Aim: To evaluate the possible mechanism of action of isolated phytoconstituents from P. amarus (PA) against ovalbumin (OVA)-induced experimental airway hyperresponsiveness (AHR).
Material and method: Phyllanthin and hypophyllanthin were isolated and characterized (HPLC) from the methanolic extract of PA. AHR was induced in Sprague-Dawley rats by OVA-challenged, and animals were treated with PA (50, 100, and 200?mg/kg, p.o.) for 28?days.
Results: The HPLC analysis showed the presence of phyllanthin and hypophyllanthin in methanolic extract of PA at RT of 25.243 and 26.832?min, respectively. OVA-induced alterations in hemodynamic parameters, lung functions test, peripheral blood oxygen level, total, and differential cell count in Bronchoalveolar Lavage Fluid was significantly attenuated (p?<?.05) by PA (100 and 200?mg/kg). It also significantly decreased (p?<?.05) the levels of total protein and albumin in serum, BALF, and lungs. OVA-induced increase in IgE (total and OVA-specific), and oxido-nitrosative stress (SOD, GSH, MDA, and NO) levels were significantly (p?<?.05) decreased by PA. RT-PCR analysis revealed that elevated oxido-nitrosative stress (Nrf2 and iNOs), immune-inflammatory makers (HO-1, TNF-α, IL-1β, and TGF-β1), Th2 cytokines (IL-4 and IL-6) levels were significantly attenuated (p?<?.05) by PA. PA also attenuated histological and ultrastructural aberrations induced by OVA.
Conclusion: Results of the present investigation demonstrated that the presence of phyllanthin and hypophyllanthin in P. amarus alleviated Th2 response in OVA-induced AHR via modulation of endogenous markers in a murine model of asthma. Thus, phyllanthin and hypophyllanthin may be a new therapeutic approach for the management of asthma. 相似文献
Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy voluntaries and Tregs were isolated using an immunomagnetic separation method. The phenotypic characteristics of Tregs were determined by flow cytometry. Tregs were expanded and then cultured with different concentrations of CsA and silymarin. The effects of CsA and silymarin on the viability, proliferation, and transforming growth factor-beta 1 (TGF-β1) production of Tregs were determined after 3 and 5 days of culture.
Results: CsA significantly decreased Treg proliferation in a dose-dependent manner (p < 0.01–0.05). CsA failed to change TGF-β1 production of Tregs. On the contrary, silymarin significantly increased the proliferation of Tregs (p < 0.01–0.05). A statistically significant increase was also observed in the TGF-β1 production of Tregs (p < 0.01–0.05). Our data showed that Treg viability was not compromised by CsA and silymarin.
Conclusion: Overall, the results of this study for the first time indicate that silymarin, unlike CsA, has the ability to increase the proliferation and TGF-β1 production of Tregs and may be beneficial in the treatment of autoimmune disorders and improvement of Treg-dependent allograft tolerance after transplantation. 相似文献
Methods: Acute colitis was induced by administration of 2?mL of diluted acetic acid (4%) solution rectally. Two hours after colitis induction, animals were treated with normal saline, dexamethasone (2?mg/kg), agmatine (2, 5, 10?mg/kg), L-NAME (30?mg/kg), Aminoguanidine (20?mg/kg), agmatine (2?mg/kg) with L-NAME (30?mg/kg) and agmatine (2?mg/kg) with aminoguanidine (20?mg/kg) intraperitoneally and continued for 3 consecutive days. Assessment of macroscopic and microscopic damage was performed. MPO activity was evaluated by biochemical method. Furthermore, the tissue level of TNF-α was determined by ELISA and the expression level of iNOS protein was detected by immunohistochemistry (IHC).
Results: Dexamethasone (2?mg/kg) and agmatine (5, 10?mg/kg) and subeffective doses of agmatine (2?mg/kg) with aminoguanidine (20?mg/kg) improved macroscopic and microscopic damage compared to acetic acid group (p?<?.001). In addition, these drugs reduced the activity of MPO (p?<?.001) and the level of TNF-α (p?<?.001) in colon tissue compared to acetic acid group. Furthermore, they decreased acetic acid-induced expression of iNOS protein in colon tissue (p?<?.01, p?<?.001).
Conclusion: It is suggested that the anti-inflammatory activity of agmatine on acetic acid-induced rat colitis may involve the inhibition of iNOS enzyme. 相似文献
Methods: The N-terminally formylated listerial peptide with amino acid sequence ‘f-MIGWII’ was tested for its adjunctive therapeutic efficacy in combination with anti-tuberculosis drugs (ATDs) in the mouse model of TB. In addition, its potential to generate reactive oxygen species (ROS) in murine neutrophils was also evaluated.
Results: The LemA peptide (f-MIGWII) induced a significant increase in the intracellular ROS levels of mouse neutrophils (p?≤?.05). The ATD treatment reduced the colony forming units (CFU) in lungs and spleen of infected mice by 2.39 and 1.67 log10 units, respectively (p?<?.001). Treatment of the infected mice with combination of ATDs and LemA peptide elicited higher therapeutic efficacy over ATDs alone. The histopathological changes in the lungs of infected mice also correlated well with the CFU data.
Conclusions: Our results clearly indicate that LemA peptide conferred an additional therapeutic effect when given in combination with the ATDss (p?<?.01) and hence can be used as adjunct to the conventional chemotherapy against TB. 相似文献
Materials and methods: Datasets of gene expression omnibus (GEO), the cancer genome atlas (TCGA), and gene set enrichment analysis (GESA) were extracted. Differential expression of CTLA4 between cancer tissues and normal mucosa, enrichment of WT (wild type) vs. CTLA4_KO (knockout) upregulated gene set and clinical significance were analyzed. The expression of CTLA4, CD3, and granzyme A (GZMA) were validated on 30 cases of Chinese GC. Microsatellite instability (MSI) marker MLH1 and Epstein-Barr virus (EBV) marker EBER were examined on 30 cases of Chinese GC by immunohistochemistry and in situ hybridization.
Results: CTLA4 was upregulated in GC tissue relative to normal mucosa in datasets of GSE27342 (fold change?=?1.586, p?<?.001) and GSE63089 (fold change?=?1.365, p?<?.001). Increased CTLA4 expression was positively related to CTLA4 activation. EBV-associated GC (EBVaGC) and microsatellite instability GC (MSIGC) disclosed higher CTLA4 levels than other GCs. Genomic stability GC (GSGC) also showed higher enrichment score of CTLA4 activation. CTLA4 activation resulted in shorter overall survival in GC. The expression level of CTLA4 was well correlated to expression levels of GZMA (R?=?0.701, p?<?.001) and CD3 (R?=?0.750, p?<?.001).
Conclusions: Based on bioinformatics analysis, GSGC should be worth noticed as a potential GC subtypes responsive to anti-CTLA4 treatment. 相似文献
Methods: Twenty-five untreated AIHA/ES patients, 28 remission AIHA/ES patients and 25 healthy controls (HCs) were enrolled in this study. The quantity of CD5+B lymphocytes which produce interleukin-10 (IL-10) (CD5+IL-10+) and transforming growth factor (TGF-β1) (CD5+TGF-β1+) were detected by flow cytometry (FCM). CD5+ B lymphocytes were sorted from peripheral blood (PB) by FCM and the expression of IL-10 and TGF-β1 mRNA in CD5+ B cells were measured by real-time PCR (RT-PCR).
Results: The percentage of CD5+IL-10+B cells in CD5+ B lymphocytes in newly diagnosed patients was 82.18?±?14.78%, which being significantly higher than that of remission AIHA/ES patients (56.68?±?24.39%) and HCs (51.90?±?22.95%) (p?<?.05). The percentage of CD5+IL-10+ B cells in CD5+ B lymphocytes in newly diagnosed patients was negatively correlated with haemoglobin (Hb), complement 3 (C3) (p?<?.05) and positively correlated with lactate dehydrogenase (LDH), total bilirubin (TBIL) and indirect unconjugated bilirubin (IBIL) (p?<?.05). The expression level of IL-10 mRNA in CD5+ B lymphocytes of newly diagnosed patients (49.34?±?22.84) was higher than that of remission patients (3.97?±?3.83) and HCs (1.78?±?1.66) (p?<?.05). There was no significant difference among three groups with the proportion of CD5+TGF-β1+ B lymphocytes and the expression level of TGF-β1 mRNA in CD5+B lymphocytes (p?>?.05).
Conclusions: CD5+ B lymphocytes could secrete IL-10 rather than TGF- β1 which control the immune response in AIHA/ES. 相似文献
Methods: Participants were 93 patients with schizophrenia and 117 healthy individuals, all right-handed and of Japanese ethnicity, and matched for age and sex. Their memory functions were assessed using the WMS-Revised (WMS-R). Their grey and white matter structure was analyzed using voxel-based morphometry and diffusion tensor imaging.
Results: Verbal memory score correlated positively with volumes of the left parahippocampal gyrus and hippocampus, while general memory score correlated positively with volumes of the left parahippocampal and fusiform gyri and hippocampus (p?<?0.05, corrected), while there was no correlation with white matter fractional anisotropy values in healthy individuals. No correlation was observed between any WMS-R score and grey or white matter structure in patients.
Conclusions: Using whole-brain structural magnetic resonance imaging, we found several significant correlations between WMS-R scores and grey matter volume in the brains of healthy individuals, while no correlation was found in those of patients with schizophrenia. 相似文献
Objectives: Our aim was to investigate the association between AA and genetic polymorphisms in the TCF7L2 gene, one of the most important components of the Wnt/β-catenin pathway.
Methods: This is a case-control study of 145 patients with AA and 152 healthy controls. Genotyping of the TCF7L2 gene (rs7903146) was performed via the ARMS—PCR method (amplification refractory mutation system- polymerase chain reaction). The allele and genotype distribution was compared between the two groups.
Results: The frequency of the T allele (0.38 vs. 0.28, odds ratio = 1.56, 95% CI = 1.09–2.17, p = 0.013) and TT + CT genotypes (0.68 vs. 0.53, odds ratio = 1.88, 95% CI = 1.17–3.02, p = 0.008) were significantly higher in AA patients.
Conclusions: This study indicates that the TCF7L2 gene variant is associated with AA. Its contribution to disease pathogenesis could either be through a hair cycling defect or dendritic cell dysregulation. 相似文献
Methods: Mice were divided into control (nonasthmatic; CON) and allergen sensitized-challenged (asthmatic; SEN) groups, and were sensitized i.p. on days 1, 6 with 0.2?μg ovalbumin (OVA) followed by 5% OVA aerosol challenges on days 11–13. RvE1 was administered i.p. postallergen challenge, while omega 3 fatty acids (fish oil) were administered via oral gavage once daily (days 1–13). Whole body plethysmography and bronchoalveolar lavage (BAL) studies were performed on day 14.
Results: RvE1 attenuated airway responsiveness to methacholine (48?mg/ml) in treated asthmatic mice vs. nontreated (150?±?27.88% in SEN vs. 54?±?7.52% in SEN?+?R, p?<?.05). No difference was observed with omega-3 supplementation (115?±?19.28% in SEN?+?O) or treatment with both RvE1 and omega 3 fatty acids (39?±?12.37% in SEN?+?R?+?O vs. 54?±?7.52% in SEN?+?R). Differential BAL cell analysis showed that RvE1 decreased eosinophils and neutrophils in SEN mice (p?<?.005) while no difference was observed with omega-3 fatty acids. SEN?+?R?+?O group had similar results as RvE1 treated mice, suggesting that only RvE1 attenuated inflammation.
Conclusions: RvE1 attenuated airway responsiveness and inflammation in asthmatic mice. Omega-3 fatty acids, although a precursor for RvE1 formation, had no additive effects on RvE1 decreases in airway inflammation and airway reactivity. Our data suggests that omega-3 supplementation has little effect on airway inflammation and reactivity in our model of asthma. 相似文献
Methods: Mice were divided into control (CON) and allergen sensitized (SEN) groups. SEN was sensitized with ovalbumin (OVA) on days 1 and 6 (30?μg; i.p.), followed by 5% OVA aerosol challenge (days 11–13). Treatments included (a) losartan (SEN?+?LOS; 20?mg/kg i.p., day 14), (b) novokinin (SEN?+?NOV; 0.3?mg/kg i.p., day 14), and (c) PD 123319 (SEN?+?PD; 5?mg/kg i.p., day 14). Experiments for airway responsiveness, bronchoalveolar lavage, and tracheal ring reactivity using isolated organ bath were performed.
Results: Airway responsiveness to methacholine (MCh) (48?mg/mL) was significantly higher in SEN (563.71?±?40% vs. 294.3?±?123.84 in CON). This response was potentiated in SEN?+?PD group (757?±?30%; p?<?.05 compared to SEN). SEN?+?LOS (247.61?±?86.85%) and SEN?+?NOV (352?±?11%) had significantly lower response compared to SEN. SEN?+?LOS (26.22?±?0.29%) and SEN?+?NOV (46.20?±?0.76%) treatment significantly (p?<?.001) attenuated total cell count and eosinophils compared to SEN group (69.38?±?1.5%), while SEN?+?PD (73.04?±?0.69%) had highest number of eosinophils. Tracheal response to MCh was significantly higher in SEN group compared to controls, and this response was significantly lowered with the losartan and novokinin treatments.
Conclusions: These data suggest that AT1 and AT2 receptors have opposite effects in modulating airway hyperresponsiveness and inflammation in asthma. 相似文献
Materials and methods: A meta-analysis of case–control studies was conducted on pharmacological management of xerostomia in patients with Sjogren’s Syndrome and the collected data are subjected to exclusion and inclusion criteria and standard mean difference (SMD), ODD’s ratio and confidence intervals (95% CI) were calculated by Review Manager software using fixed and random effects model from the data of five studies.
Results: Both objective response and subjective response evaluation favored experimental group suggesting an increase in unstimulated salivary flow rate using pharmacological agents. Interferon alpha 150?IU three times daily had a good effect in increasing the unstimulated whole saliva flow rate with SMD 2.72 at 95% CI [2.43, 3.00] p?<?.00001. Cevimeline vs placebo showed good response with ODDS ratio 2.74 at 95% CI [1.58, 4.76] p?=?.0003.
Conclusion: Interferon – α 150?IU thrice daily was proven to be effective in increasing salivary flow rate and also has an advantage of disease modification in SS patients attributing to its immunomodulatory action. Cevimeline 30?mg thrice daily also had a considerable therapeutic effect in SS patients compared to Pilocarpine. 相似文献
Method of the study: It was a comparative study in Mansoura University Hospital, Egypt, to detect the levels of serum sEng by ELISA besides the levels of cffDNA by quantitative real-time polymerase chain reaction in 80 pregnant females suffering from PE in addition to 80 normotensive pregnant ones that were included as control.
Results: Levels of serum sEng and cffDNA were higher in PE cases than control (p < 0.0001? both) and were significantly related to the severity of the disease. Levels were also higher in early than late onset PE (p < 0.003? and <0.002?, respectively). Sensitivities, specificities, positive, and negative predictive values in addition to accuracy of serum sEng and cffDNA were 97.5%, 98.8%, 98.7%, 97.5%, and 98.1% and 97.5%, 93.8%, 94.0%, 97.4%, and 95.6%, respectively.
Conclusion: Maternal serum sEng and cffDNA can be good markers for diagnosis of PE in Egyptian patients. They are positively related to the disease severity.
Abbreviations: cffDNA; Cell-Free Fetal DNA, sEng; soluble Endoglin, PE; preeclampsia, qRT PCR; Quantitative real-time polymerase chain reaction. 相似文献
Objective: to assess the relation between TLR3 rs3775290, TLR7 rs17900 and TLR9 rs352140 SNPs and chronic HCV in the Egyptian cohort and to study their relation to interferon response.
Methods: TLR3 rs3775290, TLR7 rs179008 and TLR9 rs352140 gene polymorphisms were typed by RFLP for 100 patients with chronic HCV and 25 with HCC in addition to 100 healthy controls.
Results: A significant higher frequency has been found for the CT genotype of TLR3 rs3775290 in chronic HCV infection (p < 0.001) and CC genotype and the combined genotype CC-AT-GA ♀ in controls (p < 0.001). Non-significant associations have been found for studied SNPs and HCC and response to interferon and also the viral load or the degree of fibrosis, however, the higher HCV viral load and the higher grade of fibrosis were associated with treatment failure (p < 0.001).
Conclusion: The heterozygous CT genotype of TLR3 rs3775290 may be a susceptibility risk factor for chronic HCV infection and the homozygous CC and the combined CC-AT-GA ♀ genotypes may be protective. The HCV viral load and the grades of liver fibrosis could be considered a risk factor for interferon treatment failure. It seems that the studied SNPs have no role in HCC development or failure of treatment. However, the small sample size is a limiting factor of the present study when interpreting the negative associations and that the current used cohort does not permit such conclusion.
Abbreviations: cHCV=chronic Hepatitis C virus, HCC=hepatocellular carcinoma, TLR=Toll like Receptor, RFLP=Restriction Fragment Length Polymorphism, SNP=Single Nucleotide Polymorphism, IFN-α= interferon alpha 相似文献
Methods: We retrospectively included 38 children undergoing HSCT in Denmark in 2010–2012. Opioids doses on days 0–21 post-HSCT were registered as intravenous morphine equivalents (MEs). CRP was measured daily on days 0–21. IL-6 was measured on day 7. Citrulline was measured before conditioning, on days 7 and 21.
Results: Out of 38 children, 37 (97%) received opioids during days 0–21. CRP level and ME dose peaked on days 9–10 while citrulline level reached a nadir on day 7 indicating maximum enterocyte loss. CRP was associated with ME dose, with an estimated increase of 0.030?mg/kg (95% CI 0.024–0.035) in ME for a 50% increase in CRP level on the same day (p?<?.001). IL-6 was correlated with ME on day 7 (rho = 0.55, p?=?.002). Citrulline did not correlate with ME.
Conclusions: Opioid consumption in the early post-HSCT period is associated with the degree of chemotherapy-induced systemic inflammation and not with the extent of enterocyte loss. These findings contribute to our understanding of mucositis-related pain and may be of interest for future studies on therapeutic strategies. 相似文献
Methods: WNT/β-catenin pathway and NF-κB signaling pathway were examined in LPS-stimulated human bronchial epithelial cells and effects of XAV939 on these pathways were analyzed. The effect of XAV939 was confirmed in human umbilical vein endothelial cells.
Results: LPS-induced expressions of pro-inflammatory genes IL-6, IL-8, TNF-α, IL-1β, MCP-1, MMP-9, iNOS and COX-2 were significantly and dose-dependently suppressed by XAV939. LPS-induced NF-κB signaling, such as IκB phosphorylation and degradation as well as nuclear translocation of NF-κB, was also suppressed by XAV939. Target DNA binding of NF-κB was significantly and dose-dependently suppressed by XAV939 during LPS-induced inflammatory response. The suppressive effects of XAV939 on NF-κB signaling, target DNA binding of NF-κB and pro-inflammatory gene expression were all rescued by over expression of β-catenin, which shows that the anti-inflammatory effect of XAV939 is mediated by the modulation of β-catenin, a central component of the WNT/β-catenin pathway.
Conclusion: The findings of this study showed that XAV939 exerts anti-inflammatory effects through the modulation of the Wnt/β-catenin pathway. 相似文献
Methods: Peripheral blood and EBC samples from COPD patients and healthy donors were collected. In serum and EBC, MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 proteins were detected by ELISA. The mRNA expression levels of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by qRT-PCR.
Results: The protein levels of MMP-9 (p=.034) and MMP-12 (p=.041) in the EBC of COPD smokers were higher than those of COPD never-smokers. The concentrations of TIMP-1 (p=.072) and TIMP-4 (p=.084) in the EBC of COPD smokers were higher than those of COPD never-smokers; however, the difference was not statistically significant. MMP-9 (r=–0.78, p<.0001) and TIMP-1 (r=–0.71, p<.0001) levels in EBC were significantly negatively correlated with pulmonary function FEV1%pred. The protein levels of MMP-12 (r=–0.37, p=.034) and TIMP-4 (r=–0.34, p=.041) were also negatively correlated with FEV1%pred. The expression of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in PBMCs and serum of COPD smokers were significantly higher than those of control never-smokers (p<.05).
Conclusions: Exhaled MMP-9, MMP-12, TIMP-1, and TIMP-4 levels increased in stable COPD patients and were negatively correlated with FEV1%pred, which suggests the usefulness of their measurement in EBC for the monitoring of airway inflammation. However, to better assess their diagnostic or prognostic value, larger studies are necessary. 相似文献
Aim: To estimate the effect of parental migration status on the relative length of the tibia in their school-age children.
Subjects and methods: Data included a nationwide random sample of 17,155 schoolchildren, 7–18?years of age, examined between 1966 and 1969 in Poland who provided information on anthropometric measurements and demographic and social characteristics. Parental migration status was based on paternal migration history. After standardisation by LMS method, z-scores of relative tibia length and z-scores of height were used for analysis. Three-way ANOVA was used to evaluate the influence of migration on tibia length-to-height ratio.
Results: Sons of migrants have a significantly higher tibia length-to-height ratio compared to sons of non-migrants. Children of non-migrants were taller than children of migrants among boys in medium SES and among girls in high and low SES. Relative tibia length indicated significant effects of migration among boys in all age categories and in late adolescent girls: sons of migrants had a higher ratio and daughters of migrants had a lower tibia length-to-height ratio.
Conclusion: It is possible that migration experiences of the parents may have influenced the growth of their offspring. The results emphasise the potential importance of research addressing the impact of different types of migration on growth of children. 相似文献
Objective: This study investigated pyocyanin effect on nitric oxide and cytokine production in lipopolysaccharide (LPS)-activated murine peritoneal macrophages.
Materials and methods: Macrophages were incubated in the presence and absence of pyocyanin (1, 5, 10, 50, and 100 µM) with and without LPS (1 µg/mL). Nitric oxide production was determined by Griess reagent and tumor necrosis factor (TNF)-α and interleukin (IL)-1β production was assessed by enzyme-linked immunosorbent assay. In addition, pyocyanin effects on zymosan A-induced peritonitis in mice were evaluated.
Results: Pyocyanin (5 and 10 µM) decreased nitric oxide, TNF-α, and IL-1β production independent of macrophage death. On the other hand, in vivo, pyocyanin (5 mg/kg) was not able to affect leukocyte migration into the site of inflammation.
Discussion and conclusion: Thus, our findings suggest that pyocyanin exerts anti-inflammatory effects on murine peritoneal macrophages, downregulating nitric oxide, TNF-α, and IL-1β levels, which seems to be independent of cell migration. These effects may represent a mechanism of immune evasion; nevertheless more detailed studies should be performed to confirm this hypothesis. 相似文献
Objective: To further evaluate the activity of DHMEQ in vivo modified AD-like lesion model in BALB/c mice and in vitro AD-like lesion cell model in human keratinocytes.
Materials and methods: In this study, in vivo modified AD-like lesion model in BALB/c mice was chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears, and stratum corneum of the ear skin was additionally stripped off with surgical tapes before each challenge with DNCB/OX. Moreover, in vitro AD-like lesion cell model in human keratinocytes (HaCaT) achieved by stimulating HaCaT cells with tumor necrosis factor (TNF)-α plus interferon (IFN)-γ was used to investigate mechanisms of the action.
Results: The lesions derived from the stratum corneum-removed AD-like lesion model reaches to peak as well as DHMEQ arrives to its efficacy a week earlier than the data previously obtained from the common AD-like lesion model. Results showed that the drug reduced the ear thickness, epidermal thickness, mast cell infiltration, and gene expressions of interleukin (IL)-4, IL-13, and interferon (IFN)-γ in ear tissues. It significantly inhibited the expression of cytokines IL-6 and IL-1β, chemokines thymus and activation-regulated chemokine (TARC)/CCL17, and macrophage-derived chemokine (MDC)/CCL22 in the stimulated HaCaT cells.
Discussion and conclusion: This study indicated that the action of DHMEQ’s anti-AD like lesions might be related to its inhibition on NF-κB. 相似文献