Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Pull-In Effect of Suspended Microchannel Resonator Sensor Subjected to Electrostatic Actuation.

In this article, the pull-in instability and dynamic characteristics of electrostatically actuated suspended microchannel resonators are studied. A theoretical model is presented to describe the pull-in effect of suspended microchannel resonators by considering the electrostatic field and the internal fluid. The results indicate that the system is subjected to both the pull-in instability and the flutter. The former is induced by the applied voltage which exceeds the pull-in value while the latter occurs as the velocity of steady flow get closer to the critical velocity. The statically and dynamically stable regions are presented by thoroughly studying the two forms of instability. It is demonstrated that the steady flow can remarkably extend the dynamic stable range of pull-in while the applied voltage slightly decreases the critical velocity. It is also shown that the dc voltage and the steady flow can adjust the resonant frequency while the ac voltage can modulate the vibrational amplitude of the resonator.

Identification and validation of AIB1 and EIF5A2 for noninvasive detection of bladder cancer in urine samples.

We previously demonstrated that amplified in breast cancer 1 (AIB1) and eukaryotic initiation factor 2 (EIF5A2) overexpression was an independent predictor of poor clinical outcomes for patients with bladder cancer (BCa). In this study, we evaluated the usefulness of AIB1 and EIF5A2 alone and in combination with nuclear matrix protein 22 (NMP22) as noninvasive diagnostic tests for BCa. Using urine samples from 135 patients (training set, controls [n = 50] and BCa [n = 85]), we detected the AIB1, EIF5A2, and NMP22 concentrations using enzyme-linked immunosorbent assay. We applied multivariate logistic regression analysis to build a model based on the three biomarkers for BCa diagnosis. The diagnostic accuracy of the three biomarkers and the model were assessed and compared by the area under the curve (AUC) of the receiver operating characteristic. We validated the diagnostic accuracy of these biomarkers and the model in an independent validation cohort of 210 patients. In the training set, urinary concentrations of AIB1, EIF5A2, and NMP22 were significantly elevated in BCa. The AUCs of AIB1, EIF5A2, NMP22, and the model were 0.846, 0.761, 0.794, and 0.919, respectively. The model had the highest diagnostic accuracy when compared with AIB1, EIF5A2, or NMP22 (p < 0.05 for all). The model had 92% sensitivity and 92% specificity. We obtained similar results in the independent validation cohort. AIB1 and EIF5A2 show promise for the noninvasive detection of BCa. The model based on AIB1, EIF5A2, and NMP22 outperformed each of the three individual biomarkers for detecting BCa.

Does chromophobe renal cell carcinoma have better survival than clear cell renal cell carcinoma? A clinical-based cohort study and meta-analysis.

BACKGROUND: It is controversial whether chromophobe renal cell carcinoma (chRCC) or clear cell renal cell carcinoma (ccRCC) is associated with better survival. We conducted a clinical-based cohort study and meta-analysis to evaluate the prognostic role of histology between chRCC and ccRCC. METHODS: A cohort of 1540 patients (166 with chRCC and 1374 with ccRCC) were selected from Sun Yat-sen University and The Cancer Genome Atlas databases. The clinicopathological parameters and overall survival (OS) were compared between patients with chRCC and those with ccRCC. For the meta-analysis, we searched the PubMed, Cochrane Library, and Ovid databases for studies comparing OS or cancer-specific survival (CSS) between chRCC and ccRCC. RESULTS: The cohort study revealed that patients with chRCC were younger (median 52 vs. 55 years, P < 0.001), were more commonly female (47.0 vs. 33.0%, P < 0.001), and had a larger tumor size (mean 7.1 vs. 5.9 cm, P < 0.001), and they had a lower stage compared with those with ccRCC. Five-year OS rates for chRCC and ccRCC were 90.3 and 75.3%, respectively (P < 0.001). We found significantly better survival for chRCC in stratification analysis by age, sex, tumor size, and stage. Similar results were observed on both univariate [hazard ratio (HR), 0.30; 95% confidence interval (CI) 0.16-0.55, P < 0.001] and multivariate analyses (HR 0.42; 95% CI 0.23-0.79, P = 0.006). Ten studies were included in our meta-analysis. Eight of them provided data on univariate analysis. The pooled HR was statistically significant for OS (pooled HR 0.49; 95% CI 0.30-0.79, P = 0.004) and CSS (pooled HR 0.49; 95% CI 0.37-0.64, P < 0.001). Seven studies reported the HR on multivariate analysis. The pooled HR was also statistically significant for OS (pooled HR 0.63; 95% CI 0.51-0.77, P < 0.001) and CSS (pooled HR 0.72; 95 % CI 0.57-0.90, P = 0.003). These data indicate that patients with chRCC had better outcomes than those with ccRCC. CONCLUSIONS: Our large cohort study and meta-analysis confirmed that chRCC had better survival than ccRCC.

[Study on intra-gastric floating beads of naringenin].

OBJECTIVE: To prepare calcium alginate-chitosan intra-gastric floating beads of naringenin combining with the solid dispersion method and investigate the in vitro floating characteristics, entrapment efficiency and drug release property of the beads. METHODS: The solid dispersion of naringenin was prepared by the Eudragit RLPO. Sodium alginate solution mixed with the powder of the solid dispersion of naringenin and frother was slowly dripped into chitosan-calcium chloride solution added with acetic acid. Calcium alginatechitosan intra-gastric floating beads of naringenin were obtained after drying. The effects of solid dispersion on in vitro release of naringenin were investigated. RESULTS: Intra-gastric floating beads of naringenin were acquired successfully. More than 70% of the beads kept floating in artificial gastric juice in 9 h, the release ratio of naringenin during 9 h was 65%-70% and the entrapment efficiency was about 70%-80%. CONCLUSION: The sustained release of naringenin in the calcium alginate-chitosan intra-gastric floating beads could be achieved by using the solid dispersion method and it provides some ideas of intra-gastric floating preparations.