Search Results (4,577)

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

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

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

Fermented products have recently garnered substantial interest in both research and commercial contexts. Although probiotic fermentation is predominantly practiced with dairy, fruits, vegetables, and grains, its application to dual-purpose food-medicine materials like Ganoderma lucidum has been comparatively underexplored. In this study, Ganoderma lucidum fermented juice (GFJ) served as the substrate and was fermented with five probiotic strains. The optimal inoculation ratios—determined by employing a uniform design experiment—were as follows: Bifidobacterium animalis 6.05%, Lacticaseibacillus paracasei 9.52%, Lacticaseibacillus rhamnosus 6.63%, Pediococcus pentosaceus 21.38%, and Pediococcus acidilactici 56.42%. Optimal fermentation parameters established by response surface methodology included 24 h of fermentation at 37 °C, a final cell density of 5 × 10⁶ CFU/mL, and a sugar content of 4.5 °Brix. Experiments with RAW264.7 macrophages revealed that GFJ significantly promoted both phagocytic activity and nitric oxide (NO) secretion, indicating enhanced immune characteristics as a result of fermentation. Untargeted metabolomics profiling of GFJ across different fermentation stages showed upregulation of functional metabolites, including polyphenols, prebiotics, functional oligosaccharides, and Ganoderma triterpenoids (GTs)—notably myricetin-3-O-rhamnoside, luteolin-7-O-glucuronide, raffinose, sesamose, and Ganoderma acids. These increments in metabolic compounds strongly correlate with improved functional properties in GFJ, specifically heightened superoxide dismutase activity and immunomodulatory capacity. These results highlight an effective approach for developing functionally enriched fermented products from medicinal fungi, with promising applications in functional food and nutraceutical industries. Full article

Background: Pleurodesis is a treatment method that aims to create permanent adhesion between the pleural layers to prevent recurrent fluid or air accumulation in the pleural cavity. Talc, one of the most commonly preferred agents in this procedure, is widely used in clinical practice. In this study, a new talc formulation with a modified surface to impart antibacterial and analgesic properties was experimentally evaluated for the first time. The main objective of the study was to comparatively assess the inflammatory and fibrotic responses following standard talc and modified talc applications. Methods: Thirty-six 12-week-old female Wistar albino rats were simply randomly divided into three different groups: control (n = 12), standard talc (n = 12), and modified talc (n = 12). Under anesthesia, 1 mL of physiological saline containing 17 mg of talc was injected intrapleurally into the right hemithorax. The presence of pneumothorax after the procedure was assessed by chest radiography. After a 12-day follow-up period, the animals were euthanized. Bronchoalveolar lavage (BAL) fluid samples, blood samples, and lung and pleural tissue samples were collected for biochemical, histopathological, and immunohistochemical analyses. Results: Modified talc application resulted in a significant increase in both visceral and parietal pleural thickness (p < 0.05). Granulation tissue formation and collagen deposition were significantly higher in the modified talc group. In addition, TGF-β expression and CD68-positive macrophage count increased significantly in the modified talc group (p < 0.05). Inflammatory changes in the lung parenchyma were limited and not statistically significant. Conclusions: The modified talc formulation enriched with lidocaine and antibacterial agents produced a stronger inflammatory and fibrotic response compared to standard talc. These findings indicate that modified talc may increase the effectiveness of pleurodesis. Furthermore, the absence of significant lung parenchymal damage suggests that this treatment is locally effective and feasible. However, further long-term and advanced studies are needed to translate these results into clinical use. Full article

Objective: Echinacea purpurea, an herb with diverse pharmacological activities, has its roots widely used for anti-inflammatory and immunomodulatory purposes. Interestingly, its aerial parts, which are also rich in bioactive compounds, remain underutilized. This study aims to optimize the extraction and purification processes to obtain the aerial part extract of Echinacea purpurea (APE-EP) to enhance the content of active constituents and improve its anti-inflammatory and immunomodulatory effects. Methods: We analyzed the chemical composition of APE-EP using HPLC-MS. The intestinal absorption characteristics of APE-EP were evaluated using an ex vivo everted gut sac assay. Furthermore, the anti-inflammatory and immunomodulatory effects of APE-EP were validated using a DSS-induced colitis mouse model. Results: Several phenolic acids were identified, including chicoric acid and caffeic acid, which have significant antioxidant and anti-inflammatory activities. The everted gut sac assay revealed concentration-dependent absorption of chicoric acid in the gut. Results from the mouse model showed that APE-EP promoted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 macrophages at the lesion sites, effectively suppressing inflammation and alleviating colitis-related pathological damage. Conclusions: This study enhances the medicinal value of the E. purpurea, provides new insights for the efficient utilization of plant resources, and offers a potential natural drug candidate for inflammatory bowel disease treatment. Full article

Cadmium (Cd) is a highly toxic and pervasive environmental pollutant that exerts detrimental effects on human health through diverse biochemical and molecular mechanisms. As a vital metabolic organ, the liver harbors macrophages that play a crucial role in maintaining hepatic health and function. Current research has paid relatively little attention to the role of macrophages in liver injury induced by heavy metal exposure. This review summarizes current research on the molecular mechanisms underlying cadmium-induced toxicity in hepatic macrophages, focusing on oxidative stress, signaling pathways, gene transcription, and apoptosis. It further examines how cadmium-induced macrophage dysfunction impacts hepatic immunometabolism. Specifically, we detail how cadmium triggers oxidative stress and disrupts intracellular calcium homeostasis, leading to the activation of transcription factors such as NF-κB and Nrf2, and the subsequent engagement of related signaling cascades. These perturbations alter macrophage polarization (M1/M2), promote cellular damage and apoptosis, and ultimately exacerbate hepatic inflammation and fibrosis. By synthesizing recent advances in this field, this review aims to provide a theoretical foundation and future directions for research, with the goal of informing novel strategies for the prevention and treatment of heavy metal-associated liver diseases. Full article

Inflammation plays a central role in the pathogenesis of numerous diseases through the excessive production of nitric oxide (NO), prostaglandins, and pro-inflammatory cytokines. Although bromophenols from marine algae and various phenolic compounds exhibit strong anti-inflammatory activity, the biological properties of brominated vanillin derivatives remain largely unexplored. This study aimed to investigate the anti-inflammatory effects of 2-bromo-5-hydroxy-4-methoxybenzaldehyde (2B5H4M), a brominated vanillin derivative structurally similar to marine bromophenols, in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. 2B5H4M significantly reduced LPS-induced NO and PGE₂ production by suppressing the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also downregulated the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Mechanistically, 2B5H4M inhibited the phosphorylation and degradation of IκB-α, thereby preventing NF-κB nuclear translocation, and reduced the phosphorylation of ERK and JNK. These findings demonstrate that 2B5H4M exerts potent anti-inflammatory effects by simultaneously blocking NF-κB and MAPK signaling pathways. Although not algae-derived, the structural resemblance of 2B5H4M to marine bromophenols highlights its potential as a marine-inspired reference compound. This work suggests that 2B5H4M may serve as a promising lead scaffold for developing new phenolic anti-inflammatory agents and provides a foundation for future mechanistic and in vivo studies. Full article

Background. Contributions of tumor-derived extracellular vesicles, TEX, to tumor progression and metastasis involve their crosstalk with immune cells in the tumor microenvironment. This crosstalk results in metabolic reprogramming of immune cells from anti-tumor to pro-tumor activity. Mechanistic underpinnings of the TEX entry and delivery of molecular signals responsible for metabolic reprogramming may be unique for different types of immune cells. Methods. An in vitro model of THP-1 myeloid cells co-incubated with TEX illustrates the role TEX play in polarization of macrophages to TAMs. Results. In THP-1 cells, the dominant signaling pathway of melanoma cell-derived TEX involves HSP-90/TLR2. This leads to activation of the NF-κB and MAP kinase pathways and initiates THP-1 cell polarization from M0 to M2 with strong expression of immunosuppressive PD-L1. TEX may be seen as “danger” by the myeloid cells, which utilize the pattern recognition receptors (PRR), such as PAMPs or DAMPs, for engaging the complementary ligands carried by TEX. The same melanoma TEX signaling to T cells via DAMPs induced mitochondrial stress, resulting in T-cell apoptosis. Conclusions. As the signaling receptors/ligands in TEX are determined by the tumor, it appears that the tumor equips TEX with an address recognizing specific PRRs expressed on different recipient immune cells. Thus, TEX, acting like pathogens, are equipped by the tumor to alter the context of intercellular crosstalk and impose a distinct autophagy-not-apoptosis signature in recipient THP-1 cells. The tumor might endorse TEX to promote tumor progression and metastasis by enabling them to engage the signaling system normally used by immune cells for defense against pathogens. Full article

Acute respiratory distress syndrome (ARDS) is a fatal inflammatory lung disorder with few effective treatments. Hyaluronan (HA), a major extracellular matrix component, exhibits diverse biological activities depending on its molecular weight. This study aimed to evaluate the therapeutic potential of HA of various molecular weights in a rat model of ARDS. ARDS was induced in rats via the intratracheal instillation of 5 mg of bleomycin. Seven days later, when ARDS symptoms developed, low (LHA), medium (MHA), high (HHA), and mixed (MIX HA) hyaluronan were intratracheally administered seven times from Days 7 to 28. On Day 7, arterial oxygen saturation (SpO₂) and the partial pressure of oxygen (PaO₂) decreased, carbon dioxide levels increased, the respiratory rate increased, and extensive lung cell infiltration was observed, confirming successful ARDS induction. LHA and MIX HA improved the SpO₂ and PaO₂, and the latter increased lung and alveolar volume, reduced infiltration, and normalized breathing. All HA types attenuated collagen deposition and M1 macrophage activity, while MIX HA enhanced M2 polarization and upregulated MMP-2, MMP-9, and TLR-4. LHA increased VEGF and EGF expression. These findings demonstrate that different-weight HAs provide partial ARDS protection via distinct mechanisms. MIX HA shows synergistic effects, restoring and improving lung structure and function, respectively, representing a promising ARDS therapy. Full article

Diabetic wounds remain chronically non-healing due to impaired angiogenesis, persistent inflammation, and defective extracellular matrix remodelling. In recent years, stem cell-derived exosomes have emerged as a potent cell-free regenerative strategy capable of recapitulating the therapeutic benefits of mesenchymal stem cells while avoiding risks associated with direct cell transplantation. This review critically evaluates the preclinical evidence supporting the use of exosomes derived from adipose tissue, bone marrow, umbilical cord, and induced pluripotent stem cells for diabetic wound repair. These exosomes deliver bioactive cargos such as microRNAs, proteins, lipids, and cytokines that modulate key signalling pathways, including Phosphatidylinositol 3-kinase/Protein kinase (PI3K/Akt), Nuclear factor kappa B (NF-κB), Mitogen-activated protein kinase (MAPK), Transforming growth factor-beta (TGF-β/Smad), and Hypoxia inducible factor-1α/Vascular endothelial growth factor (HIF-1α/VEGF), thereby promoting angiogenesis, accelerating fibroblast and keratinocyte proliferation, facilitating re-epithelialization, and restoring immune balance through M2 macrophage polarization. A central focus of this review is the recent advances in exosome-based delivery systems, including hydrogels, microneedles, 3D scaffolds, and decellularized extracellular matrix composites, which significantly enhance exosome stability, retention, and targeted release at wound sites. Comparative insights between stem cell therapy and exosome therapy highlight the superior safety, scalability, and regulatory advantages of exosome-based approaches. We also summarize progress in exosome engineering, manufacturing, quality control, and ongoing clinical investigations, along with challenges related to standardization, dosage, and translational readiness. Collectively, this review provides a comprehensive mechanistic and translational framework that positions stem cell-derived exosomes as a next-generation, cell-free regenerative strategy with the potential to overcome current therapeutic limitations and redefine clinical management of diabetic wound healing. Full article

Macrophages play a crucial role in regulating immune responses, inflammation, and tissue repair. Depending on environmental cues, they polarize into pro-inflammatory M1 or anti-inflammatory, pro-regenerative M2 phenotypes. Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have emerged as key mediators of intercellular communication and immune modulation. This study investigates the effects of matrix-bound vesicles (MBVs) and small extracellular vesicles (sEVs) derived from human umbilical cord MSCs (UC-MSCs) on human monocyte-derived macrophages (MDMs) in vitro. Both MBVs and sEVs reduced pro-inflammatory activation of M1 macrophages, downregulating the expression of CXCL10 and CD86 while increasing the M2 marker CD206. MBVs exerted a stronger suppressive effect on M1 MDM phenotype markers as well as on STAT1, STAT2, and IRF9 mRNA levels in M1 macrophages, indicating the inhibition of the JAK/STAT1 signaling pathway involved in the pro-inflammatory activation of macrophages. Functionally, both vesicle types enhanced phagocytosis of FITC-labeled E. coli by M1 and M0_GM macrophages, promoting a shift toward an M2-like phenotype. Moreover, MBVs and sEVs attenuated reactive oxygen species (ROS) production, with sEVs showing a more pronounced effect both on ROS generation and on the expression of NOX2 complex subunits (p47^phox, p67^phox) in M1 macrophages. These findings demonstrate that MBVs and sEVs from UC-MSCs possess distinct yet complementary immunomodulatory and antioxidant properties on MDMs, suggesting their potential as promising cell-free therapeutic agents for inflammatory and degenerative diseases. Full article

Background: Prostate cancer (PCa) is a prevalent malignancy with a rising incidence. Advanced PCa, often resistant to therapy, remains a major clinical challenge, underscoring the need to identify novel molecular drivers. Methods: Utilizing transcriptomic data from the TCGA and GEO databases, we identified APOBEC3C (A3C) as a key candidate through WGCNA, differential expression analysis, and LASSO regression. Its clinical relevance was assessed via Kaplan–Meier survival analysis. Then, we validated A3C expression patterns using immunohistochemistry and Western blot in normal and malignant prostate cell lines. The functional effects of A3C on proliferation, migration, and invasion and mechanisms of such were evaluated through in vitro gain- and loss-of-function assays (CCK-8, Ki67 staining, wound healing, Transwell, Western blot, etc.). Results:A3C was significantly downregulated in PCa, and this low expression strongly correlated with adverse clinicopathological features, including advanced T stage, higher Gleason scores, and worse survival. Bioinformatically, high A3C expression was associated with an activated anti-tumor immune microenvironment, characterized by enhanced CD8+ T cell infiltration, reduced M2 macrophage abundance, and upregulation of the immune checkpoint CD40. In vitro, A3C overexpression effectively suppressed PCa cell proliferation, migration, and invasion, while its knockdown promoted these malignant phenotypes. Mechanistically, A3C enhances the expression of the STING1 and its downstream related molecules Caspase-1, IL-18, and IL-1β; upregulates DNA damage-protective genes (GSTP1 and GPX3); and enhances the expression of cell cycle regulator GAS1. Conclusions: This study establishes A3C as a suppressor in PCa, which impedes tumor progression by regulating key molecules involved in cellular inflammation, cell cycle arrest, and DNA damage response. Full article

Melatonin, an ancient and evolutionarily conserved indolamine, has long attracted attention for its multifunctional roles in redox homeostasis. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly scavenging reactive oxygen and nitrogen species and by upregulating antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. At the same time, it exerts wide-ranging immunomodulatory functions by influencing both innate and adaptive immune responses. All these actions converge within the tumor microenvironment, where oxidative stress and immune suppression drive cancer progression. Although the antitumoral effects of melatonin have traditionally been interpreted through its actions on T cells and NK cells, recent studies identify macrophages as an underappreciated and pivotal target. Notably, melatonin influences macrophage polarization, favoring antitumor M1 phenotypes over pro-tumoral M2 states, while attenuating chronic inflammation and restoring mitochondrial function. This review summarizes current knowledge on melatonin’s antioxidant and immunoregulatory mechanisms, highlighting its impact on the tumor immune microenvironment, with a particular focus on the growing recognition of macrophages as a compelling new axis through which melatonin may exert anticancer effects. Full article

Recent studies support that hematopoietic stem cell (HSC)-derived myeloid dendritic cells, monocytes/macrophages (Mo/Mϕ), and osteoclast precursors (OCps) share common progenitor(s) during development. This occurs mainly through receptor activator of NF-κB ligand (RANKL) signaling via its cytoplasmic adaptor protein complex (TRAF6) to subsequent osteoclastogenesis for bone loss and/or remodeling. Presently, mounting new evidence suggests that erythro-myeloid progenitor (EMP)-derived macrophages (Mϕ) and HSC-derived monocytes (Mo) produce embryonic, fetal, and postnatal OCp pools (i.e., primitive OCp), pinpointing a complex network of multiple OCp developmental origins. However, their ontogenic developments, lineage interactions, and contributions to the alternative osteoclastogenesis—in contrast to overall bone remodeling or loss—remain elusive. Interestingly, studies have also elucidated the contributions of immature CD11c⁺ myeloid DC-like OCps to osteoclastogenesis, with or without the classical so-called Mo/Mϕ-derived OCp subsets, and described that CD11c⁺ myeloid DCs (mDCs) develop into functionally active OCs; meanwhile, the cytokine TGF-β mediates a stepwise regulation of de novo immature mDCs/OCps through distinct crosstalk(s) with IL-17, an unrecognized interaction featuring TRAF6^(−/−)CD11c⁺ mDDOCps that coexist and proficiently colocalize in the local environment to drive a bona fide route for alternative osteoclastogenesis in vivo. Collectively, new findings—critically hinged on progenitor osteoclastogenic pathways (primitive OCps, mDCs/OCps, osteomorphs, etc.) and involving classical and/or alternative routes to inflammation-induced bone loss—are discussed via the illustrated schemes. This review highlights plausible ontogenic vs. principal or alternative developmental paths and their consequential downstream effects. Full article