Backgroud Icariin, a major bioactive pharmaceutical component of the Chinese herbal medicine Epimedii Herba, has demonstrated lipid-lowering and anti-obesity effects. Irisin/ fibronectin type III domain-containing 5 (FNDC5) protects against obesity by inducing browning in white adipose tissue. Objectives This study investigated the effects of icariin on irisin/FNDC5 expression in C2C12 myotubes. Method Cultured murine C2C12 myocytes were used to study the effects of icariin on irisin/FNDC5 expressions by Western-blot, qPCR, Elisa and Immunofluorescence. We also investigated FNDC5 expression in icariin-treated intact mice. Results Icariin increased irisin/FNDC5 protein levels. mRNA levels of irisin/FNDC5 were also increased in C2C12 myocytes after treatment with icariin. Icariin increased peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α) protein and mRNA levels. Additionally, icariin exposure resulted in phosphorylation of AMP-activated protein kinase (AMPK) in a dose-dependent manner. The regulatory effect of icariin on FNDC5 protein expression was blocked by the AMPK antagonist compound C or silencing of AMPK, suggesting that icariin increased FNDC5 protein expression via the AMPK pathway. In vivo, icariin decreased body weight gain in C57BL/6 mice and increased FNDC5, PGC-1α, and p-AMPK expression levels in skeletal muscle. Conclusions Taken together, our results indicated that icariin induces irisin/FNDC5 expression via the AMPK pathway, indicating that icariin may be promising as an anti-obesity drug.

Migrasomes are migration‐dependent membrane‐bound vesicular structures that contain cellular contents and small vesicles. Migrasomes grow on the tips or intersections of the retraction fibers after cells migrate away. The process of releasing migrasomes into the extracellular space is named as “migracytosis”. After releasing, they can be taken up by the surrounding cells, or rupture and further release their contents into the extracellular environment. Physiologically, migrasomes provide regional cues for organ morphogenesis during zebrafish gastrulation and discard the damaged mitochondria in response to mild mitochondrial stresses. Pathologically, migrasomes are released from podocyte during early podocyte stress and/or damage, from platelets after infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), from microglia/macrophages of the ischemic brain, and from tumor necrosis factor α (TNFα)‐activated endothelial cells (ECs); thus, this newly discovered extracellular vesicle is involved in all these pathological processes. Moreover, migrasomes can modulate the proliferation of cancer cell via lateral transferring mRNA and protein. In this review, we will summarize the biogenesis, release, uptake, and rupture of migrasomes and discuss its biological roles in development, redox signalling, innate immunity and COVID‐19, cardio‐cerebrovascular diseases, renal diseases, and cancer biology, all of these highlight the importance of migrasomes in modulating body homeostasis and diseases.

Background: Perivascular adipose tissue (PVAT) can regulate vascular homeostasis by secreting various adipokines. This study investigated the effects of PVAT browning on its endocrine function. Methods: In the first section of our study, male Sprague-Dawley rats were randomly divided into cold exposure (8°C) and 24°C acclimation groups. After cold exposure for 7 days, interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue, thoracic aortic PVAT, and abdominal aortic PVAT (aPVAT) were harvested for histological and brown marker gene expression analysis. In the second part, male rats were fed a high fat diet (HFD) for 10 weeks. In the 11th week, the rats were treated with or without cold exposure. After 14-day cold exposure, aPVAT was collected for histological, gene, and protein expression analysis. Results: Cold exposure had a browning effect on aPVAT by increasing UCP-1 and PGC-1α expression levels. After HFD feeding for 10 weeks, 14-day cold exposure was still able to induce aPVAT browning. Compared with thermoneutrality acclimation rats, TNF-α, IL-6, and p-p65 expression levels were significantly lower in aPVAT from HFD-fed rats with cold exposure. In contrast, p-AMPK expression levels were increased in aPVAT from HFD-fed rats with cold exposure. Conclusions: Our study demonstrated that browning of aPVAT in HFD-fed rats lowered the pro-inflammatory adipokine expression levels and activated AMPK.

The protective effects of ilexsaponin A on ischemia-reperfusion-induced myocardial injury were investigated. Myocardial ischemia/reperfusion model was established in male Sprague–Dawley rats. Myocardial injury was evaluated by TTC staining and myocardial marker enzyme leakage. The in vitro protective potential of Ilexsaponin A was assessed on hypoxia/reoxygenation cellular model in neonatal rat cardiomyocytes. Cellular viability and apoptosis were evaluated by MTT and TUNEL assay. Caspase-3, cleaved caspase-3, bax, bcl-2, p-Akt and Akt protein expression levels were detected by western-blot. Ilexsaponin A treatment was able to attenuate the myocardial injury in ischemia/reperfusion model by reducing myocardial infarct size and lower the serum levels of LDH, AST and CK-MB. The in vitro study also showed that ilexsaponin A treatment could increase cellular viability and inhibit apoptosis in hypoxia/reoxygenation cardiomyocytes. Proapoptotic proteins including caspase-3, cleaved caspase-3 and bax were significantly reduced and anti-apoptotic protein bcl-2 was significantly increased by ilexsaponin A treatment in hypoxia/reoxygenation cardiomyocytes. Moreover, Ilexsaponin A treatment was able to increase the expression levels of p-Akt in hypoxia/reoxygenation cellular model and myocardial ischemia/reperfusion animal model. Coupled results from both in vivo and in vitro experiments indicate that Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway.

Alcoholic liver disease (ALD), which is induced by chronic heavy alcohol consumption, accompanies complicated pathological mechanisms, including oxidative stress, inflammation, cell death, epigenetic changes and acetaldehyde-mediated toxicity. Hydrogen (H₂) is the lightest gas with multiple biological effects such as high selective anti-oxidation, anti-inflammation and anti-apoptosis. However, the dose effects and innate immune mechanisms of intraperitoneal injection of H₂ on ALD are limited. Here, we used acute ethanol-induced hepatotoxicity mice models to estimate the actions of intraperitoneal injection of H₂ on ALD. The effects of H₂ on acute ethanol-induced liver damage were examined by hepatic oil red O staining, quantitative PCR (qPCR) for lipid metabolic genes, hepatic triglyceride (TG) and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Hepatic mitochondrial superoxide (MitoSOX), 3-nitrotyrosine (3-NT), malondialdehyde (MDA), and glutathione (GSH) levels were examined to evaluate oxidative stress. Immunoblot, and immunofluorescence staining were used to further confirm the innate immune molecular targets of H₂. Our results showed that intraperitoneal injection of H₂ improved acute ethanol-induced liver injury in mice in a dose dependent manner, as indicated by decreasing serum ALT and AST levels, hepatic TG levels, and increasing lipid export genes (Mttp and Apob) mRNA levels and reducing fatty acid uptake gene (CD36) mRNA levels. Mechanistically, H₂ inhibited hepatic oxidative stress as indicated by reducing reactive oxygen species (ROS), 3-NT, and MDA levels in the liver, while increasing hepatic GSH levels; inhibited the overactived TLR4/9-NF-κB-TNF-α/IL-1β/IL-18 innate immune signaling; suppressed the canonical Caspase-1-GSDMD pyroptosis signaling, and the non-canonical pyroptosis signaling, such as Caspase-11-GSDMD, Caspase-8-GSDMD and Caspase-3-GSDME signaling. Therefore, our study highlights that intraperitoneal injection of H₂ may represent a novel therapeutic and safe strategy for ALD via modulating oxidative stress, innate immunity and pyroptosis.

Sex is a science of cutting edge but bathed in mystery. Coitus or sexual intercourse, which is at the core of sexual activities, requires healthy and functioning vessels to supply the pelvic region, thus contributing to clitoris erection and vaginal lubrication in female and penile erection in male. It is well known that nitric oxide (NO) is the main gas mediator of penile and clitoris erection. In addition, the lightest and diffusible gas molecule hydrogen (H₂) has been shown to improve erectile dysfunction (ED), testis injuries, sperm motility in male, preserve ovarian function, protect against uterine inflammation, preeclampsia, and breast cancer in female. Mechanistically, H₂ has strong abilities to attenuate excessive oxidative stress by selectively reducing cytotoxic oxygen radicals, modulate immunity and inflammation, and inhibit injuries‐induced cell death. Therefore, H₂ is a novel bioactive gas molecule involved in modulating sexual organs homeostasis.