Key microRNAs in the biology of breast cancer; emerging evidence in the last decade

microRNAs (miRNAs) are a family of small noncoding RNAs that play a pivotal role in the regulation of main biological and physiological processes, including cell cycle regulation, proliferation, differentiation, apoptosis, stem cell maintenance, and organ development. Dysregulation of these tiny molecules has been related to different human diseases, such as cancer. It has been estimated that more than 50% of these noncoding RNA sequences are placed on fragile sites or cancer-associated genomic regions. After the discovery of the first specific miRNA signatures in breast cancer, many studies focused on the involvement of these small RNAs in the pathophysiology of breast tumors and their possible clinical implications as reliable prognostic biomarkers or as a new therapeutic approach. Therefore, the present review will focus on the recent findings on the involvement of miRNAs in the biology of breast cancer associated with their clinical implications.     

A recombinant Plasmodium vivax apical membrane antigen-1 to detect human infection in Iran

In Iran, Plasmodium vivax is responsible for more than 80% of the infected cases of malaria per year. Control interventions for vivax malaria in humans rely mainly on developed diagnostic methods. Recombinant P. vivax apical membrane antigen-1 (rPvAMA-1) has been reported to achieve designing rapid, sensitive, and specific molecular diagnosis. This study aimed to perform isolation and expression of a rPvAMA-1, derived from Iranian patients residing in an endemic area. Then, the diagnostic efficiency of the characterized Iranian PvAMA-1 was assessed using an indirect ELISA method. For this purpose, a partial region of AMA-1 gene was amplified, cloned, and expressed in pET32a plasmid. The recombinant His-tagged protein was purified and used to coat the ELISA plate. Antibody detection was assessed by indirect ELISA using rPvAMA-1. The validity of the ELISA method for detection of anti-P. vivax antibodies in the field was compared to light microscopy on 84 confirmed P. vivax patients and compared to 84 non-P. vivax infected individuals. The ELISA cut-off value was calculated as the mean+2SD of OD values of the people living in malaria endemic areas from a south part of Iran. We found a cut-off point of OD=0.311 that showed the best correlation between the sera confirmed with P. vivax infection and healthy control sera. A sensitivity of 81.0% and specificity of 84.5% were found at this cut off titer. A good degree of statistical agreement was found between ELISA using rPvAMA-1 and light microscopy (0.827) by Kappa analysis.     

Multi-targeting of K-Ras domains and mutations by peptide and small molecule inhibitors

K-Ras activating mutations are significantly associated with tumor progression and aggressive metastatic behavior in various human cancers including pancreatic cancer. So far, despite a large number of concerted efforts, targeting of mutant-type K-Ras has not been successful. In this regard, we aimed to target this oncogene by a combinational approach consisting of small peptide and small molecule inhibitors. Based on a comprehensive analysis of structural and physicochemical properties of predominantly K-Ras mutants, an anti-cancer peptide library and a small molecule library were screened to simultaneously target oncogenic mutations and functional domains of mutant-type K-Ras located in the P-loop, switch I, and switch II regions. The selected peptide and small molecule showed notable binding affinities to their corresponding binding sites, and hindered the growth of tumor cells carrying K-Ras^G12D and K-Ras^G12C mutations. Of note, the expression of K-Ras downstream genes (i.e., CTNNB1, CCND1) was diminished in the treated Kras-positive cells. In conclusion, our combinational platform signifies a new potential for blockade of oncogenic K-Ras and thereby prevention of tumor progression and metastasis. However, further validations are still required regarding the in vitro and in vivo efficacy and safety of this approach.     

Synthesis and characterization of cobalt oxide nanoparticles by thermal treatment process

The simple preparation of Co₃O₄ nanoparticles from a solid organometallic molecular precursor N-N′-bis(salicylaldehyde)-1,2-phenylenediimino cobalt(II); Co(salophen) has been achieved via two simple steps: firstly, the Co(salophen) precursor was precipitated from the reaction of cobalt(II) acetate and N-N′-bis(salicylaldehyde)-1,2-phenylenediimino; H₂salophen; in propanol under nitrogen condition; then, cubic phase Co₃O₄ nanoparticles with the size of mostly 30-50 nm could be produced by thermal treatment of the Co(salophen) in air at 773 K for 5 h. The as-synthesized products were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and scanning electronic microscopy (SEM). These results confirm that the resulting oxide was pure single-crystalline Co₃O₄ nanoparticles. The optical property test indicates that the absorption peak of the nanoparticles shifts towards short wavelength, and the blue shift phenomenon might be ascribed to the quantum effect. The hysteresis loops of the obtained samples reveal the ferromagnetic behaviors the enhanced coercivity (H_c) and decreased saturation magnetization (M_s) in contrast to their respective bulk materials.     

RGD conjugation to polyethyleneimine does not improve DNA delivery to bone marrow stromal cells

Bone marrow stromal cells (BMSC) modified with therapeutic genes are being actively pursued for gene therapy protocols. To develop safe and effective nonviral methods for BMSC modification, the cationic polymer polyethyleneimine (PEI) has been utilized to condense plasmid DNA for intracellular delivery. This study was conducted to explore the feasibility of increasing the PEI's effectiveness by coupling integrin-binding arginine-glycine-aspartic acid (RGD) peptides to the polymer. BMSC from rats were isolated and expanded in culture for gene transfer studies. In contrast to our expectations, RGD-conjugated PEI did not exhibit an enhanced binding to BMSC. This was the case where the peptides were conjugated to PEI by short, disulfide linkages or long poly(ethylene glycol) linkages. Using a reporter gene for the enhanced green fluorescent protein, the transfection efficiency of RGD-conjugated PEI was also lower than the delivery by the native PEI, which exhibited equivalent transfection efficiency to that of an adenovirus. We conclude that native PEI was sufficient for the transformation of BMSC and that coupling of the integrin-binding RGD-peptides did not improve the effectiveness of this polymer for BMSC transfection.     

Transient Global Amnesia after Ablation of Premature Ventricular Beats Arising from the Right Coronary Cusp

A 58-year-old female underwent PVC ablation within the right coronary cusp for symptomatic PVCs and suspected PVC-induced cardiomyopathy. Immediately after the procedure, she started to complain about feelings of impending doom, disorientation to time and place, and amnesia regarding the procedure. No sensory or motor deficits could be elicited. A thromboembolic event was suspected and she was evaluated by a neurologist. CT scan of her brain was negative. She was diagnosed with transient global amnesia and her mentation returned to baseline within 4 hours after the procedure.     

Effects of housing condition and early corticosterone treatment on learned features of song in adult male zebra finches

Early developmental stress can have long-term physiological and behavioral effects on an animal. Developmental stress and early corticosterone (Cort) exposure affect song quality in many songbirds. Early housing condition can act as a stressor and affect the growth of nestlings and adult song, and improvements in housing condition can reverse adverse effects of early stress exposure in rodents. However, little is known about this effect in songbirds. Therefore, we took a novel approach to investigate if housing condition can modify the effects of early Cort exposure on adult song in male zebra finches. We manipulated early housing conditions to include breeding in large communal flight cages (FC; standard housing condition; with mixed-sex and mix-aged birds) versus individual breeding cages (IBC, one male–female pair with small, IBC-S, or large clutches, IBC-L) in post-hatch Cort treated male birds. We found that Cort treated birds from IBC-S have higher overall song learning scores (between tutor and pupil) than from FC but there is no difference between these groups in the No-Cort treated birds. When examining the effects of Cort within each housing condition, overall song learning scores decreased in Cort treated birds from flight cages but increased in birds from IBC-S compared to controls. Likewise, the total number of syllables and syllable types increased significantly in Cort treated birds from IBC-S, but decreased in FC-reared birds though this effect was not statistically significant. These findings suggest that the effects of early Cort treatment on learned features of song depend on housing condition.