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  • Futtrup Bynum posted an update 6 days, 21 hours ago

    In ovarian carcinoma, anti-Müllerian hormone (AMH) type II receptor (AMHRII) and the AMH/AMHRII signaling pathway are potential therapeutic targets. Here, AMH dose-dependent effect on signaling and proliferation was analyzed in four ovarian cancer cell lines, including sex cord stromal/granulosa cell tumors and high grade serous adenocarcinomas (COV434-AMHRII, SKOV3-AMHRII, OVCAR8 and KGN). selleck products As previously shown, incubation with exogenous AMH at concentrations above the physiological range (12.5-25 nM) decreased cell viability. Conversely, physiological concentrations of endogenous AMH improved cancer cell viability. Partial AMH depletion by siRNAs was sufficient to reduce cell viability in all four cell lines, by 20% (OVCAR8 cells) to 40% (COV434-AMHRII cells). In the presence of AMH concentrations within the physiological range (5 to 15 pM), the newly developed anti-AMH B10 antibody decreased by 25% (OVCAR8) to 50% (KGN) cell viability at concentrations ranging between 3 and 333 nM. At 70 nM, B10 reduced clonogenic survival by 57.5%, 57.1%, 64.7% and 37.5% in COV434-AMHRII, SKOV3-AMHRII, OVCAR8 and KGN cells, respectively. In the four cell lines, B10 reduced AKT phosphorylation, and increased PARP and caspase 3 cleavage. These results were confirmed in ovarian cancer cells isolated from patients’ ascites, demonstrating the translational potential of these results. Furthermore, B10 reduced COV434-MISRII tumor growth in vivo and significantly enhanced the median survival time compared with vehicle (69 vs 60 days; p = 0.0173). Our data provide evidence for a novel pro-survival autocrine role of AMH in the context of ovarian cancer, which was targeted therapeutically using an anti-AMH antibody to successfully repress tumor growth.Recently, fructosamine has shown promising results in predicting adverse outcomes following total knee arthroplasty. The purpose of this study was to assess the utility of fructosamine to predict adverse outcomes following total hip arthroplasty (THA). A prospective multi-center study involving four institutions was conducted. All primary THA were evaluated for glycemic control using fructosamine levels prior to surgery. Adverse outcomes were assessed at a minimum 1 year from surgery. Primary outcome of interest was periprosthetic joint infection (PJI) based on the International Consensus Meeting (ICM) criteria. Secondary outcomes assessed were superficial infections, readmissions and death. Based on previous studies on the subject, fructosamine levels above 293 µmol/L were used to define inadequate glycemic control. Overall 1212 patients were enrolled in the present study and were available for follow up at a minimum 1 year from surgery. Of those, 54 patients (4.5%) had elevated fructosamine levels (> 293 µmol/L) and these patients were 6.7 times more likely to develop PJI compared to patients with fructosamine levels below 293 µmol/L (p = 0.002). Patients with elevated fructosamine were also associated with more readmissions (16.7% vs. 4.4%, p  less then  0.007) and a higher mortality rate (3.7% vs. 0.6%, p = 0.057). These associations remained statistically significant in a multi-regression analysis after adjusting for age, comorbidities and length of stay; Adjusted odds ratio were 6.37 (95% confidence interval 1.98-20.49, p = 0.002) for PJI and 2.68 (95% confidence interval 1.14-6.29, p = 0.023) for readmissions. Fructosamine is a good predictor of adverse outcomes in patients undergoing THA and should be used routinely to mitigate morbidity and mortality risk.Recent studies have found that the core-shell structured metal nanoparticles and porous carbon nanofibers (PCNF) are combined into a microwave absorbing material through electrospinning, which exhibits excellent microwave absorption performance. In this study, the core-shell structure Co nanoparticles prepared by the self-developed HEIBE process (production rate of > 50 g/h) were combined with porous carbon fibers, and their absorbing properties were greatly improved. The morphology of Co/PCNF demonstrated that CoNPs are randomly dispersed in the porous carbon nanofibers and carbon nanofiber form complex conductive network which enhances the dielectric loss of the materials. Meanwhile, the Co/PCNF has a low graphitization and shows a significant improvement in permittivity due to the combination of CoNPs and high conductivity of carbon material. The maximum reflection loss (RL) of Co/PCNF reaches - 63.69 dB at 5.28 GHz with a thickness of 5.21 mm and the absorption bandwidth (RL ≤  - 10.0 dB) is 12.92 GHz. In terms of 5.60 mm and 6.61 mm absorber, there are two absorption peaks of - 47.64 dB and - 48.30 dB appear around 12.50 GHz and 14.10 GHz, respectively. The results presented in this paper may pave a way for promising applications of lightweight and high-efficiency microwave absorbing materials (MAMs).Statins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.