Cancer cachexia is a multifactorial syndrome defined by progressive loss of body weight with specific depletion of skeletal muscle and adipose tissue. Since there are no FDA-approved drugs that are available, nutritional intervention is recommended as a supporting therapy. Creatine supplementation has an ergogenic effect in various types of sports training, but the regulatory effects of creatine supplementation in cancer cachexia remain unknown. In this study, we investigated the impact of creatine supplementation on cachectic weight loss and muscle loss protection in a tumor-bearing cachectic mouse model, and the underlying molecular mechanism of body weight protection was further assessed. We observed decreased serum creatine levels in patients with cancer cachexia, and the creatine content in skeletal muscle was also significantly decreased in cachectic skeletal muscle in the C26 tumor-bearing mouse model. Creatine supplementation protected against cancer cachexia-associated body weight loss and muscle wasting and induced greater improvements in grip strength. Mechanistically, creatine treatment altered the dysfunction and morphological abnormalities of mitochondria, thus protecting against cachectic muscle wasting by inhibiting the abnormal overactivation of the ubiquitin proteasome system (UPS) and autophagic lysosomal system (ALS). In addition, electron microscopy revealed that creatine supplementation alleviated the observed increase in the percentage of damaged mitochondria in C26 mice, indicating that nutritional intervention with creatine supplementation effectively counteracts mitochondrial dysfunction to mitigate muscle loss in cancer cachexia. These results uncover a previously uncharacterized role for creatine in cachectic muscle wasting by modulating cellular energy metabolism to reduce the level of muscle cell atrophy.

Exhaustive exercise has emerged as an important health issue nowadays. This study was designed to assess the metabolite abnormalities of rats after exhaustive exercise and the holistic efficacy of Chinese medicine Sanqi oral solution (SQ). Through exhaustive swimming, the exhaustive exercise model in rats was established. Thirty male Sprague-Dawley rats were randomly divided into control, model, and treatment groups. SQ (12 mL·kg-1·d-1) or 0.9% saline solution was administrated orally by gastric gavage. After 4 weeks, serum samples were collected for biochemical measurements and ultra performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF-MS)-based metabonomic study. It was found that rats with SQ intervention showed longer exhaustive swimming time (P < 0.05) than model rats, with an average of 1,160.36 ± 123.89 s in SQ group and 906.57 ± 172.11 s in model group. Among the biochemical indices, the levels of creatine kinase isoenzyme, lactate dehydrogenase, and glucose of exhaustive exercise rats increased, whereas levels of creatine kinase, urea, triglyceride, and total cholesterol decreased. These biochemical indices came normal after SQ administration, except for triglyceride. Twenty-seven potential biomarkers belonging to sphingolipids, phospholipids, fatty acids, amino acid, and other classes were identified in serum. This study indicated that SQ exerted protective effects on exhaustive exercise by significantly prolonging the swimming endurance time. The metabonomic-based findings of the metabolic state and analysis of potential biomarkers in serum well correlated with biochemical assessment, confirming that SQ had a definite efficacy. Moreover, the shifts in lipid-related metabolites and glycolytic pathway suggested that SQ may serve as a potential supplementation in sports nutrition for its pharmacological effect of regulating energy metabolism as well as improving signal transduction and muscle-cell physiological functions.

Since CdSe quantum dots (QDs) are increasingly used in electronics, medical, and pharmaceutical science due to their excellent optical properties, it is necessary to carry out thorough and systematic studies on their biosafety. Numerous studies have reported the toxicity of QDs on liver, kidney, immune system, and reproductive system. However, few studies have been done on the cardiotoxicity of QDs. In this study, we administered carboxylated CdSe/ZnS QDs in BALB/c mice via the tail vein and analyzed the in vivo cardiotoxicity of CdSe/ZnS QDs. The body weight, hematology, serum biochemistry, histology, heart elements concentration, echocardiography, and heart oxidative stress markers were carried out at different time. There were no significant differences in body weight and heart organ index between QDs group and the control group. Hematology results showed the platelet (PLT) counts on Day 1 and Day 42 in both high dose QDs group and low dose QDs group, and the PLT counts on Day1 in the high dose group were significantly higher than that in control group. Serum biochemistry results showed that lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase isoenzyme (CK-MB) of mice exposed to CdSe/ZnS QDs were significantly higher than that of the control group on Day 1, and CK-MB levels still remained high on Day 7. A higher concentration of Cd was observed in the heart of CdSe/ZnS QDs exposed mice on Day 42, whereas no Cd was detected in the control group, which suggested that QDs can accumulate in heart. No significant histopathological changes and cardiac function were observed in all mice at different time after treatment. Increased level of glutathione peroxidase (GPx) and malondialdehyde (MDA) was observed in mice administered with high dose QDs on Day 1, and increased level of total antioxidant capacity (T-AOC) and MDA activities was observed on Day 42. These results indicated that CdSe/ZnS QDs could accumulate in heart, cause some biochemical indicators change, induce oxidative damage, and have cardiotoxicity. Our findings might provide valuable information on the biological safety evaluation of the cardiovascular system of QDs.

8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.

Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (ΔΨm) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1α to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1α/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.