he treatment's efficacy. Oxidant-antioxidant profile merits investigation as markers of diagnosis, treatment response, survival, and recurrence in extensive prospective studies.Our results indicate that increased oxidative stress and diminished antioxidants among patients were associated with carcinoma cervix. Induced oxidative stress and decreased antioxidant parameters during CCRT among the complete responders show the treatment's efficacy. Oxidant-antioxidant profile merits investigation as markers of diagnosis, treatment response, survival, and recurrence in extensive prospective studies.Oversupply of fatty acids (FAs) to cardiomyocytes (CMs) is associated with increased ceramide content and elevated the risk of lipotoxic cardiomyopathy. Here we investigate the role of ceramide accumulation on mitochondrial function and mitophagy in cardiac lipotoxicity using CMs derived from human induced pluripotent stem cell (hiPSC). Mature CMs derived from hiPSC exposed to the diabetic-like environment or transfected with plasmids overexpressing serine-palmitoyltransferase long chain base subunit 1 (SPTLC1), a subunit of the serine-palmitoyltransferase (SPT) complex, resulted in increased intracellular ceramide levels. Accumulation of ceramides impaired insulin-dependent phosphorylation of Akt through activating protein phosphatase 2A (PP2A) and disturbed gene and protein levels of key metabolic enzymes including GLUT4, AMPK, PGC-1α, PPARα, CD36, PDK4, and PPARγ compared to controls. Analysis of CMs oxidative metabolism using a Seahorse analyzer showed a significant reduction in ATP synthesis-related O2 cserve as a novel therapeutic target to treat metabolic cardiomyopathy.Dry eye and diabetic keratopathy represent the major diabetic complications in ocular surface. Here we found that diabetic mice exhibited the early onset of reduced tear secretion and lacrimal gland weight compared to the symptoms of diabetic keratopathy. Considering to the high bioenergetic needs in lacrimal gland and cornea, we hypothesized that hyperglycemia may cause different severity of mitochondrial bioenergetic deficit between them. Through the measurement of oxygen consumption rate (OCR) and basal extracellular acidification rate (ECAR), we found the apparent alterations of mitochondrial bioenergetic profiles in diabetic lacrimal gland and cornea, accompanied with the mtDNA damage and copy number reduction, as well as the reduced glutathione content. Comparative analysis revealed that mouse lacrimal gland cells exhibited 2-3 folds higher of basal, ATP production, maximal OCR and basal ECAR than corneal epithelial cells in normoglycemia. However, the differences were slightly significant or even not detected in hyperglycemia. Accordingly, the mitochondrial bioenergetic metabolism of lacrimal gland was more compromised than that of corneal epithelium in diabetic mice. Through the administration of mitochondrial-targeted antioxidant SkQ1, the severity of dry eye and diabetic keratopathy was significantly attenuated with the improved mitochondrial function. These results indicate that the susceptibility of mitochondrial bioenergetic deficit in diabetic lacrimal gland may contribute to the early onset of dry eye, while mitochondria-targeted antioxidant possesses therapeutic potential for diabetic dry eye and keratopathy.Rapamycin is a crucial immunosuppressive regimen for patients that have undergone liver transplantation (LT). However, one of the major side effects of rapamycin include metabolic disorders such as dyslipidemia, and the mechanism remains unknown. This study aims to explore the biomolecules that are responsible for rapamycin-induced dyslipidemia and the control strategies that can reverse the lipid metabolism disorder. In this study, data collected from LT patients, cell and mouse models treated with rapamycin were analyzed. Results showed an increase of triglycerides (TGs) induced by rapamycin. MicroRNAs (miRNAs) play important roles in many vital biological processes including TG metabolism. hsa-miR-372-3p was filtered using RNA sequencing and identified as a key regulator in rapamycin-induced TGs accumulation. Using bioinformatics and experimental analyses, target genes of hsa-miR-372-3p were predicted. These genes were alkylglycerone phosphate synthase (AGPS) and apolipoprotein C4 (APOC4), which are reported to be involved in TG metabolism. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was also identified as an upstream regulatory factor of hsa-miR-372-3p. From the results of this study, NEAT1/hsa-miR-372-3p/AGPS/APOC4 axis plays a vital role in rapamycin-disruption of lipid homeostasis. Therefore, targeting this axis is a potential therapeutic target combating rapamycin-induced dyslipidemia after LT.Sepsis rapidly contributed to multiorgan failure affecting most commonly of the cardiovascular and respiratory systems and yet there were no effective therapies. The current study aimed at providing evidence on the cardioprotection of suppression of 5-Lipoxygenase (5-Lox) and identifying the possible mechanism in the mouse model of sepsis. The cecal ligation-perforation (CLP) model was applied to C57BL/6 wild-type (WT) and 5-Lox deficient (5-Lox-/-) mice to induce sepsis. 5-Lox expression was up-regulated in mouse myocardium and leukotriene B4 (LTB4) level was increased in serum after sepsis. Subsequently, we utilized a recombinant adenoviral expression vector (rAAV9) to overexpress Alox5 gene in adult mice. Compared to WT mice, 5-Lox overexpression accelerated CLP-induced myocardial injury and cardiac dysfunction. selleckchem Oppositely, 5-Lox deficiency offered protection against myocardial injury in a mouse model of sepsis and attenuated sepsis-mediated inflammation, oxidative stress and apoptosis in the mouse heart. Mechanically, 5-Lox promoted LTB4 production, which in turn contributed to the activation of leukotriene B4 receptor 1 (BLT1)/interleukin-12p35 (IL-12p35) pathway and enhanced M1 macrophage polarization. However, the suppression of BLT1 by either gene mutation or antagonist U75302 significantly inhibited the adverse effect of 5-Lox in sepsis. Further study demonstrated that pharmacological inhibition of 5-Lox prevented CLP-induced septic cardiomyopathy (SCM). Our study identified 5-Lox exacerbated sepsis-associated myocardial injury through activation of LTB4 production and promoting BLT1/IL-12p35 pathway. Hence, inhibition of 5-Lox may be a potential candidate strategy for septic cardiac dysfunction treatment.