MedComm最新文献

Cellular plasticity, the ability of cells to dynamically alter their phenotypes, is a key driver of tumor evolution. This process is a hallmark of cancer which enables the acquisition of malignant traits, leading to metastasis, progression, and therapy resistance. It is governed by cell-intrinsic factors, such as genomic instability and epigenetic reprogramming, and extrinsic stimuli from the tumor microenvironment. However, a unified framework is still needed to position plasticity as the central process that links these drivers to diverse cancer hallmarks. In this review, we first explore how plasticity enables key steps of tumor evolution, including tumorigenesis, metastasis driven by epithelial–mesenchymal plasticity (EMP), therapy resistance, and cancer stem cell (CSC) dynamics. We then summarize the intrinsic and extrinsic mechanisms that govern this adaptability. Finally, we discuss clinical advances in monitoring and targeting plasticity and highlight how new spatiotemporal technologies can address current research challenges. This review provides a framework positioning cellular plasticity as a central mechanism in cancer evolution, connecting its fundamental drivers to clinical translation. By synthesizing the latest advances, we offer perspectives for developing therapies that integrate prediction, monitoring, and targeting of plasticity to proactively guide cancer evolution toward manageable outcomes.

Poliovirus is characterized by three antigenically distinct serotypes that do not elicit cross-neutralizing antibodies. In the final stages of poliovirus eradication, the gold-standard conventional neutralization test (cNT) for detecting serum neutralizing antibodies (NAbs) is highly restricted due to biosafety concerns. To address this, we developed a high-throughput, tri-color pseudovirus-based neutralization assay (PBNA) for the simultaneous quantification of NAbs against all three poliovirus serotypes. We generated pseudoviruses by co-transfecting cells with P1 plasmids, a replication plasmid, and a T7 RNA polymerase plasmid. By optimizing P1 expression, sensitive cell selection (HEK 293T), and plasmid transfection ratios (3:3:1 for P1, replicon, and T7 plasmids), we produced high-titer pseudoviruses (>29-fold increase in titers). Based on high-titer pseudovirus encoding distinct fluorophores (E2, eGFP, and RFP), the PBNA was established, which was optimized for a 12 h incubation period, 4 × 10⁴ cells per well, and 1500 TCID₅₀/mL of pseudovirus. It demonstrated high sensitivity, strong serotype specificity, and excellent reproducibility. Furthermore, the PBNA and cNT exhibited excellent congruency (r > 0.88, all serotypes). The tri-color PBNA provides a safe, rapid, and alternative to the cNT, making it an invaluable tool for large-scale serosurveillance, novel vaccine evaluation, and fundamental virological investigations in the post-eradication era.

Traditionally considered to function solely as signaling molecules within the central nervous system (CNS), neurotransmitters are now recognized as key regulators of systemic homeostasis. They modulate interactions among the nervous, immune, and metabolic systems and influence the development of various diseases. This review systematically summarizes the fundamental properties of major neurotransmitters, including their biosynthesis, receptor subtypes, and key signaling pathways, and analyzes their context-dependent roles in cancer, neurodegenerative diseases (NDDs), and inflammatory disorders. A primary focus is the three-dimensional regulatory principle that determines their effects, namely: the receptor type they bind to, cellular microenvironment, and stage of the disease. These factors explain the bidirectional effects of neurotransmitters in disease. This review also evaluates current therapeutic approaches targeting neurotransmitter pathways, ranging from receptor-specific drugs to emerging combination therapies, and discusses challenges in clinical translation, such as off-target effects of nonspecific drugs and variable efficacy across disease types. By linking the fundamental mechanisms of neurotransmitter function to clinical challenges, this review provides a comprehensive framework for exploiting the neurotransmitter–immune axis to develop precise therapeutic strategies aimed at improving outcomes in cancer, NDDs, and inflammatory disorders.

Stroke can be classified into ischemic stroke (IS), hemorrhagic stroke (HS), and subarachnoid hemorrhage. The high incidence, disability, and mortality rates, especially from IS, place a huge burden on global health. The pathophysiological processes following IS mainly involve energy deficiency, ion homeostasis imbalance, oxidative stress, neuroinflammation, programmed cell death, blood–brain barrier disruption, and cerebral edema. Transient ischemic attack is an early warning sign of IS, characterized by temporary neurological deficits. HS mainly involves primary damage caused by the mass effect of hematoma and secondary damage caused by the toxic components of hematoma. Although advances in acute-phase reperfusion technology have reduced mortality, the fundamental challenge of a narrow therapeutic window limits patient eligibility and long-term recovery outcomes. This review aims to provide a comprehensive overview of stroke, detailing its epidemiology, risk factors, pathophysiological mechanisms, signaling pathways, and clinical management methods. Here, we focus on the latest research progress in IS and emphasize the hope that regenerative therapies, especially stem cell therapies, offer for stroke patients. This review aims to provide a detailed overview of current research and clinical practice in stroke, propose emerging strategies for treating stroke patients, and provide an outlook on future research directions in this field.

Influenza, a highly pathogenic infectious disease, causes nearly half a million deaths annually worldwide. Thus, effective vaccine-based prevention and control are crucial. Although live attenuated influenza vaccines (LAIVs) can induce mucosal immunity, existing vaccines effectiveness remains relatively low, posing a significant threat to public health. Thus, we developed a novel mosaic H1N1 LAIV candidate by integrating mosaic antigen design with established LAIV technology. This vaccine incorporates most potential T-cell epitopes of hemagglutinin and neuraminidase antigens into an attenuated master donor strain, ensuring safety and broad immunity. We compared it with commercial monovalent attenuated and inactivated vaccines in mice. The mosaic H1N1 LAIV induced robust cross-reactive humoral and mucosal immune responses, enhanced antigen-specific cellular immunity, and established tissue-resident memory T and B cells in the respiratory tract. Challenge experiments confirmed its protective efficacy against homologous and heterologous strains. It provided complete protection against homologous strains with low epitope similarity and partial protection against the ancestral H3N2 virus. Our study highlights the mosaic H1N1 LAIV as an excellent universal vaccine candidate capable of inducing broad cross-reactive immune responses and providing robust protection against distinct influenza A viruses, demonstrating a promising strategy to address the limitations of current commercial vaccines.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by excessive extracellular matrix (ECM) deposition and irreversible alveolar destruction. Despite advances in antifibrotic therapies, the underlying pathogenic mechanisms remain incompletely understood. Recent multiomic studies have revealed that IPF arises from aberrant communication among epithelial, mesenchymal, immune, and vascular cells within the fibrotic microenvironment, rather than from isolated cellular dysfunction. However, the dynamic intercellular networks and spatiotemporal regulation driving disease progression remain poorly defined. This review integrates recent single-cell RNA sequencing and spatial transcriptomic discoveries to delineate key pathogenic cell populations—including aberrant basaloids and IPF-related alveolar type 2 cells (IR_AT2), CTHRC1⁺ and meflin⁺ fibroblasts, and SPP1^hi macrophages—and their signaling crosstalk through pathways such as transforming growth factor β(TGF-β), Hippo, and Hedgehog. We further discuss how ECM feedback loops and immune-metabolic remodeling reinforce fibrogenesis and explore emerging therapeutic targets derived from these mechanisms. By synthesizing multidimensional data into a cellular and molecular framework, this review advances the understanding of IPF pathogenesis and provides a conceptual foundation for biomarker-guided precision therapies.

Chronic otitis media with effusion (COME) is a common condition that can lead to hearing loss without acute inflammation. However, its underlying pathogenesis remains poorly understood, particularly with regard to microbial contributions. In this study, we characterized and compared the microbiota of the middle ear, nasal cavity, and oral cavity in 100 patients with COME and 77 controls using 16S rRNA gene sequencing. Alpha diversity, assessed by the Pielou index, was significantly reduced in the middle ear microbiota of COME patients compared with controls, and microbial compositions differed markedly across all sampled sites. Notably, Aeromonas, Serratia, and Lactococcus were enriched in both middle ear and nasal samples from COME patients. Among these, Aeromonas achieved the highest predictive value for COME in otic samples, whereas Lactococcus showed the strongest performance in nasal samples, with strong inter-site correlations. Functional analysis revealed the enrichment of pathways related to biofilm formation and depletion of antibiotic biosynthesis in COME-associated microbiota. These findings highlight the presence of microbial dysbiosis, particularly the interplay between nasal and middle ear microbiota, as a potential contributor to the COME pathogenesis, and suggest novel microbial targets for diagnosis and therapeutic intervention.

The metabolic signature of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis remains poorly defined. We sought to delineate disease-specific ¹⁸F-FDG PET patterns and assess their relationships with clinical severity and cognition. Forty-seven patients with anti-LGI1 encephalitis and 25 healthy controls underwent ¹⁸F-FDG PET/CT, and voxel-wise comprised to identify regional metabolic alterations. A disease-specific metabolic pattern was derived with fivefold cross-validation, and a metabolic covariance network was mapped using the Brainnetome atlas. Pattern expression scores were correlated with clinical assessments. Compared to controls, patients demonstrated hypermetabolism in the hippocampal rostal, nucleus accumbens (NAc), and hypothalamus, alongside hypometabolism in the dorsolateral prefrontal cortex and posterior cingulate cortex (PCC). We identified a robust metabolic pattern centered on the NAc with extensions to the hippocampus, prefrontal cortex, and PCC; expression of this pattern correlated positively with both clinical severity and cognitive impairment. Subgroup analyses showed no significant differences in basal ganglia metabolism between patients with and without faciobrachial dystonic seizures (FBDS), or in hypothalamic metabolism between those with and without hyponatremia. Overall, ¹⁸F-FDG PET uncovers a NAc-centered metabolic network that parallels disease severity in anti-LGI1 encephalitis. Our study offers potential biomarker for clinical evaluation and provides valuable insights into the underlying pathogenesis of clinical manifestations.

Efferocytosis is the fundamental mechanism by which phagocytes clear apoptotic cells to maintain tissue homeostasis. This process is also closely linked to immune tolerance, metabolic reprogramming, inflammation resolution, and tissue repair. In recent years, research spanning cardiovascular disease, autoimmune disorders, metabolic inflammation, neurodegeneration, and cancer has revealed diverse context-dependent regulatory networks, including “eat-me” and “don't-eat-me” signals, phagocytic receptors, intracellular signaling pathways, and metabolic checkpoints. Disruption of these regulatory layers contributes to the defective resolution of inflammation, persistent immune activation, and impaired tissue regeneration. However, a unified comparative framework that integrates these mechanisms across different disease states is lacking. In this review, we provide a comprehensive overview of the biology of efferocytosis, from apoptotic cell recognition and engulfment to downstream immunometabolic rewiring. We highlight disease-specific alterations in atherosclerosis, myocardial infarction, autoimmune diseases, neuroinflammation, and the tumor microenvironment. In addition, we summarize the emerging therapeutic strategies, including receptor agonists, metabolic interventions, engineered extracellular vesicles, and immune checkpoint modulation. Finally, we propose a “full-cycle” monitoring strategy that integrates imaging-based quantification, circulating biomarkers, multiomics profiling, and artificial intelligence to enable dynamic assessment of efferocytosis in vivo.