The Therapeutic Potential of PI3K/Akt/mTOR Inhibitors in Breast Cancer: Rational and Progress

Breast cancer (BC) is the most commonly diagnosed cancer in women. The PI3K/AKT/mTOR pathway is among the most frequently dysregulated pathways in patients with BC. The activation of this pathway is associated with increased cell growth and clinical outcome, and its overexpression is associated with a poor prognosis. It has been proposed that it may be of importance as a potential therapeutic target in the treatment of BC. The aim of current review is to provide an overview of the potential utility of PI3K/Akt/mTOR inhibitors in patients with BC, with particular emphasis on recent preclinical and clinical studies. J. Cell. Biochem. 119: 213–222, 2018. © 2017 Wiley Periodicals, Inc.     

Using the PCR and Blood Agar in Diagnosis of Semen Bacterial Contamination of Fertile and Infertile Men

Background:One of the causes of male infertility is Genital tract infections (GTI). Considering the importance of GTI, widespread recognition of them seems necessary. we aimed to characterize and compare semen microbial populations in fertile and infertile men who referred to an infertility clinic in Yazd, Iran.Methods:Semen samples were collected from two groups of fertile (268) and infertile (210) men. Sperm analysis (concentration, morphology, viability and motility parameters) were performed according to the World Health Organization (WHO) 2010 guidelines laboratory manual. Bacterial isolation was performed in Sheep Blood Agar and Eosin Methylene Blue (EMB) agar plates. For PCR, samples were analyzed with genus specific primers.Results:All semen characteristics were poor in the infertile group compared to those in the fertile men (p-value< 0.05). Enterococcus spp. (18.7%, 17.1%; p= 0.814), E. coli (7.9%, 11.4%; p= 0.486), Staphylococcus aureus (6.4%, 2.9%; p= 0.398) and Proteus mirabilis (0%, 2.9%; p= 0.002) were the most common agents, respectively. Also, the results obtained from PCR were confirmed using culture-base method.Conclusion:Proteus mirabilis contamination was identified in the infertile group. While no significant association was observed between male infertility and semen microbial populations, p. mirabilis may be the leading cause of reproduction impairment in men.Key Words: Infertility, Microbial contamination, culture, PCR     

Comparison of the binding behavior of FCCP with HSA and HTF as determined by spectroscopic and molecular modeling techniques

The interaction of carbonylcyanide p‐(trifluoromethoxy) phenylhydrazone (FCCP) with human serum albumin (HSA) and human transferrin (HTF) was investigated using multiple spectroscopy, molecular modeling, zeta‐potential and conductometry measurements of aqueous solutions at pH 7.4. The fluorescence, UV/vis and polarization fluorescence spectroscopy data disclosed that the drug–protein complex formation occurred through a remarkable static quenching. Based on the fluorescence quenching, two sets of binding sites with distinct affinities for FCCP existed in the two proteins. Steady‐state and polarization fluorescence analysis showed that there were more affinities between FCCP and HSA than HTF. Far UV‐CD and synchronous fluorescence studies indicated that FCCP induced more structural changes on HSA. The resonance light scattering (RLS) and zeta‐potential measurements suggested that HTF had a greater resistance to drug aggregation, whereas conductometry measurements expressed the presence of free ions improving the resistance of HSA to aggregation. Thermodynamic measurements implied that a combination of electrostatic and hydrophobic forces was involved in the interaction between FCCP with both proteins. The phase diagram plots indicated that the presence of second binding site on HSA and HTF was due to the existence of intermediate structures. Site marker competitive experiments demonstrated that FCCP had two distinct binding sites in HSA which were located in sub‐domains IIA and IIIA and one binding site in the C‐lobe of HTF as confirmed by molecular modeling. The obtained results suggested that both proteins could act as drug carriers, but that the HSA potentially had a higher capacity for delivering FCCP to cancerous tissues. Copyright © 2013 John Wiley & Sons, Ltd.     

Analysis of Comparative Sequence and Genomic Data to Verify Phylogenetic Relationship and Explore a New Subfamily of Bacterial Lipases

Thermostable and organic solvent-tolerant enzymes have significant potential in a wide range of synthetic reactions in industry due to their inherent stability at high temperatures and their ability to endure harsh organic solvents. In this study, a novel gene encoding a true lipase was isolated by construction of a genomic DNA library of thermophilic Aneurinibacillus thermoaerophilus strain HZ into Escherichia coli plasmid vector. Sequence analysis revealed that HZ lipase had 62% identity to putative lipase from Bacillus pseudomycoides. The closely characterized lipases to the HZ lipase gene are from thermostable Bacillus and Geobacillus lipases belonging to the subfamily I.5 with ≤ 57% identity. The amino acid sequence analysis of HZ lipase determined a conserved pentapeptide containing the active serine, GHSMG and a Ca²⁺-binding motif, GCYGSD in the enzyme. Protein structure modeling showed that HZ lipase consisted of an α/β hydrolase fold and a lid domain. Protein sequence alignment, conserved regions analysis, clustal distance matrix and amino acid composition illustrated differences between HZ lipase and other thermostable lipases. Phylogenetic analysis revealed that this lipase represented a new subfamily of family I of bacterial true lipases, classified as family I.9. The HZ lipase was expressed under promoter P_lac using IPTG and was characterized. The recombinant enzyme showed optimal activity at 65°C and retained ≥ 97% activity after incubation at 50°C for 1h. The HZ lipase was stable in various polar and non-polar organic solvents.     

Modeling of habitat suitability of Asiatic black bear (Ursus thibetanus gedrosianus) in Iran in future

Future changes in climate are imminent and they threat endangered and rare species due to habitat destruction. The Asiatic black bear (Ursus thibetanus gedrosianus) is a rare and vulnerable species whose habitat fragmentation and habitat loss decreased the size of its population significantly. Climate change is another threat to this species that is investigated in this research work. Aiming at this goal, ten species distribution models (SDMs) were applied as helpful tools for evaluating the potential effectiveness of climate change in habitat suitability of Asiatic black bear in Iran. Potential dispersal of Asiatic black bear was modeled as a function of 32 environmental variables for the current time and 2070 for 44 climate change scenarios (CC scenario) of future climate. Our results showed that modeling result depended on type of model. Our results confirmed that one of the greatest threats in the near future for Asiatic black bear was the change of suitable habitat due to climate change. All the CC scenarios showed that migration of this species would be to the north and west areas with higher elevation and that an increase in area would be more than a decrease in area in all scenarios. Recognizing and protecting potential future habitats are of the important activities to conserve this species and identify areas with conservation priority.     

The Association Between rs1748195 and rs11207997 Variants of the ANGPTL3 Gene and Susceptibility to Cardiovascular Disease in the MASHAD Cohort Study

Biochemical Genetics - There is a strong genetic predisposition to cardiovascular disease (CVD). Loss-of-function variants of the angiopoietin-like 3 (ANGPTL3) gene have been reported to be...