Triple-negative breast cancer accounts for approximately 15-20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of ...1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line.
The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly.
Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC50 values 14.97 μM and 6.45 μM compared with Paclitaxel with IC50 values 49.90 μM and 25.19 μM, after 24 and 48 hours, respectively. Upon treatment with 14.97 μM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells.
The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy.
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Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient's recovery process. ...Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazoα-1,2quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study.
U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazoα-1,2quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit.
Among the 5 derivatives of tetrahydrobenzo(g)imidazoα-1,2quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazoα-1,2quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC50 (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells.
Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazoα-1,2quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention.
Considerable evidence shows that the tumor microenvironment is an active participant in preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia is a prominent ...characteristic of the solid tumor microenvironment. The transcription factor hypoxia-inducible factor-1α (HIF-1α) is an important mediator of hypoxic response of tumor cells that modulates the expression of specific genes involved in tumor immunosuppression. Using a 4T1 breast cancer model, we show that in vivo administration of PX-478, an inhibitor of oxygen-sensitive HIF-1α, led to reduced expression of Foxp3 and VEGF transcript and/or protein, molecules that are directly controlled by HIF-1. When combined with dendritic cell (DC)-based vaccination, HIF-1α inhibition resulted in an augmented cytotoxic T lymphocyte effector function, improved proliferation status of T cells, increased production of inflammatory cytokine IFN-γ, as well as reduced regulatory function of T cells in association with slower tumor growth. Taken together, our findings indicate that the use of HIF-1α inhibition provides an immune adjuvant activity, thereby improves the efficacy of tumor antigen-based DC vaccine.
The aim of this study was to assess the effect of soy flour on nutritional, physicochemical, and sensory characteristics of gluten‐free (GF) bread. In this study, corn flour was replaced with soy ...flour at different levels 5%, 10%, and 15% to produce a more nutritionally balanced GF bread. Physical and chemical properties, sensory evaluation and crust and crumb color were measured in bread samples. The results of evaluations showed that protein content of soy flour‐supplemented GF bread significantly increased from 9.8% to 12.9% as compared to control along with an increased in fat (3.3%–4.1%), fiber (0.29%– 0.38%), and ash (1.7%–2.2%) content. Moisture (27.9%–26.5%) and carbohydrate (58.3–52.3) content decreased with the incremental addition of soybean flour. The highest total score of sensory evaluation was for the bread sample containing 15% soybean flour. The evaluation of crust and crumb showed that bread samples with 15% soy flour were significantly darker than the other bread samples. In conclusion, adding higher levels of soybean flour into GF bread can improve bread quality, sensory characteristics, and nutritional properties of bread. Nutritional status in patients with celiac disease (CD) can be improved through the produce GF bread in this way.
In this study, corn flour was replaced with soy flour at different levels 5%, 10% and 15% to producing a more nutritionally balanced GF bread.The results of evaluations showed that protein, fat, fiber, and ash contents of soy flour‐supplemented GF bread increased with the incremental addition of soybean flour. The highest total score of sensory evaluation was for the bread sample containing 15% soybean flour. Adding higher levels of soybean flour into GF bread can improve bread quality, sensory characteristics and nutritional properties of bread.
Celiac disease (CD) is caused due to intake of gluten, a protein component in wheat, barley, and rye. The only treatment currently available for CD is strict lifetime adherence to a gluten-free diet ...(GFD) which is a diet that excludes wheat, barley, and rye. There is limited information on barriers to following a GFD. The present study aimed to investigate the compliance with a GFD, barriers to compliance, and the impact of compliance on the quality of life (QOL) in Iranian children and adolescents suffering from CD.
In this cross-sectional study, a total of 65 known cases of CD (both males and females), diagnosed in Namazi Hospital, a large referral center in south of Iran, selected by census were studied in 2014. Dietary compliance was assessed using a questionnaire. A disease-specific QOL questionnaire for children with CD (the celiac disease DUX CDDUX) was used. Comparisons between categorical variables were performed using chi-square test.
Sixty-five patients, 38 females (58.5%) and 27 (41.5%) males, were surveyed. Mean (± standard deviation SD) age of the respondents was 11.3 (±3.8) years. Dietary compliance was reported by 35 (53.8%) patients. The mean (± SD) CDDUX score was higher in dietary-compliant patients (33.5 ±19.4 vs 26.7 ±13.6, respectively, P=0.23). The score of CDDUX in parents of patients in dietary-compliant group was more than the noncompliant patients (28.1 ±13.5 vs 22.1 ±14, respectively, P=0.1). Barriers to noncompliance were poor or unavailability (100%), high cost (96.9%), insufficient labeling (84.6%), poor palatability (76.9%), and no information (69.23%).
Approximately half of the patients with CD reported dietary compliance. Poor or unavailability was found to be the most important barrier contributing to noncompliance. The QOL was better in compliant patients. Proposed strategies to improve compliance are greater availability of gluten-free products, better food labeling, and better education about the diet and condition.
Considerable evidence shows that the tumor microenvironment is an active participant in preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia is a prominent ...characteristic of the solid tumor microenvironment. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) is an important mediator of hypoxic response of tumor cells that modulates the expression of specific genes involved in tumor immunosuppression. Using a 4T1 breast cancer model, we show that in vivo administration of PX-478, an inhibitor of oxygen-sensitive HIF-1alpha, led to reduced expression of Foxp3 and VEGF transcript and/or protein, molecules that are directly controlled by HIF-1. When combined with dendritic cell (DC)-based vaccination, HIF-1alpha inhibition resulted in an augmented cytotoxic T lymphocyte effector function, improved proliferation status of T cells, increased production of inflammatory cytokine IFN-γ, as well as reduced regulatory function of T cells in association with slower tumor growth. Taken together, our findings indicate that the use of HIF-1alpha inhibition provides an immune adjuvant activity, thereby improves the efficacy of tumor antigen-based DC vaccine.
Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low ...concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cells-mediated immunosuppression.
To assess whether multiple low doses of 5-fluorouracil could repress myeloid derived suppressor cells in low frequency and, in turn, could enhance anti-tumor responses and promote a more prolonged survival in a murine melanoma model.
Fifty milligram per kilogram body weight dose of 5-Flourouracil was administered intraperitoneally 4 times with 3-day intervals to C57BL/6 mice after B16 melanoma tumor models were established. The frequency and suppressive functions of myeloid derived suppressor cells and induction of anti-tumor CD8+ T cells as well as tumor growth and survival were evaluated in drug treated and untreated mice.
Our results demonstrated that this therapeutic strategy increases the overall mice survival (p≤0.01) and induces melanoma-specific CD8+T cell immunity (p≤0.01) by reducing the frequency of myeloid derived suppressor cells (p≤0.01) as well as their immune suppressive functions (p≤0.05).
Altogether, our data suggest that 5-fluorouracil in multiple low regimens might be used to overcome tumor immunosuppression and improve the efficacy and outcome of anti-tumor immune responses in a mouse model.
Aim
To develop a nutritional screening tool and examine its reliability and validity in elementary school children with malnutrition based on PRECEDE–PROCEED model, in Shiraz, Iran.
Methods
A ...questionnaire was designed and its reproducibility was analysed via test–retest design among students with malnutrition. The students were in the fourth to sixth grades. Validity was assessed using face validity, content validity, construct validity, item difficulty and item discrimination. Reliability was measured by Cronbach's alpha (internal consistency), the intra‐class correlation coefficient (ICC) and κ statistics (test–retest reliability).
Results
A total of 165 primary school students (mean age of 11.21 ± 1.08 years, 65.5% females) participated in the study. The PRECEDE–PROCEED theoretical model for health education was adapted for this questionnaire. The questionnaire was divided into four main sections: predisposing, reinforcing, enabling factors and behaviour. Coefficient α reliability estimate was above 0.9 for most scales. The ICCs for different scales of the questionnaire were within the range of 0.402–0.800. Values for κ ranged from 0.412 to 0.785 for most scales.
Conclusions
The results showed reasonable validity, excellent reliability and moderate to substantial reproducibility for all scales of the questionnaire except two questions for κ statistics. The present study is of great importance, as there are no psychometrically evaluated tools (based on health behaviour models) with accepted validity and reliability for the evaluation of such factors in children with malnutrition. The questionnaire developed in the present study can be used to assess the effect of intervention among primary school students with malnutrition.
Abstract
Background The correlation between body iron stores and inflammation with insulin resistance in type 2 diabetes is not thoroughly investigated, especially in the Persian population.
Methods ...A cross-sectional study was designed in Tehran, Iran. Fifty-four people with type 2 diabetes and 53 matched healthy participants were included. Serum ferritin, total iron binding capacity, insulin resistance, C-reactive protein and tumor necrosis factor-α were measured in both groups.
Results Diabetic patients had higher insulin resistance, hemoglobin A1C and serum ferritin. Significant positive correlations were observed between insulin resistance with serum ferritin and tumor necrosis factor-α and between serum ferritin and tumor necrosis factor-α in diabetic patients.
Conclusions Inter-relationship between insulin resistance, serum ferritin and TNF-α was found in type 2 diabetic patients. Serum iron even in the normal range had positive correlation with insulin resistance. It may be because the normal ranges determined for serum ferritin are too wide and the criteria for iron overload are too high.
Abstract
BACKGROUND: Leptin, the product of the ob gene, could have a role in the pathogenesis of obesity and non-insulin dependent diabetes mellitus (NIDDM). The aim of this study was to investigate ...relationships between serum leptin concentration and insulin, glucose, HbA1c levels and insulin resistance in diabetic women.
METHODS: We studied 45 diabetic women and 45 healthy women (controls) who aged 45-60 years and had BMI of 25-30 kg/m2. Serum leptin, insulin, HbA1c, fasting blood sugar and insulin resistance were determined in the two groups.
RESULTS: There was a significant positive correlation between leptin and insulin (r = 0.295, P = 0.049) and insulin resistance (r = 0.329, P = 0.027) in controls but non-significant correlation between leptin and HbA1c and fasting blood sugar were observed in the two groups.
CONCLUSION: This study did not document any significant relationship between serum leptin and insulin, glucose, HbA1c and insulin resistance in diabetic women.
Keywords: Type 2 Diabetes Mellitus, Leptin, Insulin.
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