Frontiers in Molecular Biosciences最新文献

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α-Lipoic acid: a potential regulator of copper metabolism in Alzheimer’s disease α-硫辛酸:阿尔茨海默病中铜代谢的潜在调节剂
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-09-03 DOI: 10.3389/fmolb.2024.1451536
Sigrid Kirss, Anette Reinapu, Ekaterina Kabin, Julia Smirnova, Vello Tõugu, Peep Palumaa
{"title":"α-Lipoic acid: a potential regulator of copper metabolism in Alzheimer’s disease","authors":"Sigrid Kirss, Anette Reinapu, Ekaterina Kabin, Julia Smirnova, Vello Tõugu, Peep Palumaa","doi":"10.3389/fmolb.2024.1451536","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1451536","url":null,"abstract":"Alzheimer’s disease (AD) is characterized by classic hallmarks such as amyloid plaques and neurofibrillary tangles, however, intensive research has broadened its scope to explore additional underlying mechanisms. Notably, disruptions in metal homeostasis, particularly involving copper, have gained significant attention. In AD pathology, an imbalance is evident: there is an excess of extracellular copper alongside a deficiency in intracellular copper in brain tissue. Our previous work demonstrated that α-lipoic acid (LA) can effectively shift copper from the extracellular space to the intracellular environment in a neuronal cell model. However, the precise mechanism of action and role of LA in copper metabolism remained elusive. In this study, we compared the cellular effects of LA with those of different synthetic copper-binding ligands: diethyldithiocarbamate (DETC), clioquinol (CQ), D-penicillamine (D-PA) and elesclomol (ES). Using differentiated SH-SY5Y cell culture as a neuronal model, we found that, unlike other synthetic compounds, natural ligand LA is not toxic in the presence of extracellular copper, even at high doses. LA gradually increased intracellular copper levels over 24 h. In contrast, DETC, CQ, and ES acted as fast copper ionophores, potentially explaining their higher toxicity compared to LA. D-PA did not facilitate copper uptake into cells. We demonstrated that a slow increase of LA inside the cells is enhanced in the presence of copper. Furthermore, the ability of LA to modulate the equilibrium of extra- and intracellular copper was evident when we added copper isotope <jats:sup>65</jats:sup>Cu. The ratio of copper isotopes changed rapidly, reflecting the impact of LA on the equilibrium of copper distribution without affecting the copper transport network. Our results provide compelling evidence that α-lipoic acid holds promise as a non-toxic agent capable of normalizing copper metabolism in Alzheimer’s disease.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular dynamics simulation of the brain-isolated single-domain antibody/nanobody from camels through in vivo phage display screening 通过体内噬菌体展示筛选从骆驼中分离出脑单域抗体/纳米抗体的分子动力学模拟
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-09-02 DOI: 10.3389/fmolb.2024.1414119
Behnam Hasannejad-Asl, Hassan Hashemzadeh, Farkhondeh Pooresmaeil, Mehran Dabiri, Mohammad-Reza Pooresmaeil, Davoud Ahmadvand, Arshad Hosseini
{"title":"Molecular dynamics simulation of the brain-isolated single-domain antibody/nanobody from camels through in vivo phage display screening","authors":"Behnam Hasannejad-Asl, Hassan Hashemzadeh, Farkhondeh Pooresmaeil, Mehran Dabiri, Mohammad-Reza Pooresmaeil, Davoud Ahmadvand, Arshad Hosseini","doi":"10.3389/fmolb.2024.1414119","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1414119","url":null,"abstract":"IntroductionDuring the last decade, there has been a significant rise in the use of therapeutic antibodies or passive immunotherapy for treating various conditions like inflammation and cancer. However, these proteins face challenges reaching the brain and often require specialized delivery methods such as single-domain antibodies (sdAbs). Traditional antibodies struggle to efficiently cross the blood-brain barrier (BBB), hindering their effectiveness. Receptor-mediated transcytosis (RMT) offers a promising pathway for transporting large molecules essential for brain function and treatment across the BBB.MethodsSdAbs and peptide ligands with an affinity for RMT receptors are commonly employed to enhance the transport of biotherapeutics compounds across the BBB. This research used a sdAbs phage-displayed library from 13 <jats:italic>camelus dromedarius</jats:italic> samples to identify sdABs that specifically bind to and are internalized by human BBB endothelial cells (ECs) through <jats:italic>in vivo</jats:italic> panning.Results and discussionOne sdAb, defined as FB24, was isolated, sequenced, translated into an open reading frame (ORF), and subjected to three-dimensional (3D) modeling. Molecular docking and molecular dynamics simulations were carried out by the HADDOCK web server and GROMACS, respectively, to evaluate the interaction between FB24 and EC receptors <jats:italic>in silico</jats:italic>. The docking results revealed that FB24 exhibited binding activity against potential EC receptors with −1.7 to −2.7 ranged z score and maintained a stable structure. The docked complex of FB24-RAGE (receptor for advanced glycation end products, also known as advanced glycation end product receptor [AGER]) showed 18 hydrogen bonds and 213 non-bonded contacts. It was chosen for further analysis by molecular dynamics simulations by GROMACS. This complex showed a stable condition, and its root mean square deviation (RMSD) was 0.218 nm. The results suggest that FB24 could serve as a suitable carrier vector for transporting therapeutic and diagnostic agents across the BBB to the brain through a non-invasive route.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Death Receptor 5 (DR5) for imaging and treatment of primary bone and soft tissue tumors: an update of the literature 以死亡受体 5 (DR5) 为靶点,对原发性骨与软组织肿瘤进行成像和治疗:文献更新
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-09-02 DOI: 10.3389/fmolb.2024.1384795
Zakareya Gamie, Anja Krippner-Heidenreich, Craig Gerrand, Kenneth Samora Rankin
{"title":"Targeting Death Receptor 5 (DR5) for imaging and treatment of primary bone and soft tissue tumors: an update of the literature","authors":"Zakareya Gamie, Anja Krippner-Heidenreich, Craig Gerrand, Kenneth Samora Rankin","doi":"10.3389/fmolb.2024.1384795","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1384795","url":null,"abstract":"BackgroundDeath Receptor 5 (DR5) is expressed on the surface of primary bone and soft tissue sarcoma cells, and its activation induces cell death primarily through apoptosis. The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death. Currently, clinical trials are investigating the effectiveness of DR5 activation using new biological agents, such as bi-specific or tetravalent antibodies, in improving the survival of patients with relapsed or refractory cancers. Furthermore, investigations continue into the use of novel combination therapies to enhance DR5 response, for example, with inhibitor of apoptosis protein (IAP) antagonist agents [such as the second mitochondria-derived activator of caspase (SMAC) mimetics] and with immune checkpoint inhibitor anti-programmed death-ligand 1 (anti-PD-L1) or anti-programmed cell death-1 (anti-PD-1) antibodies. Other therapies include nanoparticle-mediated delivery of TRAIL plasmid DNA or TRAIL mRNA and stem cells as a vehicle for the targeted delivery of anti-cancer agents, such as TRAIL, to the tumor.Methodsscoping review of the literature from November 2017 to March 2024, utilizing PubMed and Google Scholar.ResultsNew agents under investigation include nanoTRAIL, anti-Kv10.1, multimeric IgM, and humanized tetravalent antibodies. Developments have been made to test novel agents, and imaging has been used to detect DR5 in preclinical models and patients. The models include 3D spheroids, genetically modified mouse models, a novel jaw osteosarcoma model, and patient-derived xenograft (PDX) animal models. There are currently two ongoing clinical trials focusing on the activation of DR5, namely, IGM-8444 and INBRX-109, which have progressed to phase 2. Further modifications of TRAIL delivery with fusion to single-chain variable fragments (scFv-TRAIL), directed against tumor-associated antigens (TAAs), and in the use of stem cells focus on targeted TRAIL delivery to cancer cells using bi-functional strategies.Conclusion<jats:italic>In vitro</jats:italic>, <jats:italic>in vivo</jats:italic>, and clinical trials, as well as advances in imaging and theranostics, indicate that targeting DR5 remains a valid strategy in the treatment of some relapsed and refractory cancers.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial: New approaches toward understanding challenges in molecular virology: computational techniques and machine learning. 社论:理解分子病毒学挑战的新方法:计算技术和机器学习。
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-09-02 DOI: 10.3389/fmolb.2024.1472796
Srirupa Chakraborty,Kun Qu,Jayaraman Valadi
{"title":"Editorial: New approaches toward understanding challenges in molecular virology: computational techniques and machine learning.","authors":"Srirupa Chakraborty,Kun Qu,Jayaraman Valadi","doi":"10.3389/fmolb.2024.1472796","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1472796","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B 开发和验证用于预测慢性乙型肝炎患者晚期肝纤维化的提名图
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-09-02 DOI: 10.3389/fmolb.2024.1452841
Kexing Han, Jianfeng Wang, Xizhen Song, Luyang Kang, Junjie Lin, Qinggang Hu, Weijie Sun, Yufeng Gao
{"title":"Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B","authors":"Kexing Han, Jianfeng Wang, Xizhen Song, Luyang Kang, Junjie Lin, Qinggang Hu, Weijie Sun, Yufeng Gao","doi":"10.3389/fmolb.2024.1452841","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1452841","url":null,"abstract":"BackgroundThe progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent.ObjectiveBased on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests.MethodsPatients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively.ResultsUltimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King’s score, the model in the training cohort (AUC = 0.834, 95% CI 0.800–0.868, <jats:italic>p</jats:italic> &amp;lt; 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742–0.866, <jats:italic>p</jats:italic> &amp;lt; 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King’s scores in all cohorts.ConclusionThis study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in understanding the molecular mechanisms of borderline ovarian tumors 了解边缘性卵巢肿瘤分子机制的进展
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-30 DOI: 10.3389/fmolb.2024.1429852
Shiying Chen, Li Huang, Meili Liang, Yajing Xie, Zhimei Zhou, Yumin Ke, Zhuna Wu
{"title":"Advances in understanding the molecular mechanisms of borderline ovarian tumors","authors":"Shiying Chen, Li Huang, Meili Liang, Yajing Xie, Zhimei Zhou, Yumin Ke, Zhuna Wu","doi":"10.3389/fmolb.2024.1429852","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1429852","url":null,"abstract":"Borderline ovarian tumors (BOTs), which are a special type of epithelial tumor of the ovary, lie between benign and malignant tumors and have low malignant potential. Due to the fact that the early symptoms of these tumors are relatively subtle, they are not easy to diagnose clinically. This study explores advancements in clinical detection methods and provides a comprehensive overview of molecules such as cell migration factors, cell transcription factors, cell damage repair factors, cell cycle regulators, and tumor suppressor genes that are related to the development of BOTs and their related mechanisms in recent years, thus aiming to provide more sensitive, specific, and efficient differential diagnosis and treatment plans for patients to improve their prognosis and survival outcomes.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptome-based identification of key actin-binding proteins associated with high metastatic potential in breast cancer 基于转录组鉴定与乳腺癌高转移潜能相关的关键肌动蛋白结合蛋白
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-30 DOI: 10.3389/fmolb.2024.1440276
Christian Müller, Leticia Oliveira-Ferrer, Volkmar Müller, Barbara Schmalfeldt, Sabine Windhorst
{"title":"Transcriptome-based identification of key actin-binding proteins associated with high metastatic potential in breast cancer","authors":"Christian Müller, Leticia Oliveira-Ferrer, Volkmar Müller, Barbara Schmalfeldt, Sabine Windhorst","doi":"10.3389/fmolb.2024.1440276","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1440276","url":null,"abstract":"IntroductionActin-binding proteins (ABPs) are essential for the regulation of morphological plasticity required for tumor cells to metastasize. The aim of this study was to perform an unbiased bioinformatic approach to identify the key ABPs significantly associated with the metastatic potential of breast cancer cells.MethodsMicroarray data from 181 primary breast cancer samples from our hospital were used, and all genes belonging to the Gene Ontology term actin cytoskeleton organization were obtained from QuickGO. Association with metastasis-free survival probability was tested using Cox proportional hazards regression, and pairwise co-expression was tested by Pearson correlations. Differential expression between different subgroups was analyzed using Wilcoxon tests for dichotomous traits and Kruskal–Wallis tests for categorical traits. Validation was performed using four publicly available breast cancer datasets.Results<jats:italic>ARHGAP25</jats:italic> was significantly associated with a low metastatic potential, and <jats:italic>CFL1</jats:italic>, <jats:italic>TMSB15A</jats:italic>, and <jats:italic>ACTL8</jats:italic> were significantly associated with a high metastatic potential. A significantly higher expression of <jats:italic>CFL1</jats:italic>, <jats:italic>TMSB15A,</jats:italic> and <jats:italic>ACTL8</jats:italic> mRNA was found in the more aggressive Her2-positive and triple-negative subtypes as well as in ER-negative samples. Also, these genes were co-expressed in the same tumors. However, only mRNA levels of <jats:italic>CFL1</jats:italic> were increased in pN1 compared to pN0 patients. External validation revealed that <jats:italic>CFL1</jats:italic> and <jats:italic>TMSB15A</jats:italic> had significant associations with consistent hazard ratios in two breast cancer cohorts, and among these, <jats:italic>CFL1</jats:italic> exhibited the highest hazard ratios.Conclusion<jats:italic>CFL1</jats:italic> showed the strongest correlation with the metastatic potential of breast tumors. Thus, targeted inhibition of <jats:italic>CFL1</jats:italic> might be a promising approach to treat malignant breast cancer cells.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antimetastatic and antitumor activities of oncolytic NDV AMHA1 in a 3D culture model of breast cancer 溶瘤 NDV AMHA1 在乳腺癌三维培养模型中的抗转移和抗肿瘤活性
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-30 DOI: 10.3389/fmolb.2024.1331369
Ahmed Majeed Al-Shammari, Marwa Ibrahim Salman
{"title":"Antimetastatic and antitumor activities of oncolytic NDV AMHA1 in a 3D culture model of breast cancer","authors":"Ahmed Majeed Al-Shammari, Marwa Ibrahim Salman","doi":"10.3389/fmolb.2024.1331369","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1331369","url":null,"abstract":"IntroductionNewcastle disease virus (NDV) AMHA1 is capable of killing cancer cells by direct replication or induction of apoptosis alongside other pathways. In this study, we report the potent antimetastatic and anticancer activities of NDV AMHA1 in a 3D spheroid model of breast cancer metastasis.Methodswe used two breast cancer cell lines AMJ13 and MCF7 in our metastasis model system.ResultsFirst, we showed that NDV AMHA1 can infect and kill breast cancer cells in proliferating adherent cells and tumor spheroids using different virus doses and studying virus replication kinetics. We showed that NDV can infect and spread within the spheroids that represent metastasis before and after reattachment. Furthermore, we evaluated the ability of NDV to induce apoptosis in cancer spheroids and by virus tracking showed that NDV infection is essential for the elimination of these metastasis spheroids.DiscussionThe mechanism by which NDV induces cell killing in the metastasis model is the induction of caspase-3 and P21 and inhibition of Ki67 in cancer cells, but not in normal cells. In conclusion, these results indicate that NDV AMHA1 has the ability to kill breast cancer metastases in suspension or attached, and this is a novel finding of NDV AMHA1 being a possibly efficient therapy against human metastatic breast cancer.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative proteomics analysis of the mouse mini-gut organoid: insights into markers of gluten challenge from celiac disease intestinal biopsies 小鼠微型肠器官比较蛋白质组学分析:从乳糜泻肠道活检样本中了解麸质挑战的标志物
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-28 DOI: 10.3389/fmolb.2024.1446822
Robert Moulder, Santosh D. Bhosale, Keijo Viiri, Riitta Lahesmaa
{"title":"Comparative proteomics analysis of the mouse mini-gut organoid: insights into markers of gluten challenge from celiac disease intestinal biopsies","authors":"Robert Moulder, Santosh D. Bhosale, Keijo Viiri, Riitta Lahesmaa","doi":"10.3389/fmolb.2024.1446822","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1446822","url":null,"abstract":"IntroductionOrganoid models enable three-dimensional representation of cellular systems, providing flexible and accessible research tools, and can highlight key biomolecules. Such models of the intestinal epithelium can provide significant knowledge for the study of celiac disease and provide an additional context for the nature of markers observed from patient biopsy data.MethodsUsing LC–MS/MS, the proteomes of the crypt and enterocyte-like states of a mouse mini-gut organoid model were measured. The data were further compared with published biopsy data by comparing the changes induced by gluten challenge after a gluten-free diet.Results and discussionThese analyses identified 4,850 protein groups and revealed how 400 putative biomarkers of dietary challenge were differentially expressed in the organoid model. In addition to the extensive changes within the differentiated cells, the data reiterated the disruption of the crypt–villus axis after gluten challenge. The mass spectrometry data are available via ProteomeXchange with the identifier PXD025690.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasma metabolites as potential markers and targets to prevent and treat urolithiasis: a Mendelian randomization study 血浆代谢物作为预防和治疗尿路结石的潜在标志物和靶点:孟德尔随机研究
IF 5 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-27 DOI: 10.3389/fmolb.2024.1426575
Wuhui Zhu, Huan Li, Ming Zhang, Bing Ji, Zongtao Liu
{"title":"Plasma metabolites as potential markers and targets to prevent and treat urolithiasis: a Mendelian randomization study","authors":"Wuhui Zhu, Huan Li, Ming Zhang, Bing Ji, Zongtao Liu","doi":"10.3389/fmolb.2024.1426575","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1426575","url":null,"abstract":"BackgroundStudies on the relationships between diseases of the urinary system and human plasma proteomes have identified several potential biomarkers. However, none of these studies have elucidated the causal relationships between plasma proteins and urolithiasis.ObjectiveThe objective of the study was to investigate the potential risks of plasma metabolites in urolithiasis using a two-sample Mendelian randomization (MR) study.MethodsA total of 1,400 metabolites were identified in the most comprehensive genome-wide association study (GWAS) of plasma metabolomics in a European population to date, and single-nucleotide polymorphisms (SNPs) were used as the instrumental variables for the plasma metabolites. The European GWAS data for urinary calculi included 482,123 case samples and 6,223 control samples (ebi-a-GCST90018935). The associations between the plasma metabolites and risk of urolithiasis were evaluated by inverse variance weighting (IVW) and supplemented by sensitivity analyses of the MR-Egger and MR-PRESSO tests.ResultsFor the first time, we found a causal relationship between two plasma metabolites (<jats:italic>p</jats:italic> &amp;lt; 1.03 × 10<jats:sup>−4</jats:sup>) and urolithiasis (<jats:italic>p</jats:italic> &amp;lt; 0.05). The chemical 4-hydroxychlorothalonil, which is an intermediate product of the pesticide hydroxychlorothalonil, could promote urolithiasis (odds ratio (OR) = 1.12) as a risk factor. Moreover, 1-stearoyl-2-arachidonoyl-GPC, which is an important component of phospholipid metabolism in the human body, can inhibit urolithiasis (OR = 0.94).ConclusionsOur results suggest that blood metabolites can be used as blood markers and drug targets in the prevention, diagnosis, and treatment of urolithiasis; furthermore, our results can provide a basis for policy makers to formulate prevention and treatment policies for urolithiasis.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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