Sepsis-induced AKI (acute kidney injury) is considered an inflammation-related disease with high mortality. LPS-induced (Lipopolysaccharide) TLR4-NFκB pathway activation plays an important role in sepsis-induced AKI. Pyroptosis closely associated with inflammation response includes inflammasome formation, caspase1 activation and GSDMD N-terminal fragment cleavage that leads to cell membrane rupture and cell death, which may be related to the pathogenesis of sepsis-induced AKI. MIF (Macrophage migration inhibitory factor), associated with inflammation response, has been proved as a biomarker of sepsis, and perhaps regulate pyroptosis in sepsis-induced AKI. In this study, we focus on investigating the mechanism of MIF promoting pyroptosis in sepsis-induced AKI. MIF and pyroptosis-related proteins were up-regulated in kidney tissue of mice with CLP (cecum ligation puncture) surgery and in LPS-injured human kidney-2 (HK-2) cells. NLRP3 was down-regulated following the suppression of MIF topoisomerase activity by ISO-1 in kidney tissue of CLP mice. Knockdown of MIF alleviated NLRP3 inflammasome mediated pyroptosis in LPS-injured HK-2 cells. Meanwhile, we noted that phosphorylation of p65 was down-regulated by knockdown of MIF. Up-regulation of NLRP3 in response to LPS stimulation could be reversed by JSH-23, an inhibitor of NFκB pathway, but MIF was not affected. In conclusion, up-regulation of MIF in sepsis-induced AKI shows a renal damaged effect that aggravates NLRP3 inflammasome mediated cell pyroptosis through promoting phosphorylation of p65. This study demonstrated a novel mechanism of MIF regulating NLRP3 inflammasome mediated pyroptosis in sepsis-induced AKI.
Tissue inhibitor of metalloproteinase 2 (TIMP2) has been recognized as an important biomarker for predicting acute kidney injury (AKI) because of its involvement in the process of inflammation and apoptosis in septic AKI. Endoplasmic reticulum (ER) stress, a condition of disrupted ER homeostasis, is implicated in multiple pathophysiological processes, including kidney disease. Herein, we investigated the correlation between ER stress and septic AKI and further explored how TIMP2 regulated ER stress‐mediated apoptosis. To assess the role of TIMP2 in sepsis‐induced AKI, we used a cecal ligation and puncture (CLP) model in mice with tubule‐specific deficiency of TIMP2 (Ksp‐Cre/TIMP2flox/flox) and their wild‐type counterparts. Compared to the wild‐type mice, TIMP2‐deficient mice demonstrated lower serum creatinine levels and decreased ER stress‐mediated apoptosis when subjected to CLP. Interestingly, in human kidney (HK‐2) cells, overexpression of TIMP2 caused ER stress, whereas TIMP2 knockdown attenuated lipopolysaccharide‐induced ER stress and apoptosis. TIMP2 interacted with the binding immunoglobulin protein, an ER chaperone, and facilitates its extracellular secretion, thereby triggering ER stress. This study identified that the deletion of TIMP2 in mouse tubules mitigated sepsis‐induced AKI by inhibiting ER stress‐mediated apoptosis, which might be a potential therapeutic strategy to alleviate renal injury.
Objective. We conducted a meta-analysis to quantitatively evaluate the effects of abdominal binder in abdominal surgeries. Methods. Through literature retrieval in globally recognized databases (MEDLINE, EMBASE, and Cochrane Central), trials investigating the application of abdominal binder in abdominal surgeries were systematically reviewed. The main outcomes, namely, 6-minute walk test (6MWT), visual analog scale (VAS) pain score, and symptom distress scale (SDS) score, were pooled to make an overall estimation. I2 index was calculated to identify heterogeneity, and sensitivity analysis was performed to validate the stability of main results and explore the source of heterogeneity. A funnel plot and Egger’s test were applied to assess publication bias. Results. Ten randomized controlled trials consisting of 968 subjects were ultimately included for the pooled estimation. Abdominal binder significantly increased the distance of 6MWT with standard mean difference (SMD) of .555 ( P < .001) and decreased the scores of VAS and SDS with SMD of −.979 ( P < .001) and −.716 ( P < .001), respectively. Despite of the significant heterogeneity indicated by I2 index statistic, the results of sensitivity analysis revealed the reliability of the main conclusions. While we identified no obvious publication bias regarding 6MWT (Egger’s test P = .321), it seemed that significant publication biases existed with respect to the estimation of VAS ( P < .001) and SDS ( P = .006). Conclusion. The current meta-analysis verified that abdominal binder efficiently promoted recovery after abdominal surgeries in terms of facilitating mobilization, alleviating pain, and reducing postoperative distress. More rigorously designed clinical trials with large sample size are expected to further elaborate its clinical value.
Background: While dexamethasone has been applied following transcatheter arterial chemoembolization (TACE) for years, its clinical effects have not been determined. In the current study, we aimed to evaluate the efficacy of dexamethasone in preventing adverse events induced by TACE. Methods: Literature retrieval was conducted using globally recognized online databases, namely MEDLINE, EMBASE, and Cochrane Central, to identify randomized controlled trials (RCTs) of dexamethasone application in patients undergoing TACE. The relative odds ratios (ORs) of incidence rates of three adverse events, namely, fever, abdominal pain and nausea/vomiting, were calculated. The value of I2 was applied to evaluate the heterogeneity of the trials, and the overall publication bias was assessed with Egger test. Results: Four RCTs containing 350 subjects were included for the pooled estimation. Dexamethasone significantly reduced the incidence rate of TACE-induced adverse events (OR = 1.237, 95% CI: 1.170–1.308, P < .001) with moderate heterogeneity (I2 = 46.0%). The result of Egger test revealed a publication bias for the included studies. Conclusion: The current meta-analysis confirmed the efficacy of dexamethasone in preventing TACE-induced adverse events. To confirm the practicality of dexamethasone use with TACE, further studies with large sample sizes are warranted to update the evidence-based analyses.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.