Honokiol Attenuates Choroidal Neovascularization by Inhibiting the Hypoxia-Inducible Factor-α/Vascular Endothelial Growth Factor Axis via Nuclear Transcription Factor-Kappa B Activation.

PURPOSE: Honokiol is a lignan isolated from Magnolia officinalis and exhibits anti-angiogenic properties. This study was conducted to investigate the role of honokiol in choroidal neovascularization. METHODS: C57BL/6 mice were treated with honokiol at 10-20 mg/kg by daily intraperitoneal injection from day 1 to 6 after laser photocoagulation. ARPE-19 cells were cultured under hypoxic conditions with or without the presence of honokiol. After laser photocoagulation and honokiol treatment, hematoxylin and eosin staining, immunofluorescence and fundus fluorescein angiography were used to analyze the effect of honokiol on choroidal neovascularization formation. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay, immunofluorescence, luciferase assay, and chromatin immunoprecipitation were performed to explore the mechanism of honokiol in the pathological process of choroidal neovascularization. Finally, the role of honokiol on the human choroidal vascular endothelial cells was detected by using 5-ethynyl-20-deoxyuridine assay, Transwell and Tube formation assays. RESULTS: The results of hematoxylin and eosin staining and immunofluorescence suggested that honokiol reduced the thickness, length, and area of choroidal neovascularization lesions in laser-induced choroidal neovascularization mouse model. Fundus fluorescein angiography showed that choroidal neovascularization leakage was reduced in honokiol group and the concentration of 20 mg/kg showed better effects. Mechanism studies have shown that honokiol exerted inhibitory effects on choroidal neovascularization by inactivating hypoxia-inducible factor-1α/vascular endothelial growth factor axis through the nuclear transcription factor-kappa B signaling pathway. The same results were obtained in ARPE-19 cells under hypoxic conditions. Furthermore, the conditional medium of retinal pigmented epithelial cells promoted the proliferation, migration, and tube formation of human choroidal vascular endothelial cells, while honokiol reversed these. CONCLUSION: We demonstrated that honokiol attenuated choroidal neovascularization formation by inactivating the hypoxia-inducible factor-1α/vascular endothelial growth factor axis through nuclear transcription factor-kappa B signaling pathway.

Joint Effect of Multiple Metals on Hyperuricemia and Their Interaction with Obesity: A Community-Based Cross-Sectional Study in China.

Metal exposures have been inconsistently related to the risk of hyperuricemia, and limited research has investigated the interaction between obesity and metals in hyperuricemia. To explore their associations and interaction effects, 3300 participants were enrolled from 11 districts within 1 province in China, and the blood concentrations of 13 metals were measured to assess internal exposure. Multivariable logistic regression, restricted cubic spline (RCS), Bayesian kernel machine regression (BKMR), and interaction analysis were applied in the single- and multi-metal models. In single-metal models, five metals (V, Cr, Mn, Co, and Zn) were positively associated with hyperuricemia in males, but V was negatively associated with hyperuricemia in females. Following the multi-metal logistic regression, the multivariate-adjusted odds ratios (95% confidence intervals) of hyperuricemia were 1.7 (1.18, 2.45) for Cr and 1.76 (1.26, 2.46) for Co in males, and 0.68 (0.47, 0.99) for V in females. For V and Co, RCS models revealed wavy and inverted V-shaped negative associations with female hyperuricemia risk. The BKMR models showed a significant joint effect of multiple metals on hyperuricemia when the concentrations of five metals were at or above their 55th percentile compared to their median values, and V, Cr, Mn, and Co were major contributors to the combined effect. A potential interaction between Cr and obesity and Zn and obesity in increasing the risk of hyperuricemia was observed. Our results suggest that higher levels of Cr and Co may increase male hyperuricemia risk, while higher levels of V may decrease female hyperuricemia risk. Therefore, the management of metal exposure in the environment and diet should be improved to prevent hyperuricemia.

Association of multi-metals with the risk of hypertension and the interaction with obesity: A cross-sectional study in China.

Background: Environmental exposure to multiple metals have been inconsistently associated with hypertension. Obesity is an important independent risk factor for hypertension, and few studies have assessed the interaction between obesity and metals in this context. We aimed to clarify their association and interaction. Methods: This cross-sectional study included 3,063 adults from 11 districts or counties, Guangdong. We measured the whole blood levels of 13 metals and used multipollutant-based statistical methods to analyze the association of metals with hypertension. The interaction between metals and obesity on hypertension was assessed on additive and multiplicative scales. Results: Four metals (manganese, arsenic, cadmium, and lead) were significantly associated with hypertension risk, five metals (manganese, zinc, arsenic, cadmium, and lead) were related to elevated SBP levels, five metals (manganese, zinc, selenium, cadmium, and lead) were associated with elevated DBP levels in single-metal model. Manganese remained significantly related to hypertension risk [odds ratio, 1.35 (1.02-1.78)] after adjusting for these four metals. Significant positive dose-response relationships between manganese, arsenic, cadmium, lead and hypertension risk were observed (P for overall < 0.001, P for non-linearity > 0.05). Compared with those in the lowest quartile, participants in the highest manganese quartile had a 2.83 mmHg (95% Cl: 0.71-4.96) (P FDR = 0.040) higher level of SBP. Individuals in the highest quartiles of zinc and lead had a 1.45 mmHg (0.10-2.81) (P FDR = 0.033) and 2.06 mmHg (0.59-3.53) (P FDR = 0.020) higher level of DBP, respectively. The negative interactions between cadmium, lead and obesity influences hypertension risk. BKMR analysis showed a significant joint effect of manganese, arsenic, cadmium and lead on hypertension when the concentrations of four metals were at or above their 55th percentile compared to their median values. Conclusions: The combined effect of four metals (manganese, arsenic, cadmium and lead) were associated with the prevalence of hypertension. Potential interaction effects of cadmium, lead and obesity on hypertension risk may exist. Further cohort studies in larger population are needed to clarify these findings.

Bioinformatic analysis and antiviral effect of Periplaneta americana defensins.

Due to the lack of an adaptive immune system, insects rely on innate immune mechanisms to fight against pathogenic infections. Two major innate immune pathways, Toll and IMD, orchestrate anti-pathogen responses by regulating the expression of antimicrobial peptide (AMP) genes. Although the antifungal or antibacterial function of AMPs has been well characterized, the antiviral role of AMPs in insects remains largely unclear. Periplaneta americana (P. americana), or the American cockroach, is used in traditional Chinese medicine as an antiviral agent; however, the underlying mechanism of action of P. americana extracts is unclear. Our previous study showed that the P. americana genome encodes multiple antimicrobial peptide genes. Based on these data, we predicted five novel P. americana defensins (PaDefensins) and analyzed their primary structure, secondary structure, and physicochemical properties. The putative antiviral, antifungal, antibacterial, and anticancer activities suggested that PaDefensin5 is a desirable therapeutic candidate against viral diseases. As the first experimental evidence of the antiviral effects of insect defensins, we also showed the antiviral effect of PaDefensin5 in Drosophila Kc cells and Drosophila embryos in vivo . In conclusion, results of both in silico predictions and subsequent antiviral experiments suggested PaDefensin5 a promising antiviral drug.

A novel multi-stimuli responsive gelator based on D-gluconic acetal and its potential applications.

We construct a simple-structured super gelator with multi-stimuli responsive properties, among which anion responsiveness follows the Hofmeister series in a non-aqueous system. Versatile applications such as being rheological and self-healing agents, waste water treatment, spilled oil recovery and flexible optical device manufacture are integrated into a single organogelator, which was rarely reported.