Clinical and translational discovery最新文献

{"title":"Nemo-like kinase orchestrates the PAMP and circumstance of macrophage death in sepsis","authors":"Julia E. Steinbeck, Adil Rasheed","doi":"10.1002/ctd2.70139","DOIUrl":"10.1002/ctd2.70139","url":null,"abstract":"<p>Sepsis is a life-threatening acute inflammatory condition characterized by dysfunctional immune responses to infection, including dangerous cytokine storms.<span><sup>1</sup></span> While sepsis can cause death within hours, the underlying risk can also extend years beyond the initial infection.<span><sup>2</sup></span> Macrophages are tissue immune sentinels that integrate external stimuli, such as pathogen-associated molecular patterns (PAMPs) found on invading microbes via pattern recognition receptors (PRRs), and dictate tissue-level and systemic inflammatory outcomes.<span><sup>3</sup></span> Therefore, it is unsurprising that macrophages strongly contribute to the overall inflammatory milieu and pathology of sepsis. Key to this network of inflammatory processes in sepsis is programmed cell death (PCD), including the recently discovered PANoptosis with features of Pyroptosis, Apoptosis and Necroptosis (Figure 1).<span><sup>4</sup></span> Unlike apoptosis, which is part of homeostasis and resolves inflammation, pyroptosis and necroptosis are lytic forms of cell death that release intracellular contents, which in turn heighten inflammatory responses, such as in sepsis.<span><sup>5</sup></span></p><p>PANoptotic cell death is characterised by the PANoptosome, a complex that coordinates PCD fate decisions, which consists of signalling partners and effector proteins of each of these PCD pathways.<span><sup>4</sup></span> Although there are different flavours of PANoptosomes, dictated by the incorporation of varying cell death effector proteins, a common and critical feature in dictating PCD is caspase-8. Upon recruitment to the PANoptosome, caspase-8 homodimerizes for its auto-cleavage and active functions. Here active caspase-8 cleaves caspase-3/7 and gasdermin-D (GSDM-D) to activate apoptotic and pyroptotic cell death, respectively (Figure 1). Inactivation or absence of caspase-8 shifts PANoptosome signalling towards necroptosis. Therefore, caspase-8 represents a critical PCD checkpoint, and a better understanding of its regulation could support therapeutic opportunities to leverage inflammatory processes and improve overall survival after infection.</p><p>A recent study by Xia et al. employed multidisciplinary approaches using mouse models and clinical samples to identify Nemo-like kinase (NLK) as a regulator of PANoptosis and inflammatory outcomes in sepsis.<span><sup>6</sup></span> NLK is a conserved kinase belonging to the mitogen-activated protein kinase (MAPK) family and has been implicated in a variety of processes including embryonic and nervous system development, regulation of cell signaling cascades such as by transcription factor phosphorylation, and in an array of diseases including cancer and neurodegenerative diseases.<span><sup>7</sup></span> Using independent transcriptomic datasets, the authors identify increased <i>NLK</i> in peripheral blood mononuclear cells (PBMCs) from sepsis patients, where higher <i>NLK</i> levels are","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147668964","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":"Nemo-like kinase orchestrates the PAMP and circumstance of macrophage death in sepsis","authors":"Julia E. Steinbeck, Adil Rasheed","doi":"10.1002/ctd2.70139","DOIUrl":"https://doi.org/10.1002/ctd2.70139","url":null,"abstract":"<p>Sepsis is a life-threatening acute inflammatory condition characterized by dysfunctional immune responses to infection, including dangerous cytokine storms.<span><sup>1</sup></span> While sepsis can cause death within hours, the underlying risk can also extend years beyond the initial infection.<span><sup>2</sup></span> Macrophages are tissue immune sentinels that integrate external stimuli, such as pathogen-associated molecular patterns (PAMPs) found on invading microbes via pattern recognition receptors (PRRs), and dictate tissue-level and systemic inflammatory outcomes.<span><sup>3</sup></span> Therefore, it is unsurprising that macrophages strongly contribute to the overall inflammatory milieu and pathology of sepsis. Key to this network of inflammatory processes in sepsis is programmed cell death (PCD), including the recently discovered PANoptosis with features of Pyroptosis, Apoptosis and Necroptosis (Figure 1).<span><sup>4</sup></span> Unlike apoptosis, which is part of homeostasis and resolves inflammation, pyroptosis and necroptosis are lytic forms of cell death that release intracellular contents, which in turn heighten inflammatory responses, such as in sepsis.<span><sup>5</sup></span></p><p>PANoptotic cell death is characterised by the PANoptosome, a complex that coordinates PCD fate decisions, which consists of signalling partners and effector proteins of each of these PCD pathways.<span><sup>4</sup></span> Although there are different flavours of PANoptosomes, dictated by the incorporation of varying cell death effector proteins, a common and critical feature in dictating PCD is caspase-8. Upon recruitment to the PANoptosome, caspase-8 homodimerizes for its auto-cleavage and active functions. Here active caspase-8 cleaves caspase-3/7 and gasdermin-D (GSDM-D) to activate apoptotic and pyroptotic cell death, respectively (Figure 1). Inactivation or absence of caspase-8 shifts PANoptosome signalling towards necroptosis. Therefore, caspase-8 represents a critical PCD checkpoint, and a better understanding of its regulation could support therapeutic opportunities to leverage inflammatory processes and improve overall survival after infection.</p><p>A recent study by Xia et al. employed multidisciplinary approaches using mouse models and clinical samples to identify Nemo-like kinase (NLK) as a regulator of PANoptosis and inflammatory outcomes in sepsis.<span><sup>6</sup></span> NLK is a conserved kinase belonging to the mitogen-activated protein kinase (MAPK) family and has been implicated in a variety of processes including embryonic and nervous system development, regulation of cell signaling cascades such as by transcription factor phosphorylation, and in an array of diseases including cancer and neurodegenerative diseases.<span><sup>7</sup></span> Using independent transcriptomic datasets, the authors identify increased <i>NLK</i> in peripheral blood mononuclear cells (PBMCs) from sepsis patients, where higher <i>NLK</i> levels are","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669018","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 and adopting mathematical models and digital twins into clinical decision-making","authors":"Heiko Enderling","doi":"10.1002/ctd2.70137","DOIUrl":"https://doi.org/10.1002/ctd2.70137","url":null,"abstract":"<p>Cancers are complex adaptive dynamic systems, and the underlying mechanisms of such systems are best understood when subjected to perturbation. Therapies such as radiation, chemotherapy, or immunotherapy, among others, introduce a substantial perturbation to a tumour, which offers the opportunity to measure response, identify putative vulnerabilities, and dynamically adapt treatment as necessary. A framework that could facilitate adaptive therapies is the so-called digital twins. Digital twins aim to mimic the structure, context, and behaviour of the physical twin—the cancer patient in oncology. Digital twins are dynamically updated with data from the patient, have predictive capability, and inform clinical decision-making.<span><sup>1</sup></span> This enables the comparison of different treatment options for individual patients through in silico trials beyond the average outcomes of historic clinical trials (Figure 1).<span><sup>2</sup></span></p><p>The power to make predictions for individual patients comes from mathematical models that are validated with the data of past patients, and iteratively calibrated to the individual with the patient's own data.<span><sup>3</sup></span> While digital twins are established in different industries such as mechanical and aerospace engineering,<span><sup>4</sup></span> their use in medicine remains to be demonstrated. One major limiting factor is the lack of continuous, accurate measurements of all variables of interest—such as tumour growth dynamics, drug concentrations, complete blood counts, patient-reported outcomes, among others. Thus, digital twins in oncology will unlikely mimic the whole patient, but rather simulate limited subsystems of the patient that realise value for clinical decision making—such as the tumour, or the vascular system, or organs at risk. For each of these subsystems of interest, a predictive mathematical model (or an ensemble of multiple predictive mechanistic mathematical models) needs to be developed, calibrated, and validated, and its predictive power needs to be assessed.<span><sup>5</sup></span> Once sufficient prediction accuracy is demonstrated on historic data (how accurate such models need to be may depend on the clinical problem, data uncertainty, and physician need), prospective clinical studies need to evaluate the clinical utility—that is, can the digital twin framework (1) iteratively use newly collected clinical data to retrain its predictive models and (2) simulate factual and (3) counterfactual treatments, and (3) communicate model predictions with (4) associated uncertainties and (5) model accuracy (6) in real time to (7) inform the physician and patient interactions with the likelihood of success of different treatment strategies. To evaluate the clinical utility of digital twin and mathematical model-guided personalized adaptive therapy, the responses and outcomes of such framework-guided therapy needs to be evaluated against either the counterfactual st","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567467","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 and adopting mathematical models and digital twins into clinical decision-making","authors":"Heiko Enderling","doi":"10.1002/ctd2.70137","DOIUrl":"https://doi.org/10.1002/ctd2.70137","url":null,"abstract":"<p>Cancers are complex adaptive dynamic systems, and the underlying mechanisms of such systems are best understood when subjected to perturbation. Therapies such as radiation, chemotherapy, or immunotherapy, among others, introduce a substantial perturbation to a tumour, which offers the opportunity to measure response, identify putative vulnerabilities, and dynamically adapt treatment as necessary. A framework that could facilitate adaptive therapies is the so-called digital twins. Digital twins aim to mimic the structure, context, and behaviour of the physical twin—the cancer patient in oncology. Digital twins are dynamically updated with data from the patient, have predictive capability, and inform clinical decision-making.<span><sup>1</sup></span> This enables the comparison of different treatment options for individual patients through in silico trials beyond the average outcomes of historic clinical trials (Figure 1).<span><sup>2</sup></span></p><p>The power to make predictions for individual patients comes from mathematical models that are validated with the data of past patients, and iteratively calibrated to the individual with the patient's own data.<span><sup>3</sup></span> While digital twins are established in different industries such as mechanical and aerospace engineering,<span><sup>4</sup></span> their use in medicine remains to be demonstrated. One major limiting factor is the lack of continuous, accurate measurements of all variables of interest—such as tumour growth dynamics, drug concentrations, complete blood counts, patient-reported outcomes, among others. Thus, digital twins in oncology will unlikely mimic the whole patient, but rather simulate limited subsystems of the patient that realise value for clinical decision making—such as the tumour, or the vascular system, or organs at risk. For each of these subsystems of interest, a predictive mathematical model (or an ensemble of multiple predictive mechanistic mathematical models) needs to be developed, calibrated, and validated, and its predictive power needs to be assessed.<span><sup>5</sup></span> Once sufficient prediction accuracy is demonstrated on historic data (how accurate such models need to be may depend on the clinical problem, data uncertainty, and physician need), prospective clinical studies need to evaluate the clinical utility—that is, can the digital twin framework (1) iteratively use newly collected clinical data to retrain its predictive models and (2) simulate factual and (3) counterfactual treatments, and (3) communicate model predictions with (4) associated uncertainties and (5) model accuracy (6) in real time to (7) inform the physician and patient interactions with the likelihood of success of different treatment strategies. To evaluate the clinical utility of digital twin and mathematical model-guided personalized adaptive therapy, the responses and outcomes of such framework-guided therapy needs to be evaluated against either the counterfactual st","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567606","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":"Periodontitis and extracellular vesicles: Emerging roles in inflammation, tissue destruction and systemic crosstalk","authors":"Mai Ahmed, Dada Oluwaseyi Temilola, Mushi Matjila, Manogari Chetty","doi":"10.1002/ctd2.70138","DOIUrl":"https://doi.org/10.1002/ctd2.70138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Periodontitis is a chronic inflammatory disease initiated by microbial dysbiosis and dysregulated host immune responses, resulting in progressive destruction of the tooth-supporting periodontal tissues. Increasing evidence recognises periodontitis as a systemic inflammatory condition associated with metabolic, cardiovascular, immune-mediated, and neuroinflammatory disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication, facilitating molecular crosstalk between periodontal pathogens, immune cells, and resident periodontal tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to synthesise current evidence on the biogenesis, microbial and cellular sources, and functional roles of EVs in periodontal inflammation, tissue destruction, and systemic inflammatory interactions, while evaluating their emerging diagnostic and therapeutic potential in periodontology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative synthesis of experimental, mechanistic, and translational studies was conducted to examine the role of EVs in periodontal disease. Evidence from studies investigating vesicle-associated molecular cargo, signalling pathways, and their involvement in local periodontal pathology and systemic inflammatory responses was critically integrated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key findings</h3>\u0000 \u0000 <p>Both bacterial-derived and host-derived EVs transport diverse bioactive cargo, including lipopolysaccharides, cytokines, proteolytic enzymes, and regulatory nucleic acids. These vesicles modulate inflammatory signalling pathways, contribute to extracellular matrix degradation, influence immune dysregulation, and promote alveolar bone remodelling. Emerging evidence suggests that periodontal EVs may disseminate systemically, contributing to chronic low-grade inflammation and influencing pathological processes in distant organs. Vesicles detected in saliva, gingival crevicular fluid, and circulation also demonstrate promise as minimally invasive biomarkers for disease detection and monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EVs represent key regulators of periodontal pathogenesis and systemic inflammatory crosstalk. Their diagnostic and therapeutic potential offers promising opportunities for precision approaches in periodontology; however, challenges including vesicle heterogeneity, methodological standardisation, an","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566242","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":"Periodontitis and extracellular vesicles: Emerging roles in inflammation, tissue destruction and systemic crosstalk","authors":"Mai Ahmed, Dada Oluwaseyi Temilola, Mushi Matjila, Manogari Chetty","doi":"10.1002/ctd2.70138","DOIUrl":"https://doi.org/10.1002/ctd2.70138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Periodontitis is a chronic inflammatory disease initiated by microbial dysbiosis and dysregulated host immune responses, resulting in progressive destruction of the tooth-supporting periodontal tissues. Increasing evidence recognises periodontitis as a systemic inflammatory condition associated with metabolic, cardiovascular, immune-mediated, and neuroinflammatory disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication, facilitating molecular crosstalk between periodontal pathogens, immune cells, and resident periodontal tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to synthesise current evidence on the biogenesis, microbial and cellular sources, and functional roles of EVs in periodontal inflammation, tissue destruction, and systemic inflammatory interactions, while evaluating their emerging diagnostic and therapeutic potential in periodontology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative synthesis of experimental, mechanistic, and translational studies was conducted to examine the role of EVs in periodontal disease. Evidence from studies investigating vesicle-associated molecular cargo, signalling pathways, and their involvement in local periodontal pathology and systemic inflammatory responses was critically integrated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key findings</h3>\u0000 \u0000 <p>Both bacterial-derived and host-derived EVs transport diverse bioactive cargo, including lipopolysaccharides, cytokines, proteolytic enzymes, and regulatory nucleic acids. These vesicles modulate inflammatory signalling pathways, contribute to extracellular matrix degradation, influence immune dysregulation, and promote alveolar bone remodelling. Emerging evidence suggests that periodontal EVs may disseminate systemically, contributing to chronic low-grade inflammation and influencing pathological processes in distant organs. Vesicles detected in saliva, gingival crevicular fluid, and circulation also demonstrate promise as minimally invasive biomarkers for disease detection and monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EVs represent key regulators of periodontal pathogenesis and systemic inflammatory crosstalk. Their diagnostic and therapeutic potential offers promising opportunities for precision approaches in periodontology; however, challenges including vesicle heterogeneity, methodological standardisation, an","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566509","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":"Cadmium exposure, lung injury, and acute respiratory distress syndrome","authors":"Yan-Ming Xu, Andy T. Y. Lau","doi":"10.1002/ctd2.70135","DOIUrl":"https://doi.org/10.1002/ctd2.70135","url":null,"abstract":"<p>The respiratory tract encounters foreign intruders at all times, such as allergy-causing airborne particles, toxic chemical agents, environmental pollutants, and harmful microorganisms (bacteria and viruses).<span><sup>1</sup></span> A functional respiratory system is crucial in maintaining the health of an individual, while a compromised state within the respiratory tract would lead to serious conditions and disease progression.</p><p>Lung injury can be classified as acute or chronic. Acute respiratory distress syndrome (ARDS), as an advanced stage of acute lung injury, is noncardiogenic pulmonary oedema that manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia,<span><sup>2</sup></span> which could be fatal if not properly treated in time. On the other hand, chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterised by persistent airflow limitation. It is progressive and not fully reversible, primarily caused by long-term exposure to air pollution and cigarette smoking, leading to chronic bronchitis and emphysema.<span><sup>3</sup></span></p><p>Cadmium (Cd) is a toxic heavy metal widely exploited in various industries, such as for the production of electronic circuits, Cd paints, Ni-Cd batteries, and Cd quantum dot displays, and is inevitably present in tobacco products.<span><sup>4</sup></span> Despite the substitution of Cd in Ni-Cd batteries and Cd quantum dot displays with other less toxic/environmental friendly elements, yet, the global use of Cd is still in big demand, and the improper handling/disposal of all these Cd-containing products would eventually pollute our living environment. Once inside the human body, Cd accumulates in multiple organs, and the biological half-time can reach decades.<span><sup>5</sup></span> In general, occupational Cd exposure can sometimes lead to acute poisoning. In one case, back in 1999, a very typical example of acute Cd inhalation leading to ARDS was documented. A 43-year-old welder developed ARDS after exposure to metal fumes, which contain an elevated air level of Cd.<span><sup>6</sup></span> In another case, a nonsmoking silversmith after smelting silver adulterated with a large amount of Cd, had a heart rate of 120 beats/min, blood pressure of 150/80, respiratory rate of 48–52/min, PaO<sub>2</sub>/FiO<sub>2</sub> ratio of 100, and central cyanosis, and was diagnosed with ARDS.<span><sup>7</sup></span> The above examples provided strong evidence of Cd inhalation in the development of ARDS in humans. On the other hand, the general public is chronically exposed to Cd on a daily basis from Cd-contaminated air (from industrial fume emission, first-hand and/or second-hand cigarette smoke), and after a certain period of time, this would likely predispose humans to various lung-related diseases.</p><p>Besides induction of pro-inflammatory cytokines,<span><sup>8</sup></span> Cd has been shown to promote various forms of cell death, depending on the concentrat","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566549","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":"Cadmium exposure, lung injury, and acute respiratory distress syndrome","authors":"Yan-Ming Xu, Andy T. Y. Lau","doi":"10.1002/ctd2.70135","DOIUrl":"https://doi.org/10.1002/ctd2.70135","url":null,"abstract":"<p>The respiratory tract encounters foreign intruders at all times, such as allergy-causing airborne particles, toxic chemical agents, environmental pollutants, and harmful microorganisms (bacteria and viruses).<span><sup>1</sup></span> A functional respiratory system is crucial in maintaining the health of an individual, while a compromised state within the respiratory tract would lead to serious conditions and disease progression.</p><p>Lung injury can be classified as acute or chronic. Acute respiratory distress syndrome (ARDS), as an advanced stage of acute lung injury, is noncardiogenic pulmonary oedema that manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia,<span><sup>2</sup></span> which could be fatal if not properly treated in time. On the other hand, chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterised by persistent airflow limitation. It is progressive and not fully reversible, primarily caused by long-term exposure to air pollution and cigarette smoking, leading to chronic bronchitis and emphysema.<span><sup>3</sup></span></p><p>Cadmium (Cd) is a toxic heavy metal widely exploited in various industries, such as for the production of electronic circuits, Cd paints, Ni-Cd batteries, and Cd quantum dot displays, and is inevitably present in tobacco products.<span><sup>4</sup></span> Despite the substitution of Cd in Ni-Cd batteries and Cd quantum dot displays with other less toxic/environmental friendly elements, yet, the global use of Cd is still in big demand, and the improper handling/disposal of all these Cd-containing products would eventually pollute our living environment. Once inside the human body, Cd accumulates in multiple organs, and the biological half-time can reach decades.<span><sup>5</sup></span> In general, occupational Cd exposure can sometimes lead to acute poisoning. In one case, back in 1999, a very typical example of acute Cd inhalation leading to ARDS was documented. A 43-year-old welder developed ARDS after exposure to metal fumes, which contain an elevated air level of Cd.<span><sup>6</sup></span> In another case, a nonsmoking silversmith after smelting silver adulterated with a large amount of Cd, had a heart rate of 120 beats/min, blood pressure of 150/80, respiratory rate of 48–52/min, PaO<sub>2</sub>/FiO<sub>2</sub> ratio of 100, and central cyanosis, and was diagnosed with ARDS.<span><sup>7</sup></span> The above examples provided strong evidence of Cd inhalation in the development of ARDS in humans. On the other hand, the general public is chronically exposed to Cd on a daily basis from Cd-contaminated air (from industrial fume emission, first-hand and/or second-hand cigarette smoke), and after a certain period of time, this would likely predispose humans to various lung-related diseases.</p><p>Besides induction of pro-inflammatory cytokines,<span><sup>8</sup></span> Cd has been shown to promote various forms of cell death, depending on the concentrat","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566550","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":"The platelet transcriptome after stem cell transplantation","authors":"Lin LI, Sidney W. Whiteheart, Reinhold Munker","doi":"10.1002/ctd2.70121","DOIUrl":"https://doi.org/10.1002/ctd2.70121","url":null,"abstract":"<p>Dear Editor,</p><p>Platelets play a role in haemostasis, vascular biology and immunity.<span><sup>1</sup></span> Activated platelets may worsen or modulate immune reactions. Stem cell transplantation is an established treatment for leukaemia, lymphoma and some other conditions. It is unclear if the platelet transcriptome displays markers of immune activation in the recovery period after transplantation. The aim of our study was to identify changes in the platelet transcriptome (being a corollary of events happening in megakaryocytes in the bone marrow) after transplantation. The study of the platelet transcriptome was found to be useful for discoveries in human health and disease.<span><sup>2</sup></span> In sepsis, altered transcriptome of human and mouse platelets was found. The sepsis-induced upregulation of the ITGA2B gene on platelets predicts mortality.<span><sup>3</sup></span> To our knowledge the platelet transcriptome has never been studied systematically after hematopoietic stem cell transplantation (HSCT). Autologous transplantation permits to deliver high-dose chemotherapy. Allogeneic transplantation in addition generates an immune response most pronounced in myeloid leukaemias. Both types of transplantation have a potential for cure. An earlier study investigated platelet markers after allogeneic transplantation using flow cytometry and found platelet receptor and granule defects.<span><sup>4</sup></span> In a recent Japanese study early thrombocytopenia was a risk factor for a poor outcome after allogeneic HSCT.<span><sup>5</sup></span> We hypothesized that an altered transcriptome could correlate with complications and possibly predict the outcome after autologous and allogeneic HSCT.</p><p>Platelets were isolated and purified according to standard methods.<span><sup>6</sup></span> This includes negative bead selection for GPA and LCA. A total of 8 patients were studied before and after HSCT. Four patients underwent an autologous HSCT, 4 patients underwent an allogeneic HSCT. Details about these patients can be found in Table 1. RNA was sequenced using an Illumina NovaSeq 6000 and transcriptomes were analysed with R, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Following the isolation of platelets and RNA, sequencing generated raw gene datasets that were compared using an R algorithm. All isolations were performed in duplicate. In the first comparison, we examined gene expression, before versus after two types of HSCT, autologous (Figure 1A) and allogeneic (Figure 1C) by aggregating all data based on type of transplant. A threshold of log2 (FC) > 1 and FDR < 0.01 (blue dots) or FDR < 0.05 (red dots) was applied. Further the top differentially expressed genes were identified and ranked according to the log2FC (Figure 1B,D). From this analysis, autologous HSCT causes fewer changes in gene expression than allogenic stem cell transplantation (SCT). In the autolo","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565466","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":"The platelet transcriptome after stem cell transplantation","authors":"Lin LI, Sidney W. Whiteheart, Reinhold Munker","doi":"10.1002/ctd2.70121","DOIUrl":"https://doi.org/10.1002/ctd2.70121","url":null,"abstract":"<p>Dear Editor,</p><p>Platelets play a role in haemostasis, vascular biology and immunity.<span><sup>1</sup></span> Activated platelets may worsen or modulate immune reactions. Stem cell transplantation is an established treatment for leukaemia, lymphoma and some other conditions. It is unclear if the platelet transcriptome displays markers of immune activation in the recovery period after transplantation. The aim of our study was to identify changes in the platelet transcriptome (being a corollary of events happening in megakaryocytes in the bone marrow) after transplantation. The study of the platelet transcriptome was found to be useful for discoveries in human health and disease.<span><sup>2</sup></span> In sepsis, altered transcriptome of human and mouse platelets was found. The sepsis-induced upregulation of the ITGA2B gene on platelets predicts mortality.<span><sup>3</sup></span> To our knowledge the platelet transcriptome has never been studied systematically after hematopoietic stem cell transplantation (HSCT). Autologous transplantation permits to deliver high-dose chemotherapy. Allogeneic transplantation in addition generates an immune response most pronounced in myeloid leukaemias. Both types of transplantation have a potential for cure. An earlier study investigated platelet markers after allogeneic transplantation using flow cytometry and found platelet receptor and granule defects.<span><sup>4</sup></span> In a recent Japanese study early thrombocytopenia was a risk factor for a poor outcome after allogeneic HSCT.<span><sup>5</sup></span> We hypothesized that an altered transcriptome could correlate with complications and possibly predict the outcome after autologous and allogeneic HSCT.</p><p>Platelets were isolated and purified according to standard methods.<span><sup>6</sup></span> This includes negative bead selection for GPA and LCA. A total of 8 patients were studied before and after HSCT. Four patients underwent an autologous HSCT, 4 patients underwent an allogeneic HSCT. Details about these patients can be found in Table 1. RNA was sequenced using an Illumina NovaSeq 6000 and transcriptomes were analysed with R, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Following the isolation of platelets and RNA, sequencing generated raw gene datasets that were compared using an R algorithm. All isolations were performed in duplicate. In the first comparison, we examined gene expression, before versus after two types of HSCT, autologous (Figure 1A) and allogeneic (Figure 1C) by aggregating all data based on type of transplant. A threshold of log2 (FC) > 1 and FDR < 0.01 (blue dots) or FDR < 0.05 (red dots) was applied. Further the top differentially expressed genes were identified and ranked according to the log2FC (Figure 1B,D). From this analysis, autologous HSCT causes fewer changes in gene expression than allogenic stem cell transplantation (SCT). In the autolo","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565352","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}