Role of the transforming growth factor-β signaling pathway in the pathogenesis of colorectal cancer

The transforming growth factor-β (TGF-β) signaling pathway plays an important role in cancer cell proliferation, growth, metastasis, and apoptosis. It has been shown that TGF-β acts as a tumor suppressor in the early stages of the disease, and as a tumor promoter in its late stages. Mutations in the TGF-β signaling components, the TGF-β receptors and cytoplasmic signaling transducers, are frequently observed in colorectal carcinomas. Exploiting specific TGF-β receptor agonist and antagonist with antitumor properties may be a way of controlling cancer progression. This review summarizes the regulatory role of TGF-β signaling in the pathogenesis of colorectal cancer.     

Genetic Diversity of Thanatephorus cucumeris Infecting Tomato in Iran

The necrotrophic fungus Thanatephorus cucumeris (anamorph Rhizoctonia solani) is among the most important soil‐borne pathogens which causes tomato foot and root rot worldwide. We investigated virulence and genetic relationships among and within different taxonomic groups of R. solani from the tomato‐growing regions in the north‐east of Iran. Characterization of R. solani taxonomic groups revealed that, of 56 isolates, four were AG‐2‐1, 16 were AG‐3 PT, 21 were AG‐4 HG‐I and 15 were AG‐4 HG‐II. Because interprimer binding site (iPBS), which is based on amplification of retrotransposons, is known as novel and powerful DNA fingerprinting technology, we selected four iPBS primers, which can detect polymorphisms of tomato foot root and root rot pathogen, for investigating genotypic variability of the isolates. The iPBS analyses separated various taxonomic groups of R. solani and showed great diversity among the isolates, demonstrating that the R. solani isolates obtained from tomato were not a clonal population. Crop rotation strategies and geographic location seem to be important factors affecting genetic structure of the isolates. Pathogenicity tests on tomato cultivar ‘Mobil’ showed significant differences in the virulence of various isolates. The overall results indicated that isolates of AG‐3 and AG‐4 were more virulent than AG‐2‐1. There was no significant correlation between genetic diversity and virulence of the isolates. This is the first report of R. solani AG‐4 HG‐II, causing tomato foot and root rot. Also, our research is the first in assessment of genetic diversity in fungal populations using iPBS molecular markers.     

Synthesis and SAR studies of 3-allyl-4-prenyloxyaniline amides as potent 15-lipoxygenase inhibitors

15-Lipoxygenases are one of the nonheme iron-containing proteins with ability of unsaturated lipid peroxidation in animals and plants. The critical role of the enzymes in formation of inflammations, sensitivities and some of cancers has been demonstrated in mammalians. Importance of the 15-lipoxygenases leads to development of mechanistic studies, products analysis and synthesis of their inhibitors. In this work new series of the 3-allyl-4-allyoxyaniline amides and 3-allyl-4-prenyloxyaniline amides were designed, synthesized and their inhibitory potency against soybean 15-lipoxygenase were determined. Among the synthetic amides, 3-allyl-4-(farnesyloxy)-adamantanilide showed the most potent inhibitory activity by IC(50) value of 0.69μM. SAR studies showed that in spite of prenyl length increases, the effects of the amide size and its electronic properties on the inhibitory potency became predominant. The SAR studies was also showed that the orientation of allyl and prenyloxy moieties toward Fe core of the SLO active site pocket is the most suitable location for enzyme inhibition.     

The effectiveness of cognitive-behavioural play therapy on the symptoms of attention-deficit/hyperactivity disorder in children aged 7–9 years

Attention-deficit/hyperactivity disorder (ADHD) is considered to be the most prevalent disorder of childhood and adolescence, and a variety of methods have been used in its diagnosis and treatment. This study was conducted to study the efficacy of play therapy on the symptoms of ADHD in children aged 7–9 years. Using a clinical trial design, we selected 30 study participants among individuals who had been referred to the Ebne-sina hospital, child and adolescent outpatient clinic, Mashhad, Iran, and who had been diagnosed with ADHD by psychiatrists. The 30 study participants were then divided into two groups, experimental and control, based on similar characteristics (Birth order, parents’ educational level, parents’ occupation and average of last year school marks). Pre-tests (the Rutter Parental Questionnaire and the Rutter Children Behaviour Questionnaire for teachers) were performed prior to play therapy, and all patients in both groups had been receiving medication. Following play therapy, post-tests were also conducted for both groups. Eight sessions of sham play therapy has been performed for case group. (Cognitive-behavioural play therapy has not been performed basically.) All results were evaluated using an independent t test and a comparative test. Play therapy appeared to significantly reduce the symptoms of ADHD. The significant differences found between the experimental and control groups indicate that play therapy could be used as an effective treatment method for children with ADHD.     

Classification of ECG arrhythmia by a modular neural network based on Mixture of Experts and Negatively Correlated Learning

In this paper, we propose a novel ECG arrhythmia classification method using the complementary features of Mixture of Experts (ME) and Negatively Correlated Learning (NCL). Negative Correlation Learning and Mixture of Experts methods utilize different error functions for simultaneous training of negatively correlated Neural Networks. The capability of a control parameter for NCL is incorporated in the error function of ME, which enables the training algorithm of ME to establish a balance in bias-variance-covariance trade-offs. ECG records from the MIT-BIH arrhythmia database are selected as test data. It is observed that the proposed classification method not only preserves the advantages and alleviates the disadvantages of its basis approaches, but also offering significantly improved performance over the original methods.