MedComm最新文献

Since 2022, mpox epidemics have been sustaining and escalating over the world, posing a significant public health challenge. While significant progress has been made in diagnostic methodologies, prophylactic vaccines, and therapeutic interventions to mitigate monkeypox virus (MPXV) infection, scientific understanding of MPXV and related orthopoxviruses continues to evolve progressively. In order to keep pace with recent advancements, herein we review progress in mpox research from five key perspectives. This article first summarizes the latest epidemiological profiles, incorporating different viral lineages globally and in China, while highlighting their evolutionary history and distinct clinical characteristics. The virological profiles of MPXV shed light on its complete infectious lifecycle and the formation of distinct virus particle types. Clinically approved classical detection methods and emerging novel testing techniques are provided, establishing a framework for early diagnosis of mpox patients. The efficacy and safety of both licensed vaccines and those under development are analyzed to underscore their value in preventing mpox infection. Additionally, progress in approved and newly identified potential therapeutic agents is summarized and discussed, aiming to provide insights for further drug development and clinical treatment strategies.

Aberrant deposition of β-amyloid (Aβ) and hyperphosphorylated tau, along with neuroinflammation, are key drivers of Alzheimer's disease (AD) pathology. Here, we identify ramalin, a natural antioxidant, as a promising therapeutic agent that alleviates AD pathology by modulating β-site APP cleaving enzyme 1 (BACE1), histone deacetylase 6 (HDAC6), and the mitogen-activated protein kinases (MAPK) pathway. Ramalin reduced BACE1 protein levels, independently of its transcription, translation, or enzymatic activity, an effect mediated by inhibition of HDAC6. Consistently, HDAC6 knockout similarly decreased BACE1 levels, highlighting HDAC6 as a key regulator of BACE1. Ramalin further suppressed neuroinflammatory responses by downregulating inducible nitric oxide synthase (iNOS) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome. In AD mouse models, ramalin treatment significantly attenuated neuroinflammation, Aβ plaque burden, and tau hyperphosphorylation, while improving cognitive performance. Notably, ramalin reversed Aβ oligomer-induced synaptic transmission impairment and restored synaptic vesicle recycling in hippocampal neurons. Transcriptomic analysis identified modulation of the MAPK pathway, with reduced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) implicated in tau pathology. These findings establish ramalin as a disease-modifying intervention that provides neuroprotection through concurrent regulation of BACE1, HDAC6, and MAPK signaling pathway. Collectively, our findings highlight ramalin as a compelling disease-modifying candidate with the potential to drive a breakthrough approach targeting AD pathology.

Tuberculosis (TB) remains a major global health challenge. In this study, we applied UPLC-MS/MS lipidomics and data-independent acquisition proteomics to profile plasma from healthy controls, active TB patients, and cured individuals to identify differentially expressed lipids and proteins. Mendelian randomization prioritized phosphatidylcholine (PC) lipids (PC(18:2/18:2), PC(14:0/20:4) and PC(18:0/20:4)) and proteins (haptoglobin [HP], retinol binding protein 4 [RBP4], coagulation factor XIII B subunit [F13B] and inter-alpha-trypsin inhibitor heavy chain 1 [ITIH1]) as candidate diagnostic and cure biomarkers. Binary multi-omics random-forest classifiers constructed with these markers achieved strong diagnostic (AUC = 0.967, 95% CI: 0.928–1.000) and cure-monitoring (AUC = 0.981, 95% CI: 0.956–1.000) performance, which was further assessed with ten-fold cross-validation. Integration with transcriptomic data and lipid-related gene analysis provided additional molecular support for HP. Independent validation in the GSE34608 cohort (AUC = 0.965) and ELISA verification (AUC = 0.969) confirmed HP's diagnostic utility at gene and protein levels. GSVA enrichment implicated HP in iron homeostasis and immune response pathways, suggesting a role in Mycobacterium tuberculosis infection and immune evasion through modulation of host iron metabolism. Overall, we present a robust lipid–protein biomarker panel and accurate multi-omics models for TB diagnosis and monitoring of cure, and propose HP as a promising biomarker and potential therapeutic target. These tools may improve clinical management and treatment evaluation.

Macrophages are innate immune cells that extensively infiltrate and play a key role in the tumor microenvironment (TME). Tumor cell–secreted factors recruit monocytes into the TME, where they differentiate into tumor-associated macrophages (TAMs), which can polarize into distinct phenotypes: M1 and M2. M1 TAMs promote antitumor immunity through cytokine secretion and antigen presentation, whereas M2 TAMs support tumor progression by facilitating angiogenesis, invasion, and immune escape. Despite these dual roles, the specific mechanisms governing macrophage plasticity and polarization remain insufficiently understood. This review comprehensively summarizes the origin, polarization, and functional diversity of macrophages in the TME, with emphasis on pathways that regulate TAM-mediated immune responses. Furthermore, this article examines current TAM-targeted therapeutic strategies, including recruitment inhibition, phenotypic reprogramming, and the development of chimeric antigen receptor macrophages (CAR-Ms), as well as macrophage-based drug delivery and exosome therapy. By integrating recent advances in cell engineering and immunometabolism, this review highlights the translational potential of TAM-targeted therapies and their value in reshaping the immunosuppressive TME to enhance cancer immunotherapy.

Organoids are three-dimensional structures that closely resemble the architecture and functions of human organs, offering key advantages over traditional models by better replicating tissue complexity and cellular interactions. These systems have become invaluable tools for disease modeling, drug screening, and regenerative medicine applications. Despite this progress, their lack of immune components limits their usefulness in diseases where immune cells are central drivers of pathology and therapy. The absence of an immune system within organoids limits their physiological relevance, particularly for cancer, inflammation, and autoimmunity research. Immune cell-containing organoids provide a comprehensive platform for immunotherapy, host–pathogen interactions, regeneration, and immune disorders. This review first highlights the transformative potential of immune cell-containing organoids across cancer, infection, inflammation, autoimmunity, regeneration, and the modeling of primary lymphoid organs. It then examines current strategies for integrating immune cells into organoids, the variety of immune cell sources employed, and the challenges in maintaining immune cell function. Finally, the role of bioengineering, biobanking, and artificial intelligence in overcoming existing limitations and enhancing immune system modeling is discussed. Overall, this study positions immune cell-containing organoids as powerful platforms for translational research and precision medicine.

Immunosenescence denotes progressive deterioration of immune system during physiological aging, initially recognized by the observation of heightened susceptibility to diverse pathologies in elder population. Beyond exhibiting canonical cellular senescence features, senescent immune cells manifest multidimensional dysfunction characterized by impaired secretory capacity and functional disorders. This process further triggers systemic epigenetic dysregulation and failure in damage repair, which collectively remodel metabolic and inflammatory microenvironments to attenuate immune responses and elevate risks of diverse degenerative diseases or multiple types of cancer. Critically, senescence-associated secretory phenotype (SASP) factors secreted by senescent cells display profound disease-associated content and spatial–temporal heterogeneity, engaging in bidirectional crosstalk with pathological progression through interconnected signaling axes. Reciprocally, both pathogenic evolution and therapeutic pressures are confirmed to exacerbate immunosenescence, driving impaired replenishment of immune cells and pathological accumulation of immunosuppressive factors that impact disease progression and poor outcomes. As indicated by clinical evidence, senotherapies designed to eliminate senescent cells or block SASP signaling have emerged as promising interventions to ameliorate age-related pathologies. In this review, we systematically combed and delineated disease-specific immunosenescent hallmarks, dissect disease–immunosenescence interplay patterns, and evaluated the translational value of immunosenescence-targeting strategies.

Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis, possesses notable anti-inflammatory, antioxidative, and anticancer properties. Despite its therapeutic potential, the full scope of its effects on healthspan and longevity remains unexplored. This study investigates the impact of baicalein on longevity and health-related biomarkers using the nematode Caenorhabditis elegans. Baicalein was administered to a wild-type N2 strain, seven mutant strains, and three reporter strains. Its influence on longevity, motility, lipofuscin accumulation, and oxidative stress resistance was assessed. The methodology included Kaplan–Meier survival analysis, in vivo imaging, fluorescence microscopy, and real-time PCR to evaluate RNA and protein expression. The findings indicate that baicalein significantly extends lifespan and enhances health markers, including improved motility, increased oxidative stress resistance, and reduced lipofuscin accumulation. Mechanistically, baicalein suppressed the DAF-2-mediated insulin/IGF-1 signaling pathway and promoted the nuclear translocation of DAF-16, a pivotal longevity transcription factor. Furthermore, baicalein upregulated the expression of the sod-3 gene, which is associated with enhanced stress tolerance and lifespan extension. These results elucidate the function of baicalein in promoting longevity and healthspan in C. elegans through modulation of insulin/IGF-1 signaling. Future studies are warranted to explore the applicability of baicalein in human aging to pave the way for innovative antiaging supplement formulations.

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.