Spexin (SPX), a recently identified adipokine, shows potential in enhancing insulin sensitivity, offering promising implications for metabolic health. This study aimed to investigate the effect of 8 weeks of high intensity interval training (HIIT) on insulin resistance through liver gluconeogenesis, lipolysis, inflammation, oxidative stress, and lipogenesis in Type 2 diabetic rats with a special focus on the role of SPX. In this study, 28 male Wistar rats were divided into four groups: Healthy Control (CON), Diabetes Control (T2D), HIIT, and Diabetes+HIIT (T2D+HIIT). After diabetes induction (high-fat diet+streptozotocin), the exercise groups underwent an 8-week HIIT protocol. HOMA-β, HOMA-IR, QUICKI, fasting blood sugar, insulin, and SPX were measured in liver and serum. The expression of Galanin/2, FOXO-1, PGC-1α, G6Pase, PEPCK, CPT1A, AMPK, PPARα, ACC, FAS, SREBP-1c, SIRT-1, and inflammatory/antioxidant markers were analyzed in the liver. Our results showed that HOMA-β, QUICKI, insulin, and serum level of SPX levels were higher in T2D+HIIT than T2D group. Similarly, SPX, GALR2, FOXO-1, PGC-1α, CPT1A, PPARα, AMPK, and SIRT-1 levels were higher in the livers of rats in the T2D+HIIT than T2D group. However, HOMA-IR, PEPCK, G6Pase, ACC, FAS, and SREBP-1c levels were lower in T2D+HIIT than T2D group. Also, HIIT+T2D reduced inflammation and increased antioxidants, indicating an improved overall health status of the liver. HIIT benefits diabetic liver with reducing gluconeogenesis, inflammation, oxidative stress, and lipogenesis while increasing lipolysis. These improvements coincided with elevated hepatic SPX signaling and are associated with reduced insulin resistance. These findings suggest a potential association between HIIT induced SPX signaling modulation in liver and improving insulin resistance, though further mechanistic studies are required to confirm the causality.

Addressing cognitive impairment (CI) represents a significant global challenge in health and social care. Evidence suggests that aging and metabolic disorders increase the risk of CI, yet promisingly, physical exercise has been identified as a potential ameliorative factor. Specifically, there is a growing understanding that exercise-induced cognitive improvement may be mediated by molecules known as exerkines. This review delves into the potential impact of aging and metabolic disorders on CI, elucidating the mechanisms through which various exerkines may bolster cognitive function in this context. Additionally, the discussion extends to the role of exerkines in facilitating stem cell mobilization, offering a potential avenue for improving cognitive impairment.

One of the most common causes of global death is cardiovascular disease (CVD). Using mesenchymal stem cell (MSC) therapy for treating CVDs is revolutionizing regenerative medicine. Some challenges that have limited MSC therapy’s practical application include cell harvesting difficulty, ectopic transplantation, spontaneous differentiation to cartilage and bone, and possible immune responses following transplantation. MSCs release extracellular vesicles and biologically active molecules such as growth factors, chemokines, and cytokines, collectively called the secretome. Recent studies have shown that secretome administration could replace MSC transplantation. The secretome of MSCs plays a crucial role in controlling inflammatory reactions, enhancing tissue reperfusion by stimulating angiogenesis and vasculogenesis, preventing apoptosis and fibrosis development, and fostering the proliferation and differentiation of cardiac stem cells. This review discusses the current knowledge of MSC secretome application in cardiac regenerative medicine. It introduces possible approaches to improve cardiac recovery outcomes by utilizing the secretome in the clinic.

Peripheral nerve tissue engineering is a field that uses cells, growth factors and biological scaffold material to provide a nutritional and physical support in the repair of nerve injuries. The specific properties of injectable human amniotic membrane-derived hydrogel including growth factors as well as anti-inflammatory and neuroprotective agents make it an ideal tool for nerve tissue repair, and metformin may also aid in nerve regeneration. The aim of this study was to investigate the effects of hydrogel derived from amniotic membrane (AM) along with metformin (MET) administration in the repair of sciatic nerve injury in male rats. We randomly divided 60 male rats into five groups. A control and four sciatic nerve compression groups including model; hydrogel; metformin and mix which received hydrogel and metformin. The recovery rate was assessed by Sciatic Functional Index (SFI), Static Sciatic Index (SSI) and von-frey test. Conduction velocity of the sciatic nerve was measured by Electrophysiological studies, and histological evaluations were performed 14 days after injury. SFI, SSI, latency time, remyelination rate and the expression of NF-200 and S-100β improved in hydrogel group. Response to mechanical stimulus, myelin density, axonal regeneration, and myelin sheath reconstruction improved in the mix group. The gastrocnemius muscle index was significantly reduced in the experimental groups while collagen fibers increased in these groups. These findings suggest that injection of hydrogel derived from decellularized amniotic membrane into the epineurium can be promoted reconstruction of peripheral nerve injury and improved functional nerve recovery. Also, metformin administration can reinforce the therapeutic effect of the hydrogel.