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IRE1α endonuclease is a key regulator of endoplasmic reticulum (ER) stress that controls cell survival/apoptosis in cancers. Inhibition of IRE1α endonuclease leads to decreased splice XBP1 which decreases cell proliferation and increases cell death in cancer cells. Therefore, this study investigated the effects and mechanism of STF-083010 (an IRE1α inhibitor) on the cell growth/apoptosis of ovarian malignant cells via the XBP1-CHOP-Bim pathway following the induction of ER stress (ERS). ERS in OVCAR3 and SKOV3 cells was measured using Thioflavin T staining. The expression of ER stress response genes was evaluated by QRT-PCR. The levels of XBP1(s), PERK, phospho-PERK, p-PP2A, ATF4, BIP/GRP78, CHOP, and Bim proteins were evaluated using western blotting. Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were assessed using BrdU, MTT, Annexin V-FITC/PI staining, and caspases-12 and -3 activity assays. The results showed increased XBP1, CHOP, and ATF-4 mRNA expression levels as well as high protein aggregation in STF-083010 and Tm co-treated cells. The IRE1α inhibitor down-regulated sXBP1 and BIP proteins, while XBP-1, p-PERK, ATF-4, CHOP, and Bim proteins were up-regulated. STF-083010 reduced cell proliferation and induced apoptosis through the activation of caspases-12 and -3 and Bax/Bcl-2 protein expression. In summary, the present data revealed the effects of STF-083010 in ER stress and apoptosis as well as signaling via XBP1/CHOP/Bim mediators. Thus, STF-083010 is proposed as a new target for the control of ERS in ovarian cancer cells.CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). In this study, we aimed to explore the anticancer effects of CUDC-907 on human breast cancer cells. Our results showed that CUDC-907 effectively inhibited breast cancer cell proliferation. Flow cytometry analysis revealed that CUDC-907 induced cell cycle arrest and apoptosis in breast cancer cells. The combined treatment of CUDC-907 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in a marked increase in apoptosis and cleavage of caspase-8, -9 and poly (ADP-ribose) polymerase (PARP) in breast cancer cells. CUDC-907 enhanced expressions of death receptor 5 (DR5), reduced the levels of anti-apoptotic molecules XIAP, Bcl-2 and Bcl-xL. Knockdown of DR5 abrogated apoptosis induced by the combination of CUDC-907 and TRAIL in breast cancer cells. CUDC-907 increased the phosphorylation of JNK and p38 MAPK. JNK inhibitor pretreatment attenuated CUDC-907-induced upregulation of DR5. In summary, CUDC-907 shows potent cytotoxicity against breast cancer cells and facilitates TRAIL-mediated apoptosis through DR5 upregulation. The combination of CUDC-907 and TRAIL may be a promising therapeutic approach in the treatment of breast cancer.Acute elevations in blood pressure (BP), usually defined as ≥ 180/110 mmHg, may present with highly heterogeneous profiles ranging from absence of symptoms to life-threatening target organ damage. In most recent years the diagnostic approach and the treatment of hypertension have gained interest by patients and physicians. The GEAR project (Gestione delle Emergenze e urgenze in ARea critica, management of hypertensive emergencies and hypertensive urgencies in the emergency setting) was proposed by the group of Young Investigators of the Italian Society of Hypertension as a survey aimed to evaluate the awareness, diagnosis and treatment of hypertensive emergencies and urgencies in Italy.Bariatric surgery is currently the most effective weight loss treatment of severe obesity and its associated comorbidities and is being increasingly used to treat children and adolescents with severe obesity, including those with Type 2 Diabetes (T2D). This review focuses on the conventional management of T2D in children and adolescents, comparison of various types of bariatric surgeries, effect of bariatric surgery on gastrointestinal physiology and metabolism, current literature on the use of bariatric surgery to treat youth with severe obesity and T2D, and the potential complications of bariatric surgery in this population.This chapter gives an overview of present knowledge and clinical aspects of antidiabetic drugs according to the recently available research evidence and clinical expertise.Many agents are acting on eight groups of pathophysiological mechanisms, which is commonly called as "Ominous Octet" by DeFronzo. The muscle, liver and β-cell, the fat cell, gastrointestinal tract, α-cell, kidney, and brain play essential roles in the development of glucose intolerance in type 2 diabetic individuals (Defronzo, Diabetes 58773-795, 2009).A treatment paradigm shift is seen in the initiation of anti-hyperglycemic agents from old friends (meglitinides or sulphonylürea) to newer agents effecting on GLP-1 RA or SGLT-2 inhibitors. It is mostly about the other protective positive effects of these agents for kidney, heart, etc. Although there are concerns for the long term safety profiles; they are used widely around the World. The delivery of patient-centered care, facilitating medication adherence, the importance of weight loss in obese patients, the importance of co-morbid conditions are the mainstays of selecting the optimal agent.BACKGROUND Physical activity recommendations for aging adults do not account for possible benefits of light-intensity physical activity on physical function. The purpose of this study was to assess if a sum of all physical activities (regardless of intensity) related to physical function for aging adults, independent of physical activity guidelines. METHODS This cross-sectional study was conducted with baseline data of the Canadian Longitudinal Study on Aging (CLSA n = 25,072) including ages from 45 to 85. Physical activity was collected via the Physical Activity Scale for Elderly questionnaire. The sum of all activities, based on the Metabolic Equivalent of a Task (MET), was called Total Index. Physical function was derived from objective measures. Logistic regression was used for statistical analysis based on the specific age and sex median values of physical function. RESULTS The Total Index was associated with being in the lowest median of physical function when adjusted for the physical activity guidelines and other potential confounders (OR = 1.02, 95% CI = 1.01-1.03, p  less then  0.05). CONCLUSION This study suggests that components of physical activity not currently included in current guidelines may be associated with better physical function outcomes for aging adults.BACKGROUND Chronic kidney disease is a global health problem that is closely related to the aging population. Although plasma glucose levels have been shown to be related to renal dysfunction, risk factors for renal functional impairment in the geriatric population are unknown. The authors therefore aimed to investigate the determinants of renal functional impairment in an elderly population. METHODS From June 2014 to August 2015, 912 participants (aged > 65 years) were recruited. Renal function was assessed at baseline; follow-up was conducted in 2016. Within the framework of comprehensive cardiovascular examinations, all conventional cardiovascular risk factors, fasting plasma glucose (FPG), and renal function were assessed. Renal function was evaluated by the estimated glomerular filtration rate (e-GFR) using a modified Modification of Diet in Renal Disease formula. Rapid decline in e-GFR was defined as an e-GFR slope > 5 mL/min per 1.73 m2 per year. RESULTS We observed that FPG levels were significantly higher in participants with (6.15 ± 2.76 mmol/L) than in those without (5.56 ± 1.61 mmol/L) a rapid decline in e-GFR (p = 0.02). The average decline in e-GFR was 0.149 mL/min/1.73m2 per year in this elderly population, and the increasing risk of having rapid decline in e-GFR was 0.44-fold each year. In the full adjustment model, decline in e-GFR (p = 0.02) and rapid decline in e-GFR (OR1.33, 95% CI 1.03-1.72) were significantly associated with FPG, independent of other conventional cardiovascular risk factors. Using the same models, decline in e-GFR (p = 0.04) and rapid decline in e-GFR (OR 1.57, 95% CI 1.05-2.35) were also significantly associated with FPG in diabetic population, but they were not in non-diabetic population. CONCLUSIONS In community-dwelling elderly Chinese, the average decline in e-GFR was 0.149 mL/min/1.73m2 per year. FPG control is important for delaying renal functional impairment in elderly population. Trial registration NSS, NCT02368938.PURPOSE To evaluate the safety and efficacy of a system aiming to correct scoliosis called "electromagnetically controlled shape-memory alloy rods" (EC-SMAR) used in a rabbit model. METHODS We heat-treated shape-memory alloy (SMA) rods to achieve a transition temperature between 34 and 47 °C and a C-shape austenite phase. this website We then developed a water-cooled generator capable of generating an alternating magnetic field (100 kHz) for induction heating. We next studied the efficacy of this system in vitro and determined some parameters prior to proceeding with animal experiments. We then employed a rabbit model, in which we fixed a straight rod along the spinous processes intraoperatively, and conducted induction heating postoperatively every 4 days for 1 month, while performing periodic X-ray assessments. RESULTS Significant kyphotic deformations with Cobb angles of about 45° (p  less then  0.01) were created in five rabbits, and no complications occurred throughout the experiment. The rabbits are still very much alive and do not show any signs of discomfort. CONCLUSIONS This is the first system that can modulate spinal deformation in a gradual, contactless, noninvasive manner through electromagnetic induction heating applied to SMA alloy rods. Although this study dealt with healthy spines, it provides promising evidence that this device also has the capacity to correct human kyphosis and even scoliosis in the future. These slides can be retrieved under Electronic Supplementary Material.Kawasaki disease (KD) is a medium vessel vasculitis that affects young children. Despite extensive research over the last 50 years, the etiology of KD remains an enigma. Seasonal change in wind patterns was shown to have correlation with the epidemics of KD in Japan. Occurrence of disease in epidemiological clusters, seasonal variation, and a very low risk of recurrence suggest that KD is triggered by an infectious agent. The identification of oligoclonal IgA response in the affected tissues suggests an antigen-driven inflammation. The recent identification of a viral antigen in the cytoplasm of bronchial ciliated epithelium also favors infection as the main trigger for KD. Pointers that suggest a genetic basis of KD include a high disease prevalence in North-East Asian populations, a high risk among siblings, and familial occurrence of cases. Dysregulated innate and adaptive immune responses are evident in the acute stages of KD. In addition to the coronary wall inflammation, endothelial dysfunction and impaired vascular remodeling contribute to the development of coronary artery abnormalities (CAAs) and thrombosis. Genetic aberrations in certain intracellular signaling pathways involving immune effector functions are found to be associated with increased susceptibility to KD and development of coronary artery abnormalities (CAAs). Several susceptible genes have been identified through genome-wide association studies (GWAS) and linkage studies (GWLS). The genes that are studied in KD can be classified under 4 major groups-enhanced T cell activation (ITPKC, ORAI1, STIM1), dysregulated B cell signaling (CD40, BLK, FCGR2A), decreased apoptosis (CASP3), and altered transforming growth factor beta signaling (TGFB2, TGFBR2, MMP, SMAD). The review aims to highlight the role of several genetic risk factors that are linked with the increased susceptibility to KD.