Clinical and translational discovery最新文献

{"title":"Drug Sensitivity patterns across FAB subtypes and molecular mutations in AML: A comprehensive analysis for precision medicine","authors":"Mobina Shrestha,&nbsp;Bishwas Mandal,&nbsp;Vishal Mandal,&nbsp;Sabin Karki,&nbsp;Reshu Thapa","doi":"10.1002/ctd2.70046","DOIUrl":"https://doi.org/10.1002/ctd2.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by distinct French–American–British (FAB) classifications and molecular mutations. Understanding how these biological markers relate to drug responses is crucial for refining therapeutic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined drug sensitivity patterns in 186 AML patients using selective Drug Sensitivity Scores (sDSS), analysing data from 515 commercially available chemotherapeutic and targeted oncology agents. Drug sensitivity was analysed across various FAB subtypes (M0, M1, M2, M4, M4 eos, M4/M5, and M5) and important mutations (NPM1, FLT3, FLT3-ITD, FLT3-TKD and KIT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Navitoclax showed greater effectiveness in M0, M1, and M2 subtypes. NPM1 mutations were linked to increased sensitivity to multiple therapeutic agents. FLT3-ITD mutations were associated with significant responsiveness to PI3K/mTOR inhibitors. Analysis of drug combinations revealed complexities in using multiple therapeutic agents, often leading to reduced effectiveness but providing insights into successful drug pairings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings underscore the necessity for personalised therapeutic strategies in AML, advocating for treatment protocols that integrate individual mutation profiles and FAB classifications to enhance patient care and improve clinical outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689234","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":"Risk of gastric cancer in autoimmune gastritis and pernicious anaemia: Insights from Mendelian randomization and multi-omics analysis","authors":"Shengan Zhang,&nbsp;Ziqi Zhang,&nbsp;Liang Dai,&nbsp;Wenjun Zhou,&nbsp;Yanqi Dang,&nbsp;Wendong Huang,&nbsp;Guang Ji","doi":"10.1002/ctd2.70036","DOIUrl":"https://doi.org/10.1002/ctd2.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The newly onset debate surrounding the risk of gastric cancer (GC) in autoimmune gastritis (AIG) and pernicious anaemia has intensified. It is necessary to supplement higher level research evidences to settle this issue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two-sample Mendelian randomization (MR) analysis using inverse variance weighted method was conducted to reveal the causal relationship between pernicious anaemia and GC. Because of the absence of available summary statistics for AIG at present, we used pernicious anaemia as a proxy exposure, as it was frequently used interchangeably. The multi-omics characteristics of AIG and pernicious anaemia were further explored through proteome-wide MR, colocalization, and transcriptome sequencing analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MR analysis found pernicious anaemia was causally associated with a higher risk of GC (odds ratio: 1.16, 95% confidence interval [1.03, 1.31], <i>p</i> = .018). Sensitivity analyses confirmed the stability of the results. The up-regulation of genes involved in gastric dysplasia and carcinogenesis, including receptor activity-modifying protein 3, fibroblast growth factor 3, transforming growth factor beta-2 and tumour-associated calcium signal transducer 2, suggested potential mechanisms underlying the risk of GC in AIG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results emphasized the independent link from AIG and pernicious anaemia to GC. Therefore, endoscopy follow-up for GC screening in AIG is still appealed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689375","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":"Structural insights into retinoic acid receptor activation and selective modulators","authors":"Yining Song,&nbsp;Wenrui Zhao,&nbsp;Xuan Huang,&nbsp;Lai Wei,&nbsp;Jingyi Han,&nbsp;Jiayun Hou,&nbsp;Min Li,&nbsp;Xin Cao","doi":"10.1002/ctd2.70043","DOIUrl":"https://doi.org/10.1002/ctd2.70043","url":null,"abstract":"<p>Retinoic acid receptors (RARs), including RARα, RARβ and RARγ, serve as essential nuclear receptors that act as transcription factors activated by ligands. They predominantly regulate gene expression and affect various biological processes, including differentiation. Their dysregulation is implicated in various cancers and other diseases, notably acute promyelocytic leukaemia (APL), where the promyelocytic leukemia (PML)‒RARα fusion protein disrupts normal granulocyte maturation. All-trans retinoic acid, which promotes the degradation of this fusion protein is a key therapeutic agent for APL and is also involved in the treatment of other diseases. Recently, various selective RAR modulators targeting specific RAR subtypes have been developed, which show promise in treating cancer and other diseases. The structural biology of RARs reveals how ligand binding induces conformational changes that facilitate co-activator recruitment, thereby modulating transcription. This review explores the crystal structures of RARs in various activation states, detailing RARs’ interactions with retinoid X receptors, ligands, DNA and co-regulators, and emphasises the importance of understanding these mechanisms for the rational design of new RAR-targeted therapies. The potential for developing selective RAR modulators is highlighted, along with the need for comprehensive structural data to enhance our understanding of RAR functions in disease contexts. Future research directions include utilising advanced imaging techniques and artificial intelligence-driven predictions to elucidate the dynamics of RAR complexes, ultimately aiming to translate structural insights into clinical applications for various diseases.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602668","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":"Towards a one-time cure for Fabry disease: Lentivirus-mediated haematopoietic stem and progenitor cell gene therapy","authors":"Rina Kansal","doi":"10.1002/ctd2.70042","DOIUrl":"https://doi.org/10.1002/ctd2.70042","url":null,"abstract":"&lt;p&gt;Fabry disease, also known as Anderson‒Fabry disease, is an X-linked systemic disease first described independently in Germany and England over 125 years ago, in 1898, in patients presenting with small, reddish purple telangiectatic cutaneous papules called &lt;i&gt;angiokeratoma corporis diffusum&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Five decades later, in 1947, the concept of a lipid storage disease emerged following postmortem studies, and the abnormal lipid was identified as trihexosyl ceramide in 1963.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Subsequently, the underlying deficiency of the lysosomal enzyme α-galactosidase, which cleaves galactose from the neutral glycosphingolipid, globotriaosylceramide (Gb&lt;sub&gt;3&lt;/sub&gt;) or trihexosyl ceramide, in the normal cellular degradation pathway, was identified.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; The enzyme activity was near-completely deficient in leukocytes in affected males and reduced in female carriers of the disease compared to normal leukocytes.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In 1978, the α-galactosidase A (&lt;i&gt;GLA)&lt;/i&gt; gene, which encodes the enzyme, was found to be located in the Xq22 chromosomal region, and the gene's nucleotide sequence was identified in 1986. Gene mutations in &lt;i&gt;GLA&lt;/i&gt; that do not allow enzyme expression were recognised as the fundamental cause of Fabry disease.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Although the clinical features of this inherited disease, including neurologic pain in the extremities, cutaneous angiokeratomas, hypohidrosis, and corneal opacities, are evident in childhood, the diagnosis of classic Fabry disease is often missed and delayed, with an average age of 29 years at diagnosis.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; The disease worsens in untreated adults due to the progressive accumulation of glycosphingolipids in various cells across multiple organ systems, leading to cardiovascular, cerebrovascular, and renal damage that shortens lifespan. Females exhibit variability in disease severity and may be asymptomatic or experience complications like affected males. Until 2001, no treatment was available to halt disease progression, when enzyme replacement therapy (ERT) was approved for treating Fabry disease in Europe, followed by approval in the United States in 2003.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Nonetheless, ERT is very expensive, requires biweekly infusions for life, and its efficacy may be reduced if the patient develops an antibody response. Migalastat, a pharmacologic chaperone therapy approved for adults with Fabry disease since 2016, is only applicable for 30%–50% of patients who have &lt;i&gt;GLA&lt;/i&gt; mutations that are amenable to increase the activity of the deficient enzyme with the drug; furthermore, the in vitro determinations of amenability do not translate to in vivo drug efficacy.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Medin et al. began their gene therapy efforts more than two decades ago with the vision of developing a one-time cure for Fabry disease.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; In an accompanying article in thi","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602776","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":"Cell therapy based on stem cells or their extracellular vesicles during kidney graft preservation: Current state of the art and novelties","authors":"Nessma Chenaf-Benabdelmoumene,&nbsp;Thierry Hauet,&nbsp;Clara Steichen","doi":"10.1002/ctd2.70040","DOIUrl":"https://doi.org/10.1002/ctd2.70040","url":null,"abstract":"&lt;p&gt;Transplantation often remains the best therapeutic option in terms of life quality and disease prognosis improvement to treat chronic or even acute organ failure. According to a report published by the World Health Organization in 2023,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; less than 10% of the world's organ needs are covered. Focusing on the kidney, which is now the most transplanted organ in the world, the latest report of the Global Observatory on Donation and Transplantation published in 2023 (based on 2022 data)&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; pointed out the gap between supply and demand: there are currently more patients on the active waiting list than there are grafts available for them worldwide. Kidney grafts can come from two main different sources: living donors, which represent a minority of donations, and deceased donors. Nevertheless, the organ shortage, which has been worsening year after year, has led to extend donation criteria over the years. This means, for example, the use of deceased donors not only after brainstem death but also after unpredictable irreversible circulatory arrest with immediate cardiopulmonary resuscitation attempted by trained providers (according to the Maastricht classification, second category) and after circulatory arrest occurring based on a decision to withhold or withdraw life-sustaining treatment (according to the Maastricht classification, third category). These death circumstances are usually associated with intensive donor reanimation processes consisting in noradrenaline administration, in massive vascular filling to prevent reanimation complications such as inflammation, haemodynamic instability or acute kidney failure. Extended criteria donors also include older donors aged over 65 years and donors with comorbidities such as arterial hypertension, cardiopathy, diabetes and even chronic kidney failure. The growing need for organs may also result in organs being transported from more distant regions. In all these situations kidney grafts are more susceptible to be affected by ischaemia‒reperfusion (IR) injuries.&lt;/p&gt;&lt;p&gt;IR is a pathophysiological phenomenon taking place from the donor's reanimation to the recipient's transplantation. Ischaemia is induced by the sudden arrest of oxygen and nutrients supply during the organ retrieval step, which may be prolonged during organ preservation sequence depending on its modalities. Reperfusion occurs when anastomoses are performed between the graft and the recipient and refers to the massive oxygen supply in a medium, which was previously deprived of oxygen.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; On a microscopic scale, this phenomenon is associated with shifts in mitochondrial metabolism and function, by a release of reactive oxidative species causing cytoskeleton destruction, complement system activation and recruitment of innate and adaptative immune cells.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Faced with these perturbations, the cell eventually dies by necrosis, phagocytosis or apoptosis. On a ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581680","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":"Involvement of S100A8 and S100A9 in nonischaemic cardiomyopathy","authors":"Qiu-Yue Lin,&nbsp;Wen-Xi Jiang,&nbsp;Hui-Hua Li","doi":"10.1002/ctd2.70039","DOIUrl":"https://doi.org/10.1002/ctd2.70039","url":null,"abstract":"<p>The heterodimeric complex of S100 calcium binding proteins A8 and A9 (S100A8/A9, also known as Calprotectin) is constitutively expressed in myeloid neutrophils and monocytes and plays a role in the modulation of the inflammatory response and cytoskeleton rearrangement. Recently, S100A8/A9 complex has garnered significant attention as a critical alarmin involved in regulating the pathogenesis of various inflammatory cardiovascular diseases, particularly nonischaemic cardiomyopathy (NICM). Furthermore, S100A8/A9 is reportedly associated with the pathophysiological processes of myocardial ischaemia‒reperfusion injury and has also been recognised as a predictor and a potential mediator of heart failure caused by acute myocardial infarction. Recent studies have attempted to provide a comprehensive and detailed overview of the involvement of the S100A8/A9 protein in NICM, covering topics such as hypertrophic myocardial remodelling, septic and dilated cardiomyopathy, myocarditis, chemotherapeutic cardiotoxicity, senescent cardiac dysfunction and cardiac allograft rejection. Ultimately, we aimed to evaluate the application of S100A8/A9 as promising biomarkers and therapeutic strategies for the prediction, prevention and treatment of NICM.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554532","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":"Commentary on ‘Lentivirus-mediated gene therapy for Fabry disease: 5-year end-of-study results from the Canadian FACTS trial’","authors":"Alessandro Rossi,&nbsp;Nicola Brunetti-Pierri","doi":"10.1002/ctd2.70038","DOIUrl":"https://doi.org/10.1002/ctd2.70038","url":null,"abstract":"&lt;p&gt;Fabry disease is an X-linked lysosomal storage disorder of glycosphingolipid catabolism caused by pathogenic variants in the &lt;i&gt;GLA&lt;/i&gt; gene encoding α-galactosidase A (α-Gal A). It is a progressive disorder with involvement of the renal, cardiac, neurologic and cerebrovascular systems, leading to reduced life expectancy.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; α-Gal A deficiency causes lysosomal accumulation of glycosphingolipids such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in the vascular endothelium, epithelial cells, podocytes, cardiomyocytes, mesangial cells and renal tubular cells. Currently available treatments for Fabry disease [enzyme replacement therapy (ERT) and chaperone therapy] are effective in mitigating the decline of renal and cardiac functions and increasing survival.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; However, ERT is hampered by the enzyme's short half-life, incomplete tissue penetration, infusion-related reactions, and the development of antidrug antibodies. On the other hand, oral chaperone therapy has broad tissue distribution and penetration, but its efficacy is restricted to patients carrying specific &lt;i&gt;GLA&lt;/i&gt; variants.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Therefore, novel and more effective treatments are needed. The Fabry Disease Clinical Research and Therapeutics (FACTs) study aimed to overcome these limitations using ex vivo lentiviral vector (LV)-mediated gene transfer into autologous haematopoietic stem/progenitor cells (HSPCs) harvested from peripheral blood after mobilisation. Following non-myeloablative conditioning, genetically corrected HSPCs were infused into each patient to engraft and proliferate with all progeny cells carrying the therapeutic gene. After LV-mediated HSPC gene therapy, tissue-resident immune cells and circulating blood cells express the therapeutic gene if they are the progeny of the genetically corrected cells. The lysosomal enzyme secreted by the cells derived from genetically corrected HPSCs is then internalised by nearby and distant uncorrected cells and directed into their lysosomes for cross-correction. LV-mediated HSPC gene therapy has been used in several clinical trials including various inherited immunodeficiencies, haematological disorders, X-linked adrenoleukodystrophy, as well as other lysosomal storage disorders, such as metachromatic leukodystrophy and mucopolysaccharidosis type I.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The FACTs trial involved five adult male individuals with classic Fabry disease. The interim results of the trial showed sustained reductions in Gb3 and lyso-Gb3.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; In their follow-up article, Khan and colleagues presented longer 5-year data of the FACTs study.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Importantly, no additional adverse events attributable to the gene therapy were observed and long-term α-Gal A expression along with sustained reductions in lyso-Gb3 and Gb3 continue to be observed in all study participants. Plasma and white blood cell α-Gal A ","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521909","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":"From multi-omics to cancer digital twins: Novel paradigm in cancer research and treatment response","authors":"Sara Sadat Aghamiri,&nbsp;Rada Amin","doi":"10.1002/ctd2.70035","DOIUrl":"https://doi.org/10.1002/ctd2.70035","url":null,"abstract":"&lt;p&gt;Integrating multi-omics in cancer research has expanded our understanding of the intricate molecular mechanisms underlying malignancies. Traditional single-omics approaches, while informative, only capture one molecular layer at a time.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, cancer is a multifaceted disease driven by genetic, epigenetic, metabolic and signalling interactions. In addition, the crosstalk between tumour cells and their environment, whether occurring during malignancies or modulated through therapy, is inherently multiscale. For instance, the crosstalk spans molecular-, cellular- and systems-level processes, operating across temporal and spatial scales. Such complexity renders the tumour ecosystem an archetype of a hierarchical system, requiring integrative approaches to fully comprehend and address.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Multi-omics bridges this gap by integrating diverse data types from the same patients to provide a multidimensional view of the tumour ecosystem. Each of these modalities contributes unique insights into the core tumour; for example, genomics focuses on the mutational landscape, transcriptomics highlights aberrant gene expression, proteomics elucidates protein interactions, epigenomics reveals regulatory mechanisms, metabolomics uncovers metabolic reprogramming and spatial omics map biomolecules directly onto the physical position of tumour niches.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Together, these multiple modalities resume tumours' molecular and functional dynamics, improving applications such as precision medicine, biomarker discovery, drug target identification and patient stratification (Figure 1).&lt;/p&gt;&lt;p&gt;Integrating multi-omics requires sophisticated computational methods capable of handling high-dimensional datasets.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; To tackle these challenges, artificial intelligence (AI), machine learning (ML) and deep learning (DL) have emerged as powerful tools. The AI- and ML/DL-based models facilitate the fusion of multiple modalities into a unified framework, addressing the challenges of disparate data types that vary in size, scales, formats, distributions and noise levels. Its ability to process and harmonize multi-omics data at scale allows this approach to analyse complex datasets, identify hidden patterns and uncover correlations across multi-omics layers often imperceptible to human analysis.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; For example, Zhang et al. developed a comprehensive multi-omics platform called COMOS, designed as a non-invasive approach to enhance the diagnosis and prognosis of diffuse large B-cell lymphoma. The authors utilized cell-free DNA (cfDNA) extracted from a single tube of patient blood to analyse several features simultaneously. Using ML algorithms, authors integrated diverse parameters, including nucleosome positioning, CpG island methylation, DNase hypersensitive sites, methylated regions, and copy number alterations, providing a comprehensive view of the cfDNA landscape. COMOS demonst","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423882","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":"Post-COVID-19 pulmonary fibrosis: Mechanisms, biomarkers, and therapeutic perspectives","authors":"Urvinder Kaur Sardarni,&nbsp;Siddappa N. Byrareddy","doi":"10.1002/ctd2.70034","DOIUrl":"https://doi.org/10.1002/ctd2.70034","url":null,"abstract":"<p>Post-COVID-19 pulmonary fibrosis (post-CPF) has emerged as a serious complication with profound implications for long-term respiratory health. This short review explores the multifactorial mechanisms underlying post-CPF, emphasising the role of oxidative stress, epithelial-to-mesenchymal transition (EMT), and dysregulated immune responses. Key signalling pathways, such as TGF-β, WNT, and Cadherin, are pivotal in fibrosis progression, offering potential therapeutic targets. Biomarkers, such as MUC4, KRT5, and ATP12A show promise for early detection and therapeutic targeting, as they share molecular features with idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (f-ILDs), suggesting opportunities to repurpose antifibrotic therapies. Despite these advancements, significant gaps remain in understanding the cellular and molecular mechanisms underlying fibrosis progression, hindering effective management of post-CPF. Addressing these challenges through a targeted approach is critical to improving outcomes for survivors of severe COVID-19.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111845","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":"Utilising single-cell sequencing in clinical nutraceutical research: Recent progress and perspectives","authors":"Xiaoqiang Wang,&nbsp;Yin S. Chan,&nbsp;David Sadava,&nbsp;Shiuan Chen","doi":"10.1002/ctd2.70032","DOIUrl":"https://doi.org/10.1002/ctd2.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Single-cell sequencing technologies have revolutionised pharmaceutical research by providing in-depth insights into human biology at the single-cell level. These tools enable researchers to identify rare cell types and analyse cellular diversity within tissues, facilitating the discovery of new therapeutic targets and biomarkers. However, their application in nutraceutical research is still in its early stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Body</h3>\u0000 \u0000 <p>Unlike pharmaceuticals, which have well-defined chemical structures and mechanisms, nutraceuticals are food-based materials intended for specific medical purposes and often contain complex and diverse food chemicals. These molecules can work synergistically, producing multi-targeted effects in various tissues. Traditional bulk profiling methods for tissues and tumours do not adequately capture cellular heterogeneity or specific cellular responses to treatments. Therefore, advanced single-cell sequencing is crucial for dissecting tissues into distinct cell types, helping to clarify the underlying mechanisms at the cellular level. Many derivatives of functional foods have been marketed or assessed, demonstrating health benefits. However, mechanistic insights are lacking, with most current data derived from observational studies or traditional in vitro and in vivo models. Human clinical trials are needed to validate these nutraceutical effects and determine effective and safe dosages. Edible mushrooms have gained attention as nutraceuticals due to their medicinal properties. They have been observed to enhance immunity, reduce inflammation, and combat cancer. These effects have been attributed to their unique bioactive components and historical uses in traditional medicine. Epidemiological studies show that higher consumption of edible mushrooms is linked to a reduced risk of certain cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this review, we share important lessons learned in the design and execution of clinical trials focusing on white button mushrooms as anti-cancer nutraceuticals. We demonstrate the use of single-cell RNA sequencing (scRNA-seq) in nutraceutical research to capture the nuanced biological responses and health effects of dietary foods and their constituents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143118527","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}