SHOCKPub Date : 2024-10-18DOI: 10.1097/SHK.0000000000002499
Yingfeng Gong, Na Wei, Peipei Shi, Gang Zhu
{"title":"CircTMCO3 alleviates sepsis-induced acute kidney injury via regulating miR-218-5p/ZEB2 axis.","authors":"Yingfeng Gong, Na Wei, Peipei Shi, Gang Zhu","doi":"10.1097/SHK.0000000000002499","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002499","url":null,"abstract":"<p><strong>Background: </strong>Growing evidence has found the critical role of circular RNAs (circRNAs) in sepsis-induced acute kidney injury (S-AKI). CircTMCO3 has been found to be involved in tumor microenvironment changes of ovarian cancer. This study aimed to explore whether circTMCO3 functions in S-AKI, and if so, to elucidate the molecular mechanism.</p><p><strong>Methods: </strong>CircTMCO3 expression was analyzed in lipopolysaccharide (LPS)-induced HK-2 cells and in the kidney tissues of mice treated with cecal ligation and puncture (CLP), respectively. Furthermore, the effects of circTMCO3 on S-AKI and the related mechanisms were evaluated in both models through gain- and/or loss-of-function strategies.</p><p><strong>Results: </strong>CircTMCO3 expression was suppressed in both S-AKI models. Upregulation of circTMCO3 mitigated LPS-induced apoptosis, oxidative stress and inflammation in HK-2 cells. In contrast, circTMCO3 downregulation exacerbated LPS-induced injuries in HK-2 cells. Intravenous injection of circTMCO3 lentivirus to increase circTMCO3 expression improved renal function and attenuated kidney injury in S-AKI mice, as evidenced by the decrease in serum creatinine and blood urea nitrogen concentrations, amelioration of tubular pathological injury, reduction of renal cell apoptosis, and mitigation of oxidative stress and proinflammatory cytokines (TNF-α, IL-1β, and IL-6). Moreover, circTMCO3 directly targeted miR-218-5p, and the mimic of which abolished the protective effect of circTMCO3 in cell models. ZEB2 was identified to be a target of miR-218-5p; its downregulation not only reversed the impacts of miR-218-5p inhibitor on S-AKI, but also mitigated the effects mediated by circTMCO3 upregulation in vitro.</p><p><strong>Conclusions: </strong>CircTMCO3 protects against S-AKI by regulating miR-218-5p/ZEB2 axis, thereby mediating anti-apoptotic, antioxidant and anti-inflammatory activities. This indicates that increasing circTMCO3 expression might be a future therapeutic method for S-AKI.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507116","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}
SHOCKPub Date : 2024-10-18DOI: 10.1097/SHK.0000000000002476
Meagan Scott Kingren, Jaycelyn Starr Hall, Taylor Joseph Ross T, Mary Claire Barre, Abigail Barlow, Martin Morales, Lillie Danielle Treas L, Robert Todd Maxson, Esther Teo, Craig Porter
{"title":"HOUSING TEMPERATURE ALTERS BURN INDUCED HYPERMETABOLISM IN MICE.","authors":"Meagan Scott Kingren, Jaycelyn Starr Hall, Taylor Joseph Ross T, Mary Claire Barre, Abigail Barlow, Martin Morales, Lillie Danielle Treas L, Robert Todd Maxson, Esther Teo, Craig Porter","doi":"10.1097/SHK.0000000000002476","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002476","url":null,"abstract":"<p><strong>Abstract: </strong>Mice used in biomedical research are typically housed at ambient temperatures (22-24 °C) below thermoneutrality (26-31 °C). This chronic cold stress triggers a hypermetabolic response that may limit the utility of mice in modeling hypermetabolism in response to burns. To evaluate the effect of housing temperature on burn-induced hypermetabolism, mice were randomly assigned to receive sham, small, or large scald burns. Mice recovered for 21 days in metabolic phenotyping cages at 24 °C or 30 °C. Regardless of sex or sham/burn treatment, mice housed at 24 °C had greater total energy expenditure (TEE, P < 0.001), which was largely attributable to greater basal energy expenditure (BEE) when compared to mice housed at 30 °C (P < 0.001). Thermoneutral housing (30 °C) altered adipose tissue mass in a sex-dependent manner. Compared to sham and small burn groups, large burns resulted in greater water vapor loss, regardless of housing temperature (P < 0.01). Compared to sham, large burns resulted in greater BEE and TEE in mice housed at 24 °C, however, this hypermetabolic response to large burns was blunted in female mice housed at 30 °C, and absent in male mice housed at 30 °C. Locomotion was significantly reduced in mice with large burns compared to sham and small burn groups, irrespective of sex or housing temperature (P < 0.05). Housing at 30 °C revealed sexual dimorphism in terms of the impact of burns on body mass and composition, where males with large burns displayed marked cachexia, whereas females did not. Collectively, this study demonstrates a sex-dependent role for housing temperature in influencing energetics and body composition in a rodent model of burn trauma.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507123","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}
SHOCKPub Date : 2024-10-18DOI: 10.1097/SHK.0000000000002495
Roman Kula, Marcin Osuchowski, Roman Kula
{"title":"Understanding the Role of NT-proBNP in Septic Shock: Beyond Cardiac Dysfunction.","authors":"Roman Kula, Marcin Osuchowski, Roman Kula","doi":"10.1097/SHK.0000000000002495","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002495","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507129","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}
SHOCKPub Date : 2024-10-18DOI: 10.1097/SHK.0000000000002498
Birun Huang, Haiyan Chen, Xiulan Zhang
{"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":"https://doi.org/10.1097/SHK.0000000000002498","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Vascular smooth muscle cells (VSMCs) were pre-treated 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 (CCK8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry. Inflammatory factors were examined by ELISA. Fe2+, glutathione (GSH) and malondialdehyde (MDA) 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 (ChIP) assay and dual-luciferase reporter assay.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","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}
SHOCKPub Date : 2024-10-18DOI: 10.1097/SHK.0000000000002497
Schmitt Johan, Cloé Jacques Sébastien, Nicolas Herzog, Mathieu Boutonnet, Christophe Giacardi, Marc Danguy des Déserts, Thibault Martinez
{"title":"Multiple organ failure following severe battle injuries during recent conflicts: a French retrospective cohort study.","authors":"Schmitt Johan, Cloé Jacques Sébastien, Nicolas Herzog, Mathieu Boutonnet, Christophe Giacardi, Marc Danguy des Déserts, Thibault Martinez","doi":"10.1097/SHK.0000000000002497","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002497","url":null,"abstract":"<p><strong>Introduction: </strong>Improvements in combat casualty care have increased survival rates, but these patients are at particular risk of developing multiple organ failure (MOF). We investigated the incidence and severity of MOF in a cohort of severe combat casualties.</p><p><strong>Materials and methods: </strong>This retrospective study included all on-duty French land army war casualties with a severe combat injury requiring intensive care unit admission during 2009-2023. Demographic data, advanced life support interventions, and outcomes were collected. Each organ failure was then analyzed during a 7-day trauma course according to the Sequential Organ Failure Assessment (SOFA) score.</p><p><strong>Results: </strong>Of the 100 patients who met the inclusion criteria, those with persistent MOF at day 4 (MOF group) represented 22% of the total population (median SOFA score 6.0 [5.3-8.0]). Compared to those without persistent MOF, these patients were more severely injured (median Military Injury Severity Score 38.0 [interquartile range 33.0-56.8] vs 26.5 [20.0-34.0], p < 0.001) by an explosive mechanism (68.2%) and sustained more traumatic brain injury (TBI; 40.9% vs 14.1%, p = 0.013). The MOF group also received significantly more blood units (median 14.0 [8.3-24.8] vs 6.0 [0.0-12.0], p < 0.001) and massive transfusions (68.2% vs 32.1%, p = 0.002). Pulmonary and cardiovascular dysfunction were the most frequently observed trauma outcomes. A multivariable logistic regression model showed that MOF persistence at day 4 was significantly associated (odds ratios [95% confidence intervals]) with severe injuries (1.5 [1-2.3], p = 0.042).</p><p><strong>Conclusion: </strong>A high number of severe lesions significantly and independently increased risk of MOF persistence at day 4 after combat-related trauma. These findings are particularly relevant to current and anticipated large-scale combat operations that will challenge battlefield casualty care and evacuation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507124","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}
SHOCKPub Date : 2024-10-18DOI: 10.1097/SHK.0000000000002483
Sameer Thadani, Anna Lang, Christin Silos, Jack Price, Ben Gelbart, Katri Typpo, Christopher Horvat, Dana Y Fuhrman, Tara Neumayr, Ayse Akcan Arikan
{"title":"Fluid Overload Modifies Hemodynamic Impact of CRRT: 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":"https://doi.org/10.1097/SHK.0000000000002483","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 non-invasive and utilizes bioimpedance, was applied to obtain hemodynamic data over the first 48 hours of CRRT. Our aim was to identify how FO >15% affects hemodynamics in children receiving CRRT.</p><p><strong>Results: </strong>Seventeen children, median age 43 months (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 (1277 [IQR 1088-1666] vs. 1030 [IQR 868-1181] dyne*s/m2/cm5, P < 0.01), and cardiac index (3.90 [IQR 3.23-4.75] vs. 5.68 [IQR 4.65-6.32] L/min/m2, P < 0.01), with no differences in heart rate or mean arterial pressure between children with and without FO.</p><p><strong>Conclusion: </strong>FO affects the hemodynamic profile of children on CRRT, with those having FO >15% showing higher SVRI and lower CI, despite HR and MAP 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":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","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}
SHOCKPub Date : 2024-10-10DOI: 10.1097/SHK.0000000000002493
Yingxin Wang, Jiaqian Wu, Tenghao Shao, Dan Su, Xin Ma, Zhanbiao Yu, Ning Li
{"title":"Prognostic Implications of Changes in Platelet Trajectories in Patients With Sepsis: A Retrospective Analysis Using the Medical Information Mart for Intensive Care-IV Database.","authors":"Yingxin Wang, Jiaqian Wu, Tenghao Shao, Dan Su, Xin Ma, Zhanbiao Yu, Ning Li","doi":"10.1097/SHK.0000000000002493","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002493","url":null,"abstract":"<p><strong>Objective: </strong>Patients with sepsis often experience reductions or increases in platelet counts, but the implications of these temporal patterns on prognosis remain unclear. The aim of this study was to investigate the impact of changes in platelet trajectories on the clinical prognosis of sepsis.</p><p><strong>Methods: </strong>This study was a retrospective analysis using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were identified from the database, and their platelet trajectories were categorized into four distinct models based on the changes in platelet counts over a period of 14 days post-diagnosis of sepsis. The effect of these trajectories on patient prognosis was subsequently evaluated.</p><p><strong>Results: </strong>A total of 15,250 patients with sepsis were included to construct a model, and the following four distinct platelet count trajectories were identified: normal platelet levels (phenotype 1); persistently low platelet levels (phenotype 2); gradually increasing platelet levels exceeding the normal range (phenotype 3); and consistently significantly elevated platelet levels (phenotype 4). Statistically significant differences were found in the 28-day mortality, in-hospital mortality, and 90-day mortality among the four phenotypes. Multivariate regression analysis showed that compared to the group with normal platelet levels (phenotype 1), the group with persistently low platelet levels (phenotype 2) had higher in-hospital mortality (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 1.16-1.54), 28-day mortality (OR = 1.69, 95% CI: 1.47-1.94), and 90-day mortality (OR = 1.50, 95% CI: 1.32-1.69). There was no difference in in-hospital mortality between phenotypes 3 and 4 compared to phenotype 1, although phenotype 4 showed an increase in 28-day mortality (p < 0.05), and phenotype 3 showed a decreasing trend in 90-day mortality (p < 0.05). The results of inverse probability weighting adjusted by regression were basically consistent with the above findings, except that there was no statistical difference in 28-day mortality between phenotype 4 and phenotype 1. In the subgroups based on age, weight, and antiplatelet drugs or therapies, there was an interaction between platelet levels and these factors.</p><p><strong>Conclusion: </strong>In patients with sepsis, a decrease in platelet count is associated with increased mortality, while a moderate increase in platelet count can reduce 90-day mortality. However, for patients with persistently elevated platelet counts, caution is advised when using antiplatelet drugs or therapies, as it may increase mortality.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507126","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}
SHOCKPub Date : 2024-10-02DOI: 10.1097/SHK.0000000000002486
Ping Lu, Lingyun Cui, Hongqiu Gu, Zixiao Li, Yi Ju, Yongjun Wang, Xingquan Zhao, Wenjuan Wang
{"title":"Complicated cardiac arrest and its resuscitation characteristics in patients with intracerebral hemorrhage: Chinese Stroke Center Alliance.","authors":"Ping Lu, Lingyun Cui, Hongqiu Gu, Zixiao Li, Yi Ju, Yongjun Wang, Xingquan Zhao, Wenjuan Wang","doi":"10.1097/SHK.0000000000002486","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002486","url":null,"abstract":"<p><strong>Objective: </strong>Cardiac arrest (CA) is one of the most severe complications in patients with intracerebral hemorrhage (ICH), increasing the risk of death. This study explored the factors influencing CA occurrence and its resuscitation characteristics in ICH patients.</p><p><strong>Methods: </strong>Data were retrieved from the Chinese Stroke Center Alliance database. The primary outcome was CA, and the secondary outcomes were in-hospital death and survival post-CA. Absolute standardized and rate differences were utilized for intergroup comparisons, while logistic regression was employed for correlation analysis.</p><p><strong>Results: </strong>A total of 85,105 patients were enrolled in this study. Among them, 1651 (1.9%) patients experienced CA, of whom 1032 (62.5%) died in hospital. At baseline, prehospital notification from the emergency medical service system (PRE-EMS) was a co-factor influencing CA occurrence and the presence of a death outcome (OR: 1.71, 95% CI: 1.47-1.98, p < 0.001; OR: 0.50, 95% CI: 0.41-0.62, p < 0.001). In terms of complications, post-hospital hematoma expansion and swallowing dysfunction were co-factors influencing CA occurrence and the presence of a death outcome (OR: 3.78, 95% CI: 3.20-4.47, p < 0.001, OR: 1.39, 95% CI: 1.11-1.76; p < 0.001; OR: 7.66, 95% CI:5.48-10.70, p < 0.001, OR: 1.66, 95% CI: 1.08-2.57, p < 0.001). The incidence of CA in ICH patients decreased annually from 2015 to 2019, while survival after CA increased annually (p < 0.001).</p><p><strong>Conclusions: </strong>PRE-EMS, posthospital hematoma expansion, and swallowing dysfunction were identified as co-factors contributing to CA occurrence and post-CA mortality following ICH. The proportion of CA patients following ICH decreased, while survival rates improved annually from 2015 to 2019.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507118","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}
SHOCKPub Date : 2024-10-02DOI: 10.1097/SHK.0000000000002488
Yan Shen, Huaxing Huang, Lianglan Shen, Wubin Yao, Rong Wang, Meizi Kang, Jiashan Huang, Yan Xie, Hongli Yang
{"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":"https://doi.org/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 cell (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack) and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) has 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 (H&E) staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR (RT-qPCR) 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 in 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 down-regulate 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":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","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}
SHOCKPub Date : 2024-10-02DOI: 10.1097/SHK.0000000000002482
Noa Galtung, Vanessa Stein, Monika Prpic, Burak Boyraz, Jannis Ulke, Stephan Kurz, Jens Dernedde, Eva Diehl-Wiesenecker, Wolfgang Bauer, Kai Kappert
{"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":" ","pages":""},"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}