Overexpression of miR-195-5p reduces osteoporosis through activating BMP-2/SMAD/Akt/RUNX2 pathway via targeting SMURF1.

Osteoporosis (OP) is among the most common frequent chronic metabolic bone diseases in postmenopausal women. Here, the effect and underlying mechanisms of miR-195-5p in OP were investigated both in vivo and in vitro. In this study, the microgravity (MG) environment was simulated in MC3T3-E1 cells, and miR-195-5p overexpression or SMURF1 knockdown model was constructed to test their effects on the proliferation, apoptosis and osteogenic differentiation of MC3T3-E1 cells. Furthermore, an OVX mouse model was constructed in vivo, and adenovirus-loaded miR-195-5p mimics were administered to the mice to overexpress miR-195-5p. HE staining and µCT were adopted to observe pathological changes of femur. The targeted relationship between miR-195-5p and SMURF1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment. The results indicated that miR-195-5p was down-regulated in the head of femur of OP mouse model and MC3T3-E1 cells subjected to MG microenvironment. In addition, overexpression of miR-195-5p promoted MC3T3-E1 cell osteogenic differentiation and inhibited apoptosis. Mechanistically, SMURF1 is identified as a target of miR-195-5p, and overexpressing miR-195-5p activates the BMP-2/SMAD/Akt/RUNX2 signal by inhibiting the SMURF1 expression. Moreover, SMURF1 downregulation accelerated the osteogenic differentiation of MC3T3-E1 cells and attenuated MG-mediated apoptosis. In addition, upregulating miR-195-5p reduced osteoporosis in the OVX mouse model, accompanied with SMURF1 downregulation and BMP-2/SMAD/Akt/RUNX2 pathway activation. Collectively, miR-195-5p enhances osteogenic differentiation of osteoclast and relieve OP progression in the mouse model through activation of the BMP-2/SMAD/Akt/RUNX2 axis by targeting SMURF1.

[The 484th case:asthma, limb numbness, diplopia, headache].

A 47-year-old female who had a history of asthma and sinusitis in the past was admitted to hospital with limbs numbness and pain for ten days. The symptoms were aggravated for eight hours. On admission, significant peripheral eosinophilia was noted. Paranasal sinusitis and transient bronchiolitis were found by CT scan.Electromyogram demonstrated multiple mononeuropathy. Eosinophilia was indicated by bone marrow biopsy. The diagnosis of eosinophilic granulomatous polyangiitis(EGPA) was determined. The patient got better after applying glucocorticoid and cyclophosphamide.Later she developed abdominal pain and partial oculomotor nerve palsy, while her condition improved after continued immunosuppression and anticoagulant therapy. She was hospitalized for the third time because of headache. Subarachnoid hemorrhage was diagnosed after lumber puncture and cranial MRI+MRA+MRV and other examinations. She was relieved after conservative treatment. Subarachnoid hemorrhage with EGPA is rare. This case may improve physicians' understanding of EGPA complicated with subarachnoid hemorrhage.

[Pepsin and bile acids detection in saliva for the diagnosis of gastroesophageal reflux disease].

Objective: To identify the value of the detection of pepsin and bile acids in saliva for the diagnosis of gastroesophageal reflux disease(GERD). Methods: From January 2018 to June 2019, 104 GERD patients and 43 healthy people in Guangdong Provincial People's Hospital were recruited. The 104 patients of GERD group were divided into four sub-groups, including esophageal symptoms GERD group, extraesophageal symptoms GERD group, anxiety or depression group, non-anxiety and non-depression group. Saliva was collected on waking in morning and 2 h after finishing lunch. The concentration of the total pepsin(TPP) and total bile acids(TBA) from saliva was detected by ELISA method. Receiver operating characteristics analysis was used to identify the sensitivity and specificity of the saliva pepsin and bile acids detection. Results: The concentration of TPP in morning waking samples and postprandial samples in the GERD group was 27.1(9.7,50.3) µg/L and 32.4(14.0,58.7) µg/L, the concentration of TBA in postprandial samples was (18.4±2.3)µmol/L, and these levels were significantly higher than that of the control group [7.0(5.1, 9.1) µg/L, 7.4(5.2, 9.4) µg/L, (12.6±5.0)µmol/L](P<0.01). The concentration of TBA in morning waking samples had no significant difference between these two groups(P>0.05). The concentration of TPP and TBA had no significant difference among the four GERD sub-groups(P>0.05).Pepsin in postprandial saliva samples had moderate diagnostic value for GERD, when the saliva pepsin concentration in postprandial samples was higher than 41.33 µg/L, it had a sensitivity of 82.8% and a specificity of 73.3%. The bile acids in saliva had no significant diagnostic value for GERD. Conclusions: Pepsin detection in saliva has a high level of sensitivity and specificity for diagnosing GERD. However, bile acids in saliva has no significant diagnostic value for GERD.

KNOCKDOWN OF CASEIN KINASE 1e INHIBITS CELL PROLIFERATION AND INVASION OF COLORECTAL CANCER CELLS VIA INHIBITION OF THE Wnt/ß-CATENIN SIGNALING.

Deregulation of casein kinase 1 epsilon (CK1ε) is involved in the development of multiple pathological disorders such as cancer, however the function and molecular mechanism of CK1εin cancer are still unclear. In the present study, we aimed to investigate the role of CK1ε in human colorectal cancer (CRC). The expression of CK1ε was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to observe the effects of lentivirus-mediated CK1ε shRNA (Lv-shCK1ε) on cell proliferation and invasive potential by MTT and Transwell assays in CRC cell line (SW480). As a result, we found that the expression of CK1ε protein was significantly increased in CRC tissues compared with that in adjacent non-cancerous tissues (ANCT) (68.9% vs 42.2%, P=0.017) and was correlated with the Duke’s staging and depth of invasion in CRC patients (P=0.012; P=0.015). Knockdown of CK1ε reduced cell proliferation and invasion of CRC cells followed by the downregulation of wnt3α, ß-catenin, PCNA and MMP-9. In conclusion, our findings show that high expression of CK1ε is positively associated with the Duke’s staging and depth of invasion in CRC patients, and knockdown of CK1ε suppresses the growth and invasion of CRC cells through inhibition of the wnt/ß-catenin signaling, suggesting that CK1ε may serve as a promising therapeutic target for the treatment of CRC.

[Advances in study on pharmacological effects of Epimedium].

OBJECTIVE: To review the progress in the research of the pharmacological activities of active ingredients and extracts of Epimedium. METHOD: Effects of Epimedium on cardiovascular system, circulatory system, immune system, genital system and bone marrow system, etc were reviewed, based on the recent 10 years pharmacological experimental studies. CONCLUSION: The results provided a rational foundation for the further development and utilization of Epimedium.