Search Results (1,348)

Background: Type 2 diabetes mellitus (DM) is a major cardiovascular risk factor that induces monocyte dysfunction and contributes to their accumulation in atherosclerotic lesions. Monocyte recruitment and accumulation in the tissues contribute to chronic inflammation and are essential to the pathobiology of diabetes-induced atherosclerosis. However, the mechanisms that drive the accumulation of monocytes in the diabetic environment are not clearly understood. Methods: Primary monocytes from type 2 (T2) DM and non-T2DM individuals were isolated using magnet-assisted cell sorting. To examine the influence of a diabetic milieu on monocyte function, monocytes from T2DM patients, db/db mice, or human monocytes subjected to hyperglycaemia were analysed for their responses to pro-atherogenic cytokines using Boyden chamber assays. Furthermore, the interactions of non-diabetic and diabetic monocytes with TNFα-inflamed endothelium were studied using live-cell imaging under physiological flow conditions. RT-qPCR and FACS were used to study the expression of relevant molecules involved in monocyte-endothelium interaction. Results: CD14⁺CD16⁻ monocytes isolated from T2DM patients or monocytes exposed to hyperglycaemic conditions showed reduced chemotactic responses towards atherosclerosis-promoting cytokines, CCL2 and CX3CL1, indicating monocyte dysfunction. Under flow conditions, the transendothelial migration (TEM) capacity of T2DM monocytes was significantly reduced. Even though these monocytes adhered to the endothelial monolayer, only a few transmigrated. Interestingly, the T2DM monocytes and monocytes exposed to hyperglycaemic conditions accumulated in the ablumen following transendothelial migration. The time period in the ablumen of T2DM cells was prolonged, as there was a significant impairment of the reverse transendothelial migration (rTEM). Mechanistically, the T2DM milieu specifically induced the activation of monocyte integrins, Macrophage-1 antigen (Mac-1; integrin αMβ2 consisting of CD11b and CD18), and Lymphocyte function-associated antigen 1 (LFA-1; αLβ2 consisting of CD11a and CD18). Furthermore, elevated levels of CD18 transcripts were detected in T2DM monocytes. Junctional Adhesion Molecule 3 (JAM-3)–MAC-1 interactions are known to impede rTEM and T2DM milieu-potentiated JAM-3 expression in human coronary artery endothelial cells (HCAEC). Finally, the overexpression of JAM-3 on HCAEC was sufficient to completely recapitulate the impaired rTEM phenotype. Conclusions: Our results revealed for the first time that the enhanced T2DM monocyte accumulation in the ablumen is not secondary to the elevated transmigration through the endothelium. Instead, the accumulation of monocytes is due to the direct consequence of a dysfunctional rTEM, potentially due to enhanced JAM3-MAC1 engagement. Our results highlight the importance of restoring the rTEM capacity of monocytes to reduce monocyte accumulation-dependent inflammation induction and atherogenesis in the T2DM environment. Full article

The immiscibility of most polymers leads to poor interfacial adhesion in blends, a critical challenge that often limits the mechanical performance of polymer composites. This research introduces shape-forming elements (SFEs), a novel class of coextrusion dies designed to create additional geometric complexity and control over interfacial architecture. Specifically inspired by Julia Set and T-Square fractals, SFEs were simulated, prototyped, and found to be effective in coextrusion of different-colored polymer clays. The SFEs were employed to coextrude architected composites consisting of a liquid crystalline polymer (Vectra A950) and a cycloaliphatic polyamide (Trogamid CX7323). Mechanical testing revealed a strong positive correlation between the draw ratio and both the tensile modulus (adjusted R² = 0.94) and tensile stress at break (adjusted R² = 0.84). However, experimental cross-sections significantly differed from simulation results. These discrepancies were attributed to interfacial instabilities caused by material incompatibility between the two polymers and potential moisture-induced defects. This finding highlights critical challenges that arise during practical processing, emphasizing the importance of addressing polymer compatibility and moisture management to realize the full potential of SFEs in designing advanced polymer composites with targeted properties. Full article

(1) Background: The present study investigated the effects of extracellular vesicles (EVs), derived from adipose tissue stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMMSCs), on atherosclerosis-associated cardiac hypertrophy. (2) Methodology: The experiments were performed on hamsters divided into the following groups: control (C) fed with a standard diet; hypertensive–hyperlipidemic (HH) generated by combining a diet enriched with 3% cholesterol, 15% butter, and by gavage with 8% NaCl on a daily basis; HH groups injected with EVs (ADSCs) or EVs (BMMSCs), either transfected with Smad2/3 siRNAs or not (HH-EVs (ADSCs), HH-EVs (BMMSCs), HH-EVs (ADSCs) + Smad2/3siRNA, HH-EVs (BMMSCs) + Smad2/3siRNA); and HH group injected with Smad2/3 siRNAs (HH-Smad2/3siRNA). (3) Results: In comparison with the HH group, the findings demonstrated that treatment using EVs (ADSCs or BMMSCs), either with or without Smad2/3 siRNAs, resulted in several significant improvements in the following aspects: the plasma levels of cholesterol, LDL, triglycerides, TGF-β1, and Ang II were decreased; the left ventricular structure and function were recovered; inflammatory markers, ROS, COL1A, α-SMA, Cx43, MIF, ANF, and M1/M2 macrophages, were reduced; the level of key protein NF-κB p50 was diminished. (4) Conclusions: These findings underscore the therapeutic potential of mesenchymal stem cell-derived EVs in atherosclerosis-associated cardiac hypertrophy. Full article

In this study, TiC_xO_y was produced by sintering in an argon atmosphere using carbon–thermal reduction with TiO₂ and graphite powder as the initial materials. The sintered TiC_xO_y was analyzed using X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. As the oxygen content increased, the grain color of the sintered TiC_xO_y gradually shifted from gray to reddish-brown. The structure of TiC_xO_y resembles that of a coral, with a uniform distribution of Ti, C, and O throughout the sample. Analysis using X-ray photoelectron spectroscopy reveals the presence of bivalent, trivalent, and tetravalent titanium. Utilizing General Structure Analysis System software(GSAS-II), the X-ray Diffraction data obtained were refined, revealing a gradual decrease in lattice parameters as the oxygen atom content increased. Furthermore, the conductivity and density of the single phase, determined through the four-probe method and the Archimedes method, respectively, exhibited an increase in tandem with the rise in C content. Full article

The prompt and reliable detection of NH₃ leakage at room temperature (RT) is considered important for safety assurance and sustainable production. Although chemiresistive NH₃ sensors feature low cost and structural simplicity, their practical application is hindered by high operating temperatures and inadequate selectivity. Metal–organic frameworks (MOFs) and their derivatives offer a promising approach to address these limitations. In this work, Ce-BDC precursors with tunable particle sizes and crystallinity were synthesized by adjusting the raw material concentration. Controlled pyrolysis yielded a series of CeO₂-C-X (X = 0.5, 1, 1.5, 2) materials with nanosized particles. Among them, the CeO₂-C-1 sensor delivered a high response of 82% toward NH₃ under 40% relative humidity at RT. Moreover, it possessed excellent selectivity, repeatability, and rapid response-recovery behavior compared with the other samples. CeO₂-C-1 also remained stable under varying oxygen and humidity conditions, demonstrating high applicability. The superior sensing properties may be attributed to its high specific surface area and optimized mesoporous structure, which facilitated efficient gas adsorption and reaction. These findings demonstrated that precise control of MOF precursors and the structure in CeO₂ nanomaterials was critical for achieving high-performance gas sensing and established Ce-MOF-derived CeO₂ as a promising sensing material for NH₃ detection at RT. Full article

Background: A major factor in the development of atherosclerosis is the presence of a chronic inflammatory state. The CX₃CL1/CX₃CR1 axis has been implicated in the development of atherosclerosis and cardiovascular disease, but until now, scarce data are available regarding the influence of the CX₃CL1/CX₃CR1 axis in familial combined hyperlipidaemia (FCH). Since FCH is associated with a high risk of cardiovascular disease, the objective of the present study was to assess the presence of alterations in the CX₃CL1/CX₃CR1 axis in patients with FCH and to evaluate the influence of insulin resistance (IR) and sex. Methods: A cohort of 47 subjects with FCH and 38 control subjects was included. We measured the lipid profile, glucose, and insulin levels in plasma, circulating blood CX₃CL1 levels, and CX₃CR1 mRNA expression. Carotid IMT and the presence of atheroma plaques were also evaluated. Results: FCH subjects showed significantly higher activation of the CX₃CL1/CX₃CR1 axis than controls. In addition, FCH individuals with IR showed the worst profile of inflammation status, higher carotid IMT, and a higher prevalence of atherosclerotic plaque compared to controls and FCH patients without IR. However, sex did not influence the CX3CL1/CX3CR1 axis. Conclusions: FCH patients showed an increased CX₃CL1/CX₃CR1 axis, which was positively correlated with IR, but not with sex. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients. Full article

Background and Objective: Cerebral cavernous malformation (CCM) is a vascular disorder causing seizures, neurological deficits, and hemorrhagic stroke. It can be sporadic or inherited via CCM1, CCM2, or CCM3 gene mutations. Inflammation is broadly recognized as a promoter of cerebral vascular malformations. This study explores inflammatory mechanisms and differences behind CCM-related hemorrhage and epilepsy. Material and Methods: The study group comprised 28 patients, ten patients with CCM-related epilepsy, and 18 patients who clinically presented with a cerebral hemorrhage at diagnosis. All patients underwent microsurgical resection of the CCMs. Formaldehyde-fixed, paraffin-embedded tissue samples were immunohistochemically stained using a monoclonal antibody against Cyclooxygenase 2 (COX-2) (Dako, Santa Clara, CA; Clone: CX-294) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) (ABCAM, Cambridge, MA, USA; ab214185). MRI and clinical data were correlated with immunohistochemical findings, and the analysis was conducted utilizing the Trainable Weka Segmentation algorithm. Results: Median CCM volume was 1.68 cm³ (IQR: 0.85–3.07 cm³). There were significantly more NLRP3-positive cells (32.56% to 91.98%; mean: 65.82%, median: 68.34%; SD: ±17.70%), compared to COX-2-positive cells (1.82% to 79.69%; mean: 45.87%, median: 49.06%; SD: ±22.56%). No correlation was shown between the volume of CCMs and a hemorrhage event (p = 0.13, 95% CI: 0.99–1.02). Symptomatic brain hemorrhage showed a significantly increased inflammatory enzyme upregulation from both COX-2 (p < 0.001) and NLRP3 (p = 0.009) versus patients with symptomatic CCM-related epilepsy at first diagnosis. Conclusions: Inflammatory processes in CCMs seem to be driven by broad and multiple pathways because both COX-2 and NLRP3-driven inflammatory pathways are consistently activated. As a novelty, this study showed that patients with symptomatic hemorrhage showed upregulated inflammatory enzyme activity compared to patients with CCM-related epilepsy. No direct links between NLRP3, COX-2 expression, and radiological, pathological, or preexisting patient conditions were found. Full article

Polyamine (PA) spermine (SPM) (i) plays an essential role in the function of neurons, while (ii) accumulating predominantly in glial cells by an unknown mechanism. In addition, the translocation of SPM synthesis and redistribution in the developing and maturating retinas remains unclear. Therefore, the expression of the SPM-synthesizing enzyme, spermine synthase (SpmS), was compared in rat retinas on postnatal days 3, 21, and 120 using immunocytochemistry, Western blot (WB), and ImageJ analyses. The anti-glutamine synthetase (GS) antibody identified glial cells, and DAPI labeled the cell nuclei. At postnatal day 3 (P3), the neonatal retina shows widespread SpmS expression throughout most neuroblast cells, but absent in the developing synaptic layers and Müller cell (MCs) processes. By day 21 (P20), SpmS becomes strongly expressed in neurons, and not in glia. On day 120 (P120), SpmS was observed in synaptic areas, with significantly less presence in neuronal soma and still none in MCs. WBs showed a decrease in SpmS expression during maturation. Therefore, glial cells do not synthesize SPM, and the accumulation of SPM in MCs found earlier suggests that glial cells take up SPM via a hypothetical high-affinity SPM transporter. In glia, SPM regulates glial connexin (Cx43) and potassium (Kir4.1) channels, being a key player in CNS diseases and aging. Full article

Members of the WRKY transcription factors (TFs) family play crucial roles in biotic and abiotic stress responses in plants, but their roles in response to drought stress in maize (Zea mays L.) have not been fully elucidated. Maize ZmWRKY82, a group IIc WRKY gene, was isolated from maize using reverse transcription polymerase chain reaction (RT-PCR). Using the UniProt online database, we found that ZmWRKY82 encodes a 222-amino protein with conserved WRKYGKK and C-X₄-C-X₂₃-H-X₁-H motifs. ZmWRKY82 is strongly induced by polyethylene glycol (PEG), abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), and ethephon (ETH) treatments. The ZmWRKY82 protein was located in the cell nucleus. ZmWRKY82 had transcriptional activation capability and was able to bind to the W-box element. ZmWRKY82-overexpressing Arabidopsis and maize exhibited stronger drought resilience, which was associated with enhanced antioxidant enzyme activity and altered transcription level of drought-related genes. These findings suggest that ZmWRKY82 plays a central role in conferring drought tolerance in maize and may contribute to crop improvement and sustainable agricultural practices. Full article

The aim of this study was to investigate the effects of apple cider vinegar (ACV), various mouthwashes and bleaching on the color and surface roughness of fiber strip-reinforced and unreinforced restorative materials. The materials were resin composite (RC), resin-nanoceramic (RNC), and polymer-infiltrated ceramic network (PICN); the mouthwashes were chlorhexidine with alcohol (CXA), chlorhexidine without alcohol (CX), herbal with alcohol (HRA), and herbal without alcohol (HR). Measurements were performed at T0 (baseline), T1 (1 day), T2 (2.5 days) and T3 (after bleaching). Analysis of variance (ANOVA) and Bonferroni analyses revealed that roughness from T0–T3 was highest for RNC and lowest for PICN. Regarding the solutions, the highest increase was in ACV and lowest in artificial saliva (p < 0.001). At T0–T2, color change (ΔE₀₀) and whiteness index change (ΔWI_D) were highest in CXA and lowest in HR. At T2–T3, ΔE₀₀ was highest in ACV, while ΔWI_D was highest in CXA (p < 0.001). Although the roughness exceeded the bacterial adhesion threshold, the effect of bleaching was not considerable. Color and whiteness changes generally did not exceed the acceptability threshold. Fiber strip position did not affect roughness. However, a strip in the middle layer had higher impact on color and whiteness than the one in the top layer. Full article

Background/Objectives: Corneal re-epithelialization is a critical process following surgical procedures such as photorefractive keratectomy (PRK), phototherapeutic keratectomy (PTK), and corneal UV cross-linking (CXL), as well as cases of corneal abrasion. Delayed epithelial healing can lead to increased discomfort, a higher risk of infection, and suboptimal visual outcomes. This retrospective case series aims to evaluate the efficacy of a novel ophthalmic solution containing cross-linked carboxymethyl cellulose (CX-CMC) and silk proteins in promoting corneal re-epithelialization and improving post-surgical recovery. Patients and methods: A total of 15 patients who underwent PRK, PTK, or CXL or who presented with corneal abrasions were included in the study. Along with standard post-surgical treatment, patients received CX-CMC and silk protein-based eye drops (CORDEV, Ophtagon, Rome, Italy) six times a day. Corneal epithelial thickness was assessed using topography at follow-up visits. Results: Corneal re-epithelialization was observed in all subjects within 24 to 48 h post-procedure. The mean corneal epithelial thickness at 48 h was 73.21 µm, which falls within the typical range of a proliferating corneal epithelium. Conclusions: The CX-CMC and silk protein-based formulation accelerated corneal healing, achieving rapid epithelial recovery. This novel ophthalmic solution offers a promising alternative to conventional post-surgical treatments, potentially improving patient outcomes by reducing healing time, minimising discomfort, and lowering the risk of complications associated with delayed re-epithelialization. Full article

Background: Although there has been an improvement in the survival rates of patients following heart transplantation, many complications, such as hypertension, continue to develop. The aim of the study was to assess the 24-hour blood pressure profile and hypertension treatment among patients after heart transplantation and comparison to the control group. Methods: A retrospective data analysis included 26 male patients post-heart transplantation and 39 male patients in the control group. During a routine visit, the following data were collected: 24-hour blood pressure monitoring, laboratory tests, and medical history. Results: Hypertension was diagnosed in 76.9% of heart transplant recipients (HTXr) and in 56.4% of the control group (Cx). During the night-time rest period, diastolic blood pressure values ≥ 70 mmHg were observed in 76.9% of HTXr (vs. 33.33% Cx, p = 0.001). The average daytime systolic/diastolic blood pressure did not differ significantly between the groups. It was also observed that the groups differed in circadian blood pressure (Chi²ML = 15.87, p < 0.001), as there were significantly more reverse dippers in HTXr than in the control group (30.8% (8) vs. 10.3% (4)). The same proportions were also noted in HTXr and the control group in terms of isolated nocturnal hypertension. Conclusions: Heart transplant recipients require a tailored approach to hypertension management, including a variety of medications and appropriate chronotherapy. Full article

Glioblastoma (GBM) is an aggressive brain tumor with a highly immunosuppressive microenvironment that promotes tumor progression and therapy resistance. Tumor-associated macrophages (TAMs), comprising up to 50% of the tumor mass, are recruited via chemokine axes such as CCL2/CCR2, CX3CL1/CX3CR1, and CXCL12/CXCR4 and adopt an M2-like immunosuppressive phenotype, facilitating immune escape and angiogenesis. Key signaling pathways, including CSF1R, STAT3, NF-κB, PI3K/Akt, and HIF-1α, regulate TAM function, making them promising therapeutic targets. Strategies such as TAM depletion, reprogramming, and immune checkpoint blockade (PD-1/PD-L1, and CD47-SIRPα) have shown potential in preclinical models. Emerging approaches, including CAR-macrophage (CAR-M) therapy, nanotechnology-based drug delivery, and exosome-mediated modulation, offer new avenues for intervention. However, clinical translation remains challenging due to GBM’s heterogeneity and adaptive resistance mechanisms. Future research should integrate multi-omics profiling and AI-driven drug discovery to refine TAM-targeted therapies and improve patient outcomes. This review provides a comprehensive analysis of TAM-mediated immune regulation in GBM and explores evolving therapeutic strategies aimed at overcoming its treatment barriers. Full article

Guided by thermodynamic calculations, this study successfully synthesized nonstoichiometric high-entropy carbide (Mo_0.2Nb_0.2Ta_0.2Ti_0.2W_0.2)C_x (x = 0.875–0.972) nanometer-sized powders using micrometer-sized metal oxides (MoO₃, Nb₂O₅, Ta₂O₅, TiO₂, and WO₃) and carbon black as raw materials through carbothermic reduction at 1400–1550 °C. The powders synthesized above 1500 °C exhibited a single-phase rock-salt structure with an average grain size as low as 270 nm. TEM analysis confirmed the lattice parameters increased from 0.4378 nm to 0.4395 nm with decreasing carbon content and synthesis temperature. After ball milling, the optimal powder was densified into a (Mo_0.2Nb_0.2Ta_0.2Ti_0.2W_0.2)C_0.9 ceramic block through spark plasma sintering (SPS, 1950 °C/10 min/20 MPa), achieving a relative density of 99.1% and an average grain size of 4.3 μm. This ceramic exhibited remarkable mechanical properties (17.3 GPa Vickers hardness, 25.9 GPa nano-hardness, 524 GPa Young’s modulus, and 4.43 MPa·m^1/2 fracture toughness) and a relatively low room-temperature thermal conductivity of 8.3 W·m⁻¹·K⁻¹. This study provides a theoretical basis and technical approach for the preparation of high-hardness and low-thermal-conductivity nonstoichiometric high-entropy carbide ceramics via low-temperature carbothermic reduction and sintering. Full article