Neuropeptide Y

神经肽 Y
  • 文章类型: Journal Article
    在这个分析中,我们的目的是调查COVID-19疾病对饮食行为的影响。共有55名惯用右手的成年人,<50岁,没有超重或肥胖,纳入了两项横断面研究.第一个受试者在2018年9月至2019年12月期间注册(非COVID-19组)。第二个包括2022年3月至2023年5月之间注册的受试者;对于此分析,保留有COVID-19病史的28例(COVID-19组)。饥饿,TFEQ-18血浆生长素释放肽,在禁食期间评估神经肽Y(NPY)和静息状态fMRI。通过基于体素的区域同质性(ReHo)和中心性(DC)评估区域内神经元的同步性和连通性。COVID-19组的ghrelin和NPY水平明显高于非COVID-19组(ghrelin197.5pg/mL与67.1pg/mL,p<0.001;NPY128.0pg/mL与84.5pg/mL,p=0.005)。NPY水平与左侧舌侧DC和ReHo呈正相关(分别为r=0.67785和r=0.73604)。认知克制的得分相似,根据TFEQ-18问卷结果,两组均有不受控制的进食和情绪进食(均p>0.05)。我们的数据显示食欲相关激素水平升高,与食欲调节相关的大脑区域的活动,在COVID-19感染后持续很长时间。
    In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection.
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  • 文章类型: Journal Article
    BACKGROUND: Depression is one of the most common mental illnesses. Impaired neurogenesis is observed in depression. Biomarkers of impaired neurogenesis in depression can act as a useful objective and diagnostic and prognostic tool to determine the severity of depression.
    OBJECTIVE: To study the concentration of biochemical indicators in the blood that may be involved in the pathogenesis of depression and their intercorrelations, and to determine any associations between the concentrations of biochemical indicators and severity of depressive symptoms.
    METHODS: We determined the plasma concentrations of serotonin, dopamine, and neurotrophic factors involved in neurogenesis (BDNF, CDNF and neuropeptide Y) using enzyme immunoassay and mass spectrometry in depressed patients (n=22) and healthy controls (n=16) matched by socio-demographic parameters. All participants were assessed using the Hamilton Depression Scale (HAMD), the Generalized Anxiety Disorder Questionnaire (GAD-7), and the Center for Epidemiologic Studies Depression Scale (CES-D) to enter the study. The standard cut-offs for the CES-D and GAD-7 scales were used to confirm the presence or absence of depression and anxiety.
    RESULTS: The concentrations of serotonin, dopamine, BDNF, CDNF, and neuropeptide Y in plasma did not differ between the groups and was not found to be associated with the scores on the scales. Positive correlations were found between the concentration of neuropeptide Y and serotonin, BDNF, and CDNF in blood plasma.
    CONCLUSIONS: Plasma concentrations of biomarkers related to the pathophysiology of depression did not correlate with the severity of its symptoms.
    UNASSIGNED: Изучение концентрации биохимических показателей в крови, принимающих возможное участие в патогенезе депрессии, поиск ассоциаций с тяжестью депрессивной симптоматики может быть полезным в качестве объективной диагностики заболевания и прогнозирования тяжести течения патологии.
    UNASSIGNED: Изучение биохимических показателей крови, которые могут быть связаны с депрессией. Определения корреляционной взаимосвязи этих показателей при депрессивных расстройствах.
    UNASSIGNED: В работе определяли концентрацию в плазме крови моноаминовых нейромедиаторов серотонина и дофамина, и нейротрофических факторов, участвующих в нейрогенезе (BDNF, CDNF и нейропептид Y) у пациентов с депрессией и здоровых добровольцев с одинаковыми социо-демографическими параметрами, используя методы иммуноферментного анализа и масс-спектрометрии. Все участники исследования были опрошены по шкале депрессии Гамильтона (HAMD), опроснику генерализованного тревожного расстройства (GAD-7) и опроснику депрессии центра эпидемиологических исследований (CES-D). Показатели шкал CES-D и GAD-7 использовались для подтверждения наличия или отсутствия депрессии и тревоги у участников исследования.
    UNASSIGNED: Суммарный балл по трем исследованным шкалам у пациентов с депрессией существенно выше, чем в контрольной группе. Содержание серотонина, дофамина, BDNF, CDNF и нейропептида Y в плазме крови не отличалось в группах испытуемых и не было ассоциировано с баллами по шкалам. Обнаружены положительные корреляции содержания нейропептида Y с серотонином, и BDNF с CDNF в плазме крови.
    UNASSIGNED: Исследованные маркеры хоть и связаны с патофизиологией депрессии, не коррелируют с тяжестью симптоматики и содержание их в плазме крови не отражает процессы, происходящие в мозге.
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  • 文章类型: Journal Article
    OBJECTIVE: To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV).
    METHODS: A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups.
    RESULTS: After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05).
    CONCLUSIONS: Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.
    目的:观察项七针联合压灸治疗颈性眩晕(CV)的临床疗效。方法:将70例CV患者随机分为观察组和对照组,每组35例。观察组采用项七针联合压灸治疗,每日1次,每周6次,连续治疗2周。对照组予口服盐酸倍他司汀片(2周)和醋氯芬酸分散片(3 d)。分别于治疗前后观察两组患者颈性眩晕症状与功能评估量表(ESCV)评分,检测血浆神经肽Y(NPY)、内皮素-1(ET-1)、降钙素基因相关肽(CGRP)含量及血液流变学、血流动力学指标,并于治疗后评定两组临床疗效。结果:治疗后,两组患者ESCV眩晕、日常生活及工作能力、心理及社会适应能力、头痛评分及总分较治疗前升高(P<0.01,P<0.05),观察组患者颈肩痛评分较治疗前升高(P<0.01);观察组患者ESCV各项评分及总分均高于对照组(P<0.01,P<0.05)。治疗后,两组患者血浆NPY和ET-1含量较治疗前降低(P<0.01),血浆CGRP含量较治疗前升高(P<0.01,P<0.05);观察组患者血浆NPY、ET-1含量低于对照组(P<0.01),血浆CGRP含量高于对照组(P<0.01)。治疗后,两组患者全血高切黏度、血浆黏度、全血低切黏度均较治疗前降低(P<0.01,P<0.05),基底动脉(BA)、左侧椎动脉(LVA)、右侧椎动脉(RVA)平均血流速度均较治疗前升高(P<0.05);观察组患者全血高切黏度、血浆黏度及全血低切黏度均低于对照组(P<0.01),BA、LVA、RVA平均血流速度均高于对照组(P<0.05)。观察组总有效率为91.4%(32/35),高于对照组的71.4%(25/35,P<0.05)。结论:项七针联合压灸可有效减轻CV患者临床症状,改善血液流变学及血流动力学。.
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  • 文章类型: Journal Article
    下丘脑的弓状核(ARN)涉及多种生物学功能,比如喂食,性活动,和心血管系统的调节。据报道,瘦素增加了前黑皮质素(POMC)中的c-Fos表达-并减少了ARN的神经肽Y(NPY)阳性神经元中的c-Fos表达,这表明它刺激了前者,并抑制了后者。这项研究旨在直接电生理检查瘦素对ARN神经元的影响,并研究潜在的性别二态变化。用氨基甲酸乙酯麻醉Wistar大鼠,并将电极插入ARN中。在记录了一个自发活跃的神经元至少一分钟后,瘦素是静脉给药,并且记录相同神经元的放电活动另外两分钟。发现大约一半的ARN神经元具有兴奋性,另一半是对瘦素给药的抑制反应。对瘦素有兴奋性反应的神经元的兴奋性在性别之间没有差异。雌性对瘦素有抑制反应的神经元的平均放电速率为,然而,明显低于男性。获得的结果表明,对瘦素具有刺激反应的ARN神经元是POMC,而具有抑制反应的ARN神经元是NPY神经元。NPYY1受体可能负责,至少在某种程度上,神经元兴奋性的性别差异被推定为NPY神经元。
    The arcuate nucleus (ARN) of the hypothalamus is involved in multiple biological functions, such as feeding, sexual activity, and the regulation of the cardiovascular system. It was reported that leptin increased c-Fos expression in the proopiomelanocortin (POMC)- and decreased it in the neuropeptide-Y (NPY)-positive neurons of the ARN, suggesting that it stimulates the former, and inhibits the later. This study aimed at the direct electrophysiological examination of the effect of leptin on ARN neurons and to investigate potential sex-dimorphic changes. Wistar rats were anesthetized with urethane and the electrodes were inserted into the ARN. After a spontaneous active neuron was recorded for at least one minute, leptin was administered intravenously, and the firing activity of the same neuron was recorded for two additional minutes. It was found that approximately half of the ARN neurons had an excitatory, and another half an inhibitory response to the leptin administration. The excitability of the neurons with excitatory response to leptin was not different between the sexes. The average firing rate of the neurons with inhibitory response to leptin in females was, however, significantly lower comparing to the males. The obtained results demonstrate that the ARN neurons with stimulatory response to leptin are POMC and those with inhibitory response are NPY neurons. NPY Y1 receptor be might responsible, at least in part, for the sex differences in the excitability of the neurons putatively identified as NPY neurons.
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  • 文章类型: Journal Article
    背景:颈动脉斑块(CP)的形成是动脉粥样硬化的重要后果,并导致严重的并发症。神经肽Y(NPY)水平,这是一种交感神经递质,在心血管疾病中升高。它在炎症中也有重要作用。本研究旨在探讨血清NPY与CP的关系,进一步研究NPY和炎症因子对CP的影响。
    方法:这项横断面研究是在福建医科大学附属第二医院进行健康检查的300名成年人中进行的,其中177人最终被录取。根据颈动脉彩色多普勒超声检查结果,将参与者分为CP组(n=120)和非CP组(n=57)或对照组(n=57)。CP组进一步分为稳定斑块(SP,n=80)和易损斑块(VP,n=40)组基于斑块特征。检测血清NPY和促炎细胞因子肿瘤坏死因子-α(TNF-α)水平。采用单因素和相关性分析评价血清NPY水平与血清NPY、促炎细胞因子,和CP表型。
    结果:CP组患者的血清NPY和TNF-α水平明显高于NCP组[(177.30±43.29)pg。mL-1vs.(121.53±40.16)pg。mL-1,P<0.001;(41.94±14.19)pg。mL-1vs.(33.54±13.37)pg。mL-1,P=0.003]。VP组患者的血清NPY水平明显高于SP组患者[(191.67±39.87)ng。L-1vs.(170.12±43.37)ng。L-1,P=0.01,P<0.05]。CP组患者血清TNF-α和NPY水平呈正相关(r=0.184,P=0.044)。二元Logistic回归分析显示,血清NPY和TNF-α是CP的独立影响因素[(OR=1.029,P<0.001);(OR=1.030,P=0.023)]。预测CP的NPY的ROC曲线下面积在0.819处具有统计学意义。
    结论:一起,血清NPY水平升高似乎与中国成年人冠状动脉粥样硬化的发生有关。
    Carotid plaque (CP) formation is an important consequence of atherosclerosis and leads to significant complications. Levels of neuropeptide Y (NPY), which is a sympathetic neurotransmitter, are elevated in cardiovascular diseases. It also has important roles in inflammatory conditions. This study aimed to explore the relationship between serum NPY and CP and to study further the influence of NPY and inflammatory factors on CP.
    This cross-sectional study was conducted among 300 adults who underwent a health examination at the Second Affiliated Hospital of Fujian Medical University in Fujian Province, of whom 177 were finally enrolled. The participants were divided into the CP (n = 120) and non-CP (NCP) or control (n = 57) groups according to the results of carotid artery color Doppler ultrasound. The CP group was further classified into stable plaque (SP, n = 80) and vulnerable plaque (VP, n = 40) groups based on plaque characteristics. Serum NPY and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) levels were examined. Univariate and correlation analyses were used to evaluate the correlation between serum NPY levels, pro-inflammatory cytokines, and the CP phenotype.
    The serum NPY and TNF-α levels of patients in the CP group were significantly higher than those in individuals from the NCP group [ (177.30 ± 43.29) pg.mL- 1 vs. (121.53 ± 40.16)pg.mL- 1, P < 0.001; (41.94 ± 14.19) pg.mL- 1 vs.(33.54 ± 13.37)pg.mL- 1, P = 0.003]. The serum NPY levels of the patients in the VP group were significantly higher than those in patients from the SP group [(191.67 ± 39.87)ng.L- 1 vs.(170.12 ± 43.37)ng.L- 1, P = 0.01, P < 0.05]. Serum TNF-α and NPY levels were positively correlated among patients from the CP group (r = 0.184, P = 0.044). The binary logistic regression analysis showed that serum NPY and TNF-α were independent influencing factors of CP [(OR = 1.029, P < 0.001);(OR = 1.030, P = 0.023)]. The area under the ROC curve of NPY predicting the CP showed statistical significance at a value of 0.819.
    Together, elevated serum NPY levels seem to be associated with the occurrence of coronary atherosclerosis in Chinese adults.
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  • 文章类型: Journal Article
    背景:岛叶皮质(aINS)的前叶是与边缘中心(例如前扣带皮质)相互联系的皮质区域,前额叶皮质,杏仁核和伏隔核(NAc)。事实上,aINS参与了情绪和动机功能的自主神经信息的整合。强迫性食用药物或高脂肪食物会导致行为和大脑水平的改变。大脑奖励回路因持续摄入而改变,特别是从腹侧被盖区(VTA)到NAc的多巴胺能投射。aINS具有与该系统的组件的多个连接。近年来,已经努力更好地理解aINS在成瘾中的基本作用,使其成为研究成瘾新疗法的关键中心之一。
    目的:本研究的重点是1.-人aINS是否表达食欲肽,如神经肽Y(NPY),一种已知能诱导饮食过多的肽,这与肥胖的发生和发展有关,2.-致肥胖饮食对C57BL/6小鼠的aINS和NAc中NPY表达的长期影响。
    方法:本研究使用总共17只雌性C57BL/6J小鼠。雌性小鼠随意喂食水,无论是标准饮食(SD)或高脂肪饮食(HFD)诱导肥胖。SD上有7只雌性小鼠,HFD上有10只。实验的持续时间为180天。我们还研究了3个成年人的大脑(1个男性和2个女性,平均年龄55.7±5.2岁)。使用免疫组织化学和双重免疫荧光技术进行形态学研究,以研究人和小鼠的aINS和NAc的NPY神经元的神经化学谱。
    结果:我们的形态学分析首次证明了NPY在人类皮质不同层中的基础表达(II,III,IV,V/VI),与以前在其他物种中的研究相似。此外,我们观察到接受长期肥胖饮食的肥胖小鼠的aINS和NAc中NPY阳性细胞数量及其胞浆内信号的增加。
    结论:据我们所知,这是第一项研究显示NPY在人类INS中的分布和表达,以及在肥胖小鼠中长时间用致肥胖饮食治疗后其表达如何改变。我们的发现可能有助于理解与奖励系统相关的地区肥胖的病理生理机制,并与高脂肪食物的不受控制的摄入有关。从而促进新的治疗靶点的识别。
    BACKGROUND: The anterior lobe of the insular cortex (aINS) is a cortical region that has reciprocal connections with limbic centers such as the anterior cingulate cortex, prefrontal cortex, amygdala and nucleus accumbens (NAc). In fact, the aINS has been involved in the integration of autonomic information for emotional and motivational functions. The compulsive consumption of drugs or high-fat foods induces alterations at both behavioural and brain levels. Brain reward circuits are altered in response to continued intake, in particular the dopaminergic projections from the ventral tegmental area (VTA) to the NAc. The aINS has multiple connections with the components of this system. In recent years, efforts have been made to better understand the fundamental role of the aINS in addiction, making it one of the key centres of interest for research into new treatments for addiction.
    OBJECTIVE: The present work focuses on studying 1.- whether the human aINS expresses orexigenic peptides such as neuropeptide Y (NPY), a peptide known to induce hyperphagia, and which has been implicated in the onset and development of obesity, 2.- the long-term effect of an obesogenic diet on NPY expression in the aINS and NAc of C57BL/6 mice.
    METHODS: A total of 17 female C57BL/6 J mice were used in this study. Female mice were fed ad libitum with water and, either a standard diet (SD) or a high-fat diet (HFD) to induce obesity. There were seven female mice on the SD and ten on the HFD. The duration of the experiment was 180 days. We also studied 3 human adult brains (1 male and 2 females, mean age 55.7 ± 5.2 years). The morphological study was performed using immunohistochemistry and double immunofluorescence techniques to study the neurochemical profile of NPY neurons of the aINS and NAc of humans and mice.
    RESULTS: Our morphological analysis demonstrates for the first time the basal expression of NPY in different layers of the human cortex (II, III, IV, V/VI), in a pattern similar to previous studies in other species. Furthermore, we observed an increase in the number of NPY-positive cells and their intracytoplasmic signal in the aINS and NAc of the obese mice subjected to a long-term obesogenic diet.
    CONCLUSIONS: To our knowledge, this is the first study to show the distribution and expression of NPY in the human INS and how its expression is altered after prolonged treatment with an obesogenic diet in obese mice. Our findings may contribute to the understanding of the pathophysiological mechanisms underlying obesity in regions related to the reward system and associated with uncontrolled intake of high-fat foods, thus facilitating the identification of novel therapeutic targets.
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  • 文章类型: Journal Article
    靶向Y4受体(Y4R)的正变构调节剂,参与饱腹感调节的G蛋白偶联受体(GPCR),在抗肥胖研究中提供了巨大的潜力。在这项研究中,我们利用定量构效关系(QSAR)模型筛选出603个化合物,并在高通量筛选(HTS)中进行测试。这里,鉴定了新型正变构调节剂(PAM)VU0506013,在天然表达Y4R的工程化细胞系和小鼠降结肠粘膜中表现出纳摩尔亲和力和对Y4R的明显选择性。基于这种引线结构,我们在支架的两个区域进行了系统的SAR研究,并提出了一系列27个类似物,这些类似物在分子的N-和C-末端杂环中进行了修饰,以深入了解功能相关的位置.通过诱变和计算对接,我们提出了VU0506013在Y4R的跨膜核心中的潜在结合模式。VU0506013提出了一种有前途的支架,用于开发体内工具,以致力于Y4R的抗肥胖药物研究。
    Positive allosteric modulators targeting the Y4 receptor (Y4R), a G protein-coupled receptor (GPCR) involved in the regulation of satiety, offer great potential in anti-obesity research. In this study, we selected 603 compounds by using quantitative structure-activity relationship (QSAR) models and tested them in high-throughput screening (HTS). Here, the novel positive allosteric modulator (PAM) VU0506013 was identified, which exhibits nanomolar affinity and pronounced selectivity toward the Y4R in engineered cell lines and mouse descending colon mucosa natively expressing the Y4R. Based on this lead structure, we conducted a systematic SAR study in two regions of the scaffold and presented a series of 27 analogues with modifications in the N- and C-terminal heterocycles of the molecule to obtain insight into functionally relevant positions. By mutagenesis and computational docking, we present a potential binding mode of VU0506013 in the transmembrane core of the Y4R. VU0506013 presents a promising scaffold for developing in vivo tools to move toward anti-obesity drug research focused on the Y4R.
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  • 文章类型: Journal Article
    背景:除了腰椎牵引对下背痛患者脊柱内结构变化的积极影响外,治疗效果可能与血液中的疼痛生物标志物相关。其中,与肥胖相关的全身代谢因素可能起重要作用。这是第一项旨在检查BMI差异很大的两个实验组中牵引治疗的有效性的研究,并评估血液生物标志物与腰痛强度之间的关系。
    方法:在前瞻性临床试验中,患有慢性下腰痛的女性被分为正常体重或肥胖组.两组患者均接受了二十次腰椎牵引治疗(每天30分钟,连续模式,力水平为体重的25-30%)。治疗前后进行疼痛主观评估(VAS和PPT),和血清聚集蛋白聚糖硫酸软骨素846表位(CS-846)的浓度,神经肽Y,瘦素,测定了脂肪素和生长和分化因子15(GDF-15)。对28名女性的数据进行了统计评估。
    结果:治疗后,两组的最大腰背痛均下降,正常体重组GDF-15浓度降低,肥胖组GDF-15浓度升高,肥胖组CS-846浓度下降。腰椎PPT的感觉和神经肽Y的平均浓度,瘦素和脂素在两组中没有变化。然而,GDF-15,瘦素,和脂肪素浓度与疼痛的感觉被揭示。
    结论:正常体重组和肥胖组之间的明显差异表明,过多的脂肪组织在加重炎症过程和下腰痛发展中的作用。Adipsin,CS-846和GDF-15渴望成为肥胖女性腰背痛的生物标志物,但需要进一步的研究来回答它们是否可能被认为是预测和监测慢性腰背治疗的可靠生物标志物.
    背景:NCT04507074,预期于2020年7月6日注册。
    BACKGROUND: Apart from the positive effect of lumbar traction on structural changes within the spine in patients with low back pain, it is likely that therapeutic effects are correlated with pain biomarkers in the blood. Among them, systemic metabolic factors related to obesity may play an important role. This is the first study designed to examine the effectiveness of traction therapy in two experimental groups with considerably different BMI and to assess relationships between blood biomarkers and low back pain intensity.
    METHODS: In the prospective clinical trial, women suffering from chronic low back pain were allocated into the normal-weight or obesity groups. Patients in both groups underwent twenty sessions of lumbar traction therapy (30 min a day, continuous mode with a force level of 25-30% of body weight). Before and after therapy subjective assessments of pain (VAS and PPT) were performed, and serum concentrations of aggrecan chondroitin sulfate 846 epitope (CS-846), neuropeptide Y, leptin, adipsin and growth and differentiation factor 15 (GDF-15) were determined. The data were statistically evaluated for 28 women.
    RESULTS: After therapy, the maximal low back pain decreased in both groups, GDF-15 concentration was reduced in the normal-weight group and increased in the obesity group, and CS-846 concentration decreased in the obesity group. The sensation of PPT in the lumbar spine and mean concentrations of neuropeptide Y, leptin and adipsin did not change in both groups. However, the relationships of GDF-15, leptin, and adipsin concentrations with the perception of pain were revealed.
    CONCLUSIONS: Distinct differences between the normal-weight and obesity groups pointed on the role of excessive adipose tissue in aggravating the inflammatory processes and in the development of low back pain. Adipsin, CS-846 and GDF-15 aspire to be the low back pain biomarkers in women with obesity, but there is a need for further research to answer whether they might be considered reliable biomarkers for the prognosis and monitoring of chronic low back treatment.
    BACKGROUND: NCT04507074, registered prospectively on July 6, 2020.
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  • 文章类型: Randomized Controlled Trial
    神经肽Y(NPIs)有助于交感神经-肾上腺刺激:NPY1-36增强儿茶酚胺(CAT)的作用,而NPY3-36抑制CAT释放。我们试图调查是否抑制二肽基肽酶-4(DPP4),将NPY1-36裂解为NPY3-36,导致NPY1-36增强作用增加,NPY3-36对CAT的抑制作用减少,从而提高耐久性能。7名男性参与者(年龄27±3岁,BMI23.1±2.4kg/m2)使用任一安慰剂在95%的峰值功率输出下进行了疲惫时间自行车运动,或者沙格列汀,DPP4抑制剂。耗氧量(V²O2),心率变异性,NPY1-36,NPY3-36,儿茶酚胺,在之前的几个时间点测量乳酸,during,锻炼后。用沙格列汀,DPP4活性(12.7±1.6vs.0.2±0.3U/L,p=0.001;d=10.7)在休息时降低,而NPY3-36(1.94±0.88vs.0.73±0.22pm;p<0.001;d=2.04)在运动过程中减少,NPY1-36增加(2.64±2.22vs.4.59±2.98pm;p<0.01;d=0.19)。CAT没有变化。沙格列汀的耗尽时间增加32%。安慰剂和沙格列汀之间的耗尽时间差异与NPY1-36差异相关(R=0.78,p<0.05)。峰值V²O2和其他心肺值没有差异,沙格列汀的NPY峰值浓度较高。DPP4封锁提高了性能,增加NPY1-36,并降低NPY3-36浓度,这可能对CAT的影响具有增强作用。然而,DPP4参与了许多不同的行动,因此,NPYs是一组可能影响其性能增强效果的因素;需要进一步的研究来确定确切的机制.
    Neuropeptide Ys (NPYs) contribute to sympathetic-adreno stimulation: NPY1-36 potentiates the effects of catecholamines (CATs), whereas NPY3-36 inhibits CAT release. We sought to investigate whether inhibiting dipeptidyl-peptidase-4 (DPP4), cleaving NPY1-36 into NPY3-36, leads to increased NPY1-36 potentiating effects and reduced NPY3-36 inhibitory effects on CATs, thereby improving endurance performance. Seven male participants (age 27 ± 3 years, BMI 23.1 ± 2.4 kg/m2 ) performed time-to-exhaustion cycling exercise at 95% of peak power output with either placebo, or saxagliptin, a DPP4 inhibitor. Oxygen consumption (V̇O2 ), heart rate variability, NPY1-36, NPY3-36, catecholamines, and lactate were measured at several time points before, during, and after exercise. With saxagliptin, DPP4 activity (12.7 ± 1.6 vs. 0.2 ± 0.3 U/L, p = 0.001; d = 10.7) was decreased at rest, while NPY3-36 (1.94 ± 0.88 vs. 0.73 ± 0.22 pm; p < 0.001; d = 2.04) decreased and NPY1-36 increased during exercise (2.64 ± 2.22 vs. 4.59 ± 2.98 pm; p < 0.01; d = 0.19). CATs were unchanged. Time-to-exhaustion was 32% higher with saxagliptin. The difference in time-to-exhaustion between placebo and saxagliptin was correlated with NPY1-36 differences (R = 0.78, p < 0.05). Peak V̇O2 and other cardio-respiratory values were not different, whereas peak NPY concentrations were higher with saxagliptin. DPP4 blockade improved performance, increased NPY1-36, and decreased NPY3-36 concentrations which may have potentiating effects on the influences of CATs. However, DPP4 is involved in many different actions, thus NPYs are one group of factors that may underly its performance-enhancing effects; further studies are required to determine the exact mechanisms.
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  • 文章类型: Journal Article
    背景:神经细胞因子可上调或下调神经性疼痛。我们假设疼痛性膝骨关节炎(KOA)中用于治疗目的的右旋糖(D-葡萄糖)注射(右旋糖治疗:DPT)会有利地影响滑液神经细胞因子的浓度。
    方法:20名IV级有症状的KOA参与者接受滑液抽吸,然后注射葡萄糖或模拟葡萄糖,一周后出现相反的情况。然后,所有参与者每月接受开放标签葡萄糖注射,为期6个月,在20分钟连续9个月进行行走疼痛的系列评估,以及滑膜-神经细胞因子浓度测量(降钙素基因相关肽,P物质(SP),和神经肽Y(NPY))在一周和三个月。
    结果:在葡萄糖注射后20分钟和9个月观察到临床重要的镇痛作用。与仅滑液抽吸相比,注射右旋糖的膝盖的一周滑液SP浓度上升了111%(组内p=0.028,组间p=0.07)。在所有膝盖中注射开放标签葡萄糖后,三个月的滑液NPY浓度显着下降(65%;p&lt;0.001)。
    结论:KOA关节内注射葡萄糖后的快速和中期镇痛伴随着滑液神经细胞因子SP和NPY的潜在有利变化,分别,虽然这些变化是孤立的。建议在将来的DPT评估中包括神经细胞因子以阐明作用机制。
    Background: Neurocytokines may upregulate or downregulate neuropathic pain. We hypothesized that dextrose (D-glucose) injections for therapeutic purposes (dextrose prolotherapy: DPT) in painful knee osteoarthritis (KOA) would favorably affect synovial-fluid neurocytokine concentrations. Methods: Twenty participants with grade IV symptomatic KOA received synovial-fluid aspiration followed by dextrose or simulated dextrose injections, followed by the reverse after one week. All participants then received open-label dextrose injections monthly for 6 months, with serial assessments of walking pain at 20 min for 9 months, as well as synovial-neurocytokine-concentration measurements (calcitonin gene-related peptide, substance P (SP), and neuropeptide Y (NPY)) at one week and three months. Results: Clinically important analgesia was observed at 20 min and for 9 months post dextrose injection. One -week synovial-fluid SP concentration rose by 111% (p = 0.028 within groups and p = 0.07 between groups) in the dextrose-injected knees compared to synovial-fluid aspiration only. Three-month synovial-fluid NPY concentration dropped substantially (65%; p < 0.001) after open-label dextrose injection in all knees. Conclusions: Prompt and medium-term analgesia after intra-articular dextrose injection in KOA was accompanied by potentially favorable changes in synovial-fluid neurocytokines SP and NPY, respectively, although these changes were isolated. Including neurocytokines in future assessments of DPT to elucidate mechanisms of action is recommended.
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