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The pathogenesis of idiopathic pulmonary fibrosis (IPF) is quite similar to that of cancer pathogenesis, and several pathways appear to be involved in both disorders. The mammalian target of the rapamycin (mTOR) pathway harbors several established oncogenes and tumor suppressors. The same signaling molecules and growth factors, such as vascular endothelial growth factor (VEGF), contributing to cancer development and progression play a part in fibroblast proliferation, myofibroblast differentiation, and the production of extracellular matrix in IPF development as well. The expression of candidate genes acting upstream and downstream of mTORC1, as well as Vegf and low-density lipoprotein receptor related protein 1(Lrp1), was assessed using specific primers and quantitative polymerase chain reaction (qPCR) within the lung tissues of bleomycin (BLM)-induced IPF mouse models. Lung fibrosis was evaluated by histological examinations and hydroxyproline colorimetric assay. BLM-exposed mice developed lung injuries characterized by inflammatory manifestations and fibrotic features, along with higher levels of collagen and hydroxyproline. Gene expression analyses indicated a significant elevation of regulatory associated protein of mTOR (Raptor), Ras homolog enriched in brain (Rheb), S6 kinase 1, and Eukaryotic translation initiation factor 4E-binding protein 1 (4Ebp1), as well as a significant reduction of Vegfa, Tuberous sclerosis complex (Tsc2), and Lrp1; no changes were observed in the Tsc1 mRNA level. Our findings support the elevation of S6K1 and 4EBP1 in response to the TSC/RHEB/mTORC1 axis, which profoundly encourages the development and establishment of IPF and cancer. In addition, this study suggests a possible preventive role for VEGF-A and LRP1 in the development of IPF. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis)RA(pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-ß, IL-6, TNF-a, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikßa and pIkßa) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-ß, IL-6, TNF-a, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikßa and pIkßa by western blot. The baseline expression of IL1-ß, IL-6, TNF-a, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1ß, IL-6, TNF-a, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkßa in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients. [ABSTRACT FROM AUTHOR]

Autism is a neurodevelopmental disorder that is recognized by stereotypic and repetitive behaviors after 2 years of old. Dysregulation of the immune system, especially inflammation which is mostly regulated by IL-6, imposes a deficit in CNS development. Along with this crucial biomarker, researchers have proposed BCL-2, micro RNA-23a-3p (miR-23a-3p), miR-181b-5p as other probable biomarkers involved in inflammation and apoptosis. The aim of the study was to evaluate the alteration in the expression of these biomarkers in a group of autism spectrum disorder (ASD) children. Peripheral blood mononuclear cells (PBMCs) were obtained from 37 autistic patients. After RNA extraction with precipitation method, the Syber green qReal-time Polymerase Chain Reaction (PCR) was performed in order to evaluate the possible alteration in the expression of IL-6, BCL-2, miR-181b-5p, and miR-23a-3p. The results were compared with healthy controls. IL-6 was significantly upregulated in ASD patients (p=0.003). On the other hand, miR-23a was upregulated and BCL-2 downregulated in ASD patients but the changes were not significant. In initial evaluations, expression changes of miR-181b-5p were not statistically significant. However, when Patients were divided into two groups of upregulated and downregulated, re-evaluation showed that both up- (p=0.005) and down-regulation (p=0.004) (i.e. changes regardless of the direction) of miR-181b were significant in autistic children. IL-6 and miR-181b-5p can have proper diagnostic values and are reliable biomarkers with high sensitivity and specificity. On the other hand, PBMC can be utilized for such studies and also evaluation of patients' condition instead of brain tissue as it is less accessible. [ABSTRACT FROM AUTHOR]

Fingolimod is a novel immunomodulatory drug used in patients with relapsing multiple sclerosis (MS) which reversibly inhibits egress of lymphocytes from lymph nodes. In this longitudinal study, the frequency of Interferon-gamma (IFN-γ)+, IL4+, IL17+ and IL10+ CD4+ and CD8+ T cell subsets were measured in Fingolimod treated patients before and after 12 months'(12M) therapy using flow cytometry and compared to those of naive, Betaferon treated MS patients and healthy individuals. Additionally, the level of transcription factor IRF4 and IL-6, IL-23, TGF-β1 cytokines, required for differentiation of IL-17+ T cells, were assessed by RT-PCR and ELISA, respectively. In Fingolimod treated MS patients, we observed a significant decrease in the percentage of IFN-γ+/IL17+ CD4+ and CD8+ T cell subsets. In contrast, Fingolimod increased IL10+ CD4+ T cells. We also showed that IFN-γ+IL17+ co-producing CD8+ T cells were reduced in patients under fingolimod therapy. furthermore, Fingolimod could reduce the expression level of IRF4 in patients while IL6 was increased in the supernatant of cultured peripheral blood mononuclear cells. Our data showed that Fingolimod treatment alters CD4+ and CD8+ T cell subsets and reduces expression of IRF-4, which affects the proportion of pathogenic memory T cells in peripheral blood. [ABSTRACT FROM AUTHOR]

Background: Nasal polyp (NP) is a benign mucosal mass located in both sinuses and nares which is mostly seen in association with cystic fibrosis, asthma or oversensitivity to aspirin. The prominent histological feature of NP is inflammatory cell infiltration with eosinophil predominance. Superantigens role in causing NP complications is already proven. Superantigens, which are mostly originated from Streptococci and Staphylococci, activate T cells strongly and increase the process of production and release of cytokines, and secretion of IgE from B cells, which in turn directly affects proinflammatory cells such as eosinophils, both in their tissues infiltration and functions. Methods: The samples are collected from patients referring to ENT clinic in Rasoul Akram training Hospital in Tehran after thorough clinical and paraclinical examinations. For control group the samples collected from patients undergoing rhinoplasty. All the samples kept frozen and sent to immunology lab. The DNA of the excised tissues extracted and amplified by using the superantigens specific primers and PCR product detected by gel electrophoresis. The date analyzed by using mean and SD and X2 analytical tools. Results: Fifteen healthy individuals, 25 patients with rhinosinusitis and 24 with polyposis entered this trial. Group A Streptococcus toxin detection was significantly more frequent in those with nasal polyp and rhinosinusitis compared to healthy individuals (P=0.001 and 0.005, respectively), but the results were almost the same for those with nasal polyp and rhinosinusitis (P=0.4). Conclusion: Streptococci may play an important role in induction or clinical exacerbation of polyposis and group A Streptococcus pyogenes exotoxin (SPEs) with superantigenic effects may have a crucial role in etiology and pathogenesis of polyps with or without rhinosinusitis. It is postulated that, T cells polyclonal activation by SPEs may cause recruitment of inflammatory cells in nasal mucosa. These inflammatory cells include IgE producing B cells laeding to allergic and inflammatory reactions in NP. [ABSTRACT FROM AUTHOR]

Background: Tonsils and adenoid hypertrophy is a major respiratory symptom in children which is partly due to recruitment of inflammatory cells in upper airway lymph nodes as a result of the effects of synthesis and release of different inflammatory cytokines. It seems that infections play role in concert with these cytokines leading to tonsilar hypertrophy and other pathologic consequences. It is proposed that cellular infiltrate of tonsils and adenoids may secrete different quantities of these cytokines compared with peripheral blood mononuclear cells (PBMC) cultures. Methods: Among patients who were admitted for adenotonsillectomy to the ENT ward, 37 patients, under 1-12 years old patients with fulfill criteria selected to include the study. Excised adenoid and tonsils cultured and inflammatory cytokines Interferon-γ (INF-γ), Interlukine-1 (IL-1), IL-6, IL-8 and tumor necrosis factor-α (TNF-α) measured in cellular culture supernatant. The same cytokines measured in PBMC cultures. Results: The data shows that there is a significant difference between IFN-γ and IL-8 amounts in adenoid tissue culture supernatant and PBMC culture of our patients. Furthermore, the amounts of IFN-γ, IL-1 and IL-8 showed considerable difference between tonsilar tissue culture supernatant and PBMC culture of these patients. Although there is a significant correlation between IL-6 amounts in tissue culture supernatant and PBMC culture (P=0.02), the respective data for TNF is only almost significant. Conclusion: Inflammatory cytokines may have significant role in the early provoke of inflammation occurred in hypertrophied tonsils and adenoid. The majority of these cytokines increase the expression of adhesion molecules on epithelial cells and influence the recruitment of leucocytes and inflamed tonsils. On the other hand lack of sufficient cytokine release may lead to persistent infections and may cause chronic inflammation and hypertrophied tissue. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus secretes numerous superantigenes which trigger the inflammatory mechanisms of sinus mucosa and cause chronic rhino-sinusitis. This study was designed to evaluate the role of staphylococcus aureus superantigens in polyp tissues of patients with chronic rhino-sinusitis in comparison with a control group. Methods: Polyp tissue samples of 28 patients and mucosal specimens of 19 healthy individuals were evaluated for staphylococcus aureus bacterium superantigens, exotoxins A, B, C and D and TSST-1 with RT-PCR and ELISA methods Rasoul Akram Hospital during 2 years. Results: Polymerase chain reaction (PCR) results revealed that 88.2% of the patients and 45.5% of the controls had at least one type of superantigen (P=0.03). Evaluation of superantigens using ELISA method showed presence of at least one type of superantigen in the nasal samples of all patients and in 35.3% of the controls (P<0.001). Conclusion: A relationship between staphylococcal superantigens and nasal polyps is concluded from this study which indicates the probable role of these superantigens in the pathogenesis of nasal polyposis. [ABSTRACT FROM AUTHOR]

Background: Too many studies are in the process of determining the probable role of immune system in the etiopathogenesis of nasal polyposis. This study was designed to identify the probable participation of Th1, Th2 lymphocytes in the induction and progression of nasal polyposis. Methods: Seventy-five patients, 42 male and 33 female, with nasal polyposis were examined for total serum IgE, specific serum IgE and reaction to skin test for differentiating allergic from non-allergic participants in Rasoul Akram Hospital during 2010. To determine the possible correlation of allergic reactions in the upper respiratory tract and nasal polyposis, cytokine gene expression was evaluated on the extracted RNA by RT-PCR. The data were analyzed by using χ2, independent t-test, correlation and Receiver operating characteristic (ROC) curve. Results: The mean age of participants was 38 years (18-81 years). IFN-γ and IL-4 gene expressions were more prevalent in allergic than non-allergic individuals (IFN-γ: 39.5% vs. 14.2%, P=0.3 and IL-4: 44.7% vs. 18.9%, P=0.02, respectively). IL-10 and IL-12 (P35 and P40 fractions) genes were not significantly different between the two groups. IL-10 and IL-12 (P35, P40) genes did not differ significantly either. Conclusion: This research suggests that overproduction of cytokines and an imbalance of Th1 and Th2 cell production may play an important role in the pathophysiology of allergic or non-allergic nasal polyp formation. Thus, although nasal polyposis is a multifactorial disease with several different etiological factors, chronic persistent inflammation is undoubtedly a major factor irrespective of the etiology. [ABSTRACT FROM AUTHOR]

Background: M. pneumoniae infection in children is usual and diagnosis of its neurologic complications for rapid treatment is very important. To compare the CSFM. pneumoniae antibody level between febrile children with acute neurologic signs (Menigoencephalitis, Guillan Barre Syndrome (GBS), Transverse myelitis, Ataxia and so on) with unaffected ones. Methods: A cross sectional/ case control study in pediatric wards of Rasoul-e-Akram & Mofid hospitals (2007-2009) was done. The amount of Specific M. pneumoniae IgG (ELISA) antibody level determined in CSF of 55 cases and in 10 controls. Chi square values (CI 95%, p< 0.05) calculated for all categorical variables. Sensitivity; specificity; Positive Predictive Value (PPV); Negative Predictive Value (NPV) of CSF antibody level determined by using the Area under the ROC Curve. Results: Cases (n= 55) aged between five month to 13 years with mean age of 3.84±3.43 years. Area Under Curve (AUC) in ROC was 0.876 (%95 CI, 0.78- 0.96; p< 0.0001). Cut off level for antibody was 0.0025 with 73% sensitivity; 90% specificity; 100% PPV; 28.8% NPV. CSF antibody level had significant difference between cases and controls [0.08± 0.26 Versus 0.001± 0.001; p: 0.02]; It had poor agreement between cases and controls (Kappa= 0.27). Lowest amount seen in cases with aseptic meningitis; highest amount observed in cases with GBS and cases with focal neurologic signs. Conclusion: The presence of very low amount (0.0025) of M. pneumoniae antibody in CSF of febrile children with acute neurologic signs had 70% sensitivity and 90% specificity; 100% PPV; but had low (28.8%) NPV. M. pneumoniae would be a rare cause in cases with aseptic meningitis. Finding the M. pneumoniae-DNAs in CSF are not so frequent (2%) but in high suspicious cases adding this test to determining the CSF antibody level might be helpful. [ABSTRACT FROM AUTHOR]

IgE-mediated hypersensitivity reaction to pollens is a common health problem in atopic patients. In this regard, the assessment of the allergenicity of highly pollinating plants would be demanding. Based on the increment of Ailanthus altissima (A. altissima) tree in some parts of Iran and considering its probable role in respiratory allergy, in this study, we aimed to investigate its IgE-immunoreactivity and in diagnostic applications. One hundred and twenty-five allergic rhinitis patients who were diagnosed as high IgE responders and demonstrated seasonal rhinitis or rhinoconjunctivitis, as well as 20 healthy controls (HCs) with no allergic symptoms, were enrolled in this study. Total protein extract was prepared from A. altissima pollens and subjected to quality control experiments and finally used in ELISA and western blotting studies. Approximately 24% of the atopic patients (30 from 125) showed positive immunoreactivity to A. altissima extract. The median (IQR) of absorbance (450 nm) of the specific IgE against A. altissima pollen extract in HCs and positive groups were 0.33 (0.28-0.42) and 0.59 (0.36-0.79), respectively (p<0.001). Receiver operating characteristics (ROC) curve analysis of the specific ELISA results, revealed a cut-off value of 0.46 and a sensitivity of 70% and specificity of 100%. Western blotting with the sera positive cases revealed that the main immunoreactive proteins range from 10 to 70 kDa. This study revealed that some of A. altissima pollen proteins ranging from 10 to 70 kDa show IgE-reactivity in atopic patients and may play a role in their allergic reaction symptoms.