BACKGROUND:Mechano growth factor has the potential to activate muscle satelite cels and promote myogenic cel growth, and has dual roles in maintaining bone mass and repairing bone defects.
OBJECTIVE: To explore the mechanism underlying osteogenic differentiation of rabbit bone marrow mesenchymal stem cels promoted by the mechano growth factor.
METHODS:The best concentration and time of mechano growth factor to promote osteogenic differentiation of rabbit bone marrow mesenchymal stem cels were detected by MTT. The mRNA and protein expressions of alkaline phosphatase and osteocalcin were detected by qPCR and western blot, respectively. The phosphorylation level of AKT and mTOR were detected by western blot assay.
RESULTS AND CONCLUSION:The best concentration and time of mechano growth factor was 45 μg/L and 5 days for promoting the osteogenic differentiation of rabbit bone marrow mesenchymal stem cels. The expressions of alkaline phosphatase and osteocalcin at mRNA and protein levels were highest after 4-hour intervention with 45 μg/L mechano growth factor, and meanwhile, the phosphorylation levels of mTOR and AKT were also highest. These findings indicate that the mechano growth factor can promote the differentiation of rabbit bone marrow mesenchymal stem cels into osteoblastsvia PI3K/AKT pathway, and its best concentration and time are 45 μg/L and 4 hours, respectively.

Objective Observation of the effects of Xinmailong injection on NGAL, hs-cTnT and RAAS in elderly patients with type 2 cardio-renal syndrome (CRS) , and EvaluatIon of the clinical efficacy and safety.Methods A total of 86 elderly patients who were collected from November 2015 to February 2017 were diagnosed as type 2 CRS in our department of geriatrics. According to the random number table method, they were randomly divided into two groups. Control group (43 cases) were treated with conventional medical therapy and xinmailong group (43 cases) were treated with xinmailong injection with a dose of 5 mg/kg twice a day for 15 days. The value of sneutrophil gelatin-associated apolipoprotein (NGAL) , hypersensitive troponin T (hs-cTnT) , brain natriuretic peptide (BNP) , plasma renin activity (PRA) , and angiotensin Ⅱ (Ang Ⅱ) , aldosterone (ALD) , left ventricular ejection fraction (LVEF) , six-minute walking test and other indicators were measured before and after treatment. Results After treatment, the value of NGAL, hs-cTnT, BNP, PRA, AngⅡ and ALD decreased in both groups, the value of LVEF and six-minute walking distance increased compared with those before treatment (P <0.05); The above indicators in the xinmailong group experienced a more significant alteration than in control group in the same period (P < 0.05); no side effect occurred in both two groups during the experiment. Conclusion Xinmailong injection can reduce the levels of NGAL, hs-cTnT and BNP in elderly patients with type 2 cardio-renal syndrome, improve heart and kidney function, and have curative positive effect and good safety. This study underlined the mechanism of Xinmailong injection may be related to the inhibition of RAAS activity.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).