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Towards Characterization of Hass Avocado Peel and Pulp Proteome during Postharvest Shelf Life. 哈斯鳄梨果皮和果肉蛋白质组在采后保质期内的特征描述。
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-28 DOI: 10.3390/proteomes12040028
Carolina Camacho-Vázquez, José Miguel Elizalde-Contreras, Francisco Antonio Reyes-Soria, Juan Luis Monribot-Villanueva, José Antonio Guerrero-Analco, Janet Juarez-Escobar, Olinda Velázquez-López, Thuluz Meza-Menchaca, Esaú Bojórquez-Velázquez, Jesús Alejandro Zamora-Briseño, Monica Ramirez-Vazquez, Guadalupe Alheli González Barrenechea, Enrique Ibarra-Laclette, Eliel Ruiz-May

In recent years, avocados have gained worldwide popularity as a nutritive food. This trend is causing a rise in the production of this fruit, which is accompanied by several problems associated with monocultural practices. Despite massive economic gains, limited molecular and structural information has been generated about avocado ripening. In fact, limited studies have attempted to unravel the proteome complexity dynamics of avocado fruit. We therefore conducted a comparative proteomics study on avocado peel and pulp during the postharvest shelf life using tandem mass tag synchronous precursor selection triple-stage mass spectrometry. We identified 3161 and 1128 proteins in the peel and pulp, respectively. Peels exhibited major over-accumulation of proteins associated with water deprivation and oxidative stress, along with abscisic acid biosynthesis. Ethylene, jasmonic acid, phenylpropanoid, and flavonoid biosynthesis pathways were activated. Structurally, we observed the accumulation of lignin and a reduction in cuticular thickness, which coincides with the reduction in the levels of long-chain acyl-coenzyme A synthetase and a marginal increase in 10,16-dihydroxyhexadecanoic acid. Our study sheds light on the association of proteome modulation with the structural features of Hass avocado. Its detailed characterization will provide an alternative for better preservation during the postharvest period.

近年来,鳄梨作为一种营养食品在全世界广受欢迎。这一趋势导致这种水果的产量上升,同时也带来了与单一种植方法相关的一些问题。尽管经济效益巨大,但有关鳄梨成熟的分子和结构信息却很有限。事实上,试图揭示鳄梨果实蛋白质组复杂性动态的研究也很有限。因此,我们使用串联质量标签同步前体选择三级质谱对采后货架期的牛油果果皮和果肉进行了蛋白质组学比较研究。我们在果皮和果肉中分别鉴定出 3161 和 1128 种蛋白质。果皮中与缺水和氧化胁迫以及脱落酸生物合成相关的蛋白质出现了严重的过度积累。乙烯、茉莉酸、苯丙氨酸和类黄酮的生物合成途径被激活。在结构上,我们观察到木质素的积累和角质层厚度的减少,这与长链酰辅酶 A 合成酶水平的降低和 10,16-二羟基十六烷酸的少量增加不谋而合。我们的研究揭示了蛋白质组调节与哈斯鳄梨结构特征之间的联系。它的详细特征将为采后期间更好的保存提供一种选择。
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引用次数: 0
Protein Extraction Methods Suitable for Muscle Tissue Proteomic Analysis. 适用于肌肉组织蛋白质组分析的蛋白质提取方法。
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-25 DOI: 10.3390/proteomes12040027
Lorenza Vantaggiato, Claudia Landi, Enxhi Shaba, Daniela Rossi, Vincenzo Sorrentino, Luca Bini

Muscle tissue is one of the most dynamic and plastic tissues of the mammalian body and covers different roles, such as force generation and metabolic control. Muscular proteomics provides an important opportunity to reveal the molecular mechanisms behind muscle pathophysiology. To ensure successful proteomic analysis, it is necessary to have an efficient and reproducible protein extraction method. This study aimed to evaluate the efficacy of two different extraction protocols of muscle samples for two-dimensional gel electrophoresis. In particular, mouse muscle proteins were extracted by an SDS-based buffer (Method A) and by a UREA/CHAPS/DTE/TRIS solution (Method B). The efficacies of the methods were assessed by performing an image analysis of the 2DE gels and by statistical and multivariate analyses. The 2DE gels in both preparations showed good resolution and good spot overlapping. Methods A and B produced 2DE gels with different means of total spots, higher for B. Image analysis showed different patterns of protein abundance between the protocols. The results showed that the two methods extract and solubilize proteins with different chemical-physical characteristics and different cellular localizations. These results attest the efficacy and reproducibility of both protein extraction methods, which can be parallelly applied for comprehensive proteomic profiling of muscle tissue.

肌肉组织是哺乳动物体内最具活力和可塑性的组织之一,具有不同的作用,如产生力量和控制新陈代谢。肌肉蛋白质组学为揭示肌肉病理生理学背后的分子机制提供了重要机会。为确保蛋白质组学分析的成功,有必要采用高效且可重复的蛋白质提取方法。本研究旨在评估两种不同的肌肉样本提取方案在二维凝胶电泳中的功效。其中,小鼠肌肉蛋白质的提取分别采用基于 SDS 的缓冲液(方法 A)和UREA/CHAPS/DTE/TRIS 溶液(方法 B)。通过对 2DE 凝胶进行图像分析以及统计和多元分析,评估了这两种方法的有效性。两种制备方法的 2DE 凝胶都显示出良好的分辨率和良好的斑点重叠。图像分析表明两种方法提取的蛋白质丰度不同。结果表明,这两种方法提取和溶解的蛋白质具有不同的化学物理特性和不同的细胞定位。这些结果证明了两种蛋白质提取方法的有效性和可重复性,可同时用于肌肉组织的全面蛋白质组分析。
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引用次数: 0
Multi-Omic Approaches in Cancer-Related Micropeptide Identification. 癌症相关微肽鉴定中的多肽方法
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-13 DOI: 10.3390/proteomes12030026
Katarina Vrbnjak, Raj Nayan Sewduth

Despite the advances in modern cancer therapy, malignant diseases are still a leading cause of morbidity and mortality worldwide. Conventional treatment methods frequently lead to side effects and drug resistance in patients, highlighting the need for novel therapeutic approaches. Recent findings have identified the existence of non-canonical micropeptides, an additional layer of the proteome complexity, also called the microproteome. These small peptides are a promising class of therapeutic agents with the potential to address the limitations of current cancer treatments. The microproteome is encoded by regions of the genome historically annotated as non-coding, and its existence has been revealed thanks to recent advances in proteomic and bioinformatic technology, which dramatically improved the understanding of proteome complexity. Micropeptides have been shown to be biologically active in several cancer types, indicating their therapeutic role. Furthermore, they are characterized by low toxicity and high target specificity, demonstrating their potential for the development of better tolerated drugs. In this review, we survey the current landscape of known micropeptides with a role in cancer progression or treatment, discuss their potential as anticancer agents, and describe the methodological challenges facing the proteome field of research.

尽管现代癌症治疗技术不断进步,但恶性肿瘤仍然是全球发病率和死亡率的主要原因。传统的治疗方法经常会导致副作用和患者产生耐药性,这凸显了对新型治疗方法的需求。最近的研究发现了非典型微肽的存在,它们是蛋白质组复杂性的另一层,也被称为微蛋白质组。这些小肽是一类很有前景的治疗药物,有可能解决目前癌症治疗的局限性。微蛋白组由基因组中历来被注释为非编码的区域编码,由于蛋白质组学和生物信息学技术的最新进展,人们对蛋白质组复杂性的认识有了极大的提高,微蛋白组的存在才得以揭示。微肽已被证明在几种癌症类型中具有生物活性,这表明了它们的治疗作用。此外,它们还具有低毒性和高靶向特异性的特点,这表明它们具有开发耐受性更好的药物的潜力。在这篇综述中,我们调查了目前已知的在癌症进展或治疗中发挥作用的微肽的情况,讨论了它们作为抗癌药物的潜力,并描述了蛋白质组研究领域所面临的方法学挑战。
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引用次数: 0
Transforming Clinical Research: The Power of High-Throughput Omics Integration. 变革临床研究:高通量 Omics 整合的力量。
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-06 DOI: 10.3390/proteomes12030025
Rui Vitorino

High-throughput omics technologies have dramatically changed biological research, providing unprecedented insights into the complexity of living systems. This review presents a comprehensive examination of the current landscape of high-throughput omics pipelines, covering key technologies, data integration techniques and their diverse applications. It looks at advances in next-generation sequencing, mass spectrometry and microarray platforms and highlights their contribution to data volume and precision. In addition, this review looks at the critical role of bioinformatics tools and statistical methods in managing the large datasets generated by these technologies. By integrating multi-omics data, researchers can gain a holistic understanding of biological systems, leading to the identification of new biomarkers and therapeutic targets, particularly in complex diseases such as cancer. The review also looks at the integration of omics data into electronic health records (EHRs) and the potential for cloud computing and big data analytics to improve data storage, analysis and sharing. Despite significant advances, there are still challenges such as data complexity, technical limitations and ethical issues. Future directions include the development of more sophisticated computational tools and the application of advanced machine learning techniques, which are critical for addressing the complexity and heterogeneity of omics datasets. This review aims to serve as a valuable resource for researchers and practitioners, highlighting the transformative potential of high-throughput omics technologies in advancing personalized medicine and improving clinical outcomes.

高通量组学技术极大地改变了生物学研究,为了解生命系统的复杂性提供了前所未有的洞察力。这篇综述全面审视了当前高通量整体组学流水线的状况,涵盖了关键技术、数据整合技术及其各种应用。它审视了新一代测序、质谱分析和微阵列平台的进展,并强调了它们对数据量和精度的贡献。此外,这篇综述还探讨了生物信息学工具和统计方法在管理这些技术产生的大型数据集方面的关键作用。通过整合多组学数据,研究人员可以全面了解生物系统,从而确定新的生物标记物和治疗目标,尤其是在癌症等复杂疾病中。这篇综述还探讨了将 omics 数据整合到电子健康记录 (EHR) 中的问题,以及云计算和大数据分析在改善数据存储、分析和共享方面的潜力。尽管取得了重大进展,但仍存在数据复杂性、技术限制和伦理问题等挑战。未来的方向包括开发更复杂的计算工具和应用先进的机器学习技术,这对于解决omics 数据集的复杂性和异质性至关重要。本综述旨在为研究人员和从业人员提供有价值的资源,强调高通量 omics 技术在推进个性化医疗和改善临床结果方面的变革潜力。
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引用次数: 0
Investigating the Prognostic Potential of Plasma ST2 in Patients with Peripheral Artery Disease: Identification and Evaluation. 研究外周动脉疾病患者血浆 ST2 的预后潜力:鉴定与评估。
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-29 DOI: 10.3390/proteomes12030024
Ben Li, Farah Shaikh, Abdelrahman Zamzam, Rawand Abdin, Mohammad Qadura

Soluble interleukin 1 receptor-like 1 (ST2) is a circulating protein demonstrated to be associated with cardiovascular diseases; however, it has not been studied as a biomarker for peripheral artery disease (PAD). Using a prospectively recruited cohort of 476 patients (312 with PAD and 164 without PAD), we conducted a prognostic study of PAD using clinical/biomarker data. Plasma concentrations of three circulating proteins [ST2, cytokine-responsive gene-2 (CRG-2), vascular endothelial growth factor (VEGF)] were measured at baseline and the cohort was followed for 2 years. The outcome of interest was a 2-year major adverse limb event (MALE; composite of major amputation, vascular intervention, or acute limb ischemia). Using 10-fold cross-validation, a random forest model was trained using clinical characteristics and plasma ST2 levels. The primary model evaluation metric was the F1 score. Out of the three circulating proteins analyzed, ST2 was the only one that was statistically significantly higher in individuals with PAD compared to patients without PAD (mean concentration in plasma of 9.57 [SD 5.86] vs. 11.39 [SD 6.43] pg/mL, p < 0.001). Over a 2-year period, 28 (9%) patients with PAD experienced MALE. Our predictive model, incorporating clinical features and plasma ST2 levels, achieved an F1 score of 0.713 for forecasting 2-year MALE outcomes. Patients identified as high-risk by this model showed a significantly increased likelihood of developing MALE (HR 1.06, 95% CI 1.02-1.13, p = 0.003). By combining clinical characteristics and plasma ST2 levels, our proposed predictive model offers accurate risk assessment for 2-year MALE in PAD patients. This algorithm supports risk stratification in PAD, guiding clinical decisions regarding further vascular evaluation, specialist referrals, and appropriate medical or surgical interventions, thereby potentially enhancing patient outcomes.

可溶性白细胞介素 1 受体样 1(ST2)是一种被证明与心血管疾病相关的循环蛋白,但尚未将其作为外周动脉疾病(PAD)的生物标记物进行研究。我们使用前瞻性招募的 476 例患者(312 例患有 PAD,164 例未患 PAD),利用临床/生物标记物数据对 PAD 的预后进行了研究。研究人员在基线时测量了三种循环蛋白(ST2、细胞因子反应基因-2(CRG-2)、血管内皮生长因子(VEGF))的血浆浓度,并对该组患者进行了为期两年的随访。关注的结果是 2 年的主要肢体不良事件(MALE;主要截肢、血管介入或急性肢体缺血的复合结果)。通过 10 次交叉验证,利用临床特征和血浆 ST2 水平训练了一个随机森林模型。模型的主要评估指标是 F1 分数。在分析的三种循环蛋白中,ST2是唯一一种与无PAD患者相比,PAD患者ST2显著高于无PAD患者的蛋白(血浆中的平均浓度为9.57 [SD 5.86] pg/mL vs. 11.39 [SD 6.43] pg/mL,P < 0.001)。在两年的时间里,28 名(9%)PAD 患者出现了 MALE。我们的预测模型结合了临床特征和血浆 ST2 水平,预测 2 年 MALE 结果的 F1 得分为 0.713。该模型确定的高危患者发生 MALE 的可能性显著增加(HR 1.06,95% CI 1.02-1.13,P = 0.003)。通过结合临床特征和血浆 ST2 水平,我们提出的预测模型可对 PAD 患者 2 年的 MALE 进行准确的风险评估。该算法有助于对 PAD 进行风险分层,指导临床做出进一步的血管评估、专家转诊以及适当的内科或外科干预等决定,从而改善患者的预后。
{"title":"Investigating the Prognostic Potential of Plasma ST2 in Patients with Peripheral Artery Disease: Identification and Evaluation.","authors":"Ben Li, Farah Shaikh, Abdelrahman Zamzam, Rawand Abdin, Mohammad Qadura","doi":"10.3390/proteomes12030024","DOIUrl":"10.3390/proteomes12030024","url":null,"abstract":"<p><p>Soluble interleukin 1 receptor-like 1 (ST2) is a circulating protein demonstrated to be associated with cardiovascular diseases; however, it has not been studied as a biomarker for peripheral artery disease (PAD). Using a prospectively recruited cohort of 476 patients (312 with PAD and 164 without PAD), we conducted a prognostic study of PAD using clinical/biomarker data. Plasma concentrations of three circulating proteins [ST2, cytokine-responsive gene-2 (CRG-2), vascular endothelial growth factor (VEGF)] were measured at baseline and the cohort was followed for 2 years. The outcome of interest was a 2-year major adverse limb event (MALE; composite of major amputation, vascular intervention, or acute limb ischemia). Using 10-fold cross-validation, a random forest model was trained using clinical characteristics and plasma ST2 levels. The primary model evaluation metric was the F1 score. Out of the three circulating proteins analyzed, ST2 was the only one that was statistically significantly higher in individuals with PAD compared to patients without PAD (mean concentration in plasma of 9.57 [SD 5.86] vs. 11.39 [SD 6.43] pg/mL, <i>p</i> < 0.001). Over a 2-year period, 28 (9%) patients with PAD experienced MALE. Our predictive model, incorporating clinical features and plasma ST2 levels, achieved an F1 score of 0.713 for forecasting 2-year MALE outcomes. Patients identified as high-risk by this model showed a significantly increased likelihood of developing MALE (HR 1.06, 95% CI 1.02-1.13, <i>p</i> = 0.003). By combining clinical characteristics and plasma ST2 levels, our proposed predictive model offers accurate risk assessment for 2-year MALE in PAD patients. This algorithm supports risk stratification in PAD, guiding clinical decisions regarding further vascular evaluation, specialist referrals, and appropriate medical or surgical interventions, thereby potentially enhancing patient outcomes.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"12 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Current Molecular and Cellular Landscape of Chronic Obstructive Pulmonary Disease (COPD): A Review of Therapies and Efforts towards Personalized Treatment. 慢性阻塞性肺病 (COPD) 目前的分子和细胞状况:慢性阻塞性肺病(COPD)当前的分子和细胞状况:疗法回顾与个性化治疗努力。
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-16 DOI: 10.3390/proteomes12030023
Luke A Farrell, Matthew B O'Rourke, Matthew P Padula, Fernando Souza-Fonseca-Guimaraes, Gaetano Caramori, Peter A B Wark, Shymali C Dharmage, Phillip M Hansbro

Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of global illness and mortality. It is commonly triggered by exposure to respiratory irritants like cigarette smoke or biofuel pollutants. This multifaceted condition manifests through an array of symptoms and lung irregularities, characterized by chronic inflammation and reduced lung function. Present therapies primarily rely on maintenance medications to alleviate symptoms, but fall short in impeding disease advancement. COPD's diverse nature, influenced by various phenotypes, complicates diagnosis, necessitating precise molecular characterization. Omics-driven methodologies, including biomarker identification and therapeutic target exploration, offer a promising avenue for addressing COPD's complexity. This analysis underscores the critical necessity of improving molecular profiling to deepen our comprehension of COPD and identify potential therapeutic targets. Moreover, it advocates for tailoring treatment strategies to individual phenotypes. Through comprehensive exploration-based molecular characterization and the adoption of personalized methodologies, innovative treatments may emerge that are capable of altering the trajectory of COPD, instilling optimism for efficacious disease-modifying interventions.

慢性阻塞性肺病(COPD)是导致全球疾病和死亡的第三大原因。它通常由接触香烟烟雾或生物燃料污染物等呼吸道刺激物引发。这种多发性疾病表现为一系列症状和肺部异常,其特点是慢性炎症和肺功能减退。目前的疗法主要依靠维持性药物来缓解症状,但无法阻止病情发展。慢性阻塞性肺病的性质多种多样,受各种表型的影响,使得诊断更加复杂,需要精确的分子特征描述。包括生物标记物鉴定和治疗靶点探索在内的表观学驱动方法为解决慢性阻塞性肺病的复杂性提供了一条前景广阔的途径。这项分析强调了改进分子特征描述以加深我们对慢性阻塞性肺病的理解并确定潜在治疗靶点的极端必要性。此外,它还提倡根据个体表型制定治疗策略。通过基于分子特征的全面探索和采用个性化方法,可能会出现能够改变慢性阻塞性肺病发展轨迹的创新治疗方法,从而为有效的疾病改变干预措施带来希望。
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引用次数: 0
The Low-Abundance Plasma Proteome Reveals Differentially Abundant Proteins Associated with Breast Implant Capsular Contracture: A Pilot Study. 低丰度血浆蛋白质组揭示了与乳房假体囊性挛缩相关的不同丰度蛋白质:一项试点研究。
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-06 DOI: 10.3390/proteomes12030022
Md Arifur Rahman, Ardeshir Amirkhani, Maria Mempin, Seong Beom Ahn, Anand K Deva, Mark S Baker, Karen Vickery, Honghua Hu

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance proteins, identifying novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples. Among them, 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. Gene Ontology enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, and complement and coagulation cascades were enriched pathways. The differentially abundant proteins from TMT-based quantitative proteomics have the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers.

囊性挛缩(CC)是乳房植入物相关感染最常见的术后并发症之一。人们对导致囊性挛缩的机制仍然知之甚少。血浆是发现早期蛋白质组学生物标志物的理想生物样本。然而,由于高丰度蛋白质会掩盖低丰度蛋白质的信号,因此将新型或特异性蛋白质鉴定为特定疾病的生物标记物一直受到阻碍。在此,我们采用去高丰度血浆蛋白,然后基于串联质量标签(TMT)的定量蛋白质组学方法,比较了 10 名健康对照组患者和 10 名乳房植入物 CC 患者。从这些样本中共鉴定出 450 种蛋白质。其中,与健康对照组相比,乳房植入物 CC 患者的 16 个蛋白质有明显的差异表达,其中 5 个蛋白质上调,11 个蛋白质下调。基因本体富集分析显示,与细胞、细胞过程和催化活性有关的蛋白质分别在细胞成分、生物过程和分子功能类别中含量最高。此外,通路分析显示,炎症反应、病灶粘附、血小板活化以及补体和凝血级联是富集的通路。基于 TMT 的定量蛋白质组学研究得出的差异丰度蛋白有可能为未来的机理研究和乳房植入物 CC 生物标记物的开发提供重要信息。
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引用次数: 0
Investigating and Annotating the Human Peptidome Profile from Urine under Normal Physiological Conditions. 调查和注释正常生理条件下尿液中的人类肽组图谱
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-25 DOI: 10.3390/proteomes12030018
Amr Elguoshy, Keiko Yamamoto, Yoshitoshi Hirao, Tomohiro Uchimoto, Kengo Yanagita, Tadashi Yamamoto

Examining the composition of the typical urinary peptidome and identifying the enzymes responsible for its formation holds significant importance, as it mirrors the normal physiological state of the human body. Any deviation from this normal profile could serve as an indicator of pathological processes occurring in vivo. Consequently, this study focuses on characterizing the normal urinary peptidome and investigating the various catalytic enzymes that are involved in generating these native peptides in urine. Our findings reveal that 1503 endogenous peptides, corresponding to 436 precursor proteins, were consistently identified robustly in at least 10 samples out of a total of 19 samples. Notably, the liver and kidneys exhibited the highest number of tissue-enriched or enhanced genes in the analyzed urinary peptidome. Furthermore, among the catalytic types, CTSD (cathepsin D) and MMP2 (matrix metalloproteinase-2) emerged as the most prominent peptidases in the aspartic and metallopeptidases categories, respectively. A comparison of our dataset with two of the most comprehensive urine peptidome datasets to date indicates a consistent relative abundance of core endogenous peptides for different proteins across all three datasets. These findings can serve as a foundational reference for the discovery of biomarkers in various human diseases.

研究典型尿液肽组的组成并确定形成肽组的酶具有重要意义,因为它反映了人体的正常生理状态。任何偏离这一正常特征的情况都可作为体内发生病理过程的指标。因此,本研究的重点是确定正常尿液肽组的特征,并调查尿液中参与生成这些原生肽的各种催化酶。我们的研究结果表明,在总共19个样本中,至少有10个样本能稳定地鉴定出1503种内源性肽,对应436种前体蛋白。值得注意的是,在分析的尿肽组中,肝脏和肾脏的组织富集基因或增强基因数量最多。此外,在催化类型中,CTSD(cathepsin D)和MMP2(matrix metalloproteinase-2)分别成为天冬氨酸肽酶和金属肽酶类别中最突出的肽酶。将我们的数据集与迄今为止最全面的两个尿液肽组数据集进行比较后发现,在所有三个数据集中,不同蛋白质的核心内源性肽的相对丰度是一致的。这些发现可作为发现各种人类疾病生物标志物的基础参考。
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引用次数: 0
How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction? 蛋白质组学如何帮助阐明肌肉萎缩症和相关多系统功能障碍的病理生理学相互关系?
IF 4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-16 DOI: 10.3390/proteomes12010004
Paul Dowling, Capucine Trollet, Elisa Negroni, Dieter Swandulla, Kay Ohlendieck

This perspective article is concerned with the question of how proteomics, which is a core technique of systems biology that is deeply embedded in the multi-omics field of modern bioresearch, can help us better understand the molecular pathogenesis of complex diseases. As an illustrative example of a monogenetic disorder that primarily affects the neuromuscular system but is characterized by a plethora of multi-system pathophysiological alterations, the muscle-wasting disease Duchenne muscular dystrophy was examined. Recent achievements in the field of dystrophinopathy research are described with special reference to the proteome-wide complexity of neuromuscular changes and body-wide alterations/adaptations. Based on a description of the current applications of top-down versus bottom-up proteomic approaches and their technical challenges, future systems biological approaches are outlined. The envisaged holistic and integromic bioanalysis would encompass the integration of diverse omics-type studies including inter- and intra-proteomics as the core disciplines for systematic protein evaluations, with sophisticated biomolecular analyses, including physiology, molecular biology, biochemistry and histochemistry. Integrated proteomic findings promise to be instrumental in improving our detailed knowledge of pathogenic mechanisms and multi-system dysfunction, widening the available biomarker signature of dystrophinopathy for improved diagnostic/prognostic procedures, and advancing the identification of novel therapeutic targets to treat Duchenne muscular dystrophy.

蛋白质组学是系统生物学的一项核心技术,已深深嵌入现代生物研究的多组学领域,本视角文章关注的问题是蛋白质组学如何帮助我们更好地理解复杂疾病的分子发病机制。杜兴氏肌营养不良症是一种单基因遗传疾病,主要影响神经肌肉系统,但具有大量多系统病理生理学改变的特征。报告介绍了营养不良症研究领域的最新成果,特别提到了神经肌肉变化和全身改变/适应的整个蛋白质组的复杂性。在介绍目前自上而下与自下而上蛋白质组学方法的应用及其技术挑战的基础上,概述了未来的系统生物学方法。设想中的整体和综合生物分析方法将包括把不同的 omics 类型研究(包括作为系统蛋白质评估核心学科的蛋白质组间和蛋白质组内研究)与复杂的生物分子分析(包括生理学、分子生物学、生物化学和组织化学)结合起来。综合蛋白质组学的研究结果将有助于增进我们对致病机制和多系统功能障碍的详细了解,拓宽肌营养不良症的可用生物标志物特征,以改进诊断/预后程序,并推动确定治疗杜氏肌营养不良症的新型治疗靶点。
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引用次数: 0
The Mechanisms of Regulated Cell Death: Structural and Functional Proteomic Pathways Induced or Inhibited by a Specific Protein—A Narrative Review 调节细胞死亡的机制:特定蛋白质诱导或抑制的结构和功能蛋白质组通路--综述
IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-05 DOI: 10.3390/proteomes12010003
Diego Fernández-Lázaro, B. Sanz, Jesús Seco-Calvo
Billions of cells die in us every hour, and our tissues do not shrink because there is a natural regulation where Cell Death (CD) is balanced with cell division. The process in which cells eliminate themselves in a controlled manner is called Programmed Cell Death (PCD). The PCD plays an important role during embryonic development, in maintaining homeostasis of the body’s tissues, and in the elimination of damaged cells, under a wide range of physiological and developmental stimuli. A multitude of protein mediators of PCD have been identified and signals have been found to utilize common pathways elucidating the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent PCD pathways. Included are studies of caspase-dependent PCD such as Anoikis, Catastrophe Mitotic, Pyroptosis, Emperitosis, Parthanatos and Cornification, and Caspase-Independent PCD as Wallerian Degeneration, Ferroptosis, Paraptosis, Entosis, Methuosis, and Extracellular Trap Abnormal Condition (ETosis), as well as neutrophil extracellular trap abnormal condition (NETosis) and Eosinophil Extracellular Trap Abnormal Condition (EETosis). Understanding PCD from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers, as well as therapeutic targets. This knowledge could provide the ability to modulate the PCD response and could lead to new therapeutic interventions in a wide range of diseases.
在我们体内,每小时都有数十亿个细胞死亡,而我们的组织却不会萎缩,这是因为细胞死亡(CD)与细胞分裂之间存在着一种平衡的自然调节。细胞以可控方式自我淘汰的过程被称为程序性细胞死亡(PCD)。程序性细胞死亡在胚胎发育、维持机体组织平衡以及在各种生理和发育刺激下消除受损细胞方面发挥着重要作用。目前已发现多种 PCD 蛋白介质,并发现了利用共同途径阐明相关蛋白的信号。这篇叙述性综述的重点是依赖于和不依赖于 Caspase 的 PCD 途径。其中包括对依赖于 Caspase 的 PCD 的研究,如 Anoikis、Catastrophe Mitotic、Pyroptosis、Emperitosis、Parthanatos 和 Cornification,以及依赖于 Caspase 的 PCD 的研究,如 Wallerian Degeneration、Ferroptosis、Paraptosis、Entosis、Methinology、Methinology、Methinology、Methinology、Methinology、Methinology、Methinology 等、细胞外陷阱异常状态(NETosis)和嗜酸性粒细胞细胞外陷阱异常状态(EETosis)。从本综述所报道的病例中了解 PCD 可为生物稳态过程提供重要启示。此外,确定参与这些过程的特定蛋白质对于确定分子生物标志物和治疗靶点至关重要。这些知识可提供调节 PCD 反应的能力,并可为多种疾病带来新的治疗干预。
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Proteomes
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