Therapeutic potential of anti-miR29a in breast cancer patients with type 2 diabetes: an in vitro and xenograft mouse-model study.

Background: MicroRNAs (miRNAs) acting as tumour suppressors or oncogenes, known as oncomiRs, are a promising new focus in targeted therapies for cancer. Approximately 16% of breast cancer patients have pre-existing diabetes. Breast cancer with type 2 diabetes mellitus (BDM) is provided with its unique biological characteristics and clinical characteristics. This study primarily investigated the therapeutic potential and regulatory mechanism of miR-29a in patients with BDM. Methods: The significance of miR-29a in BDM was analyzed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in breast tissues. A cell model for BDM was established by using MDA-MB-231 cells cultured in 3T3-L1 adipocytes cultured with high levels of glucose and insulin. A type 2 diabetes mellitus (T2DM) mouse model was induced in female BALB/c mice through a high-fat diet plus low doses of streptozotocin (STZ). The xenograft mouse-model for BDM was established on these T2DM mouse by using MDA-MB-231 cells. Then the biological effects of miR-29a knockdown mediated by lentivirus-shRNAs on cell proliferation, apoptosis, cell cycle, and migration were investigated. Results: Our results indicated that miR-29a was upregulated in patients with BDM, which correlated with a worse prognosis. In human breast cancer cells, miR-29a knockdown reduced cell proliferation and cell migration and invasion in BDM. In the T2DM xenograft, miR-29a knockdown suppressed MDA-MB-231 cells tumorigenesis and metastasis. We also demonstrated that miR-29a promoted BDM cell growth and metastasis by targeting Sirtuin 1 (SIRT1). Conclusions: Our findings indicated that anti-miR-29a inhibited cell proliferation and invasion in BDM by targeting SIRT1. We believe anti-miR-29a may represent a novel therapeutic approach for the management of patients with BDM.

LncRNA SNHG7 Mediates the Chemoresistance and Stemness of Breast Cancer by Sponging miR-34a.

Chemoresistance is considered to be a major cause of the recurrence and metastasis of breast cancer (BC). LncRNA SNHG7 has been reported to be upregulated in breast cancer and to promote tumor progression and metastasis. Nevertheless, the function and potential regulatory mechanism of SNHG7 in BC drug resistance are still largely unclear. This study indicated that SNHG7 was highly expressed in chemoresistant BC tissues and cells. Upregulated SNHG7 might predict a low pCR rate and poor clinical outcome in BC patients. Knockdown of SNHG7 enhanced drug sensitivity and drug-induced apoptosis in chemoresistant BC cells. In terms of the mechanism, miR-34a was found to be a target of SNHG7 and its expression in breast cancer tissues and chemoresistant cell lines was negatively correlated with SNHG7 expression. Importantly, sh-SNHG7 upregulated miR-34a expression, reduced the percentages of CD44+/CD24-cells, and inhibited sphere-formation and stem cell factor (Oct4, Nanog, SOX2) expression. Functional loss experiments showed that the repressive effect of SNHG7 knockdown on BC cell stemness was partially reversed by transfection with miR-34a inhibitors. In summary, this study indicated that SNHG7 contributed to the chemoresistance of BC and mediated chemoresistance and cancer stemness by sponging miR-34a.

Deep Reinforcement Learning-Based Traffic Signal Control Using High-Resolution Event-Based Data.

Reinforcement learning (RL)-based traffic signal control has been proven to have great potential in alleviating traffic congestion. The state definition, which is a key element in RL-based traffic signal control, plays a vital role. However, the data used for state definition in the literature are either coarse or difficult to measure directly using the prevailing detection systems for signal control. This paper proposes a deep reinforcement learning-based traffic signal control method which uses high-resolution event-based data, aiming to achieve cost-effective and efficient adaptive traffic signal control. High-resolution event-based data, which records the time when each vehicle-detector actuation/de-actuation event occurs, is informative and can be collected directly from vehicle-actuated detectors (e.g., inductive loops) with current technologies. Given the event-based data, deep learning techniques are employed to automatically extract useful features for traffic signal control. The proposed method is benchmarked with two commonly used traffic signal control strategies, i.e., the fixed-time control strategy and the actuated control strategy, and experimental results reveal that the proposed method significantly outperforms the commonly used control strategies.

Predictors of Ibandronate Efficacy for the Management of Osteoporosis: A Meta-Regression Analysis.

BACKGROUND: Aim of the present study was to identify the predictors of ibandronate efficacy in subjects with osteoporosis or decreased bone mineral density (BMD). METHOD: Several electronic databases were searched by using specific keywords for the acquisition of research articles reporting the efficacy of ibandronate in subjects with osteoporosis or decreased BMD. Metaregression analyses were carried out by using changes in the BMD of lumbar spine and total hip following ibandronate treatment as dependent (outcome) variables against several independent (explanatory) variables. RESULTS: Data were extracted from 34 studies (11,090 ibandronate treated subjects) which fulfilled eligibility criteria. A history of previous fracture/s was reported by 46% of these subjects. In overall population, longer treatment duration from 1 to 5 years, increasing age, history of previous fractures, lower baseline T score, and higher baseline levels of C-terminal telopeptide of type 1 collagen (CTX) predicted higher ibandronate efficacy in improving BMD of the lumbar spine as well as of the total hip. Lower baseline levels of vitamin D and higher baseline levels of bone specific alkaline phosphatase (BSAP) predicted higher efficacy of ibandronate for lumbar spine only. In postmenopausal women with osteoporosis or decreased BMD, in addition to above-mentioned predictors, better efficacy of ibandronate was also associated with increasing time since menopause for both lumbar spine and total hip and lower body weight for lumbar spine only. CONCLUSION: Longer treatment duration from 1 to 5 years, increasing age, lower baseline T scores, and higher serum CTX levels are identified as the predictors of better efficacy of ibandronate in the study subjects with osteoporosis or decreased BMD.

[Treatment of linguiform calcaneus fracture by close nail-pry reduction and internal fixation with hollow screws].

OBJECTIVE: To study the curative effects of close nail-pry reduction and internal fixation with hollow screws for treatment of linguiform calcaneus fracture. METHODS: From May 2006 to October 2009,32 patients (35 feet) with linguiform calcaneus fracture were treated by close nail-pry reduction and internal fixation with hollow screws, including 23 males and 9 females ranging in age from 25 to 46 years, with a mean of 37.6 years. According to Paley classification, 3 cases were Paley II a, and 29 cases were Paley II b. All cases were close fractures. The time from injury to operation was 3 to 10 days after most swelling subsided. Böhler angle and Gissane angle were measured by X-ray before and after operation. The therapeutic effect was assessed according to ZHANG Tie-liang's foot score. RESULTS: All the patients were followed-up for 6 to 18 months, with a mean of 12 months. All fractures gained bone healing. The time of fracture healing averaged 12 months. The fractures healed completely and no infection occurred. According to ZHANG Tie-liang's foot scale, the postoperative function was excellent in 18 feet, good in 10 feet, moderate in 5 feet and poor in 2 feet. The Böhler angle and Gissane angle were significant improved after treatment (P < 0.01). CONCLUSION: The surgical method of close nail-pry reduction and internal fixation with hollow screws for treatment of linguiform calcaneus fracture can regain the foot function, with minimal injury, fewer complications, earlier recovery and lower costs.