Rouhollah Hemmati Bushehri; Mahmoud Reza Jaafari; Ghasem Mosayebi; Ali Ghazavi; Ali Ganji
Abstract
Background: Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack ...
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Background: Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack of immunogenicity and toxicity, making them ideal for delivering various drugs.Objective: To prepare liposomes (HSPC/Chol/mPEG2000-DSPE) containing rosemary alcoholic extract (LipRos) and evaluate its antitumor properties in a mouse model of colorectal cancer (CRC).Methods: LipRos were prepared and characterized. CRC was induced in Balb/c mice by subcutaneous injection of C26 cells, and tumor size was monitored continuously. The MTT assay was performed to evaluate cytotoxicity, and liver and kidney function tests were conducted to assess safety. The expression of the pro-apoptotic gene B-cell-lymphoma-2 (Bcl-2), the anti-apoptotic gene Bcl-2-associated-X-protein (Bax), and the expression of cytokines Tumor-necrosis-factor-alpha (TNF-α), Transforming-growth-factor-beta (TGF-β), and Interferon-gamma (IFN-γ) were investigated using real-time PCR. Flow cytometry was used to evaluate the count of cytotoxic (CTL) and regulatory T lymphocytes (Tregs) in spleen and tumor tissue.Results: The results showed that the size of liposomal formulations and their encapsulation efficiency were 113.4 nm and 85%, respectively. The MTT assay demonstrated insignificant cytotoxicity of LipRos on splenocytes, and the tumor size was significantly reduced in the LipRos group (P=0.00045). LipRos also significantly decreased Bcl-2 gene expression (P=0.0086), increased Bax and IFN-γ gene expression (P=0.031), and enhanced the infiltration of CTLs in tumor tissue (P=0.023).Conclusions: This study showed that PEGylated (Poly-Ethylene-Glycol) liposomes containing rosemary extract exhibit an antitumor effect on C26 colorectal cancer cells through multiple mechanisms. These findings can be utilized in future studies.
Keyvan Ghasami; Fardin Faraji; Masoud Fazeli; Ali Ghazavi; Ghasem Mosayebi
Volume 13, Issue 1 , March 2016, , Pages 16-26
Abstract
Background: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. Objective: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled ...
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Background: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. Objective: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled clinical trial. Methods: Multiple sclerosis patients were randomized independently, in a double blind design, into one of two treatment groups. Control group (n=45) received 30 μg/week interferon β-1a via intra-muscular injection. Atorvastatin-treated group (n=50) received interferon β-1a similar to control group in addition to atorvastatin (40 mg/day) for 18-months. All clinical and immunological variables were measured at the baseline and at the end of the study. Results: There was no significant difference between the two groups in the expanded disability status scale scores and the number of gadolinium-enhancing lesions during the 18-month treatment period. After 18 months, the levels of interleukin (IL)-4, IL-10, transforming growth factor-β and serum ferric reducing antioxidant power in the atorvastatin treatment group were significantly higher than the control group. Levels of IL-17, TNF-α and lymphocyte proliferation in the atorvastatin treatment group were significantly lower than the control group. Conclusion: Although combined atorvastatin and interferon-β do not change the clinical course of MS, atorvastatin might have beneficial effects in MS treatment possibly through inducing anti-inflammatory responses.
Ghasem Mosayebi; Shaban Ali Alizadeh; Ali Alasti; Alireza Amouzandeh Nobaveh; Ali Ghazavi; Mahsa Okhovat; Mohammad Rafiei
Volume 10, Issue 4 , December 2013, , Pages 216-228
Abstract
Background: The appendix is considered as part of the gut-associated lymphoid tissue; however, lymphocyte subsets in this tissue are not fully defined. Objective: To investigate and compare the function and phenotype of lymphocyte subsets in peripheral blood and appendix of patients with normal and inflamed ...
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Background: The appendix is considered as part of the gut-associated lymphoid tissue; however, lymphocyte subsets in this tissue are not fully defined. Objective: To investigate and compare the function and phenotype of lymphocyte subsets in peripheral blood and appendix of patients with normal and inflamed appendix tissues. Methods: Peripheral blood samples and appendiceal mononuclear cells were obtained from 81 patients (mean age; 23 ± 10.5 years), clinically suspected of having appendicitis. The phenotypic characteristics of lymphocyte subsets in peripheral blood (before and 48-72 hrs after appendectomy) and in appendix tissue were analyzed by three color-flow cytometry. The proliferative response of mononuclear cells was assessed by MTT method. Results: The frequency of CD19+DR+, HLA-DR+ and CD19+ cells in the appendix tissue were significantly higher than that of the peripheral blood in all the groups (p<0.001). The percentage of CD19+ cells and HLA-DR+CD19+ cells significantly decreased after appendectomy in the peripheral blood of the patients with acute appendicitis (p=0.047 and p=0.03, respectively). CD19 and HLA-DR plus CD19 had better diagnostic efficiency compared with T cell markers (area under the ROC curve [AUC]= 0.76 and 0.73, respectively). Conclusion: These results indicate a significant difference in CD19+ and HLA-DR+ lymphocytes between peripheral blood and the appendix tissue.
