Vogt-Koyanagi-Harada-like disease secondary to anticancer treatment: a multicentre case series
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Personalized prediction of anticancer potential of non-oncology drugs through learning from genome derived molecular pathways
Advances in cancer genomics have significantly expanded our understanding of cancer biology. However, the high cost of drug development limits our ability to translate this knowledge into precise treatments. Approved non-oncology drugs, comprising a large repository of chemical entities, offer a promising avenue for repurposing in cancer therapy. Herein we present CHANCE, a supervised machine learning model designed to predict the anticancer activities of non-oncology drugs for specific patients by simultaneously considering personalized coding and non-coding mutations. Utilizing protein–protein interaction networks, CHANCE harmonizes multilevel mutation annotations and integrates pharmacological information across different drugs into a single model. We systematically benchmarked the performance of CHANCE and show its predictions are better than previous model and highly interpretable. Applying CHANCE to approximately 5000 cancer samples indicated that >30% might respond to at least one non-oncology drug, with 11% non-oncology drugs predicted to have anticancer activities. Moreover, CHANCE predictions suggested an association between SMAD7 mutations and aspirin treatment response. Experimental validation using tumor cells derived from seven patients with pancreatic or esophageal cancer confirmed the potential anticancer activity of at least one non-oncology drug for five of these patients. To summarize, CHANCE offers a personalized and interpretable approach, serving as a valuable tool for mining non-oncology drugs in the precision oncology era.
Energy metabolism in health and diseases
Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, extensive metabolic reprogramming occurs, resulting in impaired glucose metabolism and mitochondrial dysfunction, which accelerate disease progression. Recent investigations into key regulatory pathways, including mechanistic target of rapamycin, sirtuins, and adenosine monophosphate-activated protein kinase, have considerably deepened our understanding of metabolic dysregulation and opened new avenues for therapeutic innovation. Emerging technologies, such as fluorescent probes, nano-biomaterials, and metabolomic analyses, promise substantial improvements in diagnostic precision. This review critically examines recent advancements and ongoing challenges in metabolism research, emphasizing its potential for precision diagnostics and personalized therapeutic interventions. Future studies should prioritize unraveling the regulatory mechanisms of energy metabolism and the dynamics of intercellular energy interactions. Integrating cutting-edge gene-editing technologies and multi-omics approaches, the development of multi-target pharmaceuticals in synergy with existing therapies such as immunotherapy and dietary interventions could enhance therapeutic efficacy. Personalized metabolic analysis is indispensable for crafting tailored treatment protocols, ultimately providing more accurate medical solutions for patients. This review aims to deepen the understanding and improve the application of energy metabolism to drive innovative diagnostic and therapeutic strategies.
Immune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an exceptionally rare inflammatory disorder affecting choroid and retinal pigment epithelial (RPE) cells. Although recent studies suggest an immune-driven nature, the underlying etiology of APMPPE remains elusive. In this study, we conducted a comprehensive investigation on the peripheral blood mononuclear cells (PBMCs) profile of an APMPPE patient using single-cell RNA sequencing. Our analysis revealed striking transcriptional alterations in monocytes within the PBMCs, identifying five distinct subpopulations: S100A12, CD16, pro-inflammatory, megakaryocyte-like, and NK-like monocyte subsets. Employing pseudotime inference, we observed a shift in APMPPE monocytes towards differentiation into inflammation-associated pro-inflammatory monocytes and a CD16 monocyte trajectory. Furthermore, we identified IFITM3 as a key player in the immune response driving the pathogenesis of APMPPE. Notably, two disease-relevant subgroups of monocytes, pro-inflammatory and CD16 monocytes, were implicated in APMPPE. CD16 monocytes, in particular, were involved in melanogenesis, suggesting that the abnormal expression of melanin in monocytes might result from autoimmune responses against pigment-enriched RPE cells. This study provided a comprehensive view of immune landscape in APMPPE, shedding light on the previously unrecognized contributions of pro-inflammatory and CD16 monocytes to this autoimmune condition.
Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder — recommendations from ECTRIMS and the EBMT
Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing–remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD). Furthermore, treatment and monitoring protocols, rehabilitation and other supportive care before and after AHSCT need to be optimized. To address these issues, we convened a European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop in partnership with the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party, in which evidence and key questions were presented and discussed by experts in these diseases and in AHSCT. Based on the workshop output and subsequent written interactions, this Consensus Statement provides practical guidance and recommendations on the use of AHSCT in MS and NMOSD. Recommendations are based on the available evidence, or on consensus when evidence was insufficient. We summarize the key evidence, report the final recommendations, and identify areas for further research.
Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies
In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.
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