Switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration: 1-year outcomes.

This study aimed to elucidate 1-year outcomes following switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration (wAMD). In this prospective, open-label, non-controlled clinical trial, 18 patients with wAMD who had multiple recurrences or persistent exudation despite intravitreal injections of anti-vascular endothelial growth factor agents (except aflibercept) received a 3-mg intravitreal aflibercept injection every 4 weeks. Each patient received 3 to 8 injections. The central retinal thickness and fibrovascular pigment epithelial detachment height decreased significantly at 1 month after initiation of the aflibercept injection, and the values were 146 and 163.2 µm, respectively, at the final visit. The morphological improvement was sustained. The intraretinal and subretinal fluid was completely absorbed at the end of the follow-up. The logMAR vision increased from baseline 0.68 to 0.59 (P < .05). No ocular or systemic adverse events occurred. The intravitreal injection of 3-mg aflibercept seems to be feasible in the treatment of wAMD unresponsive to other anti-vascular endothelial growth factor agents.

Moisture Property and Thermal Behavior of Two Novel Synthesized Polyol Pyrrole Esters in Tobacco.

To overcome the shortcomings of high relative humidity and harmful oxidation products from traditional humectants, excellent humectants and flavor precursors were reported herein. Glucosamine hydrochloride was used as the starting material for the cyclization, oxidation, and alkylation processes that produced pyrrole acid. Then, esterification occurred with polyol catalyzed by EDC and DMAP to give the target compounds 2-(2,3-dihydroxypropyl) 4-methyl 5-methyl-1-propyl-1H-pyrrole-2,4-dicarboxylate (Gpe) and (2-hydroxypropyl) 4-methyl 5-methyl-1-propyl-1H-pyrrole-2,4-dicarboxylate (Ppe). Nuclear magnetic resonance (1H NMR, 13C NMR), infrared spectroscopy (IR), and high-resolution mass recorded spectrometry (HRMS) were used to confirm the two novel polyol pyrrole ester compounds. When Gpe and Ppe were added to the tobacco shred, low-field nuclear magnetic resonance (LF-NMR) imaging was applied to assess the hygroscopicity and moisturizing capacity. Furthermore, thermogravimetry (TG) and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) techniques were applied to study their thermal behaviors. These results showed that the target compounds (Gpe and Ppe) are good humectants with thermal properties of high-temperature stability and flavor release.

A catalytic hairpin assembly-based Förster resonance energy transfer sensor for ratiometric detection of ochratoxin A in food samples.

Ochratoxin A (OTA) poses severe risks to the environment and human health, making the development of an accurate and sensitive analytical method for OTA detection essential. In this study, a catalytic hairpin assembly (CHA)-based Förster resonance energy transfer (FRET) aptasensor was developed to detect OTA using carbon quantum dots (CDs) and 6-carboxy-fluorescein (FAM) as dual signal readout. In the presence of OTA, the aptamer specifically interacted with OTA to release the helper DNA (HP), which could open the hairpin structure of FAM-labeled hairpin DNA 1 (H1-FAM) modified on the surface of gold nanoparticles (AuNPs). CHA between H1-FAM and hairpin H2 labeled with CDs (H2-CDs) can release HP for the next cycle, resulting in the occurrence of FRET with CDs as the energy donor and FAM as the energy acceptor. According to the ratio of FCDs/FFAM, the proposed aptasensor showed a wide linear range from 5.0 pg/mL to 3.0 ng/mL and a low detection limit of 1.5 pg/mL for OTA detection. Moreover, satisfactory results were obtained for OTA detection in rice, suggesting the potential application of this sensor in food safety analysis.

Critical roles of RGS16 in the mucosal inflammation of ulcerative colitis.

BACKGROUND: Ulcerative colitis is a chronic and progressive inflammatory disorder. The regulator of the G-protein signaling (RGS) is involved in the pathogenesis of several immune system disorders. RGS16, a member of the RGS protein superfamily, has been shown to play critical roles in several immune system-related diseases. However, the roles of RGS16 in ulcerative colitis remain to be elucidated. METHODS: We analyzed the expression of RGS16 in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa of ulcerative colitis patients using quantitative reverse transcription-PCR, western blotting and immunohistochemistry. We performed Spearman's correlation to analyze the correlation between RGS16 expression and the ulcerative colitis endoscopic index of severity (UCEIS), Mayo index, erythrocyte sedimentation rate (ESR) and serum tumor necrosis factor alpha (TNF-a) and IL-17A levels. Further, PBMCs were stimulated with inflammatory cytokines in vitro . RESULTS: RGS16 expression significantly increased in the colonic mucosa and PBMCs from patients with ulcerative colitis and significantly correlated with the Mayo index, UCEIS, ESR and serum TNF-α and IL-17A levels. TNF-α upregulated RGS16 expression in PBMCs in a dose- and time-dependent manner via the nuclear factor kappa beta (NF-kB) signaling pathway. Moreover, anti-TNF treatment with infliximab significantly decreased RGS16 expression in PBMCs and intestinal mucosa of patients with ulcerative colitis. CONCLUSION: Our study revealed a novel mechanism by which RGS16 expression in ulcerative colitis is positively correlated with disease activity. Thus, RGS16 might serve as a potential therapeutic marker for the treatment of ulcerative colitis.

Nicotinamide suppresses bevacizumab-induced epithelial-mesenchymal transition of ARPE-19 cells by attenuating oxidative stress.

AIM: To investigate the effects of nicotinamide (NAM) on bevacizumab (BEV)-induced epithelial-mesenchymal transition (EMT) of human retinal pigment epithelial cells (ARPE-19) and the underling mechanisms. METHODS: ARPE-19 cells were treated with BEV for 24, 48, and 72h, and the variation degrees of EMT-related markers (fibronectin, α-SMA, vimentin, and ZO-1) were assessed by Western blotting to select the optimal treatment time point which exhibited the most obvious changes of EMT-related markers for the subsequent experiments. Furthermore, NAM was added to the medium, the mRNA and protein levels of the EMT-related markers were then measured. The accumulation of reactive oxygen species (ROS) and H2O2 and the total antioxidant capacity (TAC) of the cells were also measured to evaluate the level of oxidative stress. RESULTS: After being treated with BEV for 72h, the protein expression levels of EMT-related markers in ARPE-19 cells showed significant changes. Meanwhile the levels of ROS and H2O2 were obviously increased, and the TAC of ARPE-19 cells was decreased. Totally 72h was chosen to be the optimal treatment time point in subsequent experiments. Furthermore, NAM inhibited BEV-induced EMT by downregulating fibronectin, α-SMA, and vimentin and upregulating ZO-1, decreased the accumulation of ROS and H2O2, and enhanced TAC in BEV-treated ARPE-19 cells. CONCLUSION: This study demonstrates that NAM suppressed BEV-induced EMT in ARPE-19 cells by attenuating oxidative stress. Hence, NAM may be a potential therapeutic agent for alleviating neovascular fibrosis of the ocular fundus after anti-vascular endothelial growth factor therapy.

LRG1 promotes epithelial-mesenchymal transition of retinal pigment epithelium cells by activating NOX4.

AIM: To investigate the effect of leucine-rich-alpha-2-glycoprotein 1 (LRG1) on epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells, and to explore the role of NADPH oxidase 4 (NOX4). METHODS: RPE cells (ARPE-19 cell line) were treated with transforming growth factor-ß1 (TGF-ß1) to induce EMT. Changes of the mRNA and protein expression levels of LRG1 were tested in the TGF-ß1 treated cells. The recombinant human LRG1 protein (rLRG1) and siRNA of LRG1 were used to establish accumulation of exogenous LRG1 model and the down-regulation of LRG1 model in ARPE-19 cells respectively, and to detect EMT-related markers including fibronectin, α-smooth muscle actin (α-SMA) and zonula occludens-1 (ZO-1). The mRNA and protein expression level of NOX4 were measured according to the above treatments. VAS2870 was used as a NOX4 inhibitor in rLRG1-treated cells. EMT-related markers were detected to verify the effect of NOX4 in the process of EMT. RESULTS: TGF-ß1 promoted the expression of LRG1 at both the mRNA and protein levels during the process of EMT which showed the up-regulation of fibronectin and α-SMA, as well as the down-regulation of ZO-1. Furthermore, the rLRG1 promoted EMT of ARPE-19 cells, which manifested high levels of fibronectin and α-SMA and low level of ZO-1, whereas knockdown of LRG1 prevented EMT by decreasing the expressions of fibronectin and α-SMA and increasing the expression of ZO-1 in ARPE-19 cells. Besides, the rLRG1 activated and LRG1 siRNA suppressed NOX4 expression. EMT was inhibited when VAS2870 was used in the rLRG1-treated cells. CONCLUSION: These results for the first time demonstrate that LRG1 promotes EMT of RPE cells by activating NOX4, which may provide a novel direction to explore the mechanisms of subretinal fibrosis.

Anion exchange induced tunable catalysis properties of an uncommon butterfly-like tetranuclear copper(II) cluster and magnetic characterization.

An uncommon butterfly-like tetranuclear copper(ii) cluster with the formula {[Cu(4)(µ(3)-OH)(2)(µ(4)-Cl)(H(2)O)(2)(L)(2)]·Cl(H(2)O)(7)}(n) (1) (H(2)L = 1,2-bis[3-(1,2,4-triazolyl)-4-amino-5-carboxylmethylthio]ethane) has been synthesized. Compound 1 exhibits interesting anion exchange characteristics, in which both guest and coordinated Cl(-) can be replaced by I(-) or NO(3)(-) in water. Furthermore, a high catalytic selectivity to produce poly(phenylene ether) by the oxidative coupling of 2,6-dimethylphenol in water is found to be 74% for 1 and 87% for the anion-exchanged product 1-MI(x), respectively. Additionally, the antiferromagnetic interaction among Cu ions for compound 1 is also found.