Skeletal muscle atrophy occurs under various conditions, such as disuse, denervation, fasting, aging, and various diseases. Although the underlying molecular mechanisms are still not fully understood, skeletal muscle atrophy is closely associated with reactive oxygen species (ROS) overproduction. In this study, we aimed to investigate the involvement of ROS in skeletal muscle atrophy from the perspective of gene regulation, and further examine therapeutic effects of antioxidants on skeletal muscle atrophy. Microarray data showed that the gene expression of many positive regulators for ROS production were up-regulated and the gene expression of many negative regulators for ROS production were down-regulated in mouse soleus muscle atrophied by denervation (sciatic nerve injury). The ROS level was significantly increased in denervated mouse soleus muscle or fasted C2C12 myotubes that had suffered from fasting (nutrient deprivation). These two muscle samples were then treated with N-acetyl-L-cysteine (NAC, a clinically used antioxidant) or pyrroloquinoline quinone (PQQ, a naturally occurring antioxidant), respectively. As compared to non-treatment, both NAC and PQQ treatment (1) reversed the increase in the ROS level in two muscle samples; (2) attenuated the reduction in the cross-sectional area (CSA) of denervated mouse muscle or in the diameter of fasted C2C12 myotube; (3) increased the myosin heavy chain (MHC) level and decreased the muscle atrophy F-box (MAFbx) and muscle-specific RING finger-1 (MuRF-1) levels in two muscle samples. Collectively, these results suggested that an increased ROS level was, at least partly, responsible for denervation- or fasting-induced skeletal muscle atrophy, and antioxidants might resist the atrophic effect via ROS-related mechanisms.

Skeletal muscle atrophy is associated with pro-inflammatory cytokines. Salidroside is a biologically active ingredient of Rhodiola rosea, which exhibits anti-inflammatory property. However, there is little known about the effect of salidroside on denervation-induced muscle atrophy. Therefore, the present study aimed to determine whether salidroside could protect against denervation-induced muscle atrophy and to clarify potential molecular mechanisms. Denervation caused progressive accumulation of inflammatory factors in skeletal muscle, especially interleukin 6 (IL6) and its receptor, and recombinant murine IL6 (rmIL6) local infusion could induce target muscle atrophy, suggesting that denervation induced inflammation in target muscles and the inflammation may trigger muscle wasting. Salidroside alleviated denervation-induced muscle atrophy and inhibited the production of IL6. Furthermore, the inhibition of phosphorylation of signal transducer and activator of transcription 3 (STAT3), and the decreased levels of suppressor of cytokine signaling (SOCS3), muscle RING finger protein-1 (MuRF1), atrophy F-box (atrogin-1), microtubule-associated protein light chain 3 beta (LC3B) and PTEN-induced putative kinase (PINK1) were observed in denervated muscles that were treated with salidroside. Finally, all of these responses to salidroside were replicated in neutralizing antibody against IL6. Taken together, these results suggest that salidroside alleviates denervation-induced inflammation response, thereby inhibits muscle proteolysis and muscle atrophy. Therefore, it was assumed that salidroside might be a potential therapeutic candidate to prevent muscle wasting.

An increasing body of scientific literature suggests that dietary components may exert cancer preventive effects. Tea, soy, cruciferous vegetables and other foods have been investigated for their cancer preventive potential. Some non-edible mushrooms like Reishi (Ganoderma lucidum) have a history use, both alone and in conjunction with standard therapies, for the treatment of various diseases including cancer in some cultures. They have shown efficacy in a number of scientific studies. By comparison, the potential cancer preventive effects of edible mushrooms have been less well-studied. With similar content of putative effective anticancer compounds such as polysaccharides, proteoglycans, steroids, etc., one might predict that edible mushrooms would also demonstrate anticancer and cancer preventive activity. In this review, available data for five commonly-consumed edible mushrooms: button mushrooms (Agaricus bisporus), A. blazei, oyster mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinus edodes), and maitake (Grifola frondosa) mushrooms is discussed. The results of animal model and human intervention studies, as well as supporting in vitro mechanistic studies are critically evaluated. Weaknesses in the current data and topics for future work are highlighted.

Ferroptosis is a newly discovered form of regulated cell death dependent on iron and reactive oxygen species (ROS). It directly or indirectly affects the activity of glutathione peroxidases (GPXs) under the induction of small molecules, causing membrane lipid peroxidation due to redox imbalances and excessive ROS accumulation, damaging the integrity of cell membranes. Ferroptosis is mainly characterized by mitochondrial shrinkage, increased density of bilayer membranes, and the accumulation of lipid peroxidation. Myocardial ischemia-reperfusion injury (MIRI) is an unavoidable risk event for acute myocardial infarction. Ferroptosis is closely associated with MIRI, and this relationship is discussed in detail here. This review systematically summarizes the process of ferroptosis and the latest research progress on the role of ferroptosis in MIRI to provide new ideas for the prevention and treatment of MIRI.

Glioma is the most lethal type of primary brain tumor characterized by aggressiveness and a poor prognosis. Histone deacetylase 4 (HDAC4) is frequently dysregulated in human malignancies. However, its biological functions in the development of glioma are not fully understood. The present study aimed to evaluate HDAC4 expression in human glioma and to elucidate the mechanistic role of HDAC4 in glioma. The results suggested that HDAC4 was significantly upregulated in glioma tissues and a number of glioma cell lines compared with adjacent non-tumor tissues and the non-cancerous human glial cell line SVG p12, respectively (P<0.05). The proliferation, adenosine triphosphate (ATP) levels and invasion ability were substantially enhanced in U251 cells with HDAC4 overexpression, and suppressed in U251 cells with a knockdown of HDAC4 compared with that in U251 cells transfected with the negative control. Knockdown of HDAC4 resulted in cell cycle arrest at the G0/G1 phase and induced the increase of reactive oxygen species level in U251 cells. Furthermore, HDAC4 overexpression was revealed to substantially inhibit the expression of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and the expression of E-cadherin and β-catenin in glioma U251 cells. Knockdown of HDAC4 substantially promoted the expression of CDK1 and CDK2 and vimentin in glioma U251 cells. Mechanistically, the results of the present study demonstrated that HDAC4 displayed a significant upregulation in glioma, and promoted glioma cell proliferation and invasion mediated through the repression of p21, p27, E-cadherin and β-catenin, and the potentiation of CDK1, CDK2 and vimentin. Altogether, the present study revealed that HDAC4 overexpression was central for the tumorigenesis of glioma, which may serve as a useful prognostic biomarker and potential therapeutic target for glioma.

6-Gingerol (6-G) is known to alleviate myocardial ischemia/reperfusion injury. However, the underlying molecular mechanisms of 6-G myocardial protection are not known. In this study, the protective effect of 6-G on ischemia/reperfusion (I/R) damage and whether such a mechanism was related to apoptosis inhibition and activation of phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (Akt) signaling pathway were investigated. Rats were subjected to I/R in the presence or absence of 6-G and the changes of cardiac function, infarct size and histopathological changes, and the levels of cardiac troponin T, creatine kinase-MB, and myocardial apoptosis were examined. The expression of caspase-3, PI3K, p-Akt, and Akt was also determined. We found that 6-G (6 mg/kg) pretreatment significantly improved heart function and ameliorated infarct size and histopathological changes and cardiac troponin T and creatine kinase-MB levels induced by I/R. Moreover, pretreatment with 6-G significantly inhibited myocardial apoptosis and caspase-3 activation induced by I/R. 6-G also upregulated expression of PI3K, p-Akt, and Akt in myocardial tissues. Taken together, these findings suggest that 6-G inhibits apoptosis and activates PI3K/Akt signaling in response to myocardial I/R injury as a possible mechanism to attenuate I/R-induced injury in heart. These results might be important for developing novel strategies for preventing myocardial I/R injury.

Our previous study has demonstrated that 6-Gingerol (6-G) could alleviate myocardial ischemia/reperfusion injury (MIRI). However, the molecular mechanism underlying the process of myocardial ischemia/reperfusion (I/R) injury alleviation by 6-G remains unelucidated. The objective of the present study is to further investigate the potential mechanism for 6-G to alleviate MIRI in rats. Thirty-two Sprague-Dawley rats were randomly divided into four groups: the Sham group, the I/R group, the 6-G + I/R group, and the LY294002 (LY) + 6-G + I/R group. For the rats in each of the groups, data were collected for cardiogram, cardiac function, area of myocardial infarction, myocardial pathology, myocardial enzyme, marker of inflammatory response, and PI3K/Akt signaling pathway. We found that the pretreatment of 6-G with 6 mg/kg could shrink the ST section of cardiogram, improve the cardiac function, reduce the area of myocardial infarction and the degree of cardiac pathological injury, lower the level of myocardial enzyme, and inhibit the inflammatory response. In addition, our results also indicated that 6-G could upregulate the expression of PI3K and p-Akt and that LY294002, a blocking agent of PI3K/Akt signaling pathway, could nullify the protecting role of 6-G. Our experimental results showed that 6-G could inhibit I/R-induced inflammatory response through the activation of the PI3K/Akt signaling pathway.

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