Search Results (13,532)

Background/Objectives: Itaconic acid (ITA) is an immunometabolite with anti-inflammatory and metabolic regulatory functions, but its cellular source and role in brown adipose tissue (BAT) remain unclear. This study aims to reveal the expression patterns of the key ITA synthesis gene Irg1 in BAT at different developmental stages and to investigate the effects of cold exposure and exogenous ITA on BAT metabolic function and cardioprotection. Methods: Single-cell RNA sequencing was used to analyze the gene expression profiles of stromal vascular fraction (SVF) cells in BAT from P7 neonatal and adult mice. Bioinformatic methods were applied to identify cell types expressing Irg1. Cold exposure (4 °C) and exogenous ITA treatment were employed to evaluate BAT morphology, and the ITA content in BAT was detected using gas chromatography–triple quadrupole mass spectrometry, UCP1 protein expression, and body temperature changes. A transverse aortic constriction (TAC) surgery model was established to induce cardiac dysfunction, and BAT excision was performed to explore the BAT-dependent effects of ITA on myocardial hypertrophy, fibrosis, and cardiac function. Results: In P7 neonatal mouse BAT, Irg1 was predominantly expressed in a subset of interferon-responsive activated macrophages (macrophage27), while in adult mice, it was mainly expressed in neutrophils and a functionally similar macrophage subset (macrophage25). Cold exposure significantly suppressed Irg1 expression in neutrophils but did not affect its expression in macrophages, also resulting in a significant decrease in ITA content in BAT. Exogenous ITA significantly enhanced BAT thermogenesis under cold conditions, which manifested as reduced lipid droplets, upregulated UCP1 expression, and increased body temperature. In the TAC model, ITA treatment markedly improved cardiac function, attenuated myocardial hypertrophy and fibrosis, and these protective effects were significantly diminished after BAT excision. Conclusions: ITA promotes cold adaptation and ameliorates cardiac injury by enhancing BAT metabolic function, and its effects depend on the presence of BAT. This study provides new insights for the treatment of metabolic cardiovascular diseases. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a continuum of hepatic pathological manifestations of the metabolic syndrome. Pathogenesis is not clearly understood despite recent progress, but Kupffer cells and bone marrow-derived macrophages (BMDMs) have a fundamental role. In this review, the multiple pathophysiological aspects of MASLD are presented, including genetics, insulin resistance, lipotoxicity, and inflammation. The participation of innate and adaptive immunity, as well as the implications of the recently described trained immunity, is presented. The interplay of the liver with the gut microbiota is also analyzed. A recent adipocentric theory and the various mechanisms of hepatocyte death are also described. The fundamental role of Kupffer cells and other liver macrophages is discussed in detail, including their extreme phenotypic plasticity in both the normal and the MASLD liver. The functional differentiation between pro-inflammatory and anti-inflammatory subpopulations and their protective or detrimental involvement is further described, including the participation of Kupffer cells and BMDMs in all aspects of MASLD pathogenesis. The role of macrophages in the development of advanced MASLD, including fibrosis and hepatocellular carcinoma, is analyzed and the lack of explanation for the transition from MASLD to MASH is recognized. Finally, current modalities of drug treatment are briefly presented and the effects of different drugs on macrophage polarization and functions are discussed. Full article

Invariant chain, also known as CD74 when expressed on the plasma membrane, is classically recognized for its role in Major Histocompatibility Complex class II molecule assembly, trafficking, and peptide loading in professional antigen presenting cells. However, recent studies implicate CD74 as a broader regulator of tumor–immune interactions, modulating antigen presentation, cytokine signaling, and immune evasion across diverse cancers. This review synthesizes emerging evidence that CD74 functions as a “master regulator” of antigen presentation in cancer, integrating its canonical chaperone role with its noncanonical role in transcription regulation and in signaling via macrophage migration inhibitory factor. We explore how tumor microenvironmental contexts redefine CD74 biology, influencing antitumor immunity and therapeutic outcomes. Full article

Chemotherapy resistance in colorectal cancer (CRC) represents a critical clinical challenge leading to treatment failure and poor patient prognosis. Artemisinin is a natural product isolated from Artemisia annua, and its clinically relevant derivatives include dihydroartemisinin (DHA) and artesunate. Beyond their established antimalarial efficacy, both artemisinin and its derivatives—collectively referred to as artemisinin-derived compounds (ADs)—have been increasingly recognized for their unique potential to reverse multidrug resistance in cancer. Unlike previous reviews focusing on isolated mechanisms, this review systematically constructs a multidimensional, synergistic attack network centered on ADs to elucidate their integrated actions against chemotherapy-resistant CRC. Mechanistically, ADs suppress cancer stem cell (CSC)-associated resistance phenotypes while concurrently reshaping the tumor immune microenvironment, highlighting a functional coupling between stemness inhibition and immune remodeling. In parallel, this review presents apoptosis reactivation and ferroptosis induction as complementary, dual-track cell death strategies that collectively circumvent apoptosis resistance. Moreover, ADs exert “one-strike–multiple-effects” through coordinated regulation of pro-survival signaling networks and immune-related pathways, including the induction of immunogenic cell death (ICD) and the modulation of immunosuppressive macrophage subsets. Beyond mechanistic insights, this review integrates emerging translational considerations, including clinical pharmacokinetics, safety and tolerability, formulation and delivery strategies, and rational combination therapy paradigms in CRC. Collectively, these findings position ADs as multi-dimensional modulators rather than a single-agent cytotoxic, providing a coherent mechanistic and translational rationale for their further development in chemotherapy-resistant CRC. Full article

Vasculitides are a heterogeneous group of disorders characterized by inflammation of blood vessel walls, leading to tissue ischemia and organ injury. Traditional inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used but lack diagnostic specificity. This has driven the search for more informative biomarkers across vasculitis subtypes. This review summarizes current evidence for validated and emerging biomarkers in large-, medium-, small-, and variable-vessel vasculitis, as well as single-organ vasculitis. Key analytes reflect systemic inflammation, such as serum amyloid A (SAA) and interleukin-6 (IL-6), as well as endothelial activation, complement pathways, neutrophil and macrophage activation, and organ-specific damage. Promising candidates include pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9) in large-vessel vasculitis; N-terminal pro-B-type natriuretic peptide (NT-proBNP) and S100 proteins in Kawasaki disease; galactose-deficient immunoglobulin A1 (Gd-IgA1) and urinary angiotensinogen (AGT) in IgA vasculitis; and tissue inhibitor of metalloproteinases-1 (TIMP-1), S100 proteins, complement C3, and PTX3 in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although these biomarkers provide mechanistic insight, most lack disease-specificity, external validation, or standardized assays. Future progress will require multicenter studies, harmonized testing, and integrated biomarker panels combined with imaging modalities to improve diagnosis, activity assessment, and monitoring. Full article

Bidens pilosa L., a traditional Chinese medicinal herb, has been used in clinical practice for the treatment of inflammatory diseases and cancer. BPA, an extract derived from the whole herb of B. pilosa L., has been shown to possess potent immunomodulatory properties by regulating tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) within the tumor microenvironment (TME) in a mouse syngeneic colorectal cancer (CRC) model. RT-PCR and flow cytometry analyses showed that BPA, together with its flavonoid and polyacetylene constituents, effectively suppressed the differentiation of M2-TAMs and Tregs by downregulating Arg-1 and CD25 expression. They had minimal effects on the expression of markers associated with M1-TAMs and promoted the proliferation of CD4⁺ T cells that were inhibited by M2-TAMs and Tregs. In mice, BPA markedly inhibited the growth of syngeneic CRC tumors, accompanied by decreased serum levels of the immunosuppressive cytokine IL-10 and reduced expression of the proliferative marker Ki67 in tumor tissues. Moreover, BPA downregulated the mRNA expression of markers associated with M2-TAMs and Tregs, while increasing markers associated with M1-TAMs. Western blot analyses of tumor tissues revealed that BPA reduced the expression of marker proteins associated with M2-TAMs and Tregs, while increasing the expression of the immune-stimulatory markers CD80, GITR and CD4. In addition, combined treatment with BPA and 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent for CRC, notably enhanced the anti-tumor effect in mice. These findings indicate that BPA, an active extract of B. pilosa L., showed antitumor activity in mice by suppressing the differentiation of pro-tumorigenic TAMs and Tregs within the TME. Full article

Ovarian cancer (OC), the third most common gynecologic malignancy, is characterized by high mortality largely driven by chemotherapy resistance, leading to recurrence and metastasis. Using transcriptomic data from GSE73935, we constructed a weighted gene co-expression network and identified eight hub genes (IGF1R, CDH2, PDGFRA, CDKN1A, SHC1, SPP1, CAV1 and FGF18) associated with cisplatin resistance, among which CDH2 emerged as the most clinically relevant candidate. CDH2 demonstrated moderate diagnostic potential (AUC = 0.792) and was markedly upregulated in cisplatin-resistant A2780/CP70 cells. Independent validation using clinical single-cell RNA-seq data (GSE211956) confirmed its selective enrichment in resistant tumor cell subpopulations. Gene set enrichment analysis linked elevated CDH2 expression to p53 signaling, DNA replication, nucleotide excision repair, and Toll-like receptor pathways, with qPCR supporting upregulation of key downstream genes in resistant cells. Immune deconvolution further indicated that high CDH2 expression correlated with increased infiltration of NK cells, Tregs, macrophages, and neutrophils, and immunohistochemistry verified CDH2 overexpression in cisplatin-resistant tissues. In addition, virtual screening and drug sensitivity profiling identified several FDA-approved agents with potential relevance to CDH2-associated drug response. These findings indicate that CDH2 may serve as a candidate marker associated with cisplatin response in OC, and its association with immune cell infiltration provides further insight into mechanisms potentially underlying chemoresistance. Full article

Inconsistent conclusions on the cellular uptake of recombinant human β-glucocerebrosidase (rhGCase) for Gaucher disease stem from a fundamental limitation of existing methods: their inability to generate complete and reliable dose–response curves. This critical flaw, stemming from susceptibility to various experimental variables, prevents accurate potency comparison across different rhGCase products. To address this, we developed a robust bioassay using CHO-K1 cells stably expressing the human macrophage mannose receptor (hMMR). Our method quantifies uptake by measuring the enzymatic activity of internalized rhGCase and consistently produces a classic sigmoidal dose–response curve. Comprehensive validation and mechanistic studies, including inhibition experiments with mannose, fucose, and mannose-6-phosphate, confirmed that uptake is specifically mediated by hMMR, with successful enzyme transport to endosomes/lysosomes. Applying this assay to three commercial products yielded results contrary to prior literature: imiglucerase demonstrated superior uptake activity to velaglucerase alfa. The proposed method represents a significant improvement over existing assays, providing a more accurate and reproducible means to evaluate cellular uptake bioactivity, which is crucial for the quality control of rhGCase therapeutics. Full article

Selenium nanoparticles (SeNPs), a highly promising candidate as a nutrient fortificant and food additive, face challenges in stability and biosafety. These limitations hinder their application in the food industry. In this study, Ganoderma lucidum melanin (GLM) was utilized as a natural stabilizer. Three distinct types of GLM-stabilized SeNPs, termed GLM-SeNPs (S-GLM, D-GLM, and A-GLM), were subsequently synthesized via an ascorbic acid reduction method. The results showed that the prepared nanoparticles exhibited uniform particle size (55–75 nm) and good dispersibility. Among them, S-GLM possessed the highest selenium content (2598.90 mg/kg) and demonstrated the best stability. GLM-SeNPs significantly downregulated (p < 0.05) the mRNA expression of key pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and upregulated (p < 0.05) the mRNA expression of the anti-inflammatory factor IL-10 in LPS-induced RAW264.7 macrophages. A potential mechanism underlying this effect may be the suppression of the NF-κB signaling pathway. In addition, GLM-SeNPs exhibited potent inhibitory effects against common foodborne pathogens. This study explores a potential novel strategy for the high-value utilization of natural functional components in food systems. These preliminary findings suggest GLM-SeNPs may have application potential in areas like functional beverages and food preservation. Further research is warranted to validate their feasibility in real food systems. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. NSCLC, which constitutes approximately 85% of cases, continues to exhibit a poor prognosis despite advancements in therapeutic interventions, underscoring the urgent necessity to elucidate its molecular mechanisms and identify novel therapeutic targets. CD36, a multifunctional transmembrane glycoprotein, is integral to lipid uptake, immune recognition, inflammatory regulation, molecular adhesion, and apoptosis. Increasing evidence implicates CD36 in the progression of various cancers. In the context of lung cancer, CD36 facilitates tumorigenesis through multiple pathways, including the remodeling of tumor cell lipid metabolism, reprogramming of tumor-associated macrophages, and modulation of immune cell functions such as those of Tregs and CD8⁺ T cells. Additionally, CD36 is intricately linked with the function of cancer-associated fibroblasts and the remodeling of the tumor stromal microvasculature. This systematic review synthesizes the mechanisms by which CD36 contributes to NSCLC proliferation, migration, epithelial–mesenchymal transition, and modulation of the tumor microenvironment. Furthermore, we explore emerging therapeutic strategies that target CD36. Regulating CD36 expression effectively intervenes in the malignant behavior of NSCLC, underscoring its potential as a promising therapeutic target and prognostic marker. Full article

While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological “instruction sets,” and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing. Full article

Magnetic nanoparticles (MNPs) are widely applied in biomedicine, including bioimaging, drug delivery, and cell tracking. As central mediators of immune surveillance, macrophages phagocytize foreign substances, rendering their interactions with MNPs particularly consequential. During MNP uptake, macrophages undergo cytoplasmic remodeling that can lead to morphological alterations. Although prior studies have predominantly focused on MNP uptake efficiency and cytotoxicity, systematic quantitative assessments of macrophage morphological alterations following MNP treatment remain scarce. In this study, phase-contrast microscopy images of macrophages before and after MNP treatment were analyzed using unsupervised variational autoencoder (VAE)-based frameworks. Specifically, the β-VAE, β-total correlation VAE, and multi-encoder VAE frameworks were employed to extract latent representations of cellular morphology. The analysis revealed that MNP-treated macrophages exhibited pronounced structural alterations, including membrane expansion, central density shifts, and shape distortions. These findings were further substantiated through quantitative evaluations, including effect size analysis, kernel density estimation, latent traversal, and difference mapping. Collectively, these results demonstrate that VAE-based unsupervised learning provides a robust framework for detecting subtle morphological responses of macrophages to nanoparticle exposure and highlights its broader applicability across varied cell types, treatment conditions, and imaging platforms. Full article

Resveratrol is a natural polyphenol found in plants that has attracted significant research attention for its antitumor potential. With the continuing research on the tumor microenvironment and metabolic reprogramming, the roles of resveratrol in tumor cell metabolism and immune cell function have gained increasing attention. Recent studies have shown that resveratrol disrupts tumor cell metabolism and prevents tumor cell growth and metastasis by inhibiting metabolic processes such as glycolysis and fatty acid production. Furthermore, resveratrol regulates immune cells such as T cells, macrophages, and natural killer cells and enhances antitumor immune responses. In this article, we report the recent research progress on the use of resveratrol for tumor therapy. Specifically, we focus on its regulatory effect on tumor metabolism and the immune microenvironment and discuss its potential in combination with a new therapeutic strategy. Full article

The Rhodomyrtus tomentosa (Aiton.) Hassk. berry is rich in structurally diverse polysaccharides with potential biological activity. However, its immunomodulatory properties remain understudied, limiting our current understanding of its functional significance. Two structurally distinct polysaccharides from Rhodomyrtus tomentosa (RTP-1 and RTP-2) were evaluated for immunostimulatory activity in RAW264.7 macrophages. Phagocytic function was assessed by neutral red assay, nitric oxide (NO) and reactive oxygen species were measured using the Griess assay and fluorescent probes, and cytokines (TNF-α, IL-6 and IL-1β) were quantified by enzyme-linked immunosorbent assay. Analysis of RNA-seq data using weighted gene co-expression network analysis revealed co-expression modules. The selected transcripts were independently validated by quantitative real-time PCR (RT-qPCR). The results showed that both polysaccharides enhanced phagocytosis, increased NO/ROS levels, and promoted cytokine secretion. Transcriptome results indicated that RTP-2 activated the MEturquoise co-expression module containing 222 hub genes, whereas RTP-1 was mainly associated with the MECyan module containing 49 hub genes. Module enrichment for RTP-2 revealed links with mitophagy–immune regulation, proteostasis/stress, and innate immune signaling. RT-qPCR further confirmed that in the RTP-2 group, Dram1 expression was upregulated approximately 121 times, Bmf1 expression was upregulated approximately 18 times, and Bnip3 was significantly downregulated, whereas Bnip3l expression remained unchanged. Overall, RTP-2 exhibited a more pronounced and coherent macrophage-stimulating profile in vitro, supporting its potential as a macrophage-targeted immunostimulatory ingredient. Full article

BST2 has emerged as a multifunctional molecule that bridges antiviral defense, membrane architecture, and tumor immunity. Originally characterized as an interferon-inducible restriction factor that tethers virions to the plasma membrane, BST2 is now recognized as an oncogenic driver and immunoregulatory hub in diverse malignancies. In cancer, BST2 expression is frequently upregulated through promoter hypomethylation and transcriptional activation. Functionally, BST2 promotes proliferation, epithelial–mesenchymal transition, anoikis resistance, and chemoresistance, whereas its loss sensitizes tumor cells to proteotoxic and metabolic stresses. Beyond tumor cells, BST2 modulates the tumor microenvironment by promoting M2 macrophage infiltration, dendritic cell exhaustion, and natural killer (NK)-cell resistance, thereby contributing to immune evasion. Elevated BST2 expression correlates with poor prognosis in glioblastoma, breast, nasopharyngeal, and pancreatic cancers, and it serves as a circulating biomarker within small extracellular vesicles. In conclusion, BST2 is a dual-function molecule that integrates oncogenic signaling and immune regulation, making it an attractive diagnostic and therapeutic target for hematological and solid tumors. Full article