The crude guava polysaccharides ameliorate high-fat diet-induced obesity in mice via reshaping gut microbiota.

Guava is a popular fruit consumed worldwide with beneficial effects in regulation of glucose and lipid metabolism. Although polysaccharides are a major phytochemical component of guava, to date, the alleviative effects of polysaccharides from the guava fruit against diet-induced obesity remain unclear. The relationship between the anti-obesity effects of guava polysaccharide (GP) and gut microbiota is unknown. In current study, seven-week-old C57BL/6 mice were fed high-fat diet (HFD) supplemented with GP (100 mg/kg) by oral gavage for 11 weeks. GP supplementation alleviated HFD-induced body weight gain and visceral obesity, and reduced serum cholesterol, triglyceride, and LDL-C levels. In addition, GP ameliorated insulin resistance and prevented hepatic lipid accumulation and meta-inflammation in both liver and adipose tissues in obese mice. Remarkably, GP treatment restored the Firmicutes/Bacteroidetes ratio, induced growth of beneficial bacteria including Clostridium XlVa, Parvibacter, and Enterorhabdus, and decreased in inflammation-related bacteria Mucispirillum in mice fecal samples, accompanied with enhanced production of colonic short chain fatty acids especially butyric acid. However, the metabolic benefits of GP diminished in antibiotics-treated HFD-fed mice. Overall, GP improved metabolic profiles in HFD-induced obese mice via the mediation of gut microbiota-dependent pathways. GP might be developed and utilized as prebiotics in nutraceutical and food industry.

Extracellular vesicles derived from human bone marrow mesenchymal stem cells protect rats against acute myocardial infarction-induced heart failure.

Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stem cells (BMSCs) are suggested to promote angiogenesis in a rat model of acute myocardial infarction (AMI). This study aimed to explore the underlying mechanism of BMSCs-EVs in AMI-induced heart failure (HF). BMSCs were isolated and verified, and EVs were purified and identified. After establishment of AMI-induced HF models, rats were treated with BMSCs-EVs and/or overexpressing (ov)/knocking down (kd) bone morphogenetic protein 2 (BMP2). Cardiac function, myocardial histopathological changes, angiogenesis, and vascular regeneration density were measured. Levels of pro-angiogenesis factors and cardiomyocyte apoptosis were detected. The viability and angiogenesis of hypoxic human umbilical vein endothelial cells (HUVECs) were measured. After BMSCs-EV treatment, the cardiac function of HF rats was improved, myocardial fibrosis and inflammatory cell infiltration were decreased, angiogenesis was increased, and cardiomyocyte apoptosis was inhibited. BMP2 was significantly upregulated in the myocardium. Ov-BMP2-BMSCs-EVs alleviated myocardial fibrosis and inflammatory cell infiltration, and promoted angiogenesis of HF rats, and improved the activity and angiogenesis of hypoxic HUVECs, while kd-BMP2-BMSCs-EVs showed limited protection against AMI-induced HF. BMSCs-EVs deliver BMP2 to promote angiogenesis and improve cardiac function of HF rats.

Long non-coding RNA Sox2OT promotes coronary microembolization-induced myocardial injury by mediating pyroptosis.

OBJECTIVE: As a common complication of coronary microembolization (CME), myocardial injury (MI) implies high mortality. Long non-coding RNAs (lncRNAs) are rarely studied in CME-induced MI. Herein, this study intended to evaluate the role of lncRNA Sox2 overlapping transcript (Sox2OT) in CME-induced MI. METHODS: The CME rat models were successfully established by injection of microemboli. Rat cardiac functions and MI were observed by ultrasonic electrocardiogram, HE staining, and HBFP staining. Functional assays were utilized to test the inflammatory responses, oxidative stress, and pyroptosis using reverse transcription quantitative polymerase chain reaction, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. Dual-luciferase reporter gene assay and RNA immunoprecipitation were conducted to clarify the targeting relations between Sox2OT and microRNA (miRNA)-23b and between miR-23b and toll-like receptor 4 (TLR4). RESULTS: Rat CME disrupted the cardiac functions and induced inflammatory responses and oxidative stress, and activated the nuclear factor-kappa B (NF-κB) pathway and pyroptosis (all P < 0.05). An NF-κB inhibitor downregulated the NF-κB pathway, reduced pyroptosis, and relieved cardiomyocyte injury and pyroptosis. Compared with the sham group (1.05 ± 0.32), lncRNA Sox2OT level (4.41 ± 0.67) in the CME group was elevated (P < 0.05). Sox2OT acted as a competitive endogenous RNA (ceRNA) of miR-23b to regulate TLR4. Silencing of Sox2OT favoured miR-23b binding to 3'UTR of TLR4 mRNA leading to suppressed TLR4-mediated NFKB signalling and pyroptosis in myocardial tissues harvested from CME rat models. In addition, miR-23b overexpression could supplement the cytosolic miR-23b reserves to target TLR-4 and partially reverse Sox2OT-mediated pyroptosis in LPS-treated H9C2 cells. CONCLUSIONS: This study supported that silencing Sox2OT inhibited CME-induced MI by eliminating Sox2OT/miR-23b binding and down-regulating the TLR4/NF-κB pathway. This investigation may provide novel insights for the treatment of CME-induced MI.

Ethanol extracts of Rhaponticum uniflorum (L.) DC flowers attenuate doxorubicin-induced cardiotoxicity via alleviating apoptosis and regulating mitochondrial dynamics in H9c2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Loulu flowers (LLF) is the inflorescence of Rhaponticum uniflorum (L.) DC. (R. uniflorum), a member of the Compositae family. This plant possesses heat-clearing properties, detoxification effects, and is therefore frequently used for the treatment of cardiovascular diseases. AIM OF THIS STUDY: This study aimed to investigate the cardioprotective effects of ethanol extracts of LLF against doxorubicin (DOX)-induced cardiotoxicity and explore the associated mechanisms. MATERIAL AND METHODS: Ethanol extracts of LLF were prepared and analyzed by LC-ESI-MS/MS. DOX-treated H9c2 cells and DOX-treated zebrafish models were used to explore the cardioprotective effect of ethanol extracts on myocardial function. The effects of LLF on DOX-induced cytotoxicity in H9c2 cells were investigated by MTT assay. Reactive Oxygen Species (ROS) levels, mitochondrial membrane potential (MMP), and nuclear translocation of NF-κB p65 were examined using fluorescent probes. The expression level of Bax, Bcl-2, PARP, caspase-3, cleaved-caspase3, caspase9, IκBα, p-IκBα, IKK, p-IKK, p65, p-p65, OPA1, Mfn1, MFF and Fis 1 and GAPDH was determined by western blotting. RESULTS: Twenty-five compounds were detected in ethanol extracts of LLF, include Nicotinamide, Coumarin, Parthenolide, and Ligustilide. Pre-treatment with LLF attenuated the DOX-induced decrease in viability and ROS production in H9c2 cells. Moreover, LLF treatment maintained the mitochondrial membrane integrity and suppressed apoptosis by upregulating expression level of Bcl-2 and downregulating the expression level of Bax, cleaved-caspase-3, cleaved-caspase-9 and cleaved-PARP. In addition, LLF significantly inhibited the DOX-induced activation of NF-κB signaling. Cells treated with DOX showed aberrant expression of mitochondrial dynamics related proteins, and these effects were alleviated by LLF pre-treatment. In conclusion, these results show that LLF can alleviate DOX-induced cardiotoxicity by blocking NF-κB signaling and re-balancing mitochondrial dynamics. CONCLUSION: Ethanol extracts of LLF is a potential treatment option to against DOX-induced cardiotoxicity.

Endovascular management of vertebrobasilar artery dissecting aneurysms.

AIM: The prognosis of VBA aneurysms seems poor and surgical management of VBA dissecting aneurysms is challenging. We evaluated our endovascular experience in management of ruptured and unruptured VBA dissecting aneurysms. MATERIAL AND METHODS: Eleven consecutive patients with eleven VBA aneurysms (3 ruptured and 8 unruptured) between 2008 and 2010 were retrospectively reviewed. RESULTS: Immediate postprocedural angiograms showed complete occlusion in 5 and subtotal occlusion in 2 aneurysms treated with stentassisted coiling, whereas no occlusion in 4 aneurysms treated with stenting alone. A clinical improvement or stable outcome was achieved in all patients. There was no complication in our patients and no patient died after treatment. Angiographic follow-up (mean 9.7 months, 1 to 23 months) showed complete cure in 8 aneurysms, subtotal occlusion in 2 and no occlusion in 1. CONCLUSION: VBA dissecting aneurysms can be managed by endovascular stent placement with or without coiling. In cases that cannot be treated with neurostents, proximal occlusion could be an option.