• Booth Steffensen opublikował 1 rok, 3 miesiące temu

    Taurine has been shown to have positive effects on bone mass, which are thought to be due in part to its cytoprotective effects on osteoblasts and here we show that taurine also protects osteocytes against cell death due to reactive oxygen species. Using the IDG-SW3 cell line, the expression of the taurine uptake transporter Taut/Slc6a6 is increased during osteoblast to osteocyte differentiation. Taurine had no effect on genes associated with osteoblast to osteocyte differentiation such as Dmp1, Phex or osteocalcin, even at high doses, but a slight yet significant inhibition of alkaline phosphatase was observed at the highest dose (50 mM). No effect was seen on the osteoclast regulatory genes Rankl and Opg, however the wnt antagonist Sost/sclerostin was potently and dose-dependently downregulated in response to taurine supplementation. Taurine also significantly inhibited Dkk1 mRNA expression, but only at 50 mM. Interestingly, osteocytes were found to also be able to synthesize taurine intracellularly, potentially as a self-protective mechanism, but do not secrete the metabolite. A highly significant increase in the expression of cysteine dioxygenase (Cdo), a key enzyme necessary for the production of taurine, was observed with osteoblast to osteocyte differentiation along with a decrease in methionine, the precursor of taurine. For the first time, we describe the synthesis of taurine by osteocytes, potentially to preserve viability and to regulate bone formation through inhibition of sclerostin. Teriparatide (TPTD) reduces risk of both vertebral and nonvertebral fracture, but increases bone mineral density (BMD) much more at the spine than the hip. TPTD and mechanical loading may have a synergistic anabolic effect on BMD, which may help explain these site-specific differences. Under normal daily activity, the femoral neck (FN) is under bending, placing one side under tension and the other under compression. We sought to further understand the relationship between mechanical loading and TPTD at the hip by investigating the effect of tensile versus compressive loading on TPTD stimulated bone formation indices in the human FN. Thirty-eight patients receiving total hip replacements for osteoarthritis were randomized to receive placebo (PBO) or TPTD for a mean treatment duration of 6 weeks prior to surgery, and double tetracycline labeling was administered to allow assessment of bone formation. The FN was harvested during surgery and analyzed for dynamic bone formation indices in the compressive and tensical settings. Variations in drought responses exhibited by cohabiting tree species such as Acer sacharrum and Quercus alba have often been attributed to differences in rooting depth or water accessibility. A. sacharrum is thought to be a shallow rooted species, and is assumed to not have access to the deep and stable water resources available to Q. alba. As such, A. sacharrum conserves water by minimizing stomatal conductance under drought conditions whereas Q. alba does not. However, detailed records of sufficient temporal resolution which integrate water accessibility, meteorological drivers, and leaf level parameters (e.g., photosynthesis, stomatal conductance) are lacking, making such assumptions-though plausible- largely untested. In this study, we investigated the water accessibility of both maples (A. sacharrum) and oaks (Q. alba) during the late growing season using novel canopy stable isotope measurements. Our results showed that maples can draw from the same water pool as cohabitating oaks, but can also switch to a shallow water source in response to available moisture in the shallow soil profile. We also found that maples tended to use a deep water source under high vapor pressure deficit even when shallow soil water was available. On the other hand, oaks had consistent deep water access during our study period. It is noted that our measurements do not cover the whole growing season and should be extrapolated with caution. Such findings indicate that differences in leaf functions during drought between maples and oaks may be due to both soil water accessibility and atmospheric water demand. BACKGROUND AND AIMS We sought to understand the risk factor correlates of very early coronary artery calcium (CAC), and the potential investigational value of CAC phenotyping in adults aged 20-30 years. METHODS We studied all participants aged 20-30 years at baseline (N = 373) in the Coronary Artery Calcium Consortium, a large multi-center cohort study of patients aged 18 years or older without known atherosclerotic cardiovascular disease (ASCVD) at baseline, referred for CAC scoring for clinical risk stratification. We described the prevalence of CAC in men and women, the frequency of risk factors by the presence of CAC (CAC = 0 vs CAC >0), and assessed the association between traditional non-demographic CVD risk factors (hypertension, hyperlipidemia, smoking, family history of CHD, and diabetes) and prevalent CAC, using age- and sex-adjusted logistic regression models. RESULTS The mean age of the study participants was 27.5 ± 2.4 years; 324 (86.9%) had CAC = 0, and 49 (13.1%) had CAC >0. Among the 49 participants with CAC, 38 (77.6%) were men, and median CAC score was low at 4.6. In age- and sex-adjusted models, there was a graded increase in the odds of CAC >0 with increasing traditional cardiovascular disease (CVD) risk factor burden (p = 0.001 for linear trend). Participants with ≥3 traditional risk factors had a statistically significant higher odds of having prevalent CAC (OR 5.57, 95% CI; 1.82-17.03) compared to participants with no risk factors. CONCLUSIONS Our study demonstrates the non-negligible prevalence of CAC among very high-risk young US adults, reinforcing the critical importance of traditional risk factors in the earliest development of detectable subclinical ASCVD. BACKGROUND AND AIMS The long-term comparative results between culprit-only percutaneous coronary intervention (C-PCI) and multivessel PCI (M-PCI) or those between complete revascularization (CR) and incomplete revascularization (IR) in patients with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) after successful newer-generation drug-eluting stent (DES) implantation are limited. Therefore, we compared the 2-year clinical outcomes in such patients. METHODS A total of 4588 patients with NSTEMI and MVD (C-PCI, n = 2055; M-PCI, n = 2533; CR, n = 2029; IR, n = 504) were evaluated. The primary outcome was major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction MI, and any repeat coronary revascularization. The secondary outcome was stent thrombosis (ST). RESULTS The cumulative incidences of the primary and secondary outcomes were similar in the three comparison groups (C-PCI vs. M-PCI, CR vs. IR, or CR vs. C-PCI). However, the cumulative incidence of non-target vessel revascularization (non-TVR) was higher in the C-PCI group than in the M-PCI group (adjusted hazard ratio [aHR] 2.011; 95% confidence interval [CI] 1.942-3.985; p = 0.012), higher in the IR group than in the CR group (aHR 2.051; 95% CI 1.216-4.183; p = 0.043), and higher in the C-PCI group than in the CR group (aHR 2.099; 95% CI 1.237-3.564; p = 0.006). CONCLUSIONS Regarding the higher cumulative incidence of non-TVR, M-PCI and CR were preferred compared to C-PCI or IR in patients with NSTEMI and MVD. However, further randomized studies are required to confirm these findings. An item-method directed forgetting task was used in three studies to present photographs of happy, neutral and sad faces to participants who had been induced to adopt a happy, neutral or sad mood. At test remember, forget or new judgments of old and new photographs of happy, neutral or sad faces were collected. According to the affect-as-cognitive-feedback hypothesis positively valenced stimuli serve as 'go signals’ validating the use of currently accessible cognitions to process task demands whereas negatively valenced stimuli serve as 'stop signals’ inhibiting or reversing the use of those cognitions. Since directed forgetting tasks entail the cognitions (among others) that some stimuli should be remembered and others should be forgotten, happy faces should facilitate task demands whereas sad faces should not. As predicted, directed forgetting effects were found for happy but not sad faces in Experiments 1 and 3, and directed forgetting effects were found neutral valenced faces in Experiment 2. Across all three studies mood state did not influence directed forgetting. Findings are discussed in terms of the effects of facial valence cues on directed forgetting and some directions for future research. In this study, the influence of multi-frequency ultrasound irradiation on the functional properties and structural characteristics of gluten, as well as the textural and cooking characteristics of the noodles were investigated. Results showed that the textural and cooking characteristics of noodles that contain less gluten pretreated by multi-frequency ultrasonic were ultrasonic frequency dependent. Moreover, the noodles that contain a smaller amount of sonicated gluten could achieve the textural and cooking quality of commercial noodles. There was no significant difference in the cooking and texture characteristics between commercial noodles and noodles with 12%, 11%, and 10% gluten pretreated by single-frequency (40 kHz), dual-frequency (28/40 kHz), and triple-frequency sonication (28/40/80 kHz), respectively. Furthermore, the cavitation efficiency of triple-frequency ultrasound was greater than that of dual-frequency and single-frequency. As the number of ultrasonic frequencies increased, the solubility, wg that with increasing frequency combination increases, the ultrasound effect became more pronounced and protein unfolding increased, thereby impacting the functional properties and the quality of the final product. This study provided a theoretical basis for the application of multi-frequency ultrasound technology in the modification of gluten protein and noodle processing. BACKGROUND The presence of Programmed Death-Ligand 1 protein (PD-L1) in oral squamous cell carcinoma (OSCC) may indicate an ability to evade immune response and has been suggested as a prognostic marker, but there is controversy in the literature. OBJECTIVE To review the scientific evidence of a prognostic role for PD-L1 levels in OSCC. METHODS PubMed, Embase, Web of Science, and Scopus were searched for studies published on or before March 02, 2019. Studies measuring PD-L1 levels by immunohistochemistry (IHC) in OSCC were included. Study quality was assessed using the QUIPS tool. Meta-analysis was performed for survival outcomes and clinic-pathological parameters. RESULTS 26 articles were included comprising 2532 patients. Analysis of studies measuring PD-L1 expression in the cell membrane showed a worse prognosis for disease-specific survival (HR = 1.74, 95% CI = 1.14-2.66, p = 0.01) and disease-free survival (HR = 1.56, 95% CI = 1.16-2.09, p = 0.003). PD-L1 overexpression was more likely in females (OR = 0.69, 95% CI = 0.53-0.91, p = 0.008), non-smokers (OR = 0.45, 95% CI = 0.27-0.75, p = 0.002), non-drinkers (OR = 0.40, 95% CI = 0.16-0.97, p = 0.04), advance stage tumours (OR = 1.63, 95% CI = 1.00-2.64, p = 0.05) and in tumours with high levels of PD-1 (OR = 33.36, 95% CI = 1.88-591.69, p = 0.02), CD4+ (OR = 3.25, 95% CI = 1.36-7.76, p = 0.008) and CD8+ (OR = 3.63 , 95% CI = 1.20-10.99, p = 0.02). CONCLUSION This meta-analysis found a worse prognosis in OSCCs overexpressing PD-L1 in the cell membrane as measured by disease specific survival and disease-free survival. We also found positive correlations between PD-L1 overexpression and advanced tumours, females, non-smokers, non-drinkers and high levels of tumour PD-1, CD4, and CD8.

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