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The purpose of this study was to elucidate the potential influence of circular RNA (circRNA)_0048211/miRNA-93-5p/BMP2 regulatory loop in the progression of postmenopausal osteoporosis (PMOP).Bone marrow samples were collected from PMOP patients (n=30) and healthy subjects (n=30) for isolating hBMSCs. Relative levels of circRNA_0048211, miRNA-93-5p, and BMP2 in hBMSCs isolated from PMOP patients and healthy controls were detected. In addition, their dynamic expressions in hBMSCs isolated from PMOP patients undergoing osteogenesis for 0, 7, 14, and 21 days were examined. Then, the interaction in the circRNA_0048211/miRNA-93-5p/BMP2 regulatory loop was verified by Dual-Luciferase reporter gene assay. Next, the potential influences of circRNA_0048211/miRNA-93-5p/BMP2 regulatory loop on osteogenesis-associated gene expressions, ALP activity, and mineralization ability were assessed.CircRNA_0048211 and BMP2 were downregulated, while miRNA-93-5p was upregulated in hBMSCs isolated from PMOP patients. In hBMSCs undergoing osteogenesis, circRNA_0048211, miRNA-93-5p and BMP2 were time-dependently changed. Overexpression of circRNA_0048211 upregulated RUNX2, OPN, and OCN, which also stimulated ALP activity and mineralization ability. CircRNA_0048211 could bind to miRNA-93-5p, and BMP2 was a direct target of miRNA-93-5p. In the meantime, circRNA_0048211 was negatively correlated with miRNA-93-5p, and positively correlated with BMP2. Besides, CircRNA_0048211/miRNA-93-5p/BMP2 regulatory loop was responsible for regulating osteogenesis-associated gene expressions, ALP activity, and mineralization ability in hBMSCs.CircRNA_0048211 negatively targets miRNA-93-5p to upregulate BMP2, thus alleviating the progression of PMOP.

Colorectal carcinoma (CRC) is one of the most common factors for tumor-associated mortalities globally. In recent years, microRNAs (miRNAs) have been identified as novel therapeutic biomarkers for cancer treatment. The purpose of the current study was to unravel the clinical significance and underlying molecular mechanisms of miR-760 in CRC progression.Fifty-four pairs of CRC tissue samples and adjacent para-carcinoma tissue samples were collected from CRC patients who underwent surgical resection. We measured miR-760 expressions in CRC using quantitative Real-time polymerase chain reaction (qRT-PCR) analysis. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays were performed to determine the functions of miR-760 in CRC cell proliferation, invasion and migration. Dual-luciferase reporter assays and Western blots were used to investigate the underlying molecular mechanisms. Moreover, the association between miR-760 expressions and clinicopathological features was analyzed.In this study, the results showed that the down-regulated miR-760 expressions were related to the poor prognosis and malignant clinicopathologic features of CRC patients. Furthermore, functional assays revealed that miR-760 restoration obviously suppressed CRC cell proliferation, migration and invasion through modulating phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway and epithelial-mesenchymal transition (EMT). FOXA1 was also considered as a functional target of miR-760 in CRC cells. Furthermore, miR-760 up-regulation also significantly repressed tumorigenesis in vivo.These results suggested that miR-760 exerted cancer-suppressive functions in CRC, providing a therapeutic strategy for CRC treatment.

The purpose of this study was to investigate how miR-203 promotes osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by regulating its target gene DKK1, thereby inhibiting the occurrence of osteoporosis.A total of 60 cases with postmenopausal osteoporosis and 40 cases of normal individuals were recruited. The expression of miR-203 in serum of all cases was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The capacity of osteogenesis and adipogenic differentiation of MSCs was determined by alizarin red staining and oil red staining, respectively. Transfection of miR-203 mimics and miR-203 inhibitor were mediated by Liposomes, and then the MSCs were induced osteogenic and adipogenic differentiation. MiR-203 mimic was co-transfected with wild-type or mutant DKK1 for luciferase reporter gene detection. In the osteoporosis model of rats, the tibia was taken for micro-CT examination of bone mineral density (BMD) and bone volume/structural parameters (BV/TV), while the femur was taken for the measurement of absorption parameters (Ob.S)./BS) and the number of osteoclasts per circumference of bone (N.Oc/B.Pm).The expression level of miR-203 was significantly lower in patients with postmenopausal osteoporosis than that in normal individuals. The osteogenic capacity of BMSCs in these patients was reduced, while their adipogenic capacity was enhanced. MiR-203 promoted the expression of osteogenic genes and inhibited that of adipogenic genes. Knockdown of miR-203 decreased the level of osteogenic related genes but increased that of adipogenic related genes, while overexpression of miR-203 led to the opposite results. Furthermore, miR-203 inhibited the protein expression of DKK1. In addition, bone density and bone volume/structural parameters were lower in ovariectomized rats than those in normal rats. Meanwhile, bone resorption parameters and the number of osteoclasts per bone circumference in ovariectomized rats were higher than those in normal rats.MiR-203 can promote osteogenic differentiation of mesenchymal stem cells by downregulating the gene expression of DKK1.

Objective and Design: The aim of the study was to evaluate the effects of GMDP on angiogenesis in vivo and as a modulator of human umbilical vein endothelial cell proliferation, cell surface antigen expression and cell adhesion in vitro.¶Materials: Human umbilical vein endothelial cells (HUVEC), fertilized white leghorn chicken eggs, antibodies against adhesion molecules and glucosaminylmuramyl dipeptide (GMDP).¶Treatment: GMDP [0.01–100 μg/ml] applied to cell cultures for 6–72 h and to the chick chorioallantoic membrane (CAM) for four days.¶Methods: Angiogenic activity of GMDP in vivo was assessed using the CAM assay; HUVEC proliferation was measured by tritiated thymidine incorporation and cell cycle studies; cell surface antigen expression by indirect immunofluorescence and flow cytometry; cell adhesion by quantification of [3H]-thymidine labeled leukocyte adherence to HUVEC monolayers. Statistical analysis was performed using one-way ANOVA and if necessary was followed by Duncan's multiple range test for variables.¶Results: GMDP induced [3H]-thymidine incorporation in a concentration- and time-dependent manner (p < 0.003) and significantly increased the proportion of cells in the S phase of the cell cycle (p < 0.03). It weakly augmented the expression of ICAM-1 and CD31 but not adhesion of leukocytes to HUVEC monolayers GMDP was not angiogenic in the CAM assay.¶Conclusions: GMDP can modulate endothelial cell activity without the induction of angiogenesis in vivo which may have implications for its use as a therapeutic agent.

To assess whether the addition of a Chinese herbal medicine formula to acupuncture affects the severity of symptoms and quality-of-life scores among patients with seasonal allergic rhinitis.Randomised double-blind placebo-controlled trial.University teaching and research clinic, Australia.Sixty-five patients with seasonal allergic rhinitis, who were recruited through public media.Between July and December 1999, patients received acupuncture twice a week for 8 weeks plus either a Chinese herbal drug formula (n=33) or placebo (n=32) at a dosage of four capsules, three times daily.The severity of nasal and non-nasal symptoms on a five-point scale, as assessed by both patients and an ear, nose, and throat specialist, and quality-of-life scores as measured by the Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire.Sixty-one patients completed the study (31 in the intervention group and 30 in the control group). After 8 weeks, no significant difference was found between the two groups in the severity of nasal and non-nasal symptoms and in the Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire scores. Intention-to-treat analysis of categorical variables showed moderate-to-marked improvement rates of 72.7% and 81.2% for intervention and control groups, respectively. Six patients reported mild adverse events-three from each of the study groups.The Chinese herbal formulation under investigation did not provide additional symptomatic relief or improvement in quality-of-life scores among patients with seasonal allergic rhinitis who were receiving acupuncture.