ABSTRACT
OBJECTIVE@#To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice.@*METHODS@#Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated.@*RESULTS@#TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05).@*CONCLUSION@#Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.
Subject(s)
Animals , Mice , Asthma/chemically induced , Inflammation , Macrophages , Receptor-Interacting Protein Serine-Threonine Kinases , Respiratory System , Toluene 2,4-Diisocyanate/adverse effectsABSTRACT
Objective To evaluate the diagnostic value of interferon-γ release assay of blood and pleural effusion for tuberculous pleurisy.Methods Fifty-six adult patients with suspected tuberculous pleurisy were enrolled in our study.The blood and pleural effusion interferon-γ release assay were measured by T-SPOT.TB test in 38 pleural tuberculosis patients and 18 nontuberculous pleurisy controls.The diagnostic sensitivity,specificity,predictive value of T-SPOT.TB in pleural effusion mononuclear cells (PE-MC) and peripheral mononuclear cells (PBMC) were analyzed.Results The sensitivities and specificities,positive predictive values and negative predictive values,respectively,of the PE-MC and PBMC for diagnosing were as follows:86.5％(95％ confidence interval[CI] 71.2％-95.5％) and 100％(95％CI 90.5％-100％);52.9％(95％CI 27.8％-77.0％) and 35.3％(95％CI 14.2％-61.7％);80.0％(95％CI 64.4％-90.9％) and 77.1％(95％CI 62.7％-88.0％);64.3％(95％CI 35.1％-87.2％) and 100％(95％CI 54.1％-100％).By ROC curve analysis,a cut-off value of 47SFC/2.5 × 105 cells in PE-MC showed a sensitivity of 89.2％ and a specificity of 88.2％.Conclusion T-SPOT.TB in PE-MC could be an accurate diagnostic method for tuberculous pleurisy in TB endemic settings.Moreover,47SFC/2.5 × 105 cells might be the optimal cut-off value for diagnosing tuberculous pleurisy.
ABSTRACT
Objective To characterize the vascular cognitive impairment of stroke patients with different injury sites (right or left cerebral hemisphere) and pathological type (hemorrhage or infarct). Methods A total of 119 stroke patients were assessed with regard to their cognitive functions using the LOTCA within one week of admis-sion, and comparison was made among patients in terms of VCI characteristics, injury site, and pathological type. Results In patients with left hemisphere injury, there found no significant difference between those with cerebral in-farct and hemorrhage with regard to the total score of LOTCA, but the score of perception of those with hemorrhage was lower than those with infarct(P<0.05). in patients with right hemisphere injury, both total score of LOTCA and the subscore were not significantly different between those with infarct and hemorrhage(P>0.05). In patients with infarct in left hemisphere, the total score of LOTCA was lower than those with infarct in right hemisphere(P<0.05), but the scores of orientation and thinking operation were lower than those with infarct in right hemisphere(P<0.001 or <0.01). In patients with hemorrhage in the left hemisphere, the total score of LOTCA was not significantly different from those with hemorrhage in right hemisphere, but the scores of orientation and perception were lower than thosewith hemorrhage in right hemisphere(P<0.001 or <0.01). Conclusions More attention with regard to perception training should be paid to those with cerebral hemmorhage than those with cerebral infarct. In patients with cerebral infarct, more attention with regard to orientation and thinking operation training should be paid to those with infarct in left side, while for those with cerebral hemorrhage, more attention with regard to orientation and perception training should be paid to the left hemisphere insult.