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Eriksen Teague posted an update 6 days, 13 hours ago
Cancer cachexia is a complex metabolic disease so far lacking effective therapy, and it accounts for approximately one third of all cancer-related deaths worldwide. The extracellular ligand Wnt7a has a dual function in skeletal muscle, inducing the anabolic AKT/mammalian target of rapamycin (mTOR) pathway in myofibers and driving muscle stem cell expansion in skeletal muscle, making it a promising candidate for treatment of muscle wasting diseases. In murine and human myotubes, Wnt7a activates the anabolic AKT/mTOR pathway, thereby preventing cachexia-induced atrophy with a single application being sufficient to prevent atrophy independently of the tumor cell type causing cachexia. Addition of Wnt7a also improved activation and differentiation of muscle stem cells in cancer cachexia, a condition under which skeletal muscle regeneration is severely impaired due to stalled muscle stem cell differentiation. Finally, we show that Wnt7a prevents cancer cachexia in an in vivo mouse model based on C26 colon carcinoma cells. Wnt7a has a dual role in cachectic skeletal muscle; that is, it effectively counteracts muscle wasting through activation of the anabolic AKT/mTOR pathway and, furthermore, reverts the loss of muscle stem cell functionality due to cancer cachexia, making Wnt7a a promising candidate for an ameliorative treatment of cancer cachexia. © 2020 The Author(s).Follicular thyroid carcinoma (FTC) is a common endocrine malignancy with highly aggressive features. In this study, next-generation sequencing technology was used to identify aberrant expression of sialyltransferase (ST) family members in FTC. Aberrant high expression of alpha-2,6-sialyltransferase 2 (ST6GAL2) was demonstrated to promote tumorigenesis of FTC in vitro and in vivo. Furthermore, ST6GAL2 promoted tumorigenesis by inactivating the Hippo signaling pathway. Resveratrol is a native compound extracted from Vitis species, and many studies have confirmed its protective cardiovascular and antineoplastic effects. Here we found that resveratrol can inhibit the tumorigenesis of FTC by suppressing the expression of ST6GAL2, further activating the Hippo pathway. selleck inhibitor In summary, this study revealed the role of the ST6GAL2-Hippo signaling pathway in FTC tumorigenesis and indicated that resveratrol, a commonly found antineoplastic compound, could inhibit tumorigenesis of FTC by regulating the abovementioned pathways. © 2020 The Authors.The overexpression of ATP-binding cassette (ABC) transporters is one of the important mechanisms of multidrug resistance (MDR). Some tyrosine kinase inhibitors (TKIs) such as CM082 might be a potential ABC transporter inhibitor, thus potentially reversing MDR. We used a 3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTT) assay to determine the cytotoxicity and reversal effect of CM082. A xenograft model was established to evaluate the reversal MDR efficacy in vivo. The intracellular accumulation and efflux of ABCG2 substrates were measured by flow cytometry. We investigated the binding sites of ABCG2 via photolabeling ABCG2 with [125I]-iodoarylazidoprazosin (IAAP). Quantitative real-time PCR and western blot were utilized to analyze mRNA and protein expression. We found that CM082 could enhance the efficacy of substrate in ABCG2-overexpressing cells both in vitro and in vivo. Furthermore, CM082 significantly increased intracellular accumulation of ABCG2 substrates by inhibiting the efflux activity. CM082 stimulated ABCG2 ATPase activity and competed with [125I]-IAAP photolabeling of ABCG2 in a concentration-dependent manner. However, CM082 did not alter ABCG2 expression at protein and mRNA levels or inhibit vascular endothelial growth factor (VEGF) downstream signaling of AKT and extracellular signal-regulated kinase (ERK). Further research is encouraged to confirm whether CM082 concomitant with anticancer drugs of ABCG2 substrates could improve the clinical outcomes of cancer treatment in cancer patients with ABCG2 overexpression. © 2020 The Authors.Games from experimental economics have provided insights into the evolutionary roots of social decision making in primates and other species. Multiple primate species’ abilities to cooperate, coordinate and anti-coordinate have been tested utilizing variants of these simple games. Past research, however, has focused on species known to cooperate and coordinate in the wild. To begin to address the degree to which cooperation and coordination may be a general ability that manifests in specific contexts, the present study assessed the decisions of squirrel monkeys (Saimiri boliviensis; N = 10), a species not known for their cooperative behavior in these games. Pairs of monkeys were presented with the Assurance Game (a coordination game), the Hawk-Dove Game (an anti-coordination game) and the Prisoner’s Dilemma (a cooperation game with a temptation to defect). We then compared squirrel monkeys’ performance to existing data on capuchin monkeys (Sapajus [Cebus] apella), a closely related species that routinely cooperates, to determine what, if any, differences in decision making emerged. Some pairs of both species found the payoff-dominant Nash Equilibrium (NE) in the coordination game, but failed to find the NE in subsequent games. Our results suggest that, like capuchins, squirrel monkeys coordinate their behavior with others, suggesting that such mutual outcomes occur in at least some contexts, even in species that do not routinely cooperate.The noticeable increase in the occurrence of multidrug-resistant Klebsiella pneumoniae strains separated from different hospitals in Taif city, (Saudi Arabia) demonstrates the limitation of antibiotics used for bacterial eradication. The aim of the present study is to detect the virulence genes in some K. pneumoniae isolates that collected from different hospitals in Taif governorate in Saudi Arabia. A total of 134 clinical samples were used to isolate about twenty three K. pneumoniae strains from various clinical specimens throw six months. They were identified by microbiological method as K. pneumoniae and confirmed with 16S rRNA sequencing analysis. The antimicrobial susceptibility of K. pneumoniae isolates was determined. The existence of virulence genes (AcrAB, tolC, arb, OmpK35, RmpA, fimH-1, entB, K2, irP-1 and Mdtk) were performed by PCR. The multidrug-resistant strains were detected in 16 (69.5%), that showed the presence of the most virulence genes. The multidrug-resistant isolates showed resistance against Ampicillin (96%), Amox-Clav (90%), Cephalothin (90%), Cefuroxime (90%), Ceftriaxone (85%), Aztreonam (87%), Cefepime (80%), Ceftazidime (80%), and Trim-Sulf (82%).