Epigallocatechin-3-gallate increases autophagic activity attenuating TGF-ß1-induced transformation of human Tenon's fibroblasts.

We previously found that epigallocatechin-3-gallate (EGCG) could inhibit the myofibroblast transformation of human Tenon's fibroblasts, however, the underlying mechanism remained unclear. We therefore investigated whether the autophagic regulation involved in the anti-fibrotic function of EGCG. The fibroblasts were subjected to transforming growth factor beta-1 (TGF-ß1) induction followed by EGCG treatments. The autophagic flux was examined by transmission electron microscopy and autophagic flux analysis. The levels of autophagy-related proteins (LC3ß and p62) and alpha-smooth muscle actin (α-SMA) were measured by Western blot and immunofluorescence. Results showed that TGF-ß1 partially inhibited the autophagic function of Tenon's fibroblasts. But this inhibition effect was rescued by LY2157299, a TGF-ßR1 selective inhibitor. Compared with the cells treated with TGF-ß1 alone, EGCG treatments increased the amount of autophagosomes and autolysosomes, evaluated the ratio of LC3-II to LC3-I and decreased p62 level. Our results indicated that EGCG could recover the activity of autophagy in the TGF-ß1-treated cells. Moreover, treatments with EGCG significantly decreased the α-SMA expression. Taken together, these findings revealed that autophagic regulation involved in the action of EGCG against TGF-ß1-induced transformation of Tenon's fibroblasts. Through increasing intracellular autophagy, EGCG could be a potential anti-fibrotic reagent for preventing subconjunctival fibrosis after glaucoma filtration surgery.

Epigallocatechin-3-gallate (EGCG) inhibits myofibroblast transformation of human Tenon's fibroblasts.

Myofibroblast transformation of human Tenon's fibroblasts severely challenges the outcome of glaucoma filtration surgery. epigallocatechin-3-gallate (EGCG) is considered as a potential reagent to overcome this issue for its anti-fibrosis effect on various human diseases, but it is unclear on the fibrosis of Tenon's fibroblasts. This study was conducted to investigate the effect of EGCG on TGF-ß1-induced myofibroblast transformation of human Tenon's fibroblasts. The human Tenon's fibroblasts were incubated in the medium containing 10 ng/mL TGF-ß1, and subsequently treated with EGCG or mitomycin C (MMC). The cell proliferation and migration were analyzed. The expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col-I), and p-Smad2/3 were also evaluated. It showed that EGCG and MMC strongly inhibited the elevation in cell number in tissue explants compared to the tissues treated with TGF-ß1 alone. Scratch-Wound assay showed that 48 h after TGF-ß1 induction, only 10% of the wound width remained. But cells treated with EGCG still showed over 93% wound width. Further, EGCG effectively inhibited TGF-ß1-induced expression of α-SMA and Col-I as well as phosphorylation of Smad2/3 in Tenon's fibroblasts. Altogether, we concluded that EGCG suppressed the myofibroblast transformation in Tenon's fibroblasts through inactivating TGF-ß1/Smad signaling. These findings demonstrate that EGCG can be considered as one of the possible antifibrotic reagents for preventing postoperative scarring in glaucoma filtration surgery.

Elevated level of uric acid in aqueous humour is associated with posterior subcapsular cataract in human lens.

IMPORTANCE: Age-related cataract is the leading cause of blindness worldwide. The pathological mechanisms causing this disease remain elusive. BACKGROUND: To examine the involvement of uric acid (UA) in the pathogenesis of posterior subcapsular cataract (PSC). DESIGN: Retrospective study and experimental investigation. PARTICIPANTS: A total of 180 patients with PSC or non-PSC were included. METHODS: Samples obtained from the patients were used to analyse content of UA and for histochemical examinations. The effects of UA on human lens epithelial cells were also investigated. MAIN OUTCOME MEASURES: Aqueous humour UA and urate deposits. RESULTS: The results showed a significant increase of aqueous humour UA in patients with PSC. After adjustment for potential confounders, elevated aqueous humour UA (odds ratio [OR] = 1.45) showed a stronger association with PSC than serum UA (OR = 1.10). Gomori methenamine silver staining revealed in PSC an intense deposit of urates in the lens fibres in equatorial regions, and in subcapsular fibres in posterior regions of the lens. Such staining was not detected in the lens with non-PSC. Treatment with UA-induced senescence and apoptosis in human lens epithelial cells in a dose dependent manner. Our results suggest that the elevated level of UA in aqueous humour causes a deposition of urates in human lens epithelium, which could possibly lead to dysfunction of these cells that generates opacification in PSC. CONCLUSIONS AND RELEVANCE: These findings indicate the local action of excessive UA in the pathogenesis of PSC. Control of serum UA level could delay the progression of PSC.

Investigation of self-reported chronic urticaria among adults in grasslands of northern China.

The clinical epidemiological characteristics of chronic urticaria (CU) in different populations were not completely consistent, and the epidemiological characteristics of CU were very complex. At present, there were some patient-based studies on CU, but few natural population-based studied in the world.This study aimed to analysis the prevalence of self-reported CU among adults in grasslands of northern China and its closely related factors.A multistage and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.A total of 3406 subjects completed the study. The prevalence of self-reported CU was 5.61% (n = 191), which was higher in women than that of men (6.91% vs 4.08%, X = 12.785, P < .001). Seasonal or seasonal aggravation CU accounted for 110 (57.59%) patients. Pollen dispersal season was basically consistent with the peak season of CU, but there was no significant difference in the positive rate of pollen SPT between CU with seasonal or seasonal aggravation symptom and CU with free of symptom (X = 0.425, P = .51), as well as between CU with seasonal or seasonal aggravation symptom and perennial CU (X = 0.439, P = .51). Eczema (odds ratio [OR] = 2.807, P < .001), chronic diarrhea (OR = 2.486, P < .01), food allergy history (OR = 1.890, P < .01), history of family allergy (OR = 1.800, P < .001), and conjunctivitis (OR = 1.749, P < .01) were closely related to CU.This investigation provided the factors closely related to CU, and provided certain ideas for further research on the etiology and prevention of CU.

Comparisons of Ocular Anatomic Differences of Lens-Subluxated Eye with or without Acute Angle Closure: A Retrospective Study.

PURPOSE: To compare ocular anatomy differences of lens subluxation between eyes with or without acute angle closure (AAC). METHODS: This is a retrospective and case-control study. Sixty cases with mild lens subluxation were recruited. Among them, 30 eyes with acute angle closure were assigned to the AAC group and 30 eyes without AAC were assigned to the non-AAC group. The anterior segment was quantitatively evaluated by ultrasound biomicroscopy (UBM). The axial length (AL) was measured with IOL Master. All patients underwent lens extraction surgery and were followed up for six months. RESULTS: The history of blunt trauma accounted for 22 (73.3%) cases in the AAC group and 21 (70%) cases in the non-AAC group. Fifteen (50%) patients in the AAC group had iridotomy history, and high intraocular pressure recurred. The UBM analysis showed that the average central chamber depth of the affected eyes in the AAC group was 1.82 mm, which was significantly shallower than that in the fellow eyes (2.58 mm, P < 0.05) or both eyes in the non-AAC group.Both eyes in the AAC group presented a shorter AL and shallower anterior chamber than the eyes in the non-AAC group. CONCLUSIONS: An asymmetrical anterior chamber between bilateral eyes is an important feature in lens subluxation-induced AAC. The crowded anterior chamber and shorter AL might be the anatomic basis for the eye with lens subluxation-induced AAC.

Clinical Efficacy Evaluation of 1-Year Subcutaneous Immunotherapy for Artemisia sieversiana Pollen Allergic Rhinitis by Serum Metabolomics.

Subcutaneous immunotherapy is the only treatment that improves the natural progression of allergic rhinitis and maintains long-term outcomes after discontinuation of the drug. Metabolomics is increasingly applied in the study of allergic diseases, including allergic rhinitis. However, little is known about the discovery of metabolites that can evaluate clinical efficacy and possible mechanisms of Artemisia sieversiana pollen subcutaneous immunotherapy. Thirty-three patients with Artemisia sieversiana pollen allergic rhinitis significantly improved after 1-year subcutaneous immunotherapy treatment, while ten patients were ineffective. Pre- and post-treatment serum samples from these patients were analyzed by metabolomics based on the combined detection of liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. As a result, L-Tyrosine can be a potential biomarker because of its opposite trend in effective patients and ineffective patients. And mechanism of immunotherapy may be closely related to NO and nitric oxide synthase. The discovery of potential biomarkers and metabolic pathways has contributed to the in-depth study of mechanisms of subcutaneous immunotherapy treatment of Artemisia sieversiana pollen allergic rhinitis.

Antibiotic overuse and allergy-related diseases: an epidemiological cross-sectional study in the grasslands of Northern China.

BACKGROUND: Several studies have shown that the use of antibiotics early in life significantly increases the risk of asthma in children. It is unclear whether antibiotics are more commonly used in patients with allergy-related diseases. METHODS: A multistage, clustered and random sampling with a field-interviewer-administrated survey study was performed to investigate if there was multiple use of antibiotics (MUA) in patients with allergic rhinitis (AR), conjunctivitis, chronic urticaria (CU), and asthma in the grasslands of northern China. MUA was defined as antibiotic usage for at least 3 days and for more than 3 times a year in the past 2 years. RESULTS: A total of 5,787 subjects completed the study, with 1,079 subjects (18.6%) identified as MUA. MUA was more common in patients with AR (23.7% vs 16.2%, P<0.001), conjunctivitis (22.5% vs 17.1%, P<0.001), asthma (31.8% vs 17.7%, P<0.001), and CU (25.9% vs 18.3%, P<0.01) than in subjects without allergic diseases. There is an increasing percentage of MUA in patients with a single, two, and three or more diseases both in children (20.1%, 25.0%, and 31.4%, respectively, P=0.014) and in adults (19.1%, 23.4%, and 32.9%, respectively, P<0.001). MUA is significantly associated with AR (OR=1.7, 95% CI: 1.3-2.1, P<0.001), conjunctivitis (OR=1.6, 95% CI: 1.2-2.1, P=0.001), asthma (OR=2.3, 95% CI:1.6-3.3, P<0.001) and CU (OR=2.1, 95% CI: 1.2-3.6, P=0.006) in children aged 2-17 years; and in adults (≥18 years old) for AR (OR=1.7, 95% CI: 1.4-2.1, P<0.001), conjunctivitis (OR=1.3, 95% CI:1.1-1.6, P=0.002), and asthma (OR=2.0, 95% CI: 1.5-2.7, P<0.001). CONCLUSION: Antibiotic overuse might be associated with increased risk of allergy-related disease. It is important that implementation of the evidence-based international guidelines for the management of allergy-related diseases needs to be improved, in order to avoid unnecessary use of antibiotics.