AP5Z1 affects hepatocellular carcinoma growth and autophagy by regulating PTEN ubiquitination and modulating the PI3K/Akt/mTOR pathway DOI Creative Commons
Zhipeng Quan,

Bo Peng,

Kai Hu

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 20, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, with high incidence and mortality rates, the number cases expected to increase by 2030. Understanding molecular mechanisms HCC identifying new therapeutic targets biomarkers for are crucial. In this study, we examined adaptor-related protein complex 5 subunit ζ1 (AP5Z1) expression in liver nearby noncancerous tissues explore its effects on cell growth, death, autophagy. The functional AP5Z1 were studied using clinical sample analysis, Western blot (WB), immunohistochemistry (IHC), quantitative reverse-transcription polymerase chain reaction (qRT‒PCR), coimmunoprecipitation (Co-IP), proliferation assays, flow cytometry (FCM), autophagy electron microscopy, mass spectrometry (MS), transcriptome animal model experiments. was notably higher than normal linked poor prognosis. results both vitro vivo studies revealed that promoted growth reduced apoptosis. addition, regulates cellular ubiquitinating phosphatase tensin homolog (PTEN) modulating phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target rapamycin (mTOR) pathway. influences apoptosis cells interacting PTEN modulate PI3K/Akt/mTOR This gene might promote ubiquitination degradation recruiting tripartite motif-containing 21 (TRIM21), making it potential biomarker diagnosing predicting outcome as well treatment strategies.

Язык: Английский

The need to establish and recognize the field of clinical laboratory science (CLS) as an essential field in advancing clinical goals DOI Creative Commons
Mojtaba Aghaei, Reyhane Khademi, Seyed Sobhan Bahreiny

и другие.

Health Science Reports, Год журнала: 2024, Номер 7(8)

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

39

Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets DOI Creative Commons
Atieh Raoufi, Hamed Soleimani Samarkhazan, S Nouri

и другие.

Clinical and Experimental Medicine, Год журнала: 2025, Номер 25(1)

Опубликована: Март 6, 2025

Graft-versus-host disease remains one of the most formidable barriers to complete success hematopoietic stem cell transplantation that has emerged as curative approach for many malignancies because it affects quality life and overall survival. Macrophages are among important members immune system, which perform dual roles in GVHD both therapeutic tools targets. This review epitomizes multifunctional role macrophages pathophysiology acute chronic GVHD. play an early phase their recruitment infiltration into target organs. Furthermore, they polarize two functionally different phenotypes, including M1 M2. In case GVHD, express phenotype characterized by production pro-inflammatory cytokines contribute tissue damage. contrast, tend toward M2 associated with repair tissues fibrosis. A critical balance these phenotypes is central course severity Further interactions other lymphocytes such T cells, B fibroblast further determine Macrophage interaction alloreactive cells promotes inflammation. therefore inducing injuries during Interaction macrophages, cell, fibroblast, CD4+ fibrosis and, hence, subsequent dysfunction These some insights, while several challenges remain. First, impact dominant on polarization incompletely sometimes controversial. Second, development targeted therapies able modulate macrophage function without systemic side effects area ongoing investigation. Future directions involve exploration macrophage-targeted therapies, small molecules, antibodies, nanotechnology, behavior improve patient outcomes. underlines fact a profound understanding essential developing new more effective strategies. Targeting might represent avenue decreasing incidence improving safety HSCT.

Язык: Английский

Процитировано

6

New insights on anti-tumor immunity of CD8+ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy DOI Creative Commons

Yibin Lin,

Yifu Song, Yaochuan Zhang

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 17, 2025

Abstract Recent breakthroughs in tumor immunotherapy have confirmed the capacity of immune system to fight several cancers. The effective means treating cancer involves accelerating death cells and improving patient immunity. Dynamic changes microenvironment alter actual effects anti-tumor drug production may trigger favorable or unfavorable responses by modulating tumor-infiltrating lymphocytes. Notably, CD8 + T are one primary that provide response. Tumor stem will resist evade destruction through various mechanisms as exert their function. This paper reviews research on regulation development prognosis directly indirectly role cells. We also discuss related strategies.

Язык: Английский

Процитировано

3

Algorithms and tools for data-driven omics integration to achieve multilayer biological insights: a narrative review DOI Creative Commons
Aurelia Morabito, Giulia De Simone, Roberta Pastorelli

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 10, 2025

Systems biology is a holistic approach to biological sciences that combines experimental and computational strategies, aimed at integrating information from different scales of processes unravel pathophysiological mechanisms behaviours. In this scenario, high-throughput technologies have been playing major role in providing huge amounts omics data, whose integration would offer unprecedented possibilities gaining insights on diseases identifying potential biomarkers. the present review, we focus strategies applied literature integrate genomics, transcriptomics, proteomics, metabolomics year range 2018-2024. Integration approaches were divided into three main categories: statistical-based approaches, multivariate methods, machine learning/artificial intelligence techniques. Among them, statistical (mainly based correlation) ones with slightly higher prevalence, followed by learning Integrating multiple layers has shown great uncovering molecular mechanisms, putative biomarkers, aid classification, most time resulting better performances when compared single analyses. However, significant challenges remain. The nature platforms introduces issues such as variable data quality, missing values, collinearity, dimensionality. These further increase combining datasets, complexity heterogeneity integration. We report found cope these challenges, but some open still remain should be addressed disclose full

Язык: Английский

Процитировано

2

Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth DOI Creative Commons
Hao Wang,

Ruixue Huo,

Kexin He

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 23, 2025

The colon and rectum are highly innervated, with neural components within the tumor microenvironment playing a significant role in colorectal cancer (CRC) progression. While perineural invasion (PNI) is associated poor prognosis CRC, impact of nerve density diameter on behavior remains unclear. This study aims to evaluate prognostic value characteristics CRC verify nerves growth. Tissue samples from 129 patients were stained immunofluorescent markers NF-L S100B detect nerves. Nerve measured normalized. Kaplan-Meier survival analysis Cox regression models used identify factors. Prognostic established using receiver operating characteristic (ROC) curve assess predictive A murine chemical denervation model was employed disrupt sympathetic 6-hydroxydopamine, inhibit muscarinic receptor 3 darifenacin, ablate sensory neurons capsaicin. total 0.72 ± 0.59/mm², intratumoral (0.42 0.40/mm²) being significantly lower than extratumoral regions (1.00 0.75/mm²). average 28.14 6.04 μm, no difference between (28.2 7.65 μm) (27.86 6.72 μm). PNI observed 65 (50.4%). high normalized (NND) shorter overall disease-free patients, identified as an independent factor. Patients exhibit higher NND. Incorporating NND into ROC improved sensitivity specificity predictions. In model, sympathetic, parasympathetic, reduced rectal volume. critical factors influencing patient enhance accuracy prediction models. Moreover, effectively inhibits growth vivo, highlighting potential targeting therapeutic strategy CRC.

Язык: Английский

Процитировано

2

Neuroinflammation and energy metabolism: a dual perspective on ischemic stroke DOI Creative Commons
Lei Wen, Hao Zhuang, Weiyi Huang

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 10, 2025

Ischemic stroke is a prevalent form of cerebrovascular accident, with its pathogenesis involving the intricate interplay between neuroinflammation and energy metabolism. Cerebral ischemia disrupts oxygen supply, triggering metabolic dysregulation activating neuroinflammatory responses, ultimately resulting in cellular damage. This review provides an exhaustive analysis complex mechanisms ischemic stroke, particular focus on interaction The interruption supply due to cerebral initiates activates including release inflammatory cytokines activation immune cells, contributing damage further disturbances. Studies indicate that metabolism significantly impairs neural cell function interacts neuroinflammation, exacerbating brain injury. Therapeutic strategies primarily concentrate modulating suppressing emphasizing importance in-depth research into their provide theoretical foundation for new treatment stroke. Future should how balance anti-inflammatory regulation minimize promote recovery.

Язык: Английский

Процитировано

1

Identifying disease progression biomarkers in metabolic associated steatotic liver disease (MASLD) through weighted gene co-expression network analysis and machine learning DOI Creative Commons
Weiliang Zhang,

Weirong Lu,

Yaqi Jiao

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 24, 2025

Metabolic Associated Steatotic Liver Disease (MASLD), encompassing conditions simple liver steatosis (MAFL) and metabolic associated steatohepatitis (MASH), is the most prevalent chronic disease. Currently, management of MASLD impeded by lack reliable diagnostic biomarkers effective therapeutic strategies. We analyzed eight independent clinical datasets from GEO database. Differential expression weighted gene co-expression network analyses (WGCNA) were used to identify 23 genes related inflammation. Five hub selected using machine learning techniques (SVM-RFE, LASSO, RandomForest) combined with a literature review. Nomograms created predict incidence, potential was evaluated through receiver operating characteristic (ROC) curves. Additionally, Protein-Protein Interaction (PPI) networks, functional enrichment, immune infiltration performed. Potential transcription factors agents also explored. Finally, biological significance these validated animal model, histological examination transcriptomic profiles. identified five genes-UBD/FAT10, STMN2, LYZ, DUSP8, GPR88-that are for MASLD. These exhibited strong potential, either individually or in combination. This study highlights key as promising candidates understanding findings offer new insights into disease's pathophysiology may contribute development better approaches.

Язык: Английский

Процитировано

1

PRMT6 promotes colorectal cancer progress via activating MYC signaling DOI Creative Commons
Xin Zhang,

Mingxin Jin,

Yali Chu

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 16, 2025

Colorectal cancer (CRC) remains a major global health challenge, with high rates of incidence and mortality. This study investigates the role protein arginine methyltransferase 6 (PRMT6) as an oncogene in CRC its mechanistic involvement tumor progression. We found that PRMT6 is significantly overexpressed tissues compared to adjacent normal associated poorer patient survival. Functional assays demonstrated promotes cell proliferation, migration, invasion. Mechanistically, enhances MYC signaling by stabilizing c-MYC through mono-methylation at 371, which inhibits poly-ubiquitination subsequent degradation. post-translational modification crucial for PRMT6-induced proliferation. Xenograft models further validated knockdown results reduced growth decreased levels. Our findings highlight key regulator stability progression, suggesting targeting or effects on could offer promising strategy treatment.

Язык: Английский

Процитировано

0

Application of nanoparticles with activating STING pathway function in tumor synergistic therapy DOI
Yi Yang,

Yaning Fang,

Xin‐Yu Du

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114013 - 114013

Опубликована: Янв. 18, 2025

Язык: Английский

Процитировано

0

PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 DOI Creative Commons

Yongli Fan,

Yuqin Li,

Xia Luo

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 4, 2025

Prostate Tumor Overexpressed 1 (PTOV1) is overexpressed and associated with malignant phenotypes in various types of tumors. However, the detailed roles PTOV1 its underlying mechanism CRC remain unclear. The clinical significance was assessed databases samples. effects on tumor-associated were detected by several vitro assays vivo mouse models. Immunoprecipitation (IP) combined protein mass spectrometry Co-Immunoprecipitation (Co-IP) used to identify p53 interacting PTOV1. Immunofluorescence assay, western blot transmission electron microscopy (TEM) analysis evaluated autophagy. Here, we revealed that highly expressed human tissues, especially at advanced stages, reduced survival time among patients. upregulated promoted cell proliferation, migration, invasion, tumor growth metastasis cells vivo. At molecular level, destabilized activating autophagy recruiting for cargo receptor SQSTM1 directed autophagic degradation. There a negative expression correlation between tissues. Moreover, overexpression or knockdown reversed pro-tumor CRC. Our study unveils oncogenic role progression, which achieved promoting degradation p53. These findings highlight potential targeting PTOV1-SQSTM1-p53 axis as therapeutic approach

Язык: Английский

Процитировано

0