Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1.

BACKGROUND: The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and confirmed able to improve bone mass of OP patients. OBJECTIVE: To investigate the effect of ICA on the proliferation and osteogenic differentiation of bone-derived MSCs (BMSCs) from patients with OP and T2DM and uncover the potential mechanism. METHODS: BMSCs were treated with ICA, and proliferation and osteogenic potency were evaluated using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and detection of osteogenic markers (ALP, RUNX2, SPP1, COL1A1, and mineralized nodules) was performed. RNA sequencing and bioinformatic analysis were performed to identify differentially expressed genes (DEGs) after ICA treatment and screen proliferation- and osteogenic differentiation-related processes. Gene gain and loss were performed to confirm the role of the key candidate gene. RESULTS: ICA significantly promoted the proliferation and osteogenic differentiation of BMSCs. A total of 173 DEGs were identified after ICA treatment. Six DEGs (GLI-1, IGF2, BMP6, WNT5A, PTHLH, and MAPK14) enriched in both proliferation- and osteogenic differentiation-related processes were screened; GLI-1 had the highest validated |log2FC| value. Overexpression of GLI-1 enhanced the proliferation and osteogenic differentiation of BMSCs, and knockdown of GLI-1 weakened the positive effect of ICA on BMSCs. CONCLUSION: ICA promoted the proliferation and osteogenic differentiation of impaired BMSCs by upregulating GLI-1.

In vitro anti-synovial sarcoma effect of diallyl trisulfide and mRNA profiling.

OBJECTIVE: Synovial sarcoma (SS) is a malignant soft tissue sarcoma and its natural history is a long, indolent clinical course followed by high rate of local recurrence and distant metastasis. Current therapies are still limited in increasing satisfactory of 5-year survival, especially for patients with recurrence and metastasis. Accordingly, finding new therapeutic drug for SS treatment is clinically urgent need. Diallyl trisulfide (DATS), a bioactive compound derived from garlic, is reported as a promising anti-cancer agent for various carcinomas. However, its effect on anti-SS remains unknown. This study investigated the anti-SS effect of DATS in human synovial sarcoma SW982 cells. METHODS: CCK-8 assay were used to examine the cell viability. High-content Imaging System was used to examine the apoptosis, intracellular ROS and autophagy. Flow cytometry was used to detect cell cycle. qPCR and Western blot were used to examine the expression of related mRNA and protein. High-throughput RNA-sequencing and bio-information analysis were used to investigate the mRNA profiling. RESULTS: The results showed a suppressive effect of DATS on tumor biology of SW982 cells including inducing apoptosis, triggering G2/M cell cycle arrest, elevating intracellular ROS and damaging mitochondria. Further high-throughput RNA-sequencing analysis clarified a comprehensive molecular portrait for DATS-induced transcriptional regulation. Besides, protein-protein interaction (PPI) analysis demonstrated that a network consisted of FOXM1, CCNA2, CCNB1, MYBL2, PLK1 and CDK1 might be response for DATS-induced G2/M cell cycle arrest and increased intracellular ROS. Notably, protein feature analysis revealed structure enrichment in microtubule network like kinesin motors domain, and tubulin domain. Molecular function analysis suggested that DATS-induced dysfunction of microtubule network might be the major cause for its effect on cell cycle arrest and successive apoptosis. Furthermore, 28 hub genes (including KIF2C, PLK1, CDK1, BIRC5, CCNB2, CENPF, TPX2, TOP2A and so on) were determined. Finally, pathway analysis showed that DATS-induced differentially expressed genes were mainly involved in cell cycle. CONCLUSION: Collectively, our findings for the first time provided the DATS-induced cellular response and transcriptional profiling of SW982 cells, which proposes that suppression of DATS on SS is multi-targeted and represent a therapeutic evidence for SS.

Evaluation of Effect of Curcumin on Psychological State of Patients with Pulmonary Hypertension by Magnetic Resonance Image under Deep Learning.

This research aimed to evaluate the right ventricular segmentation ability of magnetic resonance imaging (MRI) images based on deep learning and evaluate the influence of curcumin (Cur) on the psychological state of patients with pulmonary hypertension (PH). The heart MRI images were detected based on the You Only Look Once (YOLO) algorithm, and then the MRI image right ventricle segmentation algorithm was established based on the convolutional neural network (CNN) algorithm. The segmentation effect of the right ventricle in cardiac MRI images was evaluated regarding intersection-over-union (IOU), Dice coefficient, accuracy, and Jaccard coefficient. 30 cases of PH patients were taken as the research object. According to different treatments, they were rolled into control group (conventional treatment) and Cur group (conventional treatment + Cur), with 15 cases in each group. Changes in the scores of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of the two groups of patients before and after treatment were analyzed. It was found that the average IOU of the heart target detection frame of the MRI image and the true bounding box before correction was 0.7023, and the IOU after correction was 0.9016. The Loss of the MRI image processed by the CNN algorithm was 0.05, which was greatly smaller than those processed by other algorithms. The Dice coefficient, Jaccard coefficient, and accuracy of the MRI image processed by CNN were 0.89, 0.881, and 0.994, respectively. The MRI images of PH patients showed that the anterior wall of the right ventricle was notably thickened, and the main pulmonary artery was greatly widened. After treatment, the SAR and SDS scores of the two groups were lower than those before treatment (P < 0.05), and the SAR and SDS scores of the curcumin group were lower than those of the control group (P < 0.05). To sum up, the right ventricular segmentation ability of MRI images based on deep learning was improved, and Cur can remarkably alleviate the psychological state of PH patients, which provided a reference for the diagnosis and treatment for PH patients.

[Clinical observation on cervical type cervical spondylosis treated with sword-like needle and chiropractic spinal manipulation].

OBJECTIVE: To compare the difference in the efficacy on cervical type of cervical spondylosis (CS) between the combined treatment of sword-like needle and chiropractic spinal manipulation (the combined therapy) and the simple chiropractic spinal manipulation. METHODS: One hundred and thirty-eight cases of cervical type of CS were randomized into a combined therapy group (76 cases) and a simple chiropractic spinal manipulation group (62 cases). In the combined therapy group, the sword-like needle therapy was applied at Fengchi (GB 20), Tianzhu (BL 10) and Jiaji (EX-B 2) C3-C5. The chiropractic spinal manipulation was used in combination. In the chiropractic spinal manipulation group, the simple chiropractic spinal manipulation was adopted. The treatment was given once every other day in the two groups, 10 days made one session. One session of treatment was required. Visual analog scale (VAS) score was observed before and after treatment in the two groups and the efficacies were compared between the two groups. RESULTS: VAS score after treatment was reduced obviously as compared with that before treatment in the patients of the two groups (both P < 0.01) and VAS score after treatment in the combined therapy group was lower than that in the simple chiropractic spinal manipulation group (1.50 +/- 0.58 vs 1.87+/-1.05, P < 0.01). In the combined therapy group, 48 cases were cured, 20 cases remarkably effective, 8 cases improved and 0 case failed. In the chiropractic spinal manipulation group, 30 cases were cured, 16 cases remarkably effective, 15 cases improved and 1 case failed. The overall efficacy in the combined therapy group was better than that in the chiropractic spinal manipulation (P < 0.05). CONCLUSION: The sword-like needle therapy combined with chiropractic spinal manipulation relieve effectively pain in cervical type of CS and the efficacy is superior to the simple chiropractic spinal manipulation.