{"title":"Tumorigenicity risk of iPSCs in vivo: nip it in the bud","authors":"Chaoliang Zhong, Miao Liu, Xinghua Pan, Haiying Zhu","doi":"10.1093/pcmedi/pbac004","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac004","url":null,"abstract":"Abstract In 2006, Takahashi and Yamanaka first created induced pluripotent stem cells from mouse fibroblasts via the retroviral introduction of genes encoding the transcription factors Oct3/4, Sox2, Klf44, and c-Myc. Since then, the future clinical application of somatic cell reprogramming technology has become an attractive research topic in the field of regenerative medicine. Of note, considerable interest has been placed in circumventing ethical issues linked to embryonic stem cell research. However, tumorigenicity, immunogenicity, and heterogeneity may hamper attempts to deploy this technology therapeutically. This review highlights the progress aimed at reducing induced pluripotent stem cells tumorigenicity risk and how to assess the safety of induced pluripotent stem cells cell therapy products.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76213327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liting You, Juan Zhou, Zhaodan Xin, J Spencer Hauck, Feifei Na, Jie Tang, Xiaohan Zhou, Zichen Lei, Binwu Ying
{"title":"Novel directions of precision oncology: circulating microbial DNA emerging in cancer-microbiome areas.","authors":"Liting You, Juan Zhou, Zhaodan Xin, J Spencer Hauck, Feifei Na, Jie Tang, Xiaohan Zhou, Zichen Lei, Binwu Ying","doi":"10.1093/pcmedi/pbac005","DOIUrl":"10.1093/pcmedi/pbac005","url":null,"abstract":"<p><p>Microbiome research has extended into the cancer area in the past decades. Microbes can affect oncogenesis, progression, and treatment response through various mechanisms, including direct regulation and indirect impacts. Microbiota-associated detection methods and agents have been developed to facilitate cancer diagnosis and therapy. Additionally, the cancer microbiome has recently been redefined. The identification of intra-tumoral microbes and cancer-related circulating microbial DNA (cmDNA) has promoted novel research in the cancer-microbiome area. In this review, we define the human system of commensal microbes and the cancer microbiome from a brand-new perspective and emphasize the potential value of cmDNA as a promising biomarker in cancer liquid biopsy. We outline all existing studies on the relationship between cmDNA and cancer and the outlook for potential preclinical and clinical applications of cmDNA in cancer precision medicine, as well as critical problems to be overcome in this burgeoning field.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75106826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in single-cell sequencing technologies.","authors":"Lu Wen, Fuchou Tang","doi":"10.1093/pcmedi/pbac002","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac002","url":null,"abstract":"<p><p>Single-cell omics sequencing was first achieved for the transcriptome in 2009, which was followed by fast development of technologies for profiling the genome, DNA methylome, 3D genome architecture, chromatin accessibility, histone modifications, etc., in an individual cell. In this review we mainly focus on the recent progress in four topics in the single-cell omics field: single-cell epigenome sequencing, single-cell genome sequencing for lineage tracing, spatially resolved single-cell transcriptomics and third-generation sequencing platform-based single-cell omics sequencing. We also discuss the potential applications and future directions of these single-cell omics sequencing technologies for different biomedical systems, especially for the human stem cell field.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/9e/pbac002.PMC9267251.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40584404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multivariate competing endogenous RNA network characterization for cancer microRNA biomarker discovery: a novel bioinformatics model with application to prostate cancer metastasis.","authors":"Yuxin Lin, Xin Qi, Jing Chen, Bairong Shen","doi":"10.1093/pcmedi/pbac001","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac001","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) are post-transcriptional regulators with potential as biomarkers for cancer management. Data-driven competing endogenous RNA (ceRNA) network modeling is an effective way to decipher the complex interplay between miRNAs and spongers. However, there are currently no general rules for ceRNA network-based biomarker prioritization.</p><p><strong>Methods and results: </strong>In this study, a novel bioinformatics model was developed by integrating gene expression with multivariate miRNA-target data for ceRNA network-based biomarker discovery. Compared with traditional methods, the structural vulnerability in the human long non-coding RNA (lncRNA)-miRNA-messenger RNAs (mRNA) network was comprehensively analyzed, and the single-line regulatory or competing mode among miRNAs, lncRNAs, and mRNAs was characterized and quantified as statistical evidence for miRNA biomarker identification. The application of this model to prostate cancer (PCa) metastasis identified a total of 12 miRNAs as putative biomarkers from the metastatic PCa-specific lncRNA-miRNA-mRNA network and nine of them have been previously reported as biomarkers for PCa metastasis. The receiver operating characteristic curve and cell line qRT-PCR experiments demonstrated the power of <i>miR-26b-5p, miR-130a-3p</i>, and <i>miR-363-3p</i> as novel candidates for predicting PCa metastasis. Moreover, PCa-associated pathways such as prostate cancer signaling, <i>ERK/MAPK</i> signaling, and <i>TGF-β</i> signaling were significantly enriched by targets of identified miRNAs, indicating the underlying mechanisms of miRNAs in PCa carcinogenesis.</p><p><strong>Conclusions: </strong>A novel ceRNA-based bioinformatics model was proposed and applied to screen candidate miRNA biomarkers for PCa metastasis. Functional validations using human samples and clinical data will be performed for future translational studies on the identified miRNAs.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2022-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40587482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management of severe asthma: from stepwise approach to therapy to treatable traits?","authors":"Gang Wang, V. McDonald, P. Gibson","doi":"10.1093/pcmedi/pbab028","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab028","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89285774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenxin Luo, Zhoufeng Wang, Ting Zhang, Lan Yang, Jinghong Xian, Yalun Li, Weimin Li
{"title":"Immunotherapy in non-small cell lung cancer: rationale, recent advances and future perspectives.","authors":"Wenxin Luo, Zhoufeng Wang, Ting Zhang, Lan Yang, Jinghong Xian, Yalun Li, Weimin Li","doi":"10.1093/pcmedi/pbab027","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab027","url":null,"abstract":"<p><p>Lung cancer, with non-small cell lung cancer (NSCLC) being the major type, is the second most common malignancy and the leading cause of cancer-related death globally. Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has been one of the greatest advances in recent years for the treatment of solid tumors including NSCLC. However, not all NSCLC patients experience an effective response to immunotherapy with the established selection criteria of programmed death ligand 1 (PD-L1) and tumor mutational burden (TMB). Furthermore, a considerable proportion of patients experience unconventional responses, including pseudoprogression or hyperprogressive disease (HPD), immune-related toxicities, and primary or acquired resistance during the immunotherapy process. To better understand the immune response in NSCLC and provide reference for clinical decision-making, we herein review the rationale and recent advances in using immunotherapy to treat NSCLC. Moreover, we discuss the current challenges and future strategies of this approach to improve its efficacy and safety in treating NSCLC.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chong Zhang, Jionghui Gu, Yangyang Zhu, Zheling Meng, Tong Tong, Dongyang Li, Zhenyu Liu, Yang Du, Kun Wang, Jie Tian
{"title":"AI in spotting high-risk characteristics of medical imaging and molecular pathology","authors":"Chong Zhang, Jionghui Gu, Yangyang Zhu, Zheling Meng, Tong Tong, Dongyang Li, Zhenyu Liu, Yang Du, Kun Wang, Jie Tian","doi":"10.1093/pcmedi/pbab026","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab026","url":null,"abstract":"Abstract Medical imaging provides a comprehensive perspective and rich information for disease diagnosis. Combined with artificial intelligence technology, medical imaging can be further mined for detailed pathological information. Many studies have shown that the macroscopic imaging characteristics of tumors are closely related to microscopic gene, protein and molecular changes. In order to explore the function of artificial intelligence algorithms in in-depth analysis of medical imaging information, this paper reviews the articles published in recent years from three perspectives: medical imaging analysis method, clinical applications and the development of medical imaging in the direction of pathological molecular prediction. We believe that AI-aided medical imaging analysis will be extensively contributing to precise and efficient clinical decision.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83416902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huimin Chen, Xiaohan Wu, Chunjin Xu, Jian Lin, Zhanju Liu
{"title":"Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases","authors":"Huimin Chen, Xiaohan Wu, Chunjin Xu, Jian Lin, Zhanju Liu","doi":"10.1093/pcmedi/pbab025","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab025","url":null,"abstract":"Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81886816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Flora Yu, Lok-Ting Lau, Manson Fok, Johnson Yiu-Nam Lau, Kang Zhang
{"title":"COVID-19 Delta variants-Current status and implications as of August 2021.","authors":"Flora Yu, Lok-Ting Lau, Manson Fok, Johnson Yiu-Nam Lau, Kang Zhang","doi":"10.1093/pcmedi/pbab024","DOIUrl":"10.1093/pcmedi/pbab024","url":null,"abstract":"<p><p>The SARS-CoV-2 Delta variant has evolved as the dominant strain of the current pandemic. Studies have shown that this variant has increased infectivity/viral load, and reduced neutralization by the host antibodies from convalescent patients/vaccinees. Clinically, Delta variant infection has been observed/documented in convalescent patients/vaccinees, although with less incidence of severe diseases, but can serve as reservoir to spread the infection to the unvaccinated. The current understanding (as of 18 August 2021) on the virologic aspect (including the amino acid substitutions), clinical implications, and public health implications will be discussed in this mini review, and recommendations to health authorities will be provided.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2021-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84996570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhihan Wang, Kai Guo, Pan Gao, Qinqin Pu, Changlong Li, Junguk Hur, Min Wu
{"title":"Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications.","authors":"Zhihan Wang, Kai Guo, Pan Gao, Qinqin Pu, Changlong Li, Junguk Hur, Min Wu","doi":"10.1093/pcmedi/pbab022","DOIUrl":"10.1093/pcmedi/pbab022","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. The lack of time for new drug discovery and the urgent need for rapid disease control to reduce mortality have led to a search for quick and effective alternatives to novel therapeutics, for example drug repurposing. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from patients with mild and severe COVID-19 (GEO: GSE145926, public data available and accessed on 22 April 2020). We identified 281 FDA-approved drugs that have the potential to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested and demonstrated the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a, two chemical inhibitors of glycosylation (a post-translational modification) on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus as well as on the transcription and translation of host cell cytokines and their regulators (IFNs and ISGs). In conclusion, we have identified and experimentally validated repurposable anti-SARS-CoV-2 and IAV drugs using a systems biology approach, which may have the potential for treating these viral infections and their complications (sepsis).</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/27/d2/pbab022.PMC8694063.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39792606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}