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microRNAs are short, noncoding RNA molecules involved in many inflammatory processes including bronchial asthma. Rhinoviruses are the main cause of acute asthma attack and may be involved in miRNA profile dysregulation. The aim of the study was to investigate the serum miRNA profile during asthma exacerbation in middle-aged and elderly patients. We also evaluated in this group in vitro response to rhinovirus 1b exposure. Seventeen middle-aged and elderly asthmatics were admitted to an outpatient clinic during asthma exacerbation and within a period of 6-8 weeks later. Blood samples were collected from the subjects and PBMCs were isolated. Cells were cultured in the presence of Rhinovirus 1b and with the medium only, and, after 48 h. miRNA expression (miRNA-19b, -106a, 126a, and -146a) isolated from serum and PBMCs (cultures) was evaluated with RT-PCR. Cytokines (INF-γ, TNF-α, IL6, and Il-10) in culture supernatants were evaluated with flow cytometry. On exacerbation visit patients demonstrated higher expression of serum miRNA-126a and -146a as compared to follow-up visit. There was a positive correlation between asthma control test results and miRNA-19, -126a, -146a. There was no other significant association between patient characteristics and the miRNA profile. Rhinovirus exposure did not changed miRNA expression in PBMCs as compared to medium on both visits. Cytokine production in culture supernatants significantly increased after rhinovirus infection. The group of middle-aged and elderly patients demonstrated changed levels serum miRNA during asthma exacerbation as compared to follow-up visit; however, correlations between their expression and clinical features were hardly noticeable. Rhinovirus did not affect expression of miRNA in PBMCs; yet, it induced cytokine production.
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Asma , MicroRNAs , Pessoa de Meia-Idade , Idoso , Humanos , MicroRNAs/genética , Asma/genética , Asma/complicações , Citocinas , Fator de Necrose Tumoral alfaRESUMO
Plasma from patients with Parkinson's disease (PD) is a valuable source of information indicating altered metabolites associated with the risk or progression of the disease. Neurotoxicity of dopaminergic neurons, which is triggered by aggregation of α-synuclein, is the main pathogenic feature of PD. However, a growing body of scientific reports indicates that metabolic changes may precede and directly contribute to neurodegeneration. Identification and characterization of the abnormal metabolic pattern in patients' plasma are therefore crucial for the search for potential PD biomarkers. The aims of the present study were (1) to identify metabolic alterations in plasma metabolome in subjects with PD as compared with the controls; (2) to find new potential markers, some correlations among them; (3) to identify metabolic pathways relevant to the pathophysiology of PD. Plasma samples from patients with PD (n = 25) and control group (n = 12) were collected and the gas chromatography-time-of-flight-mass spectrometry GC-TOFMS-based metabolomics approach was used to evaluate the metabolic changes based on the identified 14 metabolites with significantly altered levels using univariate and multivariate statistical analysis. The panel, including 6 metabolites (L-3-methoxytyrosine, aconitic acid, L-methionine, 13-docosenamide, hippuric acid, 9,12-octadecadienoic acid), was identified to discriminate PD from controls with the area under the curve (AUC) of 0.975, with an accuracy of 92%. We also used statistical criteria to identify the significantly altered level of metabolites. The metabolic pathways involved were associated with linoleic acid metabolism, mitochondrial electron transport chain, glycerolipid metabolism, and bile acid biosynthesis. These abnormal metabolic changes in the plasma of patients with PD were mainly related to the amino acid metabolism, TCA cycle metabolism, and mitochondrial function.
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Asma , MicroRNAs , Infecções por Picornaviridae , Humanos , Leucócitos Mononucleares , MicroRNAs/genética , RhinovirusRESUMO
BACKGROUND: The course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA. METHODS: Control and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry. RESULTS: No difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs. CONCLUSION: Serum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.
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Asma/sangue , MicroRNA Circulante/sangue , Volume Expiratório Forçado/fisiologia , Inflamação/sangue , Idoso , Asma/complicações , Asma/fisiopatologia , Biomarcadores/sangue , Citocinas/sangue , Feminino , Humanos , Inflamação/complicações , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. MATERIALS AND METHODS: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. RESULTS: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.
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COVID-19 , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Feminino , Humanos , Fatores Imunológicos , Imunossupressores , Masculino , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Polônia/epidemiologia , SARS-CoV-2RESUMO
The effect of rhinovirus on airway epithelium is very well described. However, its influence on the vascular endothelium is unknown. The current study assesses the effect of rhinovirus HRV16 on the antiviral and inflammatory response in the human vascular endothelial cells (ECs). HRV16 increased IFN-ß, RANTES, and IP-10 mRNA expression and protein release. HRV16 copy number in ECs reached maximal value 10 h after incubation. Increase in virus copies was accompanied by the enhancement of Toll- and RIG-I-like receptors: TLR3, RIG-I, and MDA5. Additionally, HRV16 increased OAS-1 and PKR mRNA expression, enzymes responsible for virus degradation and inhibition of replication. ICAM-1 blockade decreased HRV16 copy number in ECs and inhibited IFN-ß, RANTES, IP-10, OAS1, PKR, TLR3, RIG-I, and MDA5 mRNA expression increase upon subsequent induction with HRV16. The vascular endothelium may be infected by human rhinovirus and generate antiviral and inflammatory innate response. Results of the study indicate the possible involvement of the vascular endothelium in the immunopathology of rhinoviral airway infections.
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Endotélio Vascular/imunologia , Infecções por Picornaviridae/imunologia , Rhinovirus/imunologia , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/imunologia , Endotélio Vascular/virologia , Células Endoteliais da Veia Umbilical Humana/imunologia , Células Endoteliais da Veia Umbilical Humana/virologia , Humanos , Interferon beta/genética , Interferon beta/imunologia , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/virologia , Receptores Imunológicos , Rhinovirus/genética , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologiaRESUMO
Epigenetic modifications play a key role in gene regulation and expression and are involved in numerous cellular processes. Due to the limited research on nucleosides in Parkinson's disease (PD), it is very important to consider epigenetic factors and their role in the development of PD. The aim of this study was to investigate and compare the levels of modified nucleosides, such as O-methylguanosine, N6-methyl-2'-deoxyadenosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine, 3-methyladenine and 7-methylguanosine in the urine of Parkinson's disease (PD) patients and the control group, and to verify that the results obtained differ in a subgroup of patients with parkinsonian syndromes. The study group comprised 18 patients with diagnosed idiopathic Parkinson's disease and four parkinsonian syndromes. The control group consisted of 30 age- and sex-matched neurological patients without confirmation by neuroimaging brain damage and extrapyramidal symptoms. The levels of nucleosides were determined by validated liquid chromatography coupled with the mass spectrometry (LC-MS/MS) method using the multiple reaction monitoring (MRM) mode. Lower levels of O-methylguanosine, 3-methyladenine, 1-methylguanine, N6-methyl-2'-deoxyadenosine and a higher level of 7-methylguanine in the urine of 22 PD patients were observed. Moreover, elevated levels of 1-methyladenosine, 7-methylguanine, and O-methylguanosine were observed in the parkinsonian syndrome subgroup. These preliminary results may indicate that modified nucleosides describe metabolic disturbances in the metabolism of purine, which was the most severely affected pathway that mediated the detrimental effects of neuroinflammation on PD.
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Cromatografia Líquida , Doença de Parkinson/urina , Transtornos Parkinsonianos/urina , Espectrometria de Massas em Tandem , Urinálise/métodos , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hyperfibrinogenemia plays a crucial role in the coagulation cascade leading to the formation of clots. It is involved in the process of platelet aggregation, primary haemostasis, and leukocyte-endothelial cell interactions. The aim of our study was to assess the correlations between fibrinogen concentration and particular risk factors for vascular diseases and atherosclerotic changes in stroke patients. METHODS: The study group consisted with 94 patients with acute ischaemic stroke with normo- or hyperglycaemia and normoor hyperlipidemia. 21 healthy subjects served as a control group. Fibrinogen level, HbA1c, and lipid profile were measured in all patients. Using a flow cytometer, we assessed CD61 positive microparticles which were defined as platelet-derived microparticles (PDMPs). The level of sP-selectin in serum was measured using the ELISA method. RESULTS: A significant positive correlation was observed between fibrinogen concentration and sP-selectin (p = 0.001), HbA1c (p < 0.05) level, and percentage of PDMPs (p < 0.05) in the study patients. Furthermore, we noticed a significant negative correlation between fibrinogen concentration and the level of HDL (p < 0.05). No correlation was observed between fibrinogen and TC, LDL and TG levels. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our findings suggest that an elevated fibrinogen level may represent a marker of prothrombotic condition exacerbated in the state of hyperglycaemia and activation of platelets and endothelial cells. This suggests an important role played by fibrinogen in the process of thrombogenesis.
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Isquemia Encefálica , Doenças Metabólicas , Acidente Vascular Cerebral , Micropartículas Derivadas de Células , Células Endoteliais , Fibrinogênio , HumanosRESUMO
PURPOSE: Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. METHODS: Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. RESULTS: Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. CONCLUSIONS: Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.
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BACKGROUND: Epidemiologic data on primary progressive multiple sclerosis (PPMS) in Poland are limited. The aim of this study was to assess selected clinical and socio-demographic factors of Polish patients with PPMS and compare this form and relapsing-remitting (RRMS) and secondary progressive (SPMS) forms. METHODS: Patients who attended follow-up visits under the Registry of Patients with Multiple Sclerosis (RejSM) were enrolled in the study in the autumn of 2017. The prevalence of individual types of the disease was compared and the clinical, demographic, and social differences between RRMS, PPMS and SPMS were analyzed. RESULTS: Of the 8,045 registered patients, current data as on December 31, 2017 was obtained from 4,398 patients. The RRMS form was seen in 2,925 patients (66.5%); secondary progressive form, in 1.051 patients (23.9%); and PPMS, in 422 patients (9.6%). The first symptoms of PPMS appeared almost 10 years later than in patients with RRMS (39.2⯱â¯11.4â¯vs. 29.8⯱â¯9.8). The period from the first symptoms to diagnosis was more than twice as long in patients with PPMS (5.8⯱â¯3.4) than RRMS (2.4⯱â¯1.6). SPMS was diagnosed on average after 14 years of RRMS (46.2⯱â¯13.5). The RRMS form was more frequently found in women (2.4:1), while the PPMS form was almost equal in both sexes (1.2:1). The average degree of disability based on the Expanded Disability Status Scale was 3.2⯱â¯2.1 for RRMS, 4.6⯱â¯2.4 for PPMS and 5.2⯱â¯3.6 for SPMS. The dominant symptom in PPMS was paresis of the lower limbs (86%). Patients with PPMS had higher education and higher instance of marriage than those with RRMS or SPMS. CONCLUSIONS: PPMS occurs in about 10% of Polish patients with multiple sclerosis, and the first symptoms appear at around 40 years of age with the same frequency in both sexes. PPMS diagnosis takes more than twice the time for RRMS.
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Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Crônica Progressiva/epidemiologia , Adulto , Feminino , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Polônia/epidemiologiaRESUMO
Lower limb veins diseases belong to frequently occurring disease syndromes. It covers 62% of adult Poles. They are not only an aesthetic problem. They can cause a lot of subjective and objective ailments significantly reducing the quality of life - from asymptomatic spider veins to permanent pain in lower limbs, especially in standing, fixed edema, skin lesions and ulceration. Superficial chronic venous insufficiency is due to incompetence of the saphenofemoral junction and great or small saphenous vein. Conventional surgery involves high ligation, stripping and phlebectomy. Recently, at the beginning of XXI century, minimally invasive endovenous techniques which became as alternatives to conventional surgery. Currently, the number of possible methods of treatment of venous disease available for use exceeds ten.
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Varizes , Insuficiência Venosa , Adulto , Humanos , Qualidade de Vida , Veia Safena , Resultado do Tratamento , Varizes/terapiaRESUMO
PURPOSE: Respiratory viral infection and nonsteroidal anti-inflammatory drugs (NSAIDs) may affect arachidonic acid (AA) metabolism in the airway epithelium, however their joint effect has not been studied. We hypothesized, that alternations of AA metabolism in human airway epithelial cells (ECs) - induced by Parainfluenza virus type 3 (PIV3) - may be modified by concomitant treatment with NSAIDs. MATERIALS AND METHODS: Nasal (RPMI 2650) and bronchial (BEAS-2B) epithelial cells were cultured into confluence and then infected with PIV3. Prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) levels in cell supernatants were measured by ELISA and expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) mRNA in cells was evaluated after reverse transcription with real-time polymerase chain reactions. RESULTS: PGE2 generation was decreased by PIV3 infection in the upper airway epithelial cells, and increased in the lower airway epithelial cells. Both naproxen and celecoxib induced significant reduction in PGE2 release in both infected and non-infected upper and lower airway epithelial cells. However, in PIV3-infected epithelial cells celecoxib inhibited PGE2 release and COX-2 expression to significantly higher degree as compared to non-infected cells. 15-HETE generation or COX-1, 5-LO and 15-LO expression were not affected by the virus infection or by NSAIDs. CONCLUSION: Virus infection in airway epithelial cells enhances inhibitory effect of NSAIDs on prostaglandin E2 generation.
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Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Infecções por Paramyxoviridae/metabolismo , Celecoxib/farmacologia , Linhagem Celular , Células Epiteliais , Humanos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
INTRODUCTION: Respiratory pathogens are thought to be involved in the pathogenesis and exacerbations of asthma at all ages; however, little is known about the airway microbiome in the elderly. AIM OF THE STUDY: To identify respiratory pathogens in the induced sputum (IS) of elderly asthmatics, and to determine the association between pathogens and the markers of asthma activity. MATERIAL AND METHODS: Twenty-nine subjects with stable asthma, 15 above 65 years of age and 14 aged 30-49 years, underwent clinical evaluation, fractional exhaled nitric oxide measurement, and sputum induction. Pathogens were detected by multiplex reverse transcription polymerase chain reaction. The periostin concentration of IS supernatants was measured by enzyme-linked immunosorbent assay. Serum eosinophil cationic protein and total IgE levels were measured by ImmunoCAP. RESULTS: Elderly patients, as compared to non-elderly, had significantly higher eosinophilia in IS, although other markers of eosinophilic inflammation were comparable. Half of the subjects were positive for Haemophilus influenzae. Chlamydophila pneumoniae was found in two subjects. Respiratory viruses were detected in more than 70% of patients. The detection rates and profiles of atypical bacteria and respiratory viruses were similar in both groups. Only in the elderly asthmatics was influenza A positivity associated with lower predicted FVC%, RSV A positivity connected with decreased tIgE concentration, and RSV B positivity related to a lower percentage of lymphocytes in IS. CONCLUSIONS: Despite the existence of differences in some clinical and inflammatory characteristics of asthma between elderly and non-elderly asthmatics, the pathogen detection rates in the IS from the two groups are similar.
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BACKGROUND: Activation of platelets and endothelial cells plays an important role in the pathogenesis of atherosclerosis and thrombotic disorders. The aim of our study was to assess the relationship between the metabolic disorders and markers of platelet activity and vascular injury in patient with acute ischemic stroke. MATERIAL AND METHODS: The study group consisted of 84 patients with acute non-lacunar ischemic stroke divided into four subgroups with: (1) normolipidemia and normoglycemia, (2) normolipidemia and hyperglycemia, (3) hyperlipidemia and normoglycemia, (4) hyperlipidemia and hyperglycemia. 21 healthy subjects served as controls. We analyzed the concentration of adhesion molecules sP-selectin and sE-selectin in serum collected from all studied groups using ELISA method. RESULTS: We observed significantly higher sE- and sP-selectin concentration in patients with hyperglycemia and hyperlipidemia compared to both control subjects and patients with normolipidemia and normoglycemia. We did not observe additional effect of comorbid hyperlipidemia and hyperglycemia on studied markers. Soluble E- and P-selectin concentration correlated positively with LDL, TC and HbA1c level in all stroke patients. CONCLUSION: Soluble E- and P-selectin, blood markers of vascular injury and platelet activation, could be useful in the assessment of atherothrombotic properties of hyperglycemia and hyperlipidemia in stroke patients.
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Doenças Metabólicas , Acidente Vascular Cerebral , Biomarcadores , Moléculas de Adesão Celular , Humanos , Ativação Plaquetária , SelectinasRESUMO
BACKGROUND: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. OBJECTIVE: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. METHODS: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. RESULTS: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-ß and RANTES mRNA expression was higher in injured ECs and IFN-α, IFN-ß, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-α and IFN-ß mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. CONCLUSION: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors.
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Regeneração/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/fisiologia , Receptores Toll-Like/agonistas , Cicatrização/efeitos dos fármacos , Alérgenos/farmacologia , Antivirais/farmacologia , Brônquios/efeitos dos fármacos , Brônquios/lesões , Brônquios/fisiologia , Brônquios/virologia , Linhagem Celular , Humanos , Indutores de Interferon/farmacologia , Lipopolissacarídeos/farmacologia , Poli I-C/farmacologia , Mucosa Respiratória/lesões , Mucosa Respiratória/virologia , Receptores Toll-Like/antagonistas & inibidoresRESUMO
PURPOSE: In order to gain an insight into determinants of reported variability in immune responses to respiratory viruses in human bronchial epithelial cells (HBECs) from asthmatics, the responses of HBEC to viral infections were evaluated in HBECs from phenotypically heterogeneous groups of asthmatics and in healthy controls. METHODS: HBECs were obtained during bronchoscopy from 10 patients with asthma (6 atopic and 4 non-atopic) and from healthy controls (n=9) and grown as undifferentiated cultures. HBECs were infected with parainfluenza virus (PIV)-3 (MOI 0.1) and rhinovirus (RV)-1B (MOI 0.1), or treated with medium alone. The cell supernatants were harvested at 8, 24, and 48 hours. IFN-α, CXCL10 (IP-10), and RANTES (CCL5) were analyzed by using Cytometric Bead Array (CBA), and interferon (IFN)-ß and IFN-λ1 by ELISA. Gene expression of IFNs, chemokines, and IFN-regulatory factors (IRF-3 and IRF-7) was determined by using quantitative PCR. RESULTS: PIV3 and RV1B infections increased IFN-λ1 mRNA expression in HBECs from asthmatics and healthy controls to a similar extent, and virus-induced IFN-λ1 expression correlated positively with IRF-7 expression. Following PIV3 infection, IP-10 protein release and mRNA expression were significantly higher in asthmatics compared to healthy controls (median 36.03-fold). No differences in the release or expression of RANTES, IFN-λ1 protein and mRNA, or IFN-α and IFN-ß mRNA between asthmatics and healthy controls were observed. However, when asthmatics were divided according to their atopic status, HBECs from atopic asthmatics (n=6) generated significantly more IFN-λ1 protein and demonstrated higher IFN-α, IFN-ß, and IRF-7 mRNA expressions in response to PIV3 compared to non-atopic asthmatics (n=4) and healthy controls (n=9). In response to RV1B infection, IFN-ß mRNA expression was lower (12.39-fold at 24 hours and 19.37-fold at 48 hours) in non-atopic asthmatics compared to atopic asthmatics. CONCLUSIONS: The immune response of HBECs to virus infections may not be deficient in asthmatics, but seems to be modified by atopic status.
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INTRODUCTION: Platelet activation plays a key role in the pathogenesis of ischemic cerebrovascular diseases. Thus, it is very important to identify novel pharmacological targets for platelet inhibition to improve ischemic stroke treatment. The aim of the study was to assess the relationship between metabolic disorders and platelet activity markers in patients with acute ischemic stroke. MATERIAL AND METHODS: Ninety-four patients with acute ischemic stroke were divided into four groups with: normolipidemia and normoglycemia (NL/NG), n = 25; normolipidemia and hyperglycemia (NL/HG), n = 21; hyperlipidemia and normoglycemia (HL/NG), n = 27; hyperlipidemia and hyperglycemia (NL/NG), n = 21. Twenty-one healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets using the flow cytometer and anti-CD61 and anti-CD62P monoclonal antibodies. CD61-positive microparticles were defined as platelet-derived microparticles. The level of sP-selectin in serum was measured by the ELISA method. RESULTS: We observed a significant influence of hyperlipidemia and hyperglycemia on sP-selectin concentration. A strong correlation between higher sP-selectin concentration and enhanced LDL (p = 0.001), total cholesterol (p = 0.02), HbA1c level (p < 0.001) was noticed. The level of sP-selectin and PDMPs (p < 0.001) were significantly higher in all groups of stroke patients compared with the controls. CD62P expression on resting and thrombin activated platelets were significantly lower in groups of patients with stroke. CONCLUSIONS: Hyperlipidemia and hyperglycemia exert an equal stimulatory effect on tested platelet markers but with no synergistic action in stroke patients with both of the metabolic comorbidities. sP-selectin concentration in stroke patients best reflects the impact of hyperglycemia and hyperlipidemia on vascular lesions and platelet activation.
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Lambda interferons (IFNLs) have immunomodulatory functions at epithelial barrier surfaces. IFN-λ4, a recent member of this family is expressed only in a subset of the population due to a frameshift-causing DNA polymorphism rs368234815. We examined the association of this polymorphism with atopy (aeroallergen sensitization) and asthma in a Polish hospital-based case-control cohort comprising of well-characterized adult asthmatics (n = 326) and healthy controls (n = 111). In the combined cohort, we saw no association of the polymorphism with asthma and/or atopy. However, the IFN-λ4-generating ΔG allele protected older asthmatic women (>50 yr of age) from atopic sensitization. Further, ΔG allele significantly associated with features of less-severe asthma including bronchodilator response and corticosteroid usage in older women in this Polish cohort. We tested the association of related IFNL locus polymorphisms (rs12979860 and rs8099917) with atopy, allergic rhinitis and presence/absence of asthma in three population-based cohorts from Europe, but saw no significant association of the polymorphisms with any of the phenotypes in older women. The polymorphisms associated marginally with lower occurrence of asthma in men/older men after meta-analysis of data from all cohorts. Functional and well-designed replication studies may reveal the true positive nature of these results.
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Alérgenos/imunologia , Asma/etiologia , Asma/metabolismo , Interferon gama/metabolismo , Polimorfismo Genético , Adulto , Idoso , Alelos , Asma/diagnóstico , Estudos de Casos e Controles , Feminino , Frequência do Gene , Loci Gênicos , Genótipo , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Polônia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Viral infections are leading causes of both upper and lower airway acute illness in all age groups of healthy persons, and have also been implicated in the acute exacerbations of chronic respiratory disorders like asthma and COPD. Human rhinovirus, respiratory syncytial virus, influenza virus and coronavirus have been considered as the most important respiratory pathogens and relatively little attention has been paid to the role of parainfluenza viruses (hPIVs). Human parainfluenza viruses are single-stranded RNA viruses belonging to the paramyxovirus family that may evoke lower respiratory infections in infants, children and immunocompromised individuals. Among non-immune compromised adults, hPIV infection typically causes mild disease manifested as upper respiratory tract symptoms and is infrequently associated with severe croup or pneumonia. Moreover, hPIV infection may be associated with viral exacerbations of chronic airway diseases, asthma or COPD or chronic rhinosinusitis. In this review, we summarized the basic epidemiology and immunology of hPIVs and addressed the more recent data implicating the role of parainfluenza viruses in the exacerbation of chronic airway disorders.
Assuntos
Infecções por Paramyxoviridae , Infecções Respiratórias/virologia , Antivirais/uso terapêutico , Humanos , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/imunologia , Infecções por Paramyxoviridae/patologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologiaRESUMO
PURPOSE: Periostin is considered a biomarker for eosinophilic airway inflammation and have been associated with NSAID-Exacerbated Respiratory Disease (NERD) and chronic rhinosinusitis (CRS). In this study, we aimed to evaluate periostin in exhaled breath condensate (EBC) and in serum of patients with various asthma phenotypes. METHODS: The study included 40 asthmatic patients (22 with NERD) and 17 healthy controls. All the procedures (questionnaire, spirometry, FeNO, nasal swabs, EBC collecting, and blood sampling) were performed on the same day. Periostin concentrations were measured using an ELISA kit. RESULTS: Periostin was detected in EBC from 37 of 40 asthmatics and in 16 from 17 of controls. The concentration of periostin in EBC did not differ between the study groups and was not associated with NERD or asthma severity. However, the EBC periostin was significantly higher in asthmatics with CRS as compared to those without (3.1 vs 2 ng/mL, P=0.046). Patients with positive bacterial culture from nasal swabs had higher EBC periostin concentrations than those without (3.2 vs 2.1 ng/mL; P=0.046). The mean serum periostin level was higher in asthmatics with a 1-year history of exacerbation than in those without (3.2 vs 2.3 ng/mL, P=0.045). Asthmatics with skin manifestation of NSAIDs hypersensitivity had higher serum periostin levels as compared to those without (3.5 vs 2.3 ng/mL; P=0.03). CONCLUSIONS: EBC periostin levels seem to reflect intensity of upper airway disease in asthmatics, while serum levels of periostin are associated with asthma activity (exacerbations or FeNO) or NERD subphenotypes.