7 research outputs found
Mitochondrial ATPase 6,8 Associated with Brain Tumours in Patients Compared to Adjacent Normal Brain Cells
No full textAbstract | Background: Brain cancer is considered one of the most prevalent types of cancer in the world. Primary brain tumours consist of two types. Studies provide some deficiencies in mitochondrial functions that could cause different genetic. Objective: This study aimed to determine the association of ATPase 6,8 alterations of brain tumour cells in comparison with the adjacent healthy tissue cells. Methods: A group of patients was examined, and their disease was identified during precise examinations. These persons were sampled for their affected brain tissues, and these were compared with their adjacent healthy cells. Besides, the populations of 300 healthy controls were selected as the control. The DNA of the brain tumour cells was extracted and analysed using sequencing methods. Result: After the sequence analysis, T8473C, G8584A, A8701G, A8730G and A8860G variants were found—all of them had been reported in other diseases. Also, they were observed in patients with brain tumours, as compared with the adjacent normal tissues. Discussion: The A8860G variant was one of the most prevalent polymorphisms between all these alterations in brain cancer. It seems that the ATPase 6 subunit is more prone to brain cancer. The analysis shows that amongst all the five variants determined in this research, the T8473C, G8584A and A8730G variants—with the p value<0.05—were considered to affect brain tumours
Mitochondrial Polymorphisms, in The D-Loop Area, Are Associated with Brain Tumors
No full textObjective
This study was carried out to evaluate the relationship between mtDNA D-loop variations and the pathogenesis of a brain tumor.
Materials and Methods
In this experimental study, 25 specimens of brain tumor tissue with their adjacent tissues from patients and 454 blood samples from different ethnic groups of the Iranian population, as the control group, were analysed by the polymerase chain reaction (PCR)-sequencing method.
Results
Thirty-six variations of the D-loop area were observed in brain tumor tissues as well as the adjacent normal tissues. A significant difference of A750G (P=0.046), T15936C (P=0.013), C15884G (P=0.013), C16069T (P=0.049), T16126C (P=0.006), C16186T (P=0.022), T16189C (P=0.041), C16193T (P=0.045), C16223T (P=0.001), T16224C (P=0.013), C16234T (P=0.013), G16274A (P=0.009), T16311C (P=0.038), C16327T (P=0.045), C16355T (P=0.003), T16362C (P=0.006), G16384A (P=0.042), G16392A (P=0.013), G16394A (P=0.013), and G16477A (P=0.013) variants was found between the patients and the controls.
Conclusion
The results indicated individuals with C16069T [odds ratio (OR): 2.048], T16126C (OR: 2.226), C16186T (OR: 3.586), G16274A (OR: 4.831), C16355T (OR: 7.322), and T16362C (OR: 6.682) variants with an OR more than one are probably associated with a brain tumor. However, given the multifactorial nature of cancer, more investigation needs to be done to confirm this association
Chemotherapy Could Induce Antibiotic Resistance in E. Faecalis in Patients with Colorectal Cancer
No full textColorectal cancer is one of the most common cancers in Iran. There are many effective methods of treatment of it. As a conventional treatment, chemotherapy has become a part of treatment scheme for patients with colorectal cancer. Enterococci are intestinal commensals. They are opportunistic pathogens which cause millions of human and animal infections annually. The aim of this study was to investigate the side effects of chemotherapy of sufferers from colon cancer on the antibiotic resistance of microflora. Methods: In this study, participants were divided into three groups: Group A: 300 colorectal cancer patients before the start of the cancer chemotherapy, group B: 300 healthy people living with patients at least for recent 12 months and group C includes 300 patients with colorectal cancer after six weeks chemotherapy. RNA was extracted from the stool of all the participants of the study. Following the RNA extraction from stool samples, cDNA libraries were constructed. Eight virulent genes (vanA, vanB, gelE, esp, asa1, aggA, efaA and enlA) of E. faecalis were evaluated by real-time qPCR. Results: The results were showed the expression level of the virulent genes in the group of the patients after chemotherapy was significantly higher than the two groups of B and C (P<0.05). Although the expression of these genes in the group of patients before chemotherapy was higher than that of the control group, this increase was not significant (P>0.05). Conclusions: It seems that chemotherapy could change the balance of mRNA expression of microflora such as antibiotic resistance genes. These could be responsible for infections arisen after ending the chemotherapy of cancer
Identification of Single Nucleotide Polymorphisms as Markers of Genetic Susceptibility for Alopecia Areata Disease Risk
No full textAbstract | Background: Alopecia areata (AA) is an autoimmune disease, leading to disfiguring hair loss that susceptibility loci and the genetic basis of AA have been largely unknown. Objective: The aim of this study was the scrutiny the susceptible genes of Alopecia areata amongst patients and healthy adult in Iranian populations. Methods: four variants polymorphisms (rs1701704, rs10760706, rs9275572, rs694739) were studied by Tetra Arms PCR, Sequencing methods in 200 Iranian healthy adult blood donors and 200 patients with Alopecia Areata (AA). Results: Results were showed that 4 SNPs had P-values <0.05 for association with Alopecia areata. 3 of 4 SNPs, was demonstrated significant association in analyses 100 AT/AU cases versus 100 AA, which is localised in IKZF4, STX17, PRDX5, HLA-DQB1 (rs1701704, rs10760706, rs694739 and rs9275572 respectively). Conclusions: In this study, 3 of 4 SNP-associated loci were associated significantly with association with the development of Alopecia areata. In another word, the presence of them may be a contributing factor for prognosis of the development of the disease to Totalis and Universalis
Immunotherapy of Prostate Cancer may Change mRNA Level of Virulence Factor Genes in E.Faecalis of Microflora
No full textFDA has approved the immunotherapy for prostate cancer in 2010. Immunotherapy is the treatment of disease by inducing, enhancing, or suppressing an immune response and is well known as specific and noninvasive method for cancer treatment; but side effects of this method are not clarified. Enterococci are Gram positive coccies, which are intestinal commensals and microflora of humans and other mammalians. Most enterococcal infections in human such as gastroenteritis, intestinal infections, prostatitis and endocarditic are causing by Enterococcus faecalis. Present study aimed to evaluate the side effects of immunotherapy on E. faecalis of microflora. Methods: mRNA level of 10 virulent genes (gelE, esp, asa1, aggA, cylA, cylB, cylM, Eep, efaA and enlA) which are involved in pathogenesis of E. faecalis, were examined in stool samples of two groups of men by quantitative real time PCR. Group A includes 359 prostate cancer patients and group B contains 360 normal family members of patients, which were lived with them at least for recent 12 months. Gene expression assessments in patient’s group were operated before start and after finishing a six weeks’ period of cancer vaccines immunotherapy. Results: Results were showed significant (P<0.05) over expression of 8 genes (gelE(P=0.001). asa1(P=0.001), esp (P=0.002), aggA(P=0.001), efaA(P=0.002), enlA(P=0.001), cylA(P=0.003) and cylB(P=0.003) in patients after treatment compared to before treatment. Also significant over expression of these 8 genes has been detected in patients after treatment in compare with normal related subjects. No significant alterations were observed in expression of virulence genes between normal subjects and patients before treatment. Conclusions: it seems that immunotherapy may carry side effects such as increasing the pathogenicity risk of microflora in treated patients. These side effects could cause further infections after ending the immunotherapy of cancer. Based on these results, antibiotic treatments after immunotherapy for prevention of potential infections could be recommended
The prevalence of polymorphisms of thiopurine smethyltransferase gene In Iranian alopecia areata patients
No full textAzathioprine therapy was recently used to treat dermatologic conditions such as alopecia areata (AA). Previous reports showed that thiopurine s-methyltransferase (TPMT) activities in human red blood cell are associated with a polymorphism in this gene. Therefore, patients carrying mutant allele of TPMT may show severe myelosuppression when they are treated with standard doses of Azathioprine drugs. This study aimed to evaluate the TPMT gene amongst alopecia areata patients and healthy adult in Iranian populations. TPMT gene polymorphisms were investigated in 1285 Iranian healthy adult blood donors and 632 patients with Alopecia Areata Universalis (AU). Tetra Arms PCR, Real-Time PCR and Sequencing were used to evaluate the presence of allele-specific polymorphisms of TPMT gene (TPMT *2(c.238 GC,), TPMT *3A (c.460 GA and c.719 AG), TPMT *3B (c.460 GA), and TPMT *3C (c.719 AG). Results were shown that the TPMT*2 allele is associated with a low enzymatic activity that was detected in 22.51% (863 in 1917) of Iranian individuals. Heterozygous genotypes were in 827 (43.14%) subjects (232 AA and 595 healthy), and homozygous genotypes were in 18 (0.94%) individuals (3 AA and 15 healthy). The normal allele (wild-type) was found in 55.92% of the studied individuals (20.70% AA and 35.21% healthy). According to a higher frequency of TPMT polymorphism in Iranian population in comparison with other population, determination of TPMT genotype in may have the clinical benefit to thiopurine dosage selection and treat patients as well
Functional analysis of the tomato Ve resistance locus against Verticillium wilt
No full text Verticillium dahliae, V. albo-atrum and V. longisporum are soil-borne plant pathogens that are responsible for Verticillium wilt diseases in temperate and subtropical regions. Collectively they can infect over 200 hosts, including many economically important crops. Chapter 1 is a “pathogen profile” which describes the most important aspects of the biology of the Verticillium wilt pathogens. They colonize the xylem vessels of their host plants and cause symptoms such as wilting, chlorosis, stunting, necrosis and vein clearing. Verticillium species are notoriously difficult to control as there are no fungicides available to cure plants once they are infected. Therefore, genetic resistance is the preferred method for disease control. Chapter 2 describes the functional characterization of the tomato (Solanum lycopersicum) Ve locus. This locus is responsible for resistance against race 1 strains of V. dahliae and V. albo-atrum and comprises two closely linked inversely oriented genes, Ve1 and Ve2. Both genes encode cell surface receptor proteins of the extracellular leucine-rich repeat (eLRR) receptor-like protein (RLP) class of disease resistance proteins. In chapter 2, it is demonstrated that Ve1, but not Ve2, provides resistance in tomato against race 1 but not against race 2 strains of V. dahliae and V. albo-atrum. Using virus-induced gene silencing in tomato, the signaling cascade downstream of Ve1 was shown to require both EDS1 (enhanced disease susceptibility1) and NDR1 (non-race-specific disease resistance1). In addition, also NRC1 (NB-LRR protein required for hypersensitive response-associated cell death1), ACIF (Avr9/Cf-9–induced F-box1), MEK2 (MAP/ERK kinase2), and SERK3/BAK1 (somatic embryogenesis receptor kinase 3/brassinosteroid-associated kinase 1) act as positive regulators of Ve1 in tomato. In conclusion, Ve1-mediated resistance signaling only partially overlaps with signaling mediated by Cf proteins, type members of the eLRR-RLP-class of resistance proteins. In chapter 3 an attempt to introduce Nicotiana benthamiana as a model to facilitate the study of Ve1-mediated resistance is described. Challenge of wild type plants with several race 1 and race 2 strains of V. dahliae and V. albo-atrum demonstrated that N. benthamiana is susceptible to both Verticillium species. To obtain Verticillium wilt resistant plants, N. benthamiana was engineered to express the tomato Ve1 coding sequence. However, out of thirteen transgenic lines, six showed clear phenotypic aberrancies that included severe stunting and malformed leaves when compared to wild type plants. The seven Ve1-transgenic lines that did not show any phenotypic alterations were challenged with race 1 and race 2 strains. Although the pathogenicity assays indicated that in few lines Ve1 expression temporarily reduced disease development, most lines were as susceptible as wild type parental line. In conclusion, in chapter 3 it is demonstrated that the Ve1-transgenic N. benthamiana lines could not be used to study Ve1-mediated resistance signaling. In chapter 4, the use of Arabidopsis (Arabidopsis thaliana) as model to facilitate the study of Ve1-mediated resistance is presented. To this end, tomato Ve1 was expressed in susceptible Arabidopsis plants. Upon challenge with race 1 strains of V. dahliae or V. albo-atrum, Ve1-expressing plants were found to be resistant. In contrast, Ve1-expressing plants were susceptible to race 2 strains of both V. dahliae and V. albo-atrum. Furthermore, expression of Ve1 in Arabidopsis plants did not prevent colonization by V. longisporum strains. Through Ve1-expression in Arabidopsis defense signaling mutants, it was demonstrated that signaling downstream of Ve1 is highly conserved between tomato and Arabidopsis. In previous chapters it was shown that the receptor kinase SERK3/BAK1 is required for Ve1-mediated resistance in tomato as well as in Arabidopsis. In Arabidopsis, SERK3/BAK1 belongs to a gene family consisting of five members. In chapter 5, the requirement of the different SERK family members in Ve1-mediated resistance in Arabidopsis is investigated, revealing the requirement of SERK1 and, although to a lesser extent, SERK4 for resistance. Using virus-induced gene silencing, it was subsequently shown that SERK1 is also required for Ve1-mediated resistance in tomato. In conclusion, the results of chapter 5 demonstrate that Arabidopsis can be used as model to unravel the molecular mechanisms of Ve1-mediated resistance. In chapter 6, the recognition specificity of Ve1 was further investigated by performing domain-swaps with Ve2 and expressing the chimeric Ve proteins in Arabidopsis. Various domain swaps in which eLRRs from Ve1 were replaced by those of Ve2 suggest that the region between eLRR22 and eLRR35 is required for full Ve1-mediated resistance. However, plants expressing a Ve chimera in which eLRR1 to eLRR30 of Ve1 was replaced with those of Ve2 were resistant against Verticillium. Overall, these results suggest that Ve2 may still bind the elicitor in the eLRR domain, but its C-terminal domain is not able to activate a successful defense response. Finally in Chapter 7, highlights of this thesis are discussed and placed in a broader perspective. </p
