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Quercetin (QU), a hyperthermic sensitizer, when combined with cisplatin (CP) affects tumor growth. To determine the effects of QU and CP and their interactions, multimodal treatment in vitro and in vivo models under physiological and hyperthermic conditions was performed. In vitro, different sensitivity of T24 and UMUC human bladder cancer cells was observed after short-term exposure to QU (2 h) and CP (1 h). Effects of both compounds were investigated at low and high micromolar concentrations (1 and 50 µM, respectively) under both thermal conditions. QU acted in additive or synergistic manner in combination with CP between physiological condition and hyperthermia. As determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, short-term application of QU and CP reduced cell viability. Clonal assay also indicated that combined treatment with QU and CP is lethal to bladder cancer cells in both conditions. In vivo, CP (5 or 10 mg kg-1) and QU (50 mg kg-1) acted synergistically with hyperthermia (43 °C) and inhibited tumor growth, activated immune effectors and increased mice survival. Our results demonstrate that combined treatment with CP and QU may increase death of tumor cells in physiological and hyperthermic conditions which could be clinically relevant in locoregional chemotherapy.Children are increasingly exposed to electronic media, which can potentially influence their sleep habits. However, few studies have investigated the effects of children's life patterns on sleep habits and electronic media usage. This study investigated the differences in sleep habits and electronic media usage between 18- and 42-month-old children attending nursery schools, kindergartens, or staying at home, and respectively enrolled 183 (boys, n = 93; girls, n = 90) and 215 (boys, n = 104; girls, n = 111) 18- and 42-month-old children who underwent health check-ups. We found that 18-month-old children attending nursery school had significantly earlier wake times on weekdays and shorter sleep durations on weekends than children who stayed at home despite no differences in electronic media usage. There were no differences in sleep duration among 42-month-old children attending nursery schools, kindergartens, or staying at home; however, kindergarteners demonstrated a higher use of portable and home video games. Different life patterns affect electronic media usage in preschool children, especially those attending kindergarten. Particular attention should be paid to the higher usage of electronic media devices by kindergarteners, although they had the same sleep duration, as did other preschool children.Myofascial pain syndrome is widely considered to be among the most prevalent pain conditions, both in the community and in specialized pain clinics. While myofascial pain often arises in otherwise healthy individuals, evidence is mounting that its prevalence may be even higher in individuals with various comorbidities. Comorbid myofascial pain has been observed in a wide variety of medical conditions, including malignant tumors, osteoarthritis, neurological conditions, and mental health conditions. Here, we review the evidence of comorbid myofascial pain and discuss the diagnostic and therapeutic implications of its recognition.The mitogen-activated protein kinase (MAPK)/extracellular signal kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal transduction pathways have been implicated in the pathogenesis of leukemia. The aim of this study was to investigate the effect of the combination of ERK1/2 inhibitor AZD0364 and PI3K inhibitor ZSTK474 on acute lymphoblastic leukemia (ALL) REH, MOLT-4, acute myeloid leukemia (AML) MOLM-14, and chronic myeloid leukemia (CML) K562 cell lines. https://www.selleckchem.com/products/ly2606368.html To evaluate the interactions of the drugs, cells were treated for 48 h with AZD0364 or ZSTK474 alone and in combination at fixed ratios. The combinatorial effects of both inhibitors were synergistic over a wide range of concentrations in REH, MOLT-4, and MOLM-14 cell lines. However, in K562 cells, the effects were found to be antagonistic. Furthermore, AZD0364 and ZSTK474 significantly decreased both ERK1/2 and AKT activation in REH, MOLT-4, and MOLM-14 cells. The results showed that incubation with both AZD0364 and ZSTK474 inhibited cell viability, increased reactive oxygen species (ROS) production, and induced apoptosis in leukemia cells. We observed that combined treatment with AZD0364 and ZSTK474 affected nuclear factor-κB (NF-κB) and antioxidant protein levels NF-E2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), thioredoxin (Trx), thioredoxin reductase (TrxR), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. These effects were accompanied with decreased antiapoptotic survivin protein level. However, distinct cell line dependent effects were observed. In conclusion, the combination of AZD0364 and ZSTK474 can exert a synergistic anticancer effect in ALL and AML cells, which is associated with the induction of oxidative stress and the involvement of cellular antioxidant defense mechanisms.In the forging industry, surface quality and surface treatments of dies are crucial parameters to extend their life. These components are usually machined by milling or by Electrical Discharge Machining (EDM), and the final surface roughness depends on the machining techniques and operational conditions used in its fabrication. After milling, a nitriding treatment is widely applied to extend its service life. Nevertheless, no scientific report that informs about nitriding after EDM has been found. Accordingly, this work focuses on the wear and friction behavior of pins made of brass and medium carbon steel sliding over AISI H13 discs, made by wire EDM in the conditions of finishing and roughing. The discs are plasma nitride, and their effect on the wear during pin-on-disc tests is evaluated. In this sense, the analysis of the surface damage for the different pins will help us to understand the service life and wear evolution of the forging dies. The results show that plasma nitride reduces the friction and prevents the degradation of the pin, independently of the material of the pin, when sliding over finishing and roughing EDM conditions.
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