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With the development of -omics approaches, the scientific community is now submerged by a wealth of information that can be used to analyze various parameters the degree of protein sequence conservation, protein 3D structures as well as RNA and protein expression levels in various benign and tumor tissues, during organism development or upon exposure to chemicals such as endocrine disrupters. However, if such information can be used to identify genes with potentially important biological function, additional studies are needed to deeply characterize their cellular function in model organisms. Here, we discuss the case of such a gene ERH, encoding a highly conserved homodimeric protein found in unicellular eukaryotes, plants and metazoan, of yet unknown biological function, which might be linked to mRNA metabolism and that is emerging as important for cell migration and metastasis.Approximately 20% of patients have persistent unexplained pain after total knee arthroplasty (TKA). Currently available treatments are unsatisfactory. The present report describes four patients in whom transcatheter arterial embolization had a remarkable effect on pain after TKA. Abnormal neovessels were identified in all patients. selleck chemicals For 48 h, one patient experienced remarkable postprocedural pain at the inner side of the knee that was subsided by level 1 analgesics and another patient development of a spontaneous skin ulceration resolving within 8 days. The mean Knee injury and Osteoarthritis Outcome Score pain subtotal had increased from 39 to 82 one month after treatment. Endovascular occlusion of neovascularization, decreasing chronic inflammation and the growth of unmyelinated sensory nerves may be treatment options for persistent unexplained pain following TKA.Level of Evidence IV, Case report.PURPOSE Acute lymphoblastic leukemia (ALL) is curable with standardized chemotherapy. However, the development of novel therapies is still required, especially for patients with relapsed or refractory disease. By utilizing an in vitro drug screening system, active molecular targeting agents against ALL were explored in this study. METHODS By the in vitro drug sensitivity test, 81 agents with various actions were screened for their cytotoxicity in a panel of 22 ALL cell lines and ALL clinical samples. The drug effect score (DES) was calculated from the dose-response of each drug for comparison among drugs or samples. Normal peripheral blood mononuclear cells were also applied onto the drug screening to provide the reference control values. The drug combination effect was screened based on the Bliss independent model, and validated by the improved isobologram method. RESULTS On sensitivity screening in a cell line panel, barasertib-HQPA which is an active metabolite of barasertib, an aurora B kinase inhibitor, alisertib, an aurora A kinase inhibitor, and YM155, a survivin inhibitor, were effective against the broadest range of ALL cells. The DES of barasertib-HQPA was significantly higher in ALL clinical samples compared to the reference value. There were significant correlations in DES between barasertib-HQPA and vincristine or docetaxel. In the drug combination assay, barasertib-HQPA and eribulin showed additive to synergistic effects. CONCLUSION Aurora B kinase was identified to be an active therapeutic target in a broad range of ALL cells. Combination therapy of barasertib and a microtubule-targeting drug is of clinical interest.CONTEXT Cold exposure (CE) has been shown to enhance energy expenditure by activating brown adipose tissue thermogenesis and metabolism in humans. However, it remains to be elucidated if there are gender-specific differences in cold-induced thermogenesis and metabolism. OBJECTIVE To study the impact of mild CE on resting energy expenditure (REE) and metabolism in males compared to females. SETTING A cross-sectional study. PARTICIPANTS 117 healthy young Caucasians participated in this study (58 males). Mean age was 25.1 ± 3.6 years and mean BMI 22.3 ± 1.7 kg/m². INTERVENTION Participants underwent a short-term CE using water perfused mattresses to activate non-shivering thermogenesis. MAIN OUTCOME MEASURES REE was assessed before and 2 hours after CE followed by blood sampling. Selected metabolites and hormones were measured. Skin temperatures were monitored at various sites throughout the experiment. RESULTS Participants showed a significant increase in REE after CE (6.5%, p less then 0.001). This increase did not differ between genders (p=0.908). However, there were differences between males and females in changes of plasma glucose (-5.1% vs. -7.4%, p=0.024), leptin (-14.3% vs. -30.1%, p less then 0.001) and adiponectin (5.4% vs. 12.8%, p=0.018) after CE. We observed a significant decrease of the supraclavicular skin temperature in men (-0.3%, p=0.034), but not in women (0.3%, p=0.326)(p=0.019 between genders). CONCLUSIONS We did not observe a difference in the thermogenic response, measured as change of REE, to CE in women compared to men. However, we found that some metabolic and hormonal changes were more pronounced in women compared to men suggesting a gender-specific response to cold. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] Mechanobiology phenomena constitute a major element of the cellular and tissue response during orthodontic treatment and the implantation of a biomaterial. Better understanding these phenomena will improve the effectiveness of our treatments. The objective of this work is to validate a model of three-dimensional (3D) culture of osteoblasts to study mechanobiology. MATERIALS AND METHODS The hFOB 1.19 cell line was cultured either traditionally on a flat surface or in aggregates called spheroids. They were embedded in 0.8% low-melting agarose type VII and placed in a polyethylene terephthalate transwell insert. Compressive forces of 1 and 4 g/cm2 were applied with an adjustable weight. Proliferation was evaluated by measuring diameters, monitoring glucose levels, and conducting Hoechst/propidium iodide staining. Enzyme-linked immunosorbent assays focusing on the pro-inflammatory mediators interleukin (IL)-6 and IL-8 and bone remodelling factor osteoprotegerin were performed to evaluate soluble factor synthesis.
Read More: https://www.selleckchem.com/
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