Guibin Wang | Search PubMed

PubMed2026

Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection.

BACKGROUND: Monkeypox virus (MPXV) infects diverse human cell types, and human immunodeficiency virus (HIV) co-infection is common. The immunometabolic consequences of MPXV infection, and how it may be altered by HIV, remain poorly defined. METHODS: We performed quantitative plasma lipidomics and precise metabolomics in a discovery cohort (n = 81) comprising MPXV-monoinfected (MPLWOH), MPXV-HIV-coinfected (MPLWH), and HIV-monoinfected (PLWH) patients and healthy controls, integrating exosome proteomics, cytokine profiling, and transcriptomics of exosome-treated HepG2 and A549 cells for functional interpretation. An independent validation cohort (n = 65) was used to assess cross-cohort reproducibility. FINDINGS: MPXV infection induced broad lipid remodeling, with elevations in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and reductions in phosphatidylcholine (PC), lysophospholipids, cholesteryl ester (CE), and exosomal lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). These lipid alterations were correlated with tissue injury markers and inflammatory cytokines. The MPLWH group exhibited more severe metabolic disruption, including marked sulfatide (SL) depletion, lower cholesterol and high-density lipoprotein cholesterol (HDL-c), and extensive rewiring of lipid-cytokine associations. SL depletion in MPLWH correlated with abundances of COPI-mediated retrograde trafficking proteins in exosomes. Transcriptomic profiling of exosome-treated cells provided functional validation: MPLWOH exosomes induced lipid metabolism and repair-associated epithelial programs, while MPLWH exosomes drove phospholipid remodeling and acute inflammatory and mucosal barrier-stress responses. CONCLUSIONS: MPXV infection reprograms host lipid metabolism and exosome composition, with HIV co-infection amplifying inflammatory, metabolic, and trafficking disruptions. These convergent multi-omics signatures link systemic lipid dysregulation to exosome-mediated immunomodulation and identify potential targets for host-directed interventions. FUNDING: This study was funded by the Major Project of Guangzhou National Laboratory.

Adult↗

PubMed2025

Plasma Proteomic Profiling Reveals ITGA2B as A Key Regulator of Heart Health in High-altitude Settlers.

Myocardial injury is a common disease in the plateau, especially in the lowlanders who have migrated to the plateau, in which the pathogenesis is not well understood. Here, we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteomic profiling. Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude. Notably, integrin alpha-Ⅱb (ITGA2B) emerged as a potential key player in this context. Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6 (IL-6) through the integrin-linked kinase (ILK)/nuclear factor-κB (NF-κB) signaling axis under hypoxic conditions. Moreover, ITGA2B disrupted mitochondrial structure and function, increased glycolytic capacity, and aggravated energy reprogramming from oxidative phosphorylation to glycolysis. Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases, we discovered that tanshinone ⅡA (TanⅡA) effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice, thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.

Animals↗