HER2-targeted therapy reduces incidence and progression of midlife mammary tumors in female murine mammary tumor virus huHER2-transgenic mice.

PURPOSE: This study examined the effectiveness of early and prolonged mu4D5 (the murine form of trastuzumab/Herceptin) treatment in transgenic mice that overexpress human HER2 (huHER2), under the murine mammary tumor virus promoter, as a model of huHER2-overexpressing breast cancer. EXPERIMENTAL DESIGN: Mice were randomly assigned to one of three treatment groups and received i.p. injections from 17 weeks of age until either 52 weeks of age or morbidity. Fourteen mice received 100 mg/kg mu4D5, 14 mice received 100 mg/kg antiherpes simplex virus glycoprotein D control antibody, and 11 mice received a diluent control. RESULTS: High levels of huHER2 expression were detectable in mammary glands of young virgin founder mice. Mammary adenocarcinomas were frequently found in female founders and progeny at an average age of 28 weeks, with some progressing to metastatic disease. The incidence of mammary tumors was significantly reduced, and tumor growth inhibition was observed in mice receiving mu4D5 compared with control mice. In addition, Harderian gland neoplasms, highly associated with overexpression of huHER2 in this transgenic line, were entirely absent in the mu4D5 treatment group, indicating down-regulation of huHER2 in vivo activity. CONCLUSIONS: Early intervention with mu4D5 was of benefit in our transgenic mice at high risk for developing huHER2-overexpressing breast cancer. This study suggests a potential benefit of early treatment with Herceptin in HER2-positive primary breast cancer.     

Factors Associated with Tobacco Use among Iranian Adolescents: An Application of Protection Motivation Theory

Background: Tobacco use is a significant predisposing factor to many diseases. Protection motivation theory is a well-suited theory, since fear can motivate individuals to change their unhealthy behaviors. Objective: This study was conducted to examine the associations between the constructs of this theory with intention and tobacco use behavior. Method: The present cross-sectional study was conducted in Noshahr, Iran. The participants were 440 high school boys selected using a stratified random sampling in 2016. A questionnaire about tobacco use based on protection motivation theory was developed and its validity and reliability were assessed. The questionnaire included the demographic information, the constructs of theory, and tobacco use behavior. Structural equation modeling was used to test the associations between the constructs with intention and tobacco use. Results: The variables of perceived vulnerability (β = 0/137, P < 0.001), fear (β = 0/149, P < 0.001), self-efficacy (β = 0/249, P < 0.001), perceived intrinsic reward (β = ?0.285, P < 0.001), threat appraisal (β = ?0.25, P < 0.001), and coping appraisal (β = 0.358, P < 0.001) had direct effect and are significant with intention. Moreover, perceived vulnerability (β = ?0.158, P < 0.001), fear (β = ?0.172, P < 0.001), self-efficacy (β = ?0.288, P < 0.001), perceived intrinsic reward (β = 0.329, P < 0.001), threat appraisal (β = 0.265, P < 0.001), and coping appraisal (β = ?0.379, P < 0.001) affected tobacco use indirectly through intention and were significantly associated with behavior. Also, intention had direct effect and is significant with tobacco use (β = ?1.156, P < 0.001). Conclusions: The protection motivation theory provides a useful framework for investigating factors of tobacco use among male students. Future tobacco prevention interventions should focus on increasing the vulnerability and fear, decreasing intrinsic reward, and improving self-efficacy to reduce tobacco use.     

Deep eutectic solvent mediated rapid and selective one-pot synthesis of 5-alkylidene-Thiazolones

Deep eutectic solvents (DESs) were used as environmentally benign and straightforward replacements for the harmful organic solvents and transition metal-based catalysts in various organic syntheses. Here, we report a DES as a mild, biocompatible, and environmentally friendly dual solvent/catalyst for the one-pot construction of 2-amino-5-alkylidenethiazol-4-ones throw one-pot reaction of carbonyl compounds, nitrogen compounds, and rhodanine up to quantitative yields within a latent period of times. This green procedure has a more diverse and broader scope regarding starting materials and exhibits excellent conversion and high selectivity. In particular, DES displays better durability and reusability in the multicomponent reactions than traditional catalysts and solvents without distinct deterioration in catalytic activity.     

Dietary total antioxidant capacity and incidence of chronic kidney disease in subjects with dysglycemia: Tehran Lipid and Glucose Study

Purpose

We aimed to investigate the association of dietary total antioxidant capacity (TAC) with incidence of CKD in subjects with dysglycemia.

Methods

We followed-up 1179 subjects aged ≥30 years with dysglycemia from the Tehran Lipid and Glucose Study (TLGS) for 3 years, who were initially free of CKD. Dietary intakes of TAC, vitamin C, vitamin E, and β-carotene were assessed by a food-frequency questionnaire at the baseline. Dietary TAC was estimated using the oxygen radical absorbance capacity method. Estimated glomerular filtration rate (eGFR) was calculated, using the Modification of Diet in Renal Disease Study equation and CKD was defined as eGFR <60 mL/min/1.73 m². Odds ratios (ORs) using multivariable logistic regression were reported for the association of incident CKD with dietary TAC.

Results

A total of 197 (16.7%) cases of incident CKD were recorded after 3 years of follow-up. After adjustment for age, sex, smoking, physical activity, body mass index, hypertension, and total energy intake, the top tertile of dietary TAC compared to the bottom was associated with 39% [95% confidence interval (CI) = 0.40–0.93] lower risk of incident CKD (P for trend = 0.025). Furthermore, the highest tertile of vitamin C intake compared to the lowest risk of incident CKD was decreased (OR 0.60; 95% CI 0.38–0.93, P trend 0.023). Intakes of vitamin E and β-carotene were not significantly associated with incident CKD risk.

Conclusion

Our findings suggest that diets high in TAC are associated with a lower risk of incident CKD among subjects with hyperglycemia after 3 years of follow-up.

     

Comparison of Calorie-Restricted Diet and Resveratrol Supplementation on Anthropometric Indices,Metabolic Parameters,and Serum Sirtuin-1 Levels in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial

Objective: There is a promising perspective regarding the potential effect of resveratrol in preventing and treating metabolic disturbances similar to that of calorie restriction. The aim of this study was to evaluate the effects of calorie-restricted (CR) diet on metabolic parameters and then to investigate whether resveratrol supplementation has beneficial effects similar to CR diet in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: This randomized controlled clinical trial was conducted in 90 patients with NAFLD (males and females) aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m². Participants were assigned to one of three intervention groups as follows: The CR diet group (n = 30) received a prescribed low-calorie diet, the resveratrol group (n = 30) received 600 mg pure trans-resveratrol (2 × 300 mg) daily, and the placebo group (n = 30) received placebo capsules (2 × 300 mg) daily for 12 weeks. Fasting blood samples, anthropometric measurements, and dietary intake and physical activity data were collected for all participants at baseline and at the end of the trial.

Results: CR diet significantly reduced weight (by 4.5%); BMI; waist circumference; waist-to-hip ratio; and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles in participants compared to resveratrol and placebo (all p < 0.05). Significant reductions in weight (by 1.1%) and BMI were found in the resveratrol group compared to the placebo group (p < 0.05). ALT, AST, and lipid profiles did not change significantly in the resveratrol group (all p > 0.05). No significant changes were seen in hepatic steatosis grade, serum glycemic parameters, and high-density lipoprotein cholesterol and sirtuin-1 levels in any group (all p > 0.05).

Conclusions: CR diet with moderate weight loss has favorable effects on NAFLD, and resveratrol supplementation induced weight loss but failed to mimic other aspects of CR diet. Future studies are warranted to evaluate the long-term and dose-dependent effects of resveratrol on metabolic diseases.