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Aberrant Platelet Aggregation as Initial Presentation of Essential Thrombocythemia: Failure of Entero-Coated Aspirin to Reduce Platelet Hyperactivation 血小板聚集异常是原发性血小板增多症的最初表现:肠溶阿司匹林无法降低血小板高活性
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010176
A. Morotti, C. Barale, Michele Sornatale, Emilia Giugliano, Vittorio Emanuele Muccio, C. Frascaroli, Marisa Pautasso, Alessandro Fornari, Isabella Russo
Essential thrombocythemia (ET) is a myeloproliferative neoplasm variant characterized by excessive production of platelets. Since the most common cause of mortality and morbidity in ET patients is thrombosis, the excessive production of platelets may cause thrombotic events. However, little is known about the function of platelets in ET. We report a female patient who presented as asymptomatic, without a remarkable medical history, and ET was diagnosed after an incidental finding of moderate thrombocytosis. Notably, together with thrombocytosis, an abnormal platelet phenotype was found for the presence of a massive, rapid and spontaneous formation of aggregates and platelet hypersensitivity to subthreshold concentrations of aggregating agonists. Bone marrow histopathological examination and genetic analysis with the JAK2 (V617F) gene mutation findings confirmed the initial suspicion of ET. Although the ET patient was placed on aspirin, the persistence of the platelet hyperactivation and hyperaggregability prompted a switch in antiplatelet medication from entero-coated (EC) to plain aspirin. As result, platelet hypersensitivity to agonists and spontaneous aggregation were no longer found. Collectively, our study demonstrates that platelet function analysis could be a reliable predictor of ET and that plain aspirin should be preferred over EC aspirin to attenuate platelet hyperreactivity.
原发性血小板增多症(ET)是一种骨髓增生性肿瘤变种,其特点是血小板生成过多。由于 ET 患者最常见的死亡和发病原因是血栓形成,因此血小板生成过多可能导致血栓事件。然而,人们对 ET 中血小板的功能知之甚少。我们报告了一名女性患者,她没有任何症状,也没有明显的病史,在偶然发现中度血小板增多后被诊断为 ET。值得注意的是,在发现血小板增多的同时,还发现了血小板表型异常,即存在大量、快速和自发形成的聚集体,以及血小板对亚阈浓度聚集激动剂的超敏反应。骨髓组织病理学检查和 JAK2(V617F)基因突变的遗传分析结果证实了最初对 ET 的怀疑。虽然 ET 患者服用了阿司匹林,但血小板高活性和高聚集性的持续存在促使患者将抗血小板药物从肠溶阿司匹林(EC)改为普通阿司匹林。结果,血小板不再对激动剂过敏,也不再出现自发性聚集。总之,我们的研究表明,血小板功能分析可作为 ET 的可靠预测指标,而且应首选普通阿司匹林而非 EC 阿司匹林来减轻血小板高反应性。
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引用次数: 0
Comparative Evaluation of Adipokine Metrics for the Diagnosis of Gestational Diabetes Mellitus 用于诊断妊娠糖尿病的脂肪因子指标的比较评估
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010175
Maciej Kamiński, R. Mierzyński, E. Poniedziałek-Czajkowska, Agata Sadowska, Maciej Sotowski, B. Leszczyńska-Gorzelak
Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM.
妊娠糖尿病(GDM)是妊娠期最常见的疾病之一。主要由脂肪组织分泌的脂肪因子参与了许多新陈代谢过程。脂肪因子在 GDM 发病机制中的确切作用尚不十分清楚,许多脂肪因子已在整个孕期被分析,并被提议作为 GDM 的生物标志物。本研究旨在评估 GDM 和非 GDM 妇女的血清脂肪连通素、螯合素、脂钙素和凋亡素的水平,将其作为 GDM 发生的临床有用的生物标志物,并证明上述脂肪因子在血清中的水平与 GDM 发生风险增加之间的相关性。此外,还分析了这些脂肪因子在 GDM 发病机制中的作用。在 GDM 孕妇和健康孕妇之间,观察到脂肪连通素(7234.6 对 9837.5 纳克/毫升,p < 0.0001)、螯合素(264.0 对 206.7 纳克/毫升,p < 0.0001)和脂钙素(39.5 对 19.4 纳克/毫升,p < 0.0001)的水平存在明显的统计学差异。研究还评估了测试的脂肪因子在检测 GDM 方面的诊断作用。研究结果证实了关于脂肪连素、螯合素、脂钙素和凋亡素在 GDM 病理生理机制中的重要性的假设。我们推测,这些脂肪因子有可能成为预测和早期诊断 GDM 的新型生物标志物。
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引用次数: 0
Analysis of the Candidate Genes and Underlying Molecular Mechanism of P198, an RNAi-Related Dwarf and Sterile Line RNAi-Related 矮小不育系 P198 的候选基因及其分子机制分析
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010174
Shengbo Zhao, Junling Luo, Min Tang, Chi Zhang, Miaoying Song, Gang Wu, Xiaohong Yan
The genome-wide long hairpin RNA interference (lhRNAi) library is an important resource for plant gene function research. Molecularly characterizing lhRNAi mutant lines is crucial for identifying candidate genes associated with corresponding phenotypes. In this study, a dwarf and sterile line named P198 was screened from the Brassica napus (B. napus) RNAi library. Three different methods confirmed that eight copies of T-DNA are present in the P198 genome. However, only four insertion positions were identified in three chromosomes using fusion primer and nested integrated polymerase chain reaction. Therefore, the T-DNA insertion sites and copy number were further investigated using Oxford Nanopore Technologies (ONT) sequencing, and it was found that at least seven copies of T-DNA were inserted into three insertion sites. Based on the obtained T-DNA insertion sites and hairpin RNA (hpRNA) cassette sequences, three candidate genes related to the P198 phenotype were identified. Furthermore, the potential differentially expressed genes and pathways involved in the dwarfism and sterility phenotype of P198 were investigated by RNA-seq. These results demonstrate the advantage of applying ONT sequencing to investigate the molecular characteristics of transgenic lines and expand our understanding of the complex molecular mechanism of dwarfism and male sterility in B. napus.
全基因组长发夹 RNA 干扰(lhRNAi)文库是植物基因功能研究的重要资源。鉴定lhRNAi突变株的分子特征对于确定与相应表型相关的候选基因至关重要。本研究从甘蓝型油菜(B. napus)RNAi 文库中筛选出一个名为 P198 的矮小不育系。三种不同的方法证实 P198 基因组中有八个 T-DNA 拷贝。然而,使用融合引物和嵌套整合聚合酶链反应,在三条染色体上只确定了四个插入位置。因此,利用牛津纳米孔技术(ONT)测序进一步研究了 T-DNA 插入位点和拷贝数,结果发现至少有七个 T-DNA 拷贝插入了三个插入位点。根据获得的 T-DNA 插入位点和发夹核糖核酸(hpRNA)盒序列,确定了与 P198 表型相关的三个候选基因。此外,还通过 RNA-seq 研究了与 P198 矮化和不育表型有关的潜在差异表达基因和通路。这些结果证明了应用ONT测序技术研究转基因品系分子特征的优势,并拓展了我们对油菜矮化和雄性不育复杂分子机制的认识。
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引用次数: 0
The Implication of a Polymorphism in the Methylenetetrahydrofolate Reductase Gene in Homocysteine Metabolism and Related Civilisation Diseases 亚甲基四氢叶酸还原酶基因多态性在同型半胱氨酸代谢及相关文明病中的影响
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010193
Emilia Zarembska, Klaudia Ślusarczyk, M. Wrzosek
Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the one-carbon cycle. This enzyme is essential for the metabolism of methionine, folate, and RNA, as well as for the production of proteins, DNA, and RNA. MTHFR catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to its active form, 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Numerous variants of the MTHFR gene have been recognised, among which the C677T variant is the most extensively studied. The C677T polymorphism, which results in the conversion of valine to alanine at codon 222, is associated with reduced activity and an increased thermolability of the enzyme. Impaired MTHFR efficiency is associated with increased levels of homocysteine, which can contribute to increased production of reactive oxygen species and the development of oxidative stress. Homocysteine is acknowledged as an independent risk factor for cardiovascular disease, while chronic inflammation serves as the common underlying factor among these issues. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and an increased risk of cardiovascular disease, hypertension, diabetes, and overweight/obesity. There is substantial evidence supporting this association, although several studies have concluded that the polymorphism cannot be reliably used for prediction. This review examines the latest research on MTHFR polymorphisms and their correlation with cardiovascular disease, obesity, and epigenetic regulation.
亚甲基四氢叶酸还原酶(MTHFR)是一碳循环中的一种关键调节酶。这种酶对蛋氨酸、叶酸和 RNA 的代谢以及蛋白质、DNA 和 RNA 的生成至关重要。MTHFR 催化 5,10-亚甲基四氢叶酸向其活性形式 5-甲基四氢叶酸的不可逆转化,而 5-甲基四氢叶酸是同型半胱氨酸再甲基化为蛋氨酸的辅助底物。已确认的 MTHFR 基因变异体很多,其中 C677T 变异体的研究最为广泛。C677T 多态性导致缬氨酸在密码子 222 处转化为丙氨酸,与酶的活性降低和热稳定性增加有关。MTHFR 效率受损与同型半胱氨酸水平升高有关,而同型半胱氨酸水平升高会导致活性氧生成增加,并形成氧化应激。同型半胱氨酸被认为是心血管疾病的独立风险因素,而慢性炎症则是这些问题的共同潜在因素。许多研究都是为了确定 C677T 多态性与心血管疾病、高血压、糖尿病和超重/肥胖风险增加之间是否存在关联。尽管有几项研究得出结论认为该多态性不能可靠地用于预测,但仍有大量证据支持这种关联。本综述探讨了有关 MTHFR 多态性及其与心血管疾病、肥胖症和表观遗传调控的相关性的最新研究。
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引用次数: 0
Molecular Characteristics, Functional Definitions, and Regulatory Mechanisms for Cross-Presentation Mediated by the Major Histocompatibility Complex: A Comprehensive Review 主要组织相容性复合体介导的交叉呈递的分子特征、功能定义和调控机制:全面综述
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010196
Sen Liu, Shaoqiang Wei, Yan Sun, Guowei Xu, Shidong Zhang, Jianxi Li
The major histocompatibility complexes of vertebrates play a key role in the immune response. Antigen-presenting cells are loaded on MHC I molecules, which mainly present endogenous antigens; when MHC I presents exogenous antigens, this is called cross-presentation. The discovery of cross-presentation provides an important theoretical basis for the study of exogenous antigens. Cross-presentation is a complex process in which MHC I molecules present antigens to the cell surface to activate CD8+ T lymphocytes. The process of cross-representation includes many components, and this article briefly outlines the origins and development of MHC molecules, gene structures, functions, and their classical presentation pathways. The cross-presentation pathways of MHC I molecules, the cell lines that support cross-presentation, and the mechanisms of MHC I molecular transporting are all reviewed. After more than 40 years of research, the specific mechanism of cross-presentation is still unclear. In this paper, we summarize cross-presentation and anticipate the research and development prospects for cross-presentation.
脊椎动物的主要组织相容性复合物在免疫反应中起着关键作用。抗原递呈细胞上的 MHC I 分子主要递呈内源性抗原;当 MHC I 递呈外源性抗原时,这被称为交叉递呈。交叉呈递的发现为研究外源性抗原提供了重要的理论基础。交叉呈递是 MHC I 分子向细胞表面呈递抗原以激活 CD8+ T 淋巴细胞的复杂过程。交叉呈递过程包括许多环节,本文简要概述了 MHC 分子的起源和发展、基因结构、功能及其经典呈递途径。本文对 MHC I 分子的交叉呈递途径、支持交叉呈递的细胞系以及 MHC I 分子转运机制进行了综述。经过 40 多年的研究,交叉呈递的具体机制仍不清楚。本文对交叉呈递进行了总结,并展望了交叉呈递的研究和发展前景。
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引用次数: 0
Ion Channels as a Therapeutic Target: Drug Design and Pharmacological Investigation 作为治疗靶点的离子通道:药物设计与药理研究
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010171
Gabriella Guerrini, M. Giovannoni
This Special Issue intends to illustrate the novelties in the field of ion channels [...]
本特刊旨在阐述离子通道领域的新进展 [...]
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引用次数: 0
Pan-Genome Analysis of TIFY Gene Family and Functional Analysis of CsTIFY Genes in Cucumber 黄瓜 TIFY 基因家族的泛基因组分析和 CsTIFY 基因的功能分析
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010185
Kun Liu, Haiyu Xu, Xinbin Gao, Yinghao Lu, Lina Wang, Zhonghai Ren, Chunhua Chen
Cucumbers are frequently affected by gray mold pathogen Botrytis cinerea, a pathogen that causes inhibited growth and reduced yield. Jasmonic acid (JA) plays a primary role in plant responses to biotic stresses, and the jasmonate-ZIM-Domain (JAZ) proteins are key regulators of the JA signaling pathway. In this study, we used the pan-genome of twelve cucumber varieties to identify cucumber TIFY genes. Our findings revealed that two CsTIFY genes were present in all twelve cucumber varieties and showed no differences in protein sequence, gene structure, and motif composition. This suggests their evolutionary conservation across different cucumber varieties and implies that they may play a crucial role in cucumber growth. On the other hand, the other fourteen CsTIFY genes exhibited variations in protein sequence and gene structure or conserved motifs, which could be the result of divergent evolution, as these genes adapt to different cultivation and environmental conditions. Analysis of the expression profiles of the CsTIFY genes showed differential regulation by B. cinerea. Transient transfection plants overexpressing CsJAZ2, CsJAZ6, or CsZML2 were found to be more susceptible to B. cinerea infection compared to control plants. Furthermore, these plants infected by the pathogen showed lower levels of the enzymatic activities of POD, SOD and CAT. Importantly, after B. cinerea infection, the content of JA was upregulated in the plants, and cucumber cotyledons pretreated with exogenous MeJA displayed increased resistance to B. cinerea infection compared to those pretreated with water. Therefore, this study explored key TIFY genes in the regulation of cucumber growth and adaptability to different cultivation environments based on bioinformatics analysis and demonstrated that CsJAZs negatively regulate cucumber disease resistance to gray mold via multiple signaling pathways.
黄瓜经常受到灰霉病病原菌 Botrytis cinerea 的影响,这种病原菌会抑制黄瓜的生长并导致黄瓜减产。茉莉酸(JA)在植物对生物胁迫的反应中起着主要作用,而茉莉酸-ZIM-Domain(JAZ)蛋白是 JA 信号通路的关键调控因子。在这项研究中,我们利用 12 个黄瓜品种的泛基因组来鉴定黄瓜 TIFY 基因。我们的研究结果表明,两个CsTIFY基因存在于所有12个黄瓜品种中,并且在蛋白质序列、基因结构和基序组成上没有差异。这表明它们在不同黄瓜品种间的进化过程中保持不变,并暗示它们可能在黄瓜生长过程中发挥关键作用。另一方面,其他 14 个 CsTIFY 基因在蛋白质序列和基因结构或保守的主题方面表现出变异,这可能是这些基因适应不同栽培和环境条件而发生分化进化的结果。对 CsTIFY 基因表达谱的分析表明,它们受 B. cinerea 的调控存在差异。与对照植株相比,过表达 CsJAZ2、CsJAZ6 或 CsZML2 的瞬时转染植株更容易受到 B. cinerea 感染。此外,这些受病原体感染的植物显示出较低水平的 POD、SOD 和 CAT 酶活性。重要的是,黄瓜子叶感染 B. cinerea 后,植株中的 JA 含量上调,与用水预处理的植株相比,用外源 MeJA 预处理的黄瓜子叶对 B. cinerea 感染的抵抗力增强。因此,本研究基于生物信息学分析探讨了调控黄瓜生长和适应不同栽培环境的关键TIFY基因,并证明CsJAZs通过多种信号通路负向调控黄瓜对灰霉病的抗病性。
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引用次数: 0
The Discovery and Characterization of Conserved and Novel miRNAs in the Different Developmental Stages and Organs of Pikeperch (Sander lucioperca) 梭子鱼不同发育阶段和器官中保守和新型 miRNA 的发现与特征描述
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010189
Marieke Verleih, Tina Visnovska, J. A. Nguinkal, A. Rebl, T. Goldammer, R. Andreassen
Micro RNAs (miRNAs) are short non-coding RNAs that act as post-transcriptional gene expression regulators. Genes regulated in vertebrates include those affecting growth and development or stress and immune response. Pikeperch (Sander lucioperca) is a species that is increasingly being considered for farming in recirculation aquaculture systems. We characterized the pikeperch miRNA repertoire to increase the knowledge of the genomic mechanisms affecting performance and health traits by applying small RNA sequencing to different developmental stages and organs. There were 234 conserved and 8 novel miRNA genes belonging to 104 families. A total of 375 unique mature miRNAs were processed from these genes. Many mature miRNAs showed high relative abundances or were significantly more expressed at early developmental stages, like the miR-10 and miR-430 family, let-7, the miRNA clusters 106-25-93, and 17-19-92. Several miRNAs associated with immune responses (e.g., slu-mir-731-5p, slu-mir-2188-5p, and slu-mir-8159-5p) were enriched in the spleen. The mature miRNAs slu-mir-203a-3p and slu-mir-205-5p were enriched in gills. These miRNAs are similarly abundant in many vertebrates, indicating that they have shared regulatory functions. There was also a significantly increased expression of the disease-associated miR-462/miR-731 cluster in response to hypoxia stress. This first pikeperch miRNAome reference resource paves the way for future functional studies to identify miRNA-associated variations that can be utilized in marker-assisted breeding programs.
微小 RNA(miRNA)是一种短的非编码 RNA,是转录后基因表达的调节因子。脊椎动物中受调控的基因包括影响生长发育或应激和免疫反应的基因。梭子鱼(Sander lucioperca)是一种越来越多地被考虑在循环水养殖系统中养殖的物种。我们通过对不同发育阶段和器官进行小 RNA 测序,确定了梭子鱼 miRNA 的特征,以增加对影响其表现和健康性状的基因组机制的了解。研究共发现 234 个保守的 miRNA 基因和 8 个新的 miRNA 基因,隶属于 104 个家族。这些基因共加工出 375 个独特的成熟 miRNA。许多成熟的miRNA表现出较高的相对丰度,或者在早期发育阶段明显表达较多,如miR-10和miR-430家族、let-7、miRNA群106-25-93和17-19-92。一些与免疫反应相关的 miRNA(如 slu-mir-731-5p、slu-mir-2188-5p 和 slu-mir-8159-5p)在脾脏中富集。成熟的 miRNAs slu-mir-203a-3p 和 slu-mir-205-5p 在鳃中富集。这些 miRNA 在许多脊椎动物中含量相似,表明它们具有共同的调控功能。与疾病相关的miR-462/miR-731群的表达也在缺氧压力下明显增加。首个梭子鱼miRNA组参考资源为未来的功能研究铺平了道路,以确定可用于标记辅助育种计划的miRNA相关变异。
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引用次数: 0
Mass Spectrometry Study about In Vitro and In Vivo Reaction between Metformin and Glucose: A Preliminary Investigation on Alternative Biological Behavior 关于二甲双胍与葡萄糖体外和体内反应的质谱研究:关于另一种生物行为的初步研究
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010180
G. Bartolucci, M. Pallecchi, Laura Braconi, S. Dei, E. Teodori, A. Lapolla, G. Sartore, Pietro Traldi
Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ever been described. It was considered interesting to investigate the possible reaction of metformin with glucose following the Maillard reaction pattern. The reaction was first performed in in vitro conditions, showing the formation of two adducts that originated by the condensation of the two molecular species with the losses of one or two water molecules. Their structures were investigated by liquid chromatography coupled with mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and accurate mass measurements (HRMS). The species originated via the reaction of glucose and metformin and were called metformose and dehydrometformose, and some structural hypotheses were conducted. It is worth to emphasize that they were detected in urine samples from a diabetic patient treated with metformin and consequently they must be considered metabolites of the drug, which has never been identified before now. The glucose-related substructure of these compounds could reflect an improved transfer across cell membranes and, consequently, new hypotheses could be made about the biological targets of metformin.
二甲双胍是全球处方量最大的降糖药物;全球每年有超过 1 亿患者服用这种药物。人们对这种药物提出了一些不同的作用机制,但令人惊讶的是,从未有人描述过二甲双胍的代谢物。人们认为,研究二甲双胍与葡萄糖可能发生的马氏反应模式很有意义。首先在体外条件下进行了反应,结果表明,由于损失了一个或两个水分子,两种分子缩合形成了两种加合物。研究人员通过液相色谱-质谱(HPLC-MS)、串联质谱(MS/MS)和精确质量测量(HRMS)对它们的结构进行了研究。这些物质起源于葡萄糖和二甲双胍的反应,被称为甲福糖和脱水甲福糖,并进行了一些结构假说。值得强调的是,这些物质是在一名接受二甲双胍治疗的糖尿病患者的尿样中检测到的,因此它们必须被视为该药物的代谢物,而在此之前从未发现过这种代谢物。这些化合物与葡萄糖有关的亚结构可能反映出它们在细胞膜上的转移能力有所提高,因此可以对二甲双胍的生物靶标提出新的假设。
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引用次数: 0
Metabolomic Insight into Implications of Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Locally Advanced Head and Neck Cancer 代谢组学揭示局部晚期头颈癌诱导化疗和同步放化疗的影响
IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-22 DOI: 10.3390/ijms25010188
Ł. Boguszewicz, A. Bieleń, M. Ciszek, A. Skorupa, J. Mrochem-Kwarciak, Krzysztof Składowski, Maria Sokół
The present study compares two groups of locally advanced patients with head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (cCHRT), specifically those for whom it is a first-line treatment and those who have previously received induction chemotherapy (iCHT). The crucial question is whether iCHT is a serious burden during subsequent treatment for LA-HNSCC and how iCHT affects the tolerance to cCHRT. Of the 107 LA-HNSCC patients, 54 received cisplatin-based iCHT prior to cCHRT. The patients were clinically monitored at weekly intervals from the day before until the completion of the cCHRT. The 843 blood samples were collected and divided into two aliquots: for laboratory blood tests and for nuclear magnetic resonance (NMR) spectroscopy (a Bruker 400 MHz spectrometer). The NMR metabolites and the clinical parameters from the laboratory blood tests were analyzed using orthogonal partial least squares analysis (OPLS) and the Mann–Whitney U test (MWU). After iCHT, the patients begin cCHRT with significantly (MWU p-value < 0.05) elevated blood serum lipids, betaine, glycine, phosphocholine, and reticulocyte count, as well as significantly lowered NMR inflammatory markers, serine, hematocrit, neutrophile, monocyte, red blood cells, hemoglobin, and CRP. During cCHRT, a significant increase in albumin and psychological distress was observed, as well as a significant decrease in platelet, N-acetyl-cysteine, tyrosine, and phenylalanine, in patients who received iCHT. Importantly, all clinical symptoms (except the decreased platelets) and most metabolic alterations (except for betaine, serine, tyrosine, glucose, and phosphocholine) resolve until the completion of cCHRT. In conclusion, iCHT results in hematological toxicity, altered lipids, and one-carbon metabolism, as well as downregulated inflammation, as observed at the beginning and during cCHRT. However, these complications are temporary, and most of them resolve at the end of the treatment. This suggests that iCHT prior to cCHRT does not pose a significant burden and should be considered as a safe treatment option for LA-HNSCC.
本研究对两组接受同期化放疗(cCHRT)的局部晚期头颈部鳞状细胞癌(LA-HNSCC)患者进行了比较,特别是作为一线治疗的患者和之前接受过诱导化疗(iCHT)的患者。关键问题在于,iCHT 是否会对 LA-HNSCC 的后续治疗造成严重负担,以及 iCHT 如何影响对 cCHRT 的耐受性。在107名LA-HNSCC患者中,有54人在接受cCHRT治疗前接受了以顺铂为基础的iCHT治疗。从顺铂化疗前一天到顺铂化疗结束,每周对患者进行一次临床监测。采集的 843 份血液样本分为两份:一份用于血液化验,另一份用于核磁共振 (NMR) 光谱分析(布鲁克 400 MHz 光谱仪)。采用正交偏最小二乘法分析(OPLS)和曼-惠特尼 U 检验(MWU)对核磁共振代谢物和实验室血液检测的临床参数进行了分析。iCHT 后,患者在开始 cCHRT 时血清脂质、甜菜碱、甘氨酸、磷酸胆碱和网织红细胞计数显著升高(MWU p 值 < 0.05),NMR 炎症标志物、丝氨酸、血细胞比容、中性粒细胞、单核细胞、红细胞、血红蛋白和 CRP 显著降低。在 cCHRT 期间,观察到接受 iCHT 的患者白蛋白和心理压力明显增加,血小板、N-乙酰-半胱氨酸、酪氨酸和苯丙氨酸明显减少。重要的是,所有临床症状(血小板减少除外)和大多数代谢改变(甜菜碱、丝氨酸、酪氨酸、葡萄糖和磷酸胆碱除外)都会在 cCHRT 结束前消失。总之,iCHT 会导致血液毒性、血脂和一碳代谢改变以及炎症下调,正如在 cCHRT 开始和进行期间所观察到的那样。不过,这些并发症都是暂时的,大多数都会在治疗结束后消失。这表明,在 cCHRT 之前进行 iCHT 不会造成重大负担,应被视为 LA-HNSCC 的一种安全治疗方案。
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引用次数: 0
期刊
International Journal of Molecular Sciences
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