Correlation of acidic mammalian chitinase expression with disease severity in patients with moderate/severe persistent allergic rhinitis.

AIM OF THE STUDY: To assess the level of acidic mammalian chitinase (AMCase) expression and IL-8 in nasal inferior turbinate mucosa in patients with mild and moderate to severe allergic rhinitis (AR). MATERIAL AND METHODS: Participants in this case-control study were divided into three groups, including patients with moderate and severe persistent allergic rhinitis, cases with mild forms of persistent AR, and control or healthy group. We obtained biopsies of nasal inferior turbinate mucosa from all participants. Expression of AMCase and IL-8 mRNAs were evaluated by real-time polymerase chain reaction (PCR). The serum levels of AMCase and IL-8 were determined by ELISA. The number of eosinophils per field, blood eosinophils, total serum IgE levels, and specific serum IgE levels were measured. Patients' clinical manifestations were assessed by total nasal syndrome score (TNSS). RESULTS: Expression of AMCase and IL-8 in patients with moderate and severe perineal allergic rhinitis were significantly elevated compared to the control group and patients with mild persistent allergic rhinitis. Serum levels of AMCase and IL-8 were associated with specific IgE, nasal eosinophil count, and TNSS. CONCLUSIONS: According to the results of this study, there might be a relationship between the expression of AMCase and IL-8 in nasal turbinate mucosa and the severity of allergic rhinitis.

Combined Effects of Protocatechuic Acid and 5-Fluorouracil on p53 Gene Expression and Apoptosis in Gastric Adenocarcinoma Cells.

OBJECTIVES: This study evaluated the combined effects of protocatechuic acid (PCA) and 5-fluorouracil (5-FU) on gastric adenocarcinoma (AGS) cells. MATERIALS AND METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry technique, real-time quantitative polymerase chain reaction, and Western blotting were used to investigate cytotoxic effects, colony formation, apoptosis, p53 gene expression, and Bcl-2 protein level in AGS cells treated with 5-FU and PCA. RESULTS: Our results demonstrated that PCA (500 µM) alone or in combination with 5-FU (10 µM) inhibited AGS cell proliferation, inhibited a colony formation, and increased apoptosis compared with untreated control cells. Moreover, the combined 5-FU/PCA exposure led to upregulation of p53 and downregulation of Bcl-2 protein when compared to the untreated control cells. CONCLUSION: The results demonstrate that the combined 5-FU/PCA may promote antiproliferative and pro-apoptotic effects with the inhibition of colony formation in AGS cells. The mechanisms by which the combined 5-FU/PCA exposure exerts its effects are associated with upregulation of p53 gene expression and downregulation of Bcl-2 level. Therefore, the combination of 5-FU with PCA not only could be a promising approach to potentially reduce the dose requirements of 5-FU but also could promote apoptosis via p53 and Bcl-2 signaling pathways.

Protective and anti-inflammatory effects of hydroalcoholic leaf extract of Origanum vulgare on oxidative stress, TNF-α gene expression and liver histological changes in paraquat-induced hepatotoxicity in rats.

CONTEXT: Toxicity with paraquat can lead to serious damages to the liver. OBJECTIVE: The study investigates the protective effects of Origanum vulgare leaf extract against paraquat liver damage. MATERIAL AND METHODS: Rats were divided into six groups. Group 1, the control group; group 2, rats that received paraquat only; group 3, rats that received paraquat plus silymarin; and groups 4, 5, and 6 were treated with paraquat and O. vulgare leaf extract. Then, the serum and tissue parameters of the oxidative stress were examined. RESULTS: In group 2, paraquat caused a remarkable increase in the level of serum ALT, AST, ALP, lipid profiles, and liver TNF-α gene expression compared to group 1. The groups which received O. vulgare leaf extract exhibited significant ameliorations in abnormalities of paraquat-induced liver damage and serum biochemical parameters. CONCLUSION: O. vulgare leaf extract has inhibitory effects on paraquat-induced liver damage due to its antioxidant properties.

Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression.

Purpose: Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside from quercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects of rutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line (PC3) was investigated herein. Methods: Different concentrations of combined 5-FU and rutin were applied to PC3 cells compared to separate treatment for 48 hours. Cell viability, as well p53 gene expression respectively were assessed by MTT assay and real-time quantitative polymerase chain reaction (qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blot and flow cytometry procedures, respectively. Clonogenic assay was used to colony counts assessment. Results: 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and 5-FU respectively were 900 µM and 3Mm, while combination index (CI) of combined 5-FU /rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutin enhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2 signaling protein were decreased by 5-FU/rutin combination. Conclusion: Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application. 5-FU/rutin combination does seem an interesting therapeutic pathway to be further investigated.

Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats.

BACKGROUND: Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined. METHODS: Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24mg/kg bw daily, po) without treatment; group 3, rats receiving 24mg/kg bw fluoxetine, treated with 50mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out. RESULTS: Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status. CONCLUSIONS: Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α.

Aflatoxin M1 in human breast milk in Shahrekord, Iran and association with dietary factors.

This survey was conducted to determine the occurrence and levels of aflatoxin M1 (AFM1) in 250 breast milk samples of lactating mothers, obtained from urban and rural regions of Shahrekord, Iran. Moreover, the association between AFM1 occurrence levels and dietary factors was assessed. AFM1 analysis was carried out using the competitive enzyme-linked immunosorbent assay technique for screening and high-performance liquid chromatography with fluorescence detection (HPLC-FLD) for confirmatory purposes. The toxin was detected in 39 samples (15.6%), ranging from 11.1 to 39.3 ng/l, of which 8 samples (3.2%) had levels above the Iranian national standard limit (25 ng/l). AFM1 occurrence and levels in breast milk samples obtained from rural regions were significantly higher (P ≤ 0.05) than those obtained from urban ones. It might be due to the different dietary patterns in these regions. It was found that dietary habits with more tendencies to consume bread, rice and non-alcoholic beer beverage significantly increased (P ≤ 0.05) the risk of AFM1 occurrence in breast milk. In addition, higher consumption of bread, olive and traditional cream significantly increased (P ≤ 0.05) the levels of AFM1 in breast milk samples. Further investigations should be performed to determine more precisely the association between AFM1 occurrence and dietary factors and also the risk of infant exposure to this mycotoxin.

Plasma Calcitonin Levels and miRNA323 Expression in Medullary Thyroid Carcinoma Patients with or without RET Mutation

Background: Medullary thyroid cancer (MTC) is an endocrine tumor featuring parafollicular or C-cell differentiation, with calcitonin as a specific biomarker in MTC diagnosis. Germline mutations in the RET proto-oncogene are considered responsible for its familial occurrence and somatic mutations can cause sporadic lesions. MicroRNAs can act as oncogenes or tumor suppressors by inhibiting the expression of target genes.. The aim of this study was to investigate relationships between plasma levels of calcitonin and miRNA323 expression in MTC patients with or without RET mutation. Methods: In this cross-sectional study, MTC lesions (based on pathological confirmation) were investigated. Genomic DNA was extracted and Exons 10 and 11 of RET were genotyped using PCR-sequencing. Division was into two groups of 43 cases each with or without mutation. Plasma levels of calcitonin were determined in both. Results: miRNA323 was measured using real-time-PCR. After performing normality tests, independent T-tests and Mann Whitney tests were used for the statistical comparison of parametric and nonparametric data, respectively. Plasma levels of calcitonin were significantly higher in MTC cases without a RET mutation compared to those with a mutation. Conclusion: There was no significant difference between the two groups regarding the expression of miRNA323 so that this parameter could not be used as a bio-index germ line mutations in MTCs. However, determination of calcitonin levels in plasma might be helpful in this regard.

Evaluating the effects of ellagic acid on pSTAT3, pAKT, and pERK1/2 signaling pathways in prostate cancer PC3 cells.

OBJECTIVE: One of the most common malignancies among men is prostate cancer. Ellagic acid (EA), a polyphenol antioxidant, has many pharmacological actions, especially anticancer effects. The purpose of this study was to evaluate the effect of EA treatment on interleukin-6 (IL-6) gene expression, cell viability, IL-6 secretion, phosphorylated STAT3, ERK, and AKT cellular signaling proteins in human prostate cancer cells (PC3). MATERIALS AND METHODS: The cytotoxic effects of the EA (0-100 µM) on PC3 cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. IL-6 gene expression was down, using real-time quantitative polymerase chain reaction. The cellular concentration of phosphorylated ERK1/2, AKT, and STAT3 signaling pathways was assessed by Western blotting technic. RESULTS: EA treatment of PC3 cells resulted in a reduction of cell viability and phosphorylated STAT3, ERK, and AKT signaling proteins after 72 h in a dose-dependent manner. IL-6 gene expression and IL-6 levels significantly increased (P < 0.05) in a dose-dependent pattern in treated PC3 with EA. Thus, these data suggested the essential role of signaling proteins in EA-mediated anti-proliferation of PC3 cells. CONCLUSIONS: Our finding shows that EA can be considered as a potent agent that decreases cell proliferation through a reduction of phosphorylated STAT3, ERK, and AKT cellular signaling proteins.