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Background Sepsis-induced acute kidney injury (S-AKI) is a common complication in critically ill patients. Therefore, reliable biomarkers for predicting S-AKI outcomes are necessary. Serum cell-free DNA (cfDNA) is a circulating extracellular DNA fragment used as a noninvasive screening tool for many diseases, including sepsis. This study aimed to investigate the prognostic value of cfDNA in S-AKI patients and its relationship with some other parameters.Methods A total of 89 S-AKI patients admitted to the intensive care unit (ICU) from June 2021 to December 2021 were enrolled in this study. The patients were categorized into the low cfDNA group (< 855 ng/ml) and high cfDNA group (≥ 855 ng/ml) and were followed up for three months. CfDNA was extracted from serum and quantified using Quant-iT PicoGreen dsDNA Reagent.Results Overall survival was significantly lower in the high cfDNA group than in the low cfDNA group (Log-Rank p = 0.012). Univariate Cox proportional hazard model showed that cfDNA was significantly associated with all-cause mortality (HR [hazard ratio] 2.505, 95% CI [95% confidence interval] 1.184–5.298, p = 0.016). Also, serum cfDNA was a significant risk factor for all-cause mortality after adjusting for covariates (HR 2.191, 95% CI 1.017–4.721, p = 0.045). Moreover, cfDNA was positively correlated with several baseline parameters, including serum creatine, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and International Normalized Ratio.Conclusion High serum cfDNA level is associated with higher mortality among the S-AKI population, indicating that cfDNA is a valuable biomarker for S-AKI prognosis. [ABSTRACT FROM AUTHOR]

Heat stress can impair organismal growth by inducing ubiquitination, proteasome-mediated degradation, and subsequent cellular damage. Vitamin C (VC) has been shown to potentially mitigate the detrimental effects of abiotic stresses on cells. Nevertheless, the impact of heat stress on growth plate chondrocytes remains unclear, and the underlying protective mechanisms of VC in these cells warrant further investigation. In this study, we focused on pig thoracic vertebral chondrocytes (PTVCs) that are crucial for promoting the body's longitudinal elongation and treated them with 41 °C heat stress for 24 h, under varying concentrations of VC. Our findings reveal that, while oxidative stress induced by heat triggers apoptosis and inhibits the ubiquitin-mediated proteolysis pathway, the addition of VC alleviates heat-stress-induced oxidative stress and apoptosis, mitigates cell cycle arrest, and promotes cellular viability. Furthermore, we demonstrate that VC enhances the ubiquitin-proteasome proteolysis pathway by promoting the expression of ubiquitin protein ligase E3A, which thereby stabilizes the ubiquitin-mediated degradation machinery, alleviates the apoptosis, and enhances cell proliferation. Our results suggest the involvement of the ubiquitin-mediated proteolysis pathway in the effects of VC on PTVCs under heat stress, and offer a potential strategy to make use of VC to ensure the skeletal growth of animals under high temperature pressures in summer or in tropical regions. [ABSTRACT FROM AUTHOR]

Simple Summary: Castration induces fat deposition in boars and decreases carcass quality, prompting extensive research on the regulatory mechanism of fat deposition in castrated boars from a genetic perspective. Consequently, this study aimed to conduct a series of molecular biological experiments to elucidate how testosterone inhibits lipid droplet accumulation in porcine preadipocytes through ELOVL3. The findings from this study offer crucial data supporting genetic analyses of porcine fat deposition due to castration, thereby significantly contributing to enhancing pork quality and improving pig production efficiency. Castration is commonly used to reduce stink during boar production. In porcine adipose tissue, castration reduces androgen levels resulting in metabolic disorders and excessive fat deposition. However, the underlying detailed mechanism remains unclear. In this study, we constructed porcine preadipocyte models with and without androgen by adding testosterone exogenously. The fluorescence intensity of lipid droplet (LD) staining and the fatty acid synthetase (FASN) mRNA levels were lower in the testosterone-treated cells than in the untreated control cells. In contrast, the mRNA levels of adipose triglycerides lipase (ATGL) and androgen receptor (AR) were higher than in the testosterone-treated cells than in the control cells. Subsequently, transcriptomic sequencing of porcine preadipocytes incubated with and without testosterone showed that the mRNA expression levels of very long-chain fatty acid elongase 3 (ELOVL3), a key enzyme involved in fatty acids synthesis and metabolism, were high in control cells. The siRNA-mediated knockdown of ELOVL3 reduced LD accumulation and the mRNA levels of FASN and increased the mRNA levels of ATGL. Next, we conducted dual-luciferase reporter assays using wild-type and mutant ELOVL3 promoter reporters, which showed that the ELOVL3 promoter contained an androgen response element (ARE); furthermore, its transcription was negatively regulated by AR overexpression. In conclusion, our study reveals that testosterone inhibits fat deposition in porcine preadipocytes by suppressing ELOVL3 expression. Moreover, our study provides a theoretical basis for further studies on the mechanisms of fat deposition caused by castration. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance has become a an important worldwide problem to cancer treatment. Understanding the mechanism of drug resistance is the key to solve this problem and improve the survival of the patient. Doxorubicin and its analogues are widely used as antitumor drugs but many doxorubicin resistant cases have been identified in recent years. Doxorubicin (Dox) resistance is a very serious phenomenon in lung cancer treatment. As we could show previously, Shufeng Jiedu Capsule (SFJDC) can effectively reverse H69AR cells resistance to Dox, thus, the present study was designed to explore the mechanism underlying the effects of the main ingredient Emodin on chemosensitivity of H69AR cells to Dox. Methods: First, the growth inhibition rate of lung cancer cells and normal bronchial epithelial cells (BECs) was determined by MTT. Then, the resistance-induced epithelial-mesenchymal transition (EMT) of H69AR cells was examined by western blot and the effect of Emodin on Twist, Snail or Slug was assayed by Real-time PCR and Western blot. The activation of NF-kappa B was assayed by Western blot. Proliferation, apoptosis, migration and invasion of H69AR cells induced by Twist, Snail and Slug were also assayed by flow cytometry and transwell chamber. Results: The results showed that after administration of Dox (10µM) with different concentrations of Emodin, the cells exhibited a dose-dependent inhibition action to H69AR cells at 48 hours. H69AR induced the expression of Twist, Snail, and Slug when compared with Dox-sensitive H69 cells. The expression of Twist, Snail, and Slug can be effectively inhibited by combination of Dox and Emodin. The reversal of resistance was associated with the inhibition of NF-kappa B. Twist, Snail and Slug promoted proliferation, migration and invasion and inhibited apoptosis. Conclusion: Our data suggest that Emodin can effectively reverse the resistance of H69AR to Dox, an effect paralleled by inhibition of EMT, cell proliferation, apoptosis, migration and invasion.