Reactive Oxygen Species-Responsive Dual Anti-Inflammatory and Antioxidative Nanoparticles for Anterior Uveitis.

Anterior uveitis (AU) is an immune-mediated inflammatory disease that results in iritis, cyclitis, glaucoma, cataracts, and even a loss of vision. The frequent and long-term administration of corticosteroid drugs is limited in the clinic owing to the side effects and patient noncompliance with the drugs. Therefore, specifically delivering drugs to inflammatory anterior segment tissues and reducing the topical application dosage of the drug are still a challenge. Here, we developed dual dexamethasone (Dex) and curcumin (Cur)-loaded reactive oxygen species (ROS)-responsive nanoparticles (CPDC NPs) to treat anterior uveitis. The CPDC NPs demonstrated both anti-inflammatory and antioxidative effects, owing to their therapeutic characteristics of dexamethasone and curcumin, respectively. The CPDC NPs could effectively release dexamethasone and curcumin in the oxidizing physiological environment of the inflammation tissue. The CPDC NPs can effectively internalize by activated macrophage cells, subsequently suppressing the proinflammatory factor expression. Moreover, the CPDC NPs can inhibit ROS and inflammation via nuclear transcription factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway activation. In an endotoxin-induced uveitis rabbit model, the CPDC NPs show a therapeutic effect that is better than that of either free drugs or commercial eye drops. Importantly, the CPDC NPs with a lower dexamethasone dosage could reduce the side effects significantly. Taken together, we believe that the dual-drug-loaded ROS-responsive NPs could effectively target and inhibit inflammation and have the potential for anterior uveitis treatment in clinical practice.

Is There a Spatial Relationship between Urban Landscape Pattern and Habitat Quality? Implication for Landscape Planning of the Yellow River Basin.

The extent to which landscape spatial patterns can impact the dynamics and distribution of biodiversity is a key geography and ecology issue. However, few previous studies have quantitatively analyzed the spatial relationship between the landscape pattern and habitat quality from a simulation perspective. In this study, the landscape pattern in 2031 was simulated using a patch-generating simulation (PLUS) model for the Yellow River Basin. Then, the landscape pattern index and habitat quality from 2005 to 2031 were evaluated using the Fragstats 4.2 and the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model. Furthermore, we analyzed the spatial distribution characteristics and spatial spillover effects of habitat quality using spatial autocorrelation analysis. Finally, the spatial association between the landscape pattern index and habitat quality was quantitatively revealed based on a spatial lag model. The simulation results showed that: (1) from 2005 to 2031, the landscape of the Yellow River Basin would be dominated by grassland and unused land, and the areas of construction land and water body will increase significantly, while the area of grassland will decrease; (2) patch density (PD) and Shannon's diversity index (SHDI) show significant increases, while edge density (ED), landscape shape index (LSI), mean patch area (AREA_MN), and contagion index (CONTAG) decrease; (3) from 2005 to 2031, habitat quality would decrease. The high-value areas of habitat quality are mainly distributed in the upper reaches of the Yellow River Basin, and the low-value areas are distributed in the lower reaches. Meanwhile, both habitat quality and its change rate present positive spatial autocorrelation; and (4) the spatial relationships of habitat quality with PD and COHESION are negative, while ED and LSI have positive impacts on habitat quality. Specifically, landscape fragmentation caused by high PD has a dominant negative influence on habitat quality. Therefore, this study can help decision makers manage future landscape patterns and develop ecological conservation policy in the Yellow River Basin.

Spatio-Temporal Evolution and Obstacle Factors Analysis of Tourism Ecological Security in Huanggang Dabieshan UNESCO Global Geopark.

The United Nations Educational, Scientific and Cultural Organization (UNESCO) Global Geoparks (UGGp) and geotourism activities not only improve people's scientific quality by popularizing geoscience knowledge, but also play important roles in protecting precious geoheritages and promoting the development of regional economies. However, tourism activities also have a negative impact on the local ecological environment, placing the regional ecological system under great pressure. Therefore, this paper constructed a tourism ecological security evaluation indicator system suitable for geoparks by using the "Driving-Pressure-State-Impact-Response" (DPSIR) model. The spatial autocorrelation and obstacle degree model are used to analyze the spatio-temporal characteristics and influencing factors of the tourism ecological security index (TESI) of Huanggang Dabieshan UGGp in 2000, 2005, 2010, 2015 and 2018, respectively. The results indicate that the TESI of the study area has gradually improved from 2000 to 2018. Spatially, the level of TESI presents a gradient distribution from the townships where the main scenic spots are located to the surrounding townships. The main obstacle factors affecting TESI include: per capita tourism income, proportion of comprehensive tourism revenue in GDP, per capita net income of rural residents, proportion of tertiary industry in GDP, coverage of nature reserves, planning integrity of geopark, informatization of geopark, growth rate of tourists, comprehensive utilization rate of solid waste, etc. The influencing factors of TESI varied from time to time. Balancing the conflict between local tourism activities and environmental protection, encouraging the participation of local communities, and strengthening science popularization for the local public will effectively improve the tourism ecological security of geoparks.

Increased Complement 3a Receptor is Associated with Behcet's disease and Vogt-Koyanagi-Harada disease.

Behcet's disease (BD) and Vogt-Koyanagi-Harada disease (VKH) are systemic and recurrent autoimmune diseases associated with abnormal T cell immune response. Complement 3a receptor (C3aR) and complement 5a receptor (C5aR) have been reported to be involved in T cell mediated autoimmune disease. This study aimed to investigate the role of C3aR and C5aR in these two diseases. The C3aR expression in PBMCs was increased in patients with active BD (aBD) and active VKH (aVKH). No statistical difference was found concerning the expression of C5aR in PBMCs between patients with aBD or aVKH and normal controls. After the intraocular inflammation in BD and VKH patients was controlled, the C3aR expression returned back to normal levels. The serum from patients with aBD and aVKH significantly induced C3aR expression by PBMCs. C3a induced IL-6, IL-1ß and TNF-α secretion, while inhibited the production of IL-10 by monocytes. Activation of C3aR in CD4+T cells could upregulate IL-17 production and inhibit IL-10 production, but had no detectable influence on IFN-γ production. Our data indicates that increased C3aR expression may lead to over activation of the Th17 cell response and may therefore contribute to the pathogenesis of BD and VKH disease.

Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.

Complement C5 Gene Confers Risk for Acute Anterior Uveitis.

PURPOSE: Polymorphisms in the genes encoding C3 and C5 are associated with several immune-mediated diseases. However, the association of C3 and C5 SNPs with acute anterior uveitis (AAU) has not yet been investigated and was the purpose of the study described. METHODS: Genotyping was performed for six SNPs in C3 and four SNPs in C5 in 395 AAU patients with ankylosing spondylitis (AS), 397 AAU patients without AS, and 597 healthy controls by PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assay. The mRNA expression was detected by real-time PCR. Cytokine production and total C5 serum concentrations were measured by ELISA. RESULTS: The frequency of the GG genotype of rs2269067 in C5 was increased in AAU patients with or without AS compared to controls (Pc = 4.0 × 10(-5), odds ratio [OR] = 1.94 and Pc = 9.4 × 10(-5), OR = 1.89, respectively). The mRNA and serum concentrations of C5 were significantly increased in rs2269067 GG cases as compared to that in CG or CC cases (P = 0.012, P = 0.002; P = 0.021, P = 0.006, respectively). An increased production of interleukin-17 was observed in rs2269067 GG cases compared to CG or CC cases (P = 5.1 × 10(-4), P = 1.4 × 10(-4), respectively). CONCLUSIONS: The C5 rs2269067 GG genotype confers risk for AAU in a Chinese population and is associated with an elevated C5 serum concentration and an increased IL-17 production.

High-Salt Enhances the Inflammatory Response by Retina Pigment Epithelium Cells following Lipopolysaccharide Stimulation.

High-salt has been shown to play a role in the pathogenesis of autoimmune disease. In this study, we investigated the effect of high-salt on the production of inflammatory mediators by ARPE-19 cells and the possible mechanisms involved. ARPE-19 cells were cultured with LPS in DMEM to which extra NaCl had been added (20 mM and 40 mM). NaCl had no influence on the apoptosis and proliferation of ARPE-19. Addition of 40 mM NaCl significantly induced IL-6 and MCP-1 production but had no effect on IL-8 secretion. High mannitol, as an osmotic stress control, did not affect the secretion of inflammatory mediators by ARPE-19 cells indicating that the effect was not mediated by osmolarity. Coculture of ARPE-19 cells with NaCl resulted in significant increases in the phosphorylation of p38 MAPK, Akt, and NF-κB and an upregulation of the transcription factors NFAT5 and SGK1. High-salt significantly promotes IL-6 and MCP-1 production by ARPE-19 cells and is associated with activation of the p38 MAPK, Akt, and NF-κB pathway and NFAT-SGK1 pathways.