Background: Recent studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 (GDF-6) on the tenogenic differentiation of BMSCs in vitro, and then combined with small intestine submucous (SIS) to promote tendon regeneration in vivo. Methods: The BMSCs were isolated from the green fluorescent protein (GFP) rats, and were characterized by multi-differentiation assays following our previous study protocol. BMSCs cultured with different concentrations of GDF-6, without growth factors served as control. After 2 weeks, mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6. Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P ≤0.05 was regarded as statistically significant. The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model, the BMSCs combined with SIS served as control. After 12 and 4 weeks in nude mice and tendon injury model, the samples were collected for histology. Results: After the BMSCs were treated with different concentration of GDF-6 for 2 weeks, the fold changes of the specific markers (Tenomodulin and Scleraxis) mRNA expression were significantly higher in GDF-6 (20 ng/ml) group (P ≤0.05), which was also confirmed by Western blotting result. The BMSCs became parallel in orientation after GDF-6 (20 ng/ml) treatment, but the BMSCs in control group were randomly oriented. The GDF-6 (20 ng/ml) treated BMSCs were combined with SIS, and were implanted in nude mice for 12 weeks, the histology showed neo-tendon formation. In the SD rat patellar tendon window injury model, the histology also indicated the GDF-6 (20 ng/ml) treated BMSCs combined with SIS could promote tendon regeneration. Conclusions: GDF-6 has tenogenic effect on the tenogenic differentiation of BMSCs, and GDF-6 (20 ng/ml) has better tenogenic effect compared to other concentrations. The GDF-6 (20 ng/ml) treated BMSCs combined with SIS can form neo-tendons and promote tendon regeneration.

The aim of this study is to evaluate the potential of gene transfer of cell cycle control genes as treatment of corneal haze or secondary cataract formation. The guiding hypothesis is that strategic modulation of the cyclin G1 or MAT1 gene by retrovirus-mediated gene transfer will inhibit proliferation of rabbit keratocytes (RabK) and fetal human lens epithelial (FHLEpi) cells in vitro. RabK and FHLEpi cell cultures were transduced in triplicate with retroviral vectors bearing either a nuclear-targeted beta-galactosidase, an antisense cyclin G1 (aG1), an antisense MAT1 (aMAT1) construct, or the neo(r) gene. The presence of beta-galactosidase activity in the transduced cultures was detected by immunohistochemical X-Gal staining, while cyclin G1 and MAT1 protein expression levels were evaluated by Western analysis. Proliferation of RabKs and FHLEpi cells was analyzed by counting the number of cells in the aG1 and aMAT1 vector-transduced cultures over 5 days. The mean transduction efficiency was 34.4% (SD 1.41) for RabKs and 19.7% (SD 1.83) for FHLEpi cells. Downregulation of cyclin G1 and MAT1 protein expression was noted 24 hr after transduction of RabK cultures with the respective vectors. Cytostatic effects of the aG1 and aMAT1 vectors in both RabKs and FHLEpi cells were most pronounced on the fifth day (RabKs, p < 0.0007; FHEpi cells, p < 0.001). An increased incidence of apoptosis was identified in both aG1 and MAT1-transduced FHLEpi cells. Taken together, these data suggest the potential utility of developing aG1 and aMAT1 retroviral vectors in gene therapy protocols for corneal haze and secondary cataract formation.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness

Background: The effects of psychological interventions on symptoms and psychology of functional dyspepsia (FD) remain unclear. We aimed to comprehensively evaluate the effects of psychological interventions on symptoms and psychology of FD.Methods: We searched the PubMed, Cochrane Library, and Embase electronic databases for randomized controlled trials (RCTs) evaluating the role of psychological interventions in FD patients published before July 2021. Standardized mean differences (SMDs), risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by a random effects model. Subgroup analyses and sensitivity analyses were also performed.Results: Fourteen RCTs with a total of 1,434 FD patients were included. Compared with the control group, psychological interventions were significantly more likely to symptom improvement [RR = 1.74, 95% CI (1.12, 2.72), p = 0.01], relieve gastrointestinal symptoms scores at follow up [SMD = −1.06, 95% CI (−1.55, −0.57), p < 0.0001], relieve gastrointestinal symptoms scores at end of treatment [SMD = −0.98, 95% CI (−1.29, −0.67), p < 0.001], decrease anxiety [SMD = −0.8, 95% CI (−1.38, −0.22), p = 0.006] and depression levels [SMD = −1.11, 95% CI (−1.62, −0.61), p < 0.001]. The results of the subgroup analysis showed that psychotherapy was more likely to symptom improvement, relieve gastrointestinal symptoms scores and decreased depression levels compared to the control.Conclusions: Psychological interventions may be effective in alleviating the symptoms and psychology of FD, but the effect appears to be limited to psychotherapy with fewer trials for other psychological interventions. More data from high-quality RCTs are needed to confirm their use in the treatment of FD.