Precision Clinical Medicine最新文献

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Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis. 癌细胞亚型之间通过外泌体进行交流,导致鼻咽癌转移和预后不良。
IF 5.1 4区 医学
Precision Clinical Medicine Pub Date : 2024-09-23 eCollection Date: 2024-09-01 DOI: 10.1093/pcmedi/pbae018
Hao-Jun Xie, Ming-Jie Jiang, Ke Jiang, Lin-Quan Tang, Qiu-Yan Chen, An-Kui Yang, Hai-Qiang Mai
{"title":"Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis.","authors":"Hao-Jun Xie, Ming-Jie Jiang, Ke Jiang, Lin-Quan Tang, Qiu-Yan Chen, An-Kui Yang, Hai-Qiang Mai","doi":"10.1093/pcmedi/pbae018","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae018","url":null,"abstract":"<p><strong>Background: </strong>Intratumor heterogeneity is common in cancers, with different cell subtypes supporting each other to become more malignant. Nasopharyngeal carcinoma (NPC), a highly metastatic cancer, shows significant heterogeneity among its cells. This study investigates how NPC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules.</p><p><strong>Methods: </strong>Exosomes were purified and characterized. MicroRNA expression was analyzed via sequencing and qRT-PCR. The effects of miR-30a-5p on migration, invasion, and metastasis were evaluated in vitro and in vivo. Its impact on desmoglein glycoprotein (DSG2) was assessed using dual-luciferase assays and Western blotting. Immunohistochemistry (IHC) and statistical models linked miR-30a-5p/DSG2 levels to patient prognosis.</p><p><strong>Results: </strong>Different NPC cell subtypes transmit metastatic potential via exosomes. High-metastatic cells enhance the migration, invasion, and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p. Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis. miR-30a-5p may promote metastasis by targeting DSG2 and modulating Wnt signaling. Plasma exosomal miR-30a-5p inversely correlates with DSG2 levels, predicting patient outcomes.</p><p><strong>Conclusion: </strong>High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p, which is a valuable prognostic marker assessable via liquid biopsy.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355501","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}
引用次数: 0
Fecal microbiota and metabolites in the pathogenesis and precision medicine for inflammatory bowel disease. 炎症性肠病发病机制和精准医疗中的粪便微生物群和代谢物。
IF 5.1 4区 医学
Precision Clinical Medicine Pub Date : 2024-09-23 eCollection Date: 2024-09-01 DOI: 10.1093/pcmedi/pbae023
Long Ju, Zhimin Suo, Jian Lin, Zhanju Liu
{"title":"Fecal microbiota and metabolites in the pathogenesis and precision medicine for inflammatory bowel disease.","authors":"Long Ju, Zhimin Suo, Jian Lin, Zhanju Liu","doi":"10.1093/pcmedi/pbae023","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae023","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, and its pathogenesis is believed to be associated with an imbalance between commensal organisms and the intestinal immune system. This imbalance is significantly influenced by the intestinal microbiota and metabolites and plays a critical role in maintaining intestinal mucosal homeostasis. However, disturbances in the intestinal microbiota cause dysregulated immune responses and consequently induce intestinal inflammation. Recent studies have illustrated the roles of the intestinal microbiota in the pathogenesis of IBD and underscored the potential of precision diagnosis and therapy. This work summarises recent progress in this field and particularly focuses on the application of the intestinal microbiota and metabolites in the precision diagnosis, prognosis assessment, treatment effectiveness evaluation, and therapeutic management of IBD.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393860","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}
引用次数: 0
Exosomal miRNAs and isomiRs: potential biomarkers for type 2 diabetes mellitus. 外泌体 miRNAs 和 isomiRs:2 型糖尿病的潜在生物标记物。
IF 5.1 4区 医学
Precision Clinical Medicine Pub Date : 2024-09-20 eCollection Date: 2024-09-01 DOI: 10.1093/pcmedi/pbae021
Yong Ling Sou, William M Chilian, Wickneswari Ratnam, Shamsul Mohd Zain, Sharifah Zamiah Syed Abdul Kadir, Yan Pan, Yuh-Fen Pung
{"title":"Exosomal miRNAs and isomiRs: potential biomarkers for type 2 diabetes mellitus.","authors":"Yong Ling Sou, William M Chilian, Wickneswari Ratnam, Shamsul Mohd Zain, Sharifah Zamiah Syed Abdul Kadir, Yan Pan, Yuh-Fen Pung","doi":"10.1093/pcmedi/pbae021","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae021","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a metabolic disease that is characterized by chronic hyperglycaemia. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play important roles in post-transcriptional gene regulation. They are negative regulators of their target messenger RNAs (mRNAs), in which they bind either to inhibit mRNA translation, or to induce mRNA decay. Similar to proteins, miRNAs exist in different isoforms (isomiRs). miRNAs and isomiRs are selectively loaded into small extracellular vesicles, such as the exosomes, to protect them from RNase degradation. In T2DM, exosomal miRNAs produced by different cell types are transported among the primary sites of insulin action. These interorgan crosstalk regulate various T2DM-associated pathways such as adipocyte inflammation, insulin signalling, and β cells dysfunction among many others. In this review, we first focus on the mechanism of exosome biogenesis, followed by miRNA biogenesis and isomiR formation. Next, we discuss the roles of exosomal miRNAs and isomiRs in the development of T2DM and provide evidence from clinical studies to support their potential roles as T2DM biomarkers. Lastly, we highlight the use of exosomal miRNAs and isomiRs in personalized medicine, as well as addressing the current challenges and future opportunities in this field. This review summarizes how research on exosomal miRNAs and isomiRs has developed from the very basic to clinical applications, with the goal of advancing towards the era of personalized medicine.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355502","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}
引用次数: 0
Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults. 表型年龄是 "人生必修 8 "对降低美国成年人死亡风险影响的中介。
IF 5.1 4区 医学
Precision Clinical Medicine Pub Date : 2024-09-16 eCollection Date: 2024-09-01 DOI: 10.1093/pcmedi/pbae019
Yuxuan Zhao, Haiming Yang, Rong Jiao, Yueqing Wang, Meng Xiao, Mingyu Song, Huan Yu, Chunxiao Liao, Yuanjie Pang, Wenjing Gao, Tao Huang, Canqing Yu, Jun Lv, Shengxu Li, Lu Qi, Liming Li, Dianjianyi Sun
{"title":"Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults.","authors":"Yuxuan Zhao, Haiming Yang, Rong Jiao, Yueqing Wang, Meng Xiao, Mingyu Song, Huan Yu, Chunxiao Liao, Yuanjie Pang, Wenjing Gao, Tao Huang, Canqing Yu, Jun Lv, Shengxu Li, Lu Qi, Liming Li, Dianjianyi Sun","doi":"10.1093/pcmedi/pbae019","DOIUrl":"10.1093/pcmedi/pbae019","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality.</p><p><strong>Methods: </strong>We included adult participants with available data for individual phenotypic age (PhenoAge) and Life's Essential 8 (LE8) scores from the National Health and Nutrition Examination Survey 2005-2010 (three cycles) and linked mortality records until 31 December 2019. Adjusted hazard ratios (HR) were estimated to evaluate the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks.</p><p><strong>Results: </strong>A 1-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% confidence interval, 1.04-1.05]) and cardiovascular (HR = 1.04 [95% confidence interval, 1.04-1.05]) mortality, independent of chronological age, demographic characteristics, and disease history. High level of LE8 (score: 80-100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36 and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all <i>P</i> < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure, and physical activity on all-cause mortality risk, respectively (all <i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297103","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}
引用次数: 0
Multidisciplinary treatment and immunotherapy improved the prognosis of advanced small intestine sarcomatoid carcinoma 多学科治疗和免疫疗法改善了晚期小肠肉瘤样癌的预后
IF 5.1 4区 医学
Precision Clinical Medicine Pub Date : 2024-07-02 DOI: 10.1093/pcmedi/pbae014
Bo Wang, Meng Qiu
{"title":"Multidisciplinary treatment and immunotherapy improved the prognosis of advanced small intestine sarcomatoid carcinoma","authors":"Bo Wang, Meng Qiu","doi":"10.1093/pcmedi/pbae014","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae014","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688106","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}
引用次数: 0
Deep learning-based multi-modal data integration enhancing breast cancer disease-free survival prediction. 基于深度学习的多模态数据整合提高了乳腺癌无病生存率预测能力。
IF 5.1 4区 医学
Precision Clinical Medicine Pub Date : 2024-05-29 eCollection Date: 2024-06-01 DOI: 10.1093/pcmedi/pbae012
Zehua Wang, Ruichong Lin, Yanchun Li, Jin Zeng, Yongjian Chen, Wenhao Ouyang, Han Li, Xueyan Jia, Zijia Lai, Yunfang Yu, Herui Yao, Weifeng Su
{"title":"Deep learning-based multi-modal data integration enhancing breast cancer disease-free survival prediction.","authors":"Zehua Wang, Ruichong Lin, Yanchun Li, Jin Zeng, Yongjian Chen, Wenhao Ouyang, Han Li, Xueyan Jia, Zijia Lai, Yunfang Yu, Herui Yao, Weifeng Su","doi":"10.1093/pcmedi/pbae012","DOIUrl":"10.1093/pcmedi/pbae012","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of breast cancer is often unfavorable, emphasizing the need for early metastasis risk detection and accurate treatment predictions. This study aimed to develop a novel multi-modal deep learning model using preoperative data to predict disease-free survival (DFS).</p><p><strong>Methods: </strong>We retrospectively collected pathology imaging, molecular and clinical data from The Cancer Genome Atlas and one independent institution in China. We developed a novel Deep Learning Clinical Medicine Based Pathological Gene Multi-modal (DeepClinMed-PGM) model for DFS prediction, integrating clinicopathological data with molecular insights. The patients included the training cohort (<i>n</i> = 741), internal validation cohort (<i>n</i> = 184), and external testing cohort (<i>n</i> = 95).</p><p><strong>Result: </strong>Integrating multi-modal data into the DeepClinMed-PGM model significantly improved area under the receiver operating characteristic curve (AUC) values. In the training cohort, AUC values for 1-, 3-, and 5-year DFS predictions increased to 0.979, 0.957, and 0.871, while in the external testing cohort, the values reached 0.851, 0.878, and 0.938 for 1-, 2-, and 3-year DFS predictions, respectively. The DeepClinMed-PGM's robust discriminative capabilities were consistently evident across various cohorts, including the training cohort [hazard ratio (HR) 0.027, 95% confidence interval (CI) 0.0016-0.046, <i>P</i> < 0.0001], the internal validation cohort (HR 0.117, 95% CI 0.041-0.334, <i>P</i> < 0.0001), and the external cohort (HR 0.061, 95% CI 0.017-0.218, <i>P</i> < 0.0001). Additionally, the DeepClinMed-PGM model demonstrated C-index values of 0.925, 0.823, and 0.864 within the three cohorts, respectively.</p><p><strong>Conclusion: </strong>This study introduces an approach to breast cancer prognosis, integrating imaging and molecular and clinical data for enhanced predictive accuracy, offering promise for personalized treatment strategies.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443434","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}
引用次数: 0
Depletion of squalene epoxidase in synergy with glutathione peroxidase 4 inhibitor RSL3 overcomes oxidative stress resistance in lung squamous cell carcinoma 消耗角鲨烯环氧化物酶与谷胱甘肽过氧化物酶 4 抑制剂 RSL3 协同作用,可克服肺鳞状细胞癌的氧化应激抗性
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2024-05-08 DOI: 10.1093/pcmedi/pbae011
Guo Li, Lu Chen, Hua Bai, Li Zhang, Jie Wang, Weimin Li
{"title":"Depletion of squalene epoxidase in synergy with glutathione peroxidase 4 inhibitor RSL3 overcomes oxidative stress resistance in lung squamous cell carcinoma","authors":"Guo Li, Lu Chen, Hua Bai, Li Zhang, Jie Wang, Weimin Li","doi":"10.1093/pcmedi/pbae011","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae011","url":null,"abstract":"\u0000 Lung squamous cell carcinoma (LUSC) lacks effective targeted therapies and has a poor prognosis. Disruption of squalene epoxidase (SQLE) has been implicated in metabolic disorders and cancer. However, the role of SQLE as a monooxygenase involved in oxidative stress remains unclear. Here, we investigated the unique role of SQLE expression in the diagnosis and prognosis prediction of LUSC. Knockdown of SQLE or treatment with the SQLE inhibitor terbinafine (TBF) can suppress the proliferation of LUSC cells by inducing apoptosis and reactive oxygen species (ROS) accumulation. However, depletion of SQLE also results in the impairment of lipid peroxidation and ferroptosis resistance such as upregulation of glutathione peroxidase 4 (GPX4). Therefore, prevention of SQLE in synergy with GPX4 inhibitor RSL3 effectively mitigates the proliferation and growth of LUSC. Our study indicates that the low expression of SQLE employs the adaptive survival through regulating the balance of apoptosis and resistance of ferroptosis. In future, the combinational therapy of targeting SQLE and ferroptosis could be a promising approach in treating LUSC.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140999373","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}
引用次数: 0
TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer: a clinical next-generation sequencing study TP53特异性突变是乳腺癌同源重组缺陷的潜在生物标志物:一项临床新一代测序研究
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2024-04-09 DOI: 10.1093/pcmedi/pbae009
Yongsheng Huang, Shuwei Ren, Li Ding, Yuanling Jiang, Jiahuan Luo, Jinghua Huang, Xinke Yin, Jianli Zhao, Sha Fu, Jianwei Liao
{"title":"TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer: a clinical next-generation sequencing study","authors":"Yongsheng Huang, Shuwei Ren, Li Ding, Yuanling Jiang, Jiahuan Luo, Jinghua Huang, Xinke Yin, Jianli Zhao, Sha Fu, Jianwei Liao","doi":"10.1093/pcmedi/pbae009","DOIUrl":"https://doi.org/10.1093/pcmedi/pbae009","url":null,"abstract":"\u0000 \u0000 \u0000 TP53 mutations and homologous recombination deficiency (HRD) occur frequently in breast cancer. However, the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not clear.\u0000 \u0000 \u0000 \u0000 Both tumor and paired blood DNA from 119 breast cancer patients were performed clinical next-generation sequencing (NGS) by a 520-gene panel. Mutations, tumor mutation burden (TMB), and genomic HRD scores were assessed from NGS data.\u0000 \u0000 \u0000 \u0000 All TP53 pathogenic mutations in patients were the somatic origin, which was associated with the protein expression of estrogen receptor and progestogen receptor. Compared to patients without TP53 pathologic mutations, patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic alterations. The frequency of TP53 pathologic mutation was higher in the HRD-High group (HRD score≥42) relative to that in the HRD-Low group (HRD score<42). TP53 has different mutational characteristics between the HRD-Low and HRD-High groups. TP53-specific mutation subgroups had diverse genomic features and TMB. Notably, TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an AUC of 0.61. TP53-specific mutations, namely HRD-Low mutation, HRD-High mutation, and HRD common mutation, predicted the HRD status of breast cancer patients with AUC values of 0.32, 0.72, and 0.58, respectively. Interestingly, TP53 HRD-High mutation and HRD common mutation combinations showed the highest AUC values (0.80) in predicting HRD status.\u0000 \u0000 \u0000 \u0000 TP53-specific mutation combinations predict the HRD status of patients, indicating that TP53 pathogenic mutations could serve as a potential biomarker for PARP inhibitors in breast cancer patients.\u0000","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140720823","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}
引用次数: 0
Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight. 基因组和克隆造血的稳定性与短时太空飞行期间免疫、cfDNA、线粒体和端粒长度的变化形成鲜明对比。
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2024-04-08 eCollection Date: 2024-03-01 DOI: 10.1093/pcmedi/pbae007
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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.3,"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}
引用次数: 0
Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formationin cancer patients 癌症患者围手术期循环 DNA 水平的即时动态变化与中性粒细胞胞外捕获物形成的关系
IF 5.3 4区 医学
Precision Clinical Medicine Pub Date : 2024-03-27 DOI: 10.1093/pcmedi/pbae008
Andrei Kudriavtsev, B. Pastor, Alexia Mirandola, E. Pisareva, Y. Gricourt, Xavier Capdevila, Alain R. Thierry, Philippe Cuvillon
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