR process. Targeting TLR2/ATF4 signaling may offer a novel therapeutic strategy for mitigating S100A9-mediated liver injury.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"292-298"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROLE OF CASPASE-1/CASPASE-11-HMGB1-RAGE/TLR4 SIGNALING IN THE EXACERBATION OF EXTRAPULMONARY SEPSIS-INDUCED LUNG INJURY BY MECHANICAL VENTILATION.","authors":"Xibing Ding, Shuqing Jin, Weitian Tian, Yizhe Zhang, Li Xu, Tong Zhang, Zhixia Chen, Fangfang Niu, Quan Li","doi":"10.1097/SHK.0000000000002471","DOIUrl":"10.1097/SHK.0000000000002471","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;Background: Mechanical ventilation (MV) is a clinically important measure for respiratory support in critically ill patients. Although moderate tidal volume MV does not cause lung injury, it can further exacerbate lung injury in a pathological state such as sepsis. This pathological process is known as the \"two-hit\" theory, whereby an initial lung injury (e.g., infection, trauma, or sepsis) triggers an inflammatory response that activates immune cells, presenting the lung tissue in a fragile state and rendering it more susceptible to subsequent injury. The second hit occurs when MV is applied to lung tissue in a fragile state, and it is noteworthy that this MV is harmless to healthy lung tissue, further aggravating preexisting lung injury through unknown mechanisms. This interaction between initial injury and subsequent MV develops a malignant cycle significantly exacerbating lung injury and severely hampering patient prognosis. The two-hit theory is critical to understanding the complicated mechanisms of ventilator-associated lung injury and facilitates the subsequent development of targeted therapeutic strategies. Methods and Results: The cecum ligation and perforation mice model was used to mimic clinical sepsis patients. After 12 h, the mice were mechanically ventilated for 2 to 6 h. MV by itself did not lead to HMGB1 release, but significantly strengthened HMGB1 in plasma and cytoplasm of lung tissue in septic mice. Plasma and lung tissue activation of cytokines and chemokines, mitogen-activated protein kinase signaling pathway, neutrophil recruitment, and acute lung injury were progressively decreased in LysM HMGB1 -/- (Hmgb1 deletion in myeloid cells) and iHMGB1 -/- mice (inducible HMGB1 -/- mouse strain where the Hmgb1 gene was globally deleted after tamoxifen treatment). Compared with C57BL/6 mice, although EC-HMGB1 -/- (Hmgb1 deletion in endothelial cells) mice did not have lower levels of inflammation, neutrophil recruitment and lung injury were reduced. Compared with LysM HMGB1 -/- mice, EC-HMGB1 -/- mice had higher levels of inflammation but significantly lower neutrophil recruitment and lung injury. Overall, iHMGB1 -/- mice had the lowest levels of all the above indicators. The level of inflammation, neutrophil recruitment, and the degree of lung injury were decreased in RAGE -/- mice, and even the above indices were further decreased in TLR4/RAGE -/- mice. Levels of inflammation and neutrophil recruitment were decreased in caspase-11 -/- and caspase-1/11 -/- mice, but there was no statistical difference between these two gene knockout mice. Conclusions: These data show for the first time that the caspase-1/caspase-11-HMGB1-TLR4/RAGE signaling pathway plays a key role in mice model of sepsis-induced lung injury exacerbated by MV. Different species of HMGB1 knockout mice have different lung-protective mechanisms in the two-hit model, and location is the key to function. Specifically, LysM HMGB1 -/- mice ","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"299-311"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126600","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":"FLUID OVERLOAD MODIFIES HEMODYNAMIC IMPACT OF CONTINUOUS RENAL REPLACEMENT THERAPY: EVIDENCE OF A COVERT CARDIORENAL SYNDROME?","authors":"Sameer Thadani, Anna Lang, Christin Silos, Jack Price, Ben Gelbart, Katri Typpo, Christopher Horvat, Dana Y Fuhrman, Tara Neumayr, Ayse Akcan Arikan","doi":"10.1097/SHK.0000000000002483","DOIUrl":"10.1097/SHK.0000000000002483","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Fluid overload (FO) in critically ill children correlates with higher morbidity and mortality rates. Continuous renal replacement therapy (CRRT) is commonly employed to manage FO. In adults, both FO and CRRT adversely affect myocardial function. It remains unclear if children experience similar cardiovascular effects. Methods: Observational single-center study on children (<18 years) receiving CRRT at Texas Children's Hospital from 11/2019 to 3/2021. Excluded were those with end-stage renal disease, pacemakers, extracorporeal membrane oxygenation, ventricular assist devices, apheresis, or without an arterial line. Electrocardiometry (ICON Osypka Medical GmbH, Berlin, Germany) which is noninvasive and utilizes bioimpedance, was applied to obtain hemodynamic data over the first 48 h of CRRT. Our aim was to identify how FO >15% affects hemodynamics in children receiving CRRT. Results: Seventeen children, median age 43 months (interquartile range [IQR] 12-124), were included. The median FO at CRRT initiation was 14.4% (2.4%-25.6%), with 9 (53%) patients having FO >15%. Differences were noted in systemic vascular resistance index (1,277 [IQR 1088-1,666] vs. 1,030 [IQR 868-1,181] dynes/s/cm 5 /m 2 , P < 0.01), and cardiac index (3.90 [IQR 3.23-4.75] vs. 5.68 [IQR 4.65-6.32] L/min/m 2 , P < 0.01), with no differences in heart rate or mean arterial pressure between children with and without FO. Conclusion: FO affects the hemodynamic profile of children on CRRT, with those having FO >15% showing higher systemic vascular resistance index and lower cardiac index, despite heart rate and mean arterial pressure remaining unchanged. Our study illustrates the feasibility and utility of electrocardiometry in these patients, suggesting future research employ this technology to further explore the hemodynamic effects of dialysis in children.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"233-239"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507121","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}