Search Results (6,222)

Background: Post-cardiac arrest syndrome (PCAS) following out-of-hospital cardiac arrest (OHCA) is driven by global ischemia–reperfusion injury, endothelial dysfunction, and a dysregulated inflammatory response. This cascade frequently culminates in profound vasoplegia and multiorgan failure, even when guideline-directed post-resuscitation management is applied. Hemoadsorption using the CytoSorb device may attenuate hyperinflammation and vasoplegia by removing circulating inflammatory and injury-related mediators. Methods: This single-centre, retrospective cohort study compared adults with PCAS following OHCA who received hemoadsorption with propensity score-matched controls (1:1 matching; n = 50 per group). For patients treated with hemoadsorption, data were analyzed within predefined intervals covering the 24 h preceding therapy initiation (T1) and the 24 h following the completion of the hemoadsorption treatment period (T2). Controls were evaluated at time points aligned to those of their matched hemoadsorption counterparts. Hemodynamic, metabolic, respiratory, and organ injury markers were assessed. Results: Formal between-group comparisons of temporal change between T1 and T2 showed no statistically significant differences between hemoadsorption-treated patients and matched controls across key parameters, including VIS (Δ −18.7 vs. −7.7; p = 0.183) and lactate (Δ −1.8 vs. −1.25 mmol/L; p = 0.780), as well as markers of organ injury, pH, and oxygenation. In exploratory ANCOVA models, only base excess was associated with treatment group (p = 0.035). Survival to hospital discharge was comparable (48% vs. 40%; p = 0.423), with similar neurological outcomes. Within the hemoadsorption group, pre–post comparisons around hemoadsorption initiation (T1–T2) demonstrated marked improvements, including reduced vasoactive support (VIS 70.0 to 12.1; p = 0.039), substantial lactate clearance (4.1 to 1.1 mmol/L; p < 0.001), and declines in organ injury markers (AST, ALT, LDH, myoglobin), alongside more pronounced platelet reduction compared with controls (129 to 57 × 10³/µL vs. 189 to 123 × 10³/µL). However, adjusted analyses indicated that these changes were primarily driven by baseline shock severity rather than a treatment-specific effect. Conclusions: In this propensity score-matched cohort of PCAS patients after OHCA, hemoadsorption was associated with within-group physiological changes but showed no detectable advantage over matched controls, with similar survival. These findings are hypothesis-generating and warrant prospective studies with standardized timing and phenotype-guided patient selection. Full article

Cigarette smoking contributes to vascular aging through oxidative stress, inflammation, and extracellular matrix (ECM) remodeling. Cellular senescence has been recognized as an important mechanism linking tobacco exposure to vascular dysfunction, but effective pharmacological strategies targeting this process remain scarce. In this study, we examined whether Rapalink-1, a dual inhibitor of mechanistic target of rapamycin complex 1 and complex 2 (mTORC1 and mTORC2), modulates smoke condensate (SC)-induced senescence in vascular cells. Human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs) were exposed to SC with or without Rapalink-1. SC increased intracellular reactive oxygen species, induced DNA damage, and promoted senescence-associated changes, including increased senescence-associated β-galactosidase (SA-β-gal) activity, reduced Lamin B1, and elevated p21 expression. These effects were accompanied by increased expression of inflammatory and matrix-remodeling genes associated with the senescence-associated secretory phenotype (SASP). Rapalink-1 co-treatment reduced oxidative stress and DNA damage, attenuated senescence markers, and partially normalized SASP-related and ECM-associated gene expression. Mechanistically, SC activated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling and increased downstream mTOR pathway activity, whereas Rapalink-1 dampened these signaling responses. Together, these findings indicate that dual mTORC1/2 inhibition by Rapalink-1 mitigates smoke condensate-induced senescence and inflammatory responses in vascular cells. Full article

The Fukushima nuclear accident highlighted that evacuation-related psychosocial harm can outweigh direct radiation risks, underscoring the need to define the health impacts of chronic low-dose-rate (LDR) radiation and evidence-based thresholds for intervention. This study investigated the effects of continuous, postnatal LDR gamma irradiation (1.2 mGy/h, cumulative dose: 5 Gy) in male mice. While no changes in body weight, hippocampal neurogenesis, or major glial and neuronal populations were observed, persistent DNA damage (γ-H2AX foci) in dentate gyrus granule cells occurred in both irradiated male and female mice. Irradiated male mice developed anxiety-like behaviour, a phenotype not observed in a previously published study of female mice subjected to an identical irradiation protocol. Molecular profiling revealed two novel, dysregulated miRNA/mRNA axes in the hippocampus linking DNA damage to behaviour: a maladaptive miR-466i-5p/Tfcp2l1 pathway associated with genomic instability, and a potentially adaptive miR-101a-5p/BMP6 pathway promoting neuronal survival. Venn analysis further identified miR-124b-3p and novel-miR489-3p as conserved exposure biomarkers, altered in both the hippocampus and blood of irradiated animals. Our results show that a high cumulative dose of chronic LDR induces markedly less severe hippocampal pathology than has been reported for equivalent acute doses. These findings support the concept of dose-rate-dependent threshold dose and contribute to the evidence base for developing countermeasures following nuclear incidents or other radiation exposures. Full article

Inflammation can promote aggressive phenotypes in prostate cancer, including enhanced migration/EMT-like changes and inflammasome-associated cytokine release. Here, we examined whether curcumin modulates these inflammation-driven responses in androgen-independent prostate cancer cells. PC-3 and DU145 cells were treated with curcumin (10 or 25 μM) or N-acetylcysteine (NAC; 2 mM). Sub-cytotoxic dosing was defined by CCK-8 viability assays. LPS (0.5 μg/mL) was used to induce motility-, invasion-, and EMT-associated responses, assessed by wound-healing assay, Matrigel-coated Transwell invasion assay, and RT–qPCR of SNAI1, CDH1, and VIM. Intracellular ROS was quantified by CM-H₂DCFDA flow cytometry. Inflammasome-associated and EMT-related protein changes were evaluated under LPS priming (24 h) followed by ATP triggering (5 mM, 1 h), with NLRP3, cleaved caspase-1, cleaved IL-1β, vimentin, and E-cadherin assessed by immunoblotting and IL-1β secretion measured by ELISA. Curcumin at 10–25 μM did not cause overt cytotoxicity and significantly reduced LPS-induced wound closure and invasive activity in both cell lines, accompanied by attenuation of EMT-associated transcriptional changes and a decrease in ROS-positive events. Under LPS priming/ATP triggering, inflammasome-associated protein signals and IL-1β secretion were robustly induced; curcumin suppressed IL-1β release and attenuated NLRP3, cleaved caspase-1, and cleaved IL-1β signals, while reversing vimentin/E-cadherin changes. NAC produced similar inhibitory patterns, supporting a redox-linked contribution to these responses. Collectively, curcumin dampens inflammation-driven motility/invasion, EMT-associated changes, and inflammasome-associated responses in androgen-independent prostate cancer cells. Full article

Background: Androgen deprivation therapy (ADT) is widely used in the management of prostate cancer (PCa) and remains a cornerstone of treatment across multiple disease settings. Although ADT contributes substantially to disease control, it also induces significant adverse metabolic and body composition changes. These alterations include loss of lean mass, increased fat mass, and deterioration in muscle quality, together contributing to a clinical phenotype consistent with sarcopenic obesity (SO). Importantly, ADT-induced SO is characterized not only by reductions in skeletal muscle mass but also by impaired muscle quality, particularly the fatty infiltration of skeletal muscle, or myosteatosis, an underrecognized but defining feature of this syndrome. Methods: This narrative review examines current evidence regarding interventions aimed at mitigating sarcopenic obesity in men treated with ADT for prostate cancer, identifies key gaps in the literature, and proposes a mechanism-driven path forward for intervention development. Results: Several exercise- and nutrition-based interventions have been evaluated in men receiving ADT and demonstrate improvements in selected outcomes such as muscle strength, body composition, and metabolic parameters. However, most studies have been limited by small sample sizes, short intervention durations, and a focus on isolated intervention components. Importantly, muscle quality and intramuscular fat infiltration (myosteatosis), a central component of sarcopenic obesity, have rarely been incorporated as biomarkers or endpoints in intervention trials targeting men receiving ADT. Conclusions: Future interventions designed to mitigate SO and its associated metabolic abnormalities should evaluate comprehensive, bundled strategies initiated early during ADT and sustained long enough to capture clinically meaningful changes. Outcomes should include biomarkers of muscle mass, strength, and quality, including imaging-based measures of myosteatosis, along with metabolic syndrome markers, inflammatory mediators, functional outcomes, adherence, and quality of life. These changes should evaluate the correlation with underlying biological mechanisms such as NF-κB signaling and pro-inflammatory cytokines. Such data may inform future phase III trials and ultimately support clinical strategies to mitigate ADT-related sarcopenic obesity and its downstream cardiometabolic and oncologic consequences. Full article

Background/Objective: Immunoglobulin G (IgG) N-glycosylation is an important regulator of immune function and systemic inflammation and has been associated with cardiometabolic diseases. However, little is known about how IgG glycosylation changes during the course of acute coronary syndrome (ACS) and whether these alterations relate to lipid-lowering response after the initiation of statin therapy. The primary aim of this study was to investigate IgG N-glycosylation following ACS and evaluate its association with response to atorvastatin therapy defined as baseline LDL cholesterol reduction of ≥50%. Methods: In this prospective cohort study, 79 statin-naïve patients hospitalized for the first episode of ACS and treated with atorvastatin 80 mg daily after percutaneous coronary intervention were followed longitudinally. Plasma samples were collected at admission (acute phase), discharge (subacute phase), and follow-up (chronic phase). A control group of 21 individuals received atorvastatin for primary prevention. IgG was isolated from plasma, and N-glycans were released, fluorescently labeled with 2-aminobenzamide, and analyzed using hydrophilic interaction-based ultra-high-performance liquid chromatography with fluorescence detection. Derived glycan traits were calculated, including agalactosylated (G0), monogalactosylated (G1), digalactosylated (G2), core fucosylated (F), bisected (B), and sialylated (S) glycans. Results: No significant differences in derived IgG glycan traits were observed between ACS patients and controls at baseline or follow-up. Within the ACS group, a longitudinal analysis revealed significant increases in G0 and F and a decrease in G2 between the acute and chronic phases. A total of 65% of patients achieved ≥50% reduction in LDL cholesterol (LDL-C), whereas only 22% reached the guideline-recommended LDL-C target of <1.4 mmol/L. Patients achieving ≥50% LDL-C reduction exhibited consistently higher G0 and lower G2 and S across disease phases. In a subgroup of patients with baseline LDL-C >3.9 mmol/L, those who failed to achieve ≥50% LDL-C reduction had significantly lower G0 and higher S across all time points. Conclusions: Specific glycan traits are associated with the degree of LDL-C reduction achieved during statin therapy, particularly in patients with high baseline LDL-C. These findings suggest that IgG glycosylation patterns may reflect biological phenotypes associated with differential lipid-lowering responsiveness after ACS. Full article

This case highlights a novel genotype–phenotype correlation in the field of endocrinology. Specific endocrine and imaging assessment, in addition to next-generation sequencing (NGS), was performed on the Illumina MiSeq platform, using a TruSight One Sequencing Panel kit for genomic analysis of coding regions of 4813 genes. A 54-year-old female was confirmed with a papillary thyroid carcinoma after total thyroidectomy and underwent radioiodine ablative therapy. Three years later, a left femoral enchondroma of almost 3 cm was identified at computed tomography (CT) scan and magnetic resonance imaging (MRI). She experienced hypertension (in addition to obesity, dyslipidaemia and impaired glucose tolerance) and was later confirmed with ACTH-independent cortisol excess [lack of cortisol suppression at 1 mg dexamethasone testing of 13.9 (normal < 1.8 µg/dL)], noting bilateral adrenal tumors, of 4.7 cm (right), respectively, and of 1.6 cm (left) at CT. Right laparoscopic adrenalectomy was performed with post-operative adrenal insufficiency, requiring glucocorticoid replacement and stopping the anti-hypertensive medication. Pathology report confirmed an adrenocortical adenoma (a Ki67 proliferation index of 2%). Noting the unusual association of the mentioned conditions, NGS was performed in the peripheral blood and identified a heterozygote missense variant of the APC gene (c.5759G>A, p.Arg1920Gln), a heterozygote missense variant of the MSH6 gene (c.2092C>G, p.Gln698Glu), and an incidental additional finding: a heterozygote stop gain pathogenic variant of the CACNA1S gene (c.2707C>T, p.Arg903*). The first two are currently classified as variants of uncertain significance. Whether the co-presence of a triple mutation may change the clinical picture and the life-long outcomes across reciprocal influence is still an open matter. Further research will point out the clinical implications of this genotype–phenotype association, which, to our best knowledge, has not been previously reported. Full article

Arterial stiffness has traditionally been interpreted as a marker of vascular ageing and cumulative blood pressure exposure. Increasing evidence, however, indicates that it should be viewed as an active determinant of cardiovascular loading conditions rather than a passive epiphenomenon. By accelerating pulse wave velocity and altering the timing of wave reflection, large artery stiffening increases central systolic pressure, augments late systolic load, and facilitates the transmission of pulsatile energy to the microcirculation. These hemodynamic alterations shape ventricular remodeling, influence ventricular–vascular coupling, and contribute to organ vulnerability even when brachial blood pressure appears adequately controlled. In this review, population-based observations and mechanistic human studies are integrated to position arterial stiffness as a stage-dependent dimension of cardiovascular disease. Community data illustrate its association with different blood pressure phenotypes and early cardiac structural changes, whereas evidence from advanced heart failure settings helps contextualize arterial stiffness within states of marked autonomic activation. Taken together, this perspective suggests that arterial stiffness is not merely a marker of cumulative damage, but a mediator that contributes to disease progression across clinical stages and, in practical terms, a phenotyping dimension along the trajectory from hypertension to heart failure. Full article

Background: Obesity and periodontitis are linked through inflammatory and metabolic pathways, and the oral microbiota may mediate this interaction. Age-related changes in immunity, salivary function, and cumulative exposure may modify obesity-associated periodontal dysbiosis. Objective: We sought to synthesize the potential for age-related differences in the oral microbiota of adult obese patients with periodontitis and assess the strength of current literature in supporting age-specific interpretations. Methods: A systematic search of PubMed/MEDLINE, Scopus, and Embase identified 1088 records. After screening and full-text assessment, 50 studies that met the criteria for focused qualitative synthesis remained. Within that review corpus, 10 representative adult human studies provided the most direct evidence linking obesity or overweight, periodontal phenotype, oral microbiota, and age-relevant interpretation. Risk of bias was appraised with the Newcastle–Ottawa Scale. Results: Direct head-to-head microbiome comparisons between younger and older obese adults with periodontitis are rare. Direct evidence links obesity to greater periodontal inflammatory burden, enrichment of classical periopathogens and bridging taxa, and shifts in community structure. Contextual aging studies have suggested that older adults may more often harbor lower-diversity, persistence-oriented communities enriched in stress-tolerant, proteolytic, or opportunistic taxa, whereas younger obese adults more often show inflammation-amplifying consortia enriched in classical periopathogens and bridging taxa. However, these patterns remain largely hypothesis-generating because the evidence base is heterogeneous and predominantly cross-sectional. Conclusions: Age likely modifies the obesity–periodontitis–microbiota axis, but direct comparative evidence on adults remains limited. The current literature supports cautious age-aware interpretation within a systematic review framework rather than definitive age-specific microbial signatures or treatment algorithms. Full article

The formulation of the gut–brain–microbiota axis (GBA) theory has led to new research directions that have expanded our understanding of the pathogenesis, phenotypic variability, and clinical course of Parkinson’s disease (PD). Models of PD pathogenesis, based on the Braak hypothesis, suggest a subtype of the disease in which pathological changes begin in the gut many years before the onset of brain pathology and the manifestation of motor symptoms. Gut microbiota may influence nervous system function along the GBA by influencing intestinal permeability, chronic inflammation, and α-synuclein aggregation. Accumulating evidence suggests that the gut microbiota may also regulate the synthesis and metabolism of neurotransmitters, including dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and γ-aminobutyric acid (GABA), both in the gut and brain, and indirectly stimulate central nervous system activity via the vagus nerve, which receives signals from the enteric nervous system. Research on the effects of microbiota on GBA has paved the way for the identification of novel treatment strategies, including probiotics, prebiotics, synbiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT), aimed at not only symptomatic but also disease-modifying treatment of PD. In this article, we propose a novel approach to GBA as a link between gut microbiota and gut and brain neurotransmitter metabolism in PD. We review the latest research on the gut epithelial barrier. We analyze and summarize the potential of therapeutic interventions targeting gut microbiota and their impact on neurotransmitter regulation in PD. Full article

Polyols are widely used as non-cariogenic sweeteners in foods and oral care products, yet their comparative activity against diverse oral microbes and their potential relevance to the oral–systemic axis remain incompletely defined. Here, we performed an in vitro, optical density (OD)-based screening of four polyols—allulose, D-mannose, erythritol, and xylitol—against Streptococcus mutans, Streptococcus anginosus, Candida albicans, and Fusobacterium nucleatum. Cultures were grown with polyols at 1–20% (w/v), and OD600 was recorded at organism-specific endpoints (~24 h). Allulose, erythritol, and xylitol produced strong, concentration-dependent suppression of streptococcal growth at ≥5–10%, whereas C. albicans showed minimal changes across the tested range. F. nucleatum was highly sensitive to allulose, D-mannose, and xylitol at ≥5% (reducing OD to ≤13% of the untreated control), while low concentrations of D-mannose and erythritol increased OD beyond that of the control, suggesting species-specific utilization or stress responses. One-way ANOVA with Tukey’s HSD post hoc testing supported significant between-polyol differences for most concentrations in Streptococcus spp. and F. nucleatum. Collectively, these results identify polyol- and taxon-specific growth phenotypes that can inform the formulation of swallow-safe oral hygiene products and motivate follow-up work in polymicrobial biofilm models and clinical studies targeting oral inflammation and downstream systemic risk. Full article

Background: Airway mucus plugging is a key but long-overlooked mechanism of persistent airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Type 2 (T2) cytokines, particularly interleukin (IL)-4 and IL-13, drive goblet cell metaplasia, MUC5AC overexpression, and impaired mucociliary clearance, while eosinophil-derived products increase mucus viscosity and promote plug persistence. Methods: A comprehensive narrative review was conducted by searching PubMed and ClinicalTrials.gov databases from inception to February 2026. Search terms included “mucus plugs,” “mucus plugging,” “biologics,” “dupilumab,” “tezepelumab,” “mepolizumab,” “benralizumab,” “IL-4,” “IL-13,” “MUC5AC,” “quantitative CT,” “functional respiratory imaging,” “asthma,” and “COPD.” Studies were included if they reported original data or systematic evidence on mucus plug quantification, biologic-mediated changes in mucus plug scores, or imaging modalities for mucus assessment in asthma or COPD. Editorials, case reports with fewer than three patients, and studies not available in English were excluded. Two authors (P.-V.M. and A.C.) independently screened titles and abstracts; discrepancies were resolved by consensus. Randomized controlled trials, observational studies, and preclinical studies evaluating mucus plug outcomes and T2-targeted therapies were included. Reference lists of retrieved articles were hand-searched for additional relevant publications. Results: A recent systematic review identified multiple randomized controlled trials and observational studies that showed CT-assessed mucus plug scores go down with biologic therapies targeting the T2 pathway in asthma. Observational data extend this evidence to anti-IL-5/IL-5Rα agents. The VESTIGE trial provided the first functional respiratory imaging evidence of mucus plug resolution with dupilumab. In COPD, the BOREAS/NOTUS and MATINEE trials established the efficacy of dupilumab and mepolizumab in eosinophilic phenotypes; however, differences in inclusion criteria—particularly regarding FeNO thresholds and prior exacerbation burden—may explain divergent effects on lung function endpoints. Mucus plug outcomes have not been evaluated in COPD biologic trials. Quantitative imaging modalities, including HRCT mucus plug scoring, functional respiratory imaging, and hyperpolarized gas MRI, now enable objective assessment of mucus burden. Conclusions: Mucus plugging meets the definition of a treatable trait: it can be measured with CT scoring, it matters clinically, and it responds to T2 cytokine blockade. Adding mucus plug assessment to routine clinical evaluation, together with mucolytic strategies where needed, could move treatment decisions from empirical to biology-based across the asthma–COPD spectrum. Further studies are needed to confirm that mucus plug scoring works as a biomarker of treatment response in COPD and to test whether combining biologics with mucolytics improves outcomes. Full article

Skeletal muscle development and physiological homeostasis are profoundly influenced by environmental cues. Among these factors, ambient temperature represents a critical determinant of growth performance and metabolic adaptation in mammals. However, the effects of different ambient temperature ranges on skeletal muscle characteristics and on responses across multiple visceral tissues remain poorly understood. In this study, five ambient temperature conditions (16 °C, 20 °C, 24 °C, 28 °C, and 32 °C) were established to investigate their physiological impacts in a mouse model. Our results demonstrate that ambient temperature markedly influences growth performance and skeletal muscle phenotype. Notably, mice housed at 20 °C showed relatively preserved grip strength and a shift in myofiber cross-sectional area distribution, although these findings did not consistently indicate superior skeletal muscle development across all indices. Further analysis revealed that ambient temperature significantly modulated the expression profiles of myosin heavy chain (MyHC) isoforms in skeletal muscle. Specifically, cold exposure was associated with an upregulation of the slow-twitch-related MyHC I, whereas heat stress correlated with an elevation of the fast-twitch-related MyHC IIb. Functional assessments indicated that exposure to colder or hotter conditions was associated with impaired muscle performance, as reflected by reduced grip strength at 16 °C, 28 °C, and 32 °C, and decreased endurance capacity at 28 °C and 32 °C. Histological analyses of major visceral organs revealed no obvious structural alterations in the heart, liver, spleen, lung, or kidney across temperature conditions. However, exposure to thermal extremes (16 °C and 32 °C) significantly reduced intestinal villus height, suggesting compromised intestinal integrity under temperature stress. Collectively, these findings indicate that ambient temperature is associated with multi-tissue changes in skeletal muscle characteristics, functional performance, and intestinal morphology. This study provides new insights into how environmental temperature modulates tissue adaptation and physiological homeostasis in mammals. Full article

The common bean (Phaseolus vulgaris L.cv. BR-104) is the most widely cultivated legume crop and serves as a major dietary protein source worldwide. However, climate change-induced drought poses a severe threat to its productivity by disrupting key physiological and biochemical processes. Therefore, identifying effective strategies to enhance drought resilience in the common bean is of considerable importance. The present study investigates the regulatory role of hydrogen sulfide (H₂S) in improving drought tolerance. Polyethylene glycol (15% PEG) induced drought stress markedly reduced phenotypic changes (leaf area (LA), plant dry weight (PDW), root length (RL), and shoot length (SL) by 18.6, 20.5, 30.3 and 17.5% respectively), photosynthetic efficiency (Fv/Fm by 28.4%), and photosynthetic pigment concentrations (chlorophyll and carotenoids by 25.6 and 36%, respectively), while significantly elevating oxidative stress markers (H₂O₂ and TBARS by 137.1% and 169.8%, respectively), leading to impaired stomatal movement and damaged chloroplast structure. Exogenous H₂S application as sodium hydrogen sulfide (200 µM NaHS; H₂S donor) effectively alleviated drought-induced oxidative damage by boosting endogenous H₂S and GSH levels, upregulating activity of antioxidative enzymes, SOD, APX, and GR, thereby promoting reactive oxygen species (ROS) scavenging, and minimizing lipid peroxidation. Moreover, H₂S maintained photosynthetic efficiency via improved stomatal openings and chloroplast structure, thus sustaining chlorophyll levels and stabilizing photosystem-II functionality. Enhanced proline accumulation following NaHS application led to improved osmotic adjustment, thereby contributing to overall stress tolerance. The use of a H₂S scavenger at 100 µM HT (Hypotaurine) suppressed the mitigating effects of H₂S, confirming the role of H₂S in enhancing drought tolerance in the common bean. Collectively, these findings highlight the potential effect of H₂S as a regulatory signaling molecule to enhance drought resilience in the common bean under drought stress conditions. Further research should explore integrating H₂S-based treatments with breeding programs and agronomic practices to develop sustainable strategies to improve drought resilience in legumes and other staple crops under changing climatic conditions. Full article

Background/Objectives: Macrophage phenotype and function are highly sensitive to environmental cues; however, most in vitro studies rely on 2D culture systems that lack physiologically relevant structural context. The spatial dimensionality can influence immune cell signaling, yet the roles of these cells in regulating macrophage behavior remain incompletely understood. This study aimed to investigate how cultural dimensionality affects the phenotype, signaling, and functional activity of monocyte-derived macrophages. Methods: GFP-expressing THP-1 monocytes were differentiated into M0, M1, and M2 macrophages and cultured either on planar substrates or within 3D matrices composed of Matrigel or type I collagen. Macrophage morphology and viability were monitored. Membrane receptor expression and secreted cytokines were examined and quantified. Functional activity was further assessed through coculture experiments with RFP-expressing MDA-MB-231 breast cancer cells. Results: Compared with 2D culture, 3D environments induced distinct morphological and viability changes in macrophages. Collagen matrices supported sustained growth, subtype-specific morphologies, and enhanced functional activity, whereas Matrigel promoted aggregation and reduced viability. Core lineage markers remained stable across conditions, but activation-associated receptors and cytokine profiles were strongly influenced by dimensionality. 3D culture enhanced TNF-α expression and altered serglycin glycosylation patterns. In coculture assays, macrophage effects on tumor cell growth depended on polarization state and were more pronounced in 3D systems. Conclusions: These findings demonstrate that culture dimensionality and ECM composition are key regulators of macrophage phenotype and function. Collagen-based 3D systems better reproduce physiologically relevant macrophage behaviors than conventional 2D platforms, highlighting the value of structurally biomimetic models for immunological studies and therapeutic screening. Full article