NLRP3 inflammasome activation By 17ß-estradiol is a potential therapeutic target in hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it mostly arises as a consequence of persistent chronic inflammation. Recently, NLRP3 inflammasome has caught the attention of many research groups due to its involvement in different types of cancer. However, its direct role in HCC remains elusive. Our study aimed to evaluate the role of NLRP3 inflammasome and pyroptosis in HCC and to clarify the potential mechanism by which 17ß-estradiol (E2) can be used as a protective factor against HCC. NLRP3, caspase-1 (CASP1) as well as gasdermin-D (GSDMD) mRNA expression levels were assessed in human HCC tissues and adjacent non-cancerous liver tissues. Also, HepG2 HCC cells were cultured and treated with E2, followed by detection of the mRNA levels of these three genes. Our results revealed that NLRP3, CASP1, and GSDMD mRNA expressions were significantly lower in HCC tissues than in controls, and this under-expression was closely correlated with advanced HCC stages and grades. In contrast, HepG2 HCC cells displayed significantly higher expression levels of NLRP3 inflammasome components and GSDMD in the two E2-treated groups compared to the untreated group. Also, NLRP3, CASP1, and GSDMD mRNA expression levels were positively correlated with each other. This study confirmed that lack of NLRP3 inflammasome is involved in HCC progression and 17ß-estradiol-induced activation of NLRP3 inflammasome may be effective in HCC treatment as it inhibited tumor cell growth and proliferation by triggering CASP1-dependent pyroptosis in HCC cells.

Ghrelin Levels in Patients With Primary Open-Angle Glaucoma.

PURPOSE: This study was aimed to assess the levels of ghrelin in aqueous humor and plasma of human eyes with primary open-angle glaucoma (POAG) and to correlate their concentrations with the severity of glaucoma. DESIGN: This was a case-control, prospective study. METHODS: Fifty patients with POAG and 35 patients with senile nonpathologic cataract (control group) were enrolled in the study prospectively. Aqueous humor samples were obtained by paracentesis from patients with glaucoma and cataract who underwent elective surgery. Aqueous humor and corresponding plasma samples were analyzed for ghrelin concentrations by radioimmunoassay diagnostic kits assay. RESULTS: Ghrelin levels were significantly lower in aqueous humor of patients with POAG with respect to the comparative group of patients with cataract (P < 0.001). There was no significant difference in the levels of ghrelin in the plasma of patients with POAG and that of patients with cataract. A positive correlation was found between plasma/aqueous humor ghrelin concentration in patients with POAG versus the control group (P < 0.001). No significant correlation was found between the levels of ghrelin and the severity of visual field loss. CONCLUSIONS: Lower levels of aqueous humor ghrelin may be associated with POAG and may be a consequence of glaucomatous damage.

Homocysteine and hydroxyproline levels in patients with primary open-angle glaucoma.

AIM: To assess the levels of homocysteine (Hcy) and hydroxyproline (Hyp) in aqueous humor and plasma of human eyes with primary open-angle glaucoma (POAG) and to correlate their concentrations with the severity of glaucoma. METHODS: Fifty patients with POAG and 35 patients with senile cataract (control group) were enrolled in the study prospectively. Aqueous humor samples were obtained by paracentesis from glaucoma and cataract patients who were undergoing elective surgery. Aqueous humor and corresponding plasma samples were analyzed for Hcy and Hyp concentrations by high-performance liquid chromatography and spectrometry, respectively. RESULTS: Hcy and Hyp levels were significantly higher in aqueous humor of POAG patients with respect to the comparative group of cataract patients (p < 0.001). No significant difference in the levels of Hcy and Hyp in plasma of POAG and cataract patients. A positive correlation was found between Hcy and Hyp in aqueous humor of POAG patients (p < 0.001). No significant correlation was found between either Hcy or Hyp levels and the severity of visual field loss. CONCLUSION: Increased levels of aqueous humor Hcy and Hyp may be associated with POAG. In addition, Hcy and Hyp may be useful protein levels in aqueous humor of POAG patients as a consequence of glaucomatous damage.

Connective tissue growth factor and tissue inhibitor of matrix metalloproteinase-2 in patients with exfoliative glaucoma.

PURPOSE: To investigate the aqueous humor levels of connective tissue growth factor (CTGF), matrix metalloprotinease-2 (MMP-2), and tissue inhibitor of matrix metalloprotinease-2 (TIMP-2) in human eyes with exfoliative glaucoma, primary open-angle glaucoma, and senile cataract patients. PATIENTS AND METHODS: This was a prospective, comparative study. Sixty patients with glaucomas and 25 patients with senile cataract of matched age and gender were enrolled in this study. Patients were classified into three groups: group I comprised 30 patients with exfoliative glaucoma (XFG), group II comprised 30 patients with primary open-angle glaucoma (POAG), and group III comprised 25 patients with senile cataract (controls). Aqueous humor samples were obtained by paracentesis at the time of elective surgery for glaucomatous and cataractous patients. CTGF, MMP-2, and TIMP-2 were measured in aqueous humor by specific enzyme linked immunosorbent assay (ELISA) kits, and total aqueous humor protein content was assessed by the Lowry method. RESULTS: There were significant increases in aqueous humor levels of CTGF and TIMP-2 in XFG patients compared to the corresponding values of POAG patients or controls. The MMP-2 aqueous humor level was significantly increased in the XFG patients when compared with controls (P < 0.001). Moreover, the total protein level in the aqueous humor of eyes of the XFG patients was significantly higher than in POAG patients or controls (P < 0.001). A positive correlation was found between CTGF and MMP-2 in aqueous humor samples of XFG patients (P < 0.001). CONCLUSION: Increased levels of aqueous humor of CTGF and TIMP-2 may promote the abnormal extracellular matrix accumulation and may be involved in the pathogenesis of XFG.

Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy.

PURPOSE: Advanced glycation end products (AGEs) accumulation may result from chronic hyperglycemia promoting generation and onset of microangiopathy. The aim of this study was to investigate the association between diabetic retinopathy (DR) and levels of AGEs, pentosidine, and N-carboxymethyl-lysine (CML) in aqueous humor and serum of human patients and their role in predicting the progression of DR. METHODS: Ninety patients with type 2 diabetes mellitus and 30 nondiabetic patients underwent cataract surgery. The diabetic group was divided into 3 subgroups: 35 patients with mild nonproliferative diabetic retinopathy (mild NPDR), 30 patients with severe nonproliferative diabetic retinopathy (severe NPDR), and 25 patients with proliferative diabetic retinopathy (PDR). In the samples, pentosidine was measured by high-performance liquid chromatography and CML using a competitive enzyme-linked immunosorbent assay. RESULTS: Serum levels of pentosidine and CML were significantly increased in patients with type 2 diabetes compared to nondiabetic controls (p<0.001). In diabetic patients, serum pentosidine and CML levels were significantly higher in patients who had PDR than in those with mild NPDR or severe NPDR (both p<0.001). A significant difference was found between aqueous humor CML levels in diabetic and nondiabetic patients and increased along with progression of DR. Significant correlations existed between serum pentosidine and aqueous CML in severe NPDR and PDR (p<0.001). CONCLUSIONS: In patients with type 2 DM, serum levels of pentosidine and CML are related to severity of retinopathy. In addition, aqueous humor level of CML increased along with progression of DR. Pentosidine and CML can be used as biochemical markers of glycoxidation and related to onset or progression of DR.

Erythropoietin and soluble CD44 levels in patients with primary open-angle glaucoma.

PURPOSE: To investigate the levels of erythropoietin (EPO) and soluble CD44 (sCD44) in the aqueous and plasma of human eyes with primary open-angle glaucoma (POAG), and to correlate their concentration with severity of glaucoma. METHODS: A total of 30 patients with POAG and 25 patients with senile cataract (control group) of matched age and gender were included in the study prospectively. Aqueous samples were obtained by paracentesis from glaucoma and cataract patients who were undergoing elective surgery. Aqueous and corresponding plasma samples were analysed for EPO and sCD44 concentrations by enzyme-linked immunosorbent assay. RESULTS: The EPO and sCD44 levels were significantly higher in aqueous of POAG patients with respect to the comparative group of cataract patients (P < 0.001). No significant difference in the levels of EPO and sCD44 in plasma of POAG and cataract patients. A high positive correlation was found between EPO and sCD44 in aqueous of POAG patients (P < 0.001). Significant correlation was found between EPO or sCD44 levels and severity of visual field loss in mild and moderate stages (P < 0.001). CONCLUSION: Increased levels of aqueous EPO and sCD44 may be associated with POAG. In addition, EPO and sCD44 may be useful proteins levels in aqueous of POAG patients as a result of glaucoma damage and not a cause. EPO and sCD44 concentrations in aqueous are a possible biomarkers for visual field loss in patients with POAG.

Oxidative stress markers in patients with primary open-angle glaucoma.

PURPOSE: To investigate the levels of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPO), superoxide dismutase (SOD), and malondialdehyde (MDA) in human eyes with primary open-angle glaucoma (POAG) and to correlate their concentrations with severity of glaucoma. DESIGN: A prospective cases control study. PATIENTS AND METHODS: Thirty patients with primary open-angle glaucoma and twenty-five patients with senile cataracts of matched age and gender were included in the study prospectively. Aqueous humor samples were obtained by paracentesis at the time of elective surgery for glaucomatous and cataractous patients. Aqueous humor were analyzed for CAT, GPO, SOD, and MDA status. RESULTS: GPO, SOD, and MDA enzyme levels revealed a high significant increase in aqueous humor of POAG patients with respect to the comparative group of cataract patients (P < 0.001). No significant difference in the activity of CAT enzyme in aqueous humor of POAG and cataract patient (P = 0.201). Significant correlation was found between the MDA enzyme level and severe visual field loss (P < 0.001) in POAG patients. CONCLUSION: Increased levels of aqueous humor GPO, SOD, and MDA may be associated with POAG. In addition, they may be useful antioxidant enzyme levels in aqueous humor of POAG patients as a result of glaucoma disease and not a cause.

Lens cadmium, lead, and serum vitamins C, E, and beta carotene in cataractous smoking patients.

PURPOSE: To investigate the association between smoking and subcapsular cataract and blood levels of cadmium and lead, and serum levels of vitamins C, E, and beta carotene in the middle-age male population. SUBJECTS AND METHODS: The present study comprised 60 cataractous male patients aged 44-55 years who attended Mansoura University Ophthalmic Center. They were divided into two groups: the first group was comprised of 15 patients who had never smoked before with minimal exposure to cigarette smoking (control group), while the second group was comprised of 45 age and body mass index-matched smokers. Blood cadmium and lead concentrations were measured and their levels in the cataractous lenses were also estimated. The levels of some antioxidants, such as serum vitamins C, E, and beta carotene, were determined. RESULTS: Cadmium had a statistically significant higher concentration in blood and lenses of smokers compared with that of non smokers (p < 0.0001). There was a significantly high accumulation of cadmium in the lenses of cataractous smokers reaching about a four-fold increase in heavy smokers (15.4 +/- 0.4 micromol/g) and nearly a three-fold increase in light smokers (10.1 +/- 0.4 micromol/g) when compared to that of nonsmokers (3.7 +/- 0.9 micromol/g). Regarding vitamins E, C, and beta carotene, a highly significant reduction was observed in smokers when compared with nonsmokers. There was a highly positive correlation between blood cadmium concentrations and lens cadmium levels, and blood lead concentrations and lens lead levels in heavy smokers. CONCLUSION: Cadmium present in high concentrations among smokers was associated with the presence of cataracts, through induction of oxidative stress as evidenced by reduction of levels of some antioxidant studied in this work, such as vitamins E, C, and beta carotene. Thus, education of health care professionals and the public about the cataractogenic effect of cadmium is mandatory. Intake of various antioxidants may be helpful in reducing the risk of cataract formation.