No Distinct Cytokine, Chemokine, and Growth Factor Blood Profile Associated With Monkeypox Virus Clade IIb Infected PatientsBangwen, Berens-Riha, de Vrij
et alJ Med Virol (2025) 97 (4), e70320
Abstract: Previous studies indicated Clade I monkeypox virus infection to be associated with marked elevation of proinflammatory cytokines. This remains unexplored for Clade II-associated disease, which has different clinical manifestations and prognosis. We used a 65-plex cytokine, chemokine, and growth factor (CCG) panel to analyze serum samples of 100 male acute Clade IIb mpox patients and 26 healthy controls in Belgium. Cluster analyses revealed no strong or distinct CCG profiles distinguishing mpox patients from controls but suggested trends in certain cytokine modulation. Individual CCG analyses found elevated levels of cytokines (MIF, CD30, IL2R, IL18, APRIL, and TNFRII), chemokines (CCL4, CCL8, CCL22, CCL24, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13), and growth factors (HGF and VEGFA) in patients, while CCL11 and CXCL5 were significantly suppressed. We detected no differences in key proinflammatory cytokines, IL-1α, IL-1β, IL-6, IL-8 or anti-inflammatory cytokines, IL-4, IL-10, IL-13. In patients living with HIV, comparison with pre-outbreak samples showed an increase in CXCL13 and a decrease in CXCL5, CCL2, CCL24, HGF, SCF, and TWEAK. The absence of discriminatory CCG profiles in Clade IIb mpox patients compared to healthy controls suggests there may be limited clinical applications of those markers.© 2025 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.
In vivo synergistic enhancement of MIF-mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1Spiller, Zhang, Gerra
et alFASEB J (2025) 39 (6), e70489
Abstract: Recent research has uncovered Arabidopsis thaliana proteins that are similar to the human inflammatory cytokine MIF. Plant MIF/D-dopachrome tautomerase (D-DT)-like proteins (MDLs) can interact with human MIF, yet the significance of these findings in living organisms has not been investigated. Given MIF's key role in acute respiratory distress syndrome promoting pulmonary inflammation, pathology, and leukocyte infiltration, here we set out to investigate the interplay between MIF and MDL1, one of three A. thaliana MIF orthologs, in an in vivo mouse model of MIF-induced acute lung injury (ALI). Human MIF and MDL1 were administered to C57BL/6 mice via inhalation, individually or in combination. Inhalation of MIF promoted various parameters of lung injury as evaluated by flow cytometry, immunofluorescence microscopy, RT-qPCR, and ELISA, while MDL1 inhalation alone had no effect. Intriguingly, combined treatment with MIF and MDL1 synergistically enhanced pulmonary infiltration of neutrophils and monocytic cells, accompanied by an upregulation of pro-inflammatory cytokine genes. Thus, the plant-derived MIF ortholog MDL1 potentiates MIF-induced inflammation in ALI. These data support the growing evidence of interactions between plant-derived compounds and human inflammatory mediators and illustrate how they may impact human health.© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approachRamzy, Abdel-Halim, Manie
et alTransl Oncol (2025) 55, 102365
Abstract: Triple negative breast cancer (TNBC) is an immunogenic tumor; however, its tumor immune microenvironment (TIME) is densely packed with immune suppressive cytokines and immune checkpoints. The immune-suppressive features of TNBC TIME represent a considerable obstacle to any immunotherapeutic approach. The objective of this study was to develop a multimodal in-vitro strategy to manipulate the TNBC TIME and enhance patients' outcomes by employing carefully tailored hybrid chitosan-lipid Nanoparticles (CLNPs), metformin and chlorin e6 (Ce-6)-mediated PDT, alone or combined. Special focus is directed towards evaluation of the role of the selected treatment agents on the non-coding RNAs (ncRNAs) involved in tuning the immuno-oncogenic profile of TNBC, for instance, the miR-30a-5p/MALAT1 network.This study enrolled 30 BC patients. CLNPs and ce-6-loaded CLNPs with different physicochemical features were synthesized and optimized using ionotropic gelation. The intracellular concentration and effects on MDA-MB-231 cellular viability were investigated. UHPLC was used to quantify ce-6. MDA-MB-231 cells were transfected with miR-30a-5p oligonucleotides and MALAT1 siRNAs using lipofection to investigate the interaction between MIF, PD-L1, TNF-α, IL-10, and the miR-30a-5p/MALAT1 ceRNA network. qRT-PCR was used to evaluate IL-10, TNF-α, and MIF expression levels, whereas flow cytometry was used for PD-L1.Immunophenotyping of BC biopsies revealed significantly elevated levels of immunosuppressive markers, including IL-10, TNF-α, PD-L1, and MIF in BC biopsies compared to its normal counterparts. Upon patient stratification, it was shown that MIF and IL-10 are upregulated in TNBC patients compared to non-TNBC patients. Nonetheless, immune suppressive biomarkers expression investigated in the current study was generally correlated with signs of poor prognosis. CLNPs with mean particle size ranging from 50-150 nm were obtained. CLNPs exhibited different patterns of intracellular uptake, cytotoxicity and modulation of the immunosuppressive markers based on their physicochemical properties and composition. In particular, CLNP4 in-vitro effectively reduced IL-10, TNF-α, MIF, and PD-L1. Loading of Ce-6 into CLNP4 (Ce6-CLNPs) improved the in-vitro cytotoxic effects via PDT. In addition, PDT with Ce6-CLNP4 enhanced the expression of tumor-suppressive miR-30a-5p and decreased oncogenic lncRNA MALAT1 expression in MDA-MB-231 cells, suggesting a potential for modulating the TNBC immuno-oncogenic profile.This study demonstrated that CLNPs and Ce-6-mediated PDT can modulate several key immunosuppressive factors and the miR-30a-5p/MALAT1 axis in TNBC cells. These findings provide a rationale for further in-vivo investigation of this multimodal therapeutic strategy.Copyright © 2025. Published by Elsevier Inc.
MIF as an oncogenic driver of low-heterogeneity melanomasTran, Sánchez-Zuno, Kulkarni
et alMol Oncol (2025)
Abstract: Identifying targets involved in tumor evolution and immune escape is an active area of research in oncology. Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine that promotes transformed cell proliferation and survival, and generates a tumor-permissive immune landscape of immunosuppressive myeloid and T cells. Shvefel and colleagues have identified a key role for MIF in tumor progression in melanoma clones with low tumor heterogeneity. These findings provide important insights into the potential therapeutic utility of MIF antagonists and support ongoing research to utilize MIF pathway inhibitors for improved therapeutic outcomes.© 2025 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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