Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation.

Pathogenic gut microbiota is responsible for a few debilitating gastrointestinal diseases. While the host immune cells do produce extracellular vesicles to counteract some deleterious effects of the microbiota, the extracellular vesicles are of insufficient doses and at unreliable exposure times. Here we use mechanical stimulation of hydrogel-embedded macrophage in a bioelectronic controller that on demand boost production of up to 20 times of therapeutic extracellular vesicles to ameliorate the microbes' deleterious effects in vivo. Our miniaturized wireless bioelectronic system termed inducible mechanical activation for in-situ and sustainable generating extracellular vesicles (iMASSAGE), leverages on wireless electronics and responsive hydrogel to impose mechanical forces on macrophages to produce extracellular vesicles that rectify gut microbiome dysbiosis and ameliorate colitis. This in vivo controllable extracellular vesicles-produced system holds promise as platform to treat various other diseases.

Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Distribution of coronal plane alignment of the knee classification in Chinese osteoarthritic and healthy population: a retrospective cross-sectional observational study.

BACKGROUND: Few studies have reported the coronal constitutional alignment of the lower limbs in mainland China. This study aimed to analyse the distribution of the coronal plane alignment of the knee (CPAK) classification in the osteoarthritic (OA) and healthy Chinese populations. MATERIALS AND METHODS: The CPAK distributions of 246 patients (477 knees) with OA and 107 healthy individuals (214 knees) were retrospectively examined using long-leg radiographs. Radiological measurements and CPAK classification of different Kellgren-Lawrence grades in patients with unilateral total knee arthroplasty (TKA) were compared. The clinical outcomes of patients with CPAK type I who underwent mechanical alignment or restricted kinematic alignment during TKA were examined. RESULTS: The most common distributions in the OA and healthy groups were type I and type II, respectively. In patients who underwent unilateral TKA, the most common distribution of knees graded as Kellgren-Lawrence 3-4 was type I. However, the most common distributions of contralateral knees graded as Grade 0-2 were type I and II. For patients with CPAK type I, the mechanical alignment and restricted kinematic alignment groups did not differ significantly concerning postoperative clinical outcomes at 3 months. CONCLUSION: The most common distributions in Chinese osteoarthritic and healthy populations were types I and II, respectively. In addition, OA progression may lead to changes in the CPAK classification.