SHOCK最新文献

{"title":"ASSESSMENT OF EARLY INDICATORS FOR SEPSIS DEVELOPMENT IN MULTIPLE TRAUMA PATIENTS-THE SEPSIS AS TRAUMA OUTCOME PREDICTION (STOP) SCORE.","authors":"Nils Becker, Jasmin Maria Bülow, Niklas Franz, Ingo Marzi, Florian Gebhard, Akiko Eguchi, Helen Rinderknecht, Borna Relja","doi":"10.1097/SHK.0000000000002626","DOIUrl":"10.1097/SHK.0000000000002626","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Infections are common complications in critical care, particularly in patients with severe multiple trauma, who are at elevated risk due to trauma-induced immunological changes. The heterogeneity of trauma patients complicates their initial assessment, yet timely recognition of patients at risk is crucial for guiding therapy and preventive measures. This study evaluated risk factors for sepsis and pneumonia in multiple trauma patients, incorporating a novel parameter: cell-derived extracellular particles (EPs) in plasma. Methods: Severely injured multiple trauma patients aged 18-80 years with an Injury Severity Score (ISS) ≥16 were included. Patient- and injury-related parameters were assessed at the injury site, admission and during clinical course. EP counts in plasma were measured at admission using intravesicular staining. Key variables from the first 24 h were analyzed to develop an early risk assessment score. Results: Among 124 patients, 16 developed pneumonia, and 29 developed sepsis. Pneumonia was associated with significantly lower Glasgow Coma Scale scores, higher intubation rates at the injury site and elevated Sequential Organ Failure Assessment scores at admission. Sepsis correlated with higher ISS, increased 24-h transfusion rates, lower leukocyte counts on day 1, and decreased levels of small EPs in plasma at admission. These variables formed the weighted Sepsis as Trauma Outcome Prediction (STOP) score. A STOP score >3 had a positive predictive value of 59.4% within 24 h upon admission to the emergency department for subsequent sepsis development. Conclusion: The risk of pneumonia in severely injured trauma patients was linked to impaired consciousness and preexisting organ-dysfunctions at admission. High-risk sepsis patients could be identified on day 1 following trauma using the STOP score, which incorporates ISS, 24-h transfusion rates, leukocyte counts at day 1, and small EP rates at admission. This novel scoring system could facilitate targeted therapeutic and preventive strategies for distinguishing high-risk populations.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"187-197"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080064","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":"IDENTIFYING A SEPSIS SUBPHENOTYPE CHARACTERIZED BY DYSREGULATED LIPOPROTEIN METABOLISM USING A SIMPLIFIED CLINICAL DATA ALGORITHM.","authors":"Guillaume Labilloy, Sébastien Tanaka, Lauren Page Black, Beulah Augustin, Charlotte Hopson, Joanne Bethencourt, Dongyuan Wu, Dawoud Sulaiman, Andrew Bertrand, Reinaldo Salomão, Kiley Graim, Susmita Datta, Srinivasa Reddy, Faheem W Guirgis, Daniel A Hofmaenner","doi":"10.1097/SHK.0000000000002605","DOIUrl":"10.1097/SHK.0000000000002605","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Cholesterol metabolism is dysregulated in sepsis contributing to patient heterogeneity. Subphenotypes displaying lower lipoprotein levels and higher mortality (previously subphenotyped hypolipoprotein phenotype [HYPO]) or higher lipoprotein levels and lower mortality (previously subphenotyped normolipoprotein phenotype [NORMO]) were described. We developed a simplified clinical algorithm for bedside subphenotype recognition. Methods: We analyzed data from four prospective studies (internal dataset), focusing on HYPO and NORMO subphenotypes. A 1,000-tree random forest classifier and logistic regression models were built, using clinical features to predict subphenotypes. Performance was evaluated by comparing predictions to actual subphenotypes derived from a machine learning model. The model was applied to an external dataset of 281 patients from three French studies. Results: The internal cohort consisted of 386 patients (median age, 63 years; 46% female). Four clinical features (hepatic SOFA, cardiovascular SOFA, low [low-density lipoprotein cholesterol {LDL-C}] and high-density lipoprotein cholesterol [high-density lipoprotein cholesterol {HDL-C}]) predicted HYPO versus NORMO subphenotypes with an area under the receiver operating characteristic curve of 0.86, a sensitivity of 0.771, and a specificity of 0.779. In the internal dataset, 28-day mortality for HYPO versus NORMO patients was 26% versus 15%, and in the external cohort, 30% versus 10%. HYPO internal versus external dataset LDL-C levels were similar ( P = 0.99), but HDL-C ( P = 0.02) levels were different. Median NORMO internal versus external dataset LDL-C ( P = 0.99) and HDL-C ( P = 0.12) levels were similar. HYPO patients had lower LDL-C, HDL-C and total cholesterol than NORMO patients in both internal and external datasets. Conclusions: Our simplified clinical data algorithm may allow for bedside recognition of septic patients displaying lipid dysregulation subphenotypes. External validation is needed to verify these results.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"218-225"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983184","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":"PATIENT TESTIMONIALS-A NEW INTERACTIVE FORMAT FOR DIALOG BETWEEN SHOCK MEMBERS AND PATIENTS.","authors":"Antoine Herpain, Andreas Markl-Le Levé, Paul Foell, Dennis Kredler, Dietmar Fries, Ingrid Haller, Herbert Schöchl, Daniel Remick, Marcin Osuchowski","doi":"10.1097/SHK.0000000000002607","DOIUrl":"10.1097/SHK.0000000000002607","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"283-287"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051340","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":"EXOSOMES FROM WTAP-DEPLETED MESENCHYMAL STEM CELLS MITIGATE OGD/R-TRIGGERED CELLULAR INJURY IN SK-N-SH CELLS THROUGH M6A-DEPENDENT EPIGENETIC SILENCING OF RPL9.","authors":"Jianhua Wang, Xiaoxu Wang, Liangliang Feng, Xiaojing Li","doi":"10.1097/SHK.0000000000002612","DOIUrl":"10.1097/SHK.0000000000002612","url":null,"abstract":"<p><strong>Abstract: </strong>Background : Exosomes from mesenchymal stem cells (MSCs Exo) have emerged as a promising cell-free therapeutic strategy for human diseases, including ischemic stroke (IS). Here, we investigated the mechanisms underlying the therapeutic potential of MSCs Exo. Methods : SK-N-SH cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). Exosomes were isolated from untransfected (MSCs Exo) or shRNA-Wilms' tumor 1-associated protein (WTAP)-transfected MSCs (MSCs Exo-shWTAP) and used to incubate OGD/R-exposed SK-N-SH cells. The influence on cellular damage was evaluated by detecting cell viability, apoptosis, the expression of oxidative stress markers (ROS, MDA, and SOD), and the production of TNF-α, IL-6, and IL-1β cytokines. The regulation of WTAP in ribosomal protein L9 (RPL9) mRNA was assessed by mRNA stability analysis and methylated RNA immunoprecipitation (MeRIP) assay. Results : RPL9 was upregulated in IS serum and OGD/R-exposed SK-N-SH cells. RPL9 depletion attenuated OGD/R-evoked apoptosis, oxidative stress, and proinflammatory cytokine production (TNF-α, IL-6, and IL-1β) in SK-N-SH cells. Mechanistically, WTAP regulated the mRNA stability and expression of RPL9 via an m6A-dependent way. MSCs Exo reduced RPL9 expression in OGD/R-exposed SK-N-SH cells, and MSCs Exo-shWTAP exerted a stronger reduction effect on RPL9 expression. MSCs Exo-shWTAP had stronger alleviative effects on OGD/R-triggered apoptosis, oxidative stress, and inflammation in SK-N-SH cells compared with MSCs Exo. Moreover, increased RPL9 expression abolished the effects of MSCs Exo-shWTAP. Conclusion : Our findings indicate that WTAP depletion can enhance the alleviative effects of MSCs Exo on OGD/R-triggered cellular damage in SK-N-SH cells by downregulating RPL9. WTAP-depleted MSC-derived exosomes represent a promising therapeutic strategy for IS.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"245-253"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981563","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":"SVF MEDIATES IMMUNOMETABOLIC ALTERATIONS IN BURN-INDUCED HYPERMETABOLIC ADIPOSE TISSUE VIA MITOCHONDRIAL TRANSFER.","authors":"Lauar de Brito Monteiro, Shayahati Bieerkehazhi, Ayesha Aijaz, Carly M Knuth, Graham Rix, Ju Hee Lee, Hoon-Ki Sung, Mahmoud Farahat, Marc G Jeschke","doi":"10.1097/SHK.0000000000002608","DOIUrl":"10.1097/SHK.0000000000002608","url":null,"abstract":"<p><strong>Abstract: </strong>Adipose tissue (AT) browning promotes systemic alterations in energy expenditure as a response to catecholamine-induced hypermetabolism in severe burn trauma. The AT is composed of the stromal vascular fraction (SVF) and adipocytes. SVF contains a vast population of immune cells that maintain AT homeostasis. Despite evidence that local immune cell accumulation contributes to hypermetabolism, the underlying mechanism of persistent browning response is not known. Thus, we hypothesized that a specific cellular communication between adipocytes and SVF can mediate the severe metabolic alterations associated with hypermetabolism. Therefore, we used a murine burn model to show that postburn hypermetabolism compromises mitochondria respiration and alters the immune cell profile of the AT-SVF. We found that adipocyte-derived signals promote metabolic reprogramming and inflammatory responses by SVF after burns in both mice and humans. Interestingly, adipocytes transfer mitochondria to cells in the SVF including different immune cell (macrophages, T cells, B cells) uptake mitochondria from adipocytes. Such data were replicated in human samples as well. These results indicate that adipocytes play a major role in immunometabolic reprogramming following severe burns through crosstalk with the adipose immune cell population. Therefore, targeting immune cell metabolism restoration is a potential strategy to mitigate the detrimental effects of postburn hypermetabolism on systemic energy balance.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"226-235"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015869","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":"A MULTIPLE DAMAGE-ASSOCIATED MOLECULAR PATTERN-SCAVENGING COMPOUND OP18 ATTENUATES HEPATIC ISCHEMIA/REPERFUSION INJURY.","authors":"Kouhei Ishikawa, Atsushi Murao, Takuya Murao, Monowar Aziz, Ping Wang","doi":"10.1097/SHK.0000000000002624","DOIUrl":"10.1097/SHK.0000000000002624","url":null,"abstract":"<p><strong>Abstract: </strong>Introduction: Hepatic ischemia-reperfusion (I/R) can cause further liver injury through a cascade of complex cellular events. Damage-associated molecular patterns (DAMPs) released from stressed or damaged cells in the liver contribute to this pathology, leading to hyperinflammation, organ tissue damage, and high mortality. We have developed a novel compound, Opsonin Peptide 18, which exhibits strong binding affinity for multiple DAMPs, including extracellular cold-inducible RNA-binding protein, high-mobility group box 1, and histone H3, thereby enhancing the clearance of those DAMPs by phagocytic cells. In this study, we hypothesized that Opsonin Peptide 18 mitigates hepatic I/R injury by suppressing DAMPs-induced inflammation. Methods: Adult C57BL/6 mice were subjected to 70% hepatic ischemia for 60 min immediately followed by intraperitoneal ( i.p. ) administration of either formic acid in PBS (vehicle) or 0.2 mg/kg body weight OP18 (treatment). After 24 h, blood and liver tissues were collected for the measurement of systemic inflammatory markers, including cytokines, liver enzymes, chemokines, and myeloperoxidase activity. Liver tissue damage and cell death were evaluated histologically. The survival rate was monitored for 10 days post hepatic I/R. Results: In the hepatic I/R mouse model, OP18 treatment significantly decreased the elevated plasma levels of IL-6, TNFα, IL-1β, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase compared to vehicle group. Moreover, OP18 markedly decreased liver tissue mRNA levels of IL-6, TNFα, IL-1β, macrophage inflammatory protein-2, keratinocyte chemoattractant, and Z-DNA-binding protein 1, as well as myeloperoxidase activity. Histological analysis revealed that OP18 treatment significantly attenuated liver tissue damage and cell death in hepatic I/R mice. Furthermore, the administration of OP18 significantly improved the survival after hepatic I/R injury. Conclusions: OP18 mitigates inflammation and tissue damage following hepatic I/R injury and improves survival. Thus, OP18 has potential as a promising therapeutic strategy for hepatic I/R injury.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"265-271"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042160","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":"SEX AND RACE/ETHNICITY DIFFERENCES ON IN-HOSPITAL OUTCOMES IN OCTOGENARIANS WITH CARDIOGENIC SHOCK.","authors":"Carlos Diaz-Arocutipa, Rafael Salguero-Bodes, Elena Puerto, Roberto Martín-Asenjo, Lourdes Vicent","doi":"10.1097/SHK.0000000000002620","DOIUrl":"10.1097/SHK.0000000000002620","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Cardiogenic shock carries a high mortality rate, particularly among octogenarians. Our aim was to evaluate the clinical characteristics, management, and in-hospital outcomes among octogenarians, with a particular focus on sex and race/ethnicity differences. Methods: Retrospective cohort study using the National Inpatient Sample (NIS) including patients ≥80 years old hospitalized with cardiogenic shock from 2016 to 2019. Patients were stratified by sex and race/ethnicity (White, Black, Hispanic). Logistic regression was used to estimate odds ratios (OR) with their 95% confidence interval (CI). Results: Among 110,610 patients, in-hospital mortality was 44.6%, with significant differences by sex and race/ethnicity ( P = 0.013). Mortality was highest in White females (46.0%) and Black females (46.1%), while Hispanic males had the lowest rate (43.1%). After adjustment, White females had a higher mortality risk compared to White males (OR 1.07, 95% CI 1.01-1.14, P = 0.022). Black and Hispanic patients had lower utilization of intra-aortic balloon pumps and percutaneous ventricular assist devices ( P < 0.001), but experienced higher rates of major bleeding (Black males 8.0%, Black females 7.2%) and renal replacement therapy (Black males 8.4%, Black females 8.6%) ( P < 0.001). Hispanic males had the highest total hospital charges (median $133,115), while Black females had the lowest (median $77,006) ( P < 0.001). Conclusions: Significant sex and race/ethnicity differences exist in outcomes among octogenarians with cardiogenic shock. White females had the highest mortality, while Black and Hispanic patients had lower utilization of advanced therapies but higher complication rates. Addressing these differences is essential to improve equity in cardiovascular care.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"169-175"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010439","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":"PREDICTIVE VALUE OF H3K18 LACTYLATION FOR EARLY DETECTION AND PROGNOSIS OF SEPSIS-RELATED ACUTE RESPIRATORY DISTRESS SYNDROME: A PROSPECTIVE OBSERVATIONAL CLINICAL STUDY.","authors":"Xing Li, Yang Shang, Jialong Zhang, Genhua Mu, Yuxuan Duan, Zhongqian Lu, Yijun Deng","doi":"10.1097/SHK.0000000000002601","DOIUrl":"10.1097/SHK.0000000000002601","url":null,"abstract":"<p><strong>Abstract: </strong>Background: This study aimed to investigate the predictive value of histone H3 lysine 18 lactylation (H3K18la) for the early identification and prognosis of sepsis-related acute respiratory distress syndrome (ARDS). Methods: This prospective observational study included patients with sepsis admitted to the intensive care unit (ICU) between March 2023 and September 2024. The patients were divided into two groups: the sepsis with ARDS group and the sepsis without ARDS group. Clinical data were collected within 24 h of ICU admission. Bronchoalveolar lavage fluid (BALF) samples were obtained on day 1 for all participants, and a second BALF sample was collected on day 3 from patients requiring continued mechanical ventilation. Results: In total, 91 sepsis patients were enrolled in the study: 36 with ARDS and 55 without ARDS. H3K18la levels in BALF were significantly higher in the sepsis-related ARDS group than in the non-ARDS group and the control group ( P < 0.05). Elevated H3K18la levels were positively correlated with inflammatory markers (lactate, IL-6, and TNF-α), Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment scores ( P < 0.01). Logistic regression analysis revealed that H3K18la was an independent predictor of ARDS development ( P < 0.05), and ROC curve analysis revealed that H3K18la had high diagnostic accuracy (AUC = 0.804). Combining H3K18la with the Sequential Organ Failure Assessment score further improved diagnostic performance (AUC = 0.830, sensitivity = 88.9%, specificity = 67.3%). Furthermore, H3K18la levels significantly increased on day 3 in the mortality group. Conclusion: H3K18la is a promising biomarker for the early identification and prognostic prediction of sepsis-related ARDS.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"154-160"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976715","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":"CO-CHAPERONE P23 INHIBITS FERROPTOSIS IN SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY BY REGULATING GPX4 STABILITY.","authors":"Minjie Luo, Qing Xu, Ying Sun, Nina He, Zhongchi Wen, Ziqin Wang, Jie Zhao, Ying Liu","doi":"10.1097/SHK.0000000000002623","DOIUrl":"10.1097/SHK.0000000000002623","url":null,"abstract":"<p><strong>Abstract: </strong>Ferroptosis, an iron-dependent form of regulated cell death, has been implicated in severe kidney diseases, particularly those characterized by the depletion of GPX4. Despite its clinical significance, the molecular mechanisms driving GPX4 reduction in SA-AKI remain poorly understood. In this study, we uncover a novel regulatory axis involving the RNA-binding protein P23 and GPX4 mRNA stability in SA-AKI pathogenesis. Using integrated in vivo and in vitro models, we demonstrate that P23 expression is significantly upregulated during SA-AKI and functions as a critical suppressor of ferroptosis. Mechanistically, pharmacological inhibition of P23 with celastrol exacerbated renal dysfunction and amplified ferroptotic damage, as evidenced by elevated lipid peroxidation, iron overload, and GPX4 downregulation. Conversely, P23 overexpression robustly attenuated ferroptosis by stabilizing GPX4 mRNA, thereby preserving GPX4 protein levels and redox homeostasis. Crucially, RIP and Co-immunoprecipitation assays revealed that P23 directly binds to GPX4 mRNA and protein, forming a protective complex that impedes mRNA degradation and ferroptotic cascades. These findings establish P23 as a multifunctional regulator of ferroptosis and highlight its RNA-binding activity as a therapeutically targetable mechanism for mitigating SA-AKI. Our work provides a foundation for developing P23-centric interventions to combat ferroptosis-driven kidney injury in sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"254-264"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996729","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":"TEAD1 KNOCKDOWN IMPEDES THE INFLAMMATION AND FERROPTOSIS BY MEDIATING MMP3 IN CEREBRAL ISCHEMIA REPERFUSION.","authors":"Junjie Lu, Jing Su, Liang Zhu, Meng Xu, Li Zhao","doi":"10.1097/SHK.0000000000002589","DOIUrl":"10.1097/SHK.0000000000002589","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Cerebral ischemia-reperfusion (IR) injury is a frequent complication of ischemic stroke with the adverse impact on the clinical prognosis. This study focused on the molecular mechanism associated with TEA domain transcription factor 1 (TEAD1) and matrix metalloproteinase 3 (MMP3) in cerebral IR. Methods:In vitro , IR model was established using oxygen-glucose deprivation/reoxygenation (OGD/R) in human brain microvascular endothelial cells (HBMVECs). TEAD1 and MMP3 mRNA and protein examination were performed by RT-qPCR and western blot. Cell viability and apoptosis were measured using cell counting kit-8 assay and flow cytometry. Enzyme-linked immunosorbent assay was conducted for detection of inflammatory cytokines. Ferroptosis was evaluated via kits. TEAD1 and MMP3 interaction was proved by RNA immunoprecipitation assay. In vivo , IR was induced in rats by middle cerebral artery occlusion-reperfusion (MCAO/R) model. Brain injury in rats was assessed by tetrazolium chloride staining, Evans blue extravasation, neurological function score, and cerebral water content detection. Results: OGD/R-induced the prominent upregulation of MMP3 in HBMVECs. After knockdown of MMP3, apoptosis, inflammation and ferroptosis were all mitigated in OGD/R-treated HBMVECs. TEAD1 could enhance MMP3 expression by targeting the promoter. TEAD1 silence impeded OGD/R-mediated inflammation and ferroptosis via reducing MMP3. In MCAO/R model, TEAD1 inhibition protected brain tissues of rats against cerebral IR injury by affecting MMP3. Conclusion: The above evidence elucidated that TEAD1 facilitated cerebra inflammation and ferroptosis in vitro and in vivo IR models through targeting MMP3, suggesting the involvement of TEAD1/MMP3 axis in cerebral IR injury.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"205-212"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731413","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}