Electroacupuncture attenuates ischemic injury after stroke and promotes angiogenesis via activation of EPO mediated Src and VEGF signaling pathways.

Although electroacupuncture (EA) has been shown to be effective in the treatment of stroke, its mechanisms of action remain undefined. This study explored the therapeutic effects of EA in rats with cerebral ischemia-reperfusion injury (CIRI) and evaluated its possible mechanisms in promoting angiogenesis. To evaluate the effect of EA, we used 2, 3, 5-Triphenyl-2H-Tetrazolium Chloride (TTC) staining and behavior score to calculate the cerebral infarct volume and neurological deficit score after CIRI. Western blot (WB) analysis was employed to evaluate the expression of cluster of differentiation 34 (CD34), erythropoietin (EPO), vascular endothelial growth factor (VEGF) and phospho-Src (p-Src) in the brain of the rats with CIRI. On the other hand, we established an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model using brain microvascular endothelial cells (BMECs), and analyzed cell viability and expression of VEGF or p-Src using cell counting kit-8 (CCK-8) and WB, respectively. Our data showed that EA at the GV26 acupoint could significantly promote the expression of CD34, EPO, VEGF and p-Src in CIRI rats. Our CCK-8 results demonstrated that intervention with recombinant EPO and VEGF proteins remarkably improved the viability of BMECs after OGD/R, while a Src inhibitor, PP1, reversed this phenotype. The WB results showed that the recombinant EPO protein increased the expression of VEGF and p-Src, which was significantly inhibited by PP1. Taken together, our findings showed that EA at the GV26 acupoint can significantly attenuate ischemic injury after stroke and promote angiogenesis via activation of EPO-mediated Src and VEGF signaling pathways. Besides, the upregulation of VEGF may also be associated with the activation of Src by EPO.

The effects of acupuncture on psychological symptoms in patients with insomnia: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a common sleep-related condition that includes dissatisfaction with sleep quality, difficulty in initiating or maintaining sleep, and early morning waking. Insomnia can affect daytime functioning by causing fatigue, depression, and anxiety. Medications are the most common method for the management of insomnia but can cause adverse effects, including psychological and physical dependence, residual daytime sedation, and cognitive impairment. Acupuncture is a common traditional Chinese therapy. It has been used in the treatment of insomnia, depression, and anxiety in China. However, there are no high-quality studies focusing on acupuncture for insomnia, especially for depression and anxiety due to insomnia. Therefore, we have designed a randomized controlled trial (RCT) involving a placebo control to ensure blinding of participants to investigate the effects of acupuncture on insomnia in improving sleep quality and psychosocial symptoms. METHODS: We have designed a single-center, parallel-group, single-blinded RCT. A total of 252 participants who meet the eligibility criteria will be randomly allocated into a manual acupuncture group or sham acupuncture group in a 1:1 ratio. All participants will receive 24 sessions of acupuncture (30 min per session, three sessions per week for 8 weeks). Participants will be assessed using the Pittsburgh Sleep Quality Index score, self-assessment anxiety scale, self-assessment depression scale, and Medical Outcomes Study 36-Item Short-Form Health Survey at baseline and 8 weeks. All analyses will be based on an intention-to-treat principle. The results will be published in an international peer-reviewed journal. DISCUSSION: The results of this study are expected to clarify the effects of acupuncture on sleep quality and psychosocial symptoms in patients with insomnia. This will contribute to the clinical practice of acupuncture in the management of insomnia. TRIAL REGISTRATION: Chinese Clinical Trail Registry ChiCTR2100049172 . Registered on 24 July 2021.

Cyanidin-3-O-ß-glucoside attenuates allergic airway inflammation by modulating the IL-4Rα-STAT6 signaling pathway in a murine asthma model.

Cyanidin-3-O-ß-glucoside (Cy-3-g), a typical and abundant monomer of anthocyanins, exhibits a variety of biological activities, such as anti-atherosclerosis, anti-obesity, and anticancer effects. However, to date little is known about its effects on asthma. This study aimed to investigate the efficacy of dietary Cy-3-g on allergic asthma in an animal model. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. The pathological changes of the lung tissues, type 2 helper (Th2)-associated cytokine production in bronchoalveolar lavage fluid (BALF), and the interleukin 4 receptor alpha (IL-4Rα)-signal transducer and activator of transcription 6 (STAT6) signaling pathway activities were assessed. We found that Cy-3-g significantly inhibited OVA-induced inflammatory cell infiltration and mucus hyper-production in lung tissues, reduced the production of interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 13 (IL-13) in BALF. Furthermore, Cy-3-g effectively suppressed OVA-induced up-regulation of the IL-4Rα-STAT6 signaling pathway activity of the lung tissues. These results demonstrated that dietary Cy-3-g could attenuate allergic airway inflammation in a murine asthma model, and Cy-3-g might be used as an agent for asthma prevention and/or treatment in the future.

Dihydromyricetin from ampelopsis grossedentata protects against vascular neointimal formation via induction of TR3.

Vine tea has been used as a medicinal herb in traditional Chinese medicine for hundreds of years. As the most abundant ingredient in vine tea, Dihydromyricetin (DHM) has been reported to exert anti-inflammatory, antioxidant, and anti-cardiovascular disease. However, the role of DHM in injury-induced neointimal formation remains poorly characterized. We determined the effects of DHM on ligation-induced carotid artery neointimal formation. We found that ligation-induced carotid artery neointimal formation could be significantly attenuated by DHM treatment. We provide evidence that DHM increases orphan nuclear receptor TR3 expression in smooth muscle cell (SMC) and carotid artery. Moreover, overexpression and loss-of-function strategies of TR3 were done to overexpression and knockdown of TR3, and demonstrate that DHM promotes SMC differentiation, however, inhibits SMC proliferation and migration, via regulating expression of TR3. Collectively, we reveal that DHM may be a therapeutic agent for the treatment of injury-induced vascular diseases.

Plant-based Food Cyanidin-3-Glucoside Modulates Human Platelet Glycoprotein VI Signaling and Inhibits Platelet Activation and Thrombus Formation.

Background: Platelets play an important role in hemostasis, thrombosis, and atherosclerosis. Glycoprotein VI (GPVI) is a major platelet receptor that interacts with exposed collagen on injured vessel walls. Our previous studies have shown that anthocyanins (a type of natural plant pigment) attenuate platelet function; however, whether anthocyanins affect collagen-induced GPVI signaling remains unknown.Objective: The objective of this study was to explore the effects of cyanidin-3-glucoside (Cy-3-g, one of the major bioactive compounds in anthocyanins) on platelet activation and thrombosis and the GPVI signaling pathway.Methods: Platelets from healthy men and women were isolated and incubated with different concentrations (0, 0.5, 5, and 50 µM) of Cy-3-g. The expression of activated integrin αIIbß3, P-selectin, CD63, and CD40L, fibrinogen binding to platelets, and platelet aggregation were evaluated in vitro. Platelet adhesion and aggregation in whole blood under flow conditions were assessed in collagen-coated perfusion chambers. Thrombosis and hemostasis were assessed in 3-4-wk-old male C57BL/6J mice through FeCl3-induced intravital microscopy and tail bleeding time. The effect of Cy-3-g on collagen-induced human platelet GPVI signaling was explored with Western blot.Results: Cy-3-g attenuated platelet function in a dose-dependent manner. The 0.5-µM dose of Cy-3-g inhibited (P < 0.05) human platelet adhesion and aggregation to collagen at both venous (-54.02%) and arterial (-22.90%) shear stresses. The 5-µM dose inhibited (P < 0.05) collagen-induced human platelet activation (PAC-1: -48.21%, P-selectin: -50.63%), secretion (CD63: -73.89%, CD40L: -43.70%), fibrinogen binding (-56.79%), and aggregation (-17.81%). The 5-µM dose attenuated (P < 0.01) thrombus growth (-66.67%) without prolonging bleeding time in mice. The 50-µM dose downregulated (P < 0.05) collagen-induced GPVI signaling in human platelets and significantly decreased phosphorylation of Syk-linker for activation of T cells (LAT)-SLP76 (Syk: -39.08%, LAT: -32.25%, SLP76: -40.00%) and the expression of Lyn (-31.89%), Fyn (-36.27%), and phospholipase C-γ2 (-39.08%).Conclusions: Cy-3-g inhibits human platelet activation, aggregation, secretion, and thrombus formation, and downregulates the collagen-GPVI signaling pathway. Supplementation of Cy-3-g may have protective effects against atherothrombosis.