Macrophages play crucial roles in protecting our bodies from infection and cancers. As macrophages are multi-functional immune cells, they have diverse plastic subsets, such as M1 and M2, derived from naïve M0 cells. Subset-specific macrophage probes are essential for deciphering and monitoring the various activation of macrophages, but developing such probes has been challenging. Here we report a fluorescent probe, CDr17, which is selective for M1 macrophages over M2 or M0. The selective staining mechanism of CDr17 is explicated as Gating-Oriented Live-cell Distinction (GOLD) through overexpressed GLUT1 in M1 macrophages. Finally, we demonstrate the suitability of CDr17 to track M1 macrophages in vivo in a rheumatoid arthritis animal model.
Preventing disease and maintaining the health of the elderly are crucial goals for an aging population, with obesity and immune function restoration being of paramount importance. Obesity, particularly visceral obesity characterized by excessive fat accumulation around the abdominal organs, is linked to chronic conditions such as diabetes, hypertension, cardiovascular diseases, and immune dysfunction. Globally, obesity is considered a disease, prompting significant research interest in its treatment. Therefore, it is essential to explore potential therapeutic and preventive strategies to address obesity and the decline in immune function brought about by aging. Tenebrio molitor larvae (TML), commonly known as 'mealworms,' are rich in unsaturated fatty acids, including oleic and linoleic acids, and essential amino acids, such as isoleucine and tyrosine. In this study, we aimed to investigate the effects of the consumption of TML oil and mealworm fermented extract (MWF-1) on obesity and immunological changes in aged obese mice. Our data showed reduced body fat in 23-week-old C57BL/6 mice fed processed TML products for 6 weeks. Additionally, the characteristically high levels of serum triglycerides decreased by treating with TML oil. The immune responsiveness results confirmed an increase in B cells by treating with MWF-1, while cytokine levels (interferon-gamma, tumor necrosis factor-alpha, interleukin-2, and -6) were restored to levels similar to young mice. These results suggest that TML oil and MWF-1 are promising dietary supplements for addressing obesity and restoring immune function.
Aging is accompanied by profound alterations in the immune system; yet, an accurate prediction of immunological age remains challenging. While transcriptomic approaches have yielded insights into immune aging, protein-level profiling and machine learning-based prediction tools remain underdeveloped. Here, we employ mass cytometry to analyse murine splenic CD45⁺ immune cells across various age groups, profiling the expression of 30 protein markers and monitoring age-related immune changes. By analysing six major immune subsets (CD8⁺ T cells, CD4⁺ T cells, B cells, conventional type 1 and type 2 dendritic cells, and macrophages), we extract 103 molecular features and train a machine learning model using support vector regression (SVR) to predict immunological age. The model demonstrates robust generalizability by accurately predicting age in independent, test samples that were not used during model training. Furthermore, we confirm the robustness of our model using an obese mouse model, which exhibits metabolic dysfunction–associated immune senescence. Thus, our findings establish a robust framework for predicting immune-aging based on multidimensional protein expression data and machine learning. This tool enables quantitative assessment of immune aging and demonstrates strong translational potential for identifying obesity- and disease-related immune senescence.
Despite notable advancements in cancer therapeutics, metastasis remains a primary obstacle impeding a successful prognosis. Our prior study has identified heme oxygenase 2 (HO2) as a promising therapeutic biomarker for the aggressive subsets within tumor. This study aims to systematically evaluate HO2 as a therapeutic target of cancer, with a specific emphasis on its efficacy in addressing cancer metastasis. Through targeted inhibition of HO2 by TiNIR (tumor-initiating cell probe with near infrared), we observed a marked increase in reactive oxygen species. This, in turn, orchestrated the modulation of AKT and cJUN activation, culminating in a substantial attenuation of both proliferation and migration within a metastatic cancer cell model. Furthermore, in a mouse model, clear inhibition of cancer metastasis was unequivocally demonstrated with an HO2 inhibitor administration. These findings underscore the therapeutic promise of targeting HO2 as a strategic intervention to impede cancer metastasis, enhancing the effectiveness of cancer treatments.