Dysregulation of miR-638 in breast cancer patients and bioinformatics investigation of its target genes in apoptosis, angiogenesis and autophagy pathways

Background: Breast cancer, as the most frequent cancer diagnosed in women worldwide, is affected by different regulatory mechanisms and cellular processes such as microRNAs (miRNAs) and autophagy, which influence tumor cell progression. MiRNAs play a crucial role in cancer progression. Aberrant miRNA expression has been described in various human cancers. Growing evidence proposes that miRNAs have a considerable role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. Objectives: The aim of this study was to evaluate miRNA-638 (miR-638) expression level in breast cancer patients and its bioinformatics analysis. Methods: In this case-control study, miR-638 expression was examined in fresh breast tissues of 47 patients with breast cancer using real time polymerase chain reaction (PCR). Then the role of miR-638 in various signaling pathways was studied using Target Scan, the MicroRNA-Target Interactions (miRTarBase) database, miRWalk2.0 and the database for annotation, visualization and integrated discovery (DAVID). Results: The miR-638 expression level showed a significant decrease in breast cancer patients. Also, this miRNA might be involved in apoptosis, angiogenesis, and autophagy. Conclusions: According to the results, miR-638 can be used as a potential prognostic biomarker for cancer growth, and its low expression is thought to increase cancer progression by disrupting cell death and autophagy, which are considered as important pathways in breast cancer

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Preparation of ZnO and ZnS nanoparticles and in-vitro study of their antimicrobial effect

Zinc sulfide (ZnS) & zinc oxide (ZnO) nanoparticles was evaluated for their antimicrobial activity against four pathogenic strains. ZnS&ZnO nanoparticles were synthesized by simple aqueous chemical reaction in an aqueous solution. The main advantage of these nanoparticles (size of 10-30 nm) was that simply could be prepared by using cheap precursors in a cost effective and high throughput manner. Structural, morphological and chemical composition of the prepared nanoparticles were investigated by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and energy dispersion X-ray dispersive fluorescence spectroscopy (EDAX). The antimicrobial effects of the ZnS&ZnOnanoparticls were studied by serial dilution technique and also by well diffusion technique against four pathogenic microorganism strains of Staphyloccusaureus, Escherichia coli, Pseudomonas aeroginosa and Candidiaalbicans. Both nanoparticles of ZnS&ZnO showed antimicrobial activity against both Gram positive Staphyloccusaureus and Gram negative Escherichia coli and Pseudomonas aeroginosa and fungi of Candidiaalbicans. The best antimicrobial efficacy (as MIC of 50 µg/ml) was related to effect of ZnO nanoparticles on Staphyloccusaureus and most resistant pathogen was Candidiaaibicans against ZnS nanoparticles with MIC more than 250 µg/ml. Zinc sulfide (ZnS) & zinc oxide (ZnO) nanoparticles was evaluated for their antimicrobial activity against four pathogenic strains. ZnS&ZnO nanoparticles were synthesized by simple aqueous chemical reaction in an aqueous solution

TLR4 and TLR2 Expression in Biopsy Specimens from Antral and Corporal Stomach Zones in Helicobacter pylori Infections

Background: It is not yet known which types of Toll-like receptors (TLRs) are most effective in Helicobacter pylori (H. pylori) recognition. It is also not known which gastric zones have the most prominent roles in TLR-mediated bacterial recognition. The aim of this work was to analyze the expression of TLR2 and TLR4 in biopsy specimens from H. pylori-infected patients. Methods: Thirty-eight patients with gastrointestinal disorders were divided into four groups in this study. The groups were: (A) H. pylori infection and peptic ulcer (n=15), (B) peptic ulcer only (n=5), (C) H. pylori infection only (n=10) and (D) control, with neither H. pylori infection nor peptic ulcer (n=8). Biopsy specimens from sites of redness or atrophic mucosa from gastric antrum and body in patients with gastritis were collected. RNAs from the antrum and body specimens were isolated. TLR2 and TLR4 mRNA expression was assessed by RT-PCR and quantified as densitometric ratios of TLR2 and TLR4/β-actin mRNA. Results: In the antral zones of H. pylori-infected patients (Groups A and C) TLR2 and TLR4 expression was significantly greater than in uninfected patients (Groups B and D) regardless of peptic ulcers (p < 0.05). In the gastric body samples TLR2 expression was significantly greater in Group C (H. pylori infection only) than in Group B (peptic ulcer only) and TLR4 expression was significantly greater in group A (H. pylori infection and peptic ulcer) than in Group B (peptic ulcer only) (p < 0.05). No significant differences in expression of TLR4 and TLR2 were observed between samples from the antrum and body in same groups. Conclusions: We conclude that H. pylori infection leads to significant increase in TLR2 and TLR4 molecules expression in antral region related to the control group. Considering the stimulatory effect of H. pylori on TLRs expression in the gastric tissue, we assume that colonization of H. pylori infection might occurs more in the gastric antral region than in the gastric body

The effect of autophagy-related MicroRNAs on FIP200, ATG13 and HIF1A expression levels in breast cancer patients

Autophagy acts like a double-edged sword in either tumor promotion or suppression of breast cancer. Crosstalk between miRNAs and autophagic targets is one interesting scenario for the dual behavior of this pathway. On this basis the present study was designed to evaluate the expression pattern of certain candidate miRNAs and their targets in breast cancer patients. A total of 47 fresh breast carcinomas and matched adjacent non-neoplastic tissues were obtained. Bioinformatics analysis of putative miRNA binding sites identified miR-133, and miR-206, miR-199a/b, as regulating expressions of the FIP200, ATG-13 and HIF1a, respectively. The expression levels of candidate miRNAs and their targets were examined using quantitative Real-Time Polymerase Chain Reaction. Our results demonstrated that all four miRNAs expression levels are downregulated in breast tumor tissue compared with corresponding non-neoplastic tissue. Decreased expression of miR-133 and miR-199b showed a significant correlation with tumor grade. Moreover, a significant downregulation of miR-199b was observed in HER-2-negative patients. We found that FIP200 and ATG13 were downregulated in tumor tissues while HIF1a showed a significant upregulation. No significant association between the target genes and clinicopathological features was observed. Our data clarified a strong positive correlation between expression levels of miR-133 and FIP200 while the correlation between miR-206 and ATG13, and, miR-199a/b and HIF1a were not statistically significant. In conclusion, these results support the regulatory role of miR-133 during breast cancer development via the autophagy pathway and provide an opportunity to develop targeted therapeutics for breast cancer

A Patient With Desmoid Tumors and Familial FAP Having Frame Shift Mutation of the APC Gene

Desmoids tumors, characterized by monoclonal proliferation of myofibroblasts, could occur in 5-10% of patients with familial adenomatous polyposis (FAP) as an extra-colonic manifestation of the disease. FAP can develop when there is a germ-line mutation in the adenomatous polyposis coli gene. Although mild or attenuated FAP may follow mutations in 5΄ extreme of the gene, it is more likely that 3΄ extreme mutations haveamore severe manifestation of thedisease. A 28-year-old woman was admitted to the Cancer Institute of Iran with an abdominal painful mass. She had strong family history of FAP and underwent prophylactic total colectomy. Pre-operative CT scans revealed a large mass. Microscopic observation showed diffuse fibroblast cell infiltration of the adjacent tissue structures. Peripheral blood DNA extraction followed by adenomatous polyposis coli gene exon by exon sequencing was performed to investigate the mutation in adenomatous polyposis coli gene. Analysis of DNA sequencing demonstrated a mutation of 4 bpdeletions at codon 1309-1310 of the exon 16 of adenomatous polyposis coli gene sequence which was repeated in 3 members of the family. Some of them had desmoid tumor without classical FAP history. Even when there is no familial history of adenomatous polyposis, the adenomatous polyposis coli gene mutation should be investigated in cases of familial desmoids tumors for a suitable prevention. The 3΄ extreme of the adenomatous polyposis coli gene is still the best likely location in such families

Comparative Analyses of Villin and HER-2 Genes Expression in Breast Cancer

Background: It has been previously demonstrated that HER-2 (human epidermal growth Factor receptor 2) positive breast cancers are associated with an aggressive nature. Villin is an actin bundling protein that plays a key role in actin reorganization and cell remodeling during stress. In this study, we aimed to investigate the correlation of Villin gene expression with HER-2 in breast cancer patients. Methods: Samples of 42 patients with breast cancer, and 3 controls were collected. Expression of Villin and HER-2 genes were monitored with real-time PCR using pre-designed primers. Student T-test was used to compare the means between the groups. Results: The mean age of the patients was 50±4.11years. Expression of the Villin gene was decreased in 28 samples (18 and 10 samples with negative and strongly HER-2 positive, respectively). Villin gene expression was increased in 14 samples (7, 2 and 5 samples with negative, weakly positive, and strongly HER-2 positive, respectively). The expression of Villin was significantly correlated with HER-2 positive status (P = 0.00057) Conclusions: We found that Villin gene expression is associated with HER-2 positivity and may be a predicting factor in aggressive breast cancer

Intervenção educacional com base em modelo para aumentar a atividade física entre adolescentes iranianos

OBJETIVO: Avaliar um programa educacional com base no modelo de promoção da saúde (MPS) e nos estágios de mudança para melhorar a atividade física (AF) entre adolescentes iranianos. MÉTODOS: Este foi um ensaio randomizado controlado com 165 participantes divididos em dois grupos (intervenção/controle). Os dados foram coletados através de questionários de autopreenchimento com base em componentes do MPS (benefícios e barreiras para a ação, autoeficácia, sentimentos em relação ao comportamento, influências interpessoais e situacionais). A escala de estágios de mudança foi utilizada para selecionar participantes aptos (classificados nos estágios de pré-contemplação, contemplação ou preparação) e para avaliar a tendência. Após a coleta dos dados de base, a intervenção foi realizada nos participantes e os dados de acompanhamento foram coletados 3 meses depois. RESULTADOS: Ao todo, 88 meninos e 77 meninas com idade média de 13,99±0,4 participaram do estudo. As diferenças em todos os componentes do MPS, exceto os sentimentos em relação ao comportamento e as influências sociais, foram significantes (p < 0,01) entre os valores de base e de acompanhamento. Comparados aos do grupo de controle, os adolescentes do grupo de intervenção foram categorizados nos estágios de ação (70%) ou preparação (30%) no acompanhamento. A análise de regressão múltipla revelou que preferências concorrentes, normas sociais, modelos sociais (variáveis com p < 0,001) e o compromisso com o plano de ação podem prever consideravelmente o comportamento quanto à AF. O modelo representou 22,5% da variação da AF. CONCLUSÕES: Intervenções educacionais com base nos estágios de mudança podem ter implicações importantes na melhora da AF entre adolescentes em mais componentes do MPS