Search Results (29,853)

Endometriosis is a hormone-dependent gynecological disease manifested by cyclic pelvic pain and female infertility. Although many studies have shown that neoangiogenesis plays an essential role in the development of early endometriosis, the underlying pathophysiological mechanisms remain unclear. Recent evidence suggests that macrophages play an important role in the pathogenesis of endometriosis and that the hypoxia-inducible factor-1alpha (HIF-1α) may be involved, but when and how are largely unknown. Herein, we explore the role of macrophages in the early development of endometriosis using an in vivo subcutaneous implantation murine model. Upon depletion of macrophages, the subcutaneous injection of syngeneic endometrial material resulted in significant reduction in oxidative stress, endometriotic lesion size, and neovascularization. Likewise, inactivation of the lipid peroxidative gene Alox15 induced similar reduction in oxidative stress, lesion growth, and angiogenesis. Since HIF-1α is an important trigger of neoangiogenesis, we further administered a HIF-1α-specific inhibitor (PX-478) to our endometriotic model and further confirmed the same effects on the lesions. Taken together, these data suggest that an intact Alox15 pathway and HIF-1α signaling may play important roles in the macrophage-mediated oxidative stress and neovascularization of endometriosis in the early stages, suggesting anti-inflammation and antioxidation as potential therapeutic targets for the development of endometriosis. Full article

Oxidative stress is a major factor in skin aging and various skin pathologies. Environmental pollutants exacerbate this stress by generating reactive oxygen species (ROS), disrupting the skin’s redox balance. Pycnogenol^®, a French maritime pine bark, extract is standardized to contain 70 ± 5% procyanidins and known to mitigate oxidative damage and inflammation. This study aims to evaluate the potential antipollution and antioxidant effects of Pycnogenol^® on skin. Ex vivo human skin explants were treated with varying concentrations of Pycnogenol^® (0.5%, 1%, and 2%) and then exposed to a mixture of pollutants. The expression of stress markers Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) and AHR (Aryl Hydrocarbon Receptor) were evaluated using immunostaining. Lipid peroxidation levels were measured by quantifying malondialdehyde (MDA) concentrations. The extract significantly decreased Nrf2 expression by 40% (p = 0.003) and 23% (p = 0.048) with a dose of 2% and 1%, respectively. After pollutant exposure, Pycnogenol^® (0.5%, 1%, and 2%) reduced Nrf2 over-expression in a dose–response manner by 29% (p = 0.03), 58% (p = 0.004) and 64% (p = 0.002) respectively. Pycnogenol^® at 0.5%, 1%, and 2% significantly reduced AHR over-expression by 61% (p < 0.0001), 76% (p < 0.0001) and 85% (p < 0.0001), respectively. Pycnogenol^® (1%, and 2%) decreased MDA levels following pollutant exposure by 17% (p = 0.06) and 25% (p = 0.01) respectively. In a dose-dependent manner, Pycnogenol^® exhibited a strong protective effect against pollution, significantly reducing pollutant-induced basal oxidative stress (MDA) and over-expression of Nrf2 and AHR, key factors in oxidative stress and detoxification. Pycnogenol^® also increased AHR expression in the absence of pollutants, which may reflect an adaptive cellular response. Full article

Dietary fiber and phenolic compounds are key bioactives in gastrointestinal and metabolic health; however, their compositional features and metabolic implications have rarely been studied as an integrated system within realistic food matrices. Mango bagasse confectionery previously demonstrated prebiotic potential, and its reformulation with extruded mango peel showed hepatoprotective effects linked to gut microbiota modulation. In this study, mango bagasse and peel confectionery (MBPC) was characterized and its metabolic impact was evaluated in vivo. Wistar rats were fed standard or high-fat diets with or without MBPC supplementation, followed by fecal fatty acid analysis. MBPC exhibited a high dietary fiber content for a confectionery product (25 g total fiber per 100 g), with monomeric profiles indicative of cell wall-derived polysaccharides and pectic components. The fiber fraction showed a low Mw (14.71 ± 0.02 kDa), suggesting a matrix favorable for fiber–phenolic interactions. Phenolic profiling revealed substantial concentrations of free (9.0 mg/mL) and bound (16.7 mg/mL) phenolic compounds. Fecal fatty acid profiles were diet-dependent, with palmitic acid showing the highest relative abundance, followed by stearic, oleic, and linoleic acids, associated with dietary fiber intake. This study elucidates the structural and metabolic relevance of dietary fiber–phenolic interactions within a formulated food matrix. Full article

Objective: The aim of this study was to develop and evaluate non-antibiotic strategies against Helicobacter pylori by establishing a bovine immune milk platform and designing a synergistic multi-antigen immunogen to enhance humoral immune responses. Methods: Inactivated Helicobacter pylori (H. pylori) was used to immunize dairy cows, and the resulting immune milk was characterized for antibody specificity, acid stability, and target antigens via ELISA, Western blot, agglutination assays, and mass spectrometry. Key identified antigens (UreA, UreB, UreE, UreG, HypA, FlaA, and FlaB) were produced as recombinant proteins. Their immunogenicity was evaluated in a murine model, comparing single antigens with various protein combinations. Immune responses were assessed by antigen-specific IgG ELISA, bacterial agglutination titers, flow cytometry for T-cell activation, and histopathology for safety. Results: Immune milk contained high-titer, acid-stable IgG antibodies targeting multiple H. pylori virulence factors. In mice, while single proteins induced specific IgG, a multi-antigen cocktail (FlaA + FlaB + HypA + UreA + UreB + UreE + UreG) elicited significantly higher serum agglutination titers (~7 × 10³) than single antigens or inactivated whole-cell vaccine, alongside robust CD4⁺ T-cell activation. No formulations showed any hepatorenal or splenic toxicity. Conclusion: Bovine immune milk is a viable platform for acid-stable antibody delivery. A rationally designed multi-antigen cocktail synergistically enhances functional humoral immunity in vivo, providing a promising foundation for developing antibody-based or subunit vaccine strategies against H. pylori. Full article

Alzheimer’s disease and related neurodegenerative disorders are associated with progressive cognitive decline, primarily driven by cholinergic dysfunction and impaired synaptic signaling. Hericium erinaceus, also known as lion’s mane mushroom, has been reported to promote neuronal differentiation and synaptic plasticity. In this study, a standardized H. erinaceus extract powder (HEP) was prepared from fruiting bodies and quantified using hericene A as a marker compound. The neuroprotective effects of HEP were then evaluated in both cellular and animal models of scopolamine-induced cognitive dysfunction. Pretreatment of SH-SY5Y human neuroblastoma cells with HEP (5–25 μg/mL) significantly improved cell viability and reduced scopolamine-induced apoptosis, while enhancing the activation of neuroplasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). In vivo, oral administration of HEP (300 mg/kg) to scopolamine-treated ICR mice markedly improved cognitive performance, increasing the recognition index to 63.8% compared with 41.6% in the scopolamine group, and enhancing spontaneous alternation in the Y-maze test to 59.6%. These cognitive improvements were accompanied by preserved hippocampal neuronal structure and increased BDNF immunoreactivity. Additionally, HEP improved cholinergic function by restoring serum acetylcholine levels and reducing acetylcholinesterase activity. Collectively, these findings suggest that standardized HEP exerts neuroprotective and cognition-enhancing effects via modulation of cholinergic markers and activation of BDNF-mediated neuroplasticity, highlighting its potential as a functional food ingredient or nutraceutical for preventing cognitive decline related to cholinergic dysfunction. Full article

Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to aggressive progression, high recurrence, and limited selectivity of current treatments. In this study, a series of seven 4-amino-2-substituted tetrahydrobenzothieno[2,3-d]pyrimidines were evaluated for their cytotoxic, antiproliferative, and mechanistic effects against oral cancer cell lines with different metastatic potential (HSC-3 and SCC-9), alongside non-tumorigenic keratinocytes (HaCaTs). Several compounds demonstrated selective anticancer activity, with Compounds 5 and 6 showing the most favorable balance between potency and selectivity. Antiproliferative assays revealed effective inhibition of cancer cell growth, while clonogenic assays confirmed a pronounced reduction in long-term survival, particularly in highly metastatic HSC-3 cells. Mechanistic studies indicated that the anticancer effects are associated with S-phase cell cycle arrest, apoptosis induction, and profound disruption of the actin cytoskeleton. In silico ADME and drug-likeness analyses supported the lead-like properties of the most active derivatives. Overall, these findings identify thienopyrimidine derivatives as promising scaffolds for the development of targeted therapies against OSCC and warrant further optimization and in vivo evaluation. Full article

Inflammatory bowel disease (IBD) is characterized by excessive oxidative stress, mitochondrial dysfunction, and persistent activation of pro-inflammatory signaling pathways. Danthron, a natural anthraquinone derivative from rhubarb, has been reported to possess anti-inflammatory and antioxidant properties, yet its regulatory mechanisms in intestinal inflammation remain unclear. In this study, we combined network pharmacology, transcriptomic profiling, cell-based assays, intestinal organoids, and a dextran sulfate sodium (DSS)-induced colitis model to determine the protective effects of Danthron against oxidative injury. Integrated target prediction and RNA-seq analysis identified EGFR–PI3K–AKT and Nrf2–HO-1 as key signaling axes modulated by Danthron. In macrophages and intestinal epithelial cells, Danthron markedly suppressed LPS- or H₂O₂-induced ROS accumulation, lipid peroxidation, and mitochondrial membrane potential collapse, while restoring superoxide dismutase activity and reducing malondialdehyde levels. Danthron also inhibited M1 macrophage polarization, preserved epithelial tight-junction proteins, and maintained transepithelial electrical resistance. CETSA, DARTS, and molecular docking confirmed direct engagement of Danthron with components of both the EGFR–PI3K–AKT and Nrf2–HO-1 pathways. In vivo, Danthron significantly ameliorated DSS-induced colitis, reducing inflammatory cytokines, epithelial apoptosis, oxidative stress, and myeloid cell infiltration while improving mucosal architecture and enhancing organoid regenerative capacity. These findings demonstrate that Danthron exerts potent antioxidant and anti-inflammatory effects through coordinated inhibition of EGFR–PI3K–AKT signaling and activation of the Nrf2–HO-1 axis, suggesting its promise as a multi-target therapeutic candidate for IBD. Full article

Background/Objectives: Epilepsy is characterized by unpredictable seizures and drug resistance, along with rising antimicrobial resistance (AMR), highlighting the urgent need for innovative dual-action therapies. This study aimed to design, develop, and evaluate novel pyrazolone derivatives for a dual antimicrobial and antiepileptic potential. Methods: Novel pyrazolone derivatives were designed, synthesized (using 2,4-dinitrophenylhydrazine/semicarbazide condensation with ethyl acetoacetate), and evaluated through molecular docking against antimicrobial (4URM, 3FYV, 3FRA) and neuronal targets (4COF, 5TP9, 5L1F). The in vitro antimicrobial activity was assessed against Gram-positive (S. aureus) and in vitro Gram-negative (E. coli, P. aeruginosa) strains via agar cup plate assays, while in vivo antiepileptic efficacy was tested in a PTZ-induced seizure model in Swiss albino mice. Results: Compound IIa showed potent dual activity, inhibiting E. coli (9 mm zone at 80 μg/mL) and S. aureus (9.5 mm at 80 μg/mL), alongside a significantly delayed seizure onset in the PTZ-induced mouse model (100% survival rate, 45 sec delayed seizure onset, p < 0.001). Compounds Ia and Id showed selective activity against E. coli (6 mm at 80 μg/mL) and P. aeruginosa (7 mm at 80 μg/mL), respectively. Docking studies revealed that compound IIa has a superior binding affinity (−7.57 kcal/mol for 3FYV) compared to standards, driven by hydrogen bonds (SER X: 49) and hydrophobic interactions (LEU X: 20). Conclusions: This study presents a novel approach by proposing a rationally designed pyrazolone scaffold exhibiting both antimicrobial and antiepileptic activity, which integrates in silico modeling with experimental validation. Compound IIa emerged with preliminary dual biological activities, exhibiting strong antibacterial activity, a superior binding affinity toward both bacterial and neuronal targets, and notable seizure prevention in vivo. These findings show the potential of multifunctional pyrazolone derivatives as a new treatment strategy for addressing drug-resistant infections linked to epilepsy and support further optimization toward clinical development. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a refractory disease for which no established treatment currently exists. Surfactin, a biosurfactant produced by Bacillus subtilis, exhibits antimicrobial activity, anticancer effects, and anti-inflammatory properties, suggesting its potential medical applications. This study aimed to elucidate the ability of surfactin to modulate the immune response induced by lipopolysaccharide (LPS) derived from periodontal pathogens (Aggregatibacter actinomycetemcomitans), clarify the underlying molecular mechanisms, and explore its potential utility in the treatment of MRONJ. Reverse transcription quantitative polymerase chain reaction demonstrated that surfactin suppresses LPS-induced interleukin-6 (IL-6) expression and secretion in J774.1 cells in a concentration-dependent manner. Western blot analysis showed that surfactin inhibited activation of the JNK-c-Jun-AP-1 axis and the JAK/STAT signaling pathways in J774.1 cells. The effects of surfactin administration were further evaluated in an in vivo MRONJ model. Co-treatment with surfactin significantly reduced the extent of LPS-induced bone necrosis. Overall, these findings suggest that surfactin suppresses LPS-induced IL-6 expression in macrophages and inhibits osteonecrosis induced by bisphosphonate preparations and LPS through negative regulation of the JNK-c-Jun-AP-1 axis and inhibition of the JAK/STAT pathway. Hence, surfactin may represent a promising candidate for MRONJ management. Full article

Sawdust represents a locally available lignocellulosic resource that may complement ruminant diets during periods of forage shortage. This study evaluated the feeding value of birch (Betula pendula) sawdust subjected to physical and chemical processing using a stepwise experimental approach. Steam-exploded and fresh sawdust were treated with 0, 4% ammonia, or 4% sodium hydroxide in a 2 × 3 factorial design and initially evaluated by in vitro gas production, dry matter digestibility, and fermentation pH. Based on these results, selected materials were further assessed for rumen dry matter and fiber degradation using the in sacco technique in cannulated dairy cows, with untreated and ammonia-treated wheat straw included for comparison. In addition, steam-exploded sawdust was compared with wheat straw and grass silage for in vivo digestibility in sheep. A pilot study also tested aspen (Populus tremula) sawdust in lactating cow diets. Steam explosion substantially reduced fiber fractions, particularly hemicellulose, and increased residual carbohydrates, resulting in higher gas production and in vitro digestibility compared with fresh sawdust (p < 0.05). Ammonia treatment markedly increased crude protein content, whereas sodium hydroxide primarily increased ash concentration. In sacco, steam-exploded birch showed similar or higher ruminal dry matter and neutral detergent fiber degradation compared with ammonia-treated wheat straw, while untreated fresh birch remained largely undegraded. In vivo, steam-exploded sawdust exhibited greater organic matter digestibility and net energy than untreated wheat straw but remained less digestible than grass silage (p < 0.0001). A pilot feeding test with lactating dairy cows demonstrated good acceptance of untreated aspen sawdust as a partial roughage substitute under non-standardized conditions. Overall, the results indicate that steam-exploded sawdust has potential as a complementary roughage source for ruminants when conventional forages are limited. Full article

Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS/MS. Its major constituent, aucubin (AU), which mirrors the fraction’s key pharmacological activities, was evaluated both in vitro and in vivo. In H₂O₂-injured tenocytes, AU’s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1β, TNF-α) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17β-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU’s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&E, Masson’s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H₂O₂-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative/inflammatory stress. These effects were mimicked by 17β-estradiol and reversed by the selective ERβ antagonist (R, R)-THC, indicating ERβ dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ERβ-mediated mechanism. These findings position ERβ activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development. Full article

Liver fibrosis induced by Schistosoma japonicum Katsurada, 1904 (S. japonicum) infection lacks effective diagnostic markers and specific anti-fibrotic therapies. Although dysregulated iron homeostasis and ferroptosis pathways may contribute to its pathogenesis, the core regulatory mechanisms remain elusive. To unravel the ferroptosis-related molecular features, this study integrated transcriptomic datasets (GSE25713 and GSE59276) from S. japonicum-infected mouse livers. Following batch effect correction and normalization, ferroptosis-related differentially expressed genes (FRDEGs) were identified. Subsequently, core hub genes were screened through the construction of a protein–protein interaction (PPI) network, functional enrichment analysis, immune infiltration evaluation, and receiver operating characteristic (ROC) analysis. The expression patterns of these hub genes were further validated in an S. japonicum-infected mouse model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study identified 7 hub genes (Lcn2, Timp1, Cth, Cp, Hmox1, Cbs, and Gclc) as key regulatory molecules. Functional enrichment analysis revealed that these hub genes are closely associated with sulfur amino acid metabolism and oxidative stress responses. Specifically, key enzymes involved in cysteine and glutathione (GSH) synthesis (Cth, Cbs, Gclc) were consistently downregulated, suggesting a severe impairment of the host antioxidant defense capacity. Conversely, pro-fibrotic and pro-inflammatory markers (Timp1, Lcn2, Hmox1) were upregulated. This molecular pattern was significantly associated with a remodeled immune microenvironment, characterized by increased infiltration of neutrophils and eosinophils. In vivo validation confirmed the expression trends of 6 hub genes, corroborating the bioinformatics predictions, while the discrepancy in Cp expression highlighted the complexity of post-transcriptional regulation in vivo. The identified hub genes demonstrated excellent diagnostic potential, with Timp1 achieving an area under the curve (AUC) of 1.000. This study elucidates the molecular link between S. japonicum infection and the ferroptosis pathway, suggesting that these hub genes may drive liver fibrosis progression by regulating sulfur metabolism and the immune microenvironment. These findings offer potential diagnostic biomarkers and novel therapeutic targets for schistosomal liver fibrosis. Full article

Berries are an excellent source of bioactive compounds, particularly polyphenols, and have been widely used in folk medicine by the Mapuche people of southern Chile. In this study, a hydroalcoholic extract of Berberis congestiflora Gay (BE) was analyzed to determine its phytochemical composition and to evaluate its antioxidant capacity, vasorelaxant effects in rat aortas, and inhibitory activity on enzymes related to chronic non-communicable diseases, including exploration of a possible vasodilatory mechanism in isolated rat aortas. Antioxidant activity was assessed using Oxygen Radical Absorbance Capacity (ORAC), DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid)) radical scavenging assays, as well as ferric reducing antioxidant power (FRAP). Vascular responses to the Berberis extract were studied using isometric tension recordings in an ex vivo rat thoracic aortic ring model, and the chemical constituents of BE were identified for the first time by HPLC-DAD-MS. The extract itself produced a dose-dependent contraction at 100 and 1000 µg/mL and induced relaxation in phenylephrine-precontracted aortas at the same concentrations, with a maximum contraction of 71% and maximum relaxation of 70% at 1000 µg/mL. Mechanistically, the extract triggered calcium-mediated contraction primarily through calcium release from the sarcoplasmic reticulum and, to a lesser degree, via extracellular Ca²⁺ influx, while its relaxant effect depended on an intact endothelium and activation of the NO/cGMP pathway. In addition, the extract showed inhibitory activity against cholinesterase, glucosidase, and amylase, with IC₅₀ values of 7.33 ± 0.32, 243.23 ± 0.3, and 27.21 ± 0.03 µg/mL, respectively, and docking studies were carried out for selected berry compounds. Overall, these findings indicate that these berries are a rich source of bioactive constituents with antioxidant properties and endothelium-dependent vasodilator effects, supporting their traditional use and highlighting their potential as enzyme inhibitors and as promising candidates for the development of phytotherapeutic products, particularly as supplements for chronic disease management. Full article

Background/Objectives: Optical coherence tomography angiography (OCTA) is a non-invasive imaging method that enables accurate in vivo visualisation and quantification of the macular and optic nerve head microvasculature, providing an indirect assessment of local retinal perfusion. This study aimed to evaluate the changes in OCTA perfusion parameters of macula and optic nerve head in healthy individuals following different isometric exercises and to determine their association with intraocular pressure alterations. Methods: Each subject performed four isometric exercises: elbow plank, reverse plank, right-side plank, and wall sit. Measurements of intraocular pressure, systemic blood pressure, heart rate, and OCT angiography of macula and optic nerve head were conducted before each exercise, immediately after its completion, and after a five-minute rest period. Intraocular pressure was measured using a Perkins applanation tonometer, and systemic blood pressure and heart rate were recorded using an automated sphygmomanometer. The relationship between changes in intraocular pressure and OCTA perfusion parameters was analysed. Results: A total of 12 eyes of 12 healthy subjects were included in the study, with a mean age of 28.67 ± 2.39 years. An immediate reduction in optic nerve head vessel density was observed after each exercise (elbow plank: p = 0.012; wall sit: p = 0.009; reverse plank: p < 0.001; right-side plank: p < 0.001), with a sustained decrease during the rest period following right-side plank. No significant changes in vessel density were observed in the macular region. Heart rate and systemic blood pressure increased after each exercise, while intraocular pressure increased following all exercises except the wall sit. Changes in intraocular pressure were significantly negatively associated with changes in optic nerve head vessel density in the post-rest period following elbow plank (inside disc sector: b = −1.153, p = 0.02, peripapillary sector: b = −0.369, p = 0.009) and reverse plank (whole image sector: b = −0.589, p = 0.031). Conclusions: The performance of isometric exercises induced an acute reduction in optic nerve head vessel density, and a significant association with intraocular pressure changes was observed. OCTA represents a promising research tool not only for the assessment of retinal microcirculation but also in the field of sports medicine. Full article

Introduction: The one-step membrane technique, derived from the Masquelet induced membrane technique, uses human acellular dermal matrix (hADM) that is wrapped around the bone defect to bypass membrane induction, reducing treatment time. Pre-colonization of hADM with bone marrow cells (BMC), particularly after CD8⁺ T cell depletion, enhances bone regeneration. This study examined how CD8⁺ T cell depletion alters the proteins accumulated in the hADM during early healing. Materials and Methods: Eighteen male Sprague-Dawley rats received 5 mm femoral defects filled with autologous bone chips and wrapped with hADM, hADM + BMC, or hADM + BMC-CD8. hADMs were recovered on days 3 and 7 (n = 3/group/timepoint), incubated ex vivo, and conditioned medium analyzed with a proteome profiler detecting 79 proteins. Results: The protein content of the hADM evolved dynamically. At day three, 41 proteins were detected, rising to 47 by day seven, with RGM-A, osteoprotegerin, LIF, IL-6, CCL20, and CCL17 emerging late, consistent with increased regenerative activity. CD8⁺ T cell depletion suppressed early inflammatory and pro-osteogenic mediators (e.g., CCL2, IGF-I, IL-1RA) while upregulating LIX. By day seven, regenerative mediators (CCL20, GDF-15, RGM-A) were enriched, whereas inflammatory factors (CCL21, IL-1a, WISP-1) declined. MMP-9, Galectin-1, and GDF-15 increased exclusively in the CD8-depleted group. Conclusions: The hADM protein content transitions from pro-inflammatory to pro-regenerative within one week after surgery. CD8⁺ T cell depletion accelerates this shift, highlighting hADM as a dynamic scaffold that contributes to the immune–regenerative crosstalk in bone healing. Full article