Epma Journal最新文献

{"title":"Machine learning-couched treatment algorithms tailored to individualized profile of patients with primary anterior chamber angle closure predisposed to the glaucomatous optic neuropathy.","authors":"Natalia I Kurysheva,&nbsp;Oxana Y Rodionova,&nbsp;Alexey L Pomerantsev,&nbsp;Galina A Sharova,&nbsp;Olga Golubnitschaja","doi":"10.1007/s13167-023-00337-1","DOIUrl":"10.1007/s13167-023-00337-1","url":null,"abstract":"<p><strong>Background: </strong>Primary angle closure glaucoma (PACG) is still one of the leading causes of irreversible blindness, with a trend towards an increase in the number of patients to 32.04 million by 2040, an increase of 58.4% compared with 2013. Health risk assessment based on multi-level diagnostics and machine learning-couched treatment algorithms tailored to individualized profile of patients with primary anterior chamber angle closure are considered essential tools to reverse the trend and protect vulnerable subpopulations against health-to-disease progression.</p><p><strong>Aim: </strong>To develop a methodology for personalized choice of an effective method of primary angle closure (PAC) treatment based on comparing the prognosis of intraocular pressure (IOP) changes due to laser peripheral iridotomy (LPI) or lens extraction (LE).</p><p><strong>Methods: </strong>The multi-parametric data analysis was used to develop models predicting individual outcomes of the primary angle closure (PAC) treatment with LPI and LE. For doing this, we suggested a positive dynamics in the intraocular pressure (IOP) after treatment, as the objective measure of a successful treatment. Thirty-seven anatomical parameters have been considered by applying artificial intelligence to the prospective study on 30 (LE) + 30 (LPI) patients with PAC.</p><p><strong>Results and data interpretation in the framework of 3p medicine: </strong>Based on the anatomical and topographic features of the patients with PAC, mathematical models have been developed that provide a personalized choice of LE or LPI in the treatment. Multi-level diagnostics is the key tool in the overall advanced approach. To this end, for the future application of AI in the area, it is strongly recommended to consider the following:Clinically relevant phenotyping applicable to advanced population screeningSystemic effects causing suboptimal health conditions considered in order to cost-effectively protect affected individuals against health-to-disease transitionClinically relevant health risk assessment utilizing health/disease-specific molecular patterns detectable in body fluids with high predictive power such as a comprehensive tear fluid analysis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-023-00337-1.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The correlation between primary open-angle glaucoma (POAG) and gut microbiota: a pilot study towards predictive, preventive, and personalized medicine.","authors":"Si Chen,&nbsp;Nan Wang,&nbsp;Siqi Xiong,&nbsp;Xiaobo Xia","doi":"10.1007/s13167-023-00336-2","DOIUrl":"10.1007/s13167-023-00336-2","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma is the leading cause of irreversible blindness worldwide. Emerged evidence has shown that glaucoma is considered an immune system related disorder. The gut is the largest immune organ in the human body and the gut microbiota (GM) plays an irreversible role in maintaining immune homeostasis. But, how the GM influences glaucoma remains unrevealed. This study aimed at investigating the key molecules/pathways mediating the GM and the glaucoma to provide new biomarkers for future predictive, preventive, and personalized medicine.</p><p><strong>Methods: </strong>Datasets from the primary open-angle glaucoma (POAG) patients (GSE138125) and datasets for target genes of GM/GM metabolites were downloaded from a public database. For GSE138125, the differentially expressed genes (DEGs) between healthy and POAG samples were identified. And the online Venn diagram tool was used to obtain the DEGs from POAG related to GM. After which GM-related DEGs were analyzed by correlation analysis, pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Human trabecular meshwork cells were used for validation, and the mRNA level of hub genes was verified by quantitative real-time polymerase chain reaction (RT-qPCR) in the in vitro glaucoma model.</p><p><strong>Results: </strong>A total of 16 GM-related DEGs in POAG were identified from the above 2 datasets (9 upregulated genes and 7 downregulated genes). Pathway enrichment analysis indicated that these genes are mostly enriched in immune regulation especially macrophages-related pathways. Then 6 hub genes were identified by PPI network analysis and construction of key modules. Finally, RT-qPCR confirmed that the expression of the hub genes in the in vitro glaucoma model was consistent with the results of bioinformatics analysis of the mRNA chip.</p><p><strong>Conclusion: </strong>This bioinformatic study elucidates NFKB1, IL18, KITLG, TLR9, FKBP2, and HDAC4 as hub genes for POAG and GM regulation. Immune response modulated by macrophages plays an important role in POAG and may be potential targets for future predictive, preventive, and personalized diagnosis and treatment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-023-00336-2.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10050288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative phosphoproteomics reveals molecular pathway network alterations in human early-stage primary hepatic carcinomas: potential for 3P medical approach.","authors":"Yuping Zhang, Na Li, Lamei Yang, Wenshuang Jia, Zhijun Li, Qianwen Shao, Xianquan Zhan","doi":"10.1007/s13167-023-00335-3","DOIUrl":"10.1007/s13167-023-00335-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Hepatic carcinoma is one of the most common types of malignant tumors in the digestive system, and its biological characteristics determine its high rate of metastasis and recurrence after radical resection, leading to a poor prognosis for patients. Increasing evidence demonstrates that phosphoproteins and phosphorylation-mediated molecular pathways influence the occurrence and development of hepatic carcinoma. It is urgent need to develop early-stage biomarkers for improving diagnosis, therapy, medical service, and prognostic assessment. We hypothesize that phosphoproteome and phosphorylation-mediated signaling pathway networks significantly differ in human early-stage primary hepatic carcinomas relative to control liver tissues, which will identify the key differentially phosphorylated proteins and phosphorylation-mediated signaling pathway network alterations in human early-stage primary hepatic carcinoma to innovate predictive diagnosis, prognostic assessment, and personalized medical services and progress beyond the state of the art in the framework of predictive, preventive, and personalized medicine (PPPM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Tandem mass tag (TMT)-based quantitative proteomics coupled with TiO&lt;sub&gt;2&lt;/sub&gt; enrichment of phosphopeptides was used to identify phosphorylation profiling, and bioinformatics was used to analyze the pathways and biological functions of phosphorylation profiling between early-stage hepatic carcinoma tissues and tumor-adjacent normal control tissues. Furthermore, the integrative analysis with transcriptomic data from TCGA database obtained differently expressed genes (DEGs) corresponding to differentially phosphorylated proteins (DPPs) and overall survival (OS)-related DPPs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 1326 phosphopeptides derived from 858 DPPs in human early-stage primary hepatic carcinoma were identified. KEGG pathway network analysis of 858 DPPs revealed 33 statistically significant signaling pathways, including spliceosome, glycolysis/gluconeogenesis, B-cell receptor signaling pathway, HIF-1 signaling pathway, and fatty acid degradation. Gene Ontology (GO) analysis of 858 DPPs revealed that protein phosphorylation was involved in 57 biological processes, 40 cellular components, and 37 molecular functions. Protein-protein interaction (PPI) network constructed multiple high-combined scores and co-expressed DPPs. Integrative analysis of transcriptomic data and DPP data identified 105 overlapped molecules (DPPs; DEGs) between hepatic carcinoma tissues and control tissues and 125 OS-related DPPs. Overlapping Venn plots showed 14 common molecules among datasets of DPPs, DEGs, and OS-related DDPs, including FTCD, NDRG2, CCT2, PECR, SLC23A2, PNPLA7, ANLN, HNRNPM, HJURP, MCM2, STMN1, TCOF1, TOP2A, and SSRP1. The drug sensitivities of OS-related DPPs were identified, including LMOD1, CAV2, UBE2E2, RAPH1, ANXA5, HDLBP, CUEDC1, APBB1IP, VCL, SRSF10, SLC23A2, EPB41L2,","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying oxidative stress-related biomarkers in idiopathic pulmonary fibrosis in the context of predictive, preventive, and personalized medicine using integrative omics approaches and machine-learning strategies.","authors":"Fan Yang, Wendusubilige, Jingwei Kong, Yuhan Zong, Manting Wang, Chuanqing Jing, Zhaotian Ma, Wanyang Li, Renshuang Cao, Shuwen Jing, Jie Gao, Wenxin Li, Ji Wang","doi":"10.1007/s13167-023-00334-4","DOIUrl":"10.1007/s13167-023-00334-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis that currently lacks effective treatment methods. Preventing the acute exacerbation of IPF, identifying the molecular subtypes of patients, providing personalized treatment, and developing individualized drugs are guidelines for predictive, preventive, and personalized medicine (PPPM / 3PM) to promote the development of IPF. Oxidative stress (OS) is an important pathological process of IPF. However, the relationship between the expression levels of oxidative stress-related genes (OSRGs) and clinical indices in patients with IPF is unclear; therefore, it is still a challenge to identify potential beneficiaries of antioxidant therapy. Because PPPM aims to recognize and manage diseases by integrating multiple methods, patient stratification and analysis based on OSRGs and identifying biomarkers can help achieve the above goals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptome data from 250 IPF patients were divided into training and validation sets. Core OSRGs were identified in the training set and subsequently clustered to identify oxidative stress-related subtypes. The oxidative stress scores, clinical characteristics, and expression levels of senescence-associated secretory phenotypes (SASPs) of different subtypes were compared to identify patients who were sensitive to antioxidant therapy to conduct differential gene functional enrichment analysis and predict potential therapeutic drugs. Diagnostic markers between subtypes were obtained by integrating multiple machine learning methods, their expression levels were tested in rat models with different degrees of pulmonary fibrosis and validation sets, and nomogram models were constructed. CIBERSORT, single-cell RNA sequencing, and immunofluorescence staining were used to explore the effects of OSRGs on the immune microenvironment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Core OSRGs classified IPF into two subtypes. Patients classified into subtypes with low oxidative stress levels had better clinical scores, less severe fibrosis, and lower expression of SASP-related molecules. A reliable nomogram model based on five diagnostic markers was constructed, and these markers' expression stability was verified in animal experiments. The number of neutrophils in the immune microenvironment was significantly different between the two subtypes and was closely related to the degree of fibrosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Within the framework of PPPM, this work comprehensively explored the role of OSRGs and their mediated cellular senescence and immune processes in the progress of IPF and assessed their capabilities aspredictors of high oxidative stress and disease progression,targets of the vicious loop between regulated pulmonary fibrosis and OS for targeted secondary and tertiary prevention, andreferences for personalized antioxidant and antifibrotic therapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Supplement","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Royal jelly: a predictive, preventive and personalised strategy for novel treatment options in non-communicable diseases.","authors":"Beatriz G Baptista, Ligia S Lima, Marcia Ribeiro, Isadora K Britto, Livia Alvarenga, Julie A Kemp, Ludmila Fmf Cardozo, Andresa A Berretta, Denise Mafra","doi":"10.1007/s13167-023-00330-8","DOIUrl":"10.1007/s13167-023-00330-8","url":null,"abstract":"<p><p>Royal jelly (RJ) is a bee product produced by young adult worker bees, composed of water, proteins, carbohydrates and lipids, rich in bioactive components with therapeutic properties, such as free fatty acids, mainly 10-hydroxy-trans-2-decenoic acid (10-H2DA) and 10-hydroxydecanoic acid (10-HDA), and major royal jelly proteins (MRJPs), as well as flavonoids, most flavones and flavonols, hormones, vitamins and minerals. In vitro, non-clinical and clinical studies have confirmed its vital role as an antioxidant and anti-inflammatory. This narrative review discusses the possible effects of royal jelly on preventing common complications of non-communicable diseases (NCDs), such as inflammation, oxidative stress and intestinal dysbiosis, from the viewpoint of predictive, preventive and personalised medicine (PPPM/3PM). It is concluded that RJ, predictively, can be used as a non-pharmacological therapy to prevent and mitigate complications related to NCDs, and the treatment must be personalised.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 lessons to protect populations against future pandemics by implementing PPPM principles in healthcare.","authors":"Cuihong Tian,&nbsp;Lois Balmer,&nbsp;Xuerui Tan","doi":"10.1007/s13167-023-00331-7","DOIUrl":"10.1007/s13167-023-00331-7","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic has continued for more than 3 years, placing a huge burden on society worldwide. Although the World Health Organization (WHO) has declared an end to COVID-19 as a Public Health Emergency of International Concern (PHEIC), it is still considered a global threat. Previously, there has been a long debate as to whether the COVID-19 emergency will eventually end or transform into a more common infectious disease from a PHEIC, and how should countries respond to similar pandemics in the future more time-efficiently and cost-effectively. We reviewed the past, middle and current situation of COVID-19 based on bibliometric analysis and epidemiological data. Thereby, the necessity is indicated to change the paradigm from reactive healthcare services to predictive, preventive and personalised medicine (PPPM) approach, in order to effectively protect populations against COVID-19 and any future pandemics. Corresponding measures are detailed in the article including the involvement of multi-professional expertise, application of artificial intelligence, rapid diagnostics and patient stratification, and effective protection, amongst other to be considered by advanced health policy.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomic characteristics of shoulder based on MRI accurately predict incomplete rotator cuff injuries in patients: relevance for predictive, preventive, and personalized healthcare strategies.","authors":"Hangxing Wu, Zhijie Zuo, Yucong Li, Haoqiang Song, Wanyan Hu, Jingle Chen, Chao Xie, Lijun Lin","doi":"10.1007/s13167-023-00333-5","DOIUrl":"10.1007/s13167-023-00333-5","url":null,"abstract":"<p><strong>Background and pppm-related working hypothesis: </strong>In the diagnosis of incomplete rotator cuff injuries (IRCI), magnetic resonance imaging (MRI) and ultrasound examination often have false-positive and false-negative results, while arthroscopy is expensive, invasive, and complex. From the strategy of predictive, preventive, and personalized medicine (PPPM), shoulder anatomical characteristics based on MRI have been demonstrated to accurately predict IRCI and their clinical applicability for personalized prediction of IRCI.</p><p><strong>Aims: </strong>This study aimed to develop and validate a nomogram based on anatomical features of the shoulder on MRI to identify IRCI for PPPM healthcare strategies.</p><p><strong>Methods: </strong>The medical information of 257 patients undergoing preoperative MRI examination was retrospectively reviewed and served as the primary cohort. Partial-thickness rotator cuff tears (RCTs) and tendinopathy observed under arthroscopy were considered IRCI. Using logistic regression analyses and least absolute shrinkage and selection operator (LASSO), IRCI was identified among various preoperative factors containing shoulder MRI and clinical features. A nomogram was constructed and subjected to internal and external validations (80 patients).</p><p><strong>Results: </strong>The following eight independent risk factors for IRCI were identified:AgeThe left injured sidesThe Goutallier classification of supraspinatus in oblique coronal positionThe Goutallier classification of supraspinatus in the axial positionAcromial thicknessAcromiohumeral distanceCoracohumeral distanceAbnormal acromioclavicular joint signalsThe nomogram accurately predicted IRCI in the development (C-index, 0.932 (95% CI, 0.891, 0.973)) and validation (C-index, 0.955 (95% CI, 0.918, 0.992)) cohorts. The calibration curve was consistent between the predicted IRCI probability and the actual IRCI ratio of the nomogram. The decision curve analysis and clinical impact curves demonstrated that the model had high clinical applicability.</p><p><strong>Conclusions: </strong>Eight independent factors that accurately predicted IRCI were determined using MRI anatomical findings. These personalized factors can prevent unnecessary diagnostic interventions (e.g., arthroscopy) and can assist surgeons in implementing individualized clinical decisions in medical practice, thus addressing the goals of PPPM.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-023-00333-5.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically predicted the causal relationship between gut microbiota and infertility: bidirectional Mendelian randomization analysis in the framework of predictive, preventive, and personalized medicine.","authors":"Yujia Xi, Chenwei Zhang, Yiqian Feng, Shurui Zhao, Yukai Zhang, Guosheng Duan, Wei Wang, Jingqi Wang","doi":"10.1007/s13167-023-00332-6","DOIUrl":"10.1007/s13167-023-00332-6","url":null,"abstract":"<p><strong>Objective: </strong>Several studies have reported the association between gut microbiota and infertility; however, the causal association between them remains unclear. This study aimed to explore the causal relationship between gut microbiota and infertility and evaluate how specific gut microbiota can support early monitoring and prevention of infertility in the context of predictive, preventive, and personalized medicine (PPPM/3PM).</p><p><strong>Methods: </strong>The gut microbiota GWAS data included 18,340 individuals. Female infertility (6481 cases and 68,969 controls) and male infertility data (680 cases and 72,799 controls) were obtained from the FinnGen consortium. The inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran Q tests, MR-PRESSO, and leave-one-out were used as a supplement to Mendelian randomization (MR) results and sensitivity analysis.</p><p><strong>Results: </strong>The results of MR analysis indicated a significant causal association between Eubacterium oxidoreducens (OR = 2.048, <i>P</i> = 0.008), Lactococcus (OR = 1.445, <i>P</i> = 0.042), Eubacterium ventriosum (OR = 0.436, <i>P</i> = 0.018), Eubacterium rectale (OR = 0.306, <i>P</i> = 0.002), and Ruminococcaceae NK4A214 (OR = 0.537, <i>P</i> = 0.045) and male infertility. Genetically predicted Eubacterium ventriosum (OR = 0.809, <i>P</i> = 0.018), Holdemania (OR = 0.836, <i>P</i> = 0.037), Lactococcus (OR = 0.867, <i>P</i> = 0.020), Ruminococcaceae NK4A214 (OR = 0.830, <i>P</i> < 0.050), Ruminococcus torques (OR = 0.739, <i>P</i> = 0.022), and Faecalibacterium (OR = 1.311, <i>P</i> = 0.007) were associated with female infertility. Sensitivity analysis did not detect heterogeneity and pleiotropy (<i>P</i> > 0.05).</p><p><strong>Conclusions: </strong>Our results provided evidence for the causal relationship between some gut microbiota and male and female infertility. These findings might be valuable in providing personalized treatment options for preventing infertility and improving reproductive function by monitoring and regulating the gut microbiota of infertility patients in the context of PPPM. Moreover, detecting the abundance of microbiota in feces can support preventive and personalized strategies, which may benefit more infertility patients.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-023-00332-6.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitinomics revealed disease- and stage-specific patterns relevant for the 3PM approach in human sigmoid colon cancers.","authors":"Hua Yang, Na Li, Liang Chen, Lei Zhou, Yuanchen Zhou, Jixiang Liu, Wenshuang Jia, Ruofei Chen, Junwen Su, Lamei Yang, Xiaoxia Gong, Xianquan Zhan","doi":"10.1007/s13167-023-00328-2","DOIUrl":"10.1007/s13167-023-00328-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The patients with sigmoid colorectal cancer commonly show high mortality and poor prognosis. Increasing evidence has demonstrated that the ubiquitinated proteins and ubiquitination-mediated molecular pathways influence the growth and aggressiveness of colorectal cancer. It emphasizes the scientific merits of quantitative ubiquitinomics in human sigmoid colon cancer. We hypothesize that the ubiquitinome and ubiquitination-mediated pathway networks significantly differ in sigmoid colon cancers compared to controls, which offers the promise for in-depth insight into molecular mechanisms, discovery of effective therapeutic targets, and construction of reliable biomarkers in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The first ubiquitinome analysis was performed with anti-K-ε-GG antibody beads (PTMScan ubiquitin remnant motif [K-ε-GG])-based label-free quantitative proteomics and bioinformatics to identify and quantify ubiquitination profiling between sigmoid colon cancer tissues and para-carcinoma tissues. A total of 100 human sigmoid colon cancer samples that included complete clinical information and the corresponding gene expression data were obtained from The Cancer Genome Atlas (TCGA). Ubiquitination was the main way of protein degradation; the relationships between differentially ubiquitinated proteins (DUPs) and their differently expressed genes (DEGs) and between DUPs and their differentially expressed proteins (DEPs) were analyzed between cancer tissues and control tissues. The overall survival of those DUPs was obtained with Kaplan-Meier method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 1249 ubiquitinated sites within 608 DUPs were identified in human sigmoid colon cancer tissues. KEGG pathway network analysis of these DUPs revealed 35 statistically significant signaling pathways, such as salmonella infection, glycolysis/gluconeogenesis, and ferroptosis. Gene Ontology (GO) analysis of 608 DUPs revealed that protein ubiquitination was involved in 98 biological processes, 64 cellular components, 51 molecule functions, and 26 immune system processes. Protein-protein interaction (PPI) network of 608 DUPs revealed multiple high-combined scores and co-expressed DUPs. The relationship analysis between DUPs and their DEGs found 4 types of relationship models, including DUP-up (increased ubiquitination level) and DEG-up (increased gene expression), DUP-up and DEG-down (decreased gene expression), DUP-down (decreased ubiquitination level) and DEG-up, and DUP-down and DEG-down. The relationship analysis between DUPs and their DEPs found 4 types of relationship models, including DUP-up and DEP-up (increased protein expression), DUP-up and DEP-down (decreased protein expression), DUP-down and DEP-up, and DUP-down and DEP-down. Survival analysis found 46 overall survival-related DUPs in sigmoid colon cancer, and the drug sensitivity of overall sur","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone proteoformics atlas created to promote predictive, preventive, and personalized approach in overall management of pituitary neuroendocrine tumors.","authors":"Lamei Yang, Chunling Li, Tao Song, Xianquan Zhan","doi":"10.1007/s13167-023-00329-1","DOIUrl":"10.1007/s13167-023-00329-1","url":null,"abstract":"<p><p>Human growth hormone (GH) is the indispensable hormone for the maintenance of normal physiological functions of the human body, including the growth, development, metabolism, and even immunoregulation. The GH is synthesized, secreted, and stored by somatotroph cells in adenohypophysis. Abnormal GH is associated with various GH-related diseases, such as acromegaly, dwarfism, diabetes, and cancer. Currently, some studies found there are dozens or even hundreds of GH proteoforms in tissue and serum as well as a series of GH-binding protein (GHBP) proteoforms and GH receptor (GHR) proteoforms were also identified. The structure-function relationship of protein hormone proteoforms is significantly important to reveal their overall physiological and pathophysiological mechanisms. We propose the use of proteoformics to study the relationship between every GH proteoform and different physiological/pathophysiological states to clarify the pathogenic mechanism of GH-related disease such as pituitary neuroendocrine tumor and conduct precise molecular classification to promote predictive preventive personalized medicine (PPPM / 3P medicine). This article reviews GH proteoformics in GH-related disease such as pituitary neuroendocrine tumor, which has the potential role to provide novel insight into pathogenic mechanism, discover novel therapeutic targets, identify effective GH proteoform biomarker for patient stratification, predictive diagnosis, and prognostic assessment, improve therapy method, and further accelerate the development of 3P medicine.</p>","PeriodicalId":54292,"journal":{"name":"Epma Journal","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}