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1.
Braz. j. biol ; 83: e248717, 2023. graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1339344

RESUMO

Abstract The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5-16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.


Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5-16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.


Assuntos
Humanos , Pré-Escolar , Vírus Sincicial Respiratório Humano , Infecções por Vírus Respiratório Sincicial , Armadilhas Extracelulares , Células Epiteliais , Pulmão
2.
Clin Exp Allergy ; 52(1): 115-126, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34431147

RESUMO

BACKGROUND: Genetic variants of dipeptidyl peptidase 10 (DPP10) have been suggested to contribute to the development of NSAID-exacerbated respiratory disease (NERD). However, the mechanisms of how DPP10 contributes to NERD phenotypes remain unclear. OBJECTIVE: To demonstrate the exact role of DPP10 in the pathogenesis of NERD. METHODS: Patients with NERD (n = 110), those with aspirin-tolerant asthma (ATA, n = 130) and healthy control subjects (HCs, n = 80) were enrolled. Clinical characteristics were analysed according to the serum DPP10 levels in both NERD and ATA groups. The function of DPP10 in airway inflammation and remodelling was investigated with in vitro, ex vivo and in vivo experiments. RESULTS: NERD patients had higher levels of serum DPP10 and TGF-ß1 with lower FEV1 than ATA patients or HCs (p < .05 for each). NERD patients with higher DPP10 levels had higher TGF-ß1, but lower FEV1 (p < .05 for all), whilst no differences were noted in ATA patients. Moreover, the seum DPP10 levels had a positive correlation with TGF-ß1 (r = 0.384, p < .001), but a negative correlation with FEV1 (r = -0.230, p = .016) in NERD patients. In in vitro studies, expression of DPP10 in airway epithelial cells was enhanced by TGF-ß1 treatments. Furthermore, DPP10 was found to be produced from immune cells and this molecule induced the ERK phosphorylation in airway epithelial cells, which was suppressed by anti-DPP10 treatment. In asthmatic mouse models, increased levels of DPP10 in the serum and TGF-ß1 in the bronchoalveolar lavage fluid were noted, which were suppressed by anti-DPP10 treatment. Moreover, anti-DPP10 treatment inhibited the ERK phosphorylation and extracellular matrix deposition in the lungs. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that increased production of DPP10 may contribute to TGF-ß1-mediated airway dysfunction in NERD patients, where blockade of DPP10 may have potential benefits.


Assuntos
Asma , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Doenças Respiratórias , Animais , Anti-Inflamatórios não Esteroides , Asma/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Humanos , Pulmão/metabolismo , Camundongos , Doenças Respiratórias/patologia , Fator de Crescimento Transformador beta1
3.
BMC Pulm Med ; 22(1): 117, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361163

RESUMO

BACKGROUND: To investigate the value of endobronchial ultrasound (EBUS) and virtual bronchoscopic navigation (VBN) combined with rapid on-site evaluation (ROSE) in diagnosing peripheral pulmonary lesions (PPLs). METHODS: Between January 1st 2019 to September 1st 2021, EBUS and VBN examination were performed in expected consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, based on the calculation of expected diagnostic yield of R-EBUS biopsy and drop out, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). The diagnostic yield of brushing and biopsy, the complications, the procedure time, the diagnosis time and expense during diagnosis were analyzed. RESULTS: In the ROSE group, the positive rate of EBUS brushing and biopsy were 68%, 84%, respectively. The average procedure time and diagnosis time were 18.6 ± 6.8 min, 3.84 ± 4.28 days, respectively, and the average expense was 643.44 ± 706.56 US.$ (4093.15 ± 4494.67 yuan ¥). In the controls, the positive rate of brushing and biopsy were 44%, 74%, respectively. The average procedure time and diagnosis time were 15.4 ± 5.7 min, 6.46 ± 3.66 days, respectively. And the average expense during diagnosis was 1009.27 ± 713.89 US.$ (6420.28 ± 4541.33 yuan ¥). There was significant difference in the positive rate of EBUS brushing and biopsy, diagnosis time and expense during diagnosis between both groups. And no significant difference was observed in the complications and the procedure time. Additionally, the impact of ROSE on diagnostic yield in right upper lobe and the size of lesion ≤ 2 cm in diameter was significant. CONCLUSION: In combination with ROSE, EBUS could significantly improve the positive rate of diagnosing PPLs, shorten diagnosis time and reduce expense during diagnosis. ROSE will be of great importance in the diagnosis of PPLs and medical resource.


Assuntos
Neoplasias Pulmonares , Broncoscopia/métodos , Endossonografia/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia
4.
Int Arch Occup Environ Health ; 95(2): 365-375, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34609586

RESUMO

OBJECTIVE: Copper smelter workers are exposed to harmful chemical agents in dust and fumes which contain harmful metals such as copper and arsenic. These substances are known to be respiratory irritants. METHODS: This study aimed at investigating the effect of occupational exposure to copper and arsenic on the respiratory system. A group of 75 male exposed workers, and 75 male administrative employees (control group) were recruited from a secondary copper smelting factory. Full history, complete clinical examination, ventilatory function parameters (FVC, FEV1, FVC/FEV1 and FEF), and chest X-ray were done for both groups. Serum levels of ICAM-1 and IL8 (as markers of epithelial injury) were measured by ELISA. Serum copper and arsenic were measured by atomic absorption spectrophotometer. RESULTS: The exposed group was associated with increased respiratory symptoms, higher serum copper, arsenic, and ICAM-1and Il-8 as compared to the control group. There was a significant decrease in ventilatory parameters among the exposed group: 58.7% of the exposed group had restrictive lung impairment, 40% had obstructive impairment. In the exposed group a positive correlation between serum copper, arsenic and serum ICAM and IL8 was found. While a negative correlation was observed between both serum ICAM, IL8 and ventilatory parameters among the exposed group. Moreover, 36% of the exposed group had radiological infiltrates on chest X.ray. CONCLUSION: Occupational exposure to copper and arsenic was associated with ventilatory and radiological impairment, with a corresponding increase in the serum level of ICAM-1 and IL8, which can be used as biomarkers for pulmonary impairment among copper smelter workers.


Assuntos
Arsênio , Exposição Ocupacional , Cobre , Humanos , Interleucina-8 , Pulmão , Masculino , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
5.
Clin. transl. oncol. (Print) ; 24(7): 1365-1371, julio 2022.
Artigo em Inglês | IBECS | ID: ibc-203835

RESUMO

PurposeTo investigate whether γδ1 T cells derived from lung cancer tissues have immunosuppressive function and to verify the mechanism of immunosuppressive effect.MethodsFresh lung cancer tissue samples were collected, some of them were prepared tissue sections, the others were isolated and amplified into TILs cells, γδ1 T cells were isolated from TILs cells by immunomagnetic beads kits, and then cloned and amplified. The immunomodulatory effects of γδ1 T cells on naive and effector CD4+ T cells were detected by immunohistochemistry, flow cytometry, CCK8, ELISA and transwell culture.ResultsA high proportion of γδ1 T cells was found in lung cancer tissues. The cultural supernatants of γδ1 T cells could inhibit the proliferation of naive CD4+ T cells and decrease the secretion level of IL-2 by effector CD4+ T cells. Further studies showed that the expression levels of IL-8, MIP-1α, MIP-1β and RANTES were higher than that of IFN-γ, GM-CSF and TNF-α, TNF-β, however, their neutralizing antibodies could not block the immunosuppressive activity of the supernatant.Conclusionγδ1 T cells play an negative immunoregulation function in lung cancer microenvironments, and have obvious immunosuppressive effects on proliferation and cytokine release of naive CD4+ T cells and effector CD4+ T cells. Preliminary evidence from this study suggests that the mechanism of immunosuppressive effects is mediated by the soluble factors in γδ1 T cell culture supernatants, but its exact molecular mechanism needs to be further explored.


Assuntos
Humanos , Linfócitos T CD4-Positivos , Citocinas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão , Microambiente Tumoral , Linfócitos T/metabolismo
6.
Cell Death Dis ; 13(6): 525, 2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35661695

RESUMO

Long non-coding RNA (lncRNA) was reported to be a critical regulator of cellular homeostasis, but poorly understood in idiopathic pulmonary fibrosis (IPF). Here, we systematically identified a crucial lncRNA, p53-induced long non-coding RNA TP53 target 1 (TP53TG1), which was the dysregulated hub gene in IPF regulatory network and one of the top degree genes and down-regulated in IPF-drived fibroblasts. Functional experiments revealed that overexpression of TP53TG1 attenuated the increased expression of fibronectin 1 (Fn1), Collagen 1α1, Collagen 3α1, ACTA2 mRNA, Fn1, and Collagen I protein level, excessive fibroblasts proliferation, migration and differentiation induced by TGF-ß1 in MRC-5 as well as PMLFs. In vivo assays identified that forced expression of TP53TG1 by adeno-associated virus 5 (AAV5) not only prevented BLM-induced experimental fibrosis but also reversed established lung fibrosis in the murine model. Mechanistically, TP53TG1 was found to bind to amount of tight junction proteins. Importantly, we found that TP53TG1 binds to the Myosin Heavy Chain 9 (MYH9) to inhibit its protein expression and thus the MYH9-mediated activation of fibroblasts. Collectively, we identified the TP53TG1 as a master suppressor of fibroblast activation and IPF, which could be a potential hub for targeting treatment of the disease.


Assuntos
Fibrose Pulmonar Idiopática , RNA Longo não Codificante , Animais , Colágeno/metabolismo , Fibroblastos/metabolismo , Fibrose , Fibrose Pulmonar Idiopática/patologia , Pulmão/metabolismo , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
7.
Pharmazie ; 77(5): 132-136, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35655385

RESUMO

Various chemical reagents containing inhibitors of mitochondrial activity, antioxidants, nuclear factor-kappa B (NF-kB) inhibitor, mammalian target of rapamycin (mTOR) inhibitor and other clinical therapeutics were screened in order to identify those that selectively decrease the viability of senescent human lung fibroblasts. Cell viability was measured using the CCK-8 assay. The results showed that pravastatin, a drug for hyperlipidemia, decreased the viability of senescent cells but not non-senescent cells. The effect of pravastatin on senescent cells is thought to be due to the inhibition of cell proliferation, rather than cell death. The effect of pravastatin was further investigated using the glucose metabolism assay, which showed that glucose consumption was inhibited both in non-senescent and senescent cells and intracellular nicotinamide adenine dinucleotide (NAD) was decreased in senescent cells. Changes to the mRNA expression levels of senescence-associated genes in response to pravastatin treatment were quantified by real-time-qPCR. There were no significant changes in the relative mRNA expression levels of IL-1ß, p16, p21, and p53 in pravastatin-treated non-senescent cells, whereas the expression of IL-1ß and p16 were increased by pravastatin only in senescent cells. The results of this study suggest that pravastatin does not induce senolysis, but rather selectively inhibits the proliferation of senescent cells and that cellular senescence is enhanced by decreasing intracellular NAD and promoting IL-1ß production.


Assuntos
NAD , Pravastatina , Fibroblastos/metabolismo , Humanos , Pulmão , NAD/metabolismo , NAD/farmacologia , Pravastatina/farmacologia , RNA Mensageiro/metabolismo
8.
Biomed Pharmacother ; 150: 113035, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35658207

RESUMO

Naringin is one of the natural flavonoids extracted from many Chinese medicines. It ameliorates endothelial dysfunctions in atherosclerosis, diabetes, and cardiovascular diseases through free radical scavenging and antioxidant activities. The aim of the present study was to investigate the protective effects of naringin against pulmonary endothelial permeability in addition to airway inflammation in lipopolysaccharide/cigarette smoke (LPS/CS)-induced chronic obstructive pulmonary disease (COPD) mice.The COPD mice were exposed to LPS twice through intranasal inhalation and then to cigarette smoke daily for 6 weeks. The mice were orally administrated with naringin at doses of 40 or 80 mg/kg one hour before cigarette smoke exposure since the first day of the experiment. Naringin significantly alleviated pulmonary histopathological injury, and suppressed inflammatory cell infiltration and cytokine release in bronchoalveolar lavage fluid. Naringin decreased fluorescence intensity of Evans Blue in the lung tissues, and elevated the expression levels of tight junctional proteins. Meanwhile, naringin decreased neutrophil/lymphocyte/platelet counts and MDA content in blood, and upregulated Aquaporin1 (AQP1) in the lung tissues. However, the effect of naringin on airway inflammation and pulmonary endothelial permeability was inhibited in LPS/CS-treatment AQP1 deficiency mice. These results indicated that naringin attenuated LPS/CS-induced airway inflammatory and pulmonary hyperpermeability via upregulating AQP1 expression.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Flavanonas , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tabaco
9.
Proc Natl Acad Sci U S A ; 119(24): e2201707119, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35671428

RESUMO

A number of inflammatory lung diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and pneumonia, are modulated by WNT/ß-catenin signaling. However, the underlying molecular mechanisms remain unclear. Here, starting with a forward genetic screen in mouse, we identify the WNT coreceptor Related to receptor tyrosine kinase (RYK) acting in mesenchymal tissues as a cell survival and antiinflammatory modulator. Ryk mutant mice exhibit lung hypoplasia and inflammation as well as alveolar simplification due to defective secondary septation, and deletion of Ryk specifically in mesenchymal cells also leads to these phenotypes. By analyzing the transcriptome of wild-type and mutant lungs, we observed the up-regulation of proapoptotic and inflammatory genes whose expression can be repressed by WNT/RYK signaling in vitro. Moreover, mesenchymal Ryk deletion at postnatal and adult stages can also lead to lung inflammation, thus indicating a continued role for WNT/RYK signaling in homeostasis. Our results indicate that RYK signaling through ß-catenin and Nuclear Factor kappa B (NF-κB) is part of a safeguard mechanism against mesenchymal cell death, excessive inflammatory cytokine production, and inflammatory cell recruitment and accumulation. Notably, RYK expression is down-regulated in the stromal cells of pneumonitis patient lungs. Altogether, our data reveal that RYK signaling plays critical roles as an antiinflammatory modulator during lung development and homeostasis and provide an animal model to further investigate the etiology of, and therapeutic approaches to, inflammatory lung diseases.


Assuntos
Pneumonia , Receptores Proteína Tirosina Quinases , Via de Sinalização Wnt , beta Catenina , Animais , Humanos , Pulmão/enzimologia , Pulmão/crescimento & desenvolvimento , Mesoderma/metabolismo , Camundongos , NF-kappa B/metabolismo , Pneumonia/enzimologia , Pneumonia/genética , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Células Estromais/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
10.
BMJ Open ; 12(6): e055077, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705338

RESUMO

OBJECTIVES: To describe 6-min walk test (6MWT) outcomes, and to investigate their correlations with cardiopulmonary and lung function among patients with interstitial lung disease (ILD) which was not limited to idiopathic pulmonary fibrosis. METHODS: We collected patients' demographic data and obtained minute-by-minute 6MWT outcomes. Modified Borg scale was employed to assess patients' dyspnoea, whereas New York Heart Association (NYHA) classification and pulmonary function test were used to evaluate patients' cardiopulmonary functions. RESULTS: Heart rate (HR) exhibited a continuous upward trend, while SpO2 exhibited an overall downward with a slight increase at the fifth minute. The SpO2 nadir for 70 patients (9.3%) was lower than 80%. Further, the SpO2 nadir for 78.27% of the participants appeared at the end of the fourth minute. The 6-min walk distance (6MWD) had the strongest correlation with NYHA classification (r=0.82, p<0.01). The ratio of 6MWD to predicted 6MWD was most correlated to forced expiratory volume in the first second (r=0.30, p<0.01) and forced vital capacity (r=0.30, p<0.01). SpO2 at 3 min had the strongest correlation to patients' diffusing capacity of the lungs for carbon monoxide (r=0.41, p<0.01). We found significant differences in 6MWD (F=2.44, p=0.033), SpO2 change (F=2.58, p=0.025), HR at 0 min (F=2.87, p=0.014), HR at end of 6 min (F=2.58, p=0.025) and HR zenith (F=2.64, p=0.022) between the subtypes of ILD. CONCLUSION: This observation provided an important evidence regarding oxygen titration. It is better to maintain SpO2 above 88% for 4 min instead of 3 min. SpO2 at the third minute was the most valuable predictor of patients' lung function. 6MWD and SpO2 changes were more discriminative in subtypes.


Assuntos
Doenças Pulmonares Intersticiais , Dispositivos Eletrônicos Vestíveis , Teste de Esforço , Tolerância ao Exercício/fisiologia , Humanos , Pulmão , Doenças Pulmonares Intersticiais/diagnóstico , Teste de Caminhada , Caminhada/fisiologia
11.
Respir Res ; 23(1): 156, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705945

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by inhalation of cigarette smoke (CS) and other harmful gases and particles. METHODS: This study aimed to explore potential urinary biomarkers for CS-induced COPD based on LC-MS/MS analysis. RESULTS: A total of 340 urinary proteins were identified, of which 79 were significantly changed (30, 31, and 37 at week 2, 4 and 8, respectively). GO annotation of the differential urinary proteins revealed that acute-phase response, response to organic cyclic compounds, complement activation classical pathway, and response to lead ion were significantly enriched at week 2 and 4. Another four processes were only enriched at week 8, namely response to oxidative stress, positive regulation of cell proliferation, thyroid hormone generation, and positive regulation of apoptotic process. The PPI network indicated that these differential proteins were biologically connected in CS-exposed rats. Of the 79 differential proteins in CS-exposed rats, 56 had human orthologs. Seven proteins that had changed at week 2 and 4 when there were no changes of pulmonary function and pathological morphology were verified as potential biomarkers for early screening of CS-induced COPD by proteomic analysis. Another six proteins that changed at week 8 when obvious airflow obstruction was detected were verified as potential biomarkers for prognostic assessment of CS-induced COPD. CONCLUSIONS: These results reveal that the urinary proteome could sensitively reflect pathological changes in CS-exposed rats, and provide valuable clues for exploring COPD biomarkers.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Biomarcadores/metabolismo , Cromatografia Líquida , Pulmão/metabolismo , Proteoma/metabolismo , Proteômica , Doença Pulmonar Obstrutiva Crônica/metabolismo , Ratos , Espectrometria de Massas em Tandem , Tabaco
12.
BMC Res Notes ; 15(1): 206, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705999

RESUMO

OBJECTIVE: This study investigates the development of the thoracic cross-section at the nipple line level during the early stages of life. Unlike the descriptive awareness regarding chest development course, there exist no quantitative references concerning shape, circumference and possible dependencies to age, gender or body weight. The proposed mathematical relations are expected to help create guidelines for more realistic modelling and potential detection of abnormalities. One potential application is lung electrical impedance tomography (EIT) monitoring where accurate chest models are crucial in both extracting reliable parameters for regional ventilation function and design of EIT belts. Despite their importance, such reference data is not readily available for the younger age range due to insufficient data amid the regulations of neonatal imaging. RESULTS: Chest circumference shows the highest correlation to body weight following the relation [Formula: see text] where x is the body weight in grams and f(x) is the chest circumference in cm at the nipple line level. No statistically significant difference in chest circumference between genders was detected. However, the shape indicated signs of both age and gender dependencies with on average boys developing a more rectangular shape than girls from the age of 1 years and 9 months.


Assuntos
Pulmão , Tórax , Peso Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Tórax/diagnóstico por imagem , Tomografia/métodos
13.
J Biomech ; 140: 111131, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35653879

RESUMO

Treating diseased lung regions using inhalation therapy is often limited due to airway constrictions and obstructions that significantly reduce aerosol deposition efficiency. Intratracheal administration of liquid foams is a potential strategy to improve pulmonary drug delivery to these affected airway regions. Here, we use effective viscosity measurements and in vitro small-airway models to examine how shear thinning effects in the foam can be leveraged to achieve a more uniform distribution within heterogeneously constricted or partially obstructed airways. We find that a foamed solution based on the formulation of Tacholiquin® exhibited a 5.75-fold decrease in effective viscosity across a shear rate range spanning 970 to 14'500 s-1. As a result, the foam volume penetrating through the constricted airway models was up to 154% higher compared with air, depending on the cross-sectional area of the constrictions. This proof-of-concept study represents a first step towards understanding the transport mechanics of liquid foams towards future pulmonary delivery applications.


Assuntos
Pulmão , Tórax , Aerossóis , Sistemas de Liberação de Medicamentos , Viscosidade
14.
mBio ; 13(3): e0133222, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35695454

RESUMO

In the initial stage of respiratory infection, Mycobacterium tuberculosis traverses from alveolar macrophages to phenotypically diverse monocyte-derived phagocytes and neutrophils in the lung parenchyma. Here, we compare the in vivo kinetics of early bacterial growth and cell-to-cell spread of two strains of M. tuberculosis: a lineage 2 strain, 4334, and the widely studied lineage 4 strain H37Rv. Using flow cytometry, live cell sorting of phenotypic subsets, and quantitation of bacteria in cells of the distinct subsets, we found that 4334 induces less leukocyte influx into the lungs but demonstrates earlier population expansion and cell-to-cell spread. The earlier spread of 4334 to recruited cells, including monocyte-derived dendritic cells, is accompanied by earlier and greater magnitude of CD4+ T cell activation. The results provide evidence that strain-specific differences in interactions with lung leukocytes can shape adaptive immune responses in vivo. IMPORTANCE Tuberculosis is a leading infectious disease killer worldwide and is caused by Mycobacterium tuberculosis. After exposure to M. tuberculosis, outcomes range from apparent elimination to active disease. Early innate immune responses may contribute to differences in outcomes, yet it is not known how bacterial strains alter the early dynamics of innate immune and T cell responses. We infected mice with distinct strains of M. tuberculosis and discovered striking differences in innate cellular recruitment, cell-to-cell spread of bacteria in the lungs, and kinetics of initiation of antigen-specific CD4 T cell responses. We also found that M. tuberculosis can spread beyond alveolar macrophages even before a large influx of inflammatory cells. These results provide evidence that distinct strains of M. tuberculosis can exhibit differential kinetics in cell-to-cell spread which is not directly linked to early recruitment of phagocytes but is subsequently linked to adaptive immune responses.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Imunidade Inata , Pulmão/microbiologia , Macrófagos Alveolares , Camundongos , Tuberculose/microbiologia
15.
Eur J Pharm Sci ; 175: 106236, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35710078

RESUMO

Current pathophysiological findings indicate that damage to the alveolar epithelium plays a decisive role in the development of idiopathic pulmonary fibrosis (IPF). The available pharmacological interventions (i.e., oral pirfenidone and nintedanib) only slow down progression of the disease, but do not offer a cure. In order to develop new drug candidates, the pathophysiology of IPF needs to be better understood on a molecular level. It has previously been reported that a loss of caveolin-1 (Cav-1) contributes to profibrotic processes by causing reduced alveolar barrier function and fibrosis-like alterations of the lung-parenchyma. Conversely, overexpression of caveolin-1 appears to counteract the development of fibrosis by inhibiting the inflammasome NLRP3 and the associated expression of interleukin-1ß. In this study, the interaction between Fyn-kinase and caveolin-1 in the alveolar epithelium of various bleomycin (BLM)/TGF-ß damage models using precision-cut lung slices (PCLS), wildtype (WT) and caveolin-1 knockout (KO) mice as well as the human NCI-H441 cell line, were investigated. In WT mouse lung tissues, strong signals for Fyn-kinase were detected in alveolar epithelial type I cells, whereas in caveolin-1 KO animals, expression shifted to alveolar epithelial type II cells. Caveolin-1 and Fyn-kinase were found to be co-localized in isolated lipid rafts of NCI-H441 cell membrane fractions. These findings were corroborated by co-immunoprecipitation studies in which a co-localization of Cav-1 and Fyn-kinase was detected in the cell membrane of the alveolar epithelium. After TGF-ß and BLM-induced damage to the alveolar epithelium both in PCLS and cell culture experiments, a decrease in caveolin-1 and Fyn-kinase was found. Furthermore, TEER (transepithelial electrical resistance) measurements indicated that TGF-ß and BLM have a damaging effect on cell-cell contacts and thus impair the barrier function in NCI-H441 cell monolayers. This effect was attenuated after co-incubation with the Fyn-kinase inhibitor, PP-2. Our data suggest an involvement of Fyn-kinase and caveolin-1 in TGF-ß/bleomycin-induced impairment of alveolar barrier function and thus a possible role in the early stages of pulmonary fibrosis. Fyn-kinase and/or its complex with caveolin-1 might, therefore, be novel therapeutic targets in IPF.


Assuntos
Caveolina 1 , Fibrose Pulmonar Idiopática , Animais , Bleomicina/farmacologia , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Fibrose , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Crescimento Transformador beta/metabolismo
16.
STAR Protoc ; 3(2): 101447, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35712012

RESUMO

Alveolar type 2 cells (AT2s) serve as stem cells of the alveoli and restore cell numbers after injury. Here, we describe a detailed protocol for the isolation, purification, and culture of murine and human AT2s. We have developed chemically defined and stroma-free culture conditions that enable expansion and maintenance of AT2s. The culture conditions are scalable and compatible with high-throughput chemical and genetic screenings and can potentially be used to generate large AT2 numbers for cell-based therapies. For complete details on the use and execution of this protocol, please refer to Katsura et al. (2020).


Assuntos
Células Epiteliais Alveolares , Alvéolos Pulmonares , Animais , Diferenciação Celular/genética , Humanos , Pulmão , Camundongos , Células-Tronco
17.
Oxid Med Cell Longev ; 2022: 2129303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35746964

RESUMO

The small size of labelled samples is one of the challenging problems in identifying early lung nodules from CT images using deep learning methods. Recent literature on the topic shows that deep convolutional generative adversarial network (DCGAN) has been used in medical data synthesis and gained some success, but does not demonstrate satisfactory results in synthesizing CT images. It primarily suffers from the problem of model convergence and is prone to mode collapse. In this paper, we propose a generative adversarial network (GAN) model with prior knowledge to generate CT images of early lung nodules from a small-size of labelled samples, i.e., SLS-PriGAN. Particularly, a knowledge acquisition network and a sharpening network are designed for priori knowledge learning and acquisition, and then, a GAN model is developed to produce CT images of early lung nodules. To validate our method, a general fast R-CNN network is trained using the CT images generated by SLS-PriGAN. The experiment result shows that it achieved a recognizing accuracy of 91%, a recall rate of 81%, and F1 score of 0.85 in identifying clinic CT images of early lung nodules. This provides a promising way of identifying early lung nodules from CT images using deep learning with small-size labelled samples.


Assuntos
Redes Neurais de Computação , Tomografia Computadorizada por Raios X , Processamento de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
18.
Comput Math Methods Med ; 2022: 2350297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747133

RESUMO

Objective: This study is aimed at investigating the efficacy of physical exercise-assisted routine therapy on the pulmonary function of patients with stable asthma to provide clinical evidence and data support to guide disease management. Methods: Randomized controlled clinical trials of drug therapy and/or physical exercise for patients with stable asthma were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science database. The studies published between January 2000 and June 2021 that met the criteria were included, and corresponding data were extracted. The meta-analysis was performed using the statistical software Stata 16.0. Statistical pooled effect sizes and 95% confidence intervals were calculated using a random-effects or fixed-effects model, as funnel plots were made with Begg's rank correlation method to evaluate publication bias. Result: This meta-analysis included 14 randomized controlled studies. Physical exercise-assisted treatment (experiment group) or routine therapy was associated with significantly elevated levels of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (P < 0.05). As for the peak expiratory flow (PEF) level (P < 0.05), its level was significantly increased with physical exercise-assisted therapy compared with the conventional approach (P > 0.05). Subgroup analysis indicated that the FVC level in the experimental group was higher than that in the control group (P < 0.05) regardless of the adoption of aerobic exercise/anaerobic exercise. In regard to the FEV1 and PEE levels, aerobic exercise was associated with elevated levels in the experimental group (P < 0.05), while no significant difference in anaerobic exercise between both groups was observed (P > 0.05). Further, FEV1, FVC, and PEF levels in the experimental group were higher than those receiving conventional treatment in the control group (P < 0.05). Conclusion: Routine treatment combined with physical exercise could improve the levels of FEV1, FVC, and PEF in patients with bronchial asthma in the nonacute attack stage and enhance pulmonary functions. As a safe and efficient adjuvant therapy, physical exercise can contribute to an improved prognosis and quality of life for patients with asthma.


Assuntos
Asma , Qualidade de Vida , Asma/terapia , Exercício Físico , Humanos , Pulmão , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Front Biosci (Landmark Ed) ; 27(6): 182, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35748258

RESUMO

BACKGROUND: The purpose of this manuscript is to provide a comparative overview of the two global pandemics: the first on June 11th 2009 due to influenza A H1N1 (H1N1-09); the second and current pandemic caused by coronavirus 2019 (COVID-19) on March 11th 2020, focusing on how autopsy can contribute to the definition of cellular pathology, to clinical pathology and, more generally, to public health. METHODS: A systematic literature search selection was conducted on PubMed database on June 5, 2021, with this search strategy: (COVID-19) AND (H1N1 influenza) showing 101 results. The following inclusion criteria were selected: English language; published in a scholarly peer-reviewed journal; full-length articles were further elected. To further refine the research was to focus on the type of manuscript: review, systematic review, and meta-analysis. A critical appraisal of the collected studies was conducted, analyzing titles and abstracts, excluding the following topics: treatment, public health measures and perception of the general population or healthcare personnel about their quality of life. According to these procedures, 54 eligible studies were included in the present review. RESULTS: Histopathological findings play a key role in understanding the pathophysiological mechanisms of diseases and, thus possible therapeutic approaches. The evidence on the thrombo-inflammatory mechanism underlying COVID-19 is growing to a much greater magnitude than the diffuse alveolar damage in common with H1N1-09; our study appears to be in line with these results. The prevailing scientific thinking to explain the morbidity and mortality of COVID-19 patients is that it elicits an exuberant immune reaction characterized by dysregulated cytokine production, known as a "cytokine storm". CONCLUSIONS: The histological and immunohistochemical pattern demonstrated similarities and differences between the infectious manifestations of the two pathogens, which justify empirical therapeutic approaches, in the first phase of the COVID-19 pandemic. Therefore, the previous pandemic should have taught us to promote a culture of clinical and forensic autopsies in order to provide timely evidence from integration among autopsy and clinical data for early adopting adequate therapies.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Autopsia , COVID-19/epidemiologia , Humanos , Influenza Humana/epidemiologia , Pulmão/patologia , Pandemias , Qualidade de Vida
20.
BMC Surg ; 22(1): 247, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761236

RESUMO

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is an emerging technology in minimally invasive surgery, which has become recognized as standard treatments for early-stage lung cancer. Microcoil localization is considered to be a safe and effective way of preoperative localization, and is essential to facilitate VATS wedge-resection for lung nodules. CASE PRESENTATION: Here we report a rare case of a 28-year-old female who developed hemorrhagic shock caused by delayed pneumothorax after preoperative computed tomography (CT)-guided microcoil localization. The thoracic CT revealed hydropneumothorax in the right thoracic cavity at 10 h after microcoil localization, and the patient later had significant decreased hemoglobin level (87 g/L). Emergency thoracoscopic exploration demonstrated that the hemorrhagic shock was induced by delayed pneumothorax, which led to the fracture of an adhesive pleura cord and an aberrant vessel. Electrocoagulation hemostasis was then performed for the fractured vessel and the patient gradually recovered from the hypovolemic shock. CONCLUSIONS: Microcoil localization is a relatively safe and effective way of preoperative localization of lung nodules, however, hemorrhagic shock could be induced by rupture of pleural aberrant vessels subsequent to puncture related pneumothorax. Shorten the time interval between localization and thoracoscopic surgery, extend the monitoring time after localization might help to reduce the risk of these complications.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumotórax , Choque Hemorrágico , Adulto , Feminino , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Cuidados Pré-Operatórios/métodos , Radiografia Intervencionista , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Choque Hemorrágico/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos
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