Extracellular vesicles derived from hypoxia-preconditioned bone marrow mesenchymal stem cells ameliorate lower limb ischemia by delivering miR-34c.

Hypoxic mesenchymal stem cell-derived extracellular vesicles (EVs) have been suggested as a promising therapy for various diseases. This study aims to determine the effect of EVs derived from bone marrow mesenchymal stem cells (BMMSCs) under hypoxia on lower limb ischemia and the underlying mechanism. Human BMMSCs were subjected to hypoxia or normoxia followed by the isolation of EVs. Nanoparticle trafficking analysis (NTA), transmission electron microscopy (TEM), and Western Blotting using corresponding markers were performed to confirm the EVs. The EVs from BMMSCs under hypoxia condition (Hyp-EVs) or normoxia condition (Nor-EVs) were subjected to hindlimb ischemia (HI) mice. MiR-34c expression in BMMSCs and BMMSC-EVs was detected. The role of miR-34c in regulating M2 macrophage polarization, as well as the target of miR-34c, were explored. HI mice with Hyp-EV treatment, as compared to the Nor-EV or the PBS group, had better blood flow and higher capillary density. MiR-34c expression was increased in BMMSCs, BMMSC-EVs, and the adductor muscle of HI mice. Hyp-EVs promoted the M2 macrophage polarization and anti-inflammatory cytokine production, and enhanced the blood flow and capillary density in HI mice, while the knockdown of miR-34c partly reversed these effects. PTEN is a target of miR-34c, and the PTEN silencing facilitated M2 macrophage polarization, whereas the inhibition of AKT signaling partly abolished the effect. Hyp-EVs promoted M2 macrophage polarization by delivering miR-34c via PTEN/AKT pathway, which could be a promising therapeutic strategy to ameliorate lower limb ischemia.

Hypoxia pretreatment improves the therapeutic potential of bone marrow mesenchymal stem cells in hindlimb ischemia via upregulation of NRG-1.

Mesenchymal stem cells (MSCs) are considered a promising treatment for ischemic diseases, but their use is limited due to poor survival after injection. Hypoxia can significantly enhance the survival of MSCs. This study aimed to investigate hypoxia pretreatment of bone marrow mesenchymal stem cells (BM-MSCs) in hindlimb ischemia (HI) and the underlying mechanism. The HI mouse model was established and human BM-MSCs were injected into ischemic skeletal muscles. The blood flow reperfusion and capillary density were measured. In vitro, human BM-MSC cells were treated with hypoxia. The expression of NRG-1 and associated angiogenic factors were measured after knockdown or overexpression of NRG-1. The conditioned medium (CdM) of BM-MSCs was prepared and co-cultured with human umbilical vein endothelial cells (HUVECs), and then, the proliferation, migration, and angiogenesis of HUVECs were detected. After hypoxia pretreatment, NRG-1 expression, clone formation, proliferation, and angiogenic factor secretion from BM-MSCs were increased, while knockdown of NRG-1 reversed these results. In normoxia condition, overexpression of NRG-1 enhanced above factors. Additionally, hypoxia pretreatment of BM-MSCs induced the proliferation and migration of HUVECs and angiogenesis. Moreover, the injection of hypoxia pretreatment of BM-MSCs improved blood reperfusion and capillary density in HI mice, while knockdown of NRG-1 reversed the effect. Furthermore, the PI3K inhibitor and activator reversed the effect of NRG-1 overexpression and knockdown on angiogenesis. We concludes that hypoxia pretreatment of BM-MSCs facilitates angiogenesis and alleviates HI injury via NRG-1/PI3K/AKT pathway.

Clinical outcomes of endovascular aneurysm repair of abdominal aortic aneurysm complicated with hypertension: A 5-year experience.

OBJECTIVE: To evaluate the therapeutic effects of endovascular aneurysm repair (EVAR) on abdominal aortic aneurysm (AAA) complicated with hypertension. METHODS: Fifty-two patients with AAA complicated with hypertension treated in our hospital were retrospectively analyzed. They were divided into an observation group (34 cases) and a control group (18 cases). The control group was treated by incision of AAA and artificial blood vessel replacement, and the observation group was treated by EVAR. RESULTS: All surgeries were performed successfully. However, compared with the control group, the observation group had significantly less surgical time, intraoperative blood loss and blood transfusion, as well as significantly higher total hospitalization expense (P<0.05). During the one-month follow-up, the observation group was significantly less prone to pulmonary infection, surgical site infection, lower-extremity deep venous thrombosis and lower extremity weakness than the control group (P<0.05). The observation group enjoyed significantly better quality of life than the control group did one and three months after surgery (P<0.05). CONCLUSION: Given sufficient funding, EVAR should be preferentially selected in the treatment of AAA complicated with hypertension due to minimal invasion, safety, stable postoperative vital signs and improved quality of life.

Investigation of the specularite/chlorite separation using chitosan as a novel depressant by direct flotation.

Chlorite is one of the representative iron-bearing silicates gangue minerals existed in the specularite ores which the traditional depressants are incapable of action in specularite/chlorite separation flotation. An attempt was conducted for the separation of specularite/chlorite with chitosan as a novel depressant through microflotation tests, Zeta potential measurements, adsorption tests, FT-IR, and XPS analysis. The microflotation results show that chitosan selectively depresses chlorite while specularite still keeps in high floatability. Zeta potential measurements and adsorption tests indicate that chitosan mainly adsorbed on chlorite surface, hindering the subsequent adsorption of dodecan-1-amine and leading the hydrophobicity distinction. The FT-IR spectra of chlorite validate the adsorption of chitosan on chlorite. The results of XPS illustrate that electrons partially transferred from chitosan to the aluminum, iron, magnesium, silicon, and adjacent oxygen atoms of silicon atoms in chlorite during the adsorption process.