Efficacy and Safety of Tanezumab on Osteoarthritis Knee and Hip Pains: A Meta-Analysis of Randomized Controlled Trials.

Objectives: To evaluate the efficacy and safety of tanezumab for management of osteoarthritis (OA) knee and hip pain. Methods: Articles about management of OA knee and hip pains by tanezumab were systematically searched in PubMed, EBSCO, EMBASE, ScienceDirect, Web of Science, OVID, and Cochrane Library from the available date of inception until January 2016. Randomized controlled trials (RCTs) comparing the efficacy and safety of tanezumab with placebo/active comparator for management of OA knee and hip pains were included, and those with confounding conditions were excluded. Study quality was assessed using the Jadad five-point score. Finally, a meta-analysis of all eligible RCTs was performed on Review Manager 5.3 and STATA 12.0. Results: Nine studies with 10 RCTs that enrolled 7,665 patients were included. The reductions in pain intensity are significantly different between tanezumab-treated patients and placebo-treated patients (5,879 patients, mean difference [MD] = -0.98, 95% confidence interval [CI] = -1.18- -0.79). Both functional improvement (6,078 patients, MD = -1.10, 95% CI = -1.28- -0.92) and Patient's Global Assessment (PGA; 5,366 patients, MD = -0.27, 95% CI = -0.34- -0.20) are significantly different. There are significantly more discontinued patients due to adverse events (AEs) after treatment with tanezumab (6,537 patients, risk ratio = 1.62, 95% CI = 1.29-2.03). However, differences in serious AEs are not significant. Moreover, tanezumab-treated patients suffer from significantly more paraesthesia, arthralgia, hypoaesthesia, and peripheral edema. Conclusions: Tanezumab vs placebo provides superior pain relief and improvement in physical function and PGA in knee and hip osteoarthritis patients and is generally well tolerated with acceptable AEs. Low-dose tanezumab (10 or 25 µg/kg and 2.5 mg) provides similar effectiveness in reducing pain and improving function and is associated with fewer AEs. The long-term safety of tanezumab on osteoarthritis knee and hip pain needs further investigation.

Selenium-rich yeast counteracts the inhibitory effect of nanoaluminum on the formation of porcine neutrophil extracellular traps.

Aluminum is widely used in daily life due to its excellent properties. However, aluminum exposure to the environment severely threatens animal and human health. Conversely, selenium (Se) contributes to maintaining the balance of the immune system. Neutrophils exert immune actions in several ways, including neutrophil extracellular traps (NETs) that localize and capture exogenous substances. Despite the recent investigations on the toxic effects of aluminum and its molecular mechanisms, the immunotoxicity of aluminum nanoparticles on pigs and the antagonistic effect of selenium on aluminum toxicity are poorly understood. Here, we treated porcine peripheral blood neutrophils with zymosan for 3 h to induce NETs formation. Then, we investigated the effect of nanoaluminum on NETs formation in pigs and its possible molecular mechanisms. Microscopy observations revealed that NETs formation was inhibited by nanoaluminum. Using a multifunctional microplate reader, the production of extracellular DNA and the burst of reactive oxygen species (ROS) in porcine neutrophils were inhibited by nanoaluminum. Western blot analyses showed that nanoaluminum caused changes in amounts of cellular selenoproteins. After Se supplementation, the production of porcine NETs, the burst of ROS, and selenoprotein levels were restored. This study indicated that nanoaluminum inhibited the zymosan-induced burst of ROS and release of NETs from porcine neutrophils, possibly through the selenoprotein signaling pathway. In contrast, Se supplementation reduced the toxic effects of nanoaluminum and restored NETs formation.

Icaritin Inhibits Migration and Invasion of Human Ovarian Cancer Cells via the Akt/mTOR Signaling Pathway.

Ovarian cancer (OC) is the most lethal of all gynecologic malignancies with poor survival rates. Although surgical treatment and chemotherapy had advanced to improve survival, platinum-based chemoresistance remains a major hurdle in the clinical treatment of OC. The search for novel active ingredients for the treatment of drug-resistant OC is urgently needed. Here, we demonstrated that icaritin, the main active ingredient derived from the traditional Chinese herb Epimedium genus, significantly suppressed the proliferation, migration, and invasion of both drug-susceptible and cisplatin-resistant OC cells in vitro. Mechanistically, icaritin at 20 µM significantly inhibited the phosphorylation of Akt and mTOR, as well as decreased the expression of vimentin and increased the expression of E-cadherin. Our data indicate that icaritin, a prenylated flavonoid natural product, could serve as a potential inhibitor of cisplatin-resistant OC by inhibiting the Akt/mTOR signaling pathway.

Icaritin induces ovarian cancer cell apoptosis through activation of p53 and inhibition of Akt/mTOR pathway.

AIMS: Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers. Currently, the first-line OC treatment consists of cytoreductive surgery and platinum-based chemotherapy. However, most patients develop chemoresistance after the first-line treatment limits the success of treatment. Therefore, there is an urgent need to identify effective therapeutic agents. MAIN METHODS: Cell viabilities were detected by MTS assay; Annexin V-FITC/PI assay and western blotting assay were performed to analyze the apoptotic cells in vitro; An immunofluorescence assay was performed to analyze the TUNEL+ apoptotic cells in vivo; Patient-derived xenografts were established to test the in vivo antitumor effects; The key proteins of p53, caspase-mediated apoptotic pathway and Akt/mTOR pathway were detected by Western blotting. KEY FINDINGS: Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited the proliferation of drug-sensitive OC cells (OV2008 and C13*) and cisplatin resistant OC cells A2780cp. Icaritin induced OC cell apoptosis in vitro, as indicated by the increase of Annexin V+/PI+ apoptotic cells analyzed with flow cytometry, and the cleavage of caspase 9, caspase 3 and poly-ADP-ribose polymerase (PARP) detected with western blotting. Icaritin also inhibited tumor growth and induced OC cells apoptosis in patient-derived xenografts, as indicated by the tumor growth delay and increase of TUNEL-positive cells in tumor tissues. The icaritin-induced OC cell apoptosis may be associated with the activation of p53 and the suppression of Akt/mTOR pathway. SIGNIFICANCE: This study sheds light on the underlying mechanisms of antitumor effect of icaritin, and warrants clinical trial for treatment of OC.