Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.586
Filtrar
1.
Clin Nucl Med ; 46(2): e125-e126, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33156051

RESUMO

ABSTRACT: We report the case of a 9-year-old girl who presented with acute fevers, cough, and epistaxis with nasal swelling, and found to have a nasal mass. On 18F-FDG PET/CT, she was found to have marked nodal and pulmonary parenchymal disease with diffuse and symmetrical mural FDG uptake within the trachea and bronchial tree. The differential diagnosis was broad, and she was diagnosed with IgG4-RD (IgG4-related disease) and improved on appropriate treatment. To our knowledge, there are only 2 other pediatric cases of IgG4-related pulmonary disease in the literature, and our case serves as a unique constellation of intrapulmonary IgG4-RD imaging findings.


Assuntos
Fluordesoxiglucose F18/metabolismo , Doença Relacionada a Imunoglobulina G4/complicações , Pneumopatias/complicações , Pneumopatias/diagnóstico por imagem , Transporte Biológico , Criança , Feminino , Humanos , Inflamação/complicações , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Pneumopatias/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
2.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004527

RESUMO

The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung. Four kinases (PERK, PKR, GCN2 and HRI) sense a diverse range of stresses to trigger this "integrated stress response". Here we review recent advances identifying the integrated stress response as a critical pathway in the pathogenesis of pulmonary diseases, including pneumonias, thoracic malignancy, pulmonary fibrosis and pulmonary hypertension. Understanding the integrated stress response provides novel targets for the development of therapies.


Assuntos
Inflamação/metabolismo , Pneumopatias/metabolismo , Estresse Oxidativo/fisiologia , Biomarcadores/metabolismo , Humanos
3.
PLoS One ; 15(10): e0240333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33057360

RESUMO

CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known that Fibroblast growth factor 10 (Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in the Fgf10-CRISPR F0 mice. However, how the lung phenotype in the Fgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in the Fgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functional Fgf10 genotypes. Firstly, according to a previous report, Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of the Fgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 ± 6.2% in type I, 25.3 ± 2.7% in type II, and 54.3 ± 9.5% in type III (mean ± standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in the Fgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functional Fgf10 genotypes. These data suggest the Fgf10 gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, the Fgf10-CRISPR F0 mouse would present an ideal experimental system to explore it.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Fator 10 de Crescimento de Fibroblastos/genética , Edição de Genes/métodos , Pulmão/metabolismo , Células Epiteliais Alveolares/citologia , Células Epiteliais Alveolares/metabolismo , Animais , Modelos Animais de Doenças , Embrião de Mamíferos/metabolismo , Dosagem de Genes , Genótipo , Pulmão/citologia , Pulmão/patologia , Pneumopatias/metabolismo , Pneumopatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Camundongos Transgênicos
4.
Nat Commun ; 11(1): 5165, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057007

RESUMO

Angiotensin-converting enzyme 2 (ACE2) has been identified as the host entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic. ACE2 is a regulatory enzyme of the renin-angiotensin system and has protective functions in many cardiovascular, pulmonary and metabolic diseases. This review summarizes available murine models with systemic or organ-specific deletion of ACE2, or with overexpression of murine or human ACE2. The purpose of this review is to provide researchers with the genetic tools available for further understanding of ACE2 biology and for the investigation of ACE2 in the pathogenesis and treatment of COVID-19.


Assuntos
Doenças Cardiovasculares/patologia , Modelos Animais de Doenças , Pneumopatias/patologia , Peptidil Dipeptidase A/metabolismo , Animais , Betacoronavirus/fisiologia , Doenças Cardiovasculares/metabolismo , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Pneumopatias/metabolismo , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Camundongos , Camundongos Mutantes , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia
5.
Respir Res ; 21(1): 276, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087116

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. METHODS: We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. RESULTS: We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. DISCUSSION: Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04416100.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Homeostase , Ferro/metabolismo , Pneumopatias/etiologia , Pneumopatias/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Adulto , Idoso , Anemia/etiologia , Proteína C-Reativa/análise , Estudos de Coortes , Infecções por Coronavirus/fisiopatologia , Feminino , Ferritinas/sangue , Seguimentos , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Interleucina-6/sangue , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Pandemias , Pneumonia Viral/fisiopatologia , Estudos Prospectivos , Tomografia Computadorizada por Raios X
6.
Toxicology ; 445: 152598, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32976959

RESUMO

Human exposure to carbon nanotubes (CNT) has been associated with the development of pulmonary sarcoid-like granulomatous disease. Our previous studies demonstrated that multi-walled carbon nanotubes (MWCNT) induced chronic pulmonary granulomatous inflammation in mice. Granuloma formation was accompanied by decreased peroxisome proliferator-activated receptor gamma (PPARγ) and disrupted intracellular lipid homeostasis in alveolar macrophages. Others have shown that PPARγ activation increases mitochondrial fatty acid oxidation (FAO) to reduce free fatty acid accumulation. Hence, we hypothesized that the disrupted lipid metabolism suppresses mitochondrial FAO. To test our hypothesis, C57BL/6 J mice were instilled by an oropharyngeal route with 100 µg MWCNT freshly suspended in 35 % Infasurf. Control sham mice received vehicle alone. Sixty days following instillation, mitochondrial FAO was measured in permeabilized bronchoalveolar lavage (BAL) cells. MWCNT instillation reduced the mitochondrial oxygen consumption rate of BAL cells in the presence of palmitoyl-carnitine as mitochondrial fuel. MWCNT also reduced mRNA expression of mitochondrial genes regulating FAO, carnitine palmitoyl transferase-1 (CPT1), carnitine palmitoyl transferase-2 (CPT2), hydroxyacyl-CoA dehydrogenase subunit beta (HADHB), and PPARγ coactivator 1 alpha (PPARGC1A). Importantly, both oxidative stress and apoptosis in alveolar macrophages and lung tissues of MWCNT-instilled mice were increased. Because macrophage PPARγ expression has been reported to be controlled by miR-27b which is known to induce oxidative stress and apoptosis, we measured the expression of miR-27b. Results indicated elevated levels in alveolar macrophages from MWCNT-instilled mice compared to controls. Given that inhibition of FAO and apoptosis are linked to M1 and M2 macrophage activation, respectively, the expression of both M1 and M2 key indicator genes were measured. Interestingly, results showed that both M1 and M2 phenotypes of alveolar macrophages were activated in MWCNT-instilled mice. In conclusion, alveolar macrophages of MWCNT-instilled mice had increased miR-27b expression, which may reduce the expression of PPARγ resulting in attenuation of FAO. This reduction in FAO may lead to activation of M1 macrophages. The upregulation of miR-27b may also induce apoptosis, which in turn can cause M2 activation of alveolar macrophages. These observations indicate a possible role of miR-27b in impaired mitochondrial function in the chronic activation of alveolar macrophages by MWCNT and the development of chronic pulmonary granulomatous inflammation.


Assuntos
Doença Granulomatosa Crônica/induzido quimicamente , Pneumopatias/induzido quimicamente , Macrófagos Alveolares/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Animais , Doença Granulomatosa Crônica/metabolismo , Doença Granulomatosa Crônica/patologia , Pneumopatias/metabolismo , Pneumopatias/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia
7.
Kidney Blood Press Res ; 45(5): 661-670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32957112

RESUMO

BACKGROUND: The outbreak of severe acute respiratory syndrome ß-coronavirus 2 (SARS-CoV-2) has the potential to become a long-lasting global health crisis. The number of people infected with the novel coronavirus has surpassed 22 million globally, resulting in over 700,000 deaths with more than 15 million people having recovered (https://covid19.who.int). Enormous efforts are underway for rapid vaccine and treatment developments. Amongst the many ways of tackling the novel coronavirus disease 2019 (COVID-19) pandemic, extracellular vesicles (EVs) are emerging. SUMMARY: EVs are lipid bilayer-enclosed structures secreted from all types of cells, including those lining the respiratory tract. They have established roles in lung immunity and are involved in the pathogenesis of various lung diseases, including viral infection. In this review, we point out the roles and possible contribution of EVs in viral infections, as well as ongoing EV-based approaches for the treatment of COVID-19, including clinical trials. Key Messages: EVs share structural similarities to viruses and recent findings demonstrate that viruses exploit EVs for cellular exit and EVs exploit viral entry mechanisms for cargo delivery. Moreover, EV-virus interplay could be exploited for future antiviral drug and vaccine development. EV-based therapies, especially the mesenchymal stem cell-derived EVs, are being intensively studied for the treatment of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Vesículas Extracelulares/virologia , Pneumopatias/terapia , Pneumonia Viral/terapia , Antivirais/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Vesículas Extracelulares/metabolismo , Terapia Genética/tendências , Humanos , Pneumopatias/metabolismo , Pneumopatias/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Eliminação de Partículas Virais/efeitos dos fármacos , Eliminação de Partículas Virais/fisiologia
9.
Sci Rep ; 10(1): 15811, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978505

RESUMO

Hemorrhagic shock results in systemic injury to the endothelium contributing to post-shock morbidity and mortality. The mechanism involves syndecan-1, the backbone of the endothelial glycocalyx. We have shown in a rodent model that lung syndecan-1 mRNA is reduced following hemorrhage, whereas the molecular mechanism underlying the mRNA reduction is not clear. In this study, we present evidence that miR-19b targets syndecan-1 mRNA to downregulate its expression. Our results demonstrate that miR-19b was increased in hemorrhagic shock patients and in-vitro specifically bound to syndecan-1 mRNA and caused its degradation. Further, hypoxia/reoxygenation (H/R), our in vitro hemorrhage model, increased miR-19b expression in human lung microvascular endothelial cells, leading to a decrease in syndecan-1 mRNA and protein. H/R insult and miR-19b mimic overexpression comparably exaggerated permeability and enhanced endothelial barrier breakdown. The detrimental role of miR-19b in inducing endothelial dysfunction was confirmed in vivo. Lungs from mice undergoing hemorrhagic shock exhibited a significant increase in miR-19b and a concomitant decrease in syndecan-1 mRNA. Pretreatment with miR-19b oligo inhibitor significantly decreased lung injury, inflammation, and permeability and improved hemodynamics. These findings suggest that inhibition of miR-19b may be a putative therapeutic avenue for mitigating post shock pulmonary endothelial dysfunction in hemorrhage shock.


Assuntos
Modelos Animais de Doenças , Endotélio Vascular/patologia , Pneumopatias/patologia , MicroRNAs/genética , Choque Hemorrágico/complicações , Sindecana-1/metabolismo , Animais , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Humanos , Pneumopatias/etiologia , Pneumopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sindecana-1/genética
10.
Adv Exp Med Biol ; 1265: 57-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761570

RESUMO

Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host cells and disrupt lung homeostasis, therefore leading to dysfunctional epithelial barriers. Despite significant advances in therapeutic treatments for lung diseases in the last two decades, novel interventional targets are imperative, considering the side effects and limited efficacy in patients treated with currently available drugs. Nutrients, such as amino acids (e.g., arginine, glutamine, glycine, proline, taurine, and tryptophan), peptides, and bioactive molecules, have attracted more and more attention due to their abilities to reduce oxidative stress, inhibit apoptosis, and regulate immune responses, thereby improving epithelial barriers. In this review, we summarize recent advances in amino acid metabolism in the lungs, as well as multifaceted functions of amino acids in attenuating inflammatory lung diseases based on data from studies with both human patients and animal models. The underlying mechanisms for the effects of physiological amino acids are likely complex and involve cell signaling, gene expression, and anti-oxidative reactions. The beneficial effects of amino acids are expected to improve the respiratory health and well-being of humans and other animals. Because viruses (e.g., coronavirus) and environmental pollutants (e.g., PM2.5 particles) induce severe damage to the lungs, it is important to determine whether dietary supplementation or intravenous administration of individual functional amino acids (e.g., arginine-HCl, citrulline, N-acetylcysteine, glutamine, glycine, proline and tryptophan) or their combinations to affected subjects may alleviate injury and dysfunction in this vital organ.


Assuntos
Aminoácidos/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Pneumopatias/metabolismo , Pneumopatias/patologia , Animais , Humanos , Pneumopatias/fisiopatologia
13.
Am J Physiol Lung Cell Mol Physiol ; 319(2): L289-L293, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32491950

RESUMO

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley's criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.


Assuntos
Artérias/metabolismo , Pulmão/metabolismo , Oxigênio/metabolismo , Troca Gasosa Pulmonar/fisiologia , Dióxido de Carbono/metabolismo , Hemoglobinas/metabolismo , Humanos , Pulmão/fisiopatologia , Pneumopatias/metabolismo , Pneumopatias/fisiopatologia , Oximetria/métodos , Respiração
14.
J Exp Med ; 217(8)2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32556101

RESUMO

The renin-angiotensin system (RAS) has long been appreciated as a major regulator of blood pressure, but has more recently been recognized as a mechanism for modulating inflammation as well. While there has been concern in COVID-19 patients over the use of drugs that target this system, the RAS has not been explored fully as a druggable target. The abbreviated description of the RAS suggests that its dysregulation may be at the center of COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumopatias/fisiopatologia , Pulmão/virologia , Pneumonia Viral/fisiopatologia , Angiotensina I/metabolismo , Animais , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Humanos , Hipertensão/fisiopatologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Pneumopatias/metabolismo , Pneumopatias/virologia , Obesidade/fisiopatologia , Pandemias , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Índice de Gravidade de Doença
15.
Ann Clin Lab Sci ; 50(3): 308-313, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32581017

RESUMO

OBJECTIVE: The COVID-19 pandemic has challenged the world economically and medically. Understanding and defining the biology of this specific coronavirus infection may lead to targeted therapies to lessen its virulence and expand the host resistance. This study's objective was to apply morphoproteomics to pulmonary lung sections from a forensic autopsy of an untreated COVID-19 victim, so that we may better define its biology from the perspective of its interaction with the host and provide options for therapeutic targets. DESIGN: Morphoproteomic analysis from a case study of this COVID-19 pulmonary infection included immunohistochemical probes to detect phosphorylated p-STAT3 (Tyr 705), as part of the interleukin (IL)-6 pathway; cyclooxygenase (COX)-2, CD8+ cytotoxic lymphocytes, Programmed Death (PD)-1 receptor+ lymphoid cells, CD56+ NK lymphoid cells, CD163+ (M2 polarized monocytes/macrophages), and programmed death-ligand 1 (PD-L1) expression as part of the host response to interaction with the COVID-19 virus. RESULTS: Representative sections of the COVID-19 victim's lung showed: nuclear expression of p-STAT3 (Tyr 705) in many of the alveolar pneumocytes and in occasional endothelial cells; COX-2 expression in the alveolar pneumocytes; a relative paucity of CD8+ cytotoxic lymphocytes; absence of CD56+ NK lymphoid cells; abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes; PD-L1 expression on occasional macrophages, focally on collections of alveolar pneumocytes, and on cells in the alveolar interstitium; and rare PD-1+ lymphocytes in similar regions as CD8+ lymphocytes. CONCLUSION: Morphoproteomics and microanatomical features coincide with the etiopathogenic features of pulmonary coronavirus infection and the host response. This suggests that a targeted therapy could address the biology of COVID-19 pneumonia, enhance the host immune response and prevent its progression to a life-threatening, ventilator-dependent clinical situation.


Assuntos
Betacoronavirus/isolamento & purificação , Biomarcadores/metabolismo , Infecções por Coronavirus/complicações , Pneumopatias/metabolismo , Pneumopatias/patologia , Pneumonia Viral/complicações , Proteoma/análise , Biomarcadores/análise , Infecções por Coronavirus/virologia , Evolução Fatal , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Proteoma/metabolismo
16.
Cell Prolif ; 53(7): e12813, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32515860

RESUMO

OBJECTIVES: Accumulating studies have investigated the PM2.5-induced pulmonary toxicity, while gaps still remain in understanding its toxic mechanism. Due to its high specific surface area and adsorption capacity similar to nanoparticles, PM2.5 acts as a significant carrier of metals in air and then leads to altered toxic effects. In this study, we aimed to use CBs and Ni as model materials to investigate the autophagy changes and pulmonary toxic effects at 30 days following intratracheal instillation of CBs-Ni mixture. MATERIALS AND METHODS: Groups of mice were instilled with 100 µL normal saline (NS), 20 µg CBs, and 4 µg Ni or CBs-Ni mixture, respectively. At 7 and 30 days post-instillation, all the mice were weighed and then sacrificed. The evaluation system was composed of the following: (a) autophagy and lysosomal function assessment, (b) trace element biodistribution observation in lungs, (c) pulmonary lavage biomedical analysis, (d) lung histopathological evaluation, (e) coefficient analysis of major organs and (f) CBs-Ni interaction and cell proliferation assessment. RESULTS: We found that after CBs-Ni co-exposure, no obvious autophagy and lysosomal dysfunction or pulmonary toxicity was detected, along with complete clearance of Ni from lung tissues as well as recovery of biochemical indexes to normal range. CONCLUSIONS: We conclude that the damaged autophagy and lysosomal function, as well as physiological function, was repaired at 30 days after exposure of CBs-Ni. Our findings provide a new idea for scientific assessment of the impact of fine particles on environment and human health, and useful information for the comprehensive treatment of air pollution.


Assuntos
Autofagia/efeitos dos fármacos , Carbono/efeitos adversos , Pneumopatias/induzido quimicamente , Pulmão/efeitos dos fármacos , Metais/efeitos adversos , Animais , Linhagem Celular , Pulmão/metabolismo , Pneumopatias/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Células RAW 264.7 , Distribuição Tecidual
17.
J Agric Food Chem ; 68(24): 6554-6563, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32452677

RESUMO

Short-chain fatty acids (SCFAs), especially propionate, originate from the fermentation of dietary fiber in the gut and play a key role in inhibiting pulmonary inflammation. Chronic inflammation may induce an epithelial-mesenchymal transition (EMT) in alveolar epithelial cells and result in fibrotic disorders. This study was designed to investigate the beneficial effect of sodium propionate (SP) on lipopolysaccharide (LPS)-induced EMT. In cultured BEAS-2B cells, the protein expression levels of E-cadherin, α-smooth muscle actin (SMA), and vimentin were 0.66 ± 0.20, 1.44 ± 0.23, and 1.32 ± 0.21 in the LPS group vs 1.11 ± 0.36 (P < 0.05), 1.04 ± 0.30 (P < 0.05), and 0.96 ± 0.13 (P < 0.01) in the LPS + SP group (mean ± standard deviation), respectively. Meanwhile, LPS-triggered inflammatory cytokines and extracellular proteins were also reduced by SP administration in BEAS-2B cells. Moreover, SP treatment attenuated inflammation, EMT, extracellular matrix (ECM) deposition, and even fibrosis in a mouse EMT model. In terms of mechanism, LPS-treated BEAS-2B cells exhibited a higher level of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) phosphorylation, which was interrupted by SP treatment. It is worth noting that the blockade of the PI3K/Akt/mTOR signaling cascade reduced the LPS-evoked EMT process in BEAS-2B cells. These results suggest that SP can block LPS-induced EMT via inhibition of the PI3K/Akt/mTOR signaling cascade, which provides a basis for possible clinical use of SP in airway and lung diseases.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Pneumopatias/tratamento farmacológico , Fosfatidilinositol 3-Quinase/metabolismo , Propionatos/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Caderinas/genética , Caderinas/metabolismo , Humanos , Pneumopatias/genética , Pneumopatias/metabolismo , Pneumopatias/fisiopatologia , Masculino , Camundongos , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Vimentina/genética , Vimentina/metabolismo
18.
Adv Exp Med Biol ; 1195: 13-18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468452

RESUMO

The exhaled breath condensate is a source of biomarkers with many advantages and benefits compared to other traditional sampling techniques in respiratory medicine. It is a biological product that is formed by cooling the exhaled air via its guidance through a condenser. It is characterized as a cocktail of volatile and non-volatile compounds with water being the predominant constituent. Its composition presents a non-uniformed structure as the volatile and the non-volatile compounds vary in type and ratio. All these compounds originate from the whole respiratory tract. Some of them fulfil the criteria to be characterized as biomarkers since there is a similarity between the content of the exhaled breath condensate and the respiratory tract lining fluid. In addition, the potential biomarkers of the exhaled breath condensate and those from other biological fluids are equivalent.Advantages and Disadvantages Its place in the respiratory medicine as a matrix of biomarkers relies on its various strengths. Some of them are very important and make it exceptional regarding its application, such as its totally non-invasive character and its usage in all ages, while others present a more potential action regarding its purpose such as the categorization of respiratory diseases. However, there are limitations in its application due to the lack of standardization of its conduct which can be minimized by following the official recommendations. Additional studies are needed to develop said standardization.Aim The aim of this paper is to present a brief and comprehensive picture of the sampling technique of the exhaled breath condensate, as well as the criteria to make it a preferred choice as a source of biomarkers.


Assuntos
Biomarcadores/análise , Testes Respiratórios , Pneumopatias/metabolismo , Expiração , Humanos , Padrões de Referência
19.
Int J Mol Sci ; 21(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32354030

RESUMO

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.


Assuntos
Antioxidantes/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Dieta , Suplementos Nutricionais , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Adiponectina/metabolismo , Ácido Ascórbico/administração & dosagem , Infecções por Coronavirus/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Flavonoides/administração & dosagem , Humanos , Interleucina-6/imunologia , Interleucina-6/metabolismo , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Pandemias , Pneumonia Viral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Sci Rep ; 10(1): 7212, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350324

RESUMO

Metabolic Syndrome (MetS) has been related to pulmonary diseases but its relationship with lung age has not been sufficiently studied. In addition, anthropometric variables have been associated with pulmonary dysfunction, highlighting the waist-to-height ratio (WHtR). The aim was to evaluate the relationship between MetS and: lung age, anthropometric variables and the alteration of lung function. A cross-sectional study was carried out in 1901 workers, evaluating lung function through lung age (Morris & Temple equation) and spirometric values. The diagnosis of MetS was based on the harmonized criteria. We measured anthropometric variables (WHtR, waist circumference, body mass index, waist to hip ratio), blood pressure and biochemical variables (glucose, cholesterol total, HDL, triglycerides). Workers suffering from MetS showed an accelerated lung aging (59.4 ± 18.7 years vs 49 ± 18.4 years). The WHtR ≥ 0.55 was significantly related to an increase in lung age (ß = 6.393, p < 0.001). In addition, a significant linear trend was found between clinical categories of WHtR and lung dysfunction, restrictive and mixed pattern. MetS caused an accelerated lung aging and favored the presence of restrictive lung impairment. In addition, WHtR ≥ 0.55 has been shown as the best predictor for pulmonary health.


Assuntos
Envelhecimento , Pneumopatias , Síndrome Metabólica , Razão Cintura-Estatura , Adulto , Envelhecimento/metabolismo , Envelhecimento/patologia , Feminino , Humanos , Pneumopatias/metabolismo , Pneumopatias/patologia , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA