One-pot Functionalization for the Preparation of Cobaltocene-Modified Redox-Responsive Porous Microparticles.

Porous organic cobaltocenium-containing particles are scarce in literature but highly interesting for their electrochemical properties and reusability in, for example, catalysis or magnetic systems. In this work, we present a scalable one-pot strategy to introduce tailorable amounts of cobaltocenium on a porous substrate, adjusting the electrochemical switching capability. For this purpose, 3-(triethoxysilyl)propan-1-amine (APTES) and ethynyl cobaltocenium hexafluorophosphate is used as functionalization agents for in-situ catalyst-free hydroamination, followed by silane condensation at the particles' surface. Functionalized particles are characterized by attenuated total reflection infrared spectroscopy (ATR-IR), thermogravimetric analysis (TGA), laser scanning confocal microscopy (LSCM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS), powder X-ray diffraction (PXRD) and cyclic voltammetry (CV) showing excellent control over the degree of functionalization, i. e., the added cobaltocenium reagents. The electrochemical stability and good addressability while preserving the porous structure are shown. By utilizing higher amounts of APTES, the overall cobaltocenium amount can be reduced in favor of additional amine groups, strongly affecting the electrochemical behavior, making this functionalization strategy a good platform for metallopolymer immobilization and tailored functionalization. Additionally, thermal treatment of the synthesized metallopolymer microparticles paves the way to magnetic properties with tailorable microporous architectures for end-of-life and upcycling aspects.

Atomic layer deposition of SnS2film on a precursor pre-treated substrate.

Two-dimensional (2D) materials are attracting attention because of their outstanding physical, chemical, and electrical properties for applications of various future devices such as back-end-of-line field effect transistor (BEOL FET). Among many 2D materials, tin disulfide (SnS2) material is advantageous for low temperature process due to low melting point that can be used for flexible devices and back-end-of-line (BEOL) devices that require low processing temperature. However, low temperature synthesis method has a poor crystallinity for applying to various semiconductor industries. Hence, many studies of improving crystallinity of tin disulfide film are studied for enhancing the quality of film. In this work, we propose a precursor multi-dosing method before deposition of SnS2. This precursor pre-treatment was conducted by atomic layer deposition cycles for more adsorption of precursors to the substrate before deposition. The film quality was analyzed by x-ray diffraction, Raman, transmission electron microscopy, atomic force microscopy and x-ray photoelectron spectroscopy. As a result, more adsorbates by precursor pre-treatment induce higher growth rate and better crystallinity of film.

SUPERFICIAL AND DEEP VASCULAR COMPLEXES DAMAGED TO DIFFERENT EXTENTS IN ADVANCED STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To identify the extent of damage to the superficial vascular complex and deep vascular complex as the stage of diabetic retinopathy (DR) increases. METHODS: Subjects were divided into four groups: patients with type 2 diabetes without DR (Group 1), those with mild-to-moderate nonproliferative DR (Group 2), those with severe-to-very severe nonproliferative DR (Group 3), and those with proliferative DR (Group 4). The vessel densities of the superficial vascular complex (superficial vessel density, SVD) and deep vascular complex (deep vessel density, DVD) and their ratios were compared. Linear regression analyses were used to identify factors associated with the SVD/DVD ratio. RESULTS: The SVDs were 25.5% ± 6.1%, 25.1% ± 7.0%, 24.5% ± 9.0%, and 21.6% ± 6.9% (P = 0.048); the DVDs 25.6% ± 5.3%, 23.0% ± 7.0%, 22.3% ± 8.8%, and 17.5% ± 5.0% (P < 0.001); and the SVD/DVD ratios 1.00 ± 0.16, 1.12 ± 0.20, 1.14 ± 0.33, and 1.24 ± 0.27 (P < 0.001) in Groups 1 to 4, respectively. In multivariate analysis, DR severity (B = 7.16, P < 0.001) and the HbA1c level (B = 1.57, P = 0.042) were significantly associated with the SVD/DVD ratio. CONCLUSION: Both the SVD and DVD tended to decrease in the advanced stages of DR, and the SVD/DVD ratio increased, indicating more severe damage to the deep vascular complex than the superficial vascular complex. The ratio was positively associated with the HbA1c level, indicating a significant relationship between that level and DVD rather than SVD damage.

ABI3- and PIF1-mediated regulation of GIG1 enhances seed germination by detoxification of methylglyoxal in Arabidopsis.

Methylglyoxal (MG) is a toxic by-product of the glycolysis pathway in most living organisms and was previously shown to inhibit seed germination. MG is detoxified by glyoxalase I and II family proteins in plants. MG is abundantly produced during early embryogenesis in Arabidopsis seeds. However, the mechanism that alleviates the toxic effect of MG in maturing seeds is poorly understood. In this study, by T-DNA mutant population screening, we found that mutations in a glyoxalase I gene (named GERMINATION-IMPAIRED GLYOXALASE 1, GIG1) led to significantly impaired germination compared with wild-type seeds. Transformation of full-length GIG1 cDNA under the constitutively active cauliflower mosaic virus 35S promoter in the gig1 background completely recovered the seed germination phenotype. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses revealed that GIG1 is uniquely expressed in seeds and is upregulated by abscisic acid (ABA) and downregulated by gibberellic acid (GA) during seed germination. An ABA signaling component, ABI3, directly activated GIG1 in maturing seeds. In addition, PHYTOCHROME INTERACTING FACTOR 1 (PIF1) also plays cooperatively with ABI3 in the regulation of GIG1 expression in the early stage of imbibed seeds. Furthermore, GIG1 expression is stably silenced by epigenetic repressors such as polycomb repressor complexes. Altogether, our results indicate that light and ABA signaling cooperate to enhance seed germination by the upregulation of GIG1 to detoxify MG in maturing seeds.

CHARACTERISTICS OF AGE-RELATED MACULAR DEGENERATION SHOWING A POOR RESPONSE TO THREE LOADING DOSES OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: To analyze the clinical features of refractory age-related macular degeneration patients associated with the response to three consecutive loading doses of anti-vascular endothelial growth factor. METHODS: A retrospective chart review was performed on typical exudative age-related macular degeneration patients treated by three consecutive anti-vascular endothelial growth factor injections. The patients were divided into a group without residual fluid on optical coherence tomography images (Group 1) and a group with residual fluid (Group 2). We analyzed qualitative and quantitative morphologic features of optical coherence tomography and optical coherence tomography angiography. We performed univariate and multivariate logistic regression analyses to identify factors associated with the treatment response. RESULTS: We enrolled a total of 90 patients (Group 1: n = 60, Group 2: n = 30). Under optical coherence tomography, the choroidal thickness differed significantly between groups 1 and 2 (246.60 ± 67.67 vs. 286.90 ± 40.92 µ m, P = 0.001). Under optical coherence tomography angiography, the presence of branching (48.3% vs. 73.3%, P = 0.024), loops (31.7% vs. 66.7%, P = 0.002), and a peripheral arcade (40.0% vs. 76.7%, P = 0.001) differed significantly. Logistic regression analysis showed that the initial CT (B = 0.012; P = 0.007), presence of loops (B = 1.289; P = 0.015), and peripheral arcade (B = 1.483; P = 0.008) significantly affected the anti-vascular endothelial growth factor treatment response. CONCLUSION: A thicker choroid and the presence of loops and a peripheral arcade were significantly associated with a poorer response to three loading anti-vascular endothelial growth factor injections in typical exudative age-related macular degeneration patients.

Retinal microvasculature and choriocapillaris impairments according to the stage of dry age-related macular degeneration.

BACKGROUND: We aimed to analyse the retinal microvasculature and choriocapillaris according to the dry age-related macular degeneration (AMD) stage and to identify factors associated with their microvasculatures. METHODS: Patients were divided into four groups: normal controls, early, intermediate and advanced AMD groups. The vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris was compared using optical coherence tomography angiography among the groups. Linear regression analysis was performed to identify factors associated with the VD. RESULTS: The VDs of the SCP were 22.1 ± 5.7, 19.1 ± 5.4, 18.0 ± 6.4 and 12.2 ± 6.4% (p < 0.001); the VDs of the DCP were 22.4 ± 4.5, 20.7 ± 4.3, 18.1 ± 5.3 and 14.6 ± 5.8% (p < 0.001); the VDs of the choriocapillaris were 29.4 ± 3.7, 26.4 ± 4.8, 24.5 ± 4.9 and 24.2 ± 3.7% (p < 0.001) in the control, early, intermediate, and advanced groups, respectively. AMD stage and age were significantly associated with the VDs of all layers, and the VDs of the SCP and DCP were associated with visual acuity (both p < 0.001). Additionally, hypertension was associated with the VDs of the DCP (p = 0.027) and choriocapillaris (p = 0.024). CONCLUSIONS: The retinal microvasculature and choriocapillaris tended to become more impaired as the AMD stage progressed. Age was significantly associated with the microvasculature impairments of all layers, and hypertension was significantly associated with impairments of the DCP microvasculature and choriocapillaris.

Electropolymerized molecularly imprinted polypyrrole film for sensing of clofibric acid.

Piezoelectric quartz crystals and analogous gold substrates were electrochemically coated with molecularly imprinted polypyrrole films for pulsed amperometric detection (PAD) of clofibric acid, a metabolite of clofibrate. Cyclic voltammetry data obtained during polymerization and deposited weight estimations revealed a decrease of the polymerization rate with increasing clofibric acid concentration. XPS measurements indicated that clofibric acid could be removed after imprinting with an aqueous ethanol solution, which was further optimized by using PAD. Zeta potential and contact angle measurements revealed differences between molecularly imprinted (MIP) and non-imprinted polymer (NIP) layers. Binding experiments with clofibric acid and other substances showed a pronounced selectivity of the MIP for clofibric acid vs. carbamazepine, but the response of MIP and NIP to 2,4-dichlorophenoxyacetic acid was higher than that for clofibric acid. A smooth surface, revealed by AFM measurements, with roughness of 6-8 nm for imprinted and non-imprinted layers, might be a reason for an excessively low density of specific binding sites for clofibric acid. Furthermore, the decreased polymerization rate in the presence of clofibric acid might not result in well-defined polymer structures, which could be the reason for the lower sensitivity.

Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-κB-B cell lymphoma 6 signaling.

Follicular dendritic cells (FDCs) protect germinal center (GC) B cells from rapid apoptosis to allow their survival and maturation. In this article, we show that FDCs normally produce and secrete Wnt5a to protect GC B cells. Wnt5a production is upregulated by polyI:C. Purified Wnt5a protects GC B cells from apoptosis in a dose-dependent manner. GC B cells are protected by FDC coculture or conditioned medium, and the protection is inhibited significantly by anti-Wnt5a Ab, suggesting a major role of Wnt5a in the FDC-mediated GC B cell protection. A calcium chelator BAPTA-AM blocks the Wnt5a-mediated GC B cell protection, implying a role of Wnt/Ca(2+) signaling in the GC B cell survival. Wnt5a and calcium ionophore activate NFATc1, NFATc2, NF-κB, and B cell lymphoma 6 (BCL-6) promptly and upregulate CD40 expression in GC B and Ramos cells, whereas p53 and JNK are not upregulated or activated. Cyclosporine A inhibits the Wnt5a and calcium-induced activation of NF-κB and BCL-6 in Ramos cells, supporting a role of ß-catenin-independent Wnt/Ca(2+)/NFAT/NF-κB-BCL-6 signaling. Our data support that Wnt5a is a novel survival factor for GC B cells and might be a potential target for the regulation of B cell immunity.

Real-time hand gesture recognition using finger segmentation.

Hand gesture recognition is very significant for human-computer interaction. In this work, we present a novel real-time method for hand gesture recognition. In our framework, the hand region is extracted from the background with the background subtraction method. Then, the palm and fingers are segmented so as to detect and recognize the fingers. Finally, a rule classifier is applied to predict the labels of hand gestures. The experiments on the data set of 1300 images show that our method performs well and is highly efficient. Moreover, our method shows better performance than a state-of-art method on another data set of hand gestures.

Peripapillary microvasculature and retinal nerve fiber layer damage according to the severity of diabetic retinopathy.

PURPOSE: To identify damage to the inner retinal layer and microvasculature in the peripapillary area according to the severity of diabetic retinopathy (DR). METHODS: Patients were divided into four groups: control (group 1), type 2 diabetes (T2DM) without DR (group 2), mild to moderate nonproliferative DR (NPDR) (group 3), and severe NPDR (group 4). The peripapillary retinal nerve fiber layer (pRNFL) thickness and peripapillary vessel density (VD) were compared. Linear regression analysis was performed to identify factors associated with the DR severity. RESULTS: The average pRNFL thicknesses were 96.2 ± 7.1, 94.1 ± 9.6, 92.0 ± 9.9, and 90.3 ± 12.4 µm in groups 1, 2, 3, and 4, respectively (P = 0.003) (post hoc analyses: group 1 vs. group 2, P = 0.529; group 2 vs. group 3, P = 0.627; group 2 vs. group 4, P = 0.172; group 3 vs. group 4, P = 0.823). The VDs of the outer ring were 18.9 ± 0.6, 18.4 ± 0.8, 17.9 ± 1.1, and 17.3 ± 1.6 mm-1 in groups 1, 2, 3 and 4, respectively (P < 0.001) (all pairwise comparisons, P < 0.050). In multivariate analysis, the VD of the outer ring (B = - 0.35, P < 0.001) was significantly associated with the DR severity. CONCLUSIONS: The peripapillary microvasculature reflects retinal damage following DR progression better than the structure of the pRNFL.

Impact of systemic hypertension on inner retinal layer thickness and macular microvasculature in patients with diabetic retinopathy.

AIM: To investigate the effects of hypertension (HTN) on inner retinal thickness and macular microvasculature in patients with diabetic retinopathy (DR). METHODS: Subjects were classified into three groups: patients with type 2 diabetes mellitus (T2DM) (T2DM group), patients with DR (DR-HTN group), and patients with DR and HTN (DR + HTN group). The ganglion cell complex (GCC) thicknesses and the macular vessel density (VD) were compared. Linear regression analyses were performed to identify factors associated with the VD in the DR + HTN group. RESULTS: The mean GCC thicknesses were 112.2 ± 12.3, 109.2 ± 13.7, and 106.2 ± 11.2 µm in the T2DM, DR-HTN, and DR + HTN groups, respectively (P = 0.045). The mean VDs were 25.4 ± 5.0, 24.3 ± 8.9, and 21.2 ± 7.1% (P = 0.014) for the superficial capillary plexus (SCP) and 25.9 ± 4.3, 22.9 ± 8.5, and 20.2 ± 6.6% (P < 0.001) for the deep capillary plexus (DCP) in the T2DM, DR-HTN, and DR + HTN groups, respectively. In multivariate analyses, the duration of HTN was a significant factor associated with the VD of both SCP (B = -0.24, P = 0.010) and DCP (B = -0.21, P = 0.016). CONCLUSIONS: Patients with both DR and HTN had a thinner GCC and lower VDs of SCP and DCP than those with DR alone. These outcomes could be associated with the synergistic ischemic effects in DR patients with HTN. Moreover, the duration of HTN in DR patients was significantly associated with macular VD in both SCP and DCP.

Features of optical coherence tomography angiography in age-related macular degeneration with residual fluid after three loading doses of aflibercept.

BACKGROUND: To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept. METHODS: Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups. RESULTS: A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94 ± 2.51 µm2 vs. 2.22 ± 2.26 µm2, P = 0.178) or vessel density (47.1 ± 15.4 % vs. 41.3 ± 10.5%, P = 0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P = 0.026) and peripheral arcades (29.2% vs. 55.6%, P < 0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P < 0.001) and loops (P = 0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P < 0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B = 4.77, P = 0.001) was significantly associated with residual fluid. CONCLUSIONS: Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.

Safeguarding Public Health: Advanced Detection of Food Adulteration Using Nanoparticle-Based Sensors.

Food adulteration, whether intentional or accidental, poses a significant public health risk. Traditional detection methods often lack the precision required to detect subtle adulterants that can be harmful. Although chromatographic and spectrometric techniques are effective, their high cost and complexity have limited their widespread use. To explore and validate the application of nanoparticle-based sensors for enhancing the detection of food adulteration, focusing on their specificity, sensitivity, and practical utility in the development of resilient food safety systems. This study integrates forensic principles with advanced nanomaterials to create a robust detection framework. Techniques include the development of nanoparticle-based assays designed to improve the detection specificity and sensitivity. In addition, sensor-based technologies, including electronic noses and tongues, have been assessed for their capacity to mimic and enhance human sensory detection, offering objective and reliable results. The use of nanomaterials, including functionalized nanoparticles, has significantly improved the detection of trace amounts of adulterants. Nanoparticle-based sensors demonstrate superior performance in terms of speed, sensitivity, and selectivity compared with traditional methods. Moreover, the integration of these sensors into food safety protocols shows promise for real-time and onsite detection of adulteration. Nanoparticle-based sensors represent a cutting-edge approach for detecting food adulteration, and offer enhanced sensitivity, specificity, and scalability. By integrating forensic principles and nanotechnology, this framework advances the development of more resilient food-safety systems. Future research should focus on optimizing these technologies for widespread application and adapting them to address emerging adulteration threats.

Impact of high myopia on inner retinal layer thickness in type 2 diabetes patients.

To investigate the impact of the combination of type 2 diabetes (DM) and high myopia on inner retinal layer thickness of the macular area. The patients were divided into four groups: control (group 1), patients with DM without high myopia (group 2), patients with high myopia without DM (group 3), and patients with DM and high myopia (group 4). Ganglion cell complex (GCC) thickness was compared among the groups. Linear regression analysis was performed to identify factors associated with GCC thickness. A total of 194 eyes were enrolled: 59 in group 1, 52 in group 2, 49 in group 3, and 34 in group 4. The average parafovea GCC thicknesses were 113.9 ± 10.4, 112.4 ± 11.2, 112.2 ± 7.8, and 102.6 ± 15.1 µm (P < 0.001), and the average perifovea GCC thicknesses were 104.8 ± 13.2, 103.5 ± 10.8, 103.6 ± 8.8, and 93.9 ± 15.5 µm in groups 1, 2, 3 and 4, respectively (P = 0.001). In multivariate analyses, age (ß = - 0.20, P = 0.007), DM duration (ß = - 0.34, P = 0.023), and axial length (ß = - 1.64, P < 0.001) were significantly associated with parafoveal GCC thickness. The GCC was significantly thinner when high myopia and DM were combined, compared to either condition alone. Additionally, age, DM duration, and axial length were significant factors associated with GCC thickness. The combination of mechanical stretching and neurodegeneration would accelerate neural damage to the retina, resulting in greater inner retinal layer thinning.

Nutrition Therapy by Nutrition Support Team: A Comparison of Multi-Chamber Bag and Customized Parenteral Nutrition in Hospitalized Patients.

This study aimed to investigate the activity of a nutrition support team (NST) and the trends of multi-chamber bag (MCB) and customized parenteral nutrition (PN) with NST consultations in South Korea. Data were obtained from the National Inpatient Sample Cohort between 2015 and 2020. Three datasets were constructed for NST consultation, MCB-PN product prescriptions, and aseptic preparation of total PN. The intersections of the NST consultation and each PN dataset were compiled into MCB-PN with NST or customized PN with a NST sub-dataset, respectively. Using personal identifiers, the patients' characteristics were evaluated in the NST cohort. A total of 91,384 reimbursements and 70,665 patients were included. The NST activity had increased by more than 50% over 6 years. Approximately 70% and 11%, respectively, of the NST cohort were classified into two subgroups: MCB-PN with NST (M-NST) and customized PN with NST (C-NST). M-NST had many elderly patients with cancer and showed a higher in-hospital mortality than C-NST (12.6% vs. 9.5%). C-NST included a larger number of patients under the age of 5 years, and the hospitalization period was more extended than M-NST (26.2 vs. 21.2 days). The present study showed that NST activities and the proportion of PN with NST consultation are gradually increasing in South Korea.

Vertical asymmetry analysis of the macular microvasculature in epiretinal membrane patients with open-angle glaucoma.

To identify the usefulness of vertical asymmetry analysis of the retinal microvasculature in epiretinal membrane (ERM) patients accompanied by open-angle glaucoma (OAG). Subjects were divided into three groups: normal controls (group 1), patients with ERM (group 2), and patients with both ERM and OAG (group 3). Retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses, vessel density (VD), and the absolute vertical difference of pRNFL (vdRNFL), GC-IPL (vdGC-IPL), and VD (vdVD) were compared among groups. Logistic regression analysis was performed to determine the factors associated with OAG. Diagnostic accuracy based on the area under the curve (AUC) was conducted. The VD of the full area was 20.9 ± 1.2, 20.0 ± 1.9, and 18.8 ± 2.2 mm-1 (P < 0.001) for groups 1, 2, and 3, respectively. The vdVD differed significantly between group 2 and group 3 (P < 0.001), whereas vdRNFL (P = 0.531) and vdGC-IPL (P = 0.818) did not show a significant difference. Multivariate logistic analyses showed that average pRNFL thickness (OR 0.924, P = 0.001) and vdVD (OR 5.673, P < 0.001) were significant factors associated with OAG in ERM patients. The AUC of the vdVD was 0.81 (95% CI 0.72-0.89), and the combination of average pRNFL thickness and vdVD had the highest AUC (0.87; 95% CI 0.78-0.95; P < 0.001). ERM patients with OAG had a significantly thinner pRNFL thickness, lower macular VD, and higher vdVD than those without OAG. Average pRNFL thickness and vdVD were significant factors associated with OAG in patients with ERM. Additionally, the combination of average pRNFL thickness and vdVD showed good diagnostic performance for OAG in patients with ERM.

Reduced lung function is independently associated with increased risk of type 2 diabetes in Korean men.

BACKGROUND: Reduced lung function is associated with incident insulin resistance and diabetes. The aim of this study was to assess the relationship between lung function and incident type 2 diabetes in Korean men. METHODS: This study included 9,220 men (mean age: 41.4 years) without type 2 diabetes at baseline who were followed for five years. Subjects were divided into four groups according to baseline forced vital capacity (FVC) (% predicted) and forced expiratory volume in one second (FEV1) (% predicted) quartiles. The incidence of type 2 diabetes at follow-up was compared according to FVC and FEV1 quartiles. RESULTS: The overall incidence of type 2 diabetes was 2.2%. Reduced lung function was significantly associated with the incidence of type 2 diabetes after adjusting for age, BMI, education, smoking, exercise, alcohol, and HOMA-IR. Both FVC and FEV1 were negatively associated with type 2 diabetes (P < 0.05). In non-obese subjects with BMI < 25, the lowest quartile of FVC and FEV1 had a significantly higher odds ratio for type 2 diabetes compared with the highest quartile after adjusting for age and BMI (2.15 [95% CI 1.02-4.57] and 2.19 [95% CI 1.09-4.42]). CONCLUSIONS: Reduced lung function is independently associated with the incidence of type 2 diabetes in Korean men.

Wnt5a activates THP-1 monocytic cells via a ß-catenin-independent pathway involving JNK and NF-κB activation.

Wnt5a has been implicated in the activation of macrophages. However, the profile and mechanism of downstream regulation has not been characterized. In this study, we have investigated the regulation of Wnt5a-induced activation in monocytic THP-1 cells. Wnt5a activated THP-1 cells, enhancing adhesion to endothelial cells. Hypoxia induced the production of Wnt5a, suggesting a role in the hypoxia-induced activation of macrophages. Wnt5a induced the expression of various pro-inflammatory cytokines and inflammatory mediators, particularly IL8 and CXCL2, suggesting a major role in the secretion of CXC chemokines by macrophages. Wnt5a induced JNK phosphorylation and NF-κB activation via ß-catenin-independent signaling. Interestingly, SP600125, a specific inhibitor of JNK, inhibited Wnt5a-induced activation of NF-κB, supporting JNK-dependent NF-κB activation. Our data suggest that Wnt5a activates monocytic cells via JNK and NF-κB activation.

Wnt5a induces endothelial inflammation via beta-catenin-independent signaling.

Wnt signaling has been implicated in certain inflammatory diseases. However, the biological role in the inflammatory regulation remains to be characterized. We investigated the regulation by Wnt signaling in endothelial cells, which are active participants and regulators of inflammation. Wnt5a induces cyclooxygenase-2 expression and enhances inflammatory cytokines rapidly, whereas Wnt3a shows limited effects, suggesting a role for beta-catenin-independent Wnt signaling in the inflammatory endothelial activation. Pulse-like treatment of Wnt5a induces cyclooxygenase-2 more efficiently than continuous treatment. Wnt5a and TNF-alpha regulate subsets of cytokines overlapping, only partially, with each other. Calcium ionophore enhances endothelial inflammation similarly, whereas calcium chelators and protein kinase C inhibitor block Wnt5a-induced activation, suggesting a role for the Wnt/Ca(2+)/protein kinase C pathway in endothelial inflammatory regulation. Wnt5a activates RelA nuclear translocation and DNA binding. Activated blood vessels, histiocytes, and synoviocytes express Wnt5a in atherosclerosis and rheumatoid arthritis but not in normal tissue, supporting the role of Wnt5a as an inflammatory mediator in vivo. Our data suggest that endothelial inflammation is regulated by a dual system consisting of beta-catenin-independent Wnt signaling and TNF-alpha-mediated signaling.