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  • 文章类型: Journal Article
    系统性红斑狼疮(SLE)患者的代谢综合征(MetS)是动脉粥样硬化和心血管并发症发作或恶化的额外负担和不良预后因素。在许多狼疮性肾炎(LN)患者中,MetS通常最初已经显现。我们的工作旨在确定LN患者中MetS的频率和特征,以及MetS与疾病活动特征的关系。
    临床研究包括67例LN患者,54(80.59%)女性和13(19.41%)男性,平均年龄42.86±14.46岁。患者分为两组:MetS(35.82%)和无MetS(64.18%),活动LN有(34或50.74%),和LN缓解(33或49.25%)。我们监测了感兴趣的临床和生化参数。
    将患者与LN进行总体比较,以及那些有MetS和没有MetS的人,我们观察到MetS患者年龄较大(p=0.001),BMI(p<0.001),收缩压较高(p=0.002),和吸烟者在该组中更为常见(p<0.001)。在分析中,增加甘油三酯(p<0.001)和肌酐(p=0.027),在MetS组中观察到白蛋白(p=0.050)和GFR(p=0.020)降低。在活动性LN患者中,有44.11%存在MetS,在缓解LN的患者中,有27.7%存在MetS。最常见的MetS参数是动脉高血压(76.6%),与GFR和肌酐相关;高甘油三酯血症(47.8%),与抗ds-DNAAb相关,红细胞增多症,蛋白尿,SLEDAI/r指数;HDL胆固醇降低(28.4%),与白蛋白显著相关,C3和抗ds-DNAAb。
    在我们的LN患者中,MetS与年龄较大有关,肾功能受损,和吸烟。MetS最常见的参数是动脉高血压和血脂异常,与疾病活动参数显着相关,表明该组患者心血管并发症的风险增加。
    代谢酶(MetS)kodbolesnikasaSLE,pogršanjeatertenofthepattern.MetSječestoinicijalnovećispoljenkodmnogihbolesnikasalupusnevritisom(LN).CiljnašegradajebiodautvrdimoučestalostikarakteristikeMetSkodbolesnikasaLN,kaoiodnoskomponentiMetSiaktivnosti狼疮nafritisa.
    Kliničkoispitivanjejeobuhvatilogrupuod67pacijenatasaLN,54(80,59%)zenskogpolai13(19,41%)muškaraca,prosečnihgodinastarosti42,86±14,46.Pacijentisupodeljeniudvegrupe:prvasaMetS(35,82%)idrugabezMetS(64,18%),pacijentisuimaliaktivanLN(34伊利50,74%)iLNuremisiji(33伊利49,25%)。Pratilismokliničkeibiohemijskeparametreodinteresa.
    PoredećipacijentesaLNzbirnokaoionesaMetSibezMetS,utvrdlismodasupacijentisaMetSbilistariji(p=0,001),BMI(p<0,001)issistolnipritisakjebioviši(p=0,002)ipušačisubilizastupljenijiuovojgrupi(p<0,001).Uanalizamasuzapaçenipovišenitrigliceridi(p<0,001)ikreatinin(p=0,027)isniíen白蛋白(p=0,050)iGFR(p=0,020)ugrupisaMetS.MetSjebiozastupljenkod44,11%pacijenatasaaktivnimLNikod27,7%saLNuremisiji.Najzastupljeniji参数MetSjebilaarterijjskahipertenzija(76,6%)kojaznačajnokoreliralasaGFRikreatinom;hipertrigliceridemija(47,8%)kojajekorliralaanti-ds-DNAAt,eritrociturijom,proteinurijomiSLEDAI/rindeksom;snizenHDLholesteol(28,4%)kojijekoreliraoznačajnosaalubminom,C3i抗ds-DNA。
    KodnašihpacijenatasaLN,MetSjebiopovezansastarijimzivotnimdobom,poremećajembubeínefunkcijeipušenjem.Najzastupljeniji参数对upućujenapovećanrizikodkardiovaskularnihkomplikacijauovojgrupibolesnika.
    UNASSIGNED: Metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE) represents an additional burden and a poor prognostic factor for the onset or worsening of atherosclerosis and cardiovascular complications. In many patients with lupus nephritis (LN), MetS is often already manifested initially. Our work aimed to determine the frequency and characteristics of MetS in patients with LN, as well as the relationship components of MetS and characteristics of disease activity.
    UNASSIGNED: The clinical study included 67 patients with LN, 54 (80.59%) female and 13 (19.41%) male, with an average age of 42.86±14.46 years. Patients were divided into two groups: with MetS (35.82%) and without MetS (64.18%), active LN had (34 or 50.74%), and LN in remission (33 or 49.25%). We monitored clinical and biochemical parameters of interest.
    UNASSIGNED: Comparing patients with LN collectively, as well as those with MetS and without MetS, we observed that patients with MetS were older (p=0.001), BMI (p<0.001), and systolic arterial pressure was higher (p=0.002), and smokers were more common in this group (p<0.001). In the analysis, increased triglycerides (p<0.001) and creatinine (p=0.027), and decreased albumin (p=0.050) and GFR (p=0.020) were observed in the group with MetS. MetS was present in 44.11% of patients with active LN and in 27.7% with LN in remission. The most common MetS parameter was arterial hypertension (76.6%), which correlated with GFR and creatinine; hypertriglyceridemia (47.8%), which is correlated with anti-ds-DNA Ab, erythrocyturia, proteinuria, and SLEDAI/r index; decreased HDL cholesterol (28.4%) which significantly correlated with albumin, C3 and anti-ds-DNA Ab.
    UNASSIGNED: In our patients with LN, MetS was associated with older age, impaired kidney function, and smoking. The most common parameter of MetS was arterial hypertension and dyslipidemia, which were significantly correlated with disease activity parameters, indicating an increased risk of cardiovascular complications in this group of patients.
    UNASSIGNED: Metabolički sindrom (MetS) kod bolesnika sa SLE, predstavlja dodatno opterećenje i loš prognostički faktor za nastanak ili pogoršanje ateroskleroze i za kardiovaskularne komplikacije. MetS je često inicijalno već ispoljen kod mnogih bolesnika sa lupus nefritisom (LN). Cilj našeg rada je bio da utvrdimo učestalost i karakteristike MetS kod bolesnika sa LN, kao i odnos komponenti MetS i aktivnosti lupus nefritisa.
    UNASSIGNED: Kliničko ispitivanje je obuhvatilo grupu od 67 pacijenata sa LN, 54 (80,59%) ženskog pola i 13 (19,41%) muškaraca, prosečnih godina starosti 42,86±14,46. Pacijenti su podeljeni u dve grupe: prva sa MetS (35,82%) i druga bez MetS (64,18%), pacijenti su imali aktivan LN (34 ili 50,74%) i LN u remisiji (33 ili 49,25%). Pratili smo kliničke i biohemijske parametre od interesa.
    UNASSIGNED: Poredeći pacijente sa LN zbirno kao i one sa MetS i bez MetS, utvrdili smo da su pacijenti sa MetS bili stariji (p=0,001), BMI (p<0,001) i sistolni pritisak je bio viši (p=0,002) i pušači su bili zastupljeniji u ovoj grupi (p<0,001). U analizama su zapaženi povišeni trigliceridi (p<0,001) i kreatinin (p=0,027) i snižen albumin (p=0,050) i GFR (p=0,020) u grupi sa MetS. MetS je bio zastupljen kod 44,11% pacijenata sa aktivnim LN i kod 27,7% sa LN u remisiji. Najzastupljeniji parameter MetS je bila arterijska hipertenzija (76,6%) koja značajno korelirala sa GFR i kreatininom; hipertrigliceridemija (47,8%) koja je korelirala sa anti-ds-DNA At, eritrociturijom, proteinurijom i SLEDAI/r indeksom; snižen HDL holesterol (28,4%) koji je korelirao značajno sa albuminom, C3 i anti-ds-DNA At.
    UNASSIGNED: Kod naših pacijenata sa LN, MetS je bio povezan sa starijim životnim dobom, poremećajem bubrežne funkcije i pušenjem. Najzastupljeniji parameter MetS kod pacijenata sa LN je bila arterijska hipertenzija i dislipidemija koja je značajno korelirala sa parametrima aktivnosti bolesti, što upućuje na povećan rizik od kardiovaskularnih komplikacija u ovoj grupi bolesnika.
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  • 文章类型: Journal Article
    通过使用LAMOST低分辨率光谱测量(LRS)和中分辨率光谱测量(MRS)的共源光谱数据,研究了类太阳恒星的氢Balmer线的强度,以进行恒星色球层活动。BalmerHα,Hβ,Hγ,分析LRS数据中的Hδ线和MRS数据中的Hα线。绝对通量指数,定义为Balmer线中心的绝对通量与恒星辐射热通量之比,用于指示响应恒星活动的Balmer线的强度大小。从LRS数据和MRS数据导出的Hα指数,分别,被校准为在数量上彼此一致。发现,随着Hα指数的增加,Hβ,Hγ,Hδ指数呈现先上升后下降的趋势,最后与Hα指数同步增加。Balmer线指数的分布也揭示了恒星活动的三个不同阶段(正常阶段,激烈的阶段,和极其激烈的阶段),其中极其激烈的阶段的特点是四个Balmer线的指数同步增长。Hβ的不同行为,Hγ,Hα线的Hδ线可以通过形成线核心强度的不同机制来解释,三个不同的活动阶段意味着类似太阳的恒星的磁场环境和物理条件非常不同。
    The intensities of the hydrogen Balmer lines of solar-like stars are investigated for stellar chromospheric activity by using the co-source spectral data of the LAMOST Low-Resolution Spectroscopic Survey (LRS) and Medium-Resolution Spectroscopic Survey (MRS). The Balmer H α , H β , H γ , and H δ lines in the LRS data and the H α line in the MRS data are analyzed. The absolute flux indexes, defined as the ratios of the absolute fluxes at the centers of the Balmer lines to the stellar bolometric flux, are employed to indicate the intensity magnitudes of the Balmer lines in response to stellar activity. The H α indexes derived from the LRS data and the MRS data, respectively, are calibrated to be quantitatively consistent with each other. It is found that, as the H α index increases, the H β , H γ , and H δ indexes first present trend of increasing and then decreasing, and finally increase synchronously with the H α index. The distributions of the Balmer line indexes also reveal the three distinct stages of stellar activity (normal stage, intense stage, and extremely intense stage), in which the extremely intense stage is characterized by the synchronous growth of the indexes of the four Balmer lines. The different behaviors of the H β , H γ , and H δ lines from that of the H α line can be interpreted by the different mechanisms by which the line-core intensities are formed, and the three distinct activity stages imply the very different magnetic field environments and physical conditions of solar-like stars.
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  • 文章类型: Journal Article
    背景:确定类风湿关节炎患者在全髋关节置换术后发生并发症的风险较高,可以使围手术期处理更有效。在这里,我们检查了疾病活动是否与此类并发症的风险相关。
    方法:我们回顾性分析了我们医疗中心337例接受初次全髋关节置换术的类风湿关节炎患者的数据。类风湿性关节炎患者根据简化疾病活动指数(SDAI)进行分类,入院时和随访时的平均值一起计算.Logistic回归用于检查平均SDAI与脱位率的关联,感染,假体周围骨折和无菌性松动。作为控制,337名没有全身性炎症且接受相同手术的骨关节炎患者在许多临床人口统计学变量中进行了匹配。
    结果:在337名类风湿性关节炎患者中,38例(11.3%)有术后并发症,在基于平均SDAI的疾病活动被分类为高的四个亚组中,其比率从0到17.5%(p=0.003)显著变化,中度,低或缓解。平均SDAI每增加1个单位与术后并发症的风险显着增加相关(OR1.015,95%CI1.001-1.029,p=0.035)。在所有类风湿性关节炎患者中,在接受疾病缓解性抗风湿药或其他治疗的患者之间,并发症发生率无显著差异.错位率,与类风湿性关节炎患者相比,骨关节炎对照组的感染或所有合并术后并发症的发生率明显较低.
    结论:较大的平均SDAI与较高的脱位风险相关,类风湿性关节炎患者全髋关节置换术后的感染和复合术后并发症。这些患者的术后并发症发生率明显高于骨关节炎患者,可能反映了全身性炎症的影响。在接受全髋关节置换术之前,类风湿性关节炎患者应尽可能减少疾病活动。
    BACKGROUND: Identifying rheumatoid arthritis patients at higher risk of complications after total hip arthroplasty could make perioperative management more effective. Here we examined whether disease activity is associated with risk of such complications.
    METHODS: We retrospectively analyzed data for 337 rheumatoid arthritis patients at our medical center who underwent primary total hip arthroplasty. Rheumatoid arthritis patients were categorized according to the simplified disease activity index (SDAI), the values of which at admission and follow-up were averaged together. Logistic regression was used to examine associations of mean SDAI with rates of dislocation, infection, periprosthetic fracture and aseptic loosening. As controls, 337 osteoarthritis patients who did not have systemic inflammation and who underwent the same procedure were matched across numerous clinicodemographic variables.
    RESULTS: Among the 337 rheumatoid arthritis patients, 38 (11.3%) had postoperative complications, the rates of which varied significantly from 0 to 17.5% (p = 0.003) among the four subgroups whose disease activity based on mean SDAI was categorized as high, moderate, low or in remission. Each 1-unit increase in mean SDAI was associated with a significant increase in risk of postoperative complications (OR 1.015, 95% CI 1.001-1.029, p = 0.035). Across all rheumatoid arthritis patients, rate of complications did not differ significantly between patients who received disease-modifying anti-rheumatic drugs or other treatments. Rates of dislocation, of infection or of all postoperative complications combined were significantly lower among osteoarthritis controls than among rheumatoid arthritis patients.
    CONCLUSIONS: Greater mean SDAI is associated with higher risk of dislocation, infection and composite postoperative complications after total hip arthroplasty in rheumatoid arthritis patients. These patients show a significantly higher rate of postoperative complications than osteoarthritis patients, likely reflecting the influence of systemic inflammation. Disease activity should be reduced as much as possible in rheumatoid arthritis patients before they undergo total hip arthroplasty.
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  • 文章类型: Journal Article
    抗坏血酸过氧化物酶(APXs)是抗坏血酸-谷胱甘肽循环的关键成分,在去除植物中过量的活性氧(ROS)中起着重要作用。在这里,MaAPX1被证实参与了香蕉果实的成熟和衰老,对ROS的积累和蛋白质的氧化表现出响应性。采用定点突变方法探讨MaAPX1活性变化的机制。我们发现32位半胱氨酸(Cys,C)充当潜在的S-亚硝基化位点。当Cys32突变为丝氨酸时,突变体MaAPX1C32S活性显着降低(Ser,S).有趣的是,邻近的保守的36位点蛋氨酸(Met,M),当突变为赖氨酸时,与Cys32相邻的酶活性比野生型MaAPX1高约五倍(Lys,K).利用LC-MS/MS光谱结合停流分析表明,增强的MaAPX1M36K活性可能是由于Cys32的S-亚硝基化水平增加和中间体的促进(化合物I,APX与H2O2)生产反应的第一个中间产物。分子对接模拟显示MaAPX1M36K中Cys32和Lys36之间的S-N键可能具有保护Cys32的硫醇免于氧化的功能。MaAPX1M36K,一个有前途的变种人,在生物工程技术研究领域具有巨大的提高APX抗氧化能力的潜力。
    Ascorbate peroxidases (APXs) are key components of the ascorbate-glytathione cycle, which plays an important role in removing excess reactive oxygen species (ROS) in plants. Herein, MaAPX1 was verified as being involved in the ripening and senescence of banana fruit, exhibiting responsiveness to the accumulation of ROS and the oxidation of proteins. Site-directed mutation was applied to explore the mechanism of MaAPX1 activity changes. We found that the 32-site cysteine (Cys, C) served as a potential S-nitrosylation site. The mutant MaAPX1C32S activity was decreased significantly when Cys32 was mutated to serine (Ser, S). Intriguingly, the neighboring conserved 36-site methionine (Met, M), which is adjacent to Cys32, displayed an enzyme activity that was approximately five times higher than that of the wild-type MaAPX1 when mutated to lysine (Lys, K). Utilizing LC-MS/MS spectroscopy coupled with stopped-flow analysis showed that the enhanced MaAPX1M36K activity might be due to the increased S-nitrosylation level of Cys32 and the promotion of intermediate (compound I, the first intermediate product of the reaction of APX with H2O2) production. Molecular docking simulations showed that the S-N bond between Cys32 and Lys36 in MaAPX1M36K might have a function in protecting the thiol of Cys32 from oxidation. MaAPX1M36K, a promising mutant, possesses immense potential for improving the antioxidant capabilities of APX in the realm of bioengineering technology research.
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  • 文章类型: Journal Article
    青少年睡眠不足是一种地方性问题,可能导致全天功能受损,并与各种不良后果的风险增加有关。长期以来,人们一直发现,提早上学时间(SST)不利于青少年在上学之夜的睡眠成绩。然而,改变SST存在后勤障碍。有证据支持每天进行中等强度到剧烈强度的体力活动(MVPA),以提高青少年的夜间睡眠成绩。然而,MVPA在SST与睡眠持续时间之间的关联中的作用尚不清楚.这项研究考察了MVPA在青少年典型上学日SST与睡眠持续时间之间的关联中的潜在调节作用。
    这项研究调查了来自美国家庭生活中1132名青少年(年龄=14.5岁)的全国样本的数据(于2014年4月和10月收集)。活动,Sun,健康,和吃研究,横截面,基于互联网的调查。首先,计算了三个线性回归来检验SST,MVPA,和睡眠持续时间,同时控制参与者的性别,种族和民族,家庭收入,学校水平,卧室里有电视。接下来,以睡眠持续时间为因变量计算三步多元回归,最后一步包括SST和MVPA之间的相互作用项。
    随后的SST(b1=0.41,p<0.001)和MVPA增加(b1=0.39,p<0.001)都与睡眠时间增加有关,而SST与MVPA无显著相关性。在最终的多元回归模型中,其中包括交互术语,上学日MVPA调节了SST和学校夜间睡眠时间之间的正相关(B1=-3.7,p<0.05),这样,在典型的上学日,MVPA越大,早期SST与睡眠时间之间的正相关关系越弱。在事后分析中,交互效应仅对女性显著,对男性不显著。
    MVPA对SST与睡眠持续时间之间关联的显着缓冲作用表明,在没有SST变化的情况下,在青少年中推广MVPA可能是缓解美国青少年睡眠不足的有希望的策略.
    UNASSIGNED: Adolescent insufficient sleep is an endemic issue that may result in compromised functioning throughout the course of the day and is associated with increased risk for a variety of adverse outcomes. Early school start time (SST) has been consistently found to be detrimental to adolescents\' sleep achievement on school nights. However, there are logistical barriers to changing SST. Evidence supports daily engagement in moderate-to-vigorous intensity physical activity (MVPA) to enhance adolescents\' nightly sleep achievement. However, the role of MVPA in the association between SST and sleep duration is unknown. This study examines the potential moderating effect of MVPA in the association between SST and sleep duration on a typical school day among adolescents.
    UNASSIGNED: This study examined data (collected in April and October 2014) from a national sample of 1132 adolescents (m age = 14.5 years) living in the United States from the Family Life, Activity, Sun, Health, and Eating study, a cross-sectional, internet-based survey. First, three linear regressions were computed to examine bivariate associations between SST, MVPA, and sleep duration while controlling for participant sex, race and ethnicity, household income, school level, and the presence of a TV in the bedroom. Next, a three-step multiple regression was computed with sleep duration as the dependent variable, and the final step included an interaction term between SST and MVPA.
    UNASSIGNED: Later SST (b 1 = 0.41, p < 0.001) and increased MVPA (b 1 = 0.39, p < 0.001) were both associated with increased sleep duration, while SST and MVPA were not significantly associated. In the final multiple regression model, which included the interaction term, school day MVPA moderated the positive association between SST and school night sleep duration (b 1 = - 3.7, p < 0.05), such that the greater the MVPA on a typical school day, the weaker the positive association between early SST and sleep duration. In post-hoc analysis, the interaction effect was only significant for females and not males.
    UNASSIGNED: The significant buffering effect of MVPA on the association between SST and sleep duration suggests that in the absence of SST changes, promoting MVPA among adolescents may be a promising strategy to mitigate insufficient sleep among US adolescents.
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  • 文章类型: Journal Article
    背景:刺激活动与痴呆风险降低相关。然而,这在多大程度上反映了痴呆导致的活动或不参与的保护作用,目前仍存在争议.我们在长达20年的随访中调查了成年后期刺激闲暇时间活动与痴呆症风险的关系。
    方法:我们使用了来自芬兰和瑞典的五项前瞻性队列研究的数据。心理,社会,户外,消费和体育休闲活动是自我报告的。从临床诊断或医疗保健和死亡登记中确定了痴呆事件。Cox回归用于估计风险比(HRs)和95%置信区间(CIs)。
    结果:在基线时年龄≥50岁的33263名无痴呆个体中,1408在平均7.0年的随访期间患有痴呆症。积极参加精神活动(HR:0.52,95%CI:0.41至0.65),社会(HR:0.5695%CI:0.46至0.72),户外(HR:0.70,95%CI:0.58至0.85),消耗性(HR:0.67,95%CI:0.53至0.94)和身体活动(HR:0.62,95%CI:0.51至0.75),多样性(HR:0.54,95%CI:0.43~0.68)和总活动频率(HR:0.41,95%CI:0.34~0.49)与<10年随访期间痴呆风险降低相关.在≥10年的随访中,所有关联都向零衰减。
    结论:在短期而非长期随访中,刺激闲暇时间活动与降低痴呆风险相关。这些发现可能反映了临床前痴呆后休闲时间活动的减少或随着时间的推移相关性的稀释。
    BACKGROUND: Stimulating activities are associated with a decreased risk of dementia. However, the extent to which this reflects a protective effect of activity or non-participation resulting from dementia is debated. We investigated the association of stimulating leisure-time activity in late adulthood with the risk of dementia across up to two decades\' follow-up.
    METHODS: We used data from five prospective cohort studies from Finland and Sweden. Mental, social, outdoor, consumptive and physical leisure-time activities were self-reported. Incident dementia was ascertained from clinical diagnoses or healthcare and death registers. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
    RESULTS: Of the 33 263 dementia-free individuals aged ≥50 years at baseline, 1408 had dementia during a mean follow-up of 7.0 years. Active participation in mental (HR: 0.52, 95% CI: 0.41 to 0.65), social (HR: 0.56 95% CI: 0.46 to 0.72), outdoor (HR: 0.70, 95% CI: 0.58 to 0.85), consumptive (HR: 0.67, 95% CI: 0.53 to 0.94) and physical (HR: 0.62, 95% CI: 0.51 to 0.75) activity, as well as variety (HR: 0.54, 95% CI: 0.43 to 0.68) and the overall frequency of activity (HR: 0.41, 95% CI: 0.34 to 0.49) were associated with a reduced risk of dementia in <10 years\' follow-up. In ≥10 years\' follow-up all associations attenuated toward the null.
    CONCLUSIONS: Stimulating leisure-time activities are associated with a reduced risk of dementia in short-term but not long-term follow-up. These findings may reflect a reduction in leisure-time activity following preclinical dementia or dilution of the association over time.
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  • 文章类型: Journal Article
    由于上个世纪医疗和相关政策的进步,预期寿命大幅增加,并在全球范围内继续增加。然而,寿命和“健康跨度”之间的脱节(在健康状态下花费的时间长度,无病状态)也有所增加,骨骼肌是造成这种情况的重要因素。生物老化伴随着骨骼肌质量和功能的下降,称为肌少症。支撑肌肉减少症的机制是多因素的,并且已知包括肌肉蛋白质周转的显着改变和对肌肉神经输入的适应。然而,到目前为止,每个因素的相对贡献在很大程度上仍未被探索。具体来说,肌肉蛋白质对关键合成代谢刺激的合成反应随着年龄的增长而减弱,虽然改变了神经成分,从运动皮层和运动神经元兴奋性到神经肌肉接头,与质量相比,可以解释更大的功能损失。这些损失的后果对个人来说可能是毁灭性的,他们的支持网络,和医疗保健服务;对两种临床都有明显的不利影响(例如,死亡率,脆弱,和治疗后并发症)和社会(例如,独立性维护)结果。肌肉数量和质量的下降是否是衰老的必然因素仍有待完全了解。然而,减轻这些下降的策略对于改善老年人的健康状况至关重要。这篇综述旨在概述骨骼肌质量和功能随着年龄的增长而下降,描述了这些下降的广泛影响,最后提出了减轻它们的策略,包括新兴药物的优点。
    As a result of advances in medical treatments and associated policy over the last century, life expectancy has risen substantially and continues to increase globally. However, the disconnect between lifespan and \'health span\' (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.
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  • 文章类型: Journal Article
    GDP-甘露糖焦磷酸化酶B(GMPPB)功能丧失与肌营养不良和其他神经系统症状有关。GMPPB促进甘露糖-1-磷酸和GTP催化转化为GDP-甘露糖,作为糖基化的甘露糖供体。GMPPB的活性受其非催化旁系同源物GMPPA的调控,它可以结合GDP-甘露糖并与GMPPB相互作用,从而充当GMPPB的变构反馈抑制剂。使用下拉,免疫沉淀,周转实验以及免疫标记和酶活性测定,我们提供了GMPPB活性受泛素化调节的第一个直接证据。我们进一步表明E3泛素连接酶TRIM67与GMPPB相互作用,并且TRM67的敲低降低了GMPPB的泛素化,因此反映了GMPPB泛素化的候选E3连接酶。虽然抑制GMPPB的泛素化会降低其酶活性,其泛素化既不影响其与GMPPA的相互作用,也不影响其周转。一起来看,我们表明GMPPB的泛素化代表了GDP-甘露糖供应的另一个调节水平。
    GDP-mannose pyrophosphorylase B (GMPPB) loss-of-function is associated with muscular dystrophy and variable additional neurological symptoms. GMPPB facilitates the catalytic conversion of mannose-1-phosphate and GTP to GDP-mannose, which serves as a mannose donor for glycosylation. The activity of GMPPB is regulated by its non-catalytic paralogue GMPPA, which can bind GDP-mannose and interact with GMPPB, thereby acting as an allosteric feedback inhibitor of GMPPB. Using pulldown, immunoprecipitation, turnover experiments as well as immunolabeling and enzyme activity assays, we provide first direct evidence that GMPPB activity is regulated by ubiquitination. We further show that the E3 ubiquitin ligase TRIM67 interacts with GMPPB and that knockdown of TRM67 reduces ubiquitination of GMPPB, thus reflecting a candidate E3 ligase for the ubiquitination of GMPPB. While the inhibition of GMPPB ubiquitination decreases its enzymatic activity, its ubiquitination neither affects its interaction with GMPPA nor its turnover. Taken together, we show that the ubiquitination of GMPPB represents another level of regulation of GDP-mannose supply.
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  • 文章类型: Journal Article
    睡眠是一种基本的行为,人们仍然知之甚少。睡眠异常伴随着各种精神和神经系统疾病,睡眠可以作为治疗这些疾病的一种可改变的行为。斑马鱼(Daniorerio)已被证明是研究睡眠以及睡眠与这些疾病之间相互作用的强大模型生物,这是由于控制斑马鱼和人类之间睡眠和觉醒状态的神经调节机制的高度保守性。斑马鱼是一种昼夜脊椎动物,与哺乳动物模型相比神经系统相对简单,表现出不同生命阶段的睡眠个体发育的保护。斑马鱼幼虫是建立的高通量模型,用于评估睡眠表型和睡眠障碍的生物学基础。迄今为止,幼年和成年斑马鱼的睡眠测量尚未以标准化和可重复的方式进行,因为相对于其幼虫对应物而言,其通量相对较低。这在理解与许多精神病和神经退行性疾病相关的生命后期阶段的睡眠方面留下了空白。几个研究小组已经使用自制系统来解决这一差距。这里,我们报告使用市售设备来跟踪幼年和成年斑马鱼的活动和睡眠/觉醒模式。该设备使研究人员能够在隔离的环境中进行自动行为测定,并进行多天的亮/暗和温度控制。我们首先解释跟踪成年斑马鱼的睡眠和活动的实验程序,然后通过测量褪黑激素和DMSO给药的效果来验证方案。主要特点•允许在一个隔离和可控的环境中对幼年和成年斑马鱼进行活动和睡眠测定。•衡量斑马鱼在生命阶段的活动晚于早期发育,这需要在测定期间喂养动物。•需要使用商用设备系统和六个储罐。•斑马鱼的活动可以跟踪五天,包括适应步骤。
    Sleep is an essential behavior that is still poorly understood. Sleep abnormalities accompany a variety of psychiatric and neurological disorders, and sleep can serve as a modifiable behavior in the treatment of these disorders. Zebrafish (Danio rerio) has proven to be a powerful model organism to study sleep and the interplay between sleep and these disorders due to the high conservation of the neuro-modulatory mechanisms that control sleep and wake states between zebrafish and humans. The zebrafish is a diurnal vertebrate with a relatively simple nervous system compared to mammalian models, exhibiting conservation of sleep ontogeny across different life stages. Zebrafish larvae are an established high-throughput model to assess sleep phenotypes and the biological underpinnings of sleep disturbances. To date, sleep measurement in juvenile and adult zebrafish has not been performed in a standardized and reproducible manner because of the relatively low-throughput nature in relation to their larval counterparts. This has left a gap in understanding sleep across later stages of life that are relevant to many psychiatric and neurodegenerative disorders. Several research groups have used homemade systems to address this gap. Here, we report employing commercially available equipment to track activity and sleep/wake patterns in juvenile and adult zebrafish. The equipment allows researchers to perform automated behavior assays in an isolated environment with light/dark and temperature control for multiple days. We first explain the experimental procedure to track the sleep and activity of adult zebrafish and then validate the protocol by measuring the effects of melatonin and DMSO administration. Key features • Allows an isolated and controllable environment to carry out activity and sleep assays in juvenile and adult zebrafish. • Measures activity of zebrafish in life stages later than early development, which requires feeding animals during the assay. • Requires use of a commercially available equipment system and six tanks. • The activity of zebrafish can be tracked for five days including an acclimation step.
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  • 文章类型: Journal Article
    MAFLD已成为全球主要的健康问题,是全球肝病的主要原因。这种疾病从单纯的脂肪肝发展到逐渐的纤维化,进展为肝硬化,甚至肝细胞肝癌。然而,目前用于诊断的方法是侵入性的,不利于病情的临床评估。因此,对MAFLD诊断标志物的研究日益增多。此外,没有临床药物治疗MAFLD,生活方式干预在MAFLD的预防和治疗中仍然有效。在这次审查中,我们试图总结MAFLD的新兴诊断指标和有效的生活方式干预措施,并为MAFLD的诊断和治疗提供新的见解.
    MAFLD has become a major global health problem and is the leading cause of liver disease worldwide. The disease progresses from a simple fatty liver to gradual fibrosis, which progresses to cirrhosis and even hepatocellular liver cancer. However, the methods currently used for diagnosis are invasive and do not facilitate clinical assessment of the condition. As a result, research on markers for the diagnosis of MAFLD is increasing. In addition, there are no clinical medications for the treatment of MAFLD, and lifestyle interventions remain effective in the prevention and treatment of MAFLD. In this review, we attempt to make a summary of the emerging diagnostic indicators and effective lifestyle interventions for MAFLD and to provide new insights into the diagnosis and treatment of MAFLD.
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