Implication of miRNA-153 on PTEN expression in prostatic adenocarcinoma.

OBJECTIVE: A little is known about the role of miRNA-153 expression in prostate cancer (PCa), in this study we aimed to determine the prognostic value of miRNA-153 and PTEN expression in PCa, by correlating their expression with Gleason patterns, Gleason scores, and Grade groups. PATIENTS AND METHODS:  In situ hybridization for miRNA-153 and immunohistochemical staining for PTEN were applied on microarray sections of 80 PCa, with different Gleason grades, and 20 benign prostate hyperplasia (BPH) cases. RESULTS: We found that miRNA-153 expression was significantly higher and PTEN was significantly lower in PCa compared to BPH. In PCa, high miRNA-153 expression and loss of PTEN expression were associated significantly with higher Gleason patterns, higher Gleason scores, and higher Grade groups. The expression of miRNA-153 showed a significant inverse correlation with PTEN expression. CONCLUSIONS: Increased miRNA-153 expression and lost PTEN expression in PCa may provide information on their role in the progression of this cancer, suggesting that miRNA-153 could affect PTEN directly in prostatic neoplastic and hyperplastic lesions, and therefore miRNA-153 can be considered a new tool to improve the treatment efficacy and prognosis of PCa patients.

Early intervention with probiotics and metformin alleviates liver injury in NAFLD rats via targeting gut microbiota dysbiosis and p-AKT/mTOR/LC-3II pathways.

Non-alcoholic fatty liver disease (NAFLD) constitutes a major health problem worldwide and intimately links with obesity and diabetes. This study aimed to explore the therapeutic impact of early treatment with metformin (MTF) alone or in combination with Lactobacillus reuteri DSM 17938 (L. reuteri) + metronidazole (MTZ) in male Sprague Dawley rats with high-fat diet (HFD)-induced NAFLD. Hepatic steatosis was induced by feeding rats HFD for 6 weeks. MTF (150 mg/kg/day) or L. reuteri (2 × 109 colony forming unit/day) were given orally for 4 weeks; meanwhile, MTZ (15 mg/kg/day, p.o.) was administered for 1 week. Administration of L. reuteri + MTZ in combination with MTF produced a superior effect concerning insulin resistance (IR), lipid profile, liver function, oxidative stress, inflammatory and autophagic markers than using each treatment alone. Besides, this combination resulted in disappearance of steatosis, inflammation and vacuolation within hepatic architecture. Moreover, it normalized short chain fatty acids (SCFAs) as well as Firmicutes and Bacteroidetes faecal contents. In conclusion, early treatment with L. reuteri + MTZ in combination with MTF could prevent NAFLD progression and liver injury through targeting gut dysbiosis, inflammation and autophagic pathways.

α-Lipoic acid modulates liver fibrosis: A cross talk between TGF-ß1, autophagy, and apoptosis.

Autophagy and apoptosis are important players in the progression of hepatic fibrosis via activation of hepatic stellate cells (HSCs). Despite the recently depicted antifibrotic effects of alpha-lipoic acid (ALA), however, its modulatory effects on HSCs autophagy remain unverified. Our study aimed to elucidate the underlying antifibrotic mechanisms through which ALA mediates HSC autophagy and apoptosis. Liver fibrosis was induced via thioacetamide (TAA) intoxication in rats; TAA-intoxicated rats were treated with either silymarin or ALA. Effect of ALA on biochemical parameters and immunohistopathological examinations was measured and compared to silymarin. ALA restored normal hepatic architecture (S1 vs. S4), liver functions, hepatic glutathione, and transforming growth factor-ß1 levels. ALA ameliorated hepatic levels of malondialdehyde, platelet-derived growth factor, tissue inhibitor metalloproteinases-1, hydroxyproline, and expression of alpha-smooth muscle actin. Moreover, ALA significantly reduced messenger RNA expression of LC3-II genes and triggered caspase-3 expression. Interestingly, ALA exhibited superior activities over silymarin regarding suppression of proliferation, activation and autophagy of HSCs, collagen deposition, and induction of HSCs apoptosis. In conclusion, treatment of TAA-intoxicated rats with ALA inhibited autophagy and induced apoptotic clearance of activated HSCs. Accordingly, this study provides mechanistic insights into the possible applicability of ALA in the treatment of hepatic fibrosis.

Expression of Fas protein (CD95) and Fas ligand in liver tissue of patients with HCV-induced chronic liver disease and its correlation with the disease progression.

This study evaluated hepatic expression of both Fas and Fas ligand (FasL) in patients with hepatitis c virus (HCV)-induced chronic liver disease and its correlation with the histopathological activity and laboratory parameters as an early predictor of advancement of the disease. The selected patients were (39) males and (21) females, their ages ranged from (20-67years) with a mean of 43.5 +/- 4.5 years, as well as (10) subjects (normal individuals) serving as a control group. They were (7) males and (3) females, their age ranged from (26-53 years) with a mean of 39.5 +/- 7.3 years. Patients were grouped as (1) Chronic hepatitis (CH) group including (30) patients with chronic viral hepatitis C. (2) Liver cirrhosis (LC) group including (30) patients with post hepatitis C cirrhosis. Liver biopsy was done for all subjects using an automated 18-gauge true cut needle. Sections were stained with Haematoxylin and Eosin for histopathological diagnosis and with Maisson and Trichrome for assessment of fibrosis. Unstained paraffin sections from each case were subjected for immuno-histochemical procedures using indirect immunoflourescence technique for detection of apoptotic hepatic and lymphocytic cells using monoclonal antibodies. Semiquantitative analysis of the pattern and distribution of the Fas antigen and Fas Ligand as indicators for hepatic apoptosis was studied and assessed.

Prognostic impact of apoptosis marker Fas (CD95) and its ligand (FasL) on bladder cancer in Egypt: study of the effect of schistosomiasis.

OBJECTIVE: The Fas-Fas ligand (FasL) system has been recognized as a major pathway for the induction of apoptosis in cells and tissues. Fas-mediated apoptosis is deeply involved in cancer cell death brought about by the immune system. This study was performed to determine the Fas and FasL expression in human bladder cancer and the impact of schistosomiasis infection. MATERIAL AND METHODS: Of the 75 patients, 25 with chronic bilharzial cystitis and 50 with bladder cancer were included in this study. Ten control patients were included in the study, following their consent. Fas and FasL expressions in bladder tissue were determined by indirect immunohistochemistry using avidin-biotin-peroxidase complex (ABC) method. RESULTS: The association of bilharziasis with malignancy raised the incidence of Fas positive immunoreactivity to 100%. The number of malignant cases positive for Fas decreased with progress of tumour grade and stage. All control cases were negative for FasL expression. The percentage of positive FasL malignant cases increased with increasing tumour grade or stage. CONCLUSION: Malignant bladder lesions express high levels of Fas and decreased expression of Fas is associated with disease progression. Urinary bladder carcinoma acquires the functional FasL during tumour progression that may induce apoptosis of anti tumour T lymphocytes. Fas and FasL are recommended to be considered important tumour markers to define aggressive bladder cancer and may be included in defining the surveillance protocol for superficial bladder cancer.

[Analysis of a new visual field index, the VFI, in Ocular Hypertension and Glaucoma]. / Analyse d'un nouvel indice d'évaluation du champ visuel, le VFI, dans l'hypertonie oculaire et le glaucome.

OBJECTIVE: The Visual Field Index -VFI- is a new perimetric index allowing evaluation of visual function level and progression. In this study, we analysed this new index, that provides a trend analysis of visual field loss progression in Ocular Hypertension and Glaucoma. We also compared results with event analysis. METHODS: Retrospective study on 94 eyes of 54 patients: 35 OHT(ocular hypertension), 34 early POAG (primary open angle glaucoma) (0>MD>-6 dB), 13 moderate POAG (-6>MD>-12 dB) and 12 advanced POAG (MD<-12 dB), with a mean follow-up of 6.5 years (4 to 8 years). Each subject performed a mean number of 10 standard automated perimetry visual field tests (Humphrey SITA Standard 24-2), excluding tests without reliable indices. VFI progression rate was analysed. VFI progression during the first half period of follow up was compared with that during the second half period. VFI progression was confronted with script alert messages delivered by the last GPA (Guided Progression Analysis) event analysis program. RESULTS: VFI values were "stable or with low progression" in 100% of OHT patients, 88% of early POAG, 38.5% of moderate POAG, 33% of advanced POAG. Progression during the first half period (mean of 3 years) of follow-up could be extrapolated for the second half period in 97% of OHT patients, 76% of early POAG, 70% of moderate POAG, 75% of advanced POAG. Results from VFI trend analysis and GPA event analysis corresponded in 97% of OHT patients, 85% of early POAG, 85% of moderate POAG, and 87% of advanced POAG. DISCUSSION: VFI seems to be a useful indicator for glaucoma evaluation and progression follow-up. It completes the event analysis. Some very advanced POAG cannot be analysed by GPA event analysis. VFI should be able to be used for further follow-up. All these results require validation in larger population. The purpose would be to assess if VFI is able to detect different profiles of progression to help treatment decisions.

Schistosoma haematobium (Egyptian strain): rate of development and effect of praziquantel treatment.

This study investigates the development of the Egyptian strain of Schistosoma haematobium and the resultant immunohistopathology and biochemical changes in organs affected. In addition, the response of different developmental stages of S. haematobium worms to praziquantel (PZQ) was examined. Schistosoma haematobium-infected hamsters were classified into 4 groups and were treated at day 35, 55, 75, and 95 postinfection (PI), respectively. Each group was subdivided into 3 subgroups. Two of them were treated orally with PZQ (300 mg/kg or 500 mg/kg divided equally on 2 consecutive days), and the third group was left without treatment. Treated groups were killed 20 days posttreatment. Infection with S. haematobium became patent 73 days PI; tissue egg load and worm fecundity were higher at 95 days and maximal 115 days PI, with an oogram pattern comparable to that in Schistosoma mansoni infection. In the liver, small cellular granulomas were observed 75 days PI, with preponderance of CD4+ T-cell phenotypes. In the urinary bladder, only submucosal focal Brunn's-nest formation and angiogenesis without typical granulomas were observed. Ninety-five and 115 days PI, confluent granulomata with multiple eggs in the center were observed in the liver and urinary bladder, with a preponderance of CD8+ positive T cells in the liver and hyperplasia of the urinary bladder epithelium with cystitis cystica and papillae formation. One hundred percent worm eradication was recorded with the higher dose of PZQ in animals treated 75 and 95 days PI. In conclusion, in spite of the long prepatent period of the Egyptian strain of S. haematobium, sensitivity to PZQ was recorded soon after infection. Granulomata were similar to those of S. mansoni in the livers and urinary bladders, but they were confluent with multiple eggs in the centers, hyperplasia of the urinary bladder urothelium with cystitis cystica, papillae, and Brunn's-nest formation predictive of malignant changes with no hepatocyte dysplasia.

Neovascularization of the amniotic membrane as a biological immune barrier.

The clinical application of islet transplantation is limited due to the limited source and the morbidity of systemic immunosuppression to prevent rejection. The two problems can be solved by using encapsulated islets. We have used amniotic membranes as biocompatible natural immune barriers. The objective of this study was to assess the revascularization of the membrane, which is necessary to ensure islet viability when the membrane is used for islet encapsulation. The amniotic membranes, obtained from full-term pregnant female dogs, were molded to form macrocapsules, which were implanted in the peritoneal cavity. The capsules were removed after 3, 10, 15, and 30 days and examined histopathologically using hematoxylin and eosin and by immunohistochemistry for neovascularization using factor VIII to detect angiogenesis. Upon histopathological examination, all specimens showed localized, moderate inflammation and congested blood vessels with no thrombosis or rejection. There was a mild degree of fibroblast proliferation starting from day 10 to day 30. Immunohistochemical staining revealed that the number of blood vessels was 7, 11, 13, 10 per high-power microscopic field on days 3, 10, 15, and 30, respectively. We concluded from this study that implanted amniotic sac capsules were vascularized within the omental tissue from day 10 on with significant blood vessel formation starting on day 3 by immunohistochemical study.