ABSTRACT
Objective: recent studies have reported dysregulated expression of matrix metalloproteinases [MMPs], especially MMP-2, MMP-9, tissue inhibitor of metalloproteinase-1, -2 [TIMP-1, TIMP-2], and extracellular matrix metalloproteinase inducer [EMMPRIN/CD147] in activated macrophages of patients with inflammatory diseases. Therefore, MMP-2, MMP-9, and their regulators may represent a new target for treatment of inflammatory diseases. Probiotics, which are comprised of lactic acid bacteria, have the potential to modulate inflammatory responses. In this experimental study, we investigated the anti-inflammatory effects of cell-free supernatants [CFS] from Lactobacillus acidophilus [L.acidophilus] and L. rhamnosus GG [LGG] in phorbol myristate acetate [PMA]-differentiated THP-1 cells
Materials and Methods: in this experimental study, PMA-differentiated THP-1 cells were treated with CFS from L. acidophilus, LGG and uninoculated bacterial growth media [as a control]. The expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNAs were determined using real-time quantitative reverse transcription polymerase chain reaction [RTPCR]. The levels of cellular surface expression of CD147 were assessed by flow cytometry, and the gelatinolytic activity of MMP-2 and MMP-9 were determined by zymography
Results: our results showed that CFS from both L. acidophilus and LGG significantly inhibited the gene expression of MMP-9 [P=0.0011 and P=0.0005, respectively], increased the expression of TIMP-1 [P<0.0001], decreased the cell surface expression of CD147 [P=0.0307 and P=0.0054, respectively], and inhibited the gelatinolytic activity of MMP-9 [P=0.0003 and P<0.0001, respectively] in PMA-differentiated THP-1 cells. Although, MMP-2 expression and activity and TIMP-2 expression remained unchanged
Conclusion: our results indicate that CFS from L. acidophilus and LGG possess anti-inflammatory properties and can modulate the inflammatory response
ABSTRACT
Objective: Pompe disease [PD] is a progressive neuromuscular disorder that is caused by glucosidase acid alpha [GAA] deleterious mutations. Mitochondrial involvement is an important contributor to neuromuscular diseases. In this study the sequence of MT-ATP 6/8 and Cytochrome C oxidase I/II genes along with the expression levels of the former genes were compared in classic and non-classic patients
Materials and Methods: In this case-control study, the sequence of MT-ATP 6/8 and Cytochrome C oxidase was analyzed by polymerase chain reaction [PCR]-Sanger sequencing and expression of MT-ATP genes were quantified by real time-PCR [RT-PCR] in 28 Pompe patients. The results were then compared with 100 controls. All sequences were compared with the revised Cambridge reference sequence as reference
Results: Screening of MT-ATP6/8 resulted in the identification of three novel variants, namely T9117A, A8456C and A8524C. There was a significant decrease in MT-ATP6 expression between classic [i.e. adult] and control groups [P=0.030]. Additionally, the MT-ATP8 expression was significantly decreased in classic [P=0.004] and non-classic [i.e. infant] patients [P=0.013]. In total, 22 variants were observed in Cytochrome C oxidase, five of which were nonsynonymous, one leading to a stop codon and another [C9227G] being a novel heteroplasmic variant. The A8302G in the lysine tRNA gene was found in two brothers in a pedigree, while a T7572C variant in the aspartate tRNA gene was observed in two brothers in another pedigree
Conclusion: The extent of mitochondrial involvement in the classic group was more significant than in the non-classic form. Beside GAA deleterious mutations, it seems that mtDNA variants have a secondary effect on PD. Understanding, the role of mitochondria in the pathogenesis of Pompe may potentially be helpful in developing new therapeutic strategies
ABSTRACT
Background: This study aimed to evaluate the diagnostic value of outer dense fiber 4 [ODF4], melanoma associated antigen A3 [MAGEA3], and MAGEAB4 mRNAs in transitional cell carcinoma [TCC], using a small amount of cell reverse transcriptase-polymerase chain reaction [RT-PCR] on urinary exfoliated cells
Methods: We recruited a total of 105 suspected TCC patients and 54 sex- and age-matched non-TCC controls. The candidates' genetic expression patterns were investigated with RT-PCR, while reverse transcription quantitative PCR was applied to quantify and compare each mRNA level between cases and control groups
Results: The sensitivity of ODF4, MAGEA3, and MAGEAB4 RT-PCR was 54.8%, 63%, and 53.4%, whereas the specificity was 73.7%, 86%, and 94.7%, respectively. Combining ODF4, MAGEA3, and MAGEAB4 RT-PCR offered a relatively higher sensitivity [83.6%]
Conclusion: RT-PCR with ODF4, MAGEA3, and MAGEAB4 on urinary exfoliated cells could provide clinicians with a promising method to improve TCC diagnosis, especially in the case of gross hematuria and catheterization. The method used here is non-invasive, simple and convenient, and unlike cytology, it does not rely directly on expert professional opinions. These features can be of particular importance to the management of TCC patients in whom regular and lifelong surveillance is required
Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/diagnosis , Urologic Neoplasms/genetics , Biomarkers, Tumor , Sperm Tail , Seminal Plasma Proteins , Antigens, Neoplasm , Neoplasm ProteinsABSTRACT
Background: Hypertrophic cardiomyopathy is a genetic disorder with a prevalence rate of 0.2% in the general population. It comes from mutations in sarcomeric proteins. Cardiac myosin-binding protein C3 is one of the critical genes in hypertrophic cardiomyopathy [HCM] and sudden cardiac death, accounting for about 20% of HCM-causing mutations. Genetic testing is recommended in patients with HCM. The aim of the current study was to find possible disease-causing mutations in 3 exons of the gene myosin-binding protein C [MYBPC3] in patients with HCM
Methods: Fifty subjects with documented known HCM were enrolled in the study. The patients were referred to the hospitals affiliated to Tehran University of Medical Sciences between 2008 and 2011. Peripheral blood samples were collected, as well as clinical and demographic data. The nucleotide sequences of the exons number 7, 16, and 18 of MYBPC3, whose relevance to the disease was previously reported, were amplified by polymerase chain reaction. Direct DNA sequencing was applied, and the Chromas software was used to analyze the sequences to find possible disease-causing mutations
Results: The study population comprised 73% male and 27% female patients. The mean age of the patients was 33.9 +/- 20.08 years. Family history of sudden cardiac death was reported in 48.2% of the patients. About 79% of the studied subjects had a history of at least 1 other affected relative in their families. Laboratory findings did not show mutations or any nucleotide changes in the sequences of the 3 target exons in the genomic DNA of the studied patients with HCM
Conclusion: The nucleotide sequences of the exons number 7, 16, and 18 of MYBPC3 were not mutated in the 50 studied subjects with HCM
ABSTRACT
Background: A balanced reciprocal translocation is a structural abnormality, which at least consist of breakage of two non-homologous chromosomes along with pieces exchange and form quadrivalant structure that can produce unbalanced chromosomes during meiosis I and result in a fetus abortion. The aim of the present study is to offer using Preimplantation Genetic Diagnosis [PGD] 24sure array, which delivers aneuploidy screening of 24 chromosomes, within a few hours to increase fertility and bearing a child without chromosomal abnormality of this couple. This technique could replace embryo donation for child bearing of this couple
Case presentation: A young couple with recurrent pregnancy loss in 6th and 7[th] week of pregnancy without family history of recurrent miscarriage and any clinical signs had conferred. All laboratory tests including hormonal, infections, semen and hys-terosalpingography were normal except karyotype that showed balanced reciprocal translocation between chromosomes 5 and 18 in male. Chromosomal study of male parents showed normal karyotype
Conclusion: A balanced reciprocal translocation carrier is phenotypically normal, but during meiosis I, carrier chromosomes cant pair normally and form quadrivalant instead of bivalant that depend on type of their segregation [alternate, adjacent 1, adjacent 2,3:1,4:0], produce gametes that are chromosomally unbalanced which can result in early fetus abortion. Considering the number of abnormal gametes, the most effective way to help couples with this problem seems to be PGD 24sure, since it can identify reciprocal and Robertsonian translocation and allows concurrent screening of all chromosomes for aneuploidy. Another technique that can be compared with PGD 24sure is fluorescence in situ hybridization [FISH], but it has several technical limitations such as it is expensive and complexity, in addition it has only few probes [for chromosomes 21, 13, 18, X, Y] so sometimes necessary to create patient specific protocols