Synthesized Anti-HER2 Trastuzumab-MCC-DM1 Conjugate: An Evaluation of Efficacy and Cytotoxicity

Background: Trastuzumab is a humanized monoclonal antibody that targets site-specifically human epidermal growth factor-2 receptor (HER2) cell surface antigen overexpressed in approximately 20% of human breast carcinomas. Despite its positive therapeutic outcomes, a large proportion of individuals are unresponsive to the treatment with trastuzumab or develop resistance to it.Objective: To evaluate a chemically synthesized trastuzumab-based antibody-drug conjugate (ADC) to improve the trastuzumab therapeutic index.Methods: The current study explored the physiochemical characteristics of the trastuzumab conjugated to a cytotoxic chemotherapy agent DM1 via Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, created in our earlier study, using SDS-PAGE, UV/VIS, and RP-HPLC analyses. The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays. Three different formats of a HER2-targeting agent: trastuzumab, synthesized trastuzumab-MCC-DM1, and commercially available drug T-DM1 (Kadcyla®) were compared.Results: UV-VIS spectroscopic analysis showed that the trastuzumab-MCC-DM1 conjugates, on average, entailed 2.9 DM1 payloads per trastuzumab. A free drug level of 2.5% was determined by RP-HPLC. The conjugate appeared as two bands on a reducing SDS-PAGE gel. MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro. Importantly, the evaluations using LDH release and cell apoptosis assays confirmed that trastuzumab maintains its ability to induce cell death response while conjugating with the DM1. The binding efficiency of trastuzumab-MCC-DM1 was comparable to that of the naked trastuzumab.Conclusion: Trastuzumab-MCC-DM1 was found effective against HER2+ tumors. The potency of this synthesized conjugate brings it closer to the commercially available T-DM1

In vitro Cytotoxicity Effect of Lactobacillus casei on Kyse-30 Human Esophageal Cancer Cells

One of the top causes of cancer-related deaths globally is esophageal cancer. In investigations of cell toxicity, the MTT test is one of the most often used cell viability/cytotoxicity assays for cellular metabolic activity. Nowadays, lactobacilli with probiotic effectiveness are now acknowledged as a prophylactic agent against cancer. The anti-tumor product of these bacteria have been designated in numerous studies. This investigation examined the probiotic Lactobacillus casei's in vivo impact on esophageal cancer. The MTT technique was used in this work to evaluate the cytotoxicity of L. casei (supernatant and full cell culture) to 5fu on the cancer cell line Kyse30. L. casei was able to decrease cell survival in supernatant and full cell culture (Kyse30). The possible impact of L. casei, particularly their supernatant, on esophageal cancer was initially evaluated in this research. As a result, lactobacilli species show promise for future research and development as cancer treatments

The Effect of Teaching Cooking Skills to Parents on Health Status of Children and Adolescents: A Systematic Review

Background & Objectives: The present systematic review investigated and analyzed interventions in the field of parental skills in cooking healthy food in order to identify the most effective training methods to create a lasting and positive effect on the implications of health promotion of children and adolescents. Materials and Methods: Electronic search of databases was performed using the key words in English and Persian from Scopus, Proquest, Science Direct, Pub Med, Springer, Biomed Central, Google Scholar, Iran Medex and SID. The inclusion criteria were all educational interventions that included cooking healthy food with the aim to increase knowledge and skills of parents, or to assess the impact of interventions on children and adolescents, and that were published between January 2005 and September 2014. Results: Cooking skills educational interventions for parents were divided into two types 1: based on health education models and theories, and 2: without using health education models and theories. Among the seven articles reviewed, four studies were classified in the first group and three in the second group. The studies were compared based on changes in body mass index as well as the persistence of behavior change in the subsequent follow-ups. Conclusion: Use of multi-component education and follow-up that apply theories and models of health education are effective to reach the expected results. Clinical trials with several long-term strategies are required to create a favorable change in body mass index of children and teens

Texture and sensory characterization of functional yogurt supplemented with flaxseed during cold storage

In this study, flaxseed was used as a functional ingredient in yogurt formulations. The goal of this study was to produce prebiotic yogurt supplemented with flaxseed and investigation of its texture and sensory properties. Yogurt samples containing 0%–4% flaxseed was produced and stored at refrigerator (4–5°C) for 28 days. Textural properties were determined by texture analysis, and sensory characteristics were assessed by 26 trained panelists. Addition of flaxseed to yogurt samples increased the hardness, gumminess, chewiness, cohesiveness, and springiness values in produced yogurt samples. However, adhesiveness level was reduced in a sample enriched with flaxseed. By increasing flaxseed concentration, the color of samples was significantly different than the control sample; L* value was diminished and a* and b* value increased. Sensory scores including taste and mouthfeel, appearance, and overall acceptance showed reduction trend in samples containing a high level of flaxseed. In general, results showed that the addition of 2.63% flaxseed into yogurt samples lead to produce functional food with satisfactory texture, sensory characteristics that sustained these properties until 17.17 days after cold storage

Dimensions of aberrant driving behaviors and their association with road traffic injuries among drivers.

ObjectiveRoad traffic injuries (RTIs) are recognized as one of the most important causes of morbidity and mortality throughout the world, especially in developing countries. Human behavior is reportedly one of the critical factors in the occurrence of such injuries. The purpose of this study is to evaluate the correlation of abnormal driving behaviors with the frequency and severity of RTIs among drivers in Hamadan, west of Iran.MethodsThe present cross-sectional study was conducted on 800 people driving, who were selected by multistage cluster sampling technique. Data were collected using a three-part self-administered questionnaire including demographic, social and driving characteristics; the Manchester driver behavior questionnaire (DBQ); as well as information on a history of the occurrence of the injuries caused by the crashes and the severity of them. Data were statistically analyzed using numerical indices, linear regression analysis, Pearson correlation, ordinal logistic regression model and multinomial logistic regression.ResultsThe highest and lowest mean percentages of abnormal driving behavior were related to unintentional violations (19.13) and Lapses (16.44), respectively. "Changing radio stations and listening to music while driving", "overtaking a driver who drives slowly", and "unintentionally exceeding the speed limit" were the three highest behaviors associated with road traffic injuries, with the mean and standard deviation of (1.93 ± 1.4), (1.90±1.4), (1.58±1.3), respectively. Age, gender, educational level, driving experience and driving hours during the day were significantly associated with DBQ dimensions and severity of road traffic injuries.ConclusionsThe results of this study showed that socio-demographic characteristics were significantly correlated with driving behavior. In addition, driving behaviors were correlated with traffic crashes and the resulting injuries. The findings of this study can be utilized to develop driving behavior interventions among the drivers

Prevalence of depression and its associated sociodemographic factors among Iranian female adolescents in secondary schools

Abstract Background Across the globe, depression is a common psychiatric disorder and is the main cause of disability among adolescents. To this end, this study was conducted to screen for the prevalence of depression among secondary school female students in the city of Hamadan, in western Iran. Methods In this cross-sectional study, a total of 670 secondary school female students, within the age range of 15–18 years were investigated using multistage random sampling method. Moreover, the Persian version of Center for Epidemiologic Studies Depression Scale (CES-D) and a researcher-designed questionnaire containing demographic variables were employed as research instruments. Analyses of the findings were made using SPSS version 16 software followed by stratified logistic regression model, which was performed for correlation analysis. Results The mean (standard deviation) age of students was 16.2 (0.68) years. The prevalence of severe depression in female students estimated by the Center for Epidemiologic Studies Depression Scale (CES-D) was equal to 52.6%. A statistically significant relationship was also observed to exist between prevalence of depression and type of school (P < 0.001), family income (P < 0.001), living in the suburbs (P < 0.001), and field of study at school (P < 0.001). However, no statistically significant correlation was found between depression among students and school grade, type of living with parents, father’s education and occupation, mother’s education and occupation, and family size. Conclusion Depression was prevalent among the secondary school female students examined and it significantly correlated with socioeconomic status. Therefore, periodic screening, psychological training programs, proper diagnosis of high-risk individuals in secondary schools, and early intervention among secondary school female students are urgently needed

Promoting Oral Health in 6-12 Year-Old Students: A Systematic Review

Background and Objectives: The group of 6-12 year-old students are the main target of oral health programs due to the high prevalence of dental caries and the formation of permanent teeth during this age and the lifestyle-shaping nature of the period. Schools provide the easiest and most effective means of accessing this group. The present study was conducted to examine the impact of school-based interventions on improved oral health in 6-12 year-old students. Materials and Methods: The present systematic review searched for its English and Persian keywords in databases such as the Scopus, Proquest, Science Direct, Pubmed, Springer, Biomed Central, Google Scholar, IranMedex and SID and examined studies published between January 2004 and September 2014 about educational interventions aiming to prevent oral diseases and promote associated health behaviors in students. Results: The 17 studies selected for examination were divided into two categories: first, assessing an education based on self-care behaviors and preventive services second, assessing an education based on self-care behaviors only. Those interventions that were consistent in nature, involved the parents and the school personnel, used behavior change models, used a combination of several training methods, used practical experiences and provided preventive services were more effective in promoting knowledge and health behaviors and reducing dental caries and plaque in this group of children. Conclusion: Providing consistent community-based education, using a combination of several organized educational programs, following up on the children's progress, using behavior change theories and models and providing prevention services are the most effective measures for achieving the desired goals

High School Girl's Adherence to 5-a-Day Serving's Fruits and Vegetables: An Application Theory of Planned Behavior

Introduction: One of the basics of healthy eating is five times consumption of fruits and vegetable a day. Given the importance of recognizing effective factors of consuming fruit and vegetable in this group, the present study aimed to investigate high school girl's adherence to five-time serving fruits and vegetables per day in Hamadan based on the theory of planned behavior application. Materials and Methods: This descriptive-analytical study was performed on 400 girl students from high schools of Hamadan recruited with a multistage cluster sampling method. Participants filled out questionnaires including demographic variables, the theory of planned behavior constructs and a fruit and vegetable consumption measure one week later. Data analysis was performed using SPSS-18 by Chi-square, Pearson correlation and Logistic regression. Results: Fruit and vegetable consumption by female students is 3.4 times daily. Among the demographic variables, family size, mother's education, father's occupation, household income, body mass index and type of school had significant associations with fruit and vegetable consumption (P<0.05). Behavioral intention predicted 35% of the variation in daily fruit and vegetable consumption. Moreover, subjective norms, perceived behavioral control and attitude were able to predict 32% of behavioral intention. Conclusion: Fruit and vegetable consumption in female students is inadequate. The theory of planned behavior may be a useful framework to design a 5-A-Day intervention for female students

An In Vivo Study of Lactobacillus rhamnosus (PTCC 1637) as a New Therapeutic Candidate in Esophageal Cancer

OBJECTIVE: This study is aimed at investigating the effect of probiotic Lactobacillus rhamnosus on esophageal cancer in vivo and in vitro. METHODS AND RESULTS: In this study, the cytotoxicity effects of L. rhamnosus supernatant and whole-cell culture on a cancer cell line (Kyse30) compared to 5fu were evaluated by the MTT assay. The real-time PCR method was used to analyse the L. rhamnosus supernatant effect on the expression of Wnt signaling pathway genes. An in vivo investigation in nude mice was done to assess the anti-tumor activity of L. rhamnosus supernatant and whole-cell culture. Both supernatant and whole-cell culture of L. rhamnosus reduced cell survival (Kyse30) P < 0.001. The supernatant of this bacterium significantly reduced the expression of Wnt signaling pathway genes. Administration of supernatant and whole-cell culture of L. rhamnosus expressively reduced tumor growth compared to the control group. The effects of this bacterium on tumor necrosis were quite evident, pathologically P < 0.01. CONCLUSION: This study is the first report that assessed the potential impact of L. rhamnosus, especially its supernatant on esophageal cancer and Wnt signaling pathway genes. Therefore, this bacterium can be a harmless candidate for esophageal cancer therapy