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Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance.

Purpose Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. Methods We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. Results A total of 68 miRNAs showed significantly different expression patterns between the groups ( p < 0.001), and 13 of these miRNAs were significantly associated with poor survival ( p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. Conclusion The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.

Aims:To compare the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) as monotherapy or add-on to metformin (Met) in patients with type 2 diabetes mellitus (T2DM). Materials and Methods:PubMed, Embase and ClinicalTrials.gov sites were systematically searched for randomized controlled trials to assess the efficacy and safety of DPP-4is and SGLT-2is in patients with T2DM. Risk ratio (RR) and weighted mean difference (WMD) were used to evaluate outcomes.Results: In the analysis of 25 randomized trials, which involved 14 619 patients, SGLT-2is were associated with a significantly stronger reduction in haemoglobin A1c (HbA1c) (WMD 0.13%, 95% credible interval [CI], 0.04%-0.22%, P = .005) and fasting plasma glucose (FPG) (WMD 0.80 mmol/L, 95% CI, 0.58-1.01 mmol/L, P < .00001) than were DPP-4is. However, no significant difference between the 2 drug categories was found in the risk of hypoglycaemic events (RR, 0.99; 95% CI, 0.78-1.26, P = .92). SGLT-2is plus Met was associated with a more significant decrease in FPG (WMD 0.71 mmol/L, 95% CI, 0.43-1.00 mmol/L, P < .00001) than was DPP-4is plus Met. However, no differences were found in the reduction of HbA1c (WMD 0.11%, 95% CI, −0.03%-0.25%, P = .12) or the risk of hypoglycaemic events (RR, 1.02; 95% CI, 0.80-1.31, P = .86).Conclusions: This review revealed that, compared to DPP-4is, SGLT-2is significantly reduced HbA1c, FPG and body weight without increasing the risk of hypoglycaemia in diabetes treatment. | MATERIALS AND METHODS | Data sources and search strategyElectronic searches were performed in PubMed, Embase and ClinicalTrials.gov sites from inception to May 1, 2017 using the following search terms: linagliptin, saxagliptin, sitagliptin, dipeptidyl peptidase-4 inhibitors, DPP-4is, canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, ertugliflozin, sodium-glucose cotransporter-2 inhibitors, SGLT-2is. There was no restriction on language of publication.The reference lists of the related studies were manually examined to identify any additional publications relevant to our analysis. | Inclusion and exclusion criteriaInclusion criteria were as follows: (1 Exclusion criteria were as follows: (1) trials involving animals or healthy human subjects; (2) non-randomized trials; (3) letters or case reports; (4) articles that provided inadequate information of interest or primary data; (5) trials with a duration of less than 12 weeks. | Study selection and data extractionTwo independent researchers (Z. W. and J. S.) screened the search results and selected studies in strict accordance with the inclusion and exclusion criteria. Any resulting discrepancies were resolved by discussion with a third researcher (X. D.).The following data were independently extracted from the studies using a standardized form that included: trial characteristics (first author, publication year, sample size, duration of therapy, medications, the National Clinical Trial number); participants' baseline (age, gender, HbA...