Journal of proteomics最新文献

{"title":"Identification of biological pathways and putative candidate genes for residual feed intake in a tropically adapted beef cattle breed by plasma proteome analysis","authors":"Jessica M. Malheiros ,&nbsp;Henrique G. Reolon ,&nbsp;Bruna G. Bosquini ,&nbsp;Fernando Baldi ,&nbsp;Daniela Lourenco ,&nbsp;Breno O. Fragomeni ,&nbsp;Rafael M.O. Silva ,&nbsp;Claudia C.P. Paz ,&nbsp;Nedenia B. Stafuzza","doi":"10.1016/j.jprot.2024.105361","DOIUrl":"10.1016/j.jprot.2024.105361","url":null,"abstract":"<div><div>This study identified potential biomarkers for feed efficiency by blood plasma proteome analysis of a tropically adapted beef cattle breed. Two experimental groups were selected based on residual feed intake (RFI). The proteome was investigated by LC-MS/MS in a data-dependent acquisition mode. After quality control, 123 differentially abundant proteins (DAPs) were identified between the two experimental groups. Among DAPs with the highest absolute log-fold change values, the <em>PRDM2</em>, <em>KRT5</em>, <em>UGGT1</em>, <em>DENND5B</em>, <em>B2M</em>, <em>SLC44A2</em>, <em>SLC7A2</em>, <em>PTPRC</em>, and <em>FETUB</em> were highlighted as potential biomarkers because of their functions that may contribute to RFI. Furthermore, functional enrichment analysis revealed several biological processes, molecular functions and pathways that contributes to RFI, such as cell signaling, cellular responses to stimuli, immune system, calcium, hormones, metabolism and functions of proteins, lipids and carbohydrates. Protein-protein interaction analysis identified 32 and 11 DAPs as important nodes based on their interactions in the high- and low-RFI groups, respectively. This study represents the first comprehensive profiling of the blood plasma proteome of a tropically adapted beef cattle breed and provides valuable insights into the potential roles of these DAPs in key biological processes and pathways, contributing to our understanding of the mechanisms underlying feed efficiency in tropically adapted beef cattle.</div></div><div><h3>Significance</h3><div>LC-MS/MS analysis was performed to investigate changes in the blood plasma proteome associated with residual feed intake (RFI) in a tropically adapted beef cattle breed (<em>Bos taurus taurus</em>). Some putative biomarkers were identified to distinguish the high-RFI to low-RFI animals, based on their log-fold change value or on their protein-protein interaction network, which provide helpful sources in developing novel selection strategies for breeding programs. Our findings also revealed valuable insights into the metabolic pathways and biological processes that contribute to RFI in beef cattle, such as those closely linked to cell signaling, cellular responses to stimuli, immune system, calcium, hormones, metabolism and functions of proteins, lipids and carbohydrates.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"312 ","pages":"Article 105361"},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic Bacillus cereus regulates metabolic disorders and activates the cholic acid-FXR axis to alleviate DSS-induced colitis","authors":"Yixiao Liao ,&nbsp;Shihui Wu ,&nbsp;Guixian Zhou ,&nbsp;Shihui Mei ,&nbsp;Bingmin Ou ,&nbsp;Ming Wen ,&nbsp;Ying Yang ,&nbsp;Guilan Wen","doi":"10.1016/j.jprot.2024.105360","DOIUrl":"10.1016/j.jprot.2024.105360","url":null,"abstract":"<div><div>Inflammatory bowel disease is characterized by severe imbalance of intestinal flora and metabolic disorders. Recent studies have demonstrated that probiotics can effectively alleviate inflammatory bowel disease by restoring the intestinal flora structure and modulating the immune response. However, the role of probiotics in regulating intestinal metabolism disorders is still unclear. This study explores the role of probiotic <em>B. cereus</em> in alleviating DSS-induced colitis. The findings indicated probiotic <em>B. cereus</em> treatment mitigated tissue damage and apoptosis during inflammation. Metabolome and transcriptome analysis revealed <em>B. cereus</em> activated the cholic acid-FXR axis by increasing cholic acid levels, which promoted the gene expression level of NF-κB inhibitor α, reduced the IL-1β, IL-6, IL-18 and TNF-α concentrations. Furthermore, it effectively mitigated the DSS-induced disruption of bile acid metabolism, arginine metabolism, and linoleic acid metabolism. This study explores the effect and mechanisms of probiotic <em>B. cereus</em> on alleviating DSS-induced colitis. It aims to provide a theoretical basis for microbial therapy in inflammatory bowel disease.</div></div><div><h3>Significance</h3><div>This study used metabolome and transcriptome to reveal the roles and mechanisms, which probiotic <em>Bacillus cereus</em> modulates metabolic disorders and alleviate DSS-induced colitis. We identified the cholic acid-FXR axis as an important target for alleviating DSS-induced colitis. These findings provide new insights into microbial treatment strategies for IBD.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"312 ","pages":"Article 105360"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic interrogation of complex biomedical samples using the rapid denaturing organic digestion (DOD) method","authors":"Jonathan Oyler ,&nbsp;Raymond F. Sullivan ,&nbsp;Bao Q. Tran ,&nbsp;Dhanwin Baker ,&nbsp;Clare Coveney ,&nbsp;David Boocock ,&nbsp;Benjamin Oyler ,&nbsp;Carole C. Perry ,&nbsp;David P.A. Kilgour","doi":"10.1016/j.jprot.2024.105359","DOIUrl":"10.1016/j.jprot.2024.105359","url":null,"abstract":"<div><div>Limitations to many current aqueous-based tryptic digestion methods include lengthy digestion times and both relatively high inter- and intra-day variability for both characteristic peptides identified and sequence coverages. This report describes results from digestion of some complex biomedical samples using the rapid Denaturing Organic Digestion method (DOD), an organic solvent-modified digestion method previously optimized for targeted protein digestion. Advantages of the DOD method included a very rapid digestion only requiring inexpensive solvents and reagents generally available in the laboratory, with no requirement for specialized equipment or expensive, specialized consumables. For this study, samples of <em>E. coli</em> and murine ileum protein extracts, and K562, a mass spectrometry-compatible human protein extract and reference standard routinely used to evaluate methods, were digested. Sequence coverage and characteristic peptide identification results were compared to those from 18 and 24 h conventional aqueous-based digestion methods. Across the samples tested, though the number of characteristic peptides and sequence coverages produced by the 5 min DOD method were very similar to those produced by the aqueous-based digestion methods, the specific characteristic proteins and their corresponding tryptic peptides identified following DOD method digestion included more hydrophilic and less hydrophobic species. In addition, we explored the effect of increasing digestion times with complex samples from 5 to 30 and 90 min for the DOD method. Increasing the digestion time to ≥30 min resulted in improved intra-day precision and the identification of many more peptide products than the currently used aqueous methods to which it was compared. These results suggest that the DOD organic-modified digestion method could, while markedly reducing protein digestion time, also provide more precise analysis and access to a somewhat different area of the proteome than that provided by current aqueous-based digestion methods.</div></div><div><h3>Significance</h3><div>The DOD tryptic digest method is a very simple and rapid process with no requirement for expensive equipment or consumables. The method markedly reduces tryptic digestion time and cost, and substantially improves within-batch and across-analyst precision for peptide and sequence coverage results over methods to which it was compared. Importantly, it also provides access to a somewhat different subset of the proteome with different peptide products identified as compared to aqueous solvent-based digestion providing potential for increased proteome coverage for bottom-up analysis if used in conjunction with aqueous-based methods.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"312 ","pages":"Article 105359"},"PeriodicalIF":2.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B small surface protein hijacking Bip is initial and essential to promote lipid synthesis","authors":"Tao Zuo ,&nbsp;Sha Jing ,&nbsp;Peiru Chen ,&nbsp;Tao Zhang ,&nbsp;Yihao Wang ,&nbsp;Yanchang Li ,&nbsp;Lei Chang ,&nbsp;Xingyu Rong ,&nbsp;Na Li ,&nbsp;Zhenwen Zhao ,&nbsp;Chao Zhao ,&nbsp;Ping Xu","doi":"10.1016/j.jprot.2024.105358","DOIUrl":"10.1016/j.jprot.2024.105358","url":null,"abstract":"<div><div>To date, the molecular pathogenic mechanisms between HBsAg and liver metabolic disorders have not been fully understood. To explore the overall effects of HBsAg on liver tissues from HBV transgenic mice, proteome, interactome, and signal pathway analysis were employed to uncover the underlying mechanisms. Bioinformatics analysis of 191 differentially expressed proteins suggested that HBV upregulated the expression of multiple enzymes involved in lipid synthesis, and small HBs (SHBs) caused lipid accumulation in cells. Further studies showed that SHBs bound to binding immunoglobulin protein (Bip), which normally functions in cell homeostasis against the unfolded protein response (UPR) signaling via occupying inositol-requiring enzyme 1 (IRE1). Hijacking Bip by SHBs alleviated the inhibition of post-endoplasmic reticulum (ER) signaling and sequential activation of the IRE1 downstream transcription factors involved in lipid synthesis, such as spliced X-box binding protein 1 (sXBP1) and sterol regulatory element-binding protein 1 (SREBP1), leading to lipid metabolism disorder. The restoration of Bip can alleviate ER stress, and block the sequential post-ER signaling caused by SHBs. This study revealed a new pathway through which SHBs promote lipid disorder, and suggests that Bip may serve as a novel target for intervention in HBV related liver diseases.</div></div><div><h3>Significance</h3><div>In this study, we found a new pathway promoting the lipid disorder by SHBs through quantitative proteomics studies, and Bip may serve as a novel target for intervention in HBV related liver diseases. These findings highlight a novel role of SHBs in regulating cell lipid metabolism and provide an insight into the relationship between HBV infection and liver fatty disorders, which may serve as a potential therapeutic target for intervention of HBV related liver diseases.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"311 ","pages":"Article 105358"},"PeriodicalIF":2.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of urine p-cresol glucuronide as renal cell carcinoma non-invasive biomarker","authors":"Julia Oto ,&nbsp;Raquel Herranz ,&nbsp;Patricia Verger ,&nbsp;Marta Roca ,&nbsp;Emma Plana ,&nbsp;Manuel Miralles ,&nbsp;Manuel Martínez-Sarmiento ,&nbsp;César D. Vera-Donoso ,&nbsp;Pilar Medina","doi":"10.1016/j.jprot.2024.105357","DOIUrl":"10.1016/j.jprot.2024.105357","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC) stands among the most lethal urological malignancies. Most RCCs are incidentally diagnosed as initial symptoms are unspecific. Novel, minimally-invasive diagnostic and prognostic methods for RCC are needed, ideally in urine.</div><div>Using UPLC-Q-ToF MS untargeted metabolomic analysis in urine, we previously revealed p-cresol glucuronide as potential RCC diagnostic marker. Additionally, urine samples one-year post-nephrectomy revealed isobutyryl-<span>l</span>-carnitine and L-proline betaine as potential RCC prognostic markers. Our present aim was to validate these differences in an independent cohort of RCC patients and healthy controls to strengthen their value as non-invasive biomarkers.</div><div>In an independent cohort of 69 RCC patients and 52 controls we validated an increase in p-cresol glucuronide in urine from patients at diagnosis compared to controls (<em>P</em> = 0.0043). It remained increased one-year post-nephrectomy (<em>P</em> = 0.0288). The value of p-cresol glucuronide for RCC diagnosis was assessed with ROC curves analysis (AUC = 0.66, 95 % Confidence Interval 0.56–0.76). The role of isobutyryl-<span>l</span>-carnitine and L-proline betaine as prognostic markers could not be validated and will require a larger cohort.</div><div>Our findings confirm the value of p-cresol glucuronide in urine as diagnostic marker for RCC in an independent cohort. This non-invasive method holds promise for enhancing patient care by reducing the need for potentially risky diagnostic procedures. Further metaproteomics-oriented approaches towards the tyrosine oxidation pathway and microbiota metagenomics studies may promote a holistic management of RCC.</div></div><div><h3>Significance</h3><div>Current imaging techniques available to diagnose and monitor renal cell carcinoma (RCC) are harmful for the patient given the high-radiation dose, and unspecific in low-grade tumors. Thus, novel non-invasive biomarkers with diagnostic and prognostic capabilities are of utmost importance. Herein, we have validated urine p-cresol glucuronide as diagnostic marker for RCC. This novel non-invasive biomarker could improve accurate assessments of tumor behavior, while enhancing patient outcomes by reducing discomfort and detrimental side effects.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"311 ","pages":"Article 105357"},"PeriodicalIF":2.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated proteomic and phosphoproteomic landscape of chronic kidney disease","authors":"Linxiao Sun ,&nbsp;Cheng Wang ,&nbsp;Zhongjing Zhou ,&nbsp;Qiangqiang Li","doi":"10.1016/j.jprot.2024.105355","DOIUrl":"10.1016/j.jprot.2024.105355","url":null,"abstract":"<div><div>The prevalence of chronic kidney disease (CKD) is gradually rising worldwide. Patients often remain asymptomatic for an extended period, leaving them unaware of their condition, which can lead to progressing to end-stage renal disease and cause significant economic burden. Improved understanding of CKD pathogenesis can enhance early detection and facilitate advances in drug development. Here, we performed proteomic and phosphoproteomic analyses of the mouse unilateral ureteral obstruction model to explore the molecular mechanisms of chronic kidney injury. 474 significantly differentially expressed proteins and 96 significantly differentially expressed phosphoproteins were screened, respectively. Chronic kidney injury involves complex metabolic pathways such as citrate cycle and hematopoietic system in proteome, and mitochondrial oxidative phosphorylation suppression is a notable alteration. The phosphoproteomic analysis revealed a significant upregulation in epithelial mesenchymal transition and P53 pathways, with a corresponding increase in the phosphorylation of Jun at serine 73. Utilizing HK2 cells, we observed that the reduction oxidative phosphorylation was consistently associated with an augmentation in oxidative stress, which subsequently activated Jun and induced apoptosis. Proteins that act as hubs in these pathways may be candidate targets for CKD intervention. These findings contribute significantly to the current understanding of CKD and provide valuable insights for future studies.</div></div><div><h3>Significance</h3><div>Chronic kidney disease (CKD) incidence rising annually with varied etiologies, kidney often irreversibly fibrotic, the treatment options are limited and often ineffective due to deficient understanding of renal fibrosis mechanisms. Despite the extensive efforts and numerous omics studies conducted on renal fibrosis, to date, no study has been undertaken to investigate the role of phosphorylated proteins in UUO models. Previously, we performed a comprehensive transcriptome and proteome analysis based on the CKD model, but the potential alterations in the phosphoproteome were not addressed. Here, an integrated proteomic and phosphoproteomic landscape of CKD was completed, which was the the first phosphoproteomic profiles of UUO model. Phosphoproteomic profile suggests that the epithelial mesenchymal transition and P53 pathways is significantly activated in mouse models of kidney injury, and the core protein Jun played a key role in CKD. And a preliminary correlation between P-Jun and oxidative phosphorylation was found base on HK2 cells. Our work contributes to a deeper understanding of the disease characteristics and molecular mechanisms of CKD. Identifying potential CKD targets from proteome and phosphoproteome may provide valuable insights for early diagnosis and treatment of CKD.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"311 ","pages":"Article 105355"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum proteomics identifies biomarkers for predicting non-survivors in elderly COVID-19 patients","authors":"Lin Wang ,&nbsp;Wenmin Tian ,&nbsp;Sen Wang ,&nbsp;Yuhong Liu ,&nbsp;Hongli Wang ,&nbsp;Junjie Xiao ,&nbsp;Zhongkuo Yu ,&nbsp;Lixin Xie ,&nbsp;Yang Chen","doi":"10.1016/j.jprot.2024.105356","DOIUrl":"10.1016/j.jprot.2024.105356","url":null,"abstract":"<div><div>In December 2022, China ceased the zero-COVID-19 policy, resulting in an increase in hospitalizations and deaths due to COVID-19, particularly among the elderly population. Predicting non-survivors aims to identify high-risk patients and enable targeted interventions to improve survival rates. Additionally, understanding factors affecting prognosis provides essential insights for further research and optimization of treatment strategies. We applied 4D-DIA mass spectrometry for serum proteome analysis and provided a comprehensive characterization of disease features in elderly patients within the Chinese population. Our study elucidated that immune disorders, lung damage, and cardiovascular disorders are predominant causes of death in these patients. Compared to clinical indices, proteomic analysis is more sensitive in tracing these disorders. We also provided a prediction panel for survival outcomes of elderly patients using levels of CXCL10, CXCL16 and IL1RA, which were validated by ELISA. These biomarkers will help improve predictive efficacy for survival outcomes in elderly patients.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"311 ","pages":"Article 105356"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decellularized extracellular matrix from bovine ovarian tissue maintains the protein composition of the native matrisome","authors":"Cecibel M. León-Félix ,&nbsp;Emna Ouni ,&nbsp;Gaëtan Herinckx ,&nbsp;Didier Vertommen ,&nbsp;Christiani A. Amorim ,&nbsp;Carolina M. Lucci","doi":"10.1016/j.jprot.2024.105347","DOIUrl":"10.1016/j.jprot.2024.105347","url":null,"abstract":"<div><div>Recent approaches of regenerative reproductive medicine investigate the decellularized extracellular matrix to develop a transplantable engineered ovary (TEO). However, a full proteomic analysis is not usually performed after the decellularization process to evaluate the preservation of the extracellular matrix (ECM). In this study, the ECM of the bovine ovarian cortex was analyzed before and after decellularization using mass spectrometry and bioinformatics. A total of 155 matrisome proteins were identified in the native ECM of the bovine ovarian cortex, with 145 matrisome proteins detected in the decellularized ECM. After decellularization, only 10 matrisome proteins were lost, and notably, none belonged to the category of reproductive biological processes. Histology and histochemistry analyses were employed to assess the general morphology of both native and decellularized ECM, allowing for the identification of the most abundant ECM proteins. Moreover, our study highlighted collagen type VI alpha 3 and heparan sulfate proteoglycan 2 as the most abundant components in the bovine ovarian ECM, mirroring the composition observed in the human ovary. These findings enhance our understanding of the composition of both native and decellularized ECM, with the potential implications for the development of a TEO.</div></div><div><h3>Significance</h3><div>The significance of the present study lies on the possibility of advancing towards developing a bioengineered ovary, which is the ultimate strategy to regain fertility in women. The results demonstrate that the decellularized extracellular matrix of the bovine ovary maintains the protein composition of the native matrisome, using a recently described decellularization protocol. The decellularized matrix may serve as scaffolding for seeding ovarian stromal cells and follicles to create a bioengineered ovary, and as closer its composition is to the native matrix the better. Also, comparing the bovine ovarian matrisome, which was described for the first time here, with the human ovarian matrisome, we could see a great similarity, suggesting that the bovine ovary decellularized matrix may serve as a model for developing a human bioengineered ovary.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"311 ","pages":"Article 105347"},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DIA proteomic and PRM validation through human granulose cells profiles screen suitable biomarkers for polycystic ovary syndrome patients","authors":"Faying Liu ,&nbsp;Lifeng Tian ,&nbsp;Ying Zhang ,&nbsp;Wei Deng ,&nbsp;Xiaoyun Xu ,&nbsp;Yang Zou ,&nbsp;Ruifang An","doi":"10.1016/j.jprot.2024.105332","DOIUrl":"10.1016/j.jprot.2024.105332","url":null,"abstract":"<div><div>The aim of this study is to identify differentially expressed proteins (DEPs) in granulose cells (GCs) from women with or withoutpolycystic ovary syndrome (PCOS) via data independent acquisition (DIA) proteomic analysis.A total of 63 women were recruited for this study, 34 PCOS patients as experimental group (P), and 29 women without PCOS as Normal group (NP). DIA-based proteomic analysis was performed to identify DEPs in GCs between the P and NP samples. Certain typical DEPs were further validated by Parallel reaction monitoring (PRM), and correlation analysis was performed between these DEPs and the clinical characteristics.Cell vitality was measured by CCK-8 assay. DIA analysis revealed 174 significantly DEPs, of which 7 were upregulated and 167 downregulated. Bioinformatics analysis was performed to analysis the significantly DEPs. The PRM experiment confirmed TOP2A and SPHKAP were upregulated significantly in P by comparing to NP, while GM2A, MRPS16, APOA2 and FGF2 were downregulated significantly. Most notably, Correlation analysis revealed that TOP2A, SPHKAP, MRPS16 and FGF2were positively correlated with TG, AMH and Age, but negatively correlated with Menarche age, DBIL, FT3, Basal serum FSH and LH.Meanwhile, CCK-8 assay has shown that downregulation of FGF2 could weaken cell viability. Finally, a panel of DEPs were identified in the GCs of patients with PCOS, of which certain significant DEPs might play essential roles in the pathogenesis of PCOS, could be regarded as candidate biomarkers for PCOS.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"309 ","pages":"Article 105332"},"PeriodicalIF":2.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted metabolomics of 3xTg-AD neurotoxic astrocytes","authors":"Diego Carvalho ,&nbsp;Pablo Diaz-Amarilla ,&nbsp;Mathew R. Smith ,&nbsp;María Daniela Santi ,&nbsp;Marcela Martinez-Busi ,&nbsp;Young-Mi Go ,&nbsp;Dean P. Jones ,&nbsp;Pablo Duarte ,&nbsp;Eduardo Savio ,&nbsp;Juan A. Abin-Carriquiry ,&nbsp;Florencia Arredondo","doi":"10.1016/j.jprot.2024.105336","DOIUrl":"10.1016/j.jprot.2024.105336","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the most common form of dementia, affecting approximately 47 M people worldwide. Histological features and genetic risk factors, among other evidence, supported the amyloid hypothesis of the disease. This neuronocentric paradigm is currently undergoing a shift, considering evidence of the role of other cell types, such as microglia and astrocytes, in disease progression. Previously, we described a particular astrocyte subtype obtained from the 3xTg-AD murine model that displays neurotoxic properties in vitro. We continue here our exploratory analysis through the lens of metabolomics to identify potentially altered metabolites and biological pathways.</div><div>Cell extracts from neurotoxic and control astrocytes were compared using high-resolution mass spectrometry-based metabolomics. Around 12 % of metabolic features demonstrated significant differences between neurotoxic and control astrocytes, including alterations in the key metabolite glutamate. Consistent with our previous transcriptomic study, the present results illustrate many homeostatic and regulatory functions of metabolites, suggesting that neurotoxic 3xTg-AD astrocytes exhibit alterations in the Krebs cycle as well as the prostaglandin pathway.</div><div>This is the first metabolomic study performed in 3xTg-AD neurotoxic astrocytes. These results provide insight into metabolic alterations potentially associated with neurotoxicity and pathology progression in the 3xTg-AD mouse model and strengthen the therapeutic potential of astrocytes in AD.</div></div><div><h3>Biological significance</h3><div>Our study is the first high-resolution metabolomic characterization of the novel neurotoxic 3xTg-AD astrocytes. We propose key metabolites and pathway alterations, as well as possible associations with gene expression alterations in the model. Our results are in line with recent hypotheses beyond the amyloid cascade, considering the involvement of several stress response cascades during the development of Alzheimer's disease. This work could inspire other researchers to initiate similar studies in related models. Furthermore, this work illustrates a powerful workflow for metabolite annotation and selection that can be implemented in other studies.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105336"},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}