PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 21, 2023

Abstract The increase of lactate is an independent risk factor for patients with sepsis-induced acute kidney injury (SAKI). However, whether elevated directly promotes SAKI and its mechanism remain unclear. Here we revealed that downregulation the deacetylase Sirtuin 3 (SIRT3) mediated hyperacetylation inactivation pyruvate dehydrogenase E1 component subunit alpha (PDHA1), resulting in overproduction renal tubular epithelial cells. We then found incidence replacement therapy (RRT) septic blood ≥ 4 mmol/L was increased significantly, compared those < 2 mmol/L. Further vitro vivo experiments showed additional administration could promote SAKI. Mechanistically, lactylation mitochondrial fission 1 protein (Fis1) lysine 20 (Fis1 K20la). Fis1 K20la promoted excessive subsequently induced ATP depletion, reactive oxygen species (mtROS) overproduction, apoptosis. In contrast, PDHA1 activation sodium dichloroacetate (DCA) or SIRT3 overexpression decreased levels K20la, thereby alleviating conclusion, our results show enhance which mediates exacerbates Reducing attenuate

Language: Английский

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Sepsis Biomarkers: Advancements and Clinical Applications—A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9010 - 9010

Published: Aug. 19, 2024

Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by dysregulated host response to infection, posing significant challenges in critical care. The main objective this review evaluate the potential emerging biomarkers for early diagnosis and accurate prognosis sepsis management, which are pivotal enhancing patient outcomes. Despite advances supportive care, traditional like C-reactive protein procalcitonin have limitations, recent studies identified novel with increased sensitivity specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, C, triiodothyronine, prokineticin 2. These hold promising detection prognostication sepsis. They play crucial role not only but also guiding antibiotic therapy evaluating treatment effectiveness. introduction point-of-care testing technologies has brought about paradigm shift biomarker application, enabling swift real-time evaluation. these advancements, persist, notably concerning variability lack standardized thresholds. This summarizes latest advancements research, spotlighting progress clinical implications. It emphasizes significance multi-biomarker strategies feasibility personalized medicine management. Further verification on large scale their integration into practice advocated maximize efficacy future treatment.

Language: Английский

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MTHFD2 stabilizes LOX expression through RNA methylation modification to promote sepsis-induced acute kidney injury progression

Human Cell, Journal Year: 2025, Volume and Issue: 38(2)

Published: Feb. 26, 2025

Language: Английский

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Antioxidant, Antiapoptotic, and Anti-Inflammatory Effects of Hesperetin in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury

Molecules, Journal Year: 2023, Volume and Issue: 28(6), P. 2759 - 2759

Published: March 18, 2023

Sepsis is a severe inflammatory condition that can cause organ dysfunction, including acute kidney injury (AKI). Hesperetin flavonoid aglycone has potent antioxidant and anti-inflammatory properties. However, the effect of hesperetin on septic AKI not yet been fully investigated. This study examined whether renoprotective lipopolysaccharide (LPS)-induced AKI. treatment ameliorated histological abnormalities renal dysfunction in LPS-injected mice. Mechanistically, attenuated LPS-induced oxidative stress, as evidenced by suppression lipid DNA oxidation. beneficial was accompanied downregulation pro-oxidant NADPH oxidase 4, restoration glutathione levels, activation enzymes. compound also inhibited apoptotic cell death via p53-dependent caspase-3 pathway. Furthermore, alleviated Toll-like receptor 4-mediated cytokine production macrophage infiltration. Our findings suggest ameliorates structural functional through suppressing apoptosis, inflammation.

Language: Английский

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Potential therapeutic applications of circular RNA in acute kidney injury

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116502 - 116502

Published: April 3, 2024

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid deterioration in renal function, manifested significant increase creatinine and sharp decrease urine output. The incidence of morbidity mortality associated with AKI on the rise, most patients progressing to chronic disease or end-stage disease. Treatment options for remain limited. Circular RNA (circRNA) wide diverse class non-coding RNAs that are present variety organisms involved gene expression regulation. Studies have shown circRNA acts as competing RNA, occurrence development, has potential diagnostic prognostic marker. CircRNA regulation important biological processes, including apoptosis, oxidative stress, inflammation. This study reviews current status progress research context AKI.

Language: Английский

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A DNA-based and bifunctional nanomedicine for alleviating multi-organ injury in sepsis under diabetic conditions

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 177, P. 377 - 387

Published: Feb. 1, 2024

Language: Английский

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Variations of renal Doppler indices during the initial 24-hour predict acute kidney injury in patients with sepsis: A single-center observational case-control clinical study

Clinics, Journal Year: 2025, Volume and Issue: 80, P. 100538 - 100538

Published: Jan. 1, 2025

The aim of this retrospective observational case-control study was to examine the significance different renal Doppler marker variations within initial 24-hour period as potential predictors Acute Kidney Injury (AKI) in patients with sepsis. A total 198 sepsis were enrolled and categorized into two groups: AKI group (n = 136) non-AKI 62). Three indices, Renal Resistive Index (RRI), Power Ultrasound (PDU) score Venous Stasis (RVSI), measured 6h (T0) at 24h (T1) after ICU admission. had more hypertension than (p 0.047). cases showed higher levels CRP 0.001), PCT < lactate AST 0.003), ALT 0.049), bilirubin 0.034), BNP 0.019) cTnI 0.012). RRI T1 significantly 0.037). exhibited a lower incidence reduced compared 0.001). After controlling for age, sex, BMI through partial correlation analysis, results indicated significant associations between SA-AKI CVP (r -0.473), SOFA 0.425), 0.378), reduction -0.344) patients. multivariate logistic regression analysis that variables including CVP, score, CRP, lactate, VIS, not following treatment predictive indicators early detection can be utilized

Language: Английский

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Ursodeoxycholic acid protects against sepsis-induced acute kidney injury by activating Nrf2/HO-1 and inhibiting NF-κB pathway

BMC Nephrology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 30, 2025

Ursodeoxycholic acid (UDCA), traditionally recognized for its hepatoprotective effects, has also shown potential in protecting kidney injury. This study aimed to evaluate the protective effects of UDCA against sepsis-induced acute injury (AKI) and elucidate underlying mechanisms. Sixty male C57BL/6 N mice were utilized establish a AKI model through intravenous injection lipopolysaccharides (LPS, 10 mg/kg). (15, 30, 60 mg/kg) was administered intraperitoneally once daily 7 days before LPS injection. Kidney evaluated by HE staining biochemical markers, including serum creatinine (Cr), blood urea nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), retinol binding protein (RBP). Oxidative stress parameters nuclear factor erythroid 2-related 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway, pro-inflammatory cytokines factor-kappa B (NF-κB) pathway evaluated. Additionally, HK-2 cells treated with vitro, cell viability apoptosis detected using CCK-8 kit flow cytometer, respectively. significantly attenuated LPS-induced renal histopathological damage improved function, as evidenced reduction Cr, BUN, levels. up-regulated expression zonula occludens-1 (ZO-1) Ezrin kidney, reduced levels NGAL, KIM-1, NAG, RBP. Moreover, inhibited NF-κB p65 phosphorylation (TNF-α, IL-1β, IL-6) both kidney. alleviated oxidative activating Nrf2/HO-1 In cells, these being blocked Nrf2 inhibitor ML385. Our present demonstrated that exerts attenuating inflammation, primarily activation inhibition pathway. These findings highlight therapeutic preventing AKI.

Language: Английский

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L-shaped association of body mass index with prognosis in individuals with sepsis: a multicenter cohort study

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 3, 2025

The relationship between body mass index (BMI) and sepsis prognosis remains highly controversial uncertain. This study investigated the association BMI in patients with sepsis. retrospective observational cohort included adult admitted to intensive care unit (ICU) from Medical Information Mart for Intensive Care-IV version 2.2 (MIMIC-IV V2.2) eICU Collaborative Research Database (eICU-CRD). cut-off value of was identified by restricted cubic spline (RCS) curve were categorized into two groups: low group (< 28 kg/m2) high (≥ kg/m2). primary outcome ICU mortality, secondary outcomes in-hospital 28-day mortality. We performed log-rank test detect whether there is a difference among different groups cohorts. Multiple distinct models used validate robustness results. There 18,385 38,713 MIMIC-IV eICU-CRD cohorts, respectively. An L-shaped observed mortality analysis 2.2. Similar relationships found eICU-CRD. When less than cut-point, risk increased rapidly decreasing BMI. greater levelled off as increased. Sepsis higher values exhibited decreased all-cause rates cohort: HR: 0.81, 95% CI 0.75–0.88, p < 0.001; 0.75, 0.71–0.80, 0.001). Consistent trends both rates. results remained robust multiple subgroup analyses. septic patients, indicating that lower are significantly linked Targeted nutritional interventions close monitoring could potentially enhance their prognosis. Therefore, can also be utilized categorize levels effectively predict

Language: Английский

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Advancing Insights into Progression of Acute Kidney Injury with Sepsis: Early Detection and Management

Journal of Drug Delivery and Therapeutics, Journal Year: 2025, Volume and Issue: 15(2), P. 129 - 136

Published: Feb. 15, 2025

Acute kidney injury (AKI) associated with sepsis is a major contributor to morbidity and mortality in critically ill patients. The progression of sepsis-induced AKI (S-AKI) complex involves dysregulated immune response, including systemic inflammation, endothelial dysfunction, microvascular injury. These mechanisms compromise renal function, leading significant challenges management. Early detection timely intervention are crucial improving outcomes, yet effective treatment strategies remain elusive. Advances understanding the pathophysiology S-AKI have provided critical insights into underlying damage during sepsis. led identification potential biomarkers that can aid early diagnosis, predict disease progression, guide therapeutic decisions. Current management includes fluid resuscitation, broad-spectrum antibiotics, replacement therapy (RRT), aimed at stabilizing patient supporting function. Emerging therapies, such as novel pharmacological agents approaches modulate under investigation, offering promise for clinical outcomes. However, more research needed validate these treatments ensure their safety efficacy. advancing S-AKI, coupled development innovative diagnostic tools Future should focus on bridging gap between basic science, practice, large-scale trials optimize care outcomes patients suffering from S-AKI. Keywords: Sepsis, injury, Immune Systemic Endothelial Microvascular

Language: Английский

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