Biomarker Research最新文献

{"title":"Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke.","authors":"Liangzhe Wei, Siqi Chen, Xinpeng Deng, Yuchun Liu, Haifeng Wang, Xiang Gao, Yi Huang","doi":"10.1186/s40364-024-00608-7","DOIUrl":"10.1186/s40364-024-00608-7","url":null,"abstract":"<p><p>Ischemic stroke (IS), a devastating cerebrovascular accident, presents with high mortality and morbidity. Following IS onset, a cascade of pathological changes, including excitotoxicity, inflammatory damage, and blood-brain barrier disruption, significantly impacts prognosis. However, current clinical practices struggle with early diagnosis and identifying these alterations. Metabolomics, a powerful tool in systems biology, offers a promising avenue for uncovering early diagnostic biomarkers for IS. By analyzing dynamic metabolic profiles, metabolomics can not only aid in identifying early IS biomarkers but also evaluate Traditional Chinese Medicine (TCM) efficacy and explore its mechanisms of action in IS treatment. Animal studies demonstrate that TCM interventions modulate specific metabolite levels, potentially reflecting their therapeutic effects. Identifying relevant metabolites in cerebral ischemia patients holds immense potential for early diagnosis and improved outcomes. This review focuses on recent metabolomic discoveries of potential early diagnostic biomarkers for IS. We explore variations in metabolites observed across different ages, genders, disease severity, and stages. Additionally, the review examines how specific TCM extracts influence IS development through metabolic changes, potentially revealing their mechanisms of action. Finally, we emphasize the importance of integrating metabolomics with other omics approaches for a comprehensive understanding of IS pathophysiology and TCM efficacy, paving the way for precision medicine in IS management.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433353","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 CDK9 inhibitor enitociclib overcomes resistance to BTK inhibition and CAR-T therapy in mantle cell lymphoma.","authors":"Vivian Jiang, William Lee, Tianci Zhang, Alexa Jordan, Fangfang Yan, Qingsong Cai, Joseph McIntosh, Jovanny Vargas, Yang Liu, Michael Wang","doi":"10.1186/s40364-024-00589-7","DOIUrl":"10.1186/s40364-024-00589-7","url":null,"abstract":"<p><p>Inhibitors of Bruton's tyrosine kinase (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 are paradigm-shifting advances in treating patients with aggressive mantle cell lymphoma (MCL). However, clinical relapses following BTKi and CD19-directed CAR-T treatments are a fast-growing medical challenge. Development of novel therapies to overcome BTKi resistance (BTKi-R) and BTKi-CAR-T dual resistance (Dual-R) are urgently needed. Our single-cell RNA sequencing data revealed major transcriptomic reprogramming, with great enrichment of MYC-targets evolving as resistance to these therapies developed. Interestingly, cyclin-dependent kinase 9 (CDK9), a critical component of the positive transcription elongation factor-b complex, was among the top upregulated genes in Dual-R vs. BTKi-R samples. We therefore hypothesized that targeting CDK9 may turn off MYC-driven tumor survival and drug resistance. Enitociclib (formerly VIP152) is a selective CDK9 inhibitor whose potency against MCL has not been assessed. In this study, we found that enitociclib was highly potent in targeting lymphoma cells, with the half-maximal inhibitory concentration (IC₅₀) ranging from 32 to 172 nM in MCL and diffuse large B-cell lymphoma cell lines. It inhibited CDK9 phosphorylation and downstream events including de novo synthesis of the short-lived proteins c-MYC, MCL-1, and cyclin D1, and induced apoptosis in a caspase-3-dependent manner. Enitociclib potently inhibited in vivo tumor growth of cell line-derived and patient-derived xenografts having therapeutic resistance. Our data demonstrate the potency of enitociclib in overcoming therapeutic resistance in MCL models and provide evidence in favor of its clinical investigation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421868","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":"Identification of a circulating long non-coding RNA signature panel in plasma as a novel biomarker for the detection of acute/early-stage HIV-1 infection.","authors":"Santanu Biswas, Namrata Nagarajan, Indira Hewlett, Krishnakumar Devadas","doi":"10.1186/s40364-024-00597-7","DOIUrl":"10.1186/s40364-024-00597-7","url":null,"abstract":"<p><strong>Background: </strong>Individuals with acute / early HIV-1 infection are often unaware that they are infected with HIV-1 and may be involved in high-risk behavior leading to transmission of HIV-1. Identifying individuals with acute / early HIV-1 infection is critical to prevent further HIV-1 transmission, as diagnosis can lead to several effective HIV-1 prevention strategies. Identification of disease-stage specific non-viral host biomarkers would be useful as surrogate markers to accurately identify new HIV-1 infections. The goal of this study was to identify a panel of host derived plasma long non-coding RNAs (lncRNAs) that could serve as prognostic and predictive biomarkers to detect early/acute HIV-1 infection.</p><p><strong>Methods: </strong>A total of 84 lncRNAs were analyzed in sixteen plasma samples from HIV-1 infected individuals and four healthy controls using the lncRNA PCR-array. Twenty-one lncRNAs were selected and validated in 80 plasma samples from HIV-1 infected individuals [HIV-1 infected patients in the eclipse stage (n = 20), acute stage (n = 20), post-seroconversion p31 negative stage (n = 20), and post-seroconversion p31 positive stage (n = 20) of infection] and 20 healthy controls. The validation study results were used to develop a plasma lncRNA panel that was evaluated in the panel test phase to detect early/acute HIV-1 infection in 52 independent samples.</p><p><strong>Results: </strong>We identified a lncRNA panel (P_model-I) containing eight lncRNAs (DISC2, H19, IPW, KRASP1, NEAT1, PRINS, WT1-AS and ZFAS1) that could distinguish HIV-1 infection from healthy controls with high AUC 0·990 (95% CI 0.972-1.000), sensitivity (98.75%), and specificity (95%). We also found that P_model-II and P_model-III demonstrates 100% sensitivity and specificity (AUC 1·00; 95%CI:1·00-1·00) and could distinguish eclipse stage and acute stage of HIV-1 infection from healthy controls respectively. Antiretroviral treatment (ART) cumulatively restored the levels of lncRNAs to healthy controls levels.</p><p><strong>Conclusion: </strong>lncRNA expression changes significantly in response to HIV-1 infection. Our findings also highlight the potential of using circulating lncRNAs to detect both the eclipse and acute stages of HIV-1 infection, which may help to shorten the window period and facilitate early detection and treatment initiation. Initiating ART treatment at this stage would significantly reduce HIV-1 transmission. The differentially expressed lncRNAs identified in this study could serve as potential prognostic and diagnostic biomarkers of HIV-1 infection, as well as new therapeutic targets.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312275","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":"Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.","authors":"Zhiyu Zhang, Jiayi Huang, Zhibo Zhang, Hongjie Shen, Xiaowen Tang, Depei Wu, Xiebing Bao, Guoqiang Xu, Suning Chen","doi":"10.1186/s40364-024-00600-1","DOIUrl":"10.1186/s40364-024-00600-1","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the most frequent leukemia in adults with a high mortality rate. Current diagnostic criteria and selections of therapeutic strategies are generally based on gene mutations and cytogenetic abnormalities. Chemotherapy, targeted therapies, and hematopoietic stem cell transplantation (HSCT) are the major therapeutic strategies for AML. Two dilemmas in the clinical management of AML are related to its poor prognosis. One is the inaccurate risk stratification at diagnosis, leading to incorrect treatment selections. The other is the frequent resistance to chemotherapy and/or targeted therapies. Genomic features have been the focus of AML studies. However, the DNA-level aberrations do not always predict the expression levels of genes and proteins and the latter is more closely linked to disease phenotypes. With the development of high-throughput sequencing and mass spectrometry technologies, studying downstream effectors including RNA, proteins, and metabolites becomes possible. Transcriptomics can reveal gene expression and regulatory networks, proteomics can discover protein expression and signaling pathways intimately associated with the disease, and metabolomics can reflect precise changes in metabolites during disease progression. Moreover, omics profiling at the single-cell level enables studying cellular components and hierarchies of the AML microenvironment. The abundance of data from different omics layers enables the better risk stratification of AML by identifying prognosis-related biomarkers, and has the prospective application in identifying drug targets, therefore potentially discovering solutions to the two dilemmas. In this review, we summarize the existing AML studies using omics methods, both separately and combined, covering research fields of disease diagnosis, risk stratification, prognosis prediction, chemotherapy, as well as targeted therapy. Finally, we discuss the directions and challenges in the application of multi-omics in precision medicine of AML. Our review may inspire both omics researchers and clinical physicians to study AML from a different angle.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302011","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":"Gasdermin E benefits CD8⁺T cell mediated anti-immunity through mitochondrial damage to activate cGAS-STING-interferonβ axis in colorectal cancer.","authors":"Bixian Luo, Shun Zhang, Xinbo Yu, Dan Tan, Ying Wang, Mingliang Wang","doi":"10.1186/s40364-024-00606-9","DOIUrl":"10.1186/s40364-024-00606-9","url":null,"abstract":"<p><strong>Background: </strong>Pyroptosis belongs to a unique type of programmed cell death among which GSDME is reported to exert anti-tumor immunity. However, the underlying mechanisms of how to boost tumor-infiltrating lymphocytes and whether it could benefit the efficacy of ICIs are still unknown.</p><p><strong>Methods: </strong>CRC samples were used to analyze its relationship with CD8⁺T cells. GSDME in mouse CRC cell lines CT26/MC38 was overexpressed. The infiltration of CD8⁺T cells in grafted tumors was determined by multiplex flow cytometric analysis and immunohistochemistry. Transcriptomic analysis was performed in cell lines to define key signatures related to its overexpression. The mechanism of how mtDNA was released by GSDME-induced mitochondrial damage and activated cGAS-STING pathway was observed. Whether GSDME benefited ICIs and the relationships with the genotypes of CRC patients were investigated.</p><p><strong>Results: </strong>It had favorable prognostic value in CRC and was positively associated with increased number and functionality of CD8⁺T cells both in human samples and animal models. This was due to mitochondrial damage and activation of cGAS-STING-IFNβ pathway for the recruitment of CD8⁺T cells. Mechanically, GSDME overexpression enhanced N-GSDME level, leading to the mitochondrial damage and mtDNA was released into cytosol. Finally, GSDME benefited with ICIs and exhibited positive relationships with MSI in CRC patients.</p><p><strong>Conclusion: </strong>We presented the mechanism of GSDME in anti-tumor immunity through activating cGAS-STING-IFNβ axis mediated by mitochondrial damage, leading to more infiltration of CD8⁺T cells with synergistic efficacy with ICIs.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297291","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":"Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations.","authors":"Chengwei Chen, Yuting Bao, Sihan Ju, Conglin Jiang, Xiang Zou, Xin Zhang, Liang Chen","doi":"10.1186/s40364-024-00603-y","DOIUrl":"10.1186/s40364-024-00603-y","url":null,"abstract":"<p><strong>Background: </strong>Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development.</p><p><strong>Methods: </strong>Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs.</p><p><strong>Results: </strong>Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis.</p><p><strong>Conclusion: </strong>This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes-PFDN4, CEMIP, and BTBD10-may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248993","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":"Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma","authors":"Liyuan Dai, Guangyu Fan, Tongji Xie, Lin Li, Le Tang, Haizhu Chen, Yuankai Shi, Xiaohong Han","doi":"10.1186/s40364-024-00605-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00605-w","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies. This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified. High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68+CXCL10+PD-L1+) and diminished CD8+ T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077–2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207–5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p < 0.05) in DLBCL. Immunohistochemical validation of glycolysis markers (STMN1, ENO1, PKM, and CDK1) and multiple immunofluorescence validation of IFN_TAMs underscored their prognostic value (p < 0.05) in DLBCL. This study underscores the significance of glycolysis in tumor progression and modulation of the immune microenvironment. The identified glycolysis genes and IFN_TAMs represent potential prognostic markers and therapeutic targets in DLBCL.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolites signatures of clinical response in anti-PD-1/PD-L1 based immunotherapy of biliary tract cancer.","authors":"Chengpei Zhu, Yunchao Wang, Ruijuan Zhu, Shanshan Wang, Jingnan Xue, Dongya Zhang, Zhou Lan, Chenchen Zhang, Yajun Liang, Nan Zhang, Ziyu Xun, Longhao Zhang, Cong Ning, Xu Yang, Jiashuo Chao, Junyu Long, Xiaobo Yang, Hanping Wang, Xinting Sang, Xianzhi Jiang, Haitao Zhao","doi":"10.1186/s40364-024-00607-8","DOIUrl":"10.1186/s40364-024-00607-8","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers.</p><p><strong>Methods: </strong>This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored.</p><p><strong>Results: </strong>Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy.</p><p><strong>Conclusions: </strong>Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238827","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":"Single-cell and spatial transcriptomics reveal alterations in trophoblasts at invasion sites and disturbed myometrial immune microenvironment in placenta accreta spectrum disorders.","authors":"Kaiyuan Ji, Yunshan Chen, Xiuyu Pan, Lina Chen, Xiaodi Wang, Bolun Wen, Junjie Bao, Junmin Zhong, Zi Lv, Zheng Zheng, Huishu Liu","doi":"10.1186/s40364-024-00598-6","DOIUrl":"10.1186/s40364-024-00598-6","url":null,"abstract":"<p><strong>Background: </strong>Placenta accreta spectrum disorders (PAS) are a severe complication characterized by abnormal trophoblast invasion into the myometrium. The underlying mechanisms of PAS involve a complex interplay of various cell types and molecular pathways. Despite its significance, both the characteristics and intricate mechanisms of this condition remain poorly understood.</p><p><strong>Methods: </strong>Spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq), were performed on the tissue samples from four PAS patients, including invasive tissues (ST, n = 3; scRNA-seq, n = 4), non-invasive normal placenta samples (ST, n = 1; scRNA-seq, n = 2). Three healthy term pregnant women provided normal myometrium samples (ST, n = 1; scRNA-seq, n = 2). ST analysis characterized the spatial expression landscape, and scRNA-seq was used to identify specific cellular components in PAS. Immunofluorescence staining was conducted to validate the findings.</p><p><strong>Results: </strong>ST slices distinctly showed the myometrium in PAS was invaded by three subpopulations of trophoblast cells, extravillous trophoblast cells, cytotrophoblasts, and syncytiotrophoblasts, especially extravillous trophoblast cells. The pathways enriched by genes in trophoblasts, smooth muscle cells (SMC), and immune cells of PAS were mainly associated with immune and inflammation. We identified elevated expression of the angiogenesis-stimulating gene PTK2, alongside the cell proliferation-enhancing gene EGFR, within the trophoblasts of PAS group. Trophoblasts mainly contributed the enhancement of HLA-G and EBI3 signaling, which is crucial in establishing immune escape. Meanwhile, SMC regions in PAS exhibited upregulation of immunomodulatory markers such as CD274, HAVCR2, and IDO1, with CD274 expression experimentally verified to be increased in the invasive SMC areas of the PAS group.</p><p><strong>Conclusions: </strong>This study provided information of cellular composition and spatial organization in PAS at single-cell and spatial level. The dysregulated expression of genes in PAS revealed a complex interplay between enhanced immune escape in trophoblasts and immune tolerance in SMCs during invasion in PAS. These findings will enhance our understanding of PAS pathogenesis for developing potential therapeutic strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238828","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":"CRISPR/Cas-based CAR-T cells: production and application.","authors":"Ping Song, Qiqi Zhang, Zhiyong Xu, Yueli Shi, Ruirui Jing, Dingcun Luo","doi":"10.1186/s40364-024-00602-z","DOIUrl":"10.1186/s40364-024-00602-z","url":null,"abstract":"<p><p>Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment approach for cancer, autoimmune disease, and heart disease. The integration of CAR into T cells is typically facilitated by retroviral or lentiviral vectors. However, the random insertion of CARs can lead to issues like clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing. The advent of precise gene editing technology, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), allows for controlled and precise genome modification, facilitating the translation of CAR-T research to the clinical applications. This review aims to provide a comprehensive analysis of the application of CRISPR gene editing techniques in the context of precise deletion and insertion methodologies, with a specific focus on their potential for enhancing the development and utilization of CAR-T cell therapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181171","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}