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1.
Phys Rev Lett ; 132(14): 148201, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38640386

RESUMO

In a sheared steady state, glasses reach a nonequilibrium criticality called yielding criticality. We report that the qualitative nature of this nonequilibrium critical phenomenon depends on the details of the system and that responses and fluctuations are governed by different critical correlation lengths in specific situations. This scale separation of critical lengths arises when the screening of elastic propagation of mechanical signals is not negligible. We also discuss the determinant of the impact of screening effects from the viewpoint of the microscopic dissipation mechanism.

2.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612561

RESUMO

Two anti-fibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells (PBMCs) are immunocompetent cells that could orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in the bulk PBMCs of patients with IPF and the effects of anti-fibrotic drugs on these signatures. Differentially expressed genes (DEGs) between "patients with IPF and healthy controls" and "before and after anti-fibrotic treatment" were analyzed. Enrichment analysis suggested that fatty acid elongation interferes with TGF-ß/Smad signaling and the production of oxidative stress since treatment with NTD upregulates the fatty acid elongation enzymes ELOVL6. Treatment with PFD downregulates COL1A1, which produces wound-healing collagens because activated monocyte-derived macrophages participate in the production of collagen, type I, and alpha 1 during tissue damage. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinase activation, and the inhibition of PAI-1 activity attenuates lung fibrosis. DEG analysis suggested that both the PFD and NTD upregulate SERPINE1, which regulates PAI-1 activity. This study embraces a novel approach by using RNA sequencing to examine PBMCs in IPF, potentially revealing systemic biomarkers or pathways that could be targeted for therapy.


Assuntos
Fibrose Pulmonar Idiopática , Inibidor 1 de Ativador de Plasminogênio , Humanos , Leucócitos Mononucleares , Transcriptoma , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/genética , Ácidos Graxos
3.
Am J Physiol Lung Cell Mol Physiol ; 326(5): L562-L573, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469626

RESUMO

Acute respiratory distress syndrome (ARDS) is characterized by dysregulated inflammation and increased permeability of lung microvascular cells. CD26/dipeptidyl peptidase-4 (DPP4) is a type II membrane protein that is expressed in several cell types and mediates multiple pleiotropic effects. We previously reported that DPP4 inhibition by sitagliptin attenuates lipopolysaccharide (LPS)-induced lung injury in mice. The current study characterized the functional role of CD26/DPP4 expression in LPS-induced lung injury in mice, isolated alveolar macrophages, and cultured lung endothelial cells. In LPS-induced lung injury, inflammatory responses [bronchoalveolar lavage fluid (BALF) neutrophil numbers and several proinflammatory cytokine levels] were attenuated in Dpp4 knockout (Dpp4 KO) mice. However, multiple assays of alveolar capillary permeability were similar between the Dpp4 KO and wild-type mice. TNF-α and IL-6 production was suppressed in alveolar macrophages isolated from Dpp4 KO mice. In contrast, in cultured mouse lung microvascular endothelial cells (MLMVECs), reduction in CD26/DPP4 expression by siRNA resulted in greater ICAM-1 and IL-6 expression after LPS stimulation. Moreover, the LPS-induced vascular monolayer permeability in vitro was higher in MLMVECs treated with Dpp4 siRNA, suggesting that CD26/DPP4 plays a protective role in endothelial barrier function. In summary, this study demonstrated that genetic deficiency of Dpp4 attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential functional roles of CD26/DPP4 expression in resident cellular components of the lung. CD26/DPP4 may be a potential therapeutic target for ARDS and warrants further exploration to precisely identify the multiple functional effects of CD26/DPP4 in ARDS pathophysiology.NEW & NOTEWORTHY We aimed to clarify the functional roles of CD26/DPP4 in ARDS pathophysiology using Dpp4-deficient mice and siRNA reduction techniques in cultured lung cells. Our results suggest that CD26/DPP4 expression plays a proinflammatory role in alveolar macrophages while also playing a protective role in the endothelial barrier. Dpp4 genetic deficiency attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential roles of CD26/DPP4 expression in the resident cellular components of the lung.


Assuntos
Dipeptidil Peptidase 4 , Lipopolissacarídeos , Macrófagos Alveolares , Camundongos Knockout , Animais , Dipeptidil Peptidase 4/metabolismo , Dipeptidil Peptidase 4/genética , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Endogâmicos C57BL , Pulmão/patologia , Pulmão/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/induzido quimicamente , Interleucina-6/metabolismo , Interleucina-6/genética , Masculino , Permeabilidade Capilar , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Fator de Necrose Tumoral alfa/metabolismo , Líquido da Lavagem Broncoalveolar , Células Cultivadas
4.
Int J Mol Sci ; 25(2)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38255821

RESUMO

Pulmonary hypertension (PH) with interstitial lung diseases (ILDs) often causes intractable conditions. CD26/Dipeptidyl peptidase-4 (DPP4) is expressed in lung constituent cells and may be related to the pathogenesis of various respiratory diseases. We aimed to clarify the functional roles of CD26/DPP4 in PH-ILD, paying particular attention to vascular smooth muscle cells (SMCs). Dpp4 knockout (Dpp4KO) and wild type (WT) mice were administered bleomycin (BLM) intraperitoneally to establish a PH-ILD model. The BLM-induced increase in the right ventricular systolic pressure and the right ventricular hypertrophy observed in WT mice were attenuated in Dpp4KO mice. The BLM-induced vascular muscularization in small pulmonary vessels in Dpp4KO mice was milder than that in WT mice. The viability of TGFß-stimulated human pulmonary artery SMCs (hPASMCs) was lowered due to the DPP4 knockdown with small interfering RNA. According to the results of the transcriptome analysis, upregulated genes in hPASMCs with TGFß treatment were related to pulmonary vascular SMC proliferation via the Notch, PI3K-Akt, and NFκB signaling pathways. Additionally, DPP4 knockdown in hPASMCs inhibited the pathways upregulated by TGFß treatment. These results suggest that genetic deficiency of Dpp4 protects against BLM-induced PH-ILD by alleviating vascular remodeling, potentially through the exertion of an antiproliferative effect via inhibition of the TGFß-related pathways in PASMCs.


Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Osteocondrodisplasias , Humanos , Animais , Camundongos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Dipeptidil Peptidase 4/genética , Fosfatidilinositol 3-Quinases , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/genética , Bleomicina/toxicidade , Camundongos Knockout , Fator de Crescimento Transformador beta/genética
5.
Respir Investig ; 62(1): 98-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016402

RESUMO

Solid organ transplant (SOT) recipients with coronavirus disease-2019 (COVID-19) experience prolonged viral shedding, and they are forced to stay in the hospital because of the requirement for COVID-19 isolation. Here, we present two cases (lung and renal transplant recipients), wherein the isolation period was shortened by reducing the dosage of mycophenolate mofetil (MMF). Both patients recovered well from COVID-19 pneumonia. This case study suggests that a reduction in MMF dosage may lead to a shorter hospitalization period in SOT recipients with COVID-19.


Assuntos
COVID-19 , Transplante de Rim , Humanos , Ácido Micofenólico , Imunossupressores , Eliminação de Partículas Virais
6.
J Infect Chemother ; 30(6): 516-525, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38104794

RESUMO

INTRODUCTION: The accurate diagnosis of tuberculosis (TB) in children is essential for its effective management and control. Reliable diagnostic tools that are currently available for identifying TB infection include the in vivo tuberculosis skin test (TST) and ex vivo interferon-gamma release assays (IGRAs). This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of IGRAs in children. METHODS: Of the 768 screened studies, 47 met the eligibility criteria. Data from 9065 patients, including 1086 (12.0 %) with confirmed TB, were included in the analysis. The overall quality of the included studies, assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear. RESULTS: The calculated pooled sensitivity and specificity of IGRAs in children were 0.85 (95 % confidence interval [CI]: 0.79-0.89) and 0.94 (95 % CI: 0.88-0.97), respectively. Subpopulation analysis revealed that the sensitivities and specificities were as follows: QuantiFERON tests: 0.83 (95 % CI: 0.74-0.89) and 0.93 (95 % CI: 0.87-0.96), T-SPOT: 0.87 (95 % CI: 0.79-0.91) and 0.99 (95 % CI: 0.85-1.00), IGRAs in children under 15 years: 0.77 (95 % CI: 0.43-0.94) and 0.96 (95 % CI: 0.84-0.97), and IGRAs in children under 5 years: 0.85 (95 % CI: 0.52-0.97) and 0.94 (95 % CI: 0.90-0.99), respectively. CONCLUSIONS: This study demonstrated that the sensitivity and specificity of the IGRAs in children were moderate and high, respectively. Therefore, the IGRAs may be useful for detecting TB infection in children. CLINICAL TRIAL REGISTRATION: The review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000046737).


Assuntos
Tuberculose Latente , Tuberculose , Criança , Humanos , Pré-Escolar , Testes de Liberação de Interferon-gama/métodos , Interferon gama , Tuberculose/diagnóstico , Teste Tuberculínico , Sensibilidade e Especificidade
7.
Respir Investig ; 62(1): 176-178, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38154291

RESUMO

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease that often causes progressive pulmonary fibrosis (HPS-PPF) in some genetic types with high mortality rates. No effective treatment for HPS-PPF other than lung transplantation has been established. Herein, we report a case of HPS type 1 with progressive pulmonary fibrosis treated with long-term nintedanib administration followed by lung transplantation. The resected lungs revealed diffuse interstitial lung lesions, including fibroblastic foci, suggesting the potential beneficial effects of anti-fibrotic drugs in HPS-PPF. Together with previous reports, the present case suggests that nintedanib might be a safe and effective drug for HPS-PPF.


Assuntos
Albinismo , Transtornos Hemorrágicos , Síndrome de Hermanski-Pudlak , Indóis , Transplante de Pulmão , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/complicações , Síndrome de Hermanski-Pudlak/complicações , Síndrome de Hermanski-Pudlak/tratamento farmacológico , Síndrome de Hermanski-Pudlak/genética , Pulmão/patologia
8.
Ann Am Thorac Soc ; 21(3): 428-437, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38134434

RESUMO

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Pneumonia , Adulto , Humanos , Estados Unidos/epidemiologia , Readmissão do Paciente , Estudos de Coortes , Qualidade de Vida , Assistência ao Convalescente , COVID-19/epidemiologia , COVID-19/complicações , Alta do Paciente , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/terapia , Doenças Pulmonares Intersticiais/complicações , Pneumonia/complicações
9.
Sci Rep ; 13(1): 17289, 2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828047

RESUMO

Pleuroparenchymal fibroelastosis (PPFE) progresses slowly but sometimes relatively quickly, leading to decreased activities of daily living (ADL) and muscle weakness. Skeletal muscle atrophy and muscle weakness in chronic obstructive pulmonary disease (COPD) patients may be caused by cachexia and are associated with reduced ADLs and increased risk of death. However, the association between skeletal muscle mass and the prognosis of PPFE patients remains unknown. We retrospectively analysed the clinical significance of the cross-sectional area of the erector spinae muscle (ESMCSA), a skeletal muscle index, and predictors of mortality within 3 years in PPFE 51 patients, idiopathic pulmonary fibrosis (IPF) 52 patients and COPD 62 patients. PPFE patients had significantly lower ESMCSA than IPF or COPD patients, and lower ESMCSA (< 22.57 cm2) was associated with prognosis within 3 years (log-rank test; p = 0.006), whereas lower body mass index (BMI) showed no association. Multivariate analysis showed that ESMCSA was an independent predictor of mortality within 3 years in PPFE patients (hazard ratio, 0.854; 95% confidence interval: 0.737-0.990, p = 0.036). These results suggest the importance of monitoring ESMCSA in PPFE patients and that assessing ESMCSA in PPFE patients could be a more useful prognostic indicator than BMI.


Assuntos
Fibrose Pulmonar Idiopática , Doença Pulmonar Obstrutiva Crônica , Humanos , Prognóstico , Estudos Retrospectivos , Atividades Cotidianas , Músculos Paraespinais , Debilidade Muscular
10.
Clin Respir J ; 17(8): 733-739, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37343950

RESUMO

INTRODUCTION: Secondary spontaneous pneumothorax (SSP) occurs as one of the complications associated with interstitial pneumonia (IP). Chest drainage is performed when there is a large volume of air in the pleural space. Notably, SSP with IP (SSP-IP) is frequently not curable by chest drainage only. A digital drainage system (DDS) provides an objective evaluation of air leakage and maintains a pre-determined negative pressure, compared to an analog drainage system (ADS). Few studies have reported the effectiveness of DDS in the treatment of SSP-IP. This study aimed to assess the usefulness of DDS for SSP-IP. METHODS: This retrospective study included patients with SSP-IP who had undergone chest drainage. We reviewed the included patients' medical records, laboratory data, computed tomography findings, and pulmonary function data. RESULTS: DDS was used in 24 patients and ADS in 49 patients. The mean duration of chest drainage was 11.4 ± 1.9 days in the DDS group and 14.2 ± 1.3 days in the ADS group, which was not significantly different (p = 0.218). Surgery, pleurodesis, and/or factor XIII administration were performed in 40 patients. Additionally, five (20.8%) patients in the DDS group and nine (18.4%) in the ADS group had a recurrence of pneumothorax within 4 weeks (p = 1.000). One patient (14%) in the DDS group and six (12.2%) in the ADS group (p = 0.414) were cured of pneumothorax but later died. CONCLUSION: DDS did not demonstrate a significant difference in the shortening of chest drainage duration. Further study is needed to validate the results of this study.


Assuntos
Doenças Pulmonares Intersticiais , Pneumotórax , Humanos , Tubos Torácicos , Drenagem/métodos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/terapia , Pleurodese/métodos , Pneumotórax/terapia , Pneumotórax/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Intern Med ; 62(16): 2321-2328, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37225494

RESUMO

Objective We evaluated the clinical differences in coronavirus disease 2019 (COVID-19) patients between the sixth wave with the Omicron BA.1/BA.2 dominant variant (from January to April 2022) and seventh wave with the Omicron BA.5 dominant variant (from July to August 2022). Methods This retrospective, single-center, observational study included COVID-19 patients admitted to our institution in the sixth wave (sixth-wave group) and the seventh wave (seventh-wave group). Inter-group comparisons of clinical presentations, the prognosis, and proportion of nosocomial infections were performed. Results A total of 190 patients were included (93 and 97 patients in the sixth- and seventh-wave groups, respectively). While there were no significant differences in severity, significantly more patients developed pneumonia caused by COVID-19 in the sixth-wave group than in the seventh-wave group. Although there was no marked difference in in-hospital deaths, more patients died from COVID-19 in the sixth-wave group than in the seventh-wave group. There were significantly more COVID-19 inpatients with nosocomial infections in the seventh-wave group than in the sixth-wave group. Pneumonia from COVID-19 was significantly more severe in the sixth-wave group than in the seventh-wave group. Conclusion COVID-19 patients in the seventh wave are at a lower risk of pneumonia than those in the sixth wave. However, even in the seventh wave, patients with underlying diseases have a risk of death because of the exacerbation of underlying diseases triggered by COVID-19.


Assuntos
COVID-19 , Infecção Hospitalar , Humanos , COVID-19/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , SARS-CoV-2
12.
ERJ Open Res ; 9(2)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37009016

RESUMO

Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii. Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated. Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx. Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.

13.
J Sci Food Agric ; 103(11): 5609-5615, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37066700

RESUMO

BACKGROUND: It is reported that broilers with 'wooden breast' have poor processing properties, such as low binding and water-holding capacities. However, the reason for the poor functional characteristics has not been clarified. In this study, myosin was extracted from a wooden breast. Its physicochemical properties were investigated to clarify the relationship between the structure and physicochemical properties of the heating gel of myosin obtained from the wooden breast. RESULTS: The turbidity of myosin solution extracted from wooden breast increased with increase in the heat treatment to a higher value than that from the normal breast meat myosin. The solubility of myosin collected from a wooden breast after heating decreased like normal breast muscle myosin. The surface hydrophobicity of myosin removed from wooden breast increased continually above 60 °C, unlike the change in surface hydrophobicity of normal breast myosin. The free thiol group of myosin extracted from the wooden breast was higher than normal breast myosin before and after heating. The apparent elasticity of heat-induced gels and chicken meat sausages was significantly lower in sausages and gel with wooden breast than normal ones (P < 0.05). The microstructure of the heated gel of normal myosin showed a fine network structure. In contrast, the heat-induced gel of wooden breast-extracted myosin showed a structure with loosely connected aggregates and many gaps. CONCLUSION: The coarseness of the internal gel structure of myosin extracted from wooden breast was shown to affect the apparent elasticity of the gel and sausages made from the chicken meat. © 2023 Society of Chemical Industry.


Assuntos
Galinhas , Temperatura Alta , Animais , Galinhas/fisiologia , Miosinas/química , Músculos Peitorais , Géis/química
14.
Physiol Rep ; 11(6): e15645, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36949656

RESUMO

The pathogenesis of pulmonary fibrosis involves complex interplay between cell types and signaling pathways. Recurrent alveolar epithelial injury can occur during pulmonary inflammation, causing dysregulation of epithelial repair. Dysregulated repair interacts with mesenchymal, inflammatory, and endothelial cells to trigger fibroblast-to-myofibroblast activation. CD26/dipeptidyl peptidase-4 (DPP4) is a type II membrane protein mediating pleiotropic effect. However, the mechanistic role of CD26/DPP4 in pulmonary fibrosis remains unclear. In this study, we aimed to characterize Dpp4 deficiency in a mouse bleomycin (BLM)-induced pulmonary fibrosis model and in cell culture systems of human lung fibroblasts (HLFs). Dpp4 knockout (Dpp4 KO) mouse lungs exhibited lower Ashcroft scale indices, collagen content, and numbers of fibroblasts and myofibroblasts compared with those in C57BL/6 wild-type (WT) mice. Upregulation of Tgfb1 and Tgfb2 mRNA levels in the lungs after BLM treatment was lower in Dpp4 KO mice compared with those in WT mice. Although TGF-ß-driven endothelial-to-mesenchymal transition (EndMT) has been implicated as one of the mechanisms of pulmonary fibrosis, a number of partial EndMT cells in lungs did not differ between Dpp4 KO mice and WT mice. The proliferation capacity and mRNA levels of COL1A1, a collagen deposition-related gene, in cultured HLFs were suppressed in DPP4 small interfering RNA-treated cells. This study indicates that the genetic deficiency of DPP4 has protective effects against BLM-induced pulmonary fibrosis, partly through the reduction in TGF-ß expression and inhibition of fibroblast activation in the lung. Our study suggests that CD26/DPP4 inhibition is a potential therapeutic strategy for pulmonary fibrosis.


Assuntos
Fibrose Pulmonar , Animais , Humanos , Camundongos , Bleomicina/toxicidade , Colágeno/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , RNA Mensageiro/genética , Fator de Crescimento Transformador beta/metabolismo
15.
Respir Care ; 68(3): 356-365, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36828581

RESUMO

BACKGROUND: The 6-min walk test (6MWT) is a common assessment of exercise-induced hypoxemia and exercise capacity used in patients with chronic fibrosing interstitial pneumonia (CFIP). However, whether the dynamic changes in SpO2 and heart rate during the 6MWT are associated with mortality in patients with CFIP has been undefined. METHODS: This retrospective study enrolled 63 subjects with mild to severe CFIP who underwent the 6MWT. Subjects with CFIP were divided into 2 groups according to disease severity: mild, diffusing capacity of the lungs for carbon monoxide percentage predicted (%DLCO) > 55% and %FVC > 75%; and severe, %DLCO ≤ 55% and/or %FVC ≤ 75%. This study aimed to evaluate dynamic changes in the 6MWT including 6-min walk distance, change in SpO2 (ΔSpO2 ), SpO2 reduction time, SpO2 recovery time, change in heart rate (Δ heart rate), heart rate acceleration time, slope of heart rate acceleration, heart rate recovery at 1 min of rest after the 6MWT (HR-recovery), and dyspnea on exertion that are reflected by static pulmonary function and are related to exacerbation of CFIP and mortality. RESULTS: Compared with subjects with mild CFIP, subjects with severe CFIP had significantly larger ΔSpO2 and longer SpO 2 reduction time and recovery time. The slope of heart rate, heart rate immediately after the 6MWT, and HR-recovery were lower in subjects with severe CFIP than in those with mild CFIP. In multiple regression analysis, percent vital capacity was significantly associated with SpO2 reduction time, and %DLCO was significantly associated with ΔSpO2 and SpO2 recovery time. Subjects with ΔSpO2 of > 10% and SpO2 recovery time of > 79 s had a significantly higher risk for exacerbation and mortality. CONCLUSIONS: Dynamic changes in SpO2 and heart rate during the 6MWT were associated with risk for exacerbation and mortality in subjects with CFIP. Impaired dynamic response of SpO2 could reflect likelihood of exacerbation and increased mortality in CFIP.


Assuntos
Doenças Pulmonares Intersticiais , Saturação de Oxigênio , Humanos , Teste de Caminhada , Estudos Retrospectivos , Teste de Esforço , Oxigênio
16.
Int J Mol Sci ; 25(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38203236

RESUMO

Non-emphysematous chronic obstructive pulmonary disease (COPD), which is defined based on chest computed tomography findings, presented different transcriptome features of peripheral blood mononuclear cells (PBMCs) compared with emphysematous COPD. Enrichment analysis of transcriptomic data in COPD demonstrated that the "Hematopoietic cell lineage" pathway in Kyoto Encyclopedia of Genes and Genomes pathway analysis was highly upregulated, suggesting that cellular dynamic dysregulation in COPD lungs is affected by pathologically modified PBMCs. The differentially expressed genes (DEGs) upregulated in PBMCs reflected the disease state of non-emphysematous COPD. Upregulated DEGs such as XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 activate T lymphocytes and eosinophils. Upregulating keratan sulfate biosynthesis and metabolic processes is associated with protection against the destruction of the distal airways. ITGA3 upregulation augments interactions with extracellular matrix proteins, and COL6A1 augments the profibrotic mast cell phenotype during alveolar collagen VI deposition. Upregulating HSPG2, PDGFRB, and PAK4 contributes to the thickening of the airway wall, and upregulating SERPINF1 expression explains the better-preserved vascular bed. Therefore, gene expression and pathway analysis in PBMCs in patients with non-emphysematous COPD represented type 2 immune responses and airway remodeling features. Therefore, these patients have asthmatic potential despite no clinical signs of asthma, in contrast to those with emphysematous COPD.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Transcriptoma , Leucócitos Mononucleares , Doença Pulmonar Obstrutiva Crônica/genética , Genes Reguladores , Quinases Ativadas por p21
17.
J Poult Sci ; 59(4): 378-383, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36348647

RESUMO

This study investigated whether freezing or warming water-in-oil (W/O) vaccines affected the immune responses of chickens. One of the conditions affecting the efficacy of commercially available animal vaccines is the storage temperature range. Previous studies have shown that the properties of some inactivated vaccines change owing to freezing, leading to reduced immune responsiveness after inoculation. In this study, we first determined the freezing temperatures of a commercial W/O vaccine using freezers maintained at -10, -13, -15, and -20°C. The results showed that the W/O vaccine froze from -10 to -12°C. Next, we evaluated the effect on antibody level transitions (sample-to-positive ratio) in 46-day-old broiler chickens vaccinated with the W/O vaccine that was maintained at -20°C, 5°C, and -10°C, in that order. In addition, the effect on antibody value transitions was evaluated in 45-day-old broiler chickens vaccinated with the W/O vaccines that were frozen and thawed between -20°C and 5°C repeatedly or warmed to 45°C. In these experiments, no remarkable effect of the freeze-thawing or warming treatments on antibody value transitions was observed. These results suggested that the efficacy of the W/O vaccine was not significantly affected when placed in a frozen environment or left in a room temperature environment of 42°C or lower for approximately 5 d. These data indicate the possibility of expanding the temperature range for handling W/O vaccines.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35973649

RESUMO

The growth rate of broiler chickens has increased by 400% over the past 50 years, and breast yields continue to increase. This has led to an increase in thoracic muscle abnormalities in broilers, with wooden breast becoming a major issue worldwide. The etiology and the mechanism underlying the etiology of wooden breasts have not yet been elucidated; however, it occurs due to oxidative stress. Reactive oxygen species, which cause oxidative stress, are mainly produced in mitochondria. Thus, in this study, we investigated the relationship between the severity of wooden breast in broilers and the characteristics of mitochondria as the source of reactive oxygen species. Sampling of the pectoralis major muscle at the ventral cranial position was conducted in 50-day-old broilers. The severity of wooden breast was classified into three groups based on the muscle fiber roundness and wing-wing contact test, with highest severity in severe wooden breast and lowest severity in normal breast. Nicotinamide adenine dinucleotide tetrazolium reductase staining revealed an increase in darkly stained muscle fibers, indicating high severity of wooden breast. The mitochondria were swollen in severe wooden breast cases, with highest swelling in severe wooden breast and lowest swelling in normal breast. The expression levels of the mitochondrial antioxidant enzyme genes superoxide dismutase 1 and superoxide dismutase 2 were significantly lower in wooden breast-severe tissue than in normal tissue. These results suggest that when the levels of reactive oxygen species in muscle fibers, which should be constant, are increased, mitochondrial homeostasis is not maintained and the damage levels increase in various membranes of the cell, leading to the disruption of normal physiological functions.


Assuntos
Doenças Musculares , Doenças das Aves Domésticas , Animais , Galinhas/metabolismo , Mitocôndrias/metabolismo , Doenças Musculares/genética , Doenças Musculares/metabolismo , Doenças Musculares/veterinária , Músculos Peitorais/metabolismo , Doenças das Aves Domésticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
19.
BMJ Open ; 12(8): e057216, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953247

RESUMO

BACKGROUND/OBJECTIVES: Urinary antigen tests have been used for the rapid identification of Streptococcus pneumoniae infection in patients with pneumonia, thereby leading to earlier targeted therapy than when using conventional diagnostic culture methods. This study aimed to update the knowledge on the diagnostic accuracy of urinary antigen tests for S. pneumoniae among patients with acute respiratory failure suspected of pneumonia based on a systematic review and meta-analysis. METHODS: A systematic search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials for studies published up to 3 June 2020. Prospective and retrospective cohort studies (in English) that reported on the diagnostic performance of urinary antigen tests versus culture or smear diagnostic methods in adult patients with clinically diagnosed pneumonia were selected and analysed. The QUADAS-2 tool was used to assess the risk of bias, and a bivariate random effects model was applied to perform a meta-analysis of the selected studies. RESULTS: A total of 2179 studies were screened, of which 30 met the eligibility criteria for quality assessment and meta-analysis. Overall, data from 12 366 patients, including 1548 patients (12.5%) with the target condition and suspected pneumococcal pneumonia, were included in the analysis. The overall quality of the included studies was determined to be serious. The calculated pooled sensitivity and specificity were of 0.66 (95% CI 0.62 to 0.69) and 0.90 (95% CI 0.85 to 0.93), respectively. CONCLUSIONS: The urinary antigen test is useful for achieving a definitive diagnosis of S. pneumoniae infection in patients with pneumonia.


Assuntos
Pneumonia Pneumocócica , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Adulto , Humanos , Pneumonia Pneumocócica/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Streptococcus pneumoniae
20.
Am J Case Rep ; 23: e936832, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35802524

RESUMO

BACKGROUND Although sotrovimab reduces the risk of hospitalization or death due to COVID-19, there have been few reports of its use in clinical practice. Particularly, information on the effectiveness of sotrovimab against the omicron variant of the virus is limited. We present 10 cases of COVID-19 treated with sotrovimab at our unit between December 2021 and February 2022. CASE REPORT The age of the patients ranged from 32 to 81 years (median: 40 years). The comorbidities included lung cancer, cardiovascular disease, chronic kidney disease requiring hemodialysis, and AIDS. Two of the patients were also organ recipients. Oxygen saturation (SpO2) was above 97% in all patients. None of the patients presented with pneumonia on admission. However, blood test results showed that all patients had risk factors for severe COVID-19 outcomes. The interval from symptom onset to sotrovimab administration and resolution ranged from 2 to 5 days (median: 2 days) and 2 to 15 days (median: 5 days), respectively. Only 1 patient developed pneumonia and was treated with remdesivir after sotrovimab administration. However, this patient did not require oxygen therapy. Although no moderate to severe adverse events were observed, a mild adverse event was observed in 1 patient. CONCLUSIONS Sotrovimab could be safe and effective in preventing progression of COVID-19 in patients with a variety of underlying diseases and who are at high risk of severe disease outcomes.


Assuntos
COVID-19 , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes , Humanos , Pessoa de Meia-Idade , SARS-CoV-2
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