J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason
{"title":"Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.","authors":"J Sebastian Garcia-Medina, Karolina Sienkiewicz, S Anand Narayanan, Eliah G Overbey, Kirill Grigorev, Krista A Ryon, Marissa Burke, Jacqueline Proszynski, Braden Tierney, Caleb M Schmidt, Nuria Mencia-Trinchant, Remi Klotz, Veronica Ortiz, Jonathan Foox, Christopher Chin, Deena Najjar, Irina Matei, Irenaeus Chan, Carlos Cruchaga, Ashley Kleinman, JangKeun Kim, Alexander Lucaci, Conor Loy, Omary Mzava, Iwijn De Vlaminck, Anvita Singaraju, Lynn E Taylor, Julian C Schmidt, Michael A Schmidt, Kelly Blease, Juan Moreno, Andrew Boddicker, Junhua Zhao, Bryan Lajoie, Andrew Altomare, Semyon Kruglyak, Shawn Levy, Min Yu, Duane C Hassane, Susan M Bailey, Kelly Bolton, Jaime Mateus, Christopher E Mason","doi":"10.1093/pcmedi/pbae007","DOIUrl":"10.1093/pcmedi/pbae007","url":null,"abstract":"<p><strong>Background: </strong>The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.</p><p><strong>Methods: </strong>To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden.</p><p><strong>Result: </strong>Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.</p><p><strong>Conclusion: </strong>Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"7 1","pages":"pbae007"},"PeriodicalIF":5.1,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858430","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":"Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging.","authors":"Qixiang Gui, Neng Ding, Zuochao Yao, Minjuan Wu, Ruifeng Fu, Yue Wang, Yunpeng Zhao, Lie Zhu","doi":"10.1093/pcmedi/pbae004","DOIUrl":"10.1093/pcmedi/pbae004","url":null,"abstract":"<p><p>Owing to its constant exposure to the external environment and various stimuli, skin ranks among the organs most vulnerable to manifestations of aging. Preventing and delaying skin aging has become one of the prominent research subjects in recent years. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential. MSC-derived extracellular vesicles (MSC-EVs) are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior. Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory, anti-oxidative stress, and wound healing promoting abilities. This review presents the latest progress of MSC-EVs in delaying skin aging. It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts, reducing the expression of matrix metalloproteinases, resisting oxidative stress, and regulating inflammation. We then briefly discuss the recently discovered treatment methods of MSC-EVs in the field of skin anti-aging. Moreover, the advantages and limitations of EV-based treatments are also presented.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"7 1","pages":"pbae004"},"PeriodicalIF":5.3,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185854","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}
Zhen Zeng, Mingshan Jiang, Xi Li, Jing Yuan, Hu Zhang
{"title":"Precision medicine in inflammatory bowel disease","authors":"Zhen Zeng, Mingshan Jiang, Xi Li, Jing Yuan, Hu Zhang","doi":"10.1093/pcmedi/pbad033","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad033","url":null,"abstract":"\u0000 Inflammatory bowel disease (IBD) is an incurable disease characterized by remission-relapse cycles throughout its course. Both Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of IBD, exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse, thus posing great challenges to the clinical management for IBD. Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD. Recent advances in studies of genetics, pharmacogenetics, proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response, which should help clinicians manage IBD patients more effectively, and then, improve clinical outcomes and reduce treatment costs of patients. In this review, we summarize and discuss precision medicine in IBD, focusing on predictive markers of disease course and treatment response, and monitoring indices during therapeutic drug monitoring.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"143 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138965021","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}
{"title":"The significance of long non-coding RNAs in the pathogenesis, diagnosis and treatment of inflammatory bowel disease.","authors":"Fei Jiang, Min Wu, Rongpeng Li","doi":"10.1093/pcmedi/pbad031","DOIUrl":"10.1093/pcmedi/pbad031","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBD) are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence. Although the pathomechanism of IBD has been extensively investigated, several aspects of its pathogenesis remain unclear. Long non-coding RNAs (lncRNAs) are transcripts with more than 200 nucleotides in length that have potential protein-coding functions. LncRNAs play important roles in biological processes such as epigenetic modification, transcriptional regulation and post-transcriptional regulation. In this review, we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment, as well as their potential roles as immune regulators, diagnostic biomarkers and therapeutic targets or agents for IBD.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"6 4","pages":"pbad031"},"PeriodicalIF":5.3,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10757071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075226","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}
Chao Ye, Anmin Wang, Wei Li, Wenyuan Li, Qi shen, Zhangfei Wang, Li Xie, Qiuxia Jiang, Kaiguang Zhang, Shu Zhu
{"title":"Prealbumin as a prognostic indicator for hospital readmission of ulcerative colitis patients","authors":"Chao Ye, Anmin Wang, Wei Li, Wenyuan Li, Qi shen, Zhangfei Wang, Li Xie, Qiuxia Jiang, Kaiguang Zhang, Shu Zhu","doi":"10.1093/pcmedi/pbad026","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad026","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":" 392","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135186888","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}
{"title":"Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas","authors":"Yina Jiang, YinYing Wu, Liwen Zhang, Yan Wang, Guiping Xu, Yuan Deng, Liang Han, Enxiao Li, Qingyong Ma, Mian Xu, Zheng Wu, Zheng Wang","doi":"10.1093/pcmedi/pbad030","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad030","url":null,"abstract":"Abstract Adenosquamous carcinoma of the pancreas (ASCP) is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate. However, little is known about its genomic landscape and prognostic biomarkers. Forty-eight ASCP specimens and 98 pancreatic ductal adenocarcinoma (PDAC) tumours pecimens were sequenced to explore the genomic landscape and prognostic biomarkers. The homozygous deletion of the 9p21.3 region (including CDKN2A, CDKN2B, and MTAP) (9p21 loss) occurred in both ASCP and PDAC, and a higher frequency of 9p21 loss was observed in ASCP (12.5% vs. 2.0%, p = 0.022). Notably, 9p21 loss was significantly associated with poor disease-free survival (DFS) in ASCP patients (mDFS = 4.17 vs. 7.33 months, HR = 3.70, p = 0.009). The most common gene alterations in patients with ASCP were KRAS (96%), TP53 (81%), CDKN2A (42%), SMAD4 (21%), CDKN2B (13%), and FAT3 (13%). The mutation rates of ACVR2A (6.25% vs. 0), FANCA (6.25% vs. 0), RBM10 (6.25% vs. 0), and SPTA1 (8.33% vs. 1.02%) were significantly higher in ASCP than in PDAC. In conclusion, we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP, which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"121 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135541640","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}
{"title":"A pairwise radiomics algorithm - lesion pair relation estimation (PRE) model for distinguishing multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM)","authors":"Ting-Fei Chen, Lei Yang, Hai-Bin Chen, Zhi-Guo Zhou, Zhen-Tian Wu, Hong-He Luo, Qiong Li, Ying Zhu","doi":"10.1093/pcmedi/pbad029","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad029","url":null,"abstract":"Abstract Background Distinguishing multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM) is critical for their disparate treatment strategy and prognosis. This study aimed to establish a non-invasive model to make the differentiation pre-operatively. Methods We retrospectively studied 168 patients with multiple lung cancers (307 pairs of lesions) including 118 cases for modeling and internal validation, and 50 cases for independent external validation. Radiomic features on computed tomography (CT) were extracted to calculate the absolute deviation of paired lesions. Features were then selected by correlation coefficients and random forest classifier five-fold cross-validation, based on which the lesion pair relation estimation (PRE) model was developed. A major voting strategy was used to decide diagnosis for cases with multiple pairs of lesions. Cases from another institute were included as the external validation set for the PRE model to compete with two experienced clinicians. Results Seven radiomic features were selected for the PRE model construction. With major voting strategy, the mean area under receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the training vs. internal validation vs. external validation cohort to distinguish MPLC were 0.983 vs. 0.844 vs. 0.793, 0.942 vs. 0.846 vs. 0.760, 0.905 vs. 0.728 vs. 0.727, and 0.962 vs. 0.910 vs. 0.769, respectively. AUCs of the two clinicians were 0.619 and 0.580. Conclusions The CT radiomic feature-based lesion PRE model is potentially an accurate diagnostic tool for the differentiation of MPLC and IPM, which could help with clinical decision making.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136069325","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}
{"title":"Investigating the gut microbiota's influence on psoriasis and psoriatic arthritis risk: a Mendelian randomization analysis.","authors":"Nianzhou Yu, Jiayi Wang, Yuancheng Liu, Yeye Guo","doi":"10.1093/pcmedi/pbad023","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad023","url":null,"abstract":"<p><strong>Background: </strong>Numerous investigations have revealed the interplay between gut microbiota (GM) and psoriasis (Ps) and psoriatic arthritis (PsA). However, the causal relationship between them remains unknown.</p><p><strong>Methods: </strong>We curated a collection of genetic variants (<i>P</i> < 1 × 10<sup>-5</sup>) associated with GM (<i>n</i> = 18 340) derived from the MiBioGen study. To explore the intricate relationship between GM and Ps as well as PsA, we harnessed the comprehensive resources of the FinnGen database, encompassing a vast cohort of individuals, including 4510 Ps cases and 212 242 controls and 1637 PsA cases and 212 242 controls. Mendelian randomization (MR) was used, including an inverse variance weighting method, followed by a sensitivity analysis to verify the robustness of the results.</p><p><strong>Results: </strong>For Ps, some bacterial taxa, including <i>Lactococcus, Ruminiclostridium 5</i>, and <i>Eubacterium fissicatena</i>, were identified as risk factors; but <i>Odoribacter</i> demonstrated a protective effect against Ps. In the case of PsA, <i>Lactococcus, Verrucomicrobiales, Akkermansia, Coprococcus 1</i>, and <i>Verrucomicrobiaceae</i> were identified as risk factors; <i>Odoribacter</i> and <i>Rikenellaceae</i> exhibited a protective effect against the development of PsA.</p><p><strong>Conclusion: </strong>Our study establishes a causal link between the GM and Ps and PsA. These findings provide insights into the underlying mechanisms and suggest potential therapeutic targets.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"6 3","pages":"pbad023"},"PeriodicalIF":5.3,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463075","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}