Mapping Inflammatory Markers in Cerebrospinal Fluid Following Aneurysmal Subarachnoid Hemorrhage: An Age- and Sex-Matched Analysis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1302 - 1302

Published: Feb. 3, 2025

Despite extensive research on aneurysm treatment and neurocritical care, aneurysmal subarachnoid hemorrhage (SAH) is still a life-threatening disease, often leaving survivors with lasting neurological cognitive impairments. Early brain injury (EBI) delayed cerebral ischemia (DCI) are the main contributors to damage, neuroinflammation being critical shared pathophysiological process. While numerous inflammatory markers their temporal profiles in cerebrospinal fluid (CSF) have already been identified, comparisons age- sex-matched controls limited. This study analyzed CSF from 17 SAH patients requiring an external ventricular drain (EVD) due symptomatic hydrocephalus, sampled days 4 10 post-ictus. An control group included cerebrovascularly healthy lumbar drains during aortic surgery. Chemokines cytokines were quantified using immunoassays. Significantly elevated across both time points MCP-1, CXCL-13, Eotaxin-1, CXCL-10, IL-8, MIF. MIP-1α MIP-1β showed significant differences at particular points, indicating distinct profile for each parameter. These findings highlight neuroinflammation’s key role intracranial systemic pathophysiology following SAH, emphasizing its complexity individual variability. Knowing demographic factors impact specific manifestations of processes, comparison meaningful.

Language: Английский

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An adoptive cell therapy with TREM2‐overexpressing macrophages mitigates the transition from acute kidney injury to chronic kidney disease

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Abstract Background Macrophages have been shown to contribute renal injury and fibrosis as well repair. Recently, Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)‐positive macrophages play important roles in regulating tissue inflammation However, it remains unclear whether they can mitigate the transition from acute kidney chronic disease (the AKI–CKD transition). Methods The was generated by unilateral ischaemia–reperfusion (UIRI) wild‐type (WT) Trem2 knockout mice. F4/80 magnetic beads were used isolate macrophages. Flow cytometry determine levels of TREM2 CD11b levels. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blotting histological staining performed expression cytokines fibrotic markers. RNA‐seq investigate transcriptomic changes between WT bone marrow‐derived (BMDMs). TREM2‐overexpressing using lentivirus transferred intravenously UIRI Results exhibited a strong protective effect transition. Genetic deletion resulted increased exacerbated Interestingly, we found that hypoxia could increase via HIF‐1α. Upregulated enhanced macrophage phagocytosis suppressed pro‐inflammatory cytokines, resulting lower apoptosis tubular epithelial cells. Using analysis, showed regulatory effects orchestrated PI3K‐AKT pathway. Pharmacological regulation pathway modulate macrophage‐mediated phagocytosis. In addition, an adoptive cell therapy effectively reduced immune infiltration, Conclusion Our study not only provides valuable mechanistic insights into role but also offers new avenue for macrophage‐based treat diseases. Key points worsens accelerates is upregulated HIF1α An reduces fibrosis.

Language: Английский

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Macrophage diversity in cancer dissemination and metastasis

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(11), P. 1201 - 1214

Published: Oct. 14, 2024

Invasion and metastasis are hallmarks of cancer. In addition to the well-recognized hematogenous lymphatic pathways metastasis, cancer cell dissemination can occur via transcoelomic perineural routes, which typical ovarian pancreatic cancer, respectively. Macrophages a universal major component tumor microenvironment and, in established tumors, promote growth secondary sites. Here, we review role tumor-associated macrophages (TAMs) emphasizing diversity myeloid cells different tissue contexts (lungs, liver, brain, bone, peritoneal cavity, nerves). The generally used models lung fail capture microenvironments. A better understanding TAM may pave way for tailored diagnostic therapeutic approaches.

Language: Английский

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TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 21, 2025

Abstract Background Triggering receptor expressed on myeloid cells 2 (TREM2), a surface predominantly cells, is major hub gene in pathology-induced immune signaling. However, its function hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 tumor microenvironment context HCC progression. Methods was experimentally induced wild-type (WT) and Trem2 -deficient ( −/− ) mice, clinical sample analysis vitro studies macrophages were conducted. treated with conditioned medium from WT or macrophages, their malignant phenotypes underlying mechanisms analyzed. Results deficiency reduced liver burden orthotopic subcutaneous models by altering CD8 + T cell infiltration. presented increased chemokine secretion. TGF-β1 found be positively correlated expression HCC, TGF-β blockade reversed induction. On other hand, associated glycolysis PKM2 cells; this association may related secretion IL-1β, which enhances cells. Conclusions These results reveal that play driving progression suppressing infiltration promoting glycolysis, providing new therapeutic target for HCC.

Language: Английский

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TREM2+ macrophages: a key role in disease development

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 2, 2025

Triggering receptors expressed on myeloid cells 2 (TREM2), an immune receptor cells, has garnered considerable attention in recent years due to its role unique signaling pathways and diverse biological functions, including phagocytosis, lipid metabolism, cell survival, inflammatory responses. Although TREM2 is various types, such as macrophages, dendritic (DCs), osteoclasts, others, where it exhibits context-dependent functional characteristics, mainly macrophages. Notably, implicated the development progression of multiple diseases, playing dual often opposing roles noncancerous diseases cancers. This review aims highlight pivotal macrophages immune-related elucidate underlying mechanisms action, explore potential a clinical diagnostic prognostic marker, propose therapeutic strategies targeting based current trial data, providing comprehensive guidance references for practice.

Language: Английский

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Pan-cancer human brain metastases atlas at single-cell resolution

Cancer Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications

Molecular Brain, Journal Year: 2024, Volume and Issue: 17(1)

Published: Nov. 20, 2024

Abstract CNS tumours encompass a diverse group of neoplasms with significant morbidity and mortality. The SHH signalling pathway plays critical role in the pathogenesis several tumours, including gliomas, medulloblastomas others. By influencing cellular proliferation, differentiation migration has emerged as promising target for therapeutic intervention. Current strategies such vismodegib sonidegib have shown efficacy targeting activation. However, challenges resistance mechanisms paradoxical effects observed clinical settings underscore complexity effectively this pathway. Advances gene editing technologies, particularly CRISPR/Cas9, provided valuable tools studying biology, validating targets exploring novel treatment modalities. These innovations paved way better understanding dynamics development more precise interventions. In addition, identification validation biomarkers activation are to guide decision making improve patient outcomes. Molecular profiling biomarker discovery efforts steps towards personalised medicine approaches pathway-associated tumours. While progress been made tumorigenesis, ongoing research is essential overcome current refine strategies. integration molecular insights advanced technologies expertise holds great promise developing effective therapies patients pathway-driven Graphical

Language: Английский

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Mapping myeloid cell function: Spatial diversity in tumor and neuronal microenvironment

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(6), P. 934 - 936

Published: June 1, 2024

Language: Английский

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Identification of hypoxic macrophages in glioblastoma: Unveiling therapeutic insights from tumour microenvironment analysis

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(9)

Published: Sept. 1, 2024

Tumor-associatedmacrophages (TAMs) exhibit remarkable heterogeneity in glioblastoma. Spatially resolved single-cell transcriptomic studies identified a monocyte-derived TAM subset localized the peri-necrotic niche, driven by hypoxic cues to acquire ahypoxia response signature. These hypoxia-TAMs destabilize endothelial adherens junctions through adrenomedullin paracrine signaling, promoting formation of hyperpermeable neovasculature that impedes drug delivery. Blocking produced restores vascular integrity, increases deliveryinto tumors, and provides combinatorial therapeutic benefits. Here we discuss TAMs regarding functional states locations glioblastomas, propose future directions for studying temporospatial dynamics multifaceted TAM. HIGHLIGHTS: Single-cell omics reveal functionally spatially distinct hypoxia-TAM Adrenomedullin secreted destabilizes tumor vasculature its blockade enhances vessel integrity

Language: Английский

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