Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in asthma.This study investigated the impact of Bcl-6 on asthmatic traits.Methods The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference mice.The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,respectively.The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were determined.Results Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these changes.The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM treatment.RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM treatment.The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend.In asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 levels.Conclusion The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

The Clinical Role of Changes of Maximum Expiratory Flow at 25%and 50%of Vital Capacity before and after Bronchodilator Reversibility Test in Diagnosing Asthma

Summary:Changes of maximum expiratory flow at 25%and 50%of vital capacity(MEF2s and MEFso,respectively),and predominant parameters indicating small airways function in asthmatics before and after bronchodilator(BD)reversibility test have been less interpreted.Our study aimed to investigate the clinical role of changes of MEF2s and MEFso before and after BD reversibility test in diagnosing asthma.Forced expiratory volume in the first second(FEV),MEF2s,and MEFso were measured before and after BD reversibility test in 207 asthmatic patients using standard process.Forty healthy individuals were enrolled as controls.Receiver operating characteristic(ROC)curve was used to assess the diagnostic accuracy of reversibility of MEF2s and MEFgo before and after BD reversibility test(OMEF 2s%and AMEF so%,respectively)in diagnosing asthma.Among these functional criteria,AMEF2;%and 0MEFs%≥25%performed the best diagnostic performance.The sensitivity,specificity,and accuracy of AMEF 25%≥25%as an objcctive diagnostic test for asthma were 63.29%,87.50%,and 67.21%,and of AMEFs0%≥25%were 79.23%,85.00%,and 80.16%,respectively.The area under the ROC curve of the indicators was 0.8203 and 0.9104,respectively.By contrast,an increase in FEV≥12%and 200 mL demonstrated a sensitivity of 62.32%,specificity of 82.50%,and accuracy of 65.59%in diagnosing asthma.The changes of MEF2s and MEFso before and after BD reversibility test may be of additional value in the clinical diagnosis of asthma,with cutoff values of 25%being the most.

Affected cortico-striatal-cerebellar network inschizophrenia with catatonia revealed by magneticresonance imaging:indications for electroconvulsive therapy and repetitive transcranial magnetic stimulation

Catatonia is a psychomotor syndrome that can occur in a broad spectrum of brain disorders,including schizophrenia.Current findings suggest that the neurobiological process underlying catatonia symptoms in schizophrenia is poorly understood.However,emerging neuroimaging studies in catatonia patients have indicated that a disruption in anatomical connectivity of the cortico-striatal-cerebellar system is part of the neurobiology of catatonia,which could serve as a target of neurostimulation such as electroconvulsive therapy and repetitive transcranial magnetic stimulation.

Magnetic Resonance Imaging-Guided and Navigated Individualized Repetitive Transcranial Magnetic Stimulation for Cognitive Impairment in Schizophrenia

Schizophrenia(SZ)is a chronic,serious,and recurrent mental illness,characterized by cognitive impairment as the core symptom,which can be an important sign before the onset of psychosis[1].Furthermore,persistent cognitive impairment is specific to the disease and disrupts the cognitive trajectory of patients with SZ[2].

Ultrastructural alterations of megakaryocytes in thrombocytopenia:A review of 43 cases

Thrombocytopenia is a frequent occurrence in a variety of hematopoietic diseases;however,the details of the mechanism leading to low platelet count remain elusive.Megakaryocytes are a series of progenitor cells responsible for the production of platelets.Alterations in megakaryocytes in the bone marrow are a causative factor resulting in thrombocytopenia in varied diseases.Based on ultrastructural analysis of incidentally encountered megakaryocytes in 43 patients with blood diseases marked by low platelet counts,electron micrographs demonstrated that aberrant megakaryocytes predominated in idiopathic thrombocytopenic purpura,aplastic anemia,and myelodysplastic syndrome;autophagy,apoptosis,and cellular damage in megakaryocytes were a prominent feature in aplastic anemia.On the other hand,poorly differentiated megakaryocytes predominated in acute megakaryoblastic leukemia(AMKL)although damaged megakaryocytes were seen in non-AMKL acute leukemia.This paper documents the ultrastructural alterations of megakaryocytes associated with thrombocytopenia and reveals distinctive features for particular blood diseases.A comment is made on future avenues of research emphasizing membrane fusion proteins.