Precision Clinical Medicine最新文献

{"title":"Protein modification systems as cancer biomarkers and therapeutic targets.","authors":"Li Gao, Yueqin He, Kexin Wang, Qin Li, Litong Nie, Lunzhi Dai","doi":"10.1093/pcmedi/pbag014","DOIUrl":"10.1093/pcmedi/pbag014","url":null,"abstract":"<p><p>Protein post-translational modifications (PTMs), such as acetylation, lactylation, methylation, phosphorylation, ubiquitination, and glycosylation, play central roles in regulating diverse cellular processes, including signal transduction, metabolic adaptation, chromatin organization, and proteostasis. In cancer, PTM networks are extensively rewired, with profound alterations in enzyme levels, protein modification landscapes, and crosstalk among different modification types. These changes collectively shape key cancer hallmarks, such as sustained proliferative signaling, immune evasion, and therapeutic resistance. Recent advances in proteomic technologies have enabled comprehensive mapping of PTM landscapes and their regulatory mechanisms, facilitating the identification of PTM signatures associated with tumor subtyping, disease progression, and treatment response. This review summarized biomarkers and therapeutic targets associated with dysregulated PTM regulatory pathways in cancer.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag014"},"PeriodicalIF":6.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13220048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139030","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":"JS-K induces autophagy-dependent ferroptosis in bladder cancer: a multimodal mechanistic and translational study.","authors":"Zhuo Li, Haitao Zhong, Daniel Baptista-Hon, Jingping Qiu, Zhongwei Zhang, Xinrui Zhang, Yuwan Zhao, Lugang Zhu, Sheng Gao, Bin Li, Olivia Monteiro, Jianjun Liu, Yumin Zhuo","doi":"10.1093/pcmedi/pbag012","DOIUrl":"10.1093/pcmedi/pbag012","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer is the most common urological malignancy. Bladder cancer has limited therapeutic options, especially in advanced stages. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a promising target for cancer therapy. However, the role of autophagy in modulating ferroptosis remains incompletely understood.</p><p><strong>Methods: </strong>We investigated the anti-tumor effects of JS-K, a nitric oxide-releasing prodrug, in bladder cancer through integrated cell, animal, and patient data studies. <i>In vitro</i> experiments with T24 and UM-UC-3 cells were used to explore how JS-K influences cancer cell survival and the interplay between autophagy and ferroptosis. <i>In vivo</i>, a BALB/c nude mouse tumor model provided a system to examine tumor response and tissue-level changes. To extend these findings to the clinical setting, we analyzed <i>LC3B</i> expression and its associations with ferroptosis-related genes, patient prognosis, and the tumor immune microenvironment.</p><p><strong>Results: </strong>JS-K induced mitochondrial damage, lipid peroxidation, reactive oxygen species accumulation, and intracellular iron overload in bladder cancer cells in a concentration-dependent manner. These changes were accompanied by downregulation of GPX4 and SLC7A11 and upregulation of FTH1 and TFR1, indicative of ferroptosis. Inhibition or knockdown of the autophagy marker <i>LC3B</i> reversed these effects, establishing the role of autophagy in mediating ferroptosis. In xenograft models, JS-K suppressed tumor growth, an effect abrogated by <i>LC3B</i> silencing. Integrated transcriptomic and single-cell analyses revealed a strong correlation between <i>LC3B</i> and ferroptosis-related genes, with <i>CISD1</i> identified as a key prognostic marker.</p><p><strong>Conclusions: </strong>JS-K induces autophagy-dependent ferroptosis in bladder cancer cells and significantly suppresses tumor progression. Targeting the autophagy-ferroptosis axis offers a novel therapeutic strategy for bladder cancer treatment.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag012"},"PeriodicalIF":6.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017744","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":"Circular RNA as emerging precision therapeutics: from RNA regulation to peptide translation.","authors":"Nan Wu, Jeremiah Amalraj, Burton B Yang","doi":"10.1093/pcmedi/pbag011","DOIUrl":"10.1093/pcmedi/pbag011","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs characterized by a covalently closed-loop structure. Although initially regarded as splicing byproducts, circRNAs are now recognized as essential regulators of gene and protein expression and play important roles in various human diseases. In recent years, growing evidence has indicated that a subset of circRNAs can be translated through cap-independent mechanisms to produce bioactive peptides or proteins. These findings expand the functional scope of circRNAs and offer new opportunities for RNA therapy. This review summarizes recent advances in circRNA biology, with an emphasis on their potential in diagnosis and treatment. We also review the therapeutic strategies targeting circRNAs at both the RNA and protein levels and the delivery systems that support circRNA-directed therapies. After we discuss how circRNA therapeutics may be integrated into precision medicine, we further highlight the current clinical progress and key challenges for advancing circRNA-based therapies toward clinical application.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag011"},"PeriodicalIF":6.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782763","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":"Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.","authors":"Hao Liu, Shuaiyong Zhao, Huiqin Gao, Yue Wang, Junyan Gao, Ping Guo, Yiting Yang, Wenrui Cui, Shuanglin Zhang, Yaping Shi, Guanxing Xie, Yutong Han, Junya Zhou, Qingqi Zhang, Yunzeng Zou","doi":"10.1093/pcmedi/pbag010","DOIUrl":"10.1093/pcmedi/pbag010","url":null,"abstract":"<p><p>Atherosclerosis is a disease centered on chronic inflammation, in which mitochondrial damage plays a key role in its initiation and progression. Traditionally, atherosclerosis is thought to be triggered by cholesterol accumulation, but recent studies have revealed that mitochondrial dysfunction has emerged as an important driving factor by inducing innate immune imbalance. In atherosclerosis, mitochondria undergo changes in membrane permeability, metabolic disorders, and dynamic imbalance due to oxidative stress and other factors, releasing mitochondrial damage-associated molecular patterns (mt-DAMPs). These mt-DAMPs activate innate immune pathways, promote the production of type I interferons and the release of pro-inflammatory factors such as interleukin 1β, and accelerate plaque progression. Mitophagy exerts a protective effect by eliminating damaged mitochondria. Specifically, the PINK1-Parkin pathway labels damaged mitochondria through ubiquitination; mitophagy receptors (such as NIX, FUNDC1, and BNIP3) directly bind to LC3 to initiate ubiquitination-independent mitophagy; and mitochondrial-derived vesicles selectively encapsulate damaged components and target them to lysosomes for degradation. All these processes can reduce mt-DAMP-induced damage and inhibit excessive immune activation. In this review, we summarize that innate immune imbalance caused by mitochondrial damage is a key mechanism for atherosclerosis progression. Mitochondrial quality control clears damaged mitochondria through multiple pathways, alleviates inflammatory responses and plaque burden, and provides potential targets for atherosclerosis treatment. Its precise regulatory mechanisms and drug development are future research directions.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag010"},"PeriodicalIF":6.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677099","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":"Agrimol B inhibits pancreatic ductal adenocarcinoma by induction of lethal mitophagy through decreasing mitochondrial transcription termination factor 3.","authors":"Yifei Ma, Ying Zheng, Ying Zhou, Yang Yang, Jinlu Liu, Ningna Weng, Junhong Han, Qing Zhu","doi":"10.1093/pcmedi/pbag009","DOIUrl":"10.1093/pcmedi/pbag009","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the inhibitory effect of the natural polyphenol Agrimol B on pancreatic ductal adenocarcinoma (PDAC) and its underlying molecular mechanisms.</p><p><strong>Methods: </strong>The effects of Agrimol B on PDAC cell proliferation and apoptosis were assessed using Cell Counting Kit-8, colony formation, and flow cytometry assays. An <i>in vivo</i> PDAC xenograft mouse model was established for evaluation. Label-free quantitative proteomics, western blotting, immunofluorescence, and transmission electron microscopy were employed to analyze mitochondrial function, autophagy, and related signaling pathways. A patient-derived organoid model was used to evaluate the synergistic effects of Agrimol B with first-line chemotherapy drugs.</p><p><strong>Results: </strong>Agrimol B significantly inhibited PDAC growth and induced apoptosis both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, Agrimol B downregulated the expression of mitochondrial transcription termination factor 3, and promoted the accumulation of PTEN induced kinase 1 (PINK1) in mitochondria and Parkin translocation, thereby excessively activating PINK1/Parkin-dependent mitophagy. Concurrently, Agrimol B blocked lysosome biogenesis, leading to autophagosome accumulation and impaired autophagic flux. This dysfunctional autophagy ultimately mediated the anti-PDAC effect of Agrimol B. Furthermore, in PDAC patient-derived organoids, Agrimol B exhibited synergistic effects with first-line chemotherapy drugs such as gemcitabine and nab-paclitaxel.</p><p><strong>Conclusion: </strong>Agrimol B exerts its anti-PDAC effects by downregulating mitochondrial transcription termination factor 3, hyperactivating PINK1/Parkin-mediated mitophagy, and obstructing autophagic flux. Its synergistic effect with chemotherapy drugs provides experimental evidence supporting its potential clinical translation.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag009"},"PeriodicalIF":6.4,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677074","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":"Artificial intelligence-driven peptide blocks gasdermin pyroptosis and alleviates inflammation.","authors":"Mingsheng Liu, Hongqing Zhou, Min Wu","doi":"10.1093/pcmedi/pbag004","DOIUrl":"10.1093/pcmedi/pbag004","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag004"},"PeriodicalIF":6.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469574","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":"Linking first-pass reperfusion success to proteomic markers in large and medium vessel ischemic stroke: an exploratory study.","authors":"Crhistian-Mario Oblitas, Sabela Fernández-Rodicio, Manuel Rodríguez-Yáñez, Emilio Rodríguez-Castro, Arturo Gonzalez-Quintela, Jacobo Porto-Álvarez, Javier Martínez-Fernández, Miguel Blanco, Jose Luis Taboada, Sara Martnez-Reiriz, Susana B Bravo, Carmen Pena, José Castillo, Maria Luz Alonso-Alonso, Pablo Hervella, Antonio J Mosqueira, Ramón Iglesias-Rey","doi":"10.1093/pcmedi/pbag008","DOIUrl":"10.1093/pcmedi/pbag008","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag008"},"PeriodicalIF":6.4,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515243","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":"Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.","authors":"Xiaohong Liu, Hongye Gao, Jianhua Yu","doi":"10.1093/pcmedi/pbag007","DOIUrl":"10.1093/pcmedi/pbag007","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-engineered immune cells have revolutionized cancer immunotherapy, expanding from the established success of CAR-T cells to a diverse array of cellular platforms. While seven Food and Drug Administration-approved CAR-T cell products demonstrate unprecedented efficacy in hematologic malignancies, significant limitations persist, including severe inflammatory toxicities, resistance in solid tumors, and manufacturing barriers. These challenges have catalyzed extensive research to extend CAR engineering into alternative effector cell types, such as unconventional T cell subsets, natural killer (NK) cells, macrophages, neutrophils, and dendritic cells, as well as non-immune platforms. Each cell type exhibits distinct antitumor mechanisms, persistence profiles, safety characteristics, and manufacturing requirements, positioning them to address complementary therapeutic needs. This review provides a comprehensive overview of diverse CAR-engineered cellular platforms, encompassing their biological properties, advantages, sourcing strategies, and manufacturing processes, alongside current clinical progress and optimization approaches. Beyond oncology, these platforms have demonstrated significant potential in treating autoimmune diseases, infections, cardiac fibrosis, and senescence-associated disorders. By leveraging distinct immune and non-immune cell types to mediate cytotoxicity or suppress pathogenic cells, CAR technology provides versatile therapeutic avenues across varied disease contexts. Through synthesis of recent advances in CAR platform diversity, this review identifies opportunities for targeted optimization and explores future directions for broadening CAR-based therapeutic applications.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag007"},"PeriodicalIF":6.4,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469568","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":"Pressure cycling technology-assisted data-independent acquisition proteomics reveals molecular alterations and potential therapeutic targets in minor glomerular abnormalities.","authors":"Ling Li, Yingying Ling, Fei Cai, Yi Zhong, Hao Yang, Fang Liu, Guisen Li, Xinfang Xie, Rajeev K Singla, Dengyan Ma, Yong Zhang","doi":"10.1093/pcmedi/pbag006","DOIUrl":"10.1093/pcmedi/pbag006","url":null,"abstract":"<p><strong>Background: </strong>Minor glomerular abnormalities (MGAs) are histopathologically heterogeneous renal lesions with subtle structural changes and latent clinical manifestations, yet their molecular mechanisms remain poorly characterized and underexplored.</p><p><strong>Methods: </strong>In this study, we employed pressure cycling technology-assisted sample preparation combined with data-independent acquisition mass spectrometry to systematically compare the proteomic profiles of distant non-neoplastic tissues (<i>n</i> = 24) and MGA tissues (<i>n</i> = 27).</p><p><strong>Results: </strong>A total of 9 529 protein groups were quantified with a false discovery rate < 1%, and 1 338 differentially expressed protein groups were identified (fold-change > 2 or < 0.5, <i>P</i> < 0.05), including 190 downregulated and 1 148 upregulated protein groups in MGA tissues. Gene ontology analysis revealed that the downregulated proteins were enriched in cell adhesion, ion binding, and molecular transport, whereas the upregulated proteins were enriched in transcriptional regulation, DNA replication/repair, and nucleic acid binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated inhibition of metabolic pathways and the peroxisome proliferator-activated receptor signaling pathway, as well as the activation of basal transcription factors and nucleotide excision repair in MGAs. Further screening revealed 13 core upregulated nuclear proteins (e.g. YY1, TAF9, RFC1, and POLR1D) with a >90% detection rate in MGA tissues; these proteins are functionally associated with renal inflammation, cell proliferation, and the DNA damage response.</p><p><strong>Conclusion: </strong>Our study establishes a high-resolution proteomic landscape of MGAs, provides novel insights into their molecular pathogenesis, and identifies potential tissue biomarkers and therapeutic targets. The pressure cycling technology-assisted data-independent acquisition workflow also offers a robust technical framework for proteomic analysis of microscale renal biopsy samples.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag006"},"PeriodicalIF":6.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499957","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":"Spatial genomics and brain spatial transcriptomic atlas for precision medicine.","authors":"Wei Xiong, Alexander Hindeleh, Charles Wang","doi":"10.1093/pcmedi/pbag005","DOIUrl":"10.1093/pcmedi/pbag005","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag005"},"PeriodicalIF":6.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469579","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}