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  • Item type: Item ,
    Tumor angiogenesis and anti-angiogenic therapies
    (2013) Shahneh, FZ; Baradaran, B; Zamani, F; Aghebati-Maleki, L
    Angiogenesis, the development and growth of blood vessels, is a major topic of research which began in 1971 with Folkman's original hypothesis. Different mechanisms of blood vessel growth are sprouting and intussusceptive angiogenesis, vascular mimicry, and blood vessel cooption. Dis-regulated angiogenesis may result in numerous angiogenic diseases and is responsible for solid tumor growth and metastasis. Vascular endothelial cells are generally dormant in adult but in pathological conditions when tumors reach a size of about 0.2-2.0 mm in diameter, they become hypoxic and hindered in tumor growth in the lack of angiogenesis. During angiogenic switch pro-angiogenic factors predominate and result in angiogenesis and tumor progression. Angiogenesis switch leads to the increased production of vascular endothelial growth factor (VEGF) following up-regulation of the hypoxia-inducible transcription factor. The VEGF family comprises from VEGF (VEGF-A), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). The VEGF family of receptors consists of three protein-tyrosine kinases. Now, the most conventional approach for controlling tumor angiogenesis is blockade of the vascular endothelial growth factor (VEGF) pathway. The results of preclinical studies, substantial therapeutic effects of VEGF blockers have been stated in various types of human cancers, even in progressive or recurrent cancer cases. © 2013 - IOS Press and the authors. All rights reserved.
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    Topical application of Mentha piperita essential oil accelerates wound healing in infected mice model
    (2018) Modarresi, M; Farahpour, M-R; Baradaran, B
    This study was conducted to evaluate the effects of the prepared ointments from Mentha piperita essential oil (M. piperita) on wound healing in the infected mice models. Each circular full-thickness wound was inoculated with 25 -- 107 units of Staphylococcus aureus and Pseudomonas aeruginosa bacteria strains. The tissue bacterial count, histological analyses and expression levels of IL-10, TNF-?, TGF-?1, IL-1?, CCL2, CXCL1, VEGF and FGF-2 were assessed to identify the different doses of M. piperita on wound healing. Total tissue bacterial count, edema and inflammation level were declined, but the migration of fibroblasts, collagen synthesis and re-epithelization were increased in treated animals with M. piperita. The expression levels of CCL2, CXCL1, IL-1?, TGF-?1 and IL-10 genes were up-regulated in the M. piperita-treated animals compared to the control group. While the expression of TNF-?, VEGF and FGF-2 was down-regulated in comparison to the control group. This study indicated that M. piperita can be used for treatment of the infected wound. © 2018 Springer International Publishing AG, part of Springer Nature
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    Toll-like receptor signaling and serum levels of interferon β and lipopolysaccharide binding protein are related to abdominal obesity: a case-control study between metabolically healthy and metabolically unhealthy obese individuals
    (2018) Naghizadeh, M; Baradaran, B; Saghafi-Asl, M; Amiri, P; Shanehbandi, D; Karamzad, N; Mohamed-Khosroshahi, L
    It is still unclear whether toll-like receptor (TLR) signaling and serum levels of inflammatory markers in metabolically unhealthy abdominally obese (MUAO) are due to their obesity and/or their metabolic state. We hypothesized that abdominal obesity is an important mediator of the association of metabolic state with TLR signaling and serum inflammatory markers. Therefore, in this case-control study, we compared the expression levels of TLR4 and Toll/interleukin-1 receptor domain containing adaptor protein-inducing interferon β (TRIF) and serum concentrations of interferon β and lipoprotein-binding protein (LBP) in metabolically healthy abdominally obese (MHAO) and MUAO individuals. Basal blood samples from 65 abdominally obese subjects with waist circumference (WC) of at least 95 cm were collected to determine serum metabolic parameters, IFNβ, and LBP. Those with 3 or more metabolic alterations were defined as MUAO (n = 34), and those having 2 or less were classified as MHAO (n = 31). Furthermore, messenger RNA (mRNA) was isolated from peripheral blood mononuclear cells. TLR4 and TRIF gene expression assay was performed using quantitative real-time polymerase chain reaction. There were significant differences in serum fasting blood sugar (P = .017), triglyceride (P < .001), cholesterol (P = .002), and lowdensity lipoprotein cholesterol (P = .034) between the MUAO and MHAO groups, whereas no Keywords: Toll-like receptor 4 Toll/interleukin-1 receptor domain containing adaptor proteininducing interferon Interferon β Abdominal obesity Metabolic health NUTRITION RESEARCH 55 (2018) 11 – 2 0 Abbreviations: BMI, body mass index; BP, blood pressure; CRP, C-reactive protein; FBS, fasting blood sugar; HDL-C, high-density lipoprotein cholesterol; IFNs, Interferons; IFNβ, interferon β; ILs, interleukins; LBP, lipopolysaccharide-binding protein; LPS, Lipopolysaccharide; LBP, lipopolysaccharide-binding protein; MetS, metabolic syndrome; MHAO, metabolically healthy abdominally obese; MUAO, metabolically unhealthy abdominally obese; PA, physical activity; PBMCs, peripheral blood mononuclear cells; TG, triglyceride; TLRs, toll-like receptors; TNF-α, tumor necrosis factor α; TRIF, Toll/IL-1 receptor domain containing adaptor protein-inducing interferon β; WC, waist circumference
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    TLR-2, IL-10 and IL-17-mediated immunity in experimental chemotherapy murine model of systemic candidiasis; cyclophosphamides' impact and roles
    (2018) Dehghan, P; Tolouie, S; Baradaran, B; Nami, S; Morovati, H
    The majority of immune components such as Toll-like receptor (TLR)-2, interleukin (IL)-17, neutrophils, and IL-10 play pivotal roles in immunity to Candida albicans (C. albicans) through identifying and launching inflammatory and regulatory responses. Chemotherapy is one of the most potent risk factors for systemic candidiasis through inducing immunosuppression (mostly cyclophosphamide induced immunosuppression) and there is a sensible lack of study around the immunity to C. albicans in such a situation. In this study, following the establishment of infection and immunosuppression in Balb/c mice model, the mRNA/protein levels of TLR-2, IL-10, IL-17, and Myeloperoxidase (MPO) in serum/kidney were measured using Real-time PCR and ELISA respectively. The survival of mice was checked daily and organ fungal burden was calculated and the histology samples were prepared. Results indicated that the mRNA and protein levels of IL-10, IL-17 and MPO were significantly elevated in immunosuppressed-infected mice (P?
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    Time - and concentration - dependent effects of resveratrol on miR 15a and miR16-1 expression and apoptosis CCRF-CEM acute lymphoblastic leukemia cell line
    (2015) Azimi, A; Hagh, MF; Talebi, M; Yousefi, B; Hossein Pour Feizi, AA; Baradaran, B; Movassaghpour, AA; Shamsasenjan, K; Khanzedeh, T; Ghaderi, AH; Heydarabad, MZ
    Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p < 0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.
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    The relationship between trace mineral concentrations of amniotic fluid with placenta traits in the pregnancy toxemia Ghezel ewes
    (2016) Olfati, A; Moghaddam, G; Kor, NM; Baradaran, B
    Objective This study was conducted to investigate the trace mineral concentrations (Mg, Se, Zn, Cu and Fe) in amniotic fluid (AF) in 40 pregnancy toxemia Ghezel ewes at the time of parturition phase and its association with placental traits. Methods Animals were treated with controlled internal drug release for 14 d and injected 400 IU pregnant mare serum gonadotropin at the time of controlled internal drug release removal. After the detection of estrus by use of teaser rams, ewes were hand-mated. Ewes were classified as having subclinical pregnancy toxemia on the basis of beta-hydroxy butyrate (BHBA) results (BHBA > 0.86 mmol/L). Results The overall mean AF traces of mineral concentrations were 3.13 ng/mL, 22.1 ?g/dL, 134.7 ?g/dL, 122.5 ?g/dL and 166.6 ?g/dL, respectively. There was a significant positive correlation between placental efficiency and Zn concentration in AF ewes (r = 0.633, P < 0.01), while the relationship was significantly negative between total volume of amniotic fluid and Fe concentration in AF ewes (r = ?0.717, P < 0.01). In this research, no relationship between Se, Mg and Cu trace minerals was observed in AF ewes with placental traits ewes. Results of laboratory analyses demonstrated no relationship between BHBA concentrations and placental traits (P > 0.01), except for placental weight (r = 0.808, P < 0.01). Also, no significant correlation was detected between BHBA with the above trace minerals. Conclusions Overall, determinations of these trace minerals in the AF ewes could have been used to obtain information on nutritional and reproductive status for the diagnosis of pregnancy toxemia in Ghezel ewes. © 2016 Hainan Medical College
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    The interaction between the light source dose and caspase-dependent and -independent apoptosis in human SK-MEL-3 skin cancer cells following photodynamic therapy with zinc phthalocyanine: A comparative study
    (2017) Doustvandi, MA; Mohammadnejad, F; Mansoori, B; Mohammadi, A; Navaeipour, F; Baradaran, B; Tajalli, H
    The aim of this study is to determine the behavior of relative expression of Bcl-2, caspase-8, caspase-9, and caspase-3 genes of/in SK-MEL-3 cancer cells and explore molecular mechanisms responsible for the apoptosis response during an in vitro photodynamic therapy (PDT) with Zinc Phthalocyanine (ZnPc) using different doses of the light source. In this study, firstly the cytotoxic effects of ZnPc-PDT on SK-MEL-3 cells were evaluated. By irradiating the laser, ZnPc induced a significant amount of apoptosis on SK-MEL-3 cells in three IC50s including 0.064 ± 0.01, 0.043 ± 0.01, and 0.036 ± 0.01 ?g/mL at the doses of 8, 16, and 24 J/cm2, respectively. Moreover, flow cytometry and QRT-PCR experiments were done. The high percentage of apoptotic cells was seen in the early apoptosis stage. The expression of Bcl-2 and caspase-8 genes at all doses of laser experienced an obvious reduction in comparison to the control group. On the other hand, although the expression of caspase-9 and caspase-3 genes remains almost constant at 8 J/cm2, but they faced an increment at 16 and 24 J/cm2 doses. These data reveal caspase-dependent apoptosis in high and caspase-independent apoptosis in low doses of laser. Based on the results of present work, it can be suggested that the dose of the light source is a key factor in induction of caspase-dependent and caspase-independent apoptosis pathways following PDT. © 2017
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    The Herbal Medicine Utrica Dioica Inhibits Proliferation of Colorectal Cancer Cell Line by Inducing Apoptosis and Arrest at the G2/M Phase
    (2016) Mohammadi, A; Mansoori, B; Aghapour, M; Baradaran, PC; Shajari, N; Davudian, S; Salehi, S; Baradaran, B
    Background: One of the major causes of cancer death internationally and the third most prevalent cancer in the world has been diagnosed with colorectal cancer. Although current routine treatments of cancer have been successful in some extent, mortality caused by adverse effects of these strategies is still raising. Medicinal plants are potential sources of anticancer compounds and can be exploited as a powerful complementary tool. This study aimed to investigate the cytotoxic effects of nettle extract on mouse colorectal cancer cells, HCT. Materials and Methods: In the present study, to evaluate the cytotoxicity of nettle extract, MTT assay and trypan blue were performed. Subsequently, DNA fragmentation and TUNEL test was carried out for determination of apoptosis. Real-time PCR test was used to quantify the expression of Caspase-3, Caspase-9, and Bcl-2 which is involved in apoptosis regulation. Finally, cell cycle analysis was conducted by using flow cytometry. Results: The results of MTT assay showed that the dichloromethane extract of U. dioica extract significantly destroyed cancer cells HCT-116. DNA fragmentation and TUNEL test demonstrated that Utrica extract elicited apoptotic response in the cancer cells. The messenger RNA (mRNA) expression levels of Caspase-3 and Caspase-9 markedly increased, while the Bcl-2 gene was conversely downregulated. Findings of flow cytometry confirmed that cell cycle arrest has occurred at the G2 phase. Conclusion: Taken together, our experiment showed that subjecting HCT-116 cells to dichloromethane extract of nettle (U. dioica), increases turnover of these cells. Thus, it may be a useful agent in the treatment of colorectal cancer. © 2016, Springer Science+Business Media New York.
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    The effect of tween excipients on expression and activity of P-glycoprotein in Caco-2 cells
    (2014) Hodaei, D; Baradaran, B; Valizadeh, H; Mohammadnezhad, L; Zakeri-Milani, P
    Purpose: The present study was designed to investigate the effects of Tween excipients (polysorbates; Tween 20, Tween 40 and Tween 80) on the activity and expression of P-glycoprotein (P-gp). Methods: An MTT (3-[4,5-dimethylthiazol-2- yl]-2,5-diphenyl tetrazolium bromide) assay test was conducted to determine the non-toxic concentration of the excipients. Moreover, the uptake of Rhodamine-123, a P-gp fluorescence substrate, was measured through Caco-2 cell monolayer encountering with excipients overnight to investigate whether sub-toxic concentrations of Tween excipients are able to affect the P-gp activity. Furthermore, Western blotting was performed to investigate the P-gp protein expression. Results: The results showed that Tween 20 and Tween 80 at concentrations below 0.01% (w/v), and Tween 40 at concentrations below 0.05% (w/v) were non-toxic to Caco-2 cells. Results from the Rho-123 uptake test assay and Western blotting showed that Tween 20 at concentration of 0.01% (w/v) and Tween 40 at concentration of 0.05% (w/v) were able to block P-gp significantly. Conclusion: Based on the obtained results it is concluded that Tween excipients at the defined concentrations could be used to inhibit the P-gp efflux transporter resulting in an altered bioavailability of drugs.
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    The effect of cyclophosphamide on TLR2 gene expression in Balb/c Mice with systemic candidiasis
    (2016) Morovati, H; Tolouei, S; Dehghan, P; Baradaran, B; Mohammadifard, A; Yousefi, Z
    Background: Toll like receptor-2 (TLR2) plays an important role in the process of detection and launching the immune response against Candida albicans. Cyclophosphamide is one of the most widely used chemotherapy drugs, which causes severe neutropenia and suppression of the immune system. In this study Balb/c mice were infected to disseminated candidiasis and neutropenia and expression of TLR2 gene was measured in whole blood samples of each mice. Methods: Twenty-eight mice were divided into 4 groups and injected with Cyclophosphamide and C. albicans. Blood samples were used for RNA extraction and cDNA synthesis, and expression of TLR2 gene was measured by real-time polymerase chain reaction (Real-time PCR). Statistical analysis was performed using Kruskal-Wallis and 2-??CT method. Findings: Gene expression was increased in the group receiving Candida albicans and also in group receiving both Cyclophosphamide and Candida albicans but decreased in the group just receiving Cyclophosphamide. Conclusion: There was no significant difference between the control group and experimental groups for TLR2 gene expression (P = 0.478). However, the results of this study can be regarding in selecting TLR2 or its receptor as a therapeutic target with monoclonal antibodies or gene therapy techniques. © 2016, Isfahan University of Medical Sciences(IUMS). All rights reserved.