Clinical and translational discovery最新文献

{"title":"Multi-omics integration driving precision medicine in non-small cell lung cancer: From molecular mechanisms to clinical translation","authors":"Yuang Gao,&nbsp;Liyan Lin,&nbsp;Hongrui Zhou,&nbsp;Muchen Li,&nbsp;Yunye Mao,&nbsp;Xiangwei Ge,&nbsp;Yangyang Jia,&nbsp;Yupu Li,&nbsp;Shu Sheng,&nbsp;JinZhao Zhai,&nbsp;Boyu Qin,&nbsp;Jinliang Wang","doi":"10.1002/ctd2.70187","DOIUrl":"https://doi.org/10.1002/ctd2.70187","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The molecular heterogeneity and therapeutic resistance of non-small cell lung cancer (NSCLC) remain significant clinical challenges. In recent years, the integration of multi-omics technologies has driven a paradigm shift in NSCLC research, evolving from static bulk sequencing to dynamic evolutionary tracking and high-resolution single-cell analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main body</h3>\u0000 \u0000 <p>Rather than a conventional catalogue of sequencing technologies, this review systematically addresses precision oncology through a clinical-problem-oriented framework. We emphasise the role of single-cell and spatial multi-omics in decoding the tumour immune microenvironment and uncovering rare, aggressive cellular subpopulations responsible for therapeutic resistance. Furthermore, we highlight the integration of metabolomics—particularly lipid metabolic reprogramming—in understanding adaptive resistance to tyrosine kinase inhibitors (TKI). We also comprehensively discuss current precision medicine practices, including spatial transcriptomics-guided antibody-drug conjugate (ADC) development, the clinical rationale for dual-target bispecific antibodies, and liquid biopsy for real-time longitudinal tracking. Crucially, we critically evaluate the current translational chasm and reproducibility crisis, demonstrating how artificial intelligence and advanced bioinformatics pipelines (e.g., MOFA+ and LASSO) can overcome data heterogeneity to extract robust prognostic signatures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By bridging the gap between high-dimensional data and prospective clinical validation, integrated multi-omics holds unprecedented promise for advancing personalised NSCLC management and ultimately improving patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of monocyte in pulmonary embolism via single-cell transcriptome sequencing of peripheral blood","authors":"Tang Luojia,&nbsp;Tang Cheng,&nbsp;Liu Xuanqi,&nbsp;Huang Yunchuan,&nbsp;Han Yi,&nbsp;Min Min,&nbsp;Song Dongli,&nbsp;Qie Jingbo,&nbsp;Lin Xiaolei,&nbsp;Tong Chaoyang","doi":"10.1002/ctd2.70208","DOIUrl":"https://doi.org/10.1002/ctd2.70208","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Research has shown that inflammation is crucial during the occurrence and development of pulmonary embolism (PE), but few of them focused specifically on the role of monocyte. This study aims to explore the pathological response of monocyte during the course of acute PE through single-cell RNA sequencing (scRNA-seq), providing cellular and genetic insights for early recognition, intervention and therapeutics of PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study recruited five patients with PE who received diagnosis and treatment at Zhongshan Hospital, Fudan University, from July 2021 to December 2021 and utilised publicly available PBMC scRNA-seq data from four healthy volunteers in the GEO dataset GSE149689 (GSM4509015, GSM4509023, GSM4509024 and GSM4509029). Fifteen PE time-point samples were initially collected; one PE Day 3 sample was excluded because it failed quality control, leaving 14 PE samples and four healthy donor samples, for a total of 18 peripheral blood single-cell sequencing datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The communication signals of peripheral blood mononuclear cells dynamically changed during PE. Inflammatory regulatory genes in monocytes exhibited significant changes along the cell developmental trajectory, and monocyte dysfunction persisted throughout the onset and progression of PE. The ANNEXIN signalling pathway in CD16+ monocytes and CD16- monocytes may play an important role, particularly suggesting that communication between CD16+ monocytes and CD16- monocytes is an indicator of PE progression and may be involved in the regulation of PE exacerbation and recovery. The S100 calcium-binding protein A8/A9 (S100A8/A9) genes and ferritin heavy chain 1/light chain (FTH1/FTL) genes may also play crucial roles in PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CD16+ monocytes and CD16- monocytes exhibited pathological responses during PE. The ANNEXIN pathway, S100A8/A9 genes and FTH1/FTL genes may also play significant roles.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability-guided transition modelling reveals an Active-to-Evasive immune ecosystem continuum in cervical cancer","authors":"Chia-Hung Chen,&nbsp;Tzu-Hsiang Weng,&nbsp;Hui-Ju Kao,&nbsp;Chen-Lin Yu,&nbsp;Cheng-Yi Pan,&nbsp;Chen-Chen Huang,&nbsp;Kai-Yao Huang,&nbsp;Shun-Long Weng","doi":"10.1002/ctd2.70214","DOIUrl":"https://doi.org/10.1002/ctd2.70214","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The transcriptomic organization of tumour immune ecosystems in cervical cancer remains poorly defined beyond conventional static immunophenotyping frameworks.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In the present study, we developed a stability-guided and transition-aware systems immuno-oncology framework to characterise immune ecosystem organisation in TCGA-CESC.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This framework identified a biologically coherent Active-to-Evasive immune ecosystem continuum through continuous transcriptomic modelling, stability analysis, and complementary immune ecosystem characterisation. Active tumours demonstrated preserved interferon-associated and cytotoxic immune programs, whereas Evasive tumours exhibited coordinated immune attenuation accompanied by hypoxia-associated and adaptive ecosystem-remodelling programs. The Intermediate subgroup occupied a biologically structured region between the Active and Evasive ends of the continuum, characterised by graded attenuation of immune-active programs, altered immune-gene coordination, and transition-associated transcriptomic remodelling.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;Bootstrap-guided repeated-convergence analyses identified reproducible transition-associated sentinel genes, including &lt;i&gt;SIRPG&lt;/i&gt;, &lt;i&gt;TIGIT&lt;/i&gt;, &lt;i&gt;CD96&lt;/i&gt;, &lt;i&gt;PRF1&lt;/i&gt;, &lt;i&gt;NKG7&lt;/i&gt;, and &lt;i&gt;TRAC&lt;/i&gt;, which consistently converged across trajectory-associated analyses, stability profiling, Evidence Matrix prioritisation, biologically anchored compression, and complementary analytical layers. Single-cell localisation analyses demonstrated preferential enrichment of these sentinel genes within activated cytotoxic immune compartments, whereas LM22-based deconvolution supported graded immune compositional remodelling across the continuum, including reduced CD8 T-cell and M1 macrophage-associated components together with relative enrichment of neutrophil- and macrophage M0-associated fractions towards the Evasive end. Sensitivity analyses further demonstrated that the underlying continuum was retained after outcome-independent reconstruction, exclusion of immune-definition genes, and adjustment for tumour purity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;These findings support a cross-sectional systems immuno-oncology model in which cervical cancer tumours are organised along an Active-to-Evasive immune ecosystem continuum characterised by graded immune attenuation, adaptive transcriptomic remodelling, and increasing immune–tumour uncoupling. The In","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149145564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in CRISPR-based detection technologies for severe fever with thrombocytopenia syndrome virus (Dabiebanda virus): A mini review","authors":"Junhu Wang,&nbsp;Changqiang Zhu,&nbsp;Jinzhao Chu,&nbsp;Yingqing Mao,&nbsp;Yixin Ge,&nbsp;Haiming Yi,&nbsp;Hongming Wang,&nbsp;Yuexi Li,&nbsp;Yong Qi","doi":"10.1002/ctd2.70216","DOIUrl":"https://doi.org/10.1002/ctd2.70216","url":null,"abstract":"<p>Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by the Dabiebanda virus, also referred to as the SFTS virus (SFTSV). Primarily transmitted via tick bites, SFTS occurs sporadically in East Asia and poses a serious threat to human health, with a reported mortality rate of up to 30%. In 2018, the World Health Organization designated SFTSV infection as a priority disease requiring urgent research and therapeutic development. In recent years, the prevalence range of this virus has shown a tendency to expand gradually. Rapid, sensitive, and specific detection of SFTSV is therefore essential for effective disease prevention and control. The CRISPR-Cas system has emerged as a promising molecular diagnostic technology. By employing specifically designed guide RNAs (such as sgRNA or crRNA) to direct Cas proteins for targeted nucleic acid recognition and cleavage, it offers superior sensitivity and specificity compared to conventional detection methods. This approach has been increasingly applied in SFTS diagnosis. Despite its significant advantages over traditional techniques, challenges remain in terms of technical stability, cost-effectiveness, and integration with existing diagnostic platforms. This mini review highlights recent advances in CRISPR-based detection of SFTSV and discusses its potential to enable rapid diagnosis and support precise disease management.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149145705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin L in cancer: Context-dependent functions, microenvironmental regulation and translational opportunities","authors":"Yujun Wu,&nbsp;Qin Huang,&nbsp;Zixuan Ding,&nbsp;Lin Fu,&nbsp;Mu Yang,&nbsp;Bi Peng,&nbsp;Pengbo Hu,&nbsp;Yuanhui Liu","doi":"10.1002/ctd2.70215","DOIUrl":"https://doi.org/10.1002/ctd2.70215","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cathepsin L (CTSL), a lysosomal cysteine endopeptidase, is implicated in multiple facets of tumour biology beyond its canonical role in intracellular protein turnover.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review provides a comprehensive synthesis of the current evidence regarding CTSL in cancer, evaluating its biochemical constraints, substrate selectivity within the cysteine cathepsin family, and context-dependent functions across diverse malignancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key findings</h3>\u0000 \u0000 <p>Mechanistically, across solid and haematological malignancies, such as breast and gastrointestinal cancers as well as paediatric acute myeloid leukaemia, CTSL promotes progression and therapy resistance through diverse processes, including extracellular matrix degradation, epithelial–mesenchymal transition, angiogenesis, and cell proliferation. These oncogenic functions are strongly context- and lineage-dependent rather than operating through a universal mechanism. Conversely, in stratified squamous epithelia, including the epidermis and cutaneous squamous cell carcinoma models, CTSL can exert tumour-suppressive effects by promoting EGFR degradation and limiting aberrant mitogenic signalling. In the tumour microenvironment, CTSL influences tumour immune evasion, myeloid-cell polarisation, and lymphocyte homeostasis. Translational studies have investigated CTSL in relation to prognosis and treatment response. In addition, its proteolytic activity has been exploited in engineered applications, including protease-cleavable antibody-drug conjugate linkers and activity-based diagnostic probes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Rather than acting as a universal driver, CTSL is a context-dependent modulator in cancer biology. Although no CTSL inhibitor has yet received clinical approval due to unfavourable ADME properties, off-target toxicity, and compensatory mechanisms, the development of selective extracellular-targeting strategies and companion diagnostics highlights its continuing promise as a therapeutic and diagnostic target in oncology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian cancer during pregnancy: Pregnancy-adjusted inflammatory and haematologic signatures for earlier risk recognition and clinical decision-making","authors":"Emmanuel Ifeanyi Obeagu","doi":"10.1002/ctd2.70213","DOIUrl":"https://doi.org/10.1002/ctd2.70213","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Ovarian cancer during pregnancy presents a diagnostic challenge because physiological pregnancy-associated haematologic and inflammatory changes can overlap with malignancy-associated abnormalities, while conventional tumour biomarkers, particularly cancer antigen 125 (CA-125), may have reduced specificity. Histopathological examination remains the definitive diagnostic standard, with ultrasound and, when indicated, magnetic resonance imaging providing the principal basis for non-invasive assessment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This mini-review examines the potential contribution of inflammatory markers and haematologic shifts to improving risk recognition and clinical decision-making in ovarian cancer during pregnancy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A focused narrative literature review was conducted using relevant peer-reviewed literature on ovarian cancer during pregnancy, pregnancy-associated haematologic changes, inflammatory mediators, systemic inflammatory indices, tumour biomarkers, imaging, and clinical decision-making. Evidence was critically synthesised to examine diagnostic limitations and the potential role of pregnancy-adjusted inflammatory and haematologic profiles in improving risk recognition and clinical assessment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pregnancy-associated changes in neutrophils, lymphocytes, platelets, haemoglobin and monocytes are considered alongside tumour-associated inflammatory processes involving interleukin-6, interleukin-8, tumour necrosis factor-α, transforming growth factor-β, vascular endothelial growth factor and related pathways. The potential utility of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index and lymphocyte-to-monocyte ratio is critically evaluated. Particular emphasis is placed on the distinction between physiological gestational variation and persistent or disproportionate inflammatory trajectories.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Inflammatory and haematologic markers should not be regarded as stand-alone diagnostic tests for ovarian cancer during pregnancy. Their greatest potential may lie in pregnancy-adjusted, longitudinal interpretation integrated with clinical assessment, imaging and tumour biomarkers. Prospective multicentre studies are required to establish gestational-age-specific reference ranges","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149047806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive peptides in cancer and inflammation: Mechanisms, model systems and clinical translation","authors":"Najwa Doha,&nbsp;Richa Gill,&nbsp;Sergio Crovella,&nbsp;Haissam Abou-Saleh,&nbsp;Sahar Isa Da'as","doi":"10.1002/ctd2.70209","DOIUrl":"https://doi.org/10.1002/ctd2.70209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bioactive peptides (BAPs), derived from both natural and synthetic sources, are increasingly recognized as multifunctional agents with potential roles in the management of cancer and inflammatory conditions, in addition to their well-established antimicrobial activity. Their biological activity is critically governed by their sequence-dependent physicochemical properties, including charge hydrophobicity, amphipathicity, and well-defined three-dimensional conformation, such as α-helices, β-sheets, and coils, which collectively determine target specificity, membrane interaction, and intracellular activity, ultimately determining therapeutic effectiveness and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Aside from in vitro models, animal models further validated their efficacy, enabling mechanistic insights and high-throughput screening.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>In cancer models, BAPs induce anti-cancer activity through various mechanisms such as membrane disruption, mitochondrial dysfunction, ROS generation, apoptosis, inhibition of invasion, migration, and angiogenesis across multiple cancer types, including breast cancer, particularly triple-negative breast cancer, colorectal, lung and melanoma, highlighting BAPs broad antitumor properties. Concurrently, BAPs regulate the immune system through cytokine modulation, NF-κB signalling suppression, reduced immune cell infiltration and macrophage polarization promotion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>However, despite these advances, clinical translation remains limited due to poor stability, short half-life, cytotoxicity, high production costs and optimized drug delivery systems. An integrated multidisciplinary approach with AI-guided design places BAPs as promising precision medicine tools for specific, immunomodulatory, and personalized anticancer and anti-inflammatory therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-based therapeutic and modelling approaches in Huntington's disease: Progress, challenges and future directions","authors":"Kairat Zhakipbekov,&nbsp;Surayyo Eshkabilova,&nbsp;Zokir Raximov,&nbsp;Sharof Eshonov,&nbsp;Abdusaid Khasanov,&nbsp;Ziyodulla Tokhtamurod,&nbsp;Axmadjan Ashurmetov,&nbsp;Avazbek Abduraxmanov,&nbsp;Niyozbek Abdurakhmonov,&nbsp;Elmurod Eshqobilov,&nbsp;Seyed Mohsen Mirhosseini,&nbsp;Amir Arsalan Ghahari","doi":"10.1002/ctd2.70211","DOIUrl":"https://doi.org/10.1002/ctd2.70211","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-repeat expansion in exon 1 of the huntingtin gene (&lt;i&gt;HTT&lt;/i&gt;). Mutant huntingtin accumulation and somatic repeat expansion contribute to neuronal dysfunction, making HD a compelling target for CRISPR-based intervention.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate CRISPR technologies for &lt;i&gt;HTT&lt;/i&gt; modulation, validation of somatic CAG-expansion modifiers, and HD modeling, with emphasis on efficacy, selectivity, delivery, and safety.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This narrative review synthesizes preclinical evidence on DNA-targeting nucleases, CRISPR interference, RNA-targeting Cas13 systems, repeat stabilization, functional screens, and cellular and animal models. Approaches are compared by mechanism, durability, allele selectivity, central nervous system delivery, and translational limitations.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cas9-based strategies can disrupt &lt;i&gt;HTT&lt;/i&gt; or excise exon 1, while SNP-linked PAMs and guide mismatches may enable allele-selective editing in genetically eligible patients. dCas9-KRAB represses &lt;i&gt;HTT&lt;/i&gt; transcription without DNA cleavage, whereas RfxCas13d/CasRx reduces &lt;i&gt;HTT&lt;/i&gt; RNA without permanent genome modification; for both, selectivity and durability depend on guide design and delivery. CRISPR screens have identified expansion-promoting DNA repair factors, including MSH3, MLH3, and PMS1, whereas protective factors such as FAN1 should be preserved. CAG-to-CAA base editing offers a complementary repeat-stabilizing strategy. CRISPR-corrected isogenic induced pluripotent stem cell-derived neurons, organoids, and CRISPR-generated large-animal models strengthen mechanistic studies; conventional Q140 and zQ175 knock-in mice remain useful for testing interventions but were not generated using CRISPR. Evidence remains preclinical. Major barriers include brain-wide delivery, incomplete neuronal coverage, loss of wild-type HTT function, heterogeneous on-target repair, off-target DNA or RNA activity, immune responses, durability, patient stratification, and long-term safety.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;CRISPR is a versatile platform for HD research and development, but no approach yet combines adequate central nervous system distribution, mutant-allele selectivity, durable neurological benefit, and established long-term safet","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallstone formation and hepatobiliary tumour risk: Clinical implications of the bile acid–gut microbiota axis","authors":"Rui Li,&nbsp;Yong Zhang,&nbsp;Kaishuang Cai,&nbsp;Shaojun Deng,&nbsp;Chaofeng Tan,&nbsp;Yunjie Li,&nbsp;Wenjin Liang","doi":"10.1002/ctd2.70207","DOIUrl":"https://doi.org/10.1002/ctd2.70207","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gallstones affect approximately 6%–15% of adults worldwide and represent a common condition that also serves as a risk factor for hepatobiliary malignancies. Conventional ultrasound cannot provide early warning during the early metabolic phase before crystallization occurs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review provides a critical synthesis of the mechanisms, clinical evidence, and translational perspectives of the bile acid–gut microbiota axis in gallstone development and hepatobiliary tumour risk. Relevant publications up to September 2026 were identified through searches of MEDLINE/PubMed, EMBASE, and Web of Science, with additional manual screening of reference lists. Randomized clinical trials, systematic reviews, meta-analyses, key mechanistic studies, and guidelines were preferentially included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with gallstones exhibit characteristic alterations, including elevated serum glycocholic acid (+ 0.83 µmol/L) and taurocholic acid (+ 0.51 µmol/L), reduced microbial diversity (<i>Proteobacteria</i> accounting for 91.59%), and a 2.5 - fold increase in <i>bai</i> gene cluster abundance (<i>r</i> = 0.609). Conjugated bile acids show a dose-response relationship with hepatocellular carcinoma risk (OR = 1.28–5.62), while late breakfast increases gallstone risk (OR = 1.435). The combination of dried blood spot sampling (<i>R</i>² &gt; 0.92) and AI-based prediction models (AUC = 0.82–0.90) offers a feasible approach for dynamic \u0000monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review proposes a three-tiered stratified management strategy—DBS sampling, targeted metabolomics, and AI assessment—to provide a clinical translational reference for early warning and precision prevention of gallstones and hepatobiliary tumours.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of red and infrared light on the modulation of microglial activities","authors":"Hossein Chamkouri","doi":"10.1002/ctd2.70210","DOIUrl":"https://doi.org/10.1002/ctd2.70210","url":null,"abstract":"&lt;p&gt;Red and near-infrared (NIR) photobiomodulation (PBM) is emerging as a non-invasive strategy for regulating neuroimmune function by coupling photon absorption to mitochondrial and redox signalling (Figure 1).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Microglia, as highly plastic resident immune cells of the central nervous system, represent a particularly important cellular target because their metabolic state, inflammatory phenotype, phagocytic capacity and interactions with neurons and vascular cells strongly influence neurological homeostasis.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Increasing evidence indicates that red and NIR light can remodel microglial bioenergetics and inflammatory activity rather than simply suppressing inflammation.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Photon-dependent modulation of mitochondrial respiration, reactive oxygen species (ROS), nitric oxide (NO), calcium signalling and transcriptional pathways can shift microglia towards repair-competent states, enhance pathological protein clearance and reduce neurotoxicity. This perspective therefore positions microglial PBM as a wavelength-, dose- and temporal-dependent bioenergetic intervention with potential relevance to neurodegenerative disease.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Microglia continuously survey the neural environment and rapidly transform their morphology, metabolism, transcriptional programs and secretory profiles in response to tissue injury, infection, protein aggregation, vascular dysfunction or neuronal stress.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Although inflammatory activation is essential for acute host defence, persistent microglial activation can generate excessive cytokines, ROS, reactive nitrogen species and complement-associated signals that propagate neuronal and synaptic injury. This maladaptive state is particularly relevant to Alzheimer's disease (AD), Parkinson's disease, traumatic brain injury and other disorders characterised by chronic neuroinflammation (Figure 1).&lt;span&gt;&lt;sup&gt;2-4&lt;/sup&gt;&lt;/span&gt; Importantly, microglia should not be conceptualised as a binary M1/M2 system; rather, they occupy dynamic and context-dependent molecular states along an injury–repair continuum. Red and NIR PBM provides a physical means of perturbing this continuum through controlled photon delivery. Experimental studies have shown that NIR exposure can alter microglial morphology, increase association with amyloid-β (Aβ), enhance phagocytic activity and reduce inflammatory signalling, establishing microglia as a mechanistically relevant target rather than a secondary consequence of neuronal photostimulation.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;At the mechanistic level, the biological response begins with wavelength-dependent photon absorption by endogenous chromophores. Cytochrome c oxidase (CCO; mitochondrial complex IV) is a leading candidate photoreceptor for red-to-NIR PBM, although the initiating mechanisms become less certain at longer wavelengths. CCO contains haem and copper centres capable of interacting w","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}