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Utility of an Untargeted Metabolomics Approach Using a 2D GC-GC-MS Platform to Distinguish Relapsing and Progressive Multiple Sclerosis 使用二维 GC-GC-MS 平台的非靶向代谢组学方法在区分复发性和进行性多发性硬化症方面的实用性
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-11 DOI: 10.3390/metabo14090493
Indrani Datta, Insha Zahoor, Nasar Ata, Faraz Rashid, Mirela Cerghet, Ramandeep Rattan, Laila M. Poisson, Shailendra Giri
Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS, which ultimately progresses to secondary progressive MS (SPMS), while primary progressive MS (PPMS) is a type of MS that worsens gradually over time without remissions. There is a gap in knowledge regarding whether the relapsing form can be distinguished from the progressive course, or healthy subjects (HS) based on an altered serum metabolite profile. In this study, we performed global untargeted metabolomics with the 2D GC-GC-MS platform to identify altered metabolites between RRMS, PPMS, and HS. We profiled 235 metabolites in the serum of patients with RRMS (n = 41), PPMS (n = 31), and HS (n = 91). A comparison of RRMS and HS patients revealed 22 significantly altered metabolites at p < 0.05 (false-discovery rate [FDR] = 0.3). The PPMS and HS comparisons revealed 28 altered metabolites at p < 0.05 (FDR = 0.2). Pathway analysis using MetaboAnalyst revealed enrichment of four metabolic pathways in both RRMS and PPMS (hypergeometric test p < 0.05): (1) galactose metabolism; (2) amino sugar and nucleotide sugar metabolism; (3) phenylalanine, tyrosine, and tryptophan biosynthesis; and (4) aminoacyl-tRNA biosynthesis. The Qiagen IPA enrichment test identified the sulfatase 2 (SULF2) (p = 0.0033) and integrin subunit beta 1 binding protein 1 (ITGB1BP1) (p = 0.0067) genes as upstream regulators of altered metabolites in the RRMS vs. HS groups. However, in the PPMS vs. HS comparison, valine was enriched in the neurodegeneration of brain cells (p = 0.05), and heptadecanoic acid, alpha-ketoisocaproic acid, and glycerol participated in inflammation in the CNS (p = 0.03). Overall, our study suggests that RRMS and PPMS may contribute metabolic fingerprints in the form of unique altered metabolites for discriminating MS disease from HS, with the potential for constructing a metabolite panel for progressive autoimmune diseases such as MS.
多发性硬化症(MS)是青壮年最常见的中枢神经系统(CNS)炎症性神经退行性疾病,会导致进行性神经功能缺陷。复发-缓解表型(RRMS)是多发性硬化症最常见的病程,最终发展为继发性进展型多发性硬化症(SPMS),而原发性进展型多发性硬化症(PPMS)是一种随着时间推移逐渐恶化且无缓解的多发性硬化症。关于能否根据血清代谢物谱的改变将复发性多发性硬化症与进展性多发性硬化症或健康受试者(HS)区分开来,目前尚存在知识空白。在这项研究中,我们利用二维 GC-GC-MS 平台进行了全球非靶向代谢组学研究,以确定 RRMS、PPMS 和 HS 之间代谢物的变化。我们分析了 RRMS(41 人)、PPMS(31 人)和 HS(91 人)患者血清中的 235 种代谢物。对 RRMS 和 HS 患者进行比较后发现,有 22 种代谢物发生了明显变化,P < 0.05(假发现率 [FDR] = 0.3)。PPMS 和 HS 的比较显示,28 个代谢物发生了改变,p < 0.05(FDR = 0.2)。使用 MetaboAnalyst 进行的通路分析显示,在 RRMS 和 PPMS 中,有四种代谢通路发生了富集(超几何检验 p <0.05):(1)半乳糖代谢;(2)氨基糖和核苷酸糖代谢;(3)苯丙氨酸、酪氨酸和色氨酸生物合成;以及(4)氨基酰-tRNA生物合成。Qiagen IPA富集测试发现,在RRMS组与HS组中,硫酸酯酶2(SULF2)(p = 0.0033)和整合素亚基β1结合蛋白1(ITGB1BP1)(p = 0.0067)基因是代谢物改变的上游调控因子。然而,在 PPMS 与 HS 的比较中,缬氨酸富集于脑细胞的神经变性(p = 0.05),而十七酸、α-酮异己酸和甘油参与了中枢神经系统的炎症(p = 0.03)。总之,我们的研究表明,RRMS和PPMS可能以独特的代谢物改变形式提供代谢指纹,用于区分MS疾病和HS,并有可能为MS等进行性自身免疫性疾病构建代谢物面板。
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引用次数: 0
Organic Trace Minerals Enhance the Gut Health of British Shorthair Cats by Regulating the Structure of Intestinal Microbiota 有机微量元素通过调节肠道微生物群的结构增强英国短毛猫的肠道健康
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-11 DOI: 10.3390/metabo14090494
Yingyue Cui, Mingrui Zhang, Haotian Wang, Tong Yu, Anxuan Zhang, Gang Lin, Yuhan Guo, Yi Wu
Trace minerals are essential for biological processes, including enzyme function, immune response, and hormone synthesis. The study assessed the effects of different dietary trace minerals on the gut health, microbiota composition, and immune function of cats. Eighteen adult British Shorthair cats were divided into three groups receiving inorganic trace minerals (ITM), a 50/50 mix of inorganic and organic trace minerals (ITM + OTM), or organic trace minerals (OTM) for 28 days. The OTM showed enhanced immune capacities, reduced intestinal barrier function, and lower inflammation condition. The OTM altered gut microbiota diversity, with a lower Simpson index and higher Shannon index (p < 0.05). Specifically, the abundance of Bacteroidota, Lachnospiraceae, and Prevotella in the OTM group were higher than the ITM group (p < 0.05). Metabolomic analysis identified 504 differential metabolites between the OTM and ITM groups (p < 0.05, VIP-pred-OPLS-DA > 1), affecting pathways related to steroid hormone biosynthesis and glycerophospholipid metabolism (p < 0.05, VIP-pred-OPLS-DA > 2). Additionally, there was a significant correlation between intestinal microbiota and differential metabolites. To conclude, dietary OTM can modulate the gut metabolite and microbiota composition, enhance immune and intestinal barrier function, and mitigate inflammation in cats, highlighting the benefit of using OTM in feline diet to promote the intestinal and overall health.
微量元素是生物过程(包括酶功能、免疫反应和激素合成)所必需的。这项研究评估了不同膳食微量矿物质对猫肠道健康、微生物群组成和免疫功能的影响。18 只成年英国短毛猫被分为三组,分别接受无机微量矿物质(ITM)、无机微量矿物质和有机微量矿物质 50/50 混合(ITM + OTM)或有机微量矿物质(OTM),为期 28 天。结果显示,OTM 增强了免疫能力,降低了肠道屏障功能,降低了炎症状况。OTM 改变了肠道微生物群的多样性,辛普森指数降低,香农指数升高(p < 0.05)。具体来说,OTM 组的类杆菌属、拉克氏菌属和普雷沃特菌的丰度高于 ITM 组(P < 0.05)。代谢组学分析在 OTM 组和 ITM 组之间发现了 504 种不同的代谢物(p < 0.05,VIP-pred-OPLS-DA > 1),影响了与类固醇激素生物合成和甘油磷脂代谢相关的途径(p < 0.05,VIP-pred-OPLS-DA > 2)。此外,肠道微生物群与不同代谢物之间存在显著相关性。总之,饮食中的 OTM 可以调节猫的肠道代谢物和微生物群组成,增强免疫和肠道屏障功能,减轻炎症反应,突出了在猫饮食中使用 OTM 促进肠道和整体健康的益处。
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引用次数: 0
Sarcosine, Trigonelline and Phenylalanine as Urinary Metabolites Related to Visceral Fat in Overweight and Obesity. 超重和肥胖症患者尿液中与内脏脂肪有关的代谢物肌氨酸、川芎氨酸和苯丙氨酸
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-10 DOI: 10.3390/metabo14090491
Aline Maria Cavalcante Gurgel, Aline Lidiane Batista, Diogo Manuel Lopes de Paiva Cavalcanti, Alviclér Magalhães, Denise Engelbrecht Zantut-Wittmann

The objective of the present study is to analyze the urinary metabolome profile of patients with obesity and overweight and relate it to different obesity profiles. This is a prospective, cross-sectional study in which patients with a body mass index (BMI) ≥25 kg/m were selected. Anthropometric data were assessed by physical examination and body composition was obtained by bioimpedance (basal metabolic rate, body fat percentile, skeletal muscle mass, gross fat mass and visceral fat). Urine was collected for metabolomic analysis. Patients were classified according to abdominal circumference measurements between 81 and 93, 94 and 104, and >104 cm; visceral fat up to 16 kilos and less than; and fat percentiles of <36%, 36-46% and >46%. Spectral alignment of urinary metabolite signals and bioinformatic analysis were carried out to select the metabolites that stood out. NMR spectrometry was used to detect and quantify the main urinary metabolites and to compare the groups. Seventy-five patients were included, with a mean age of 38.3 years, and 72% females. The urinary metabolomic profile showed no differences in BMI, abdominal circumference and percentage of body fat. Higher concentrations of trigonelline (p = 0.0488), sarcosine (p = 0.0350) and phenylalanine (p = 0.0488) were associated with patients with visceral fat over 16 kg. The cutoff points obtained by the ROC curves were able to accurately differentiate between patients according to the amount of visceral fat: sarcosine 0.043 mg/mL; trigonelline 0.068 mg/mL and phenylalanine 0.204 mg/mL. In conclusion, higher visceral fat was associated with urinary levels of metabolites such as sarcosine, related to insulin resistance; trigonelline, related to muscle mass and strength; and phenylalanine, related to glucose metabolism and abdominal fat. Trigonelline, sarcosine and phenylalanine play significant roles in regulating energy balance and metabolic pathways essential for controlling obesity. Our findings could represent an interesting option for the non-invasive estimation of visceral fat through biomarkers related to alterations in metabolic pathways involved in the pathophysiology of obesity.

本研究旨在分析肥胖和超重患者的尿液代谢组特征,并将其与不同的肥胖特征联系起来。这是一项前瞻性横断面研究,研究对象是体重指数(BMI)≥25 kg/m的患者。体格检查评估了人体测量数据,生物阻抗测量了身体成分(基础代谢率、体脂百分位数、骨骼肌质量、总脂肪量和内脏脂肪)。收集尿液用于代谢组学分析。根据腹围测量值在 81 厘米至 93 厘米、94 厘米至 104 厘米和大于 104 厘米之间;内脏脂肪在 16 公斤以下;脂肪百分位数在 46%之间对患者进行分类。通过对尿液代谢物信号进行光谱配准和生物信息学分析,筛选出突出的代谢物。核磁共振光谱法用于检测和量化尿液中的主要代谢物,并对各组进行比较。研究共纳入 75 名患者,平均年龄为 38.3 岁,72% 为女性。尿液代谢组学特征显示,体重指数、腹围和体脂百分比没有差异。内脏脂肪超过 16 公斤的患者体内三尖杉碱(p = 0.0488)、肌氨酸(p = 0.0350)和苯丙氨酸(p = 0.0488)的浓度较高。ROC 曲线得出的临界点能够根据内脏脂肪量准确区分患者:肌氨酸为 0.043 毫克/毫升;三尖杉碱为 0.068 毫克/毫升;苯丙氨酸为 0.204 毫克/毫升。总之,较高的内脏脂肪与尿液中的代谢物水平有关,如肌氨酸(与胰岛素抵抗有关)、甘氨酸(与肌肉质量和力量有关)和苯丙氨酸(与葡萄糖代谢和腹部脂肪有关)。甘氨酸、肌氨酸和苯丙氨酸在调节能量平衡和控制肥胖所必需的代谢途径方面发挥着重要作用。我们的研究结果可能是通过与肥胖病理生理学代谢途径改变有关的生物标志物对内脏脂肪进行无创估测的一个有趣选择。
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引用次数: 0
Application of Eight Machine Learning Algorithms in the Establishment of Infertility and Pregnancy Diagnostic Models: A Comprehensive Analysis of Amino Acid and Carnitine Metabolism. 应用八种机器学习算法建立不孕症和妊娠诊断模型:氨基酸和肉碱代谢综合分析》。
IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-10 DOI: 10.3390/metabo14090492
Rui Zhang, Lei Zhou, Xiaoyan Hao, Liu Yang, Li Ding, Ruiqing Xing, Juanjuan Hu, Fengjuan Wang, Xiaonan Zhai, Yuanbing Guo, Zheng Cai, Jiawei Gao, Jun Yang, Jiayun Liu

To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis.

为了探索与非怀孕妇女(NPW)相比,非怀孕不孕妇女(NPW)、未怀孕不孕妇女(PWI)和接受过不孕症治疗的怀孕妇女(ITPW)体内氨基酸(AAs)和肉毒碱代谢改变的影响,并建立更有效的不孕症和妊娠诊断模型、研究人员采用高效液相色谱-串联质谱法(HPLC-MS/MS)对 496 份样本中的 21 种 AA 和 55 种肉毒碱含量进行了评估。)使用三种方法筛选生物标志物进行建模,并使用八种算法建立和验证模型。不孕症诊断训练模型的ROC、灵敏度、特异性和准确性分别高于0.956%、82.89%、66.64%和82.57%,而验证模型的ROC、灵敏度、特异性和准确性分别高于0.896%、77.67%、69.72%和83.38%。妊娠诊断训练模型的 ROC、灵敏度、特异性和准确性分别大于 0.994、96.23、97.79 和 97.69%,而验证模型的 ROC、灵敏度、特异性和准确性分别大于 0.572、96.39、93.03 和 94.71%。我们的研究结果表明,妊娠可能会改变不孕症妇女体内的 AA 和肉碱代谢,从而与 PWI 的内部环境相匹配。所开发的模型性能良好,灵敏度高,有助于不孕症和妊娠诊断。
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引用次数: 0
Natural Products and Derivatives Targeting Metabolic Reprogramming in Colorectal Cancer: A Comprehensive Review 针对结直肠癌代谢重编程的天然产品和衍生物:全面综述
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-09 DOI: 10.3390/metabo14090490
Mengyu Wang, Liqun Qu, Xinying Du, Peng Song, Jerome P. L. Ng, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Xianjun Fu
Metabolic reprogramming is a critical pathogenesis of colorectal cancer (CRC), referring to metabolic disorders that cancer cells make in response to the stimulating pressure. Metabolic reprogramming induces changes in genetic material and promotes CRC progression and has been proven to be an efficient target of CRC. As natural products have garnered interest due to notable pharmacological effects and potential in counteracting chemoresistance, an increasing body of research is delving into the impact of these natural products on the metabolic reprogramming associated with CRC. In this review, we collected published data from the Web of Science and PubMed, covering the period from January 1980 to October 2023. This article focuses on five central facets of metabolic alterations in cancer cells, glucose metabolism, mitochondrial oxidative phosphorylation (OXPHOS), amino acid metabolism, fatty acid synthesis, and nucleotide metabolism, to provide an overview of recent advancements in natural product interventions targeting metabolic reprogramming in CRC. Our analysis underscores the potential of natural products in disrupting the metabolic pathways of CRC, suggesting promising therapeutic targets for CRC and expanding treatment options for metabolic-associated ailments.
代谢重编程是结直肠癌(CRC)的一个重要发病机制,指的是癌细胞在刺激压力下产生的代谢紊乱。代谢重编程会诱导遗传物质的变化,促进 CRC 的发展,已被证明是 CRC 的有效靶点。由于天然产品具有显著的药理作用和对抗化疗耐药性的潜力,因此引起了人们的兴趣,越来越多的研究正在深入探讨这些天然产品对与 CRC 相关的代谢重编程的影响。在这篇综述中,我们从 Web of Science 和 PubMed 收集了从 1980 年 1 月到 2023 年 10 月期间发表的数据。本文重点关注癌细胞代谢改变的五个核心方面:葡萄糖代谢、线粒体氧化磷酸化(OXPHOS)、氨基酸代谢、脂肪酸合成和核苷酸代谢,概述了针对 CRC 代谢重编程的天然产物干预的最新进展。我们的分析强调了天然产物在破坏 CRC 代谢途径方面的潜力,为 CRC 的治疗靶点提出了建议,并扩大了代谢相关疾病的治疗选择范围。
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引用次数: 0
Association of Whole Blood Amino Acid and Acylcarnitine Metabolome with Anthropometry and IGF-I Serum Levels in Healthy Children and Adolescents in Germany 德国健康儿童和青少年全血氨基酸和乙酰肉碱代谢组与人体测量和 IGF-I 血清水平的关系
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-09 DOI: 10.3390/metabo14090489
Ricky Jensch, Ronny Baber, Antje Körner, Wieland Kiess, Uta Ceglarek, Antje Garten, Mandy Vogel
Background: Physiological changes of blood amino acids and acylcarnitines during healthy child development are poorly studied. The LIFE (Leipziger Forschungszentrum für Zivilisationserkrankungen) Child study offers a platform with a large cohort of healthy children to investigate these dynamics. We aimed to assess the intra-person variability of 28 blood metabolites and their associations with anthropometric parameters related to growth and excess body fat. Methods: Concentrations of 22 amino acids (AA), 5 acylcarnitines (AC) and free carnitine of 2213 children aged between 3 months and 19 years were analyzed using liquid chromatography/tandem mass spectrometry. Values were transformed into standard deviation scores (SDS) to account for sex- and age-related variations. The stability of metabolites was assessed through the coefficient of determination. Associations with parameters for body composition and insulin-like growth factor-I (IGF-I) SDS were determined by the Pearson correlation and linear regression. Results: Our research revealed substantial within-person variation in metabolite concentrations during childhood and adolescence. Most metabolites showed a positive correlation with body composition parameters, with a notable influence of sex, pubertal status and weight group. Glycine exhibited negative associations with parameters of body fat distribution, especially in normal weight girls, overweight/obese boys and during puberty. Conclusion: Blood AA and AC measurements may contribute to elucidating pathogenesis pathways of adiposity-related comorbidities, but the specific timings and conditions of development during childhood and adolescence need to be taken into consideration.
背景:人们对儿童健康成长过程中血液氨基酸和酰肉碱的生理变化研究甚少。LIFE(Leipziger Forschungszentrum für Zivilisationserkrankungen)儿童研究为研究这些动态变化提供了一个由大量健康儿童组成的平台。我们的目的是评估 28 种血液代谢物的人体内变异性,以及它们与与生长和体内脂肪过多有关的人体测量参数之间的关系。研究方法采用液相色谱/串联质谱法分析了 2213 名 3 个月至 19 岁儿童的 22 种氨基酸 (AA)、5 种酰基肉碱 (AC) 和游离肉碱的浓度。为了考虑与性别和年龄有关的差异,这些数值被转换成标准偏差分数(SDS)。代谢物的稳定性通过测定系数进行评估。通过皮尔逊相关性和线性回归确定了代谢物与身体成分参数和胰岛素样生长因子-I(IGF-I)标准偏差分数之间的关系。结果:我们的研究发现,在儿童和青少年时期,代谢物浓度在人体内存在很大差异。大多数代谢物与身体成分参数呈正相关,其中性别、青春期状况和体重组别影响显著。甘氨酸与身体脂肪分布参数呈负相关,尤其是在体重正常的女孩、超重/肥胖的男孩和青春期。结论血液中 AA 和 AC 的测量有助于阐明与脂肪相关的合并症的发病机制,但需要考虑儿童和青少年发育的具体时间和条件。
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引用次数: 0
The Endogenous Inhibitor of CETP, apoC1, Remains Ineffective In Vivo after Correction of Hyperglycemia in People with Type 1 Diabetes CETP 的内源性抑制剂 apoC1 在纠正 1 型糖尿病患者的高血糖后仍然无效
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-07 DOI: 10.3390/metabo14090487
Alexia Rouland, Thomas Gautier, Damien Denimal, Laurence Duvillard, Isabelle Simoneau, David Rageot, Bruno Vergès, Benjamin Bouillet
ApolipoproteinC1 (apoC1) is the main physiological inhibitor of the cholesterol ester transfer protein (CETP). Increased CETP activity is associated with macrovascular complications in patients with type 1 diabetes (T1D). ApoC1 has lost its ability to inhibit CETP in patients with T1D, and in vitro glycation of apoC1 increases CETP activity, suggesting that hyperglycemia could be a factor implicated in the loss of the inhibitory effect of apoC1 on CETP. Thus, we aimed to see whether improvement of glycemic control might restore apoC1 inhibitory effect on CETP. We studied 98 patients with T1D and HbA1c > 9% at baseline and 3 months after improvement of glycemic control by a medical intervention (insulin introduction or changes in multi-injection therapy or pump therapy introduction/therapeutic education for all patients). CETP activity was assessed by a radioactive method and plasma apoC1 levels were measured by ELISA. The different isoforms of apoC1 were determined by mass spectrometry. CETP activity was not significantly modified after improvement of glycemic control, despite a significant reduction in mean HbA1c (8.7 ± 1.7 vs. 10.8 ± 2, p < 0.0001). No association between plasma apoC1 and CETP activity was observed in patients with T1D at baseline, nor at 3 months, even in the subgroup of patients with optimal control (3-month HbA1c < 7%). We did not find any glycated form of apoC1 using mass spectrometry in people with T1D. Hyperglycemia in vivo does not seem to be a major factor implicated in the loss of apoC1 ability to inhibit CETP activity observed in T1D. Other factors, such as qualitative abnormalities of lipoproteins, could be involved. Our data emphasize the fact that hyperglycemia is not the only factor involved in lipid abnormalities and macrovascular complications in T1D. Clinical trial reg. no. NCT02816099 ClinicalTrials.gov.
载脂蛋白C1(apoC1)是胆固醇酯转移蛋白(CETP)的主要生理抑制剂。CETP 活性的增加与 1 型糖尿病(T1D)患者的大血管并发症有关。T1D患者体内的载脂蛋白C1失去了抑制CETP的能力,而体外糖化载脂蛋白C1会增加CETP的活性,这表明高血糖可能是导致载脂蛋白C1失去抑制CETP作用的一个因素。因此,我们的目的是研究改善血糖控制是否能恢复载脂蛋白 C1 对 CETP 的抑制作用。我们对 98 例 T1D 患者进行了研究,这些患者在基线时 HbA1c > 9%,在通过医疗干预(所有患者均使用胰岛素或改变多种注射疗法或泵疗法/治疗教育)改善血糖控制后 3 个月 HbA1c > 9%。CETP 活性通过放射性方法进行评估,血浆载脂蛋白 C1 水平通过 ELISA 方法进行测量。质谱法测定了载脂蛋白C1的不同异构体。尽管平均 HbA1c 显著降低(8.7 ± 1.7 vs. 10.8 ± 2,p < 0.0001),但血糖控制改善后,CETP 活性并无明显变化。在 T1D 患者的血浆载脂蛋白 C1 和 CETP 活性之间,在基线和 3 个月时均未观察到任何关联,即使在血糖得到最佳控制的患者亚组(3 个月的 HbA1c < 7%)中也是如此。通过质谱分析,我们在 T1D 患者中未发现任何糖化形式的 apoC1。体内高血糖似乎不是导致 T1D 患者丧失载脂蛋白 C1 抑制 CETP 活性能力的主要因素。其他因素,如脂蛋白的质量异常,也可能与此有关。我们的数据强调了一个事实,即高血糖并不是导致 T1D 血脂异常和大血管并发症的唯一因素。临床试验注册号NCT02816099 ClinicalTrials.gov.
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引用次数: 0
Thioredoxin-Interacting Protein’s Role in NLRP3 Activation and Osteoarthritis Pathogenesis by Pyroptosis Pathway: In Vivo Study 硫氧还蛋白交互蛋白在NLRP3活化和骨关节炎发病机制中的作用(通过热蛋白沉积途径):体内研究
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-07 DOI: 10.3390/metabo14090488
Ruba Altahla, Xu Tao
Thioredoxin-interacting protein (TXNIP) has been involved in oxidative stress and activation of the NOD-like receptor protein-3 (NLRP3) inflammasome, directly linking it to the pyroptosis pathway. Furthermore, pyroptosis may contribute to the inflammatory process in osteoarthritis (OA). The purpose of this study was to investigate the role of TXNIP in activating the NLRP3 inflammasome through the pyroptosis pathway in an OA rat model. Destabilization of the medial meniscus (DMM) was induced in the OA model with intra-articular injections of adeno-associated virus (AAV) overexpressing (OE) or knocking down (KD) TXNIP. A total of 48 healthy rats were randomly divided into six groups (N = 8 each). During the experiment, the rats’ weights, mechanical pain thresholds, and thermal pain thresholds were measured weekly. Morphology staining, micro-CT, 3D imaging, and immunofluorescence (IF) staining were used to measure the expression level of TXNIP, and ELISA techniques were employed. OE-TXNIP-AAV in DMM rats aggravated cartilage destruction and subchondral bone loss, whereas KD-TXNIP slowed the progression of OA. The histological results showed that DMM modeling and OE-TXNIP-AAV intra-articular injection caused joint structure destruction, decreased anabolic protein expression, and increased catabolic protein expression and pyroptosis markers. Conversely, KD-TXNIP-AAV slowed joint degeneration. OE-TXNIP-AVV worsened OA by accelerating joint degeneration and damage, while KD-TXNIP-AAV treatment had a protective effect.
硫氧还蛋白相互作用蛋白(TXNIP)参与了氧化应激和 NOD 样受体蛋白-3(NLRP3)炎性体的激活,并将其与热蛋白沉积途径直接联系起来。此外,热蛋白沉积还可能导致骨关节炎(OA)的炎症过程。本研究的目的是在 OA 大鼠模型中研究 TXNIP 通过热蛋白沉积途径激活 NLRP3 炎症小体的作用。通过关节内注射过表达(OE)或敲除(KD)TXNIP的腺相关病毒(AAV),在OA模型中诱导内侧半月板失稳(DMM)。48 只健康大鼠被随机分为六组(每组 8 只)。实验期间,每周测量大鼠体重、机械痛阈和热痛阈。采用形态学染色、显微 CT、三维成像和免疫荧光(IF)染色来测量 TXNIP 的表达水平,并采用 ELISA 技术。OE-TXNIP-AAV在DMM大鼠中的应用加重了软骨破坏和软骨下骨流失,而KD-TXNIP则减缓了OA的进展。组织学结果显示,DMM模型和OE-TXNIP-AAV关节内注射导致关节结构破坏,合成代谢蛋白表达减少,分解代谢蛋白表达和热蛋白标志物增加。相反,KD-TXNIP-AAV 可减缓关节退化。OE-TXNIP-AVV通过加速关节退化和损伤而使OA恶化,而KD-TXNIP-AAV治疗则具有保护作用。
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引用次数: 0
Selenium, Zinc, and Plasma Total Antioxidant Status and the Risk of Colorectal Adenoma and Cancer 硒、锌和血浆总抗氧化剂状态与结直肠腺瘤和癌症风险
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-06 DOI: 10.3390/metabo14090486
Miłosława Zowczak-Drabarczyk, Jacek Białecki, Teresa Grzelak, Mikołaj Michalik, Dorota Formanowicz
Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant status (TAS) in the diagnosis of colorectal cancer (CRC) and colorectal adenoma (CRA) in a population of low Se and borderline Zn status. Based on clinical examination and colonoscopy/histopathology, the patients (n = 79) were divided into three groups: colorectal cancer (n = 30), colorectal adenoma (n = 19), and controls (CONTROL, n = 30). The serum Se concentration was lower in the CRC group than in the CRA group (by 9.1%, p < 0.0001) and the CONTROL group (by 7.9%, p < 0.0001). In turn, the serum Zn concentration was decreased in the CRA group (by 17.9%, p = 0.019) when compared to the CONTROL group. Plasma TAS was lower in the CRC group (by 27.8%, p = 0.017) than in the CONTROL group. In turn, the serum Zn concentration was decreased in the CRA group when compared to the CONTROL group. Plasma TAS was lower in the CRC group than in the CONTROL group. ROC (receiver operating characteristic) curve analysis revealed that the Se level was of the highest diagnostic utility for the discrimination of the CRC group from both the CRA group (area under ROC curve (AUC) 0.958, sensitivity 84.21%, specificity 100%) and the CONTROL group (AUC 0.873, sensitivity 100%, specificity 66.67%). The Zn and TAS levels were significantly accurate in the differentiation between the groups. An individualised risk of colorectal adenoma and cancer approach could comprise Se, Zn, and TAS assays in the population.
众所周知,硒(Se)、锌(Zn)和铜(Cu)与致癌有关,并参与防御活性氧(ROS)。本研究旨在评估血清中硒、锌和铜的浓度以及血浆总抗氧化状态(TAS)在低硒和低锌人群中诊断结直肠癌(CRC)和结直肠腺瘤(CRA)的临床实用性。根据临床检查和结肠镜/组织病理学检查,患者(n = 79)被分为三组:结直肠癌(n = 30)、结直肠腺瘤(n = 19)和对照组(CONTROL,n = 30)。CRC 组的血清 Se 浓度比 CRA 组(低 9.1%,P < 0.0001)和 CONTROL 组(低 7.9%,P < 0.0001)低。与对照组相比,CRA 组的血清锌浓度降低了 17.9%,p = 0.019。与对照组相比,CRC 组的血浆 TAS 降低了 27.8%,p = 0.017。与对照组相比,CRA 组的血清锌浓度也有所下降。CRC 组的血浆 TAS 低于对照组。ROC(接收器操作特征)曲线分析表明,Se水平在区分CRC组与CRA组(ROC曲线下面积(AUC)为0.958,灵敏度为84.21%,特异度为100%)和CONTROL组(AUC为0.873,灵敏度为100%,特异度为66.67%)方面的诊断效用最高。Zn 和 TAS 水平在区分不同组别方面具有显著的准确性。在人群中,Se、Zn 和 TAS 检测可用于个体化的结直肠腺瘤和癌症风险分析。
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引用次数: 0
The Impact of Metabolic Syndrome on Heart Failure in Young Korean Population: A Nationwide Study 代谢综合征对韩国年轻人群心力衰竭的影响:一项全国性研究
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-04 DOI: 10.3390/metabo14090485
Tae-Eun Kim, Do Young Kim, Hyeongsu Kim, Jidong Sung, Duk-Kyung Kim, Myoung-Soon Lee, Seong Woo Han, Hyun-Joong Kim, Hyun Kyun Ki, Sung Hea Kim, Kyu-Hyung Ryu
Limited data are available regarding the effect of metabolic syndrome on heart failure (HF) development in young individuals. Utilizing data from the Korean National Health Insurance Service, we included a total of 1,958,284 subjects in their 40s who underwent health screening between January 2009 and December 2009 in Korea. Subjects were classified into three groups: normal, pre-metabolic syndrome (Pre-MetS), and metabolic syndrome (MetS). MetS was identified in 10.58% of males and 5.21% of females. The hazard ratio for HF in subjects with MetS was 1.968 (95% CI: 1.526–2.539) for males and 2.398 (95% CI: 1.466–3.923) for females. For those with Pre-MetS, the hazard ratio was 1.607 (95% CI: 1.293–1.997) in males and 1.893 (95% CI: 1.43–2.505) in females. Additionally, acute myocardial infarction and low hemoglobin levels were identified as significant risk factors for HF in both genders. MetS approximately doubled the risk of developing HF in individuals in their 40s. Pre-MetS was also a significant risk factor for HF in this population.
关于代谢综合征对年轻人心力衰竭(HF)发展的影响,目前只有有限的数据。利用韩国国民健康保险服务机构的数据,我们纳入了 2009 年 1 月至 2009 年 12 月期间在韩国接受健康检查的 1,958,284 名 40 多岁的受试者。受试者被分为三组:正常、代谢综合征前期(Pre-MetS)和代谢综合征(MetS)。10.58%的男性和5.21%的女性被发现患有代谢综合征。患有代谢综合征的受试者中,男性患高血压的危险比为 1.968(95% CI:1.526-2.539),女性为 2.398(95% CI:1.466-3.923)。对于患有前MetS的患者,男性的危险比为1.607(95% CI:1.293-1.997),女性为1.893(95% CI:1.43-2.505)。此外,急性心肌梗死和低血红蛋白水平也被认为是导致男性和女性患心房颤动的重要风险因素。MetS 使 40 多岁人群罹患心房颤动的风险增加了约一倍。MetS前期也是该人群罹患心房颤动的重要风险因素。
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