Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells

Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic fac- tor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neuro- trophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when al- lografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and cili- ary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.

The therapeutic efficacy and safety of Gongxuening capsule in dysfunctional uterine bleeding:a systematic review and meta-analysis

Background:Gongxuening capsule is a Chinese patent medicine for treating the dysfunctional uterine bleeding.We report a meta-analysis of the combination efficacy between conventional medicines with Chinese patent drug Gongxuening in the treatment of dysfunctional uterine bleeding.Materials and methods:Seven databases were used to retrieve the relevant research of Chinese patent drug Gongxuening treatment for dysfunctional uterine bleeding from the databases establishment to 2020.The data were extracted independently by 2 researchers according to the described selection research.The meta-analysis was performed using RevMan5.3 software.Results:This study included 23 randomized trials,with a total of 1,836 dysfunctional uterine bleeding patients.Chinese patent drug Gongxuening could significantly improve the effective rate,and reduce endometrial thickness,control bleeding time,complete hemostasis time and sex hormone level,and no serious adverse events.Based on sensitivity analysis and subgroup analysis,the heterogeneity sources of endometrial thickness,complete hemostasis time and sex hormone level were found.In follicle stimulating hormone and luteinizing hormone,there was no significant difference between the two groups when Chinese patent drug Gongxuening combined with desogestrel ethinylestradiol.Conclusion:Conventional medicines combined with Chinese patent drug Gongxuening can make patients with dysfunctional uterine bleeding achieve better effective rate,and no serious adverse events occurred.

TOSO interacts with SYK and enhances BCR pathway activation in chronic lymphocytic leukemia

Background:TOSO,also named Fas inhibitory molecule 3(FAIM3),has recently been identified as an immunoglobulin M(IgM)Fc receptor(FcμR).Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia(CLL).However,the functions of TOSO in CLL remain unknown.The B-cell receptor(BCR)signaling pathway has been reported to be constitutively activated in CLL.Here,we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL.Methods:We over-expressed TOSO in B-cell lymphoma cell lines(Granta-519 and Z138)by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells.The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting.Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry(IP/LCMS)was used to identify TOSO interacting proteins.Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2(BCL-2).Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD.One-way analyses of variance were used for intergroup comparisons,while independent samples t tests were used for two-sample comparisons.Results:From IP/LCMS,we identified spleen tyrosine kinase(SYK)as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation.After stimulation with anti-IgM,TOSO over-expression increased the phosphorylation of SYK,and subsequently activated the BCR signaling pathway,which could be reversed by a SYK inhibitor.TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway.The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were(8.46±2.90)%and(4.20±1.21)%,respectively,significantly lower than the rates of the control groups,which were(25.20±4.60)%and(19.72±1.10)%,respectively(P<0.05 for both).The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells.In addition,we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis,and vice versa in the cell line.Conclusions:TOSO might be involved in the pathogenesis of CLL by interacting with SYK,enhancing the BCR signaling pathway,and inducing apoptosis resistance.