Let-7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin-like growth factor 1 receptor

Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let-7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let-7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin-like growth factor 1 receptor (IGF-1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF-1R is a direct target of the let-7e member. Consistent with this, we identified that increased levels of let-7e in CRC cells reduced IGF-1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let-7e by targeting the IGF-1R signaling pathway might serve as therapeutics in anticancer therapy.     

Association of BMPR-1B and GDF9 genes polymorphisms and secondary protein structure changes with reproduction traits in Mehraban ewes

BMPR-1B and GDF9 genes are well known due to their important effects on litter size and mechanisms controlling ovulation rate in sheep. In the present study, polymorphisms of BMPR-1B gene exon 8 and GDF9 gene exon 1 were detected by single strand conformational polymorphism (SSCP) analysis and DNA sequencing methods in 100 Mehraban ewes. The PCR reaction forced to amplify 140 and 380-bp fragments of BMPR-1B and GDF9 genes, respectively. Two single nucleotide polymorphisms (SNP_S) were identified in two different SSCP patterns of BMPR-1B gene (CC and CA genotypes) that deduced one amino acid exchange. Also, two SNP_S were identified in three different SSCP patterns of GDF9 gene (AA, AG and GG genotypes) that deduced one amino acid exchanges. Two different secondary structures of protein were predicted for BMPR-1B exon 8, but the secondary protein structures predicted for GDF9 exon 1 were similar together. The evaluation of the associations between the SSCP patterns and the protein structure changes with reproduction traits showed that BMPR-1B exon 8 genotypes have significant effects on some of reproduction traits but the GDF9 genotypes did not have any significant effect. The CA genotype of BMPR-1B exon 8 had a significant positive effect on reproduction performance and could be considered as an important and new mutation, affecting the ewes reproduction performance. Marker assisted selection using BMPR-IB gene could be noticed to improve the reproduction traits in Mehraban sheep.     

The Role of Calcium in Differentiation of Human Adipose-Derived Stem Cells to Adipocytes

Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca²⁺ play important roles in different stages of this process. Because of the complicated roles of Ca²⁺ in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca²⁺ into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca²⁺ or 1.8 mM Ca²⁺ plus calcium ionophore, A23187, for 3 days. Lipid staining, triglycerides (TG) content, and glyceraldehyde phosphate dehydrogenase (GAPDH) activity were evaluated to confirm the efficiency of the differentiation. Gene expression of GLUT4, PPARγ2, RAR-α, and calreticulin, as well as the protein levels of GLUT4 and PPARγ2 were determined. Ca²⁺ and in particular Ca²⁺ plus A23187 significantly lowered the efficiency of differentiation accompanied by decrease in intracellular TG deposits, GAPDH activity and alleviation of gene, and protein levels of GLUT4 and PPARγ2. While calreticulin and RAR-α were remarkably upregulated in A23187 group. This study showed the inhibitory effects of calcium in adipogenesis. Additionally, it indicated the greater inhibitory effect of calreticulin and RAR-α in controlling adipogenesis by higher levels of calcium.     

Further records of ants (Hymenoptera: Formicidae) from Iran

Wide ranging surveys of the ant fauna of Iran have enabled us to add a further 30 named species to the country list. A review of almost all the published literature and of photographs of unidentified specimens within the public domain gives a grand total of 248 species, from seven subfamilies and 37 genera. In the majority of instances, our own specimens were compared with type images available from antweb.com. This has led us to propose new or revised status for Cataglyphis turcomanica Crawley 1920, Lepisiota integrisquama (Kuznetsov-Ugamsky, 1929), Lepisiota surchanica (Kuznetsov-Ugamsky, 1929) and Messor obscurior Crawley 1920. We note that the total includes a number of what may be misidentifications and a small number of named species that seem unlikely to occur in Iran.     

Etiology of severe hospital infections in intensive care units and antibiotic resistance of pathogens]

The leading pathogens of severe infections in intensive care units were the following: respiratory tract infections--bacteria of the famility of Enterobacteriaceae (33.8%), Pseudomonas spp. (24.9%), Acinetobacter spp. (18.1%), Staphylococcus aureus (16.0%), blood flow infections--coagulase negative staphylococci (33.6%), S. aureus (26.1%), Enterobacteriaceae (17.6%), wound infections--Enterobacteriaceae (35.7%), coagulase negative staphyloccocci (17.8%), Pseudomonas spp. (14.3%). As for various species of Enterobacteriaceae, susceptibility was preserved in 91-100% of the isolates to meropenem, in 72-100% to cefoperazone/sulbactam, in 51-65% to cefepime, in 72-86% to amikacin, and in less than 50% to cephalosporins and fluoroquinolones. As for P.aeruginosa, 28% of the isolates was resistant to all the antibacterials, except polymyxin. The highest susceptibility to cefoperazone/sulbactam and meropenem was revealed in the isolates of Acinetobacter baumannii. Oxacillin resistance was detected in 64.9% of the S.aureus isolates. The oxacillin resistance as a rule was associated with resistance to macrolides, aminoglycosides and fluoroquinolones. As for coagulase negative staphylococci, oxacillin resistance was stated in 75.6% of the isolates. All the isolates of the Staphylococcus spp. preserved their susceptibility to vancomycin and linezolid.     

Circular dichroic, infrared and other studies on the protein component of pig brain thromboplastin.

1. A four-step procedure used to isolate the protein component (apoprotein III) of pig brain thromboplastin yielded approximately 25 mg from 500g of brain. 2. In the absence of detergent, apoprotein III had an apparent mol.wt. of 360 000 by gel-filtration, and, after electrophoresis on polyacrylamide gels in the presence of sodium docecyl sulphate, it appeared as a major protein band of mol.wt.59 000, suggesting the existence of polymeric and monomeric forms. 3. Chemical analyses of apoprotein III revealed that hydrophilic and hydrophobic amino acids were present in a ratio of 3:2, together with approx, 9% (w/w) of carbohydrate. 4. The far-u.v.c.d. and i.r. spectral data indicated that, like other membrane proteins, apoprotein III has a high percentage of unordered structure with lesser amounts of alpha and beta-forms. 5. Relipidation of apoprotein III to restore clotting activity caused no extensive alteration in the c.d. and i.r. spectra, indicating that the phospholipid associates with a comparatively small hydrophobic segment. The constrained unordered conformation, which makes the major contribution to the c.d. spectrum, probably forms a separate domain in the aqueous phase. The absence of any increase in the amplitude of both negative c.d. extrema, following relipidation, contrasted with the substantial increase observed in a helix-forming solvent and raises the possibility that the more stable polymeric form of apoprotein III is retained as the active form in the lipid phase. 6. We suggest that as a consequence of cell membrane damage, the recognition and activation of factor VII may involve minor changes of conformation that are dependent upon the flexibility inherent in an unordered secondary structure.     

Biological method of identifying antibiotic substances at an early screening stage

A biological method was used in addition to the chemical methods of identification in the screening programme of new antibiotics. The method consists of evaluation of the effect of the crude antibiotic preparations on microbial forms resistant to various antibiotics. The efficiency of the biological method is shown. It provides more complete and rapid characterization of the properties of the new antibiotics and their rough identification at early screening stages.     

Salusin-α attenuates inflammatory responses in vascular endothelial cells

Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have a critical role in acceleration or suppression of disease. Salusin-α presents a new class of bioactive peptides that can have anti-atherogenic properties. Therefore, the effects of salusin-α on the expression of some pro- and anti-inflammatory cytokines and on TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) were examined. The involvement of the NF-κB pathway in effects of salusin-α in HUVECs was checked using Bay 11-7082 as an NF-κB inhibitor. The mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was assessed by real-time PCR. The protein levels of cytokines were measured by the ELISA method. Salusin-α suppressed both mRNA and protein expression of pro-inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in HUVECs. Salusin-α suppressed TNF-α-induced inflammatory responses in HUVECs. The down-regulatory or up-regulatory effects of salusin-α on expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our findings indicate anti-inflammatory effects of salusin-α and suggest a novel peptide-based therapeutic strategy for atherosclerosis.