Search Results (7,540)

Zinc oxide nanoparticles (ZnO NPs) are widely used in biomedical, agricultural, and industrial applications, raising concerns about their potential hepatotoxicity. This study investigated the effects of 28-day oral ZnO NP exposure on hepatic function, oxidative stress, apoptosis, inflammatory signaling, and microRNA expression in rats. Sixty male Wistar albino rats were allocated to three groups (n = 20 each),control, low dose (30 mg/kg), and high dose (100 mg/kg), and treated by oral gavage. The administered material had a nominal particle size of 50 nm and a supplier-stated purity of 99.9%. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and reduced glutathione (GSH), histopathology, immunohistochemistry, mRNA expression, and hepatic microRNAs were assessed. ZnO NPs induced dose-related liver injury: ALT increased from 31.26 ± 2.5 to 75.48 ± 12.3 IU/L, while AST increased from 32.47 ± 4.1 to 85.57 ± 18.9 IU/L. Hepatic MDA increased, whereas GSH increased at the low dose but was depleted at the high dose. Histopathology demonstrated sinusoidal congestion, hepatocellular necrosis, and inflammatory infiltration. Immunohistochemistry indicated reduced B-cell lymphoma 2 (Bcl-2) and increased caspase-3 and tumor necrosis factor-alpha (TNF-α) immunoreactivity. Interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) were upregulated, whereas superoxide dismutase 2 (SOD2) was downregulated. At the high dose, miR-122-5p, miR-34a-5p, and miR-21-5p increased by 8.74-, 6.53-, and 4.38-fold, respectively (all p< 0.05). Their expression levels were also strongly and positively correlated with biochemical, oxidative, and histopathological indicators of liver injury. These findings indicate that ZnO NP exposure is associated with oxidative, inflammatory, apoptotic, and microRNA responses; the altered hepatic microRNAs may represent candidate tissue indicators of ZnO NP-induced liver injury. Full article

A water-soluble, low-molecular-weight polysaccharide fraction, designated OJP-2, was extracted from the roots of Ophiopogon japonicus; its structural characteristics and immunomodulatory activity in macrophages were subsequently investigated. OJP-2 exhibited a narrow apparent molecular weight distribution with an average molecular weight (Mw) of 3568 Da and was primarily composed of fructose (0.784) and glucose (0.208). Structural analysis—integrating UV spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy—revealed that OJP-2 is an inulin-type fructan. Its structure is characterized predominantly by β-(2→1)-linked Fruf chains and terminal α-D-Glcp residues, with potential signals indicating C-6-substituted Fruf units. In vitro immunological studies demonstrated that OJP-2 promoted nitric oxide (NO) production and enhanced the secretion of IL-6, IL-1β, and TNF-α in RAW264.7 macrophages. Under LPS/IFN-γ stimulation, OJP-2 induced non-monotonic changes in the CD86/CD206 macrophage phenotype, with the most pronounced effects observed at a concentration of 50 μg/mL. Furthermore, Western blot analysis showed that, compared to the Model group, treatment with OJP-2 resulted in a downward trend in the relative levels of p-p65/p65 and p-IκBα/IκBα across the tested concentration range. Collectively, these findings indicate that OJP-2 modulates macrophage activation phenotypes and influences NF-κB-related signaling pathways. Thus, OJP-2 is a candidate fructan for further investigation of immunomodulatory activity. Full article

Background/Objectives: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), show substantial variability in response to biologic therapies. Ustekinumab, which targets the IL-12/23 pathway, is an established treatment for moderate-to-severe IBD; however, a proportion of patients fail to achieve sustained remission or discontinue treatment over time. This study aimed to evaluate the effectiveness and persistence of ustekinumab and to explore the potential role of pharmacogenetic markers in predicting treatment outcomes. Methods: In this observational cohort study, 98 IBD patients treated with ustekinumab, with or without corticosteroid bridge therapy, in routine clinical practice were enrolled. The primary endpoint was steroid-free remission (SFR) at 12 months, defined as clinical remission without concomitant corticosteroid use, whereas treatment discontinuation was evaluated during follow-up. Genomic DNA was extracted from peripheral blood samples, and four single-nucleotide polymorphisms (SNPs) in selected immune-related genes were analyzed: PTPN2 rs7234029, HLA-C rs10484554, IL23R rs11209026, and IL12B rs6887695. Results: Of the 98 patients included, 73 (74.5%) achieved SFR, whereas 25 (25.5%) did not. Carriers of IL12B rs6887695 variant genotypes showed higher odds of achieving SFR than wild-type patients after adjustment for disease type and baseline disease activity (OR = 4.77; 95% CI, 1.60–14.23; p = 0.005). During follow-up, 16 patients (16.3%) discontinued treatment. Carriers of IL12B rs6887695 variant genotypes also showed a significantly lower hazard of ustekinumab discontinuation than wild-type patients (HR = 0.29; 95% CI, 0.10–0.85; p = 0.024). Conclusions: This study provides real-world evidence supporting the effectiveness and persistence of ustekinumab in IBD patients. IL12B rs6887695 emerged as a potential pharmacogenetic marker associated with favorable ustekinumab outcomes; however, this exploratory and hypothesis-generating finding requires external validation in larger, independent cohorts before clinical application. Full article

Oxidative stress contributes to hair follicle degeneration by inducing inflammation and apoptosis in dermal papilla cells. This study investigated whether Saccharomyces cerevisiae fermentation enhances the anti-hair loss potential of Laminaria japonica (kelp) by-products by improving their antioxidant, anti-inflammatory, and cytoprotective activities. Fermentation significantly increased the superoxide dismutase (SOD) activity of kelp. In H₂O₂-stimulated human hair follicle dermal papilla cells, fermented kelp culture (KF) dose-dependently protected against oxidative-stress-induced cytotoxicity, reduced IL-6 and IL-8 secretion, inhibited NFκB phosphorylation, restored insulin-like growth factor-1 (IGF-1) expression, enhanced AKT phosphorylation, reduced Bax expression, and restored total caspase-3 expression. These findings indicate that KF attenuates oxidative-stress-induced inflammation and apoptosis while preserving dermal papilla cell function. A four-week application study further showed that a shampoo containing KF reduced hair loss and improved hair gloss, scalp sebum, and scalp scaling. Together, these findings suggest that S. cerevisiae fermentation enhances the biological activity of kelp by-products and supports the potential of KF as a functional cosmetic ingredient for anti-hair loss applications. Full article

T helper cells (Th) are central to mucosal IgA induction and key targets for modulation by vaccine adjuvants. To improve understanding of cellular mechanisms underlying mucosal vaccine-induced immunity, we analyzed antigen-specific peripheral blood Th responses elicited by the oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, administered with or without the double mutant heat-labile toxin (dmLT) adjuvant. ETVAX, consisting of inactivated E. coli overexpressing colonization factors CFA/I, CS3, CS5, and CS6 with a heat-labile toxin B-subunit toxoid, was given orally in two doses to adult volunteers, either alone or with 10 or 25 µg dmLT. Antigen-specific Th-associated cytokine responses were assessed in stimulated peripheral blood mononuclear cells isolated from 15 to 18 individuals/group using ELISA and electrochemiluminescence assays. ETVAX predominantly induced Th1 (IFN-γ) and Th17 (IL-17A) responses, with minimal Th2-associated cytokines. Responses were markedly reduced after CD4+ T-cell depletion, supporting a Th cell origin. The strongest responses targeted LTB and CS3, with IFN-γ responses detected in 60–80% and IL-17A in 40–60% across all vaccinees. Responses to CFA/I, CS5 and CS6 were generally weaker. Exploratory comparisons suggested broader IFN-γ responses and more consistent IFN-γ and IL-17A responses to lower-dose antigens, particularly CS6, in recipients receiving vaccine plus 10 µg dmLT. These trends paralleled IgA antibody-secreting cell response patterns, with significantly enhanced IgA responses to CS6 in the vaccine plus 10 µg dmLT group. In conclusion, ETVAX induces antigen-specific Th1- and Th17-type responses in peripheral blood, supporting a role for cellular immunity in mucosal responses to oral ETEC vaccines. Full article

The study seeks to develop a multifunctional germanium-enriched nanocomposite coating on titanium and to evaluate its ability to modulate early inflammatory responses while promoting osteogenic differentiation in a dental pulp stem cell (DPSC)-based regenerative model. A multifunctional Ti/Coating composed of nanohydroxyapatite (nHAp) particles, chitosan-oligolactate (ChOL), and germanium (Ge) was developed using a combined anodizing/anaphoretic electrodeposition approach. The Ti/Coating system exhibited good biocompatibility, as confirmed by microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, with cell viability consistently exceeding 90% and moderate LDH release across all time points. Annexin V/PI assay demonstrated a predominance of viable cells (>94%), while intracellular ROS analysis indicated moderate oxidative activity. Gene expression analysis revealed significant downregulation of pro-inflammatory markers (TNF-α, IL-1β, IL-6, COX-2, and MAPK), suggesting attenuation of inflammatory signalling. Flow cytometry further demonstrated reduced CD120b (TNFR2) expression, while intracellular TNF-α levels remained unchanged, indicating selective modulation at the receptor level. In addition, the Ti/Coating promoted osteogenic differentiation, as evidenced by enhanced mineralization, and upregulation of osteogenic genes (ALP, RUNX2, BMP2). Full article

Pseudomonas aeruginosa ST235 isolates drive a distinct macrophage inflammatory program characterized by IL-1β axis dominance and suppression of canonical NF-κB-associated cytokine responses. In THP-1-derived macrophages, ST235 isolates induce robust inflammasome activation, resulting in elevated IL-1β production and altered cell death responses, while eliciting markedly lower TNFα, IL-6, IL-8, and IL-10 responses than non-ST235 isolates. In contrast, nonST235 isolates preferentially stimulate NF-κB-dependent cytokine production with weaker inflammasome activation. Mechanistically, ST235 infection suppresses NF-κB signaling and reduces caspase-1 expression, whereas caspase-8 remains unchanged, indicating that increased IL-1β production can be due to alternative inflammasome pathways or posttranscriptional modifications. Rapid macrophage death further restricts overall cytokine production, reinforcing an IL-1β-dominant inflammatory profile. ST235 isolates also selectively reprogram M2-polarized macrophages toward an M1 phenotype, as demonstrated by increased CD86 expression, while both isolate groups promote M1 polarization in unpolarized macrophages. Importantly, pyoverdine purified from ST235 isolates reproduced aspects of these responses by inducing IL-1β production and cytotoxicity more effectively than pyoverdine from non-ST235 isolates, supporting a potential contribution of ST235-derived pyoverdine to the IL-1β-dominant inflammatory phenotype. Collectively, these findings suggest that ST235 isolates modulate macrophage immune responses through suppression of NF-κB-associated responses and promotion of IL-1β-dominant inflammation, providing insights into the virulence of this high-risk clone and highlighting potential therapeutic targets. Significant statement: ST235 isolates of P. aeruginosa uniquely modulate macrophage immune responses by robustly activating inflammasome signaling, inducing IL-1β expression while suppressing other cytokines, and driving macrophage polarization toward a pro-inflammatory M1 phenotype. These findings highlight distinct pathogenic strategies of ST235 isolates that may inform targeted therapeutic interventions. Full article

The triterpenoid and polysaccharide constituents of Ganoderma lucidum (GL) are believed to influence key pathogenic pathways in Alzheimer’s disease (AD). This study first examined the molecular rationale for GL’s neuroprotective properties by subjecting its principal triterpenoids, Ganoderic Acid A&B, to computational profiling. Molecular docking was performed against human acetylcholinesterase (AChE), TNF-α, COX-2, IL-6, caspase-3, Bcl-2, and the Keap1–Nrf2 complex using CB-Dock2, alongside SwissADME-based physicochemical and ProTox-3.0-based toxicological screening. These targeted pathways were then biologically validated in an in vitro AD model induced by Aβ_1–42 toxicity in SH-SY5Y cells, assessing AChE activity, apoptosis, ROS levels, mitochondrial membrane potential (MMP), and cytokine expression (COX-2, TGF-β1, IL-6, TNF-α, IL-10). Docking revealed high binding affinities of both triterpenoids toward all seven targets (Vina scores: −7.3 to −10.4 kcal/mol), predicting strong modulation of cholinergic, inflammatory, apoptotic, and antioxidant pathways. Consistent with these predictions, GL extract significantly reduced TNF-α, COX-2, and IL-6 mRNA and protein levels, attenuated ROS accumulation, preserved MMP except at 500 µg/mL, and exerted a concentration-dependent antiapoptotic effect. IL-10 and TGF-β1 showed complex, dose-dependent patterns, reflecting indirect regulatory responses. Together, these findings support GL’s neuroprotective potential against Aβ-induced toxicity through direct engagement of cholinergic, inflammatory, apoptotic, and antioxidant regulatory proteins. Full article

Background: Hypoxia triggers pulmonary inflammation and oxidative stress, leading to endothelial dysfunction, apoptosis and lung injury. Although the flavonoid orientin exhibits potent antioxidant and anti-inflammatory properties, its pharmacokinetic behavior remains incompletely characterized. Nanoparticle-based delivery systems may enhance efficacy. This study investigated whether Orientin delivered via chitosan nanoparticles (CNP–orientin) protects against hypoxia-induced pulmonary inflammation, oxidative stress, and tissue injury in rats. Methods: A total of 48 female Sprague–Dawley rats were randomized into four normoxic and four hypoxic groups (n = 6 per group). Rats in the hypoxic groups were exposed to intermittent hypoxia (7% O₂, 8 h/day for 7 days). Hypoxic rats were allocated to experimental groups, including an untreated hypoxia group and groups receiving orientin alone, chitosan nanoparticles alone or orientin-loaded chitosan nanoparticles (CNP–orientin), while normoxic rats served as controls. Hypoxic exposure was conducted using a controlled glove box system. At the end of the protocol, blood samples were collected for serum inflammatory marker analysis, and lung tissues were harvested to assess oxidative stress parameters, hypoxia- and inflammation-related signaling pathways, apoptosis-related gene expression, and histopathological lung injury and fibrosis. Results: Intermittent hypoxia significantly increased pulmonary HIF-1α and iNOS expression, oxidative stress markers (increased malondialdehyde and decreased superoxide dismutase and glutathione), pro-inflammatory cytokines (TNF-α, IL-1β), apoptotic signaling and histopathological lung injury compared with normoxic controls (p < 0.05). Treatment with orientin or chitosan nanoparticles alone attenuated hypoxia-associated biochemical and molecular alterations compared to untreated hypoxic rats (p < 0.05). Notably, CNP–orientin treatment significantly attenuated multiple oxidative stress, inflammatory, and apoptosis-related alterations compared with untreated hypoxic rats (p < 0.05). These protective effects were observed despite the substantially lower orientin-equivalent dose in the CNP–orientin formulation compared with free orientin. NF-κB and TNF-α expression, caspase-3 levels, antioxidant markers, and Bcl-2 expression differed significantly among hypoxic groups (p < 0.05). Histopathological lung injury and Modified Ashcroft fibrosis scores were significantly lower in the CNP–orientin group than in the untreated hypoxic group (p < 0.01 and p < 0.001, respectively). Conclusions: Orientin-loaded chitosan nanoparticles effectively mitigate hypoxia-induced pulmonary inflammation, oxidative stress, apoptosis and fibrotic injury. These findings identify CNP–orientin as a promising nanotherapeutic strategy for hypoxia-associated lung diseases and support further translational investigations. Full article

Background/Objectives: Reflux esophagitis (RE) is a chronic inflammatory disorder caused by reflux of gastric contents into the esophagus, leading to mucosal injury and epithelial barrier dysfunction. Although proton pump inhibitors are widely used, persistent inflammation and oxidative stress remain important therapeutic challenges. Yeokwisan (YWS) is prescribed for gastroesophageal reflux disease and functional dyspepsia; however, its protective mechanisms against RE remain unclear. This study investigated the protective and anti-inflammatory effects of YWS. Methods: We integrated network pharmacology analysis, mechanistic studies in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and efficacy evaluation in a rat model of acute RE induced by pyloric and forestomach ligation. Results: Network pharmacology identified 174 common targets between YWS and RE and 23 hub genes through protein–protein interaction network and topological analyses, implicating PI3K/Akt, MAPK, Ras, HIF-1, chemokine, and other inflammation-related signaling pathways. In LPS-stimulated RAW264.7 macrophages, YWS significantly reduced intracellular reactive oxygen species, nitric oxide, TNF-α, and IL-6 production without inducing cytotoxicity and suppressed MAPK, PI3K/Akt, and NF-κB activation. In vivo, YWS attenuated acute reflux-induced esophageal mucosal injury and histopathological alterations, restored esophageal superoxide dismutase activity, reduced malondialdehyde levels, and lowered serum TNF-α, IL-6, and IL-1β levels. YWS also suppressed NF-κB/IκB activation and COX-2 expression in esophageal tissue. Conclusions: YWS exerted protective effects against acute reflux-induced esophageal injury and anti-inflammatory effects in activated macrophages, accompanied by attenuation of oxidative stress and inflammation-associated signaling. These findings support further investigation of YWS for reflux-associated esophageal inflammation. Full article

Background: Osteoarthritis (OA) is a chronic whole-joint disease involving extracellular matrix remodeling, inflammatory signaling, immune–stromal interactions, and sensory-associated processes. MicroRNAs (miRNAs) may contribute to post-transcriptional regulation within these interconnected molecular domains, but concurrent mRNA and miRNA expression patterns remain insufficiently characterized in naturally occurring canine OA. Methods: A total of 12 formalin-fixed, paraffin-embedded (FFPE) canine tissue specimens were classified as osteoarthritic joint tissues (OA; n = 7) and control joint tissues without radiographic or histopathological evidence of OA (C-JT; n = 5). RT-qPCR was used to quantify 17 selected mRNAs involved in extracellular matrix remodeling, chronic inflammatory signaling, immune–stromal interactions, and neuroinflammatory and sensory-associated processes, together with five miR-30 family members. Statistical comparisons were performed on ΔCq values using two-sided unpaired Welch’s t-tests followed by Benjamini–Hochberg false discovery rate correction. Results: Compared with C-JT, OA tissues showed significantly higher expression of ADAMTS5, MMP2, MMP13, COL2A1, SPARC, HP, VEGFA, IGFBP6, and ASIC3 after false discovery rate correction. MMP9, IL1B, IL1R1, IL1RAP, JAK2, TYK2, NGFB, and NTRK1 did not differ significantly between the two joint-tissue groups. MiR-30b was significantly downregulated in OA, whereas miR-30c, miR-30d, and miR-30e were significantly upregulated; miR-30a did not differ significantly. Exploratory database-supported miRNA–gene connectivity was used for candidate prioritization but was not interpreted as evidence of direct regulation in canine joint tissue. Conclusions: Canine osteoarthritic capsulosynovial tissues exhibit concurrent alterations in selected mRNAs and miR-30 family members across matrix-remodeling, immune–stromal, and sensory-associated molecular domains. These findings identify OA-associated expression patterns but do not establish pathway activation, direct miRNA–mRNA regulation, or disease progression. They provide a focused molecular basis for future mechanistic studies of post-transcriptional regulation in naturally occurring canine OA. Full article

Pseudomonas aeruginosa (PA) is a formidable environmental pathogen. It causes severe and refractory bovine mastitis. The escalating threat of antimicrobial resistance requires new non-antibiotic therapies. These alternative therapies should focus on targeting host-directed responses. Sodium butyrate (SB) is a prominent short-chain fatty acid. It possesses potent immunomodulatory properties. However, its protective mechanisms against PA-induced mammary injury remain elusive. This study investigated the efficacy and underlying molecular mechanisms of SB. bMECs were pretreated with 0.5 mmol/L SB for 18 h prior to challenge with P. aeruginosa (1 × 10⁷ CFU/mL, 6 h). We evaluated its ability to alleviate PA-induced cytotoxicity in bovine mammary epithelial cells (bMECs). Flow cytometry and ELISA demonstrated the strong protective effects of SB. SB pretreatment significantly reduced PA-induced cellular apoptosis. It also suppressed the hypersecretion of pro-inflammatory cytokines, including IL-6 and TNF-α. Next, transcriptomic sequencing (RNA-seq) was performed. We identified 589 differentially expressed genes (DEGs) between the PA-challenged and SB-treated groups. These DEGs were significantly enriched in the Toll-like receptor (Tlr), Mapk, and autophagy signaling pathways. We subsequently conducted molecular validations via RT-qPCR, Western blotting, and immunofluorescence. The results revealed that SB significantly suppressed the overactivation of the TLR4/MAPK cascade. Specifically, SB significantly downregulated the expression of TLR4. It also decreased the downstream phosphorylation levels of p38, ERK, and JNK. Furthermore, PA infection induced a severe blockade of autophagic flux. This dysfunction was evidenced by the concurrent cellular accumulation of LC3-II and the autophagic substrate p62. Remarkably, SB intervention was associated with the reduction in autophagic marker accumulation, evidenced by facilitated lysosomal clearance of p62. Collectively, sodium butyrate protects bMECs against PA-induced inflammation and apoptosis. These protective effects are closely associated with the suppression of the TLR4/MAPK signaling cascade and the alleviation of autophagic marker accumulation. This highlights the potential of SB as a promising preventive strategy for the clinical management of bovine mastitis. Full article

Objective: This study aimed to evaluate the long-term degradation behavior, biostimulatory effects, and biocompatibility of a novel poly-L-lactic acid-block-polyethylene glycol/hyaluronic acid (PLLA–b–PEG/HA) composite filler for soft tissue augmentation. Methods: PLLA–b–PEG/HA microsphere properties were characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance hydrogen spectroscopy (¹H NMR), thermogravimetry (TG) and differential scanning calorimetry (DSC). A 104-week in vivo rabbit model was established to systematically observe filler degradation and tissue responses. Ultrasound monitoring, histological staining, ELISA and RT-PCR were performed to assess volumetric changes, inflammatory reactions and collagen synthesis-related signaling. Results: Physicochemical property tests demonstrated that PLLA–b–PEG retains the fundamental physicochemical properties of pristine PLLA while exhibiting enhanced hydrophilicity. B-ultrasound demonstrated a presented uniform in vivo distribution without displacement or diffusion over time, confirming steady and predictable degradation. SEM verified progressive morphological degradation and porous evolution of the microspheres. The filler induced a mild, balanced inflammatory microenvironment with early expression of both pro-inflammatory (IL-12, TNF-α) and anti-inflammatory (IL-4) cytokines, which resolved gradually over time. Sustained TGF-β upregulation persisted throughout the 104-week observation period, driving continuous neocollagenesis and prominent neoelastogenesis, thereby achieving favorable and long-term tissue remodeling with excellent biocompatibility. Conclusions: The PLLA–b–PEG/HA composite filler exhibits controllable degradation properties and homeostatic regulatory effects, along with outstanding long-term biosafety and tissue integration capacity. As an ideal biostimulatory filler for soft tissue augmentation, it can effectively facilitate the regeneration of high-quality functional extracellular matrix rich in collagen fibers and elastic fibers, and holds promising clinical prospects for natural and long-lasting soft tissue filling applications. Full article

Background/Objectives: Meningiomas frequently involve the adjacent skull bone. The bone tumor microenvironment (TME) represents a unique niche in bone-invasive tumors and bone metastases, and can promote tumor progression through tumor–stromal interactions. We hypothesized that the bone TME may contribute to tumor cell transcriptional changes and tumor growth in meningioma. Methods: Human malignant meningioma cell lines, IOMM-Lee and HKBMM, were implanted over the calvarial bone (bone TME) and into the dorsal skin (non-bone TME) of BALB/c-nu/nu mice. Tumors from the IOMM-Lee model underwent bulk RNA sequencing with computational separation of human- and mouse-derived reads, enabling ligand–target interaction analysis of stromal cell-to-tumor cell signaling. Differential gene expression analysis, enrichment analysis, ligand–target interaction analysis, multiplex immunofluorescence, and immunohistochemistry were performed. Results: Tumor volume was significantly greater in the bone TME than in the non-bone TME in both models, whereas the Ki-67 labeling index was significantly reduced. Transcriptomic analysis revealed distinct tumor cell transcriptional states in the bone TME, characterized by upregulation of inflammation-related genes and enrichment of inflammatory signaling pathways, including interferon responses and NF-κB signaling. Ligand–target interaction analysis of stromal cell-to-tumor cell signaling identified stromal IL1B as a candidate regulator of inflammatory transcriptional programs in tumor cells. F4/80-positive macrophages expressed IL-1β, and tumor cells were positive for phospho-IKKα/β and phospho-IκBα in the bone TME. Conclusions: Tumor–stromal interactions potentially involving macrophage-derived IL-1β may be associated with inflammatory transcriptional programs in meningioma cells and with meningioma enlargement in the bone TME. These interactions may be therapeutically relevant in meningioma with bone involvement. Full article

Background/Objectives: Thrombotic cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Current antithrombotic therapies are limited by insufficient thrombus targeting. This study aimed to develop a fibrin-binding peptide-functionalized, hydrogen peroxide (H₂O₂)-responsive polymeric micelle and to evaluate its physicochemical properties and biological effects under H₂O₂-induced endothelial oxidative stress and preliminary FeCl₃-induced thrombosis conditions. Methods: A fibrin-binding peptide, P2 (VTFIKC), was screened using computer-aided drug design and evaluated through microscale thermophoresis and in vitro thrombus adhesion assays. An all-trans retinoic acid (atRA)-based boronate ester prodrug, BORA, was synthesized to enable H₂O₂-triggered degradation and drug release. BORA was co-assembled with P2-modified Mal-PEG-b-PAsp to prepare P2-Mal-PEG-b-PAsp/BORA micelles. Their physicochemical properties, H₂O₂ responsiveness, H₂O₂-scavenging activity, cytocompatibility, cytoprotective effects, anti-inflammatory activity, and preliminary in vivo efficacy were evaluated. Results: The resulting micelles exhibited a suitable nanoscale size, acceptable cytocompatibility, H₂O₂-responsive changes in particle size distribution, and concentration-dependent H₂O₂-scavenging activity. In H₂O₂-stimulated human umbilical vein endothelial cells, micelle treatment was associated with improved cell viability, lower intracellular ROS-associated fluorescence, and reduced TNF-α and IL-1β concentrations. In a FeCl₃-induced rat carotid artery thrombosis model, P2-Mal-PEG-b-PAsp/BORA micelles altered platelet- and leukocyte-related hematological indices and exhibited preferential accumulation in the thrombotic carotid artery. Conclusions: P2-Mal-PEG-b-PAsp/BORA micelles combine P2-mediated fibrin-binding potential, H₂O₂-responsive release behavior, and H₂O₂-scavenging activity. The findings provide preliminary support for further investigation of this peptide-functionalized nanoplatform. Full article