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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 Q1 MEDICINE, RESEARCH & EXPERIMENTAL 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

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景:肿瘤内异质性在癌症中很常见,不同的细胞亚型相互支持,恶性程度更高。鼻咽癌(NPC)是一种高度转移性癌症,其细胞间存在显著的异质性。本研究探讨了具有不同转移潜能的鼻咽癌细胞亚型如何通过外泌体传递的分子相互影响:方法:纯化并鉴定外泌体。通过测序和 qRT-PCR 分析了微 RNA 的表达。在体外和体内评估了 miR-30a-5p 对迁移、侵袭和转移的影响。使用双荧光素酶测定法和 Western 印迹法评估了 miR-30a-5p 对去甲斑鸠蛋白糖蛋白(DSG2)的影响。免疫组织化学(IHC)和统计模型将 miR-30a-5p/DSG2 水平与患者预后联系起来:结果:不同的鼻咽癌细胞亚型通过外泌体传递转移潜能。结果:不同的鼻咽癌细胞亚型通过外泌体传递转移潜能。高转移细胞通过外泌体传递的 miR-30a-5p 增强低转移细胞的迁移、侵袭和转移。miR-30a-5p可能通过靶向DSG2和调节Wnt信号来促进转移。血浆外泌体miR-30a-5p与DSG2水平成反比,可预测患者的预后:结论:高转移性鼻咽癌细胞可通过外泌体传递的miR-30a-5p增加低转移性细胞的转移潜能,而miR-30a-5p是一种有价值的预后标志物,可通过液体活检进行评估。
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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 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-23 eCollection Date: 2024-09-01 DOI: 10.1093/pcmedi/pbae023
Long Ju, Zhimin Suo, Jian Lin, Zhanju Liu

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.

炎症性肠病(IBD)是一种胃肠道慢性炎症性疾病,其发病机制被认为与共生生物和肠道免疫系统之间的失衡有关。这种失衡在很大程度上受到肠道微生物群和代谢产物的影响,并在维持肠道粘膜稳态方面发挥着关键作用。然而,肠道微生物群的紊乱会导致免疫反应失调,进而诱发肠道炎症。最近的研究表明了肠道微生物群在 IBD 发病机制中的作用,并强调了精准诊断和治疗的潜力。本研究总结了这一领域的最新进展,尤其关注肠道微生物群和代谢物在 IBD 的精准诊断、预后评估、疗效评价和治疗管理中的应用。
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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 Q1 MEDICINE, RESEARCH & EXPERIMENTAL 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

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.

2 型糖尿病(T2DM)是一种以慢性高血糖为特征的代谢性疾病。微小核糖核酸(miRNA)是单链的小型非编码核糖核酸,在转录后基因调控中发挥重要作用。它们是目标信使 RNA(mRNA)的负调控因子,与目标信使 RNA 结合可抑制 mRNA 翻译或诱导 mRNA 衰减。与蛋白质类似,miRNA 也存在不同的异构体(isomiRs)。miRNA 和 isomiRs 被选择性地装载到细胞外小泡(如外泌体)中,以防止它们被 RNase 降解。在 T2DM 中,由不同细胞类型产生的外泌体 miRNA 在胰岛素作用的主要部位之间传递。这些器官间的串联调节着各种与 T2DM 相关的通路,如脂肪细胞炎症、胰岛素信号传导、β 细胞功能障碍等。在这篇综述中,我们首先关注外泌体的生物生成机制,然后是 miRNA 的生物生成和异构体的形成。接下来,我们讨论了外泌体 miRNAs 和 isomiRs 在 T2DM 发病过程中的作用,并提供了临床研究证据来支持它们作为 T2DM 生物标志物的潜在作用。最后,我们强调了外泌体 miRNA 和异构体 Rs 在个性化医疗中的应用,并探讨了这一领域当前的挑战和未来的机遇。本综述总结了外泌体 miRNA 和异构体 Rs 的研究是如何从基础研究发展到临床应用的,其目标是迈向个性化医疗时代。
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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 Q1 MEDICINE, RESEARCH & EXPERIMENTAL 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

Objective: This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality.

Methods: 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.

Results: 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 P < 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 P < 0.05).

Conclusion: Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.

研究目的本研究旨在探究表型年龄是否能调节健康生活方式对死亡率的保护作用:我们纳入了2005-2010年全国健康与营养调查(三个周期)中有个人表型年龄(PhenoAge)和生命必备8(LE8)评分数据的成年参与者,并链接了截至2019年12月31日的死亡记录。估算了调整后的危险比(HR),以评估 PhenoAge 和 LE8 分数与全因和心血管死亡风险的关联。进行了中介分析,以估算 PhenoAge 对 LE8 对死亡风险影响的比例贡献:结果:PhenoAge 每增加 1 年,全因(HR = 1.04 [95% 置信区间,1.04-1.05])和心血管(HR = 1.04 [95% 置信区间,1.04-1.05])死亡风险就会增加,与实际年龄、人口特征和疾病史无关。LE8水平高(80-100分)与PhenoAge年轻3.30岁有关。据估计,LE8 对全因死亡率和心血管死亡率的影响中,年龄分别占 36% 和 22%(均为 P P P 结论):遵守LE8的建议可延缓表型老化。PhenoAge可以调节LE8对死亡风险的影响。
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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 Q1 MEDICINE, RESEARCH & EXPERIMENTAL 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

Background: 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).

Methods: 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 (n = 741), internal validation cohort (n = 184), and external testing cohort (n = 95).

Result: 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, P < 0.0001], the internal validation cohort (HR 0.117, 95% CI 0.041-0.334, P < 0.0001), and the external cohort (HR 0.061, 95% CI 0.017-0.218, P < 0.0001). Additionally, the DeepClinMed-PGM model demonstrated C-index values of 0.925, 0.823, and 0.864 within the three cohorts, respectively.

Conclusion: 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.

背景:乳腺癌的预后往往不佳,因此需要进行早期转移风险检测和准确的治疗预测。本研究旨在利用术前数据开发一种新型多模态深度学习模型,以预测无病生存期(DFS):我们回顾性地收集了来自癌症基因组图谱和中国一家独立机构的病理成像、分子和临床数据。我们开发了一种新型的基于深度学习的临床医学病理基因多模态(DeepClinMed-PGM)模型,将临床病理数据与分子洞察力相结合,用于预测无病生存期。患者包括训练队列(n = 741)、内部验证队列(n = 184)和外部测试队列(n = 95):结果:将多模态数据整合到DeepClinMed-PGM模型中能显著提高接收者工作特征曲线下面积(AUC)值。在训练队列中,1 年、3 年和 5 年 DFS 预测的 AUC 值分别增至 0.979、0.957 和 0.871,而在外部测试队列中,1 年、2 年和 3 年 DFS 预测的 AUC 值分别达到 0.851、0.878 和 0.938。DeepClinMed-PGM 强大的判别能力在包括训练队列在内的不同队列中始终如一地表现出来[危险比(HR)0.027,95% 置信区间(CI)0.0016-0.046,P P P 结论:这项研究介绍了一种乳腺癌预后的方法,它整合了成像、分子和临床数据,提高了预测的准确性,为个性化治疗策略带来了希望。
{"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":"7 2","pages":"pbae012"},"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
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 Q1 MEDICINE, RESEARCH & EXPERIMENTAL 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

Background: 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.

Methods: 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.

Result: 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.

Conclusion: 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.

背景:Inspiration4(I4)任务是首次全民用轨道飞行任务,它通过多原子方法研究了短期太空飞行的生理影响。尽管取得了进展,但在人类适应太空飞行的独特挑战(包括微重力、免疫系统扰动和辐射暴露)方面仍有许多东西需要学习:为了对飞行任务进行详细的遗传学分析,我们收集了飞行前、飞行中和飞行后的干血迹,以提取 DNA。通过定量 PCR 测量端粒长度,同时进行全基因组和 cfDNA 测序,以深入了解基因组稳定性和免疫适应性。数据分析使用了强大的生物信息学管道,包括评估突变负担的变异调用:结果:端粒在太空飞行期间延长,返回地球后缩短。无细胞DNA分析显示飞行后免疫细胞特征增加。没有观察到明显的不确定潜能克隆造血(CHIP)或全基因组不稳定性。免疫细胞基因表达的长期变化表明,细胞对太空环境的适应在飞行数月后仍然存在:我们的研究结果为了解短时太空飞行的生理后果提供了有价值的见解,端粒动态和免疫细胞基因表达适应太空飞行,并在返回地球后持续存在。CHIP测序数据将成为研究宇航员CHIP早期发展的参考点,由于以往的研究主要集中在职业宇航员身上,因此对这一现象的研究不够。这项研究将成为未来商业和非商业航天飞行、低地球轨道(LEO)任务和深空探索的参考点。
{"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":"7 1","pages":"pbae007"},"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
Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging. 源自间充质干细胞的细胞外囊泡:Hebe手中治疗皮肤老化的美酒。
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-02-24 eCollection Date: 2024-03-01 DOI: 10.1093/pcmedi/pbae004
Qixiang Gui, Neng Ding, Zuochao Yao, Minjuan Wu, Ruifeng Fu, Yue Wang, Yunpeng Zhao, Lie Zhu

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.

由于经常暴露在外部环境和各种刺激下,皮肤是最容易出现衰老表现的器官之一。预防和延缓皮肤衰老已成为近年来的重要研究课题之一。间充质干细胞(MSCs)是一种多能干细胞,来源于中胚层,具有很强的自我更新能力和多线分化潜能。间充质干细胞衍生的细胞外囊泡(MSC-EVs)是一种纳米级生物囊泡,可促进细胞间的交流并调节生物行为。最近的研究表明,间充质干细胞胞外小泡具有抗炎、抗氧化应激和促进伤口愈合的能力,因此在抗衰老治疗中具有潜在的应用前景。本综述介绍了间充质干细胞-EV 在延缓皮肤衰老方面的最新进展。它主要包括间充质干细胞-EV促进角质形成细胞和成纤维细胞的增殖和迁移、减少基质金属蛋白酶的表达、抗氧化应激和调节炎症。然后,我们简要讨论了最近发现的间充质干细胞-EVs 在皮肤抗衰老领域的治疗方法。此外,我们还介绍了基于间充质干细胞-EV 的治疗方法的优势和局限性。
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引用次数: 0
SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike induced intestinal inflammation 由穗状病毒诱发的肠道炎症介导的 SARS-CoV-2 在胃肠道的致病机制
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-21 DOI: 10.1093/pcmedi/pbad034
Zhan-yu Li, Jian-zhong He, Yun Yin, Lei Tang, Ye Liu, Olivia Monteiro, Fa-min Zeng
{"title":"SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike induced intestinal inflammation","authors":"Zhan-yu Li, Jian-zhong He, Yun Yin, Lei Tang, Ye Liu, Olivia Monteiro, Fa-min Zeng","doi":"10.1093/pcmedi/pbad034","DOIUrl":"https://doi.org/10.1093/pcmedi/pbad034","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"20 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948280","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
Precision medicine in inflammatory bowel disease 炎症性肠病的精准医疗
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-18 DOI: 10.1093/pcmedi/pbad033
Zhen Zeng, Mingshan Jiang, Xi Li, Jing Yuan, Hu Zhang
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.
炎症性肠病(IBD)是一种不治之症,其特点是在整个病程中会出现缓解-复发循环。克罗恩病(CD)和溃疡性结肠炎(UC)是 IBD 的两种主要形式,这两种疾病都有并发症倾向,而且在复发频率和严重程度方面存在很大的异质性,因此给 IBD 的临床治疗带来了巨大挑战。目前的治疗策略对 IBD 的诱导治疗和维持治疗有不同的效果。遗传学、药物遗传学、蛋白质组学和微生物组研究的最新进展为确定预后和治疗反应的分子标记提供了强大的推动力,有助于临床医生更有效地管理 IBD 患者,进而改善临床疗效并降低患者的治疗费用。在这篇综述中,我们总结并讨论了 IBD 的精准医疗,重点是疾病过程和治疗反应的预测标志物以及治疗药物监测期间的监测指标。
{"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}
引用次数: 0
The significance of long non-coding RNAs in the pathogenesis, diagnosis and treatment of inflammatory bowel disease. 长非编码 RNA 在炎症性肠病的发病机制、诊断和治疗中的意义。
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-12-11 eCollection Date: 2023-12-01 DOI: 10.1093/pcmedi/pbad031
Fei Jiang, Min Wu, Rongpeng Li

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.

炎症性肠病(IBD)是一组慢性复发性胃肠道炎症性疾病,在全球发病率很高。虽然 IBD 的病理机制已被广泛研究,但其发病机制的几个方面仍不清楚。长非编码 RNA(lncRNA)是长度超过 200 个核苷酸的转录本,具有潜在的蛋白质编码功能。LncRNA 在表观遗传修饰、转录调控和转录后调控等生物过程中发挥着重要作用。在这篇综述中,我们从整体肠道微环境的角度总结了与 IBD 相关的 lncRNA 的最新研究进展,以及它们作为免疫调节剂、诊断生物标志物和 IBD 治疗靶标或药物的潜在作用。
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引用次数: 0
期刊
Precision Clinical Medicine
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