Na Li

Background: Sepsis leads to multiorgan damage, with the liver being the main target. Sirtuin 4 (Sirt4) plays a regulatory role in mitochondrial function and metabolism, but its mechanism in liver injury caused by sepsis remains unclear. Methods: The mouse model of liver injury caused by sepsis was established by cecal ligation and puncture (CLP) surgery. The degree of liver injury in wild‐type (WT) and Sirt4 gene total knockout (Sirt4‐KO) mice was compared by serum AST, alanine aminotransferase (ALT), and histological analysis. The expression of mitophagy and mitochondrial dynamic indicators was detected by biochemical experiments. Results: Liver injury in Sirt4‐KO mice was more severe than that in WT mice after CLP, manifested as significant upregulation of mitophagy and mitochondrial dynamics imbalance. Mechanistically, Sirt4 deficiency increases mitochondrial fission and mitophagy, thereby leading to cellular damage. Conclusions: Sirt4 knockout (KO) aggravates liver injury in sepsis through increasing mitochondrial fission and mitophagy, which indicates a promising direction for future clinical treatment.

Background: Previously, research has reported associations of lipid and lipoprotein imbalances with carcinogenesis and cancer progression, so they have been considered as promising prognostic biomarkers for cancer in recent years. However, the correlation of preoperative serum triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) with non-small cell lung carcinoma (NSCLC) prognosis remains under exploration. Here, the study investigated the prognostic function of TG/HDL-C for NSCLC. Methods: The total combined group of this retrospective study enrolled 479 NSCLC patients from two tertiary referral hospitals, of which 223 patients were defined as the training group (Nanchang) and the remaining 256 were defined as the validation group (Wuhan). The cut-off of preoperative TG/HDL-C was determined through ROC curve in the training group and verified in the validation and combined groups subsequently. With one Cox proportional hazards model and K-M survival curves, a survival analysis was conducted. Results: In the training group, the optimal cut-off of TG/HDL-C was 1.02. Furthermore, the data based on the training group revealed a greater, shorter, overall survival (OS) in patients having a high TG/HDL-C (>1.02) than those having low TG/HDL-C (≤1.02). Meanwhile, in univariate and multivariate analysis, for prognostic OS among NSCLC patients, TG/HDL-C acted as one independent factor. All the results above were confirmed in the validation and combined groups. Conclusion: NSCLC patients with a comparatively low preoperative serum TG/HDL-C level had a correlation with well OS. TG/HDL-C possibly acted as one novel, effective prognostic biomarker for NSCLC patients.

Cardiac fibrosis critically injured the cardiac structure and function of the hypertensive patients. However, the anti‐fibrotic strategy is still far from satisfaction. This study aims to determine the effect and mechanism of Pirfenidone (PFD), an anti‐lung fibrosis medicine, in the treatment of cardiac fibrosis and heart failure induced by pressure overload. Male C57BL/6 mice were subjected to thoracic aorta constriction (TAC) or sham surgery with the vehicle, PFD (300 mg/kg/day) or Captopril (CAP, 20 mg/kg/day). After 8 weeks of surgery, mice were tested by echocardiography, and then sacrificed followed by morphological and molecular biological analysis. Compared to the sham mice, TAC mice showed a remarkable cardiac hypertrophy, interstitial and perivascular fibrosis and resultant heart failure, which were reversed by PFD and CAP significantly. The enhanced cardiac expression of TGF‐β1 and phosphorylation of Smad3 in TAC mice were both restrained by PFD. Cardiac fibroblasts isolated from adult C57BL/6 mice were treated by Angiotensin II, which led to significant increases in cellular proliferation and levels of α‐SMA, vimentin, TGF‐β1 and phosphorylated TGF‐β receptor and Smad3. These changes were markedly inhibited by pre‐treatment of PFD. Collectively, PFD attenuates myocardial fibrosis and dysfunction induced by pressure overload via inhibiting the activation of TGF‐β1/Smad3 signalling pathway.