• Williams Nyholm opublikował 1 rok, 3 miesiące temu

    Interestingly, pre-incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine-induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS-driven increase in mitochondrial permeability transition.Most prostate carcinomas require androgen stimulation to grow, and for nearly 70 years, androgen ablation therapy has been one of the central therapeutic strategies against advanced prostate cancer. Although most tumours initially respond to this therapy, some will be acquired resistant and progress to metastatic castration-resistant (mCRPC) disease which clinically tends to progress more rapidly than earlier disease manifestations. The underlying molecular biology of mCRPC is highly complex, and numerous mechanisms have been proposed that promote and retain androgen independence. In various clinical and preclinical data explored, the nature of intracellular signalling pathways mediating mitogenic acquired resistant effects of GPCRs in prostate cancer is poorly defined. G-protein-coupled receptor kinase 2 (GRK2) contributes to the modulation of basic cellular functions-such as cell proliferation, survival or motility-and is involved in metabolic homeostasis, inflammation or angiogenic processes. Moreover, altered GRK2 levels are starting to be reported in different tumoural contexts and shown to promote breast tumourigenesis or to trigger the tumoural angiogenic switch. Thus, we are exploring recent findings that present unexpected opportunities to interfere with major tumourigenic signals by manipulating GPCR-mediated pathways.

    Inadequate intake of choline commonly leads to liver diseases. Methionine- and choline-deficient diets (MCDD) induce fatty liver in mice which is partly mediated by triglyceride (TG) lipolysis in white adipose tissues (WATs). Because Fatp4 knockdown has been shown to increase adipocyte lipolysis in vitro, here, the effects of MCDD on WAT lipolysis in aP2-Cre Fatp4-knockout (Fatp4

    ) mice are determined.

    Isolated WATs of Fatp4

    mice exposed to MCD medium show an increase in lipolysis, and the strongest effect is noted on glycerol release from subcutaneous fat. Fatp4

    mice fed with MCDD for 4 weeks show an increase in serum glycerol, TG, and leptin levels associated with the activation of hormone-sensitive lipase in subcutaneous fat. Chow-fed Fatp4

    mice also show an increase in serum leptin and very-low-density lipoproteins as well as liver phosphatidylcholine and sphingomyelin levels. Both chow- and MCDD-fed Fatp4

    mice show a decrease in serum ketone and WAT sphingomyelin levels which supports a metwhich are exaggerated by MCDD. The data imply hyperlipidemia risk by a low dietary choline intake and gene mutations that increase adipose TG levels.Fibromyalgia (FM) was frequently observed in patients with rheumatoid arthritis (RA). We aimed to evaluate the differences in psychiatric comorbidities and life adversities between patients with Rheumatoid arthritis + FM (secondary fibromyalgia [SFM]) and people with primary FM (PFM). In a cross-sectional, observational study, patients with PFM and SFM underwent a structured interview for the lifetime diagnosis of major depression (MDD), panic disorder (PD) and post-traumatic stress disorder (PTSD) and were assessed for childhood/adulthood adversities and FM-related symptoms severity. Thirty patients with PFM and 40 with SFM were recruited. The univariate analysis showed that the lifetime rates of MDD were significantly higher in PFM versus SFM (76.7 % and 40%, respectively, p less then 0.003), as well as the rates of PD (50 % and 15%, respectively, p less then 0.003), whereas there was no difference in PTSD rates. The rates of sexual abuse and physical neglect were significantly higher in PFM patients versus SFM patients (p less then 0.005 and p less then 0.023). Life events occurring before FM onset were different in PFM and SFM groups. In the logistic regression model, lifetime PD and physical neglect remain independent risk factors for PFM. PFM and SFM differ in psychiatric comorbidities and environmental adversities, suggesting that common pathogenesis may develop through different pathways.The purpose of our study was to develop a simple clinical pre-procedure risk model based on clinical characteristics for the prediction of contrast-induced nephropathy (CIN) and major adverse cardiac events (MACEs) after percutaneous coronary intervention (PCI) in patients with diabetes. A total of 1113 patients with diabetes who underwent PCI with contrast exposure were randomized into a development group (n = 742) and a validation group (n = 371) in a 21 ratio. CIN was defined as an increase of either 25% or 0.5 mg/dL (44.2 μmol/L) in serum creatinine within 72 hours after contrast infusion. A simple CIN risk score based on independent predictors was established. Four variables were identified for our risk score model LVEF 300 mL. Based on this new CIN risk score, the incidence of CIN had a significant trend with increased predicting score values of 5.9%, 32.9% and 60.0%, corresponding to low-, moderate- and high-risk groups, respectively. The novel risk assessment exhibited moderate discrimination ability for predicting CIN, with an AUC of 0.759 [95% CI 0.668-0.852, P = .001] in the validation cohort. It also had similar prognostic values for one-year follow-up MACE (C-statistic 0.705 and 0.606 for new risk score and Mehran score, respectively). This novel risk prediction model could be effective for preventing nephropathy in diabetic patients receiving contrast media during surgical procedures.

    The implementation of lateral ventricle puncture (LVP) operation is challenging due to the complex anatomy structure of human brains. Surgical simulator has been proved to be effective in surgical training. However, few works consider the integration of visual and haptic feedback.

    Aim at achieving a realistic haptic interaction, this paper proposes a haptic-based virtual reality (VR) simulator for the LVP operation. In this simulator, we first reconstruct the three-dimension (3D) model of human brains for tissue/instrument interaction. Then a preoperative planning method based on geometry analysis is introduced to find the feasible entry point of LVP operation. A hierarchical bounding-box collision detection approach is proposed to render haptic feedback that is transferred to humans. Finally, a set of experiments on the proposed simulator and 3D printed models of human brains is carried out.

    Two sets of experiments are conducted to evaluate the effectiveness of the proposed haptic-based simulator experiments in the simulator and experiments on a 3D printed brain model. The proposed simulator allows neurosurgeons to train the LVP operation by visualizing the 3D virtual human brain and feeling realistic haptic feedback.

    We demonstrated that the proposed haptic-based VR simulator can improve the performance of the LVP operation effectively and reduce the operation time.

    We demonstrated that the proposed haptic-based VR simulator can improve the performance of the LVP operation effectively and reduce the operation time.

    Physical activity is lower and rates of preventable common diseases are higher in regional/rural than urban Australia. Active commuting (walking/bicycling to get from one place to another) may benefit health through increased physical activity, but most evidence of its correlates come from urban studies. This study aimed to investigate associations between active commuting, socio-demographic characteristics, behaviours, total physical activity and health in a regional/rural Australian state.

    This study used data from the 2016 Tasmanian Population Health Survey, a representative cross-sectional self-report survey of 6,300 adults in Tasmania, Australia. Logistic regression modelling investigated associations between socio-demographic, behavioural and health characteristics and past week active commuting frequency.

    In multivariable models, being younger, having tertiary qualifications, living in a socio-economically advantaged area, being physically active, having a healthy body mass index and good/excellehy these groups appear to be less active for commuting purposes. SO WHAT? Increasing physical activity and active commuting may help to reduce rates of preventable common diseases in regional/remote areas.Both non-suicidal self-injury (NSSI) and risky drinking are positively associated with alexithymia, a personality trait characterized by difficulties appraising feelings and an externally orientated thinking style. Although researchers have studied the associations between alexithymia and both NSSI and risky drinking, the underlying factors of both associations are rarely compared. Using path analysis, we compared the mediating effects of behaviour-specific outcome expectancies and self-efficacy beliefs on the associations between alexithymia and both NSSI and risky drinking. A sample of 627 university students (76.10% female, Mage = 20.75, SD = 1.88) completed a battery of questionnaires. Alexithymia exhibited indirect effects on NSSI via affect regulation expectancies, pain expectancies, communication expectancies, and low self-efficacy to resist NSSI. Alexithymia exhibited indirect effects on risky drinking via expectations of increased confidence and negative consequences. However, the indirect effects differed depending on the valance of the emotion the individual had difficulties appraising. Our findings indicate that the underlying factors in the associations between alexithymia and both NSSI and risky drinking could differ. Where individuals who have difficulties appraising negative emotions may engage in NSSI to help regulate negative feelings, they may consume alcohol to gain more confidence in expressing their feelings. Clinical implications are discussed.Flavonoid glycosides exist widely in medicine herbs and often used as nutraceuticals because of their excellent bioactivity and low toxicity. For accurate quality control and bioactivity assessment of Sphaerophysa salsula, a rapid and productive method to isolate flavonoid glycosides is needed. Therefore, this work reports the development of a novel comprehensive strategy based on an online middle-pressure chromatography and preparative high-performance liquid chromatography for rapid enrichment and separation of flavonoid glycosides from S. salsula. First, the flavonoid glycosides were enriched using an online middle-pressure chromatographic column containing stationary middle chromatogram isolated phase. During this process, the high-volume injection of the extracting solution was realized by an empty precolumn positioned before the main chromatographic tower. Then, the compounds were separated through preparative high-performance liquid chromatography with Megress C18. As a result, one new flavonol 3-O-glycoside (2) and two known flavonol 3-O-glycosides (1, 3) were targetedly isolated from S. salsula. The content of compounds 1-3 in S. salsula was 0.09, 0.11, and 0.18 wt%, respectively. Comparing to traditional enrichment and separation methods, our technique offers significantly shorter sample pretreatment time as well as high reproducibility. We believe that our separation method has a strong potential to be used for the processing of other medicinal plants.

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