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Interpretable machine learning for cognitive impairment assessment: integration of clinical and radiomic white matter hyperintensities features. 认知障碍评估的可解释机器学习:临床和放射学白质高信号特征的整合。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-11 DOI: 10.1186/s12967-026-07843-6
Mengchen Wang, Tianci Wang, Xiaoxiao Wang, Chun Liu, Frankliu Gao, Bensheng Qiu, Tao Guo, Yu Huang
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引用次数: 0
TCF21-WNT5A axis drives metastasis of colorectal cancer via stromal-tumor cell communication. TCF21-WNT5A轴通过间质-肿瘤细胞通讯驱动结直肠癌转移。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-11 DOI: 10.1186/s12967-026-07835-6
Qingxing Huang, Aigang Ren, Xiaolong Cui, Dianfeng Tian, Hui Liu, Liwei Wang, Aihong Cao

Introduction: The third most prevalent form of cancer, colorectal cancer (CRC), is associated with a high mortality rate due to colorectal liver metastases (CRLM). However, the molecular mechanisms underlying CRLM remain poorly understood.

Methods: ScRNA-seq data and Bulk RNA-seq data were collected from GEO database. First, we screened genes that showed differentially expression in three groups of colorectal tissues (normal vs. primary tumor vs. metastases). We then performed machine learning to identify signature genes involved in colorectal cancer. We further investigated the expression patterns of these core genes at the single-cell level. Through the integration of single-cell and bulk RNA-seq data, we have identified pivotal genes linked to CRC liver metastasis. Furthermore, we revealed that TCF21 is overexpressed in colorectal tumor tissues with metastases using clinical samples and HCT116 cells.

Results: We have identified 12 pivotal genes linked to CRC liver metastasis, which aims to dissect the molecular underpinnings of colorectal cancer and pave the way for novel therapeutic targets in clinical practice. Using scRNA-seq analysis, our findings revealed unique cellular communication features in CRC metastasis. Besides, TCF21high stromal cells were mainly enriched in metastatic tissues and TCF21 RNA level is associated with CRC metastasis, indicating vital role of TCF21 in CRC. Mechanistically, TCF21 regulates the expression of WNT5A and overexpression of WNT5A could reverse the effect of TCF21 deficiency in CRC.

Conclusions: We identified 12 signature hub genes associated with CRLM by using both scRNA-seq and bulk RNA-seq analysis. Further, we revealed the vital role of TCF21, which promotes CRLM by regulating WNT5A in CRC metastasis. The revelations have illuminated the pivotal function of the TCF21-WNT5A pathway in the development of colorectal cancer, indicating possible avenues for therapeutic intervention aimed at preventing and managing the spread of CRC.

导论:第三种最常见的癌症,结直肠癌(CRC),由于结直肠癌肝转移(CRLM),其死亡率很高。然而,CRLM的分子机制仍然知之甚少。方法:从GEO数据库中收集ScRNA-seq数据和Bulk RNA-seq数据。首先,我们筛选了在三组结直肠组织(正常、原发、转移)中表现出差异表达的基因。然后,我们使用机器学习来识别与结直肠癌有关的特征基因。我们进一步研究了这些核心基因在单细胞水平上的表达模式。通过整合单细胞和大量RNA-seq数据,我们已经确定了与结直肠癌肝转移相关的关键基因。此外,我们通过临床样本和HCT116细胞发现TCF21在结直肠肿瘤转移组织中过表达。结果:我们确定了12个与结直肠癌肝转移相关的关键基因,旨在剖析结直肠癌的分子基础,为临床实践中新的治疗靶点铺平道路。通过scRNA-seq分析,我们的发现揭示了CRC转移中独特的细胞通讯特征。此外,TCF21高基质细胞主要富集于转移组织,且TCF21 RNA水平与结直肠癌转移相关,提示TCF21在结直肠癌中的重要作用。机制上,TCF21调节WNT5A的表达,过表达WNT5A可以逆转TCF21缺乏对CRC的影响。结论:通过scRNA-seq和大量RNA-seq分析,我们确定了12个与CRLM相关的标志性枢纽基因。此外,我们揭示了TCF21在CRC转移中的重要作用,TCF21通过调节WNT5A促进CRLM。这些发现揭示了TCF21-WNT5A通路在结直肠癌发展中的关键功能,为预防和控制结直肠癌扩散的治疗干预提供了可能的途径。
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引用次数: 0
Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review. 基于脑肠轴的治疗在长期COVID和ME/CFS中的潜在应用:一项基于病例的系统评价。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-10 DOI: 10.1186/s12967-026-07807-w
Do-Young Kim, Jaeyoung Youn, Naeun Kang, Sung-Il Cho, In-Hyuk Ha

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.

Methods: We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.

Results: The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n = 8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.

Conclusion: Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.

背景:肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)和长COVID具有持续疲劳、运动后乏力(PEM)和胃肠道(GI)功能障碍等临床特征。越来越多的证据表明,在其病理生理中,以生态失调、中枢神经系统(CNS)神经炎症、肠道通透性增加和微生物易位为特征的脑肠轴失调。然而,针对这些途径的治疗策略仍然不明确。方法:我们报告了一例成功治疗covid - 19后ME/CFS的病例,电针(EA)为基础的腓深神经刺激用于增强迷走反射。在12周内使用多维疲劳量表评估疲劳轨迹。基于该病例,对评估脑-肠轴调节干预治疗ME/CFS或Long COVID的随机对照试验(rct)进行了系统综述。结果:患者表现出明显的总疲劳减轻,在动力和精神疲劳方面有早期改善,在短暂的全身症状发作后,身体疲劳的改善延迟。在纳入的随机对照试验(n = 8,790名参与者)中,4项研究了肠道微生物组调节疗法,4项研究了神经刺激疗法。合成和草药干预显示出对疲劳或PEM的益处,并伴有特定细菌群或中枢神经系统代谢的改变。在神经刺激方面,经颅直流电刺激(tDCS)联合运动方案可改善疲劳,而单独的tDCS、耳部或外周TENS的效果有限。结论:基于脑肠轴的干预可能通过调节神经炎症、恢复微生物群平衡和改善上皮屏障功能来缓解ME/CFS和Long COVID的疲劳。基于ea的迷走神经刺激对于症状严重或治疗抵抗的患者是一种可行的选择。需要更大规模的机制研究和严格设计的随机对照试验来确定治疗靶点和优化干预策略。
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引用次数: 0
PUF, a biflavone monomer, triggers DNA damage through SLC25A15 downregulation and purine metabolic suppression in DLBCL. PUF是一种双黄酮单体,在DLBCL中通过SLC25A15下调和嘌呤代谢抑制引发DNA损伤。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-10 DOI: 10.1186/s12967-026-07797-9
Chang Su, Guige Lu, Lijia Ou, Liang Liang, Caiqin Wang, Yizi He, Ruolan Zeng, Yajun Li, Hui Zhou, Ling Xiao
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引用次数: 0
Extracellular vesicles derived from astrocytes pretreated with melatonin promoted neuro-angiogenesis in mice with ischemic medial prefrontal cortex. 褪黑素预处理的星形胶质细胞产生的细胞外囊泡促进了缺血内侧前额皮质小鼠的神经血管生成。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-09 DOI: 10.1186/s12967-026-07709-x
Behnaz Mirzaahmadi, Hajar Shafaie, Javad Mahmoodi, Parinaz Haddadi, Ali Hassanzadeh, Russel J Reiter, Farzaneh Fazli, Mohammad Karimipour, Reza Rahbarghazi
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引用次数: 0
Disruption of the NDC80-Nek2 axis suppresses glioblastoma stemness and enhances therapeutic efficacy. 破坏NDC80-Nek2轴可抑制胶质母细胞瘤的干性并提高治疗效果。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-09 DOI: 10.1186/s12967-026-07829-4
Rui Niu, Rui Gong, Wanjun Wang, Meichen Liu, Cheng-Xiong Xu, Hong-Lin Liu, Lingling Lin, Tao Jiang, Jinlong Yin
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引用次数: 0
Engineered exosomes from umbilical cord mesenchymal stem cells with pPB modification attenuate hepatic fibrosis via hepatic stellate cell targeting. pPB修饰的脐带间充质干细胞工程外泌体通过肝星状细胞靶向减轻肝纤维化。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-09 DOI: 10.1186/s12967-025-07658-x
Fanghong Wang, Zongbin Sun, Qiuxia Zheng, Xiaofeng Wei, Lu Zhang, Xiaoliang Zhu, Kexiang Zhu, Xiaojing Song, Ping Yue, Fanghui Ding, Lei Zhang, Xun Li
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引用次数: 0
MaR1 and NGF combine to inhibit autophagy through the GSK-3β/β-catenin pathway to promote sciatic nerve repair. MaR1和NGF通过GSK-3β/β-catenin途径联合抑制自噬,促进坐骨神经修复。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-09 DOI: 10.1186/s12967-026-07804-z
Yuanhao Zhang, Shuang Zhao, Shaoni Wu, Haonan Niu, Lincong Gu, Youxin Song

Background: Peripheral nerve injury (PNI) is a public health problem that can lead to sensory and motor deficits as well as neuropathic pain and secondary lesions. We explored the effects of the combination of MaR1 and NGF on sciatic nerve regeneration, reduction of neuropathic pain, and anti-inflammation, and further elucidated the associated molecular mechanisms.

Methods: After treatment of PC12 (adrenal pheochromocytoma cells) cells with NGF, MaR1 and H₂O₂, changes in proliferation were detected by CCK8; cell migration ability was detected by Transwell; reactive oxygen species (ROS) and apoptosis were detected by flow cytometry; and the mRNA expression of the inflammatory factors IL-1β, IL-6, and TNF-α was detected by qRT-PCR. Western blot detected the protein expression of β-catenin, P62, GSK-3β, LC3B, NF200, S100, MBP; Immunofluorescence analysis of LC3B expression; During recovery experiments, observe changes following treatment with GSK-3β activators and the autophagy agonist rapamycin. PNI model was constructed using 6-week-old male SD rats, NGF, MaR1 or saline was injected locally, and the drug was administered 3 times on alternate days after surgery, sciatic nerve function index analysis and muscle atrophy test were performed after surgery; the gastrocnemius muscle wet weight ratio and HE staining were observed after the samples were taken after surgery, and NF200, S100, MBP, β-catenin, and P62 were detected by Western blot, GSK-3β, LC3B levels; the expression of NF200, β-catenin, P62, GSK-3β, LC3B was detected by immunohistochemistry.

Results: NGF and MaR1 were non-toxic and the combination of NGF and MaR1 increased the proliferation and migration of PC12 cells, reduced H₂O₂ induced ROS production, inhibited apoptosis, and had a significant anti-inflammatory effect. In vivo studies showed that MaR1 and NGF combined could more effectively promote nerve repair and recovery of sensory and motor functions in SD rats, and reduce gastrocnemius muscle atrophy.The combination of MaR1 and NGF inhibited autophagy through GSK-3β/β-catenin signaling pathway to regulate the growth and repair of sciatic nerve. And the GSK-3β agonist DIF-3 and the autophagy activator rapamycin antagonize this effect.

Conclusion: The combination of MaR1 and NGF promotes sciatic nerve repair and motor function recovery and reduces local inflammation by inhibiting autophagy through the GSK-3β/β-catenin pathway.

背景:周围神经损伤(PNI)是一个公共卫生问题,可导致感觉和运动障碍,以及神经性疼痛和继发性病变。我们探讨了MaR1和NGF联合使用对坐骨神经再生、减轻神经性疼痛和抗炎症的影响,并进一步阐明了相关的分子机制。方法:用NGF、MaR1和H₂O₂处理PC12(肾上腺嗜铬细胞瘤细胞)细胞后,CCK8检测细胞增殖的变化;Transwell检测细胞迁移能力;流式细胞术检测活性氧(ROS)和细胞凋亡;qRT-PCR检测炎症因子IL-1β、IL-6、TNF-α mRNA表达。Western blot检测β-catenin、P62、GSK-3β、LC3B、NF200、S100、MBP的蛋白表达;LC3B表达的免疫荧光分析;在恢复实验中,观察GSK-3β激活剂和自噬激动剂雷帕霉素治疗后的变化。取6周龄雄性SD大鼠构建PNI模型,局部注射NGF、MaR1或生理盐水,术后隔天给药3次,术后进行坐骨神经功能指数分析和肌肉萎缩试验;术后取标本后观察腓肠肌湿重比及HE染色,Western blot检测NF200、S100、MBP、β-catenin、P62、GSK-3β、LC3B水平;免疫组化检测NF200、β-catenin、P62、GSK-3β、LC3B的表达。结果:NGF和MaR1均无毒,且NGF和MaR1联合使用可增加PC12细胞的增殖和迁移,减少h2o2诱导的ROS产生,抑制细胞凋亡,并具有明显的抗炎作用。体内研究表明,MaR1和NGF联合使用能更有效地促进SD大鼠神经修复和感觉、运动功能恢复,减轻腓肠肌萎缩。MaR1与NGF联合通过GSK-3β/β-catenin信号通路抑制自噬,调节坐骨神经的生长和修复。GSK-3β激动剂DIF-3和自噬激活剂雷帕霉素可拮抗这种作用。结论:MaR1联合NGF通过GSK-3β/β-catenin通路抑制自噬,促进坐骨神经修复和运动功能恢复,减轻局部炎症。
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引用次数: 0
The neuropeptide in ischemic brain injury: insights, challenges, and horizon of targeted interventions. 缺血性脑损伤中的神经肽:见解、挑战和目标干预的视野。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-09 DOI: 10.1186/s12967-026-07801-2
Jianzhong Yu, Min Shen, Teng He
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引用次数: 0
Multiomics: the intersection of personalized nutrition in cardiometabolic diseases. 多组学:个性化营养在心脏代谢疾病中的交叉。
IF 7.5 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-02-09 DOI: 10.1186/s12967-026-07836-5
Elif Çelik, Emine Kocyigit, Feray Gençer Bingöl, Cansu Karaçolak, Özge Cemali, Martina Simonelli, Duygu Ağagündüz, Raffaele Capasso
{"title":"Multiomics: the intersection of personalized nutrition in cardiometabolic diseases.","authors":"Elif Çelik, Emine Kocyigit, Feray Gençer Bingöl, Cansu Karaçolak, Özge Cemali, Martina Simonelli, Duygu Ağagündüz, Raffaele Capasso","doi":"10.1186/s12967-026-07836-5","DOIUrl":"https://doi.org/10.1186/s12967-026-07836-5","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Translational Medicine
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