Clinical and translational discovery最新文献

{"title":"The role of microglia in neurocognitive deficits induced by general anaesthetic agents during neurodevelopment","authors":"Xinyue Liang,&nbsp;Fang Fang,&nbsp;Xiaoqing Wang,&nbsp;Ming Jiang,&nbsp;Jing Cang","doi":"10.1002/ctd2.70012","DOIUrl":"https://doi.org/10.1002/ctd2.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Microglia are the innate immune cells of central nervous system which play critical roles in brain homeostasis. Recently, the effects of general anesthetic agents (GAAs) on microglia and their potential neurotoxicity in neurodevelopment have attracted the attention of anesthesiologists and neuroscientists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we review the physiology of microglia in neurodevelopment, the potential mechanisms of GAAs on microglia and the consequent changes in microglial function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Outcomes</h3>\u0000 \u0000 <p>Microglia-mediated neuroinflammation is a key mechanism of neurocognitive deficits during neurodevelopment. In addition, microglia could be primed by active inflammatory processes and have innate immune memory, both of which make them a potential candidate responsible of long-term neural deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review aims in summarizing the in vivo and in vitro studies associating microglia with general anesthesia and describing how GAAs induce neurocognitive deficits via microglia to further explore the effects of GAAs on neurodevelopment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541074","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":"Organoid-driven diagrammatic devolution: Elevating precision in pancreatic cystic lesions diagnosis","authors":"Fei Jiang,&nbsp;Dongyan Cao,&nbsp;Gengming Niu,&nbsp;Hui Jiang,&nbsp;Zhendong Jin,&nbsp;Yingbin Liu,&nbsp;Dongxi Xiang","doi":"10.1002/ctd2.70008","DOIUrl":"https://doi.org/10.1002/ctd2.70008","url":null,"abstract":"<p>Dear Editor,</p><p>Pancreatic cystic lesions pose a diagnostic challenge. The accuracy of distinguishing low-grade from high-grade dysplasia is suboptimal, with the progression risk varying based on the types of cysts (simple retention cysts, pseudocysts and cystic neoplasms).<span>¹</span> Traditional imaging-based radiological approaches (computed tomography [CT] and magnetic resonance imaging [MRI]), endoscopic ultrasound (EUS)-guided fine needle aspiration, including analysis of cystic fluid components such as amylase, glucose, carcinoembryonic antigen (CEA) levels, liquid-based cytology and more recently molecular markers can enhance the diagnosis of pancreatic cystic lesions.<span>²</span> Even though, there is a pressing need for a stable and accurate model that allows in-depth analysis of cell components of cystic lesions and reflects their behaviour. Organoids as 3D multicellular structures resemble features of their original tissue individually for self-organization and self-renewal.<span>^{3, 4}</span> Organoid-based longitudinal testing aids in monitoring translational diagnosis, disease progression, treatment response and adapting therapies. To enhance precision in diagnosing pancreatic cystic lesions, we collected cystic fluids for organoid culture, evaluating their growth phenotypes and molecular markers. The cell context of successfully constructed organoids was further validated by single-cell RNA sequencing (scRNA-Seq) (Figure 1A).</p><p>A comprehensive explanation of the methods is in the Supporting Information. A 34-year-old female (patient #<i>X</i>) complained of epigastric pain persisting for 5 years with recurrent pancreatitis. The CT data showed a pancreatic cystic lesion measuring 5 cm in diameter within the pancreatic body, raising suspicion of a pancreatic pseudocyst (Figure 1B). Subsequent enhanced MRI and contrast EUS suggested the lesion as a mucinous cystic neoplasm with enhanced mural nodules (Figure 1C). An EUS-guided fine needle aspiration was conducted and approximately 40 mL of cystic fluid was aspirated. The cystic fluid revealed amylase at a level of 165 328 U/L (&gt;250 U/mL suggests the possibility of pancreatic pseudocyst), CEA level of 261.98 ng/mL (&gt;192 ng/mL indicates the possibility of pancreatic mucinous cystic neoplasm) and glucose level of 9 mg/dL (&lt;50 mg/dL suggests the possibility of pancreatic mucinous cystic neoplasm). Meanwhile, a small volume of cyst fluid (∼3 mL) from the puncture was performed for organoid culture (Figure 1D). Notably, organoids derived from this case exhibited robust growth. Haematoxylin and eosin staining highlighted abnormal structures in cell nuclei (Figure 1E). Immunohistochemical staining for CEA, TP53 and MIK67, as well as immunostaining for MUC5AC, all yielded positive results (Figure 1F,G). These staining data may confirm the diagnosis of this patient with high-grade intraepithelial neoplasia.</p><p>The patient eventually unde","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540906","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":"Effects of microRNA on the growth and targeted therapy response on lung cancer","authors":"Mengchen Zhu,&nbsp;Yi Jiang,&nbsp;Lingshuang Liu","doi":"10.1002/ctd2.70011","DOIUrl":"https://doi.org/10.1002/ctd2.70011","url":null,"abstract":"<p>Lung cancer represents a significant public health concern worldwide. Lung cancer typically receives a diagnosis at a late stage, leading to a generally unfavourable prognosis. Additionally, traditional treatments frequently fail in cases of metastatic lung cancer. However, targeted therapy has advanced considerably in the management of lung cancer, and overcoming drug resistance has emerged as a significant hurdle in achieving optimal treatment outcomes. As a result, there has been a new trend toward precision therapy for lung cancer based on changes at the molecular and genetic levels. On the other hand, for lung cancer, early diagnosis plays a crucial role in treatment and prognosis. Based on existing knowledge, we strongly believe that it is imperative to promptly identify innovative biomarkers. The emergence of microRNAs (miRNAs) provides new ideas. The expression profiles of miRNAs have been investigated using noninvasive blood samples to explore the regulatory mechanisms played by miRNAs during the progression and targeted therapy resistance of lung cancer. Due to the complexity of miRNA profiles, they may play the role of tumour suppressors or oncogenes. However, specific regulatory mechanisms are still a huge topic to be explored. In this Review, we summarize the latest research that has shed light on the potential regulatory mechanisms of miRNAs in driving lung cancer progression, their value for clinical application as biomarkers and their role in targeted therapy resistance.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540847","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":"Otubain 2 promotes muramyl dipeptide-mediated anti-colitogenic effects due to de-ubiquitination of receptor interaction protein 2","authors":"Jochen Mattner","doi":"10.1002/ctd2.70014","DOIUrl":"https://doi.org/10.1002/ctd2.70014","url":null,"abstract":"&lt;p&gt;Immune responses in the gut need to be tightly controlled in order to maintain mucosal immune tolerance and proper interactions with intestinal microbiota. Disruptions of these immune-microbiota circuits presumably underlie different immune-mediated disorders including inflammatory bowel disease (IBD). Distinct genetic traits that alter the expression and/or function of molecules and consequently the immune signalling networks they are embedded in can disrupt immune-microbiota interactions and microbe recognition and thus, promote mucosal inflammation. However, the molecular mechanisms and cellular circuits underlying the pathogenesis of IBD are only incompletely understood. Du and colleagues investigated the influence of posttranslational modifications on the complex signalling network in the gut in an experimental colitis model and in patients with ulcerative colitis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor which contributes to intestinal homeostasis through the regulation of epithelial cell functions and innate and adaptive immune responses. Hematopoietic cells of both myeloid and lymphoid origin as well as intestinal epithelial cells and Paneth cells express NOD2.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; NOD2 senses intracellular muramyl dipeptide (MDP), a peptidoglycan component conserved in Gram-positive and Gram-negative bacteria. Following engagement by MDP, NOD2 undergoes oligomerization and subsequently attracts and activates receptor interaction protein 2 (RIPK2) through homotypic interactions, followed by transforming growth factor-beta-activated kinase 1 recruitment and activation which engages nuclear factor kappa-beta (NFκB) and mitogen-activated protein kinase pathways for pro-inflammatory cytokine production.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Allelic variations of the gene encoding NOD2 have been associated with IBD. The three most common risk variants of the more than 2400 NOD2 variant genes reported to date are typically present in a heterozygous state and account for more than 80% of the NOD2 variations.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; These allelic risk variants are predicted to encode loss-of-function mutations that impair NFκB activation in response to MDP and to promote the onset and progression of IBD by altering the interaction with and the composition of intestinal microbiota.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; Along with this assumption, MDP administration protects from experimental colitis and this protective effect of MDP is lost when NOD2 signalling is defective,&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; Thus, proper NOD2 signalling is pivotal for the maintenance of intestinal immune tolerance and the restriction of inflammatory insults.&lt;/p&gt;&lt;p&gt;Next to genetic NOD2 mutations, the versatile and complex signalling network NOD2 is embedded in as well as various posttranslational modifications regulate NOD2 function and thus, influence the outcome of d","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524933","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":"EccDNA, STING activation, and their potential roles in DLBCL prognosis and therapy","authors":"Xi-Bo Hu,&nbsp;Wei-Ying Wang,&nbsp;Xiao-Jian Sun,&nbsp;Qun-Ling Zhang","doi":"10.1002/ctd2.70013","DOIUrl":"https://doi.org/10.1002/ctd2.70013","url":null,"abstract":"&lt;p&gt;Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma in adults, poses a significant clinical challenge due to its marked heterogeneity and high incidence of patients suffering relapse or becoming refractory after the first-line immunochemotherapy. DLBCL cells may originate from different stages of lymphoid differentiation, and thus their gene expression profiling can delineate two distinct molecular subtypes of DLBCL: germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes, with a minority of cases remaining unclassifiable. Alternatively, immunohistochemistry-based algorithms can also dichotomize DLBCL into GCB and non-GCB subtypes. In addition to these classifications related to cell-of-origin, recent in-depth genomic analyses have also revealed recurrent genomic aberrations, prompting the proposal of new classification systems for DLBCL.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; However, as yet the correlation between prognosis and molecular subtypes remains elusive.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; As an effort to further explore the heterogeneity of DLBCL, in an article recently published in &lt;i&gt;Clinical and Translational Medicine&lt;/i&gt;, Wu et al. reported the first profiling of extrachromosomal circular DNA (eccDNA) in DLBCL cells and identified the oncogenic role and prognostic significance of the eccDNAs in DLBCL. Meanwhile, their multi-omic and mechanistic studies uncovered an activation of the stimulator of interferon genes (STING) signalling pathway by eccDNAs in DLBCL cells, thus suggesting a potential therapeutic approach combining chemotherapy with STING inhibition (Figure 1).&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;EccDNAs are circular double-strand DNA molecules that are originally derived from, but physically independent of, chromosomal DNA. They are heterogeneous in size ranging from a few hundred to millions of base pairs and appear to be derived from either repetitive sequences or unique genomic sequences, and many eccDNAs can be self-replicated. While the biogenesis and functions of eccDNAs remain to be fully understood, an increase in eccDNA has been observed in several types of human cancers. Importantly, because the eccDNAs provide a significant source of oncogene amplification and can be segregated unequally to daughter cells, they are believed to contribute enormously to tumour evolution and intratumor heterogeneity,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; and the presence of eccDNAs in patient tumour samples has been found to be associated with poor outcomes across many types of cancers.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Furthermore, studies have shown that eccDNAs can function as potent innate immunostimulants, which require the STING signalling pathways to serve as intracellular DNA sensors.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;By integrating circular DNA sequencing (circle-seq), atomic force microscopy, whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq) techniques, Wu et al. performed a comprehensive eccDNA profiling of 18 DLBC","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524934","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":"Integrating single-cell RNA sequencing data to decipher heterogeneity and function of macrophages in various organs and diseases","authors":"Xinjie Xu,&nbsp;Zichen Wu,&nbsp;Zhiwei Zeng,&nbsp;Jiaying Cao,&nbsp;Liang Chen","doi":"10.1002/ctd2.70005","DOIUrl":"https://doi.org/10.1002/ctd2.70005","url":null,"abstract":"&lt;p&gt;Macrophages are essential components of the innate immune system, playing crucial roles in host defence, immune surveillance and tissue repair processes. Developmentally, macrophages can be divided into embryonic origin and postnatal origin.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Embryonic-origin macrophages are derived from the yolk sac and foetal liver during embryogenesis. They migrate to tissues early in development and maintain their populations with self-renewal mechanisms throughout the lifecycle. These macrophages are commonly found in tissues such as the brain (microglia), liver (Kupffer cells) and lungs (alveolar macrophages). In contrast, postnatal-origin macrophages are derived from hematopoietic stem cells in the bone marrow. During instances of injury, inflammation or tumorigenesis, monocytes are mobilized from the bone marrow to the blood and differentiate into macrophages upon reaching distinct tissues. Functionally, macrophages have traditionally been classified into M1 and M2 types based on in vitro activation modes. M1 macrophages exhibit pro-inflammatory properties, while M2 macrophages are involved in anti-inflammatory responses and tissue repair. M2 macrophages are further classified into subtypes M2a, M2b, M2c and M2d based on distinct activation signals.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; However, recent perspectives suggest that macrophage functions exist on a spectrum rather than binary states, with significant heterogeneity across organs and diseases, challenging the simplistic polarization classification in explaining diverse pathophysiological processes.&lt;/p&gt;&lt;p&gt;The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized the study of macrophages, providing unprecedented resolution to unravel their origin, heterogeneity and functional diversity in various physiological and pathological contexts. The integrated multi-organ scRNA-seq studies of macrophages aim to address the following key scientific questions: 1. Deciphering macrophage heterogeneity: Several studies integrated macrophages from normal tissues and tumour tissues of different organs for fine annotation, revealing significant heterogeneity of macrophages, rather than polarized classification.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; 2. Functional regulation of macrophage: In-depth analysis of macrophage function is crucial, such as inflammatory response and metabolism, thus informing therapeutic strategies aimed at modulating macrophage activity. For instance, TREM2+ macrophages have been identified in the brain, fat, liver, blood vessels and other physiological and pathological conditions, and have diverse functions such as phagocytosis, metabolism and pro-inflammatory effects.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; SPP1+ macrophages have been identified in different diseases such as tumours and atrial fibrillation, and have diverse functions such as promoting fibrosis and regulating immunity.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; 3. Inference of macrophage lineage origin and differentiation traj","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142524932","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":"“Single-cell multimodal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma”","authors":"Vikas Kumar,&nbsp;Samuel Beck","doi":"10.1002/ctd2.70002","DOIUrl":"https://doi.org/10.1002/ctd2.70002","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC), with its increasing prevalence globally, is emerging as a major health challenge. Hepatocellular carcinoma cells exhibit both significant homogeneity and heterogeneity, governed by complex epigenomic regulations. Recently, numerous single-cell unimodal techniques have been used to study HCC at various levelswhich have already revealed a complex interplay at genomic, transcriptomic, spatial and epigenomic levels. However, the use of single-cell multimodal techniques combining different unimodal layers in HCC remains quite limited, necessitating further studies focusing on these methods to uncover novel markers, and mechanisms at epigenetic levels. In this commentary, we highlight how integrating multimodal approaches with epigenetic modifications can provide new insights into HCC and foster future therapeutic advancements.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449214","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":"Liquid biopsy—A biomarker-based revolutionising technique in cancer therapy","authors":"Subham Sarkar,&nbsp;Samraggi Chakraborty,&nbsp;Soubhagya Ghosh,&nbsp;Ekanansha Roy Chowdhury,&nbsp;Jenifer Rajak,&nbsp;Arup Kumar Mitra,&nbsp;Ajoy Kumer,&nbsp;Bikram Dhara","doi":"10.1002/ctd2.70006","DOIUrl":"https://doi.org/10.1002/ctd2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Cancer has grabbed the attention of scientists and medical professionals all over the world much more than any other disease. In the past few decades, the medical field has improved quite a lot but progress in the path to find a solution for cancer is very less. As the popularity of invasive technologies is diminishing in cancer treatment, scientists have come up withminimally invasive or non-invasive alternatives, among which liquid biopsy, by far is the most suitable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Liquid biopsy is used to analyse nucleic acids, subcellular components and circulating tumour cells in various biological fluids for diagnosis of cancer. It can also be used to know the efficacy of cancer drugs in a patient by analysing multiple samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Outcomes</h3>\u0000 \u0000 <p>Liquid biopsy is becoming standard of care as it allows biopsy of those samples in which solid tumour biopsies are not possible. The diversity of sampling procedures, such as collection of urine for urothelial carcinoma or bladder or prostate cancer and phlebotomy for other types of cancer, make liquid biopsy one of the best methods for diagnosis of cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review aims in discussing the several techniques used for the detection of cancer biomarkers and some clinical manifestations due to the changes in the biomarkers which are analysed by liquid biopsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404561","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":"Developing messenger RNA biomarkers: A workflow to characterise and identify transcript target sequences unaffected by alternative splicing for reproducible gene transcript quantification by reverse transcriptase quantitative polymerase chain reaction","authors":"Bhaja Krushna Padhi,&nbsp;Guillaume Pelletier","doi":"10.1002/ctd2.70009","DOIUrl":"https://doi.org/10.1002/ctd2.70009","url":null,"abstract":"<p>Most eukaryotic genes generate multiple messenger RNA (mRNA) transcript variants by alternative splicing. The incomplete annotation of gene transcripts in genomic databases can result in improper primer design, adversely affecting the reliability of gene expression measurements by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Hence, we present a workflow combining bioinformatics analyses, to select two to three evolutionarily conserved constitutive exons in rats, mice and humans as target sequences for PCR primer design, with experimental RT-PCR amplification and amplicon sequencing to confirm the expression and identity of gene transcript targets. The application of this workflow to the characterization of neurodevelopmental biomarker genes identified an unannotated exon in the rat Map2 gene, illustrating the importance of target sequence validation for the development of translational mRNA biomarkers for toxicological and biomedical studies.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404298","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":"Endothelial cell senescence contributes to pathological retinal angiogenesis","authors":"Zehui Shi,&nbsp;Bo Liu,&nbsp;Jinhui Dai,&nbsp;Xiuping Chen","doi":"10.1002/ctd2.70007","DOIUrl":"https://doi.org/10.1002/ctd2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathological retinal neovascularization is marked by microvascular lesions manifested initially as endothelial cell dysfunction and metabolic disturbances. However, the regulatory mechanism guiding retinal vascular endothelial cell function remian controversial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main body</h3>\u0000 \u0000 <p>Previous studies have demonstarted that high glucose or oxidative stress can induce premature senescence in endothelial cells, triggering inflammatory responses within the vascular system and promoting the secretion of pro-inflammatory factors, ultimately leading to pathological angiogenesis. Endothelial cell senescence has thus become a key target for anti-angiogenic therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review delves into current research on the mechanisms driving senescence-induced retinal angiogenesis and highlights potential target protein pathways, aiming to provide insights for future investigations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404185","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}