ABSTRACTBackgroundTwo antiphagocytic (“don't eat me”) signals that allow tumor immune evasion have been discovered, including CD24 and CD47. This study explored the association between CD24/CD47 expression and macrophage infiltration and clinical outcomes in cervical cancer.MethodsRNA expression and survival data of the Cancer Genome Atlas (TCGA) cohort were extracted from OncoLnc. The macrophage infiltration level was calculated using xCell, TIMER, and ImmuCellAI. The expression of CD24 and CD47 was detected by immunohistochemistry in tissue microarrays composed of 130 clinical cervical cancer specimens from Fudan University Shanghai Cancer Center (FUSCC). Patients' medical records were also retrospectively assessed to correlate demographic and survival data.ResultsExpression levels of both CD24 and CD47 in the cancer population were higher than those in the normal population. Patients with high CD24 expression had poorer survival than those with low CD24 expression in the TCGA and FUSCC cervical cancer cohorts. Although CD47 alone was not statistically significant in predicting outcomes, patients with high CD47 and low CD11c expression, a specific marker of M1‐polarized macrophages, exhibited worse survival in the TCGA cohort.ConclusionsOur study implies that high CD24 expression is an important predictor of a worse prognosis, and CD24 blockade might have therapeutic potential for the treatment of cervical cancer. High expression levels of CD47 and low M1‐polarized macrophage infiltration predict a worse prognosis.

In naturally infested sheep, two genera and four species of Ixodidae, two genera and two species of mites, two genera and two species of lice, three genera and three species of myiasis, and three genera and three species of fleas. Highly infested, as described in sheep, with Arachnida at 55%, comprising 46% Hard ticks and 9% Mites. The overall number of skins refused to the tanning industry was 100 (21.21%) in sheep. Histological and blood values analysis of the skin of sheep repeatedly infested with the Hyalomma anatolicum anatolicum was studied in vitro. Infiltration of neutrophils, macrophages, and lymphocytes adjacent to the tick bite site was observed. In this review, the presence of ectoparasites affected both the red and white blood cell series of hematological parameters. Among the main parameters analyzed, hematocrit, red blood cells, hemoglobin, and lymphocytes showed reductions, while eosinophils, neutrophils, and basophils increased in infested animals as a result of the host immune response. A t-test, p < 0.05, in this study reveals a statistically significant difference in blood values between individuals with naturally infested ectoparasites. This study highlights the species of Ixodidae and other ectoparasites (mites, myiasis, fleas, and lice) that cause various patterns of cutaneous lesions (as observed through histopathology) in sheep, which affects their industry.

Photo-crosslinked carboxymethyl cellulose/collagen hydrogel-infused mesh for preventing postoperative pelvic adhesions in a rat model.

Bronchopulmonary dysplasia (BPD), a frequent complication in preterm infants receiving supplemental oxygen, is characterized by hyper-activation of macrophage inflammasomes, exuberant release of pro-inflammatory cytokines such as interleukin-1β (IL-1β), and Gasdermin D (GSDMD)-driven pyroptosis. However, the precise contribution of macrophage pyroptosis to BPD pathogenesis remains incompletely defined, and effective pharmacological interventions are still lacking. Using neonatal C57BL/6 wild-type (WT) and GSDMD-knockout (GSDMD-/-) mice, we established a hyperoxia-induced BPD model (85% FiO₂, 14 days) and administered the GSDMD inhibitor disulfiram (50 mg kg⁻¹ intraperitoneally, once daily for 7 days). In vivo, we assessed lung histopathology, IL-1β levels, alveolarization, and vascular development; ex vivo, we isolated bone-marrow-derived macrophages (BMDMs) to quantify pyroptotic markers, M1/M2 polarization, and antibacterial capacity. GSDMD deletion or disulfiram treatment significantly attenuated macrophage and neutrophil infiltration, decreased pulmonary IL-1β concentrations, improved alveolar architecture and vascular density, and reduced overall cell death. BMDMs from GSDMD-/- mice displayed diminished M1 polarization, enhanced bacterial killing, yet unaltered zymosan phagocytosis. Collectively, these findings identify GSDMD-mediated macrophage pyroptosis as a critical driver of BPD-related lung injury. Targeted GSDMD inhibition, whether genetic or pharmacologic, alleviates experimental BPD by down-regulating IL-1β and promoting alveolar development, thereby providing a promising therapeutic avenue for this devastating neonatal disorder.

Abstract The introduction of bowel cancer screening has led to an increase in the detection and removal of pre-malignant adenomas, however many of these would never progress to colorectal cancer (CRC) within a patient’s lifetime. This implies a key evolutionary bottleneck at the transition from adenoma to carcinoma, with immune surveillance likely playing a central role in suppressing the outgrowth of invasive cells. Here we analysed a cohort of “ca-in-ads” (adenomas with a small focus of cancer) to provide a unique snapshot of the invasive transition. We combined genomics, spatial transcriptomics, digital pathology and multiplex imaging, concurrently deriving the distribution of tumour clones, their gene expression and their interplay with the immune microenvironment. We performed multi-region low-coverage whole genome sequencing (lcWGS) and T-cell receptor sequencing (using FUME-TCRseq, a novel method developed in our lab) on archival ca-in-ads from 40 patients. For a subset of cases we performed spatial transcriptomics using the 10x Genomics Visium platform, including custom probes to detect T-cell clonotypes of interest. We applied a deep learning cell classifier to haematoxylin and eosin (H&E) stained sections to determine the abundance and spatial distribution of eight cell types, with detailed immunophenotyping on selected cases (using a 50-marker panel on Akoya’s PhenoCycler-Fusion platform). We found a significant increase in copy number alterations in carcinoma regions relative to adenomas, and this was accompanied by a large shift in the composition of the local T-cell repertoire. TCR sequencing revealed expanded T-cell clonotypes that were adenoma-specific or carcinoma-specific, and we validated the spatial exclusivity of these using a custom Visium assay. Although overall lymphocyte density remained unchanged, digital pathology and cyclic immunofluorescence revealed significantly increased infiltration of macrophage and neutrophil populations in regions of invasive cancer. Taken together our analysis suggests a striking reshaping of tumour-immune dynamics at the transition to an invasive phenotype in CRC. Understanding what governs this invasive shift could highlight new avenues for cancer prevention or identify individuals at risk of CRC. Citation Format: Ann-Marie Baker, Eleanor Smith, Chirine Sakr, Konstantin Bräutigam, Nick Trahearn, Holly Eggington, Miangela M. Lacle, Manuel Rodriguez-Justo, Simon J. Leedham, Trevor A. Graham. Multi-omic spatial analysis reveals reshaping of tumour-immune dynamics at the transition to invasive colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr PR004.

HIF-1α/A2BAR signalling pathway alleviates kidney fibrosis after ischemia-reperfusion injury by preventing macrophage-to-myofibroblast transition.

SPP1-mediated crosstalk between macrophage and fibroblasts promotes benign airway stenosis.

Harnessing PD-1-overexpressing macrophage membrane for preparation of lenvatinib-loaded vesicles to boost immunotherapy against HCC recurrence after radiofrequency ablation.

Esaxerenone inhibits renal macrophage proliferation through MR/TGF-β1 pathway in db/db mice.

Mild and reversible nephrotoxicity following repeated administration of damnacanthal in nude mice.

Polystyrene nanoplastics induce ovarian injury by PI3K-Akt pathway-driven macrophage extracellular trap formation.

BackgroundBreast cancer is the most common cancer among women and a leading contributor to disease-related mortality. While advancements in diagnostic techniques and the widespread dissemination of medical knowledge have improved outcomes, immunotherapy targeting the tumor microenvironment offers a promising approach to further reducing the disease burden.MethodsWe first explored cellular heterogeneity within breast cancer tumors using single-cell RNA sequencing and subsequently analyzed the association between the infiltration levels of various cell types and survival prognosis using a deconvolution algorithm combined with bulk RNA sequencing. Our analysis identified CXCL9 + macrophages as being associated with improved survival outcomes. Next, WGCNA was used to identify genes related to CXCL9 + macrophage infiltration, and a survival risk model was constructed based on these genes. Finally, experiments were conducted to validate the effects of CXCL9 + macrophages on breast cancer cells.ResultsWe found that CXCL9 + macrophage primarily interacted with cytokines and activated T and NK cells through the CXCL9/10/11-CXCR3 axis. Increased infiltration, as observed in bulk RNA sequencing, was associated with improved patient survival. The risk model constructed based on CXCL9 + macrophage infiltration-related genes demonstrated strong efficacy in predicting patient survival outcomes. Finally, in vitro experiments confirmed that CXCL9 + macrophages inhibited the viability of breast cancer cells.ConclusionCXCL9 + macrophages could play a significant role in inhibiting breast cancer, and their infiltration into tumor tissues is associated with improved survival in breast cancer patients. Immunotherapy targeting CXCL9 + macrophages hold great potential as a therapeutic strategy.

Selective inhibition of histone deacetylase 3 (HDAC3) prevents vincristine-induced peripheral neuropathy via macrophage polarization.

ICAT drives lactylation of tumor-associated macrophages via the c-Myc-ENO1 axis to promote cervical cancer progression.

Oncoprotein SND1-enriched exosomes facilitate melanoma lung metastasis by regulating CD47-SIRPα-mediated macrophage reprogramming.

Identification of DNA damage repair-related diagnostic markers for idiopathic pulmonary fibrosis via WGCNA.

Targeting the colony-stimulating factor 1 axis for the treatment of Tenosynovial Giant Cell Tumors.

Sepsis-induced cardiac dysfunction: Gender bias role of allograft inflammatory factor-1.

There is no safe level of exposure to air pollution, including particulate matter smaller than 2.5 µm (PM2.5), to human health. Whilst it is well known that exposure to heavily polluted air is associated with several liver disorders, it is unclear how long-term exposure to low-level traffic-derived PM2.5 affects liver health. BALB/c mice (5 weeks, male) were exposed to traffic-derived PM2.5 (10 µg/mouse/day, intranasally) daily for 4, 8 and 12 weeks. Markers of inflammation and fibrosis were measured at each time point. Changes in liver proteome and lipid profiles were measured using proteomics and lipidomics at 12 weeks. Low-dose PM2.5 exposure increased macrophage infiltration, pro-inflammatory cytokine production, and increased collagen deposition at 12 weeks. Despite liver lipid metabolism being increased, the abundance of triglycerides, precursor diacylglycerols, and ceramide was also significantly increased by PM2.5 exposure, whereas glycogen content was reduced. Proteomics analysis revealed 64 proteins to be significantly changed in PM2.5-exposed mice, and KEGG pathway enrichment analysis indicated their involvement in lipid metabolism, alcohol-related liver disease, neutrophil extracellular trap formation, and transcriptional dysregulation related to cancer. In conclusion, prolonged exposure to low-dose traffic-derived PM2.5 promotes pathological changes in the liver, suggestive of an increased risk of metabolic dysfunction-associated fatty liver disease. Future studies can enable the identification of the signalling pathways underlying low-dose PM2.5-induced lipid accumulation in the liver.

To explore the mechanism of regulatory genes related to reactive oxygen species (ROS) in glioblastoma (GBM). GBM is a brain malignancy with a poor prognosis. ROS plays a critical role in cellular metabolism, signaling, and senescence, and abnormalities in ROS are closely associated with cancer initiation and development. However, the role of ROSregulated genes in GBM remained unknown. To explore the role of ROS-regulated genes in GBM and to build a ROS-related prognostic model. RNA sequencing and clinical data from GBM patients were collected from public databases. The enrichment scores of ROS-correlated pathway gene sets obtained from The Molecular Signatures Database (MSiDB) were calculated using single sample gene set enrichment analysis (ssGSEA). Subsequently, key ROS-correlated gene modules were sectioned by weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed to screen ROS-related genes, which were used to develop a risk model. In addition, the correlation between patients in high-risk and low-risk groups and clinicopathological features, metabolism-related pathways, and pathways related to tumor progression was analyzed. Finally, the difference in immune cell infiltration between patients in the two risk groups was calculated using CIBERSORT. We found that ROS-related genes could predict the prognosis of patients suffering from GBM and that abnormal activation of the ROS pathway increased the metabolism of sugars, fats, and amino acids. WGCNA identified gene modules closely associated with ROS. A prognostic risk model was created using three key genes (OSMR, SLC6A6, and UPP1). Immune infiltration analysis showed that high-risk Patients had higher levels of macrophage infiltration, and a high-RiskScore was positively correlated with multiple metabolism processes, programmed death, and epithelial-mesenchymal transition (EMT) pathway activity. The ROS-associated risk model could accurately predict tumor immunity and progression for GBM patients, acting as an effective predictor of GBM prognosis. The present discovery provided a novel understanding of the diagnosis and treatment of GBM patients.