Under the hypoxic condition, organs or cells trigger a series of reactions or responses to adapt to the physiological requirement. These responses involve a complex regulation at different levels from organs, in particular the kidney (producing erythropoietin), to cells throughout the body. Actually, the responses to hypoxia from adaption to injury largely depend on the degree and time of hypoxia. In the past two decades, with the discovery of hypoxia-inducible factor (HIF), the mechanisms of erythropoiesis regulation were elucidated gradually, which has provided a novel therapeutic strategy for hypoxia-related diseases, especially renal anemia. In this review we focus on the latest advances in oxygen sensing and adaptive mechanism.

Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.

The aim of the present study was to investigate the role of chemokine CCL2 in angiogenesis of primary adult rat cardiac microvascular endothelial cells (CMEC). The rat CMECs were isolated and identified through morphology examination and immunostaining with CD31 and factor VIII antibodies. The angiogenesis of CMEC on Matrigel was evaluated at different time points. The expression and secretion of CCL2 during the process of angiogenesis was detected by real-time RT-PCR and ELISA, respectively. The results showed that, the primary rat CMEC was isolated successfully, and the angiogenesis of CMEC was significantly induced after Matrigel treatment for 4 h. The expression of CCL2 and CCR2 were increased during angiogenesis, and the secretion of CCL2 was detected after 2 h of angiogenesis and reached the peak concentration of 1 588.1 pg/mL after 4 h. Either CCL2 blocking antibody or CCR2 antagonist significantly reduced the angiogenesis of CMEC. These results suggest that CCL2 is secreted during the process of angiogenesis of CMEC, and CCL2/CCR2 signaling pathway may play an important role in promoting angiogenesis.

Stress is the non-specific systemic response that occurs when the body is stimulated by various factors, and it can affect multiple systems of the body. Recent studies have shown that gut microbiota is an essential part of human microecology, and plays a pivotal role in keeping the body healthy. Stress can result in gut dysbiosis by affecting the function of intestinal mucosal barrier, intestinal immune and gastrointestinal motility. This article reviewed the alteration of gut microbiota caused by stress and the possible mechanisms involved.

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.

Growth hormone (GH), as a vital hormone, has to experience a series of processes to fulfill its function including secretion, entering the circulation to reach target tissues (pre-receptor process), binding on the GH receptor (GHR) and triggering signaling inside cells (post-GHR process). Insulin can directly or indirectly influence part of these processes. GH secretion from pituitary somatotropes is regulated by GH-releasing hormone (GHRH) and somatostatin (SS) from hypothalamus. Insulin may exert positive or negative effects on the neurons expressing GHRH and SS and somatotropes under healthy and pathological conditions including obesity and diabetes. Glucose and lipid levels in circulation and dietary habits may influence the effect of insulin on GH secretion. Insulin may also affect GHR sensitivity and the level of insulin-like growth factor 1 (IGF-1), thus influence the level of GH. The GH signaling is also important for GH to play its role. GH signaling involves GHR/JAK2/STATs, GHR/JAK2/SHC/MAPK and GH/insulin receptor substrate (IRS)/PI3K/Akt pathways. These pathways may be shared by insulin, which is the basis for the interaction between insulin and GH, and insulin may attenuate or facilitate the GH signal by influencing molecules in the pathways. Many factors are related to the effect of insulin, among them the most important ones are duration of action and amount of insulin. The tendency of insulin-reduced GH signaling becomes obvious with increased dose and acting time of insulin. The participation of suppressor of cytokine signaling (SOCS), the interaction between JAK2 and IRS, and GHR sensitivity should also be considered when discovering GH signal. The involvement of SS in response to insulin is not clear yet. The details of how GH secretion, level and signaling change in response to time and dose of insulin treatment warrant further studies.

The incidence and mortality rates of diabetes with cardiovascular complications are continually rising, and diabetic cardiovascular disease is becoming a major public health issue that threatens human health. Acute endothelial dysfunction and chronic cellular damage caused by diabetes are important risk factors for diabetic cardiovascular disease and related mortality. Adiponectin is an adipocyte-derived molecule with significant cytoprotective effects, including the protection against diabetes-induced vascular endothelial injury. Here we review the mechanisms of adiponectin protective effects on acute vascular endothelial dysfunction and chronic structural damage induced by diabetes.