Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson's disease.

Introduction: Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear. Methods: In this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients. Results: Covariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (ß = -0.27, p = 0.003) and the putamen (ß = -0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: ß = -0.37, p = 0.013; putamen: ß = -0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011). Conclusion: Dopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.

Evaluation of risk factors for impulse control disorder in Parkinson's disease in northern China.

Introduction: Impulse control disorder (ICD) is a common non-motor symptom of Parkinson's disease (PD), but its risk factors are still controversial. This study aimed to determine the prevalence of ICD in northern China and analyze the risk factors associated with ICD, multiple ICDs, and four subtypes. Methods: A total of 285 PD patients were enrolled in this study. Each patient was screened using the Questionnaire for Impulse and Compulsive Control Disorders (QUIP). Stepwise regression analysis was performed to identify independent risk factors, and a prediction model was developed. Results: The prevalence of ICD in the study population was 11.6%. Stepwise regression analysis showed that ICD was associated with disease duration, motor symptoms, dyskinesia, depression, REM sleep behavior disorder (RBD) and cognitive decline; multiple ICDs were related to coffee history, motor symptoms, dyskinesia, depression, apathy and RBD. The prediction model demonstrated good performance with AUC values of 0.93, 0.88, and 0.66 on the balanced train set, balanced test set, and the original imbalanced data set, respectively. Conclusion: The risk factors for PD-ICD are complex and influenced by regional economic and cultural backgrounds. Clarifying these factors and developing predictive models can help to delay or even prevent the development of ICD through early screening and intervention.

Neither Eastern nor Western: Patterns of independence and interdependence in Mediterranean societies.

Social science research has highlighted "honor" as a central value driving social behavior in Mediterranean societies, which requires individuals to develop and protect a sense of their personal self-worth and their social reputation, through assertiveness, competitiveness, and retaliation in the face of threats. We predicted that members of Mediterranean societies may exhibit a distinctive combination of independent and interdependent social orientation, self-construal, and cognitive style, compared to more commonly studied East Asian and Anglo-Western cultural groups. We compared participants from eight Mediterranean societies (Spain, Italy, Greece, Turkey, Cyprus [Turkish Cypriot and Greek Cypriot communities], Lebanon, Egypt) to participants from East Asian (Korea, Japan) and Anglo-Western (the United Kingdom, the United States) societies, using six implicit social orientation indicators, an eight-dimensional self-construal scale, and four cognitive style indicators. Compared with both East Asian and Anglo-Western samples, samples from Mediterranean societies distinctively emphasized several forms of independence (relative intensity of disengaging [vs. engaging] emotions, happiness based on disengaging [vs. engaging] emotions, dispositional [vs. situational] attribution style, self-construal as different from others, self-directed, self-reliant, self-expressive, and consistent) and interdependence (closeness to in-group [vs. out-group] members, self-construal as connected and committed to close others). Our findings extend previous insights into patterns of cultural orientation beyond commonly examined East-West comparisons to an understudied world region. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Endoscopic closure of refractory upper GI-tracheobronchial fistulas with a novel occluder: a prospective, single-arm, single-center study (with video).

BACKGROUND AND AIMS: Upper GI-tracheobronchial fistula is a morbid condition with high mortality. It is a challenge for endoscopists because currently available treatments have severe limitations. In this study we assessed the efficacy and safety of an occluder we invented for endoscopic closure of refractory upper GI-tracheobronchial fistulas. METHODS: This was a prospective, single-arm, single-center trial conducted between September 2020 and March 2022. All patients undergoing occluder placement were eligible to enroll. The primary endpoints were clinical success rate (CSR) and complete closure rate (CCR) at 3 months and safety. Secondary efficacy endpoints were technical success rates, CSRs and CCRs at 1 and 6 months, near-complete closure rates, change from baseline in body mass index (BMI), and health-related quality of life (HRQoL) at 1, 3, and 6 months. RESULTS: Twenty-eight patients (mean age, 63.2 years; 23 men) were enrolled. Eighteen through-the-scope occluders (TTSOs) and 10 through-the-overtube occluders (TTOOs) were implanted, with a technical success rate of 100%. The mean procedure time for the TTSO and TTOO groups were 28.0 ± 8.0 minutes and 31.8 ± 7.7 minutes, respectively. The CSRs at 1, 3, and 6 months were 92.9%, 96.4%, and 92.0% and the CCRs were 60.7%, 60.7%, and 60.0%, respectively. The mean BMI at 3 and 6 months and HRQoL at 1, 3, and 6 months were significantly increased compared with baseline (P < .05). Two completely occluded fistulas had 1-sided or complete healing by coverage of granulation tissue and re-epithelialized mucosa at a follow-up of 6 and 12 months. All 14 adverse events were either mild and transient or easily corrected. CONCLUSIONS: Our clinical outcomes suggest that this novel GI occluder is a safe and effective salvage option for patients with refractory upper GI-tracheobronchial fistulas. (Clinical trial registration number: ChiCTR2000038566.).

Family Function and Post-Traumatic Stress Disorder in Children and Adolescents: A Meta-Analysis.

Family function reflects the operating status of the family system, which plays a vital role in children's mental health. The current meta-analysis examined the association between family function and post-traumatic stress disorder (PTSD) in children and adolescents for the first time. Studies published from 1980 to 2021 were identified via searching and screening. We identified 31 studies (91 unique effects) with 8,684 children. A three-level meta-analysis revealed that overall family function was negatively associated with PTSD (r = -0.205). Among elements of family function, family affect (r = -0.251), communication (r = -0.221), and cohesion (r = -0.184) were associated with less PTSD, whereas family conflict (r = 0.228) was associated with more PTSD in children. Family flexibility (r = -0.103) was not associated with PTSD. Moderator analyses revealed differences between various types of trauma events and family function scales. The findings highlight the differences in the roles of the elements of family function and suggest that interventions should be focused on targeting specific elements of family function.

Gender differences in cooperation across 20 societies: a meta-analysis.

Past research hypothesized that men and women differ in their tendency to cooperate with strangers in situations that involve a conflict of interests. However, recent empirical research has provided converging evidence that men and women cooperate to a similar extent, and that differences in cooperation can emerge in response to specific situational and societal contexts. Here we analyse six decades of empirical research on human cooperation using social dilemmas (1961-2017, k = 126) conducted across 20 industrialized societies, testing pre-registered hypotheses derived from evolutionary theory and social role theory. Overall, our findings revealed little-to-no evidence for an association between gender and cooperation using different meta-analytic approaches. We did not find within-study differences in cooperation between men and women (d = 0.011, 95% CI [-0.038, 0.060]). However, cooperation was slightly higher across studies with predominantly female samples (k = 972). In addition, contrary to our predictions, gender differences in cooperation did not emerge in response to the degree of conflicting interests in the situation, and societal levels of gender equality and economic development. We discuss the implications of these findings for our understanding of gender differences in cooperation. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

Distribution and Clinical Significance of IL-17A in Tumor-Infiltrating Lymphocytes of Non-Small Cell Lung Cancer Patients.

Objective: To investigate the distribution of IL-17A and its clinical significance in tumor infiltrating lymphocytes (TILs) of patients with non-small cell lung cancer (NSCLC). Methods: Expression level of IL-17A in TILs of 3 paired NSCLC and paracancerous specimens was measured by qRT-PCR. The distribution of IL-17A in immune cell subsets of 15 paired NSCLC and paracancerous specimens was examined by flow cytometry. The correlation between IL-17A and clinical features of NSCLC was identified. Results: IL-17A was significantly upregulated in TILs of NSCLC specimens than those of paracancerous ones (p < 0.0001). Meanwhile, T helper 17 cells (Th17 cells, p < 0.001), IL-17-secreting CD8+ T cells (Tc17 cells, p < 0.001) and IL-17-producing cells (γδT17 cells, p < 0.0001) were significantly abundant in TILs of NSCLC specimens than those of controls, and the higher abundance of the latter was much pronounced than that of the former two. Moreover, γδT17 cells in TILs were significantly correlated with lymphatic metastasis and CYFRA 21-1 level of NSCLC patients (p < 0.05). Conclusion: Tumor infiltrated γδT cells are the main source of IL-17 in early-stage NSCLC, and IL-17 may be a vital regulator involved in the development of NSCLC.

The Cooperation Databank: Machine-Readable Science Accelerates Research Synthesis.

Publishing studies using standardized, machine-readable formats will enable machines to perform meta-analyses on demand. To build a semantically enhanced technology that embodies these functions, we developed the Cooperation Databank (CoDa)-a databank that contains 2,636 studies on human cooperation (1958-2017) conducted in 78 societies involving 356,283 participants. Experts annotated these studies along 312 variables, including the quantitative results (13,959 effects). We designed an ontology that defines and relates concepts in cooperation research and that can represent the relationships between results of correlational and experimental studies. We have created a research platform that, given the data set, enables users to retrieve studies that test the relation of variables with cooperation, visualize these study results, and perform (a) meta-analyses, (b) metaregressions, (c) estimates of publication bias, and (d) statistical power analyses for future studies. We leveraged the data set with visualization tools that allow users to explore the ontology of concepts in cooperation research and to plot a citation network of the history of studies. CoDa offers a vision of how publishing studies in a machine-readable format can establish institutions and tools that improve scientific practices and knowledge.

Cross-cultural variation in cooperation: A meta-analysis.

Impersonal cooperation among strangers enables societies to create valuable public goods, such as infrastructure, public services, and democracy. Several factors have been proposed to explain variation in impersonal cooperation across societies, referring to institutions (e.g., rule of law), religion (e.g., belief in God as a third-party punisher), cultural beliefs (e.g., trust) and values (e.g., collectivism), and ecology (e.g., relational mobility). We tested 17 preregistered hypotheses in a meta-analysis of 1,506 studies of impersonal cooperation in social dilemmas (e.g., the Public Goods Game) conducted across 70 societies (k = 2,271), where people make costly decisions to cooperate among strangers. After controlling for 10 study characteristics that can affect the outcome of studies, we found very little cross-societal variation in impersonal cooperation. Categorizing societies into cultural groups explained no variance in cooperation. Similarly, cultural, ancestral, and linguistic distance between societies explained little variance in cooperation. None of the cross-societal factors hypothesized to relate to impersonal cooperation explained variance in cooperation across societies. We replicated these conclusions when meta-analyzing 514 studies across 41 states and nine regions in the United States (k = 783). Thus, we observed that impersonal cooperation occurred in all societies-and to a similar degree across societies-suggesting that prior research may have overemphasized the magnitude of differences between modern societies in impersonal cooperation. We discuss the discrepancy between theory, past empirical research and the meta-analysis, address a limitation of experimental research on cooperation to study culture, and raise possible directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intergenerational conflicts of interest and prosocial behavior during the COVID-19 pandemic.

The COVID-19 pandemic presents threats, such as severe disease and economic hardship, to people of different ages. These threats can also be experienced asymmetrically across age groups, which could lead to generational differences in behavioral responses to reduce the spread of the disease. We report a survey conducted across 56 societies (N = 58,641), and tested pre-registered hypotheses about how age relates to (a) perceived personal costs during the pandemic, (b) prosocial COVID-19 responses (e.g., social distancing), and (c) support for behavioral regulations (e.g., mandatory quarantine, vaccination). We further tested whether the relation between age and prosocial COVID-19 responses can be explained by perceived personal costs during the pandemic. Overall, we found that older people perceived more costs of contracting the virus, but less costs in daily life due to the pandemic. However, age displayed no clear, robust associations with prosocial COVID-19 responses and support for behavioral regulations. We discuss the implications of this work for understanding the potential intergenerational conflicts of interest that could occur during the COVID-19 pandemic.

Carcinoembryonic antigen in pleural effusion of patients with lung adenocarcinoma: a predictive marker for EGFR mutation.

BACKGROUND: Carcinoembryonic antigen (CEA) can reflect tumor growth, recurrence and metastasis, and also predict the clinical efficacy of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). In the present study, we investigated the association between CEA in serum and pleural effusion (PE) and EGFR mutations in patients with lung adenocarcinoma. METHODS: We retrospectively investigated 114 lung adenocarcinoma patients with malignant pleural effusion (MPE). CEA levels in serum and MPE were measured by immunoradiometric assay, we analysed the correlation between CEA and EGFR mutation status. RESULTS: Fifty-three cases had EGFR mutation (46.5%). EGFR mutations were more common in females, patients with high levels of PE (≥107.2 ng/mL) and serum CEA (≥87 ng/mL). There was no significant difference in EGFR mutation rate between in tumor tissue and PE samples (49.3% vs. 41.9%, P=0.440). The result of receiver operating characteristic (ROC) indicated that the cut off value of CEA in MPE was 107.2 ng/mL, which had the highest sensitivity (SEN) and specificity (SPE) for predicting EGFR mutation [SEN 66%, and SPE 62.3%, AUC =0.668, 95% confidence interval (CI): 0.569-0.767, P=0.025]. The combination of gender, smoking history, serum and MPE CEA level had a higher calculated AUC (0.718, 95% CI: 0.622-0.813, P=0.000). Moreover, multivariate analysis showed that CEA level in MPE but not in serum was confirmed as the only independent factor associated with EGFR gene mutation status (P=0.026) with an odds ratio of 2.885 (95% CI: 1.137-7.317). CONCLUSIONS: MPE CEA can probably serve as a predictive marker for EGFR mutation in advanced lung adenocarcinoma. Combining gender, smoking history, and CEA has a relatively better predictive value. However, detecting EGFR mutations in lung adenocarcinomas is necessary for determining EGFR-TKI treatment in clinic.

Aberrant Peripheral Immune Function in a Good Syndrome Patient.

Good's syndrome (GS) is often accompanied by recurrent respiratory infections and chronic diarrhea. The main purpose was to evaluate the peripheral immune status of a GS patient after thymoma resection. Twenty healthy volunteers were recruited as healthy controls (HCs). Flow cytometry was applied to determine the proportions of circuiting CD4+ T cells, CD8+ T cells, γδT cells, and regulatory T (Treg) cells in our GS patient. We also examined the proliferation capability of ex vivo CD4+ T cells and detected the levels of cytokines interferon- (IFN-) γ and interleukin-17A secreted by ex vivo immune cells from this GS patient. Compared with healthy control subjects, this GS patient had fewer B cells, an inverted ratio of CD4+/CD8+ cells, and more Treg cells in his peripheral blood. Additionally, the patient's Vδ2 T cell levels were significantly decreased despite having a normal percentage of γδT cells. Ex vivo peripheral CD4+ T cells from the patient showed insufficient proliferation and division potential as well as excessive expression of PD-1. Moreover, IFN-γ was predominantly derived from CD8+ T cells in this GS patient, rather than from CD4+ T cells and γδT cells. This GS patient had impaired T and B cell immunological alternations and cytokine disruptions after thymectomy. Detailed research should focus on therapies that can adjust the immune status in such patients for a better outcome.

Glomus tumors of the trachea: 2 case reports and a review of the literature.

Glomus tumors (GTs) of the trachea are very rare neoplasms that usually arise from the distal portion of the respiratory tree. The origin of these tumors is modified smooth muscle cells of glomus bodies. In this study, we describe two cases of GT of the trachea, as well as the histologic features of these tumors and their treatments. One tumor was diagnosed via bronchoscopic biopsy, and the other tumor was diagnosed via surgery. Clinical follow-up showed that the two patients are alive and well after 8 and 15 months post-treatment, respectively. We also review the literature regarding GTs and discuss the clinical presentation, histologic features, differential diagnosis, treatment and prognosis of these tumors.

Anaplastic lymphoma kinase-positive lung adenocarcinoma patient with development of sick sinus syndrome while on targeted treatment with crizotinib.

The anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are younger and have never smoked, while pathologically are predominately adenocarcinomas. Crizotinib as an ALK inhibitor has been used in treating ALK positive NSCLC patients for several years and some adverse effects should be paid attention to. We now describe a case of ALK positive NSCLC patient with development of sick sinus syndrome (SSS) while on targeted treatment with crizotinib. A 46-year-old non-smoking woman with right hilar mass and underwent transesophageal endoscopic ultrasonography lymph node biopsy showed low differentiation adenocarcinoma, immunohistochemistry (IHC) of tumor samples revealed the ALK overexpression. The severe sinus bradycardia and RR interval prolongation were detected 3 months after crizotinib treatment, she underwent pacemaker implantation. Although the severe sinus bradycardia and RR interval prolongation were unusual adverse effects, physicians should be aware of these side effects when using crizotinib.

[The effects of imiquimod on an animal model of asthma].

OBJECTIVE: To study the mechanism of imiquimod on asthma animals. METHODS: (1) 40 mice and 48 rats were divided into 4 groups: control, asthma, dexamethasone and imiquimod groups. The asthma model was established. The mice and rats in the imiquimod group were exposed to an aerosol of 0.15% imiquimod. Lung inflammation and airway responsiveness were measured 24 h after the last ovalbumin (OVA) challenge. The expression of Interleukin-4 (IL-4), interferon gamma (IFN-gamma), eotaxin, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), T-bet, GATA-3, STAT6 mRNA in the lung were determined by reverse transcription polymerase chain reaction (RT-PCR). The levels of eotaxin, MDC, and TARC in sera were tested by enzyme linked immunosorbent assay (ELISA). The expression of T-bet, GATA-3 and STAT6 proteins in the lung were measured by Western blot. (2) Parabronchial lymphnodes (PBLN) were isolated and cultured. The PBLN cells were divided into blank control, positive control, dexamethasone and drug groups (1 - 3 subgroups), cultured for different hours, and the expressions of IL-4 and IFN-gamma in supernatants were determined by ELISA, The mRNA expressions of the cytokines in cells weredetected by RT-PCR. (3) Flow cytometry was used to detect intracellular IL-4 and IFN-gamma production in spleen T lymphocytes. (4) CD(4)(+) T cell of spleen pellets were subject to assessment of T-bet and GATA-3 protein and mRNA expression respectively. RESULTS: The expiration resistance was determined before and after injection of acetylcholine chloride (20 - 160 microg/ml), and expiration resistances of the asthmatic group (6.26 +/- 0.85), (11.55 +/- 3.09), (28.74 +/- 5.94), (3710.83 +/- 197.49) cm H(2)Oxml(-1)xs(-1), were significantly elevated compared with those of the control group (1.34 +/- 0.16), (3.47 +/- 0.49), (9.29 +/- 1.27), (25.22 +/- 5.44) cm H(2)Oxml(-1)xs(-1), D = 88.98, 56.00, 45.00, 108.00, all P < 0.01). The numbers of eosinophils and lymphocytes, the thicknesses of WA/Pi and ASM/Pi in the asthmatic group [(26.0 +/- 1.6)/mm(2), (45.2 +/- 3.2)/mm(2), 12.0 +/- 1.4, 6.7 +/- 0.6] were all significantly higher than those of the imiquimod group [(12.4 +/- 2.9)/mm(2), (24.2 +/- 3.7)/mm(2), 9.2 +/- 0.6, 4.0 +/- 0.5, D or q = 193.00, 16.92, 185.50, 7.66, all P < 0.01]. In the imiquimod group, the mRNA and protein expressions of T-bet (0.48 +/- 0.08, 0.48 +/- 0.17) were significantly increased compared with those of the asthmatic group (0.08 +/- 0.12, 0.18 +/- 0.06, D = 120.96, 177.98, all P < 0.01), the mRNA and protein expressions of GATA-3 in the imiquimod group were both significantly decreased compared with those of the asthmatic group (D = 166.96, 310.97, all P < 0.01). In the control group, only low concentrations of IFN-gamma [(22 +/- 5, 31 +/- 5) pg/ml] were detected in PBLN cell cultures. After 24 or 48 h stimulation, the concentrations of IFN-gamma in drug 2 subgroup [(149 +/- 31), (154 +/- 28) pg/ml] and drug 3 subgroup [(166 +/- 30), (158 +/- 31) pg/ml] were increased significantly; Levels of IL-4 [druug 2 subgroup: (23 +/- 5), (39 +/- 11) pg/ml, drug 3 subgroup: (43 +/- 13), (56 +/- 12) pg/ml] were increased slowly compared with those in the OVA group (drug 2 subgroup 24 h IL-4, D = 9.90; drug 3 subgroup 24 h IL-4, D = 8.79, drug 2 subgroup 48 h IL-4, D = 8.80, drug 3 subgroup 48 h IL-4, D = 8.10, drug 2 subgroup 24 h IFN-gamma, q = 4.80, drug 3 subgroup 24 h IFN-gamma, q = 6.40, drug 2 subgroup 48 h IFN-gamma, q = 3.95, drug 3 subgroup 48 h IFN-gamma, q = 4.31, all P < 0.05). After imiquimod treatment, the mRNA and protein levels of T-bet in imiquimod group CD(4)(+) T cells were increased significantly compared with those in OVA group, and the mRNA and protein levels of GATA-3 were decreased significantly in CD(4)(+) T cells of imiquimod group compared with those in OVA group. The eotaxin, MDC and TARC levels of serum in asthma group [(593 +/- 41) pg/ml, (170 +/- 20) pg/ml, (221 +/- 25) pg/ml] were significant different from those in control group [(288 +/- 66) pg/ml, (100 +/- 33) pg/ml, (84 +/- 49) pg/ml], (eotaxin: q = 12.20, MDC: q = 8.00, TARC: q = 10.50, all P < 0.01). MDC and TARC levels of serum in imiquimod group [(84 +/- 13) pg/ml, (163 +/- 35) pg/ml] decreased as compared with those in asthma group (MDC: q = 9.80, TARC: q = 4.50, all P < 0.01) and MDC levels in imiquimod group were no different with normal group (q = 1.80, P > 0.05). eotaxin levels of serum in imiquimod group [(501 +/- 76) pg/ml] increased as compared with those from normal group (q = 8.50, P < 0.01), and decreased as compared with those from asthma group (q = 3.70, P < 0.05). (4) The expression of eoaxin, MDC, TARC and STAT(6) on the bronchial epithelium in imiquimod group was decreased as compared with asthma group, but increased as compared with normal group. The eotaxin, MDC and TARC mRNA expression of the lung in asthma group (0.85 +/- 0.11, 0.96 +/- 0.10, 0.94 +/- 0.28) had significant differences from those in the control group (0.45 +/- 0.08, 0.39 +/- 0.09, 0.24 +/- 0.08, eotaxin: q = 3.00, MDC: q = 15.40, TARC: q = 5.90, all P < 0.01) and those in imiquimod group (0.65 +/- 0.17, 0.66 +/- 0.12, 0.66 +/- 0.34, eotaxin: q = 1.50, MDC: q = 8.10, TARC: q = 2.40, all P < 0.05). CONCLUSION: These findings suggested that imiquimod can inhibit the airway inflammation of asthma animals by reducing GATA-3 mRNA and protein expression and increasing T-bet, STAT(6) mRNA and protein expression.

[Imbalanced T cell-specific transcription factors T-bet and GATA-3 and relationship to airway inflammation in asthmatic rats].

OBJECTIVE: To identify the change of the mRNA and protein expression of T-bet and GATA-3 in lung tissues, and to investigate the association between the imbalanced T cell-specific transcription factors T-bet/GATA-3 and the airway inflammation in asthmatic rats. METHODS: Twenty-four male SD rats were randomly divided into a control group and an asthmatic group. Airway responsiveness was measured and the change of airway histology was observed. The concentrations of interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in the lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. RESULTS: The expiration resistance after injection of acetylcholine chloride (20, 40, 80, 160 microg/ml) in the asthmatic group was (6.26 +/- 0.85), (11.55 +/- 3.09), (28.74 +/- 5.94), (3,710.83 +/- 197.49) cm H2O.ml(-1).s(-1) respectively; and that in the control group was (1.51 +/- 0.18), (2.15 +/- 0.36), (6.08 +/- 1.06), (37.17 +/- 6.12) cm H2O.ml(-1).s(-1) respectively; the difference being significant between the two groups (all P < 0.01). In the asthmatic group, the numbers of eosinophils and lymphocytes, the thicknesses of WA/Pi and ASM/Pi were (26.0 +/- 1.6)/mm(2), (45.2 +/- 3.2)/mm(2), 12.0 +/- 1.4, 6.7 +/- 0.6, respectively; and those of the control group were (2.9 +/- 1.2)/mm(2), (8.8 +/- 1.8)/mm(2), 6.4 +/- 0.8, 2.7 +/- 0.5, respectively; all were significantly different between the two groups (all P < 0.01). In the asthmatic group, the concentrations of IL-4, IL-5, and IFN-gamma in BALF were (23.4 +/- 0.7) pg/ml, (24.8 +/- 0.5) pg/ml, (21.7 +/- 1.1) pg/ml, respectively, and those of the control group were (9.3 +/- 0.3) pg/ml, (12.5 +/- 0.3) pg/ml, (65.8 +/- 2.1) pg/ml, respectively; all were significantly different between the two groups (all P < 0.01). In the control group, the mRNA ratio of T-bet to GATA-3 (0.73 +/- 0.32) was significantly increased compared with the asthmatic group (0.06 +/- 0.09, P < 0.01). There was also a significant difference in the ratio of protein expression of T-bet to GATA-3 between the control group (0.75 +/- 0.25) and the asthmatic group (0.09 +/- 0.04, P < 0.01). The ratio of protein expression of T-bet and GATA-3 was correlated negatively with expiration resistance (r = -0.959, -0.919, -0.949, all P < 0.01), the numbers of eosinophils and lymphocytes in lung tissues (r = -0.832, -0.831, all P < 0.01), the thicknesses of WA/Pi and ASM/Pi (r = -0.837, -0.863, all P < 0.01) and the concentrations of IL-4, IL-5 in BALF (r = 0.921, 0.920, all P < 0.01), the mRNA of IL-4, IL-5 in lung tissues (r = -0.964, -0.931, all P < 0.01), but positively with the concentrations of IFN-gamma in BALF and the mRNA of IFN-gamma in lung tissues (r = -0.934, 0.983, all P < 0.01). CONCLUSION: Imbalance of transcription factors T-bet and GATA-3, a reflection of the immune imbalance in asthma, may play a key role in the formation of airway inflammation in the disease.

Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3.

BACKGROUND: Imiquimod is an imidazoquinoline, which class of compounds are known to have antiviral and antitumoural properties. In recent studies, it was shown that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the production of Th1 cytokines like IFN-gamma, and by inhibiting the Th2 cytokines like interleukin (IL)-4. Several investigators have shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. This study investigated whether imiquimod treatment inhibited airway inflammation by modulating transcription factors T-bet and GATA-3. METHODS: Thirty-six male SD rats were randomly divided into a control group, an asthmatic group, and an imiquimod group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured and changes in airway histology were observed. The concentrations of IL-4, IL-5 and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in lung and in CD4(+) T cells were determined by reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of T-bet and GATA-3 were measured by Western blot. RESULTS: It was demonstrated that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the degree of airway hyperresponsiveness (AHR); 3) decreased the Th2 type cytokines and increased Th1 type cytokines mRNA and protein levels; 4) modulated the Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production. CONCLUSION: Imiquimod treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in committing T helper cells to a Th1 phenotype.