Wnt pathway targeting reduces triple-negative breast cancer aggressiveness through miRNA regulation in vitro and in vivo

Triple-negative breast cancer, devoid of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is deprived of commonly used targeted therapies. MicroRNAs (miRNAs) are undergoing a revolution in terms of potentially diagnostic or therapeutic elements. Combining computational approaches, we enriched miRNA binding motifs of Wnt pathway-associated upregulated genes. Our in-depth bioinformatics, in vitro and in vivo analyses indicated that miR-381 targets main genes of the Wnt signaling pathway including CTNNB1, RhoA, ROCK1, and c-MYC genes. The expression level of miR-381 and target genes was assessed by quantitative real-time polymerase chain reaction (RT-qPCR) in MCF-7, MDA-MB-231, and MCF-10A as well as 20 breast cancer samples and normal tissues. Luciferase reporter assay was performed. Lentiviral particles containing miR-381 were used to evaluate the effect of miR-381 restoration on cell proliferation, migration, and invasion of the invasive triple-negative MDA-MB-231 cell line and also in a mouse model of breast cancer. The expression of miR-381 was lower than that of normal cells, especially in TNBC cell line and breast tissues. Luciferase assay results confirmed that miR-381 targets all the predicted 3′-untranslated regions (3′-UTRs). Upon miR-381 overexpression, the expression of target genes declined, and the migration and invasion potential of miR-381-receiving MDA-MB-231 cells decreased. In a mouse model of triple-negative breast cancer, miR-381 re-expression inhibited the invasion of cancer cells to lung and liver and prolonged the survival time of cancer cell-bearing mice. Therefore, miR-381 is a regulator of Wnt signaling and its re-expression provides a potentially effective strategy for inhibition of TNBC.     

2q35-rs13387042 variant and the risk of breast cancer: a case–control study

Molecular Biology Reports - Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease...     

A comparison study of the interaction between β-lactoglobulin and retinol at two different conditions: spectroscopic and molecular modeling approaches

The interaction between bovin β-Lactoglobulin (β-LG) and retinol at two different pH values was investigated by multispectroscopic, zeta potential, molecular modeling, and conductometry measurements. The steady state and polarization fluorescence spectroscopy revealed that complex formation at two different pH values could occur through a remarkable static quenching. According to fluorescence quenching, one set of binding site at pH 2 and two sets of binding sites at pH 7 were introduced for binding of retinol to β-LG that show the enhancement of saturation score of β-LG to retinol in dimmer condition. The polarization fluorescence analysis represented that there is more affinity between β-LG and retinol at pH 7 rather than at pH 2. The effect of retinol on β-LG was studied by UV-visible, circular dichroism (CD), and synchronous fluorescence, which indicated that retinol induced more structural changes on β-LG at pH 7. β-LG–retinol complex formation at two different pH values was recorded via applying resonance light scattering (RLS) and zeta potential. Conductometry and RLS showed two different behaviors of interaction between β-LG and retinol at two different pH values; therefore, dimmer formation played important roles in different behaviors of interaction between β-LG and retinol. The zeta potential was the implied combination of electrostatic and hydrophobic forces which are involved in β-LG–retinol complex at two different pH values, and the hydrophobic interactions play a dominant role in complex formation. Molecular modeling was approved by all experimental results. The acquired results suggested that monomer and dimmer states of β-LG can be induced by retinol with different behaviors.     

ARRHYTHMIA WITH MITRAL VALVE PROLAPSE: RESULTS OF ANNULOPLASTY IN TWO PATIENTS

The effectiveness of posterior annuloplasty in two patients who failed to respond to medical treatment for atrial and ventricular arrhythmias related to mitral valve prolapse (MVP) is reported. Although the etiology of arrhythmia in MVP remains mostly speculative, anatomic correction of prolapse or billowing of the mitral leaflets appears to reverse the anatomic and pathologic conditions that cause the arrhythmia.     

MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle,apoptosis, and proliferation

Molecular Biology Reports - Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the...     

Experimental measurements and Monte Carlo calculations for 103Pd dosimetry of the 12 mm COMS eye plaque

Monte Carlo simulations and TLD dosimetry have been performed to determine the dose distributions along the central axis of the 12 mm COMS eye plaques loaded with IRA1-¹⁰³Pd seeds. Several simulations and measurements have been employed to investigate the effect of Silastic insert and air in front of the eye on dosimetry results along the central axis of the plaque and at some critical ocular structures. Measurements were performed using TLD-GR200A circular chip dosimeters in a PMMA eye phantom. The central axis TLD chips locations were arranged in one central column of eye phantom, in 3 mm intervals. The off-axis TLD chips locations were arranged in three off-axis columns around the central axis column. Version 5 of the MCNP code was also used to evaluate the dose distribution around the plaque. The presence of the Silastic insert results in dose reduction of 14% at 5 mm; also about 7% dose reduction appears at the interface point, due to the air presence and lack of the scattering condition. The overall dosimetric parameters for the COMS eye plaque loaded with new palladium seeds are similar to a commercial widely used seed such as Theragenics200. As the dose calculations under TG-43 assumptions do not consider the effect of the plaque backing and Silastic insert for accurate dosimetry, it's suggested to apply the effect of the eye plaque materials and air on dosimetry results along the central axis of the plaque and at some critical ocular structures.     

Truncatella angustata associated with grapevine trunk disease in northern Iran

In recent years, grapevine trunk diseases have gained growing attentions due to worldwide incidence of the disease. In a survey on fungal agents associated with grapevine trunk diseases in northern Iran, wood samples were collected from grapevines having the symptoms of declination. Isolation was made using routine plant pathology methods. A coelomycetous fungus with appendage-bearing conidia was recovered from symptomatic tissues. Based on morphological and cultural characteristics, the causal agent of the disease was identified as Truncatella angustata. The identity of the species was further confirmed by sequence data of internal transcribed spacer-rDNA region. A phylogeny inferred using sequence data obtained in this study, together with the sequences from GenBank, clustered our isolates together with T. angustata known from other host plant species. Pathogenicity tests performed on detached shoots of grapevines led to the same symptoms as observed in field conditions. This is first study on the pathogenicity of T. angustata on grapevine in Iran and first report on the occurrence of T. angustata on grapevine in Iran.     

Secretory Expression of a Chimeric Peptide in Lactococcus lactis: Assessment of its Cytotoxic Activity and a Deep View on Its Interaction with Cell-Surface Glycosaminoglycans by Molecular Modeling

Probiotics and Antimicrobial Proteins - Nowadays, cancer remains a major cause of death affecting millions of people. Currently, the antimicrobial peptides (AMPs) as potent anticancer therapeutic...