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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Journal of Applied Biotechnology Reports
- نوع مقاله: Journal Article
- کلمات کلیدی: Drug resistance,Ovarian Cancer,Proteasome Inhibitors,Carfilzomib
- چکیده:
- چکیده انگلیسی: Introduction: Resistance to selective small-molecule inhibitors has been a substantial factor for limiting the efficacy of ovarian cancer. Recent studies have revealed that proteasome inhibitors induce acquired drug resistance. The possible mechanisms underlying the resistance to carfilzomib (CFZ), a recently developed inhibitor of proteasome, has not been well studied. This experimental study has aimed to determine if CFZ induces drug resistance in A2780 ovarian cancer cells through p53- and caspase-3 dependent pathways.
Materials and Methods: The A2780CFZ cells were generated by continuous culturing of A2780S cells in the presence of CFZ for 4 months. The MTT cytotoxic assay was applied to compare the survival rates in A2780CFZ and A2780S cells. Also, the relative expression of p53 and caspase-3 genes were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The nonparametric ANOVA and Friedman tests were used for data analysis.
Results: A significant difference was observed between the viability of resistant- and sensitive-A2780 cells exposed to various concentrations of CFZ, indicating that A2780S cells have become resistant to this drug under long-term culture. Compared with A2780CFZ cells, the mRNA levels of p53 gene in A2780S cells were significantly increased after 12 (P = 0.008), and 24 hours (P = 0.034) . Also, no significant differences were observed regarding caspase-3 mRNA levels between both cell lines (P > 0.05).
Conclusions: The findings of this study suggest that regulation of p53 gene expression in A2780CFZ cells might be the possible primary mechanism for gaining resistance against CFZ, but this might be independent of caspase cascades activation. Further studies are required to find strategies for overcoming CFZ resistance.- انتشار مقاله: 12-12-1397
- نویسندگان: Sadegh Zarei,Javad Zavar Reza,Hossein Zarei Jaliani,Mohammad Reza Hajizadeh,Saman Sargazi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Diabetes Mellitus,Testosterone,Morus alba
- چکیده:
- چکیده انگلیسی: Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE) has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts) as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde) in the testis of control, untreated and MAE-treated (1 g/day/kg) diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc), by real-time PCR.Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group.Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion.
- انتشار مقاله: 10-12-1392
- نویسندگان: Mohammad Reza Hajizadeh,Ebrahim Eftekhar,Fatemeh Zal,Aida Jafarian,Zohreh Mostafavi-Pour
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Inflammation,TLR4,TLR2,Cerebral ischemia,TRPV1
- چکیده:
- چکیده انگلیسی: Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats
Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke.
Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4.
Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.- انتشار مقاله: 14-05-1396
- نویسندگان: Elham Hakimizadeh,Ali Shamsizadeh,Ali Roohbakhsh,Mohammad Kazemi Arababadi,Mohammad Reza Hajizadeh,Mehdi Shariati,Iman Fatemi,Amir Moghadam-ahmadi,Gholamreza Bazmandegan,Hossein Rezazadeh,Mohammad Allahtavakoli
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Apoptosis,Gastric cancer,Cornus mass L. extract,L929 cells,AGS cell line
- چکیده:
- چکیده انگلیسی: Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to the
cure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction of
apoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGS
and L929 cells were cultured and treated with different concentrations (0–10 mg/ml) of Cornus mass L. extract for 48
and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantified
at 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI and
double staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed by
ANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviation
among various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line in
comparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximately
several-fold increased anti-cancer potency in AGS compared to L929 cells. The IC50 value in AGS cells (evaluated
after 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p≤0.05). The analysis results of flow cytometry
indicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Each
of our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferation
in in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers.- انتشار مقاله: 17-02-1397
- نویسندگان: Farzaneh Sadat Hosseini,Mojgan Noroozi Karimabad,Mohammad Reza Hajizadeh,Alireza Khoshdel,Soudeh Khanamani Falahati-Pour,Mohammad Reza Mirzaei,Seyed Mehdi Mirmohamadi,Mehdi Mahmoodi
- مشاهده