Sherwooddevine7001
82%), Primary Myelofibrosis (MF, 12.28%), and Chronic Myeloid Leukemia (CML, 10.5%). A significant relationship between all types of MPDs and the clinical course (p< 0.05) was observed. The relationship between age and gender among all types of MPD disease was not significant (p> 0.05).
Of the examined cohort in North Eastern Iran, 28% of the patients with MPNs were found to have the
(V617F) mutation which determining the presence of the
(V617F) mutation helps to decide the correct form of treatment.
Of the examined cohort in North Eastern Iran, 28% of the patients with MPNs were found to have the JAK2 (V617F) mutation which determining the presence of the JAK2 (V617F) mutation helps to decide the correct form of treatment.
Targeted therapy is an important treatment strategy that is widely used for cancer therapy. Epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of Triple-negative breast cancer (TNBC) patients. Although Cetuximab, which targets EGFR, has shown some inhibitory effects on TNBC cells, Cetuximab resistance cases due to ligand-independent activating mutations in the EGFR gene limit its application. Due to various benefits of single chain antibodies (scFvs), the use of these antibodies in cancer targeted therapy is increasing. In this study, a specific anti-EGFR antibody was isolated and evaluated.
Panning procedure was used against an immunodominant epitope of EGFR in its dimerization arm using a diverse phage library. Polymerase Chain Reaction (PCR) and fingerprinting were applied to identify the specific clones. The MTT tetrazolium assay was performed to evaluate the inhibitory effects of selected anti- EGFR scFv phage antibody on MDA-MB-468, a TNBC cell line.
After four round of panning, one dominant pattern was observed in DNA fingerprinting with frequency of 85%. The growth of MDA-MB-468 cells was decreased dose-dependently after treatment with anti-EGFR scFv phage antibody. No significant inhibitory effect of M13KO7 helper phage as negative control on the cell growth of MDA-MB-468 was observed (p> 0.05).
The selected anti-EGFR scFv with high anti proliferative effect on TNBC cells offers an effective alternative for TNBC targeted therapy. The antibody, which binds to the dimerization arm of EGFR and inhibits EGFR dimerization, could also overcome TNBC cases with Cetuximab resistance due to ligandindependent activating mutations.
The selected anti-EGFR scFv with high anti proliferative effect on TNBC cells offers an effective alternative for TNBC targeted therapy. The antibody, which binds to the dimerization arm of EGFR and inhibits EGFR dimerization, could also overcome TNBC cases with Cetuximab resistance due to ligandindependent activating mutations.
Over 90% of oral cancers including oral squamous cell carcinoma (OSCC), originate from the oral cavity epithelium. Early detection for this lesion is as important. Evaluating cancer stem cell markers can improve the accuracy of early diagnosis, and be used as an OSCC prognostic indicator. We aimed to evaluate SOX2 and OCT4 gene expression among different grades of OSCC and oral epithelial dysplasia (OED) lesions.
Sixty samples that contains 45 OSCC and 15 OED samples were retrieved from the pathology department archives at the dental school of Mashhad. Demographic and pathological patient data including the tumor stage and tumor grade were assessed. Finally, SOX2 and OCT4 expression was examined using qRT-PCR.
There was a significant difference in SOX2 and OCT4 expression between OSCC and OED samples (p< 0.001). The mean expression of SOX2 and OCT4 in OSCC samples were significantly higher than in the OED group (p< 0.001). The mean expression of SOX2 and OCT4 was higher in grade II and grade III OSCC compared to grade I. There was no significant relationship between the gene expression of SOX2 or OCT4 to the demographic, site and stage of tumors. The correlation between SOX2 and OCT4 expression (p= 0.001) was significant in grade III OSCC specimens compared to other grades (p= 0.005, r= 0.68).
The increased expression of SOX2 and OCT4 in higher grades and the significant correlation of these genes with each other among OSCC specimens could suggest the role of SOX2 or OCT4 in oral mucosal carcinogenesis.
The increased expression of SOX2 and OCT4 in higher grades and the significant correlation of these genes with each other among OSCC specimens could suggest the role of SOX2 or OCT4 in oral mucosal carcinogenesis.
The Ccr4-Not protein complex (CNOT complex) is a key regulator of gene expression in eukaryotic cells. Ccr4-Not Complex is composed of at least nine conserved subunits in mammalian cells with two main enzymatic activities. CNOT8 is a subunit of the complex with deadenylase activity that interacts transiently with the CNOT6 or CNOT6L subunits. Here, we focused on the role of the human CNOT8 subunit in the DNA damage response (DDR).
Cell viability was assessed to measure ATP level using a Cell Titer-Glo Luminescence reagent up to 4 days' post CNOT8 siRNA transfection. In addition, expression level of phosphorylated proteins in signalling pathways were detected by western blotting and immunofluorescence microscopy. CNOT8- depleted Hela cells post- 3 Gy ionizing radiation (IR) treatment were considered as a control.
Our results from cell viability assays indicated a significant reduction at 72-hour post CNOT8 siRNA transfection (p= 0.04). Western blot analysis showed slightly alteration in the phosphorylation of DNA damage response (DDR) proteins in CNOT8-depleted HeLa cells following treatment with ionizing radiation (IR). Increased foci formation of γH2AX, RPA, 53BP1, and RAD51 foci was observed after IR in CNOT8-depleted cells compared to the control cells.
We conclude that CNOT8 deadenylase subunit is involved in the cellular response to DNA damage.
We conclude that CNOT8 deadenylase subunit is involved in the cellular response to DNA damage.
is one of the widespread causes of community-acquired pneumonia (CAP). Over recent years, the widespread use of macrolides has led to the emergence of macrolide-resistant
(MRMP) resulted from mutations at specific positions of domain V of the
gene.
We collected 100 samples of throat swabs from patients with respiratory infections. After extraction of DNA from bacterial cell cultured in PPLO broth media using Roche kit (Germany), the PCR was performed on specific samples of
using specific primers for
gene.Afterwards, for positive samples, minimum inhibitory concentration (MIC) was determined using the broth microdilution with Clarithromycin. Finally, the PCR product was sequenced to detect mutations related to macrolide resistance in domain V of
.
According to the analysis of the sequenced PCR product of
gene using Clustalw2 online software, one of the samples were shown to have a mutation at A2431G and G2491A positions. The MIC measurement also revealed that all isolates were sensitive to Clarithromycin, and there was no macrolide resistance to Clarithromycin in all isolates.
Sequence analysis of the
gene in
, revealed no macrolide resistance of
to Clarithromycin. Thus, the use of these antibiotics should be restricted to prevent the development of macrolide-resistant
in Iran.
Sequence analysis of the 23S rRNA gene in M. pneumoniae , revealed no macrolide resistance of M. pneumoniae to Clarithromycin. Thus, the use of these antibiotics should be restricted to prevent the development of macrolide-resistant M. pneumoniae in Iran.
Introduction Oxytocin (OT) has been proposed to assist in the regulation of bone remodeling and to exert an antiosteoporotic effect. We evaluated the possible protective effect of OT against bone degeneration in ovariectomized (OVX) rats.
The study was performed on three groups of adult female rats; group I was subjected to sham operation, group II was subjected to ovariectomy, and group III was subjected to ovariectomy and intraperitoneal injection with OT for eight successive weeks. At the end of the study, bone mass density (BMD) was measured; then the rats were euthanized and their blood and bone tissues were examined.
The group II rats had significantly less BMD and greater serum bone-specific alkaline phosphatase (bALP), osteocalcin (OC), and tartrate-resistant acid phosphatase (TRAP) levels than the group I rats. Furthermore, group II rats had fewer osteocytes and osteoblasts, and less OPG/RANKL mRNA expression than group I rats. The groups I and III and rats showed no significant differences in BMD, bALP, OC, TRAP, OPG/RANKL mRNA expression, or osteocyte and osteoblast numbers.
Oxytocin may have an antiosteoporotic effect in OVX rats.
Oxytocin may have an antiosteoporotic effect in OVX rats.
Due to extensive damage to the skin, burn victims may acquire life-threatening infections. Though the skin primarily protects against microbial invasions, a large number of bacteria, fungi, and viruses can be isolated from burn patients, specifically
, a gram-negative bacterium with both intrinsic and acquired antibiotic resistance (AR) properties.
mutations can be found on the
in the
chromosome. This mutation can induce overexpression of the mexAB-oprMoperon, and affect the MexAB-OprM efflux pump, which removes antimicrobial agents from the bacterial cell. Identifying nalB mutants can be useful for monitoring factors affecting AR.
In this study, 70
isolates identified from burn patients and antibacterial sensitivity was evaluated using the Kirby-Bauer method. We also investigated
mutations in samples using molecular methods including Polymerase reaction chain (PCR) and Sequencing.
We identified
mutations in 16 isolates. We also found that the increasing effect of
mutants induces hyper production activity of MexAB-OprM resulting in AR. Overall, these findings compliment the findings of previous reports.
According to the resistance patterns of the samples, both Amikacin and Ciprofloxacin showed the highest resistance (%). Further, the relationship between Ciprofloxacin resistance and
mutations was statistically significant (
= 0.016). EGF816 mouse The results confirm that the increasing effect of
mutants on hyper production activity of MexAB-OprM leads to AR.
According to the resistance patterns of the samples, both Amikacin and Ciprofloxacin showed the highest resistance (%). Further, the relationship between Ciprofloxacin resistance and nalB mutations was statistically significant (p= 0.016). The results confirm that the increasing effect of nalB mutants on hyper production activity of MexAB-OprM leads to AR.
Multiple sclerosis (MS) is a multifactorial condition in which many genetic and environmental factors interfere. The association between genes involved in the immune system and MS was previously reported. The aims of this study were to evaluate 14 SNPs of
, 14 SNPs of
with severity of MS through Expanded Disability Status Scale (EDSS) and Annualized Relapse Rate (ARR).
102 patients with MS referred to Sina hospital in Tehran, Iran, were diagnosed and studied based on McDonald's guideline, clinical signs, and brain imaging procedures. All patients were included in the study following informed consent. Genotyping study of 14 variants in the
, and 14 variants in
was conducted by Sanger sequencing. Disease outcomes including EDSS and ARR were registered. Outcome measures between different genotypes of each SNPs were compared separately.
Among 14 SNPs in IL 2RA the genotypes of rs12722489 showed a significant association with ARR in two consecutive years. Mean ARR1 was 1.06±1.12, 0.20±0.34 and 0.31±.