Role of gut microbiota in the pathogenesis of colorectal cancer; a review article

Colorectal cancer [CRC] is one of the most frequently diagnosed cancers worldwide. Lifestyle is identified as one of the most important risk factors for CRC, especially in sporadic colorectal cancer. The natural composition of the gut microbiota changes rapidly during the first decade of life. Maintaining homeostasis in the gut is essential as structural and metabolic functions of the commensal microbiota inhibit gut colonization of pathogens. Dysbiosis, imbalance in function or structure of gut microbiota, has been associated with a variety of diseases, such as colorectal cancer. The aim of this review was to investigate the possible links between the dysbiosis in gut microbiota and colorectal cancer, and the potential role of anaerobic gut microbiota in the pathogenesis of colorectal cancer. Based on this review, various studies have shown that some of the gut microbiota such as anaerobic bacteria significantly increased in CRC patients, but we suggest more investigations are required to assess the importance of these bacteria and their metabolites in the pathogenesis of CRC are required

Urinary BK virus excretionÿin children newly diagnosed with acute lymphoblastic leukemia

Determining the risk factors in developing or increasing the relapses of acute lymphoblastic leukemia [ALL] may help health and preventive systems to launch new programs. Up to 90% of normal population changes to seropositive for BK virus by the age of 10 years. Whether this oncogenic virus is responsible for evolving ALL is unclear. In this study, we evaluated the excretion of urinary BK virus in newly diagnosed children with ALL compared with normal population. This case-control study was carried out on 62 participants [32 ALL patients and 32 normal subjects], aged 1-18 years, in Saint Al-Zahra and Sayyed-Al-Shohada University Hospitals, Isfahan, Iran. A polymerase chain reaction [PCR] method was used to detect the BK virus in specimens. PCR amplification was performed using specific primers of PEP-1 [5?-AGTCTTTAGGGTCTTCTACC-3?] and PEP-2 [5?-GGTGCCAACCTATGGAACAG-3?]. Thirty-five out of 62 participants [54.8%] were males and the remaining were females. The mean duration of disease was 9.6 +/- 9.69 months. Central nervous system [CNS] relapse was seen in 29% of the patients. Positive PCR for urine BK virus was seen in three children with ALL [9.7%]. No positive result for urine BKV was achieved in the control group. However, Fisher's exact test did not show any significant difference between the two groups [P > 0.05]. In addition, there was no significant correlation between BKV positivity and frequency of relapses. To demonstrate the role of BK virus in inducing ALL or increasing the number of relapses, prospective studies on larger scale of population and evaluating both serum and urine for BK virus are recommended

Comparison of epothilone and taxol binding in yeast tubulin using molecular modeling

Microtubules are unique cytoskeletal structures that have structural subunits of alphabeta tubulin. Taxol is a typical microtubule stabilizing drug. The epothilones are other natural products with similar mechanism of action totaxol. Despite the highly conserved nature of beta-tubulin, some organism like Saccharomyces cerevesia is resistance to taxol, but sensitive to epothilones. In order to find differences in sensitivity of yeast tubulin to these molecules, we investigated binding mode of the taxol and epothilone A to yeast tubulin using molecular modeling. The multiple sequence alignment of beta-tubulin of different species was performed using ClustalW2. Protein structure of yeast beta-tubulin was constructed with Swiss Model 8.05 by using 1TVK. Modeled tubulin was superimposed with PyMol on 1JFF for comparison of three-dimensional structure of two proteins. Our results showed that one of the most interesting differences in binding mode of these molecules is residue 227. The His227 in bovine makes a hydrogen bond by means of its delta-nitrogen with epothilone A and by means of its epsilon-nitrogen with taxol. The Asn227 of yeast can play role of the delta-nitrogen of imidazole ring of H227, but not of epsilon-nitrogen of it. So yeast tubulin in contrast to taxol can interact with epothilone A. Due to conservation of essential residues for binding [T274, R282 and Q292], epothilone A in comparison with taxol can tolerate the interchange in the binding pocket [R276I]. Our findings may be of a great aid in the rational design of anti-tumor agents that bind to the taxol binding region of tubulin

Construction of a new fusion protein vector associated to fibronectin binding protein A and clumping factor A derived from Staphylococcus aureus NCTC 8325

Staphylococcus aureus is a leading cause of many nosocomial and community acquired infections. According to many reports, antibiotic therapy cannot guarantee the eradication of S. aureus infections. Thus designing an adhesin based vaccine could restrain the S. aureus infections. This study designed for construction of a new fusion protein vaccine against S. aureus infections based on adhesin molecules fibronectin binding protein A [FnBPA] and clumping factor A [ClfA]. Bioinformatic experiments were performed using Oligo analyzer and DNAMAN softwares. The fragments corresponding to fnbA binding domain and a C-terminal fragment from clfA were amplified from S. aureus NCTC8325 genomic DNA. Purified PCR products and the vector, pET15b, were digested with NcoI and BamHI. The digested PCR products were hybridized together and then ligated to digested vector. Finally incomplete construct was assembled by Taq DNA polymerase. To quick confirmation of cloning procedure the new construct designated pfnbA-clfA was digested with NcoI and BamHI. To further verification, the product was sent for sequencing. The data based on bioinformatics analysis showed no homology between fusion protein and human proteins. Digestion of new vector with NcoI and BamHI confirmed the ligation of fusion protein sequence into pET15b. Sequencing results verified the integrity of target sequences. This study is the first effort to construct a new fusion protein vector based on S. aureus adhesins using a new design. This project is being continued to study the expression and biological activity of the fusion protein in a cell culture model