Optic atrophy 1 (OPA1)‐related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1‐related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial stress in the setting of cardiac ischemia‐reperfusion (I/R) injury. Our results indicated that OPA1, mitochondrial fusion, and mitophagy were significantly repressed by I/R injury, accompanied by infarction area expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte oxidative stress. However, melatonin treatment maintained myocardial function and cardiomyocyte viability, and these effects were highly dependent on OPA1‐related mitochondrial fusion/mitophagy. At the molecular level, OPA1‐related mitochondrial fusion/mitophagy, which was normalized by melatonin, substantially rectified the excessive mitochondrial fission, promoted mitochondria energy metabolism, sustained mitochondrial function, and blocked cardiomyocyte caspase‐9‐involved mitochondrial apoptosis. However, genetic approaches with a cardiac‐specific knockout of OPA1 abolished the beneficial effects of melatonin on cardiomyocyte survival and mitochondrial homeostasis in vivo and in vitro. Furthermore, we demonstrated that melatonin affected OPA1 stabilization via the AMPK signaling pathway and that blockade of AMPK repressed OPA1 expression and compromised the cardioprotective action of melatonin. Overall, our results confirm that OPA1‐related mitochondrial fusion/mitophagy is actually modulated by melatonin in the setting of cardiac I/R injury. Moreover, manipulation of the AMPK‐OPA1‐mitochondrial fusion/mitophagy axis via melatonin may be a novel therapeutic approach to reduce cardiac I/R injury.
CVP-guided fluid administration can safely and effectively reduce the risk of CIN in patients with CKD and CHF. (Central Venous Pressure Guided Hydration Prevention for Contrast-Induced Nephropathy; NCT02405377).
It is well established that the altered metabolism exhibited by cancer cells, including high rates of glycolysis, lactate production, and biosynthesis of lipids, nucleotides, and other macromolecules, and which may occur either as a consequence or as a cause of tumorigenesis, plays an essential role in cancer progression. Recently, the tumor suppressor p53 was found to play a central role in this process. Here, we review the role of p53 in modulating tumor metabolism. Specifically, we focus on the functions of p53 in regulating aerobic glycolysis, oxidative phosphorylation, the pentose phosphate pathway, fatty acid synthesis and oxidation, and glutamine metabolism, and we discuss the therapeutic strategy whereby p53 helps to prevent malignant progression.
Melatonin is a pleiotropic, indole secreted, and synthesized by the human pineal gland. Melatonin has biological effects including anti-apoptosis, protecting mitochondria, anti-oxidation, anti-inflammation, and stimulating target cells to secrete cytokines. Its protective effect on cardiomyocytes in acute myocardial infarction (AMI) has caused widespread interest in the actions of this molecule. The effects of melatonin against oxidative stress, promoting autophagic repair of cells, regulating immune and inflammatory responses, enhancing mitochondrial function, and relieving endoplasmic reticulum stress, play crucial roles in protecting cardiomyocytes from infarction. Mitochondrial apoptosis and dysfunction are common occurrence in cardiomyocyte injury after myocardial infarction. This review focuses on the targets of melatonin in protecting cardiomyocytes in AMI, the main molecular signaling pathways that melatonin influences in its endogenous protective role in myocardial infarction, and the developmental prospect of melatonin in myocardial infarction treatment.
Organ shortage has led to an increased use of kidneys from cardiac death donors (DCDs), but controversies about the methods of organ preservation still exist. This study aims to compare the effect of machine perfusion (MP) and cold storage (CS) in protecting kidneys harvested from DCDs. 141 kidney pairs from DCDs between July 2010 and July 2015 were included in this randomized controlled study. One kidney from each donor was randomly assigned to MP and the contralateral kidney was assigned to CS. Delayed graft function (DGF) rate, resistance index of renal arteries, early renal function, and survival rates were used to estimate the effect of preservation. The results showed that MP decreased the rate of DGF from 33.3 to 22.0% (P = 0.033). Ultrasound of the kidneys within 48 h after transplantation showed that the resistance index of renal main artery (0.673 ± 0.063 vs. 0.793 ± 0.124, P < 0.001), sub segmental artery (0.66 ± 0.062 vs. 0.764 ± 0.077, P < 0.001) and interlobular artery (0.648 ± 0.056 vs. 0.745 ± 0.111, P = 0.023) were all significantly lower in the MP group than those in the CS group. Furthermore, compared to the CS group, in the first 7 days following transplantation, the median urine volume was significantly higher (4080 mL vs. 3000 mL, P = 0.047) in kidneys sustained using MP and the median serum creatinine was remarkably lower (180 µmol/L vs. 390 µmol/L, P = 0.024). More importantly, MP group had higher 1- and 3-year graft survival rates (98% vs. 93%, P = 0.026; 93% vs. 82%, P = 0.036, respectively). Hypothermic MP improved the outcomes of DCD kidney transplantation.
Background With the advancement of the world population aging, more attention should be paid to the prognosis of elderly patients with acute coronary syndrome (ACS). Triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance (IR) and is closely related to traditional risk factors of cardiovascular disease (CVD). However, the effect of TyG index on the prognosis of long-term adverse events in elderly ACS patients has not been reported. This study evaluated the prognostic power of TyG index in predicting adverse events in elderly ACS patients. Methods In this study, 662 ACS patients > 80 years old who were hospitalized from January 2006 to December 2012 were enrolled consecutively and the general clinical data and baseline blood biochemical indicators were collected. The follow-up time after discharge was 40–120 months (median, 63 months; interquartile range, 51‒74 months). In addition, the following formula was used to calculate the TyG index: Ln [fasting TG (mg/dL) × FBG (mg/dL)/2], and patients were divided into three groups according to the tertile of the TyG index. Results The mean age of the subjects was 81.87 ± 2.14 years, the proportion of females was 28.10%, and the mean TyG index was 8.76 ± 0.72. The TyG index was closely associated with the traditional risk factors of CVD. In the fully-adjusted Cox regression model, the Hazard ratio (95% CI) of all-cause mortality (in tertile 3) was 1.64 (1.06, 2.54) and major adverse cardiac event (MACE) (in tertile 3) was 1.36 (1.05, 1.95) for each SD increase in the TyG index. The subgroup analyses also confirmed the significant association of the TyG index and long-term prognosis. Conclusion The TyG index is an independent predictor of long-term all-cause mortality and MACE in elderly ACS patients.
Hypothermic machine perfusion (MP) can reduce graft's injury after kidney transplantation; however, the mechanism has not been elucidated. In the past decade, many studies showed that aldehyde dehydrogenase 2 (ALDH2) is a protease which can inhibit cell apoptosis. Therefore, this study aims to explore whether ALDH2 takes part in reducing organ damage after MP. Eighteen healthy male New Zealand rabbits (12 weeks old, weight 3.0 ± 0.3 kg) were randomly divided into three groups: normal group, MP group, and cold storage (CS) group (n = 6). The left kidney of rabbits underwent warm ischemia for 35 min through clamping the left renal pedicle and then reperfusion for 1 h. Left kidneys were preserved by MP or CS (4°C for 4 h) in vivo followed by the right nephrectomy and 24-h reperfusion, and then the specimens and blood were collected. Finally, concentration of urine creatinine (Cr), blood urea nitrogen (BUN), and 4-HNE were tested. Renal apoptosis was detected by TUNEL staining, and the expression of ALDH2, cleaved-caspase 3, bcl-2/ bax, MAPK in renal tissue was detected by immunohistochemistry or Western blot; 24 h after surgery, the concentration of Cr in MP group was 355 ± 71μmol/L, in CS group was 511 ± 44 μmol/L (P < 0.05), while the BUN was 15.02 ± 2.34 mmol/L in MP group, 22.64 ± 3.58 mmol/L in CS group (P < 0.05). The rate of apoptosis and expression of cleaved caspase-3, p-P38, p-ERK, and p-JNK in MP group was significantly lower than that in CS group (P < 0.05), while expression of ALDH2 and bcl-2/bax in MP group was significantly higher than that in CS group (P < 0.05); expression of cleaved caspase-3 in both MP and CS group significantly increased as compared with that in normal group (P < 0.05). In conclusion, increased expression of ALDH2 can reduce the renal cell apoptosis through inhibiting MAPK pathway during ischemia/reperfusion injury (IRI) after hypothermic MP.
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.