Long Noncoding RNA NORAD Promotes Fracture Healing through Interacting with Osteoblast Differentiation via Targeting miR-26a.

The present study was designed to evaluate the dynamic expression of lncRNA NORAD in fracture healing of patients with brittle fractures and explore the function and mechanism of NORAD in regulating osteoblastic proliferation, differentiation, and apoptosis. The expression level of NORAD was detected by quantitative real-time PCR. The proliferation, differentiation, and apoptosis of osteoblasts were analyzed by MTT assay, ELISA, and flow cytometry. Luciferase report analysis was used to confirm the interaction between NORAD and its target ceRNA miR-26a. This study showed no significant differences in serum NORAD expression on the 7th day during fracture healing in patients, but increased expression of NORAD was certified on the 14, 21, and 28 days after fixation. Overexpression of NORAD promoted the proliferation and differentiation of osteoblasts and suppressed the apoptosis of osteoblasts. miR-26a proved to be the target gene of NORAD and was inhibited by overexpression of NORAD in osteoblasts. The enhanced expression of miR-26a was negatively linked to the lessened expression of NORAD. NORAD could accelerate the proliferation and differentiation of osteoblasts and inhibit apoptosis, thereby promoting fracture healing.

MicroRNA-455-3p promotes osteoblast differentiation via targeting HDAC2.

BACKGROUND: Fragility fracture commonly occurs in the elderly, the basis of fracture healing is osteoblast regeneration. The study measured the expression changes of microRNA-455-3p during fracture healing in patients with fragility fractures, and explored its influence on osteoblast differentiation. METHODS: 108 postmenopausal women with osteoporosis were recruited, in which 58 cases with fragility fracture. qRT-PCR was used for the measurement of miR-455-3p levels. MC3T3-E1 cells were induced differentiation by BMP-2. ELISA was performed for the measurement of alkaline phosphates (ALP), runt-related transcription factor-2 (RUNX2), osteocalcin (OCN), and Collagen I. Luciferase reporter gene assay was done for the target gene analysis. RESULTS: Serum miR-455-3p was significantly decreased in both osteoporosis and fragility fracture patients compared with the control group, which was most deficient in patients with fragility fracture. With the extension of treatment time, the level of miR-455-3p in serum increased gradually and reached the highest level at 4 weeks of treatment. Levels of miR-455-3p continued to increase on the 7th and 14th days after induction of cell differentiation. MiR-455-3p overexpression promoted cell proliferation, and increased the levels of osteoblast differentiation markers, including ALP, OCN, Collagen I, and RUNX2. MiR-455-3p in MC3T3-E1 cells was directly bound to HDAC2 and negatively regulated. Both MC3T3-E1 differentiation and the fracture healing of patients were accompanied by progressively reduced HDAC2. CONCLUSIONS: MiR-455-3p promotes osteogenic differentiation which may be associated with fracture healing, HDAC2 acts as a target of miR-455-3p in the underlying mechanism.

The curative effect of Shenfu-injection in the treatment of burn sepsis and its effect on the patient's immune function, HMGB, and vWF.

OBJECTIVE: To investigate and analyze the immune regulatory effect of Shenfu-Injection (SFI) on patients with burn-injured sepsis by monitoring the serum level of high mobility group box 1 (HMGB1) and von Willebrand factor (vWF). METHODS: In this retrospective study, the Acute Physiology and Chronic Health Evaluation (APACHE II) score, Marshall score, peripheral blood T lymphocyte count, and NK cell concentration, levels of cytokines such as HMGB-1, and vWF in peripheral blood before and after treatment in patients from the control group (convention treatments, n=51) and the observation group (convention treatments plus SFI treatment, n=57) were analyzed. The prognosis of the two groups of patients at 28 days was analyzed and compared. RESULTS: After treatment, APACHE II score, Marshall score, IL-6, CPR, HMGB-1, and vWF in patients from the two groups decreased greatly when compared with those before the treatment (P<0.05). The APACHE II score, Marshall score, IL-6, CPR, HMGB-1, and vWF in the group for observation were significantly lower (P<0.05) than those in the control group. Concentrations of CD3+, CD4+, and NK cells in these two groups after 7 days of treatment were greatly higher than those before the treatment (P<0.05). Concentrations of CD3+, CD4+, and NK cells in the observation group were higher than those in the control group after treatment (P<0.05). There was no significant difference in terms of mortality between these two groups after 28 days (P<0.05). The average survival time of the non-survivors in the observation group was significantly longer than that in the control group (P<0.05). CONCLUSION: SFI can effectively improve the immunity of patients with burn-injured sepsis, reduce the expression of cytokines such as HMGB and vWF, and is of great help for the improvement of clinical prognosis.

miR-876-3p suppresses the progression of colon cancer and correlates the prognosis of patients.

BACKGROUND: miR-876-3p has been identified to be downregulated in colon cancer, implying the potential biological function in the progression and prognosis of colon cancer. The clinical significance and the biological function of miR-876-3p were investigated in this study to assess the potential of miR-876-3p in acting as a novel biomarker of the progression of colon cancer. METHODS: The expression of miR-876-3p in colon cancer was evaluated by RT-qPCR. The clinical significance of miR-876-3p was assessed by associated its expression level with the clinical features and prognosis of patients. The biological function of miR-876-3p was estimated by the CCK8 and Transwell assay in vitro. RESULTS: The significant downregulation of miR-876-3p was observed in colon cancer tissues and cells, which was closely associated with the lymph node metastasis status, TNM stage, and the perineural invasion of patients. miR-876-3p served as an independent indicator that was negatively associated with the prognosis of patients. In colon cancer cells, miR-876-3p showed significant inhibitory effects on cell proliferation, migration, and invasion, indicating its tumor suppressor role in the progression of colon cancer. CONCLUSION: miR-876-3p might be involved in colon cancer development, which provides a potential therapeutic target for colon cancer treatment.