Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38.528
Filtrar
1.
Respirar (Ciudad Autón. B. Aires) ; 16(3): 311-314, sept.2024.
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1570689

RESUMO

El síndrome de Williams-Campbell (SWC) es una entidad clínica caracterizada por la deficiencia de cartílago en la pared bronquial de los bronquios subsegmentarios. Es una condición congénita que por lo general se diagnostica en la niñez, pero hay reportes de caso en la población adulta y se cree que esto se debe a un menor déficit de cartílago. Los síntomas principales de esta condición son la presencia de tos, disnea e infecciones respiratorias a repetición. Radiológicamente, se evidencia la presencia de bronquiectasias de pared delgada. El diagnóstico se basa en descartar otras causas más comunes de bronquiectasias, así como en la identificación de las características radiológicas y la presencia del componente congénito. Presentamos el caso de un joven con síntomas respiratorios desde la infancia, con necesidad de múltiples hospitalizaciones por procesos infecciosos de origen pulmonar a repetición, con lo cual se llega al diagnóstico de un síndrome de Williams-Campbell.


Williams-Campbell syndrome (WCS) is a clinical entity characterized by cartilage deficiency in the bronchial wall of the subsegmental bronchi. It is a congenital condition that is usually diagnosed in childhood, but there are case reports in the adult population, and it is believed that this is due to a minor cartilage deficiency. The main symptoms of this condition are the presence of cough, dyspnea and repeated respiratory infections. Radiologically, the presence of thin-walled bronchiectasis is evident. The diagnosis is based on ruling out other more common causes of bronchiectasis, as well as identifying the radiological characteristics and the presence of the congenital component. We present the case of a young man with respiratory symptoms since childhood requiring multiple hospitalizations due to repeated infectious processes of pulmonary origin, in which the diagnosis of Williams-Campbell syndrome was reached.


Assuntos
Humanos , Masculino , Adulto , Bronquiectasia , Traqueobroncomalácia/diagnóstico , Sinais e Sintomas Respiratórios , Anormalidades Congênitas/diagnóstico , Brônquios , Tomografia , Cartilagem , Iontoforese
2.
Environ Int ; 191: 109001, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39284259

RESUMO

Carbon black nanoparticles (CBNPs) have been demonstrated to induce DNA damage in epithelial cells. However, the potential of the damage to initiate carcinogenesis and the underlying mechanism remain poorly understood. Therefore, we constructed an in vitro model of malignant transformation of human bronchial epithelial cells (16HBE-T) by treating 40 µg/mL CBNPs for 120 passages. We observed tumor-like transformation and sustained DNA damage. Using transcriptome sequencing and RIP-seq, we identified the overexpression of the critical DNA mismatch repair genes MutS homolog 2 (MSH2) and its related circular RNA, circ_0025373, in the 16HBE-T cells. Mechanistically, circ_0025373 was found to inhibit DNA damage by binding to MSH2, thereby modifying its expression and influencing its nuclear and cytoplasmic distribution, which lead to inhibition of CBNP-induced malignant transformation of human bronchial epithelial cells. Our findings provide novel evidence on the carcinogenicity of CBNPs, and offer biological insights into the potential epigenetic regulation and potential therapeutic targets for lung carcinogenesis.


Assuntos
Brônquios , Transformação Celular Neoplásica , Dano ao DNA , Células Epiteliais , Proteína 2 Homóloga a MutS , Nanopartículas , Fuligem , Humanos , Proteína 2 Homóloga a MutS/metabolismo , Proteína 2 Homóloga a MutS/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fuligem/toxicidade , Nanopartículas/química , Brônquios/patologia , RNA Circular/genética , RNA Circular/metabolismo , Linhagem Celular
3.
BMC Pulm Med ; 24(1): 466, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304863

RESUMO

BACKGROUND: Most malignant peripheral pulmonary lesions (PPLs) are situated in the peripheral region of the lung. Although the ultrathin bronchoscope (UTB) can access these areas, a robust navigation system is essential for precise localisation of these small peripheral PPLs. Since many UTB procedures rely on automated virtual bronchoscopic navigation (VBN), this study aims to determine the accuracy and diagnostic yield of the manual bronchial branch tracing (BBT) navigation in UTB-guided radial endobronchial ultrasound (rEBUS) procedures. METHODS: Single-centre retrospective study of UTB-rEBUS patients with PPLs smaller than 3 cm over a two year period. RESULTS: Our cohort consisted of 47 patients with a mean age of 61.6 (SD 9.53) years and a mean target size of 1.91 (SD 0.53) cm. Among these lesions, 46.8% were located in the 6th airway generation, and 78.7% exhibited a direct bronchus sign. Navigation success using BBT was 91.5% based on positive rEBUS identification. The index diagnostic yield was 82.9%, increasing to 91.5% at 12 months of follow-up. Malignant lesions accounted for 65.1% of cases, while 34.9% were non-malignant. The presence of a direct bronchus sign was the sole factor associated with higher navigation success and diagnostic yield. Cryobiopsy outperformed forceps biopsy in non-concentric rEBUS lesions (90.9% vs. 50.0%, p < 0.05), but not in concentric orientated lesions. One pneumothorax occurred in our cohort. CONCLUSIONS: BBT as an exclusive navigation method for small PPLs in UTB-rEBUS procedures has proved to be safe and feasible. Combination of UTB with cryobiopsy remains efficient for eccentric and adjacently oriented rEBUS lesions.


Assuntos
Broncoscopia , Endossonografia , Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Broncoscopia/métodos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Endossonografia/métodos , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Brônquios/patologia , Brônquios/diagnóstico por imagem
4.
Medicine (Baltimore) ; 103(36): e39636, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252260

RESUMO

RATIONALE: Bronchial Dieulafoy disease (BDD), a rarely reported disease, comes from dilated or abnormal arteries under the bronchial mucosa. Patients with BDD are generally asymptomatic so this disease is frequently misdiagnosed. However, the submucosal arteries may dilate and rupture for various reasons, leading to recurrent respiratory tract bleeding and potentially life-threatening conditions. With the change of reversible factors such as intravascular pressure, the arteries may return to normal, allowing patients to recover to an asymptomatic state. This phenomenon has not been mentioned and concerned in previous studies, but it may have important implications for our correct understanding of this disease. PATIENT CONCERNS: A 44-year-old female was admitted to intensive care unit with recurrent malignant arrhythmias. With the assistance of VA-extracorporeal membrane oxygenation (ECMO), both her vital signs and internal environment were all gradually stabilized. However, she had been experiencing recurrent respiratory tract bleeding. While removing the bloody secretion with a fiber bronchoscopy, a congested protruding granule on the wall of the patient's left principal bronchus was found. DIAGNOSIS: The patient was diagnosed with BDD and the granule was thought to be an abnormal artery of BDD. INTERVENTIONS: For the patient's condition, we did not implement any targeted interventions with the abnormal artery. OUTCOMES: After the weaning of VA-ECMO, the patient's granule could not be found and the bleeding had also disappeared. She gradually weaned off the mechanical ventilation and was transferred to the Department of Cardiology. Then the patient was discharged after her condition stabilized. In more than half a year, the patient is in a normal physical condition. LESSONS: The appearance and disappearance of abnormal artery is an interesting phenomena of BDD. The change of intravascular pressure due to various causes such as VA-ECMO may be the primary factor of it.


Assuntos
Broncoscopia , Oxigenação por Membrana Extracorpórea , Humanos , Feminino , Adulto , Oxigenação por Membrana Extracorpórea/métodos , Broncoscopia/métodos , Broncopatias/etiologia , Broncopatias/diagnóstico , Brônquios/irrigação sanguínea , Doenças Vasculares/diagnóstico , Doenças Vasculares/etiologia
5.
Ecotoxicol Environ Saf ; 283: 116985, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39217894

RESUMO

Cigarette smoke, a complex mixture produced by tobacco combustion, contains a variety of carcinogens and can trigger DNA damage. Overactivation of c-MET, a receptor tyrosine kinase, may cause cancer and cellular DNA damage, but the underlying mechanisms are unknown. In this work, we investigated the mechanisms of cigarette smoke extract (CSE) induced malignant transformation and DNA damage in human bronchial epithelial cells (BEAS-2B). The results demonstrated that CSE treatment led to up-regulated mRNA expression of genes associated with the c-MET signaling pathway, increased expression of the DNA damage sensor protein γ-H2AX, and uncontrolled proliferation in BEAS-2B cells. ATR, ATR, and CHK2, which are involved in DNA damage repair, as well as the phosphorylation of c-MET and a group of kinases (ATM, ATR, CHK1, CHK2) involved in the DNA damage response were all activated by CSE. In addition, CSE activation promotes the phosphorylation modification of ATR, CHK1 proteins associated with DNA damage repair. The addition of PHA665752, a specific inhibitor of c-MET, or knock-down with c-MET both attenuated DNA damage, while overexpression of c-MET exacerbated DNA damage. Thus, c-MET phosphorylation may be involved in CSE-induced DNA damage, providing a potential target for intervention in the prevention and treatment of smoking-induced lung diseases.


Assuntos
Brônquios , Dano ao DNA , Células Epiteliais , Nicotiana , Proteínas Proto-Oncogênicas c-met , Fumaça , Humanos , Proteínas Proto-Oncogênicas c-met/metabolismo , Fosforilação/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Brônquios/citologia , Fumaça/efeitos adversos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Linhagem Celular , Transdução de Sinais/efeitos dos fármacos , Produtos do Tabaco
6.
J Virol ; 98(9): e0012824, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39162434

RESUMO

Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with critical coronavirus disease 2019 (COVID-19) present with life-threatening respiratory distress, pulmonary damage, and cytokine storm. One unexplored component in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which is highly abundant in the airways and could converge in multiple aspects of COVID-19-related pulmonary pathophysiology. Whether CGRP affects SARS-CoV-2 infection directly remains elusive. We show that in critical COVID-19 patients, CGRP is increased in both plasma and lungs. Importantly, CGRP pulmonary levels are elevated in early SARS-CoV-2-positive patients and restored to baseline upon subsequent viral clearance in SARS-CoV-2-negative patients. We further show that CGRP and its stable analog SAX directly inhibit infection of bronchial Calu-3 epithelial cells with SARS-CoV-2 Omicron and Alpha variants in a dose-dependent manner. Both pre- and post-infection treatments with CGRP and/or SAX are enough to block SARS-CoV-2 productive infection of Calu-3 cells. CGRP-mediated inhibition occurs via activation of the CGRP receptor and involves down-regulation of both SARS-CoV-2 entry receptors at the surface of Calu-3 cells. Together, we propose that increased pulmonary CGRP mediates beneficial viral clearance in critical COVID-19 patients by directly inhibiting SARS-CoV-2 propagation. Hence, CGRP-based interventions could be harnessed for management of COVID-19.IMPORTANCEThe neuropeptide CGRP is highly abundant in the airways. Due to its immunomodulatory, vasodilatory, and anti-viral functions, CGRP could affect multiple aspects of COVID-19-related pulmonary pathophysiology. Yet, the interplay between CGRP and SARS-CoV-2 during COVID-19 remains elusive. Herein, we show that pulmonary levels of CGRP are increased in critical COVID-19 patients, at an early stage of their disease when patients are SARS-CoV-2-positive. Upon subsequent viral clearance, CGRP levels are restored to baseline in SARS-CoV-2-negative patients. We further show that pre- and post-infection treatments with CGRP directly inhibit infection of Calu-3 bronchial epithelial cells with SARS -CoV-2, via activation of the CGRP receptor leading to decreased expression of both SARS-CoV-2 entry receptors. Together, we propose that increased pulmonary CGRP is beneficial in COVID-19, as CGRP-mediated inhibition of SARS-CoV-2 infection could contribute to viral clearance in critical COVID-19 patients. Accordingly, CGRP-based formulations could be useful for COVID-19 management.


Assuntos
COVID-19 , Peptídeo Relacionado com Gene de Calcitonina , Células Epiteliais , Pulmão , SARS-CoV-2 , Humanos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Células Epiteliais/virologia , Células Epiteliais/metabolismo , Pulmão/virologia , Pulmão/metabolismo , Brônquios/virologia , Brônquios/metabolismo , Masculino , Linhagem Celular , Feminino , Pessoa de Meia-Idade , Tratamento Farmacológico da COVID-19 , Idoso , Antivirais/uso terapêutico
7.
J Nucl Med ; 65(9): 1383-1386, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39089815

RESUMO

We evaluated the incidence and potential etiology of tracheobronchial uptake in patients being evaluated by 18F-DCFPyL PET/CT for prostate cancer (PCa). Methods: The study included a consecutive 100 PCa patients referred for 18F-DCFPyL PET/CT. The PET/CT scans were retrospectively reviewed. The presence or absence of physiologic tracheobronchial uptake on PET/CT was recorded. To further evaluate tracheal prostate-specific membrane antigen (PSMA) expression, immunohistochemistry was performed on tracheal samples taken from 2 men who had surgical resection of lung cancer. Results: Tracheal uptake was present in 31 of 100 patients (31%). When tracheal uptake was present, the SUVmax was significantly higher in the left main bronchus (mean, 2.7) than in the right (mean, 2.3) (P < 0.001). Histopathologic testing of tracheobronchial samples showed PSMA expression in bronchial submucosal glands. Conclusion: In PCa patients undergoing 18F-DCFPyL PET/CT, tracheobronchial uptake occurred in 31% of patients. This is attributed to normal physiologic PSMA expression in bronchial submucosal glands.


Assuntos
Brônquios , Glutamato Carboxipeptidase II , Lisina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Traqueia , Ureia , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Traqueia/diagnóstico por imagem , Traqueia/metabolismo , Idoso , Glutamato Carboxipeptidase II/metabolismo , Brônquios/diagnóstico por imagem , Brônquios/metabolismo , Pessoa de Meia-Idade , Lisina/análogos & derivados , Lisina/metabolismo , Estudos Retrospectivos , Ureia/análogos & derivados , Ureia/metabolismo , Antígenos de Superfície/metabolismo , Idoso de 80 Anos ou mais , Transporte Biológico , Compostos Radiofarmacêuticos
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 852-860, 2024 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-39148391

RESUMO

OBJECTIVES: To investigate the effect of reactive oxygen species (ROS)/silent information regulator 1 (SIRT1) on hyperoxia-induced mitochondrial injury in BEAS-2B cells. METHODS: The experiment was divided into three parts. In the first part, cells were divided into H0, H6, H12, H24, and H48 groups. In the second part, cells were divided into control group, H48 group, H48 hyperoxia+SIRT1 inhibitor group (H48+EX 527 group), and H48 hyperoxia+SIRT1 agonist group (H48+SRT1720 group). In the third part, cells were divided into control group, 48-hour hyperoxia+N-acetylcysteine group (H48+NAC group), and H48 group. The ROS kit was used to measure the level of ROS. Western blot and immunofluorescent staining were used to measure the expression levels of SIRT1 and mitochondria-related proteins. Transmission electron microscopy was used to observe the morphology of mitochondria. RESULTS: Compared with the H0 group, the H6, H12, H24, and H48 groups had a significantly increased fluorescence intensity of ROS (P<0.05), the H48 group had significant reductions in the expression levels of SIRT1 protein and mitochondria-related proteins (P<0.05), and the H24 and H48 groups had a significant reduction in the fluorescence intensity of mitochondria-related proteins (P<0.05). Compared with the H48 group, the H48+SRT1720 group had significant increases in the expression levels of mitochondria-related proteins and the mitochondrial aspect ratio (P<0.05), and the H48+EX 527 group had a significant reduction in the mitochondrial area (P<0.05). Compared with the H48 group, the H48+NAC group had a significantly decreased fluorescence intensity of ROS (P<0.05) and significantly increased levels of SIRT1 protein, mitochondria-related proteins, mitochondrial area, and mitochondrial aspect ratio (P<0.05). CONCLUSIONS: The ROS/SIRT1 axis is involved in hyperoxia-induced mitochondrial injury in BEAS-2B cells.


Assuntos
Brônquios , Células Epiteliais , Hiperóxia , Espécies Reativas de Oxigênio , Sirtuína 1 , Sirtuína 1/metabolismo , Sirtuína 1/fisiologia , Sirtuína 1/genética , Humanos , Espécies Reativas de Oxigênio/metabolismo , Hiperóxia/complicações , Hiperóxia/metabolismo , Células Epiteliais/metabolismo , Brônquios/metabolismo , Mitocôndrias/metabolismo , Células Cultivadas , Linhagem Celular
9.
Respir Res ; 25(1): 317, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160511

RESUMO

RATIONAL: Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases). METHODS: Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot. RESULTS: (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs. CONCLUSIONS: These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis.


Assuntos
Brônquios , Proliferação de Células , Neoplasias Pulmonares , Transdução de Sinais , Fumar , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Transdução de Sinais/fisiologia , Masculino , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Proliferação de Células/fisiologia , Fumar/efeitos adversos , Fumar/metabolismo , Idoso , Brônquios/metabolismo , Brônquios/patologia , Células Cultivadas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética
10.
Respir Res ; 25(1): 321, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174953

RESUMO

BACKGROUND: Mitochondria is prone to oxidative damage by endogenous and exogenous sources of free radicals, including particulate matter (PM). Given the role of mitochondria in inflammatory disorders, such as asthma and chronic obstructive pulmonary disease, we hypothesized that supplementation of vitamin D may play a protective role in PM-induced mitochondrial oxidative damages of human bronchial epithelial BEAS-2B cells. METHODS: BEAS-2B cells were pretreated with 1,25(OH)2D3, an active form of vitamin D, for 1 h prior to 24-hour exposure to PM (SRM-1648a). Oxidative stress was measured by flow cytometry. Mitochondrial functions including mitochondrial membrane potential, ATP levels, and mitochondrial DNA copy number were analyzed. Additionally, mitochondrial ultrastructure was examined using transmission electron microscopy. Intracellular and mitochondrial calcium concentration changes were assessed using flow cytometry based on the expression of Fluo-4 AM and Rhod-2 AM, respectively. Pro-inflammatory cytokines, including IL-6 and MCP-1, were quantified using ELISA. The expression levels of antioxidants, including SOD1, SOD2, CAT, GSH, and NADPH, were determined. RESULTS: Our findings first showed that 24-hour exposure to PM led to the overproduction of reactive oxygen species (ROS) derived from mitochondria. PM-induced mitochondrial oxidation resulted in intracellular calcium accumulation, particularly within mitochondria, and alterations in mitochondrial morphology and functions. These changes included loss of mitochondrial membrane integrity, disarrayed cristae, mitochondrial membrane depolarization, reduced ATP production, and increased mitochondrial DNA copy number. Consequently, PM-induced mitochondrial damage triggered the release of certain inflammatory cytokines, such as IL-6 and MCP-1. Similar to the actions of mitochondrial ROS inhibitor MitoTEMPO, 1,25(OH)2D3 conferred protective effects on mtDNA alterations, mitochondrial damages, calcium dyshomeostasis, thereby decreasing the release of certain inflammatory cytokines. We found that greater cellular level of 1,25(OH)2D3 upregulated the expression of enzymatic (SOD1, SOD2, and CAT) and non-enzymatic (GSH and NADPH) antioxidants to modulate cellular redox homeostasis. CONCLUSION: Our study provides new evidence that 1,25(OH)2D3 acts as an antioxidant, enhancing BEAS-2B antioxidant responses to regulate mitochondrial ROS homeostasis and mitochondrial function, thereby enhancing epithelial defense against air pollution exposure.


Assuntos
Brônquios , Cálcio , Células Epiteliais , Homeostase , Mitocôndrias , Material Particulado , Humanos , Material Particulado/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Cálcio/metabolismo , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Vitamina D/farmacologia , Espécies Reativas de Oxigênio/metabolismo
11.
J Cell Mol Med ; 28(15): e18577, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39099000

RESUMO

Lung cancer remains the leading cause of cancer-related deaths, with cigarette smoking being the most critical factor, linked to nearly 90% of lung cancer cases. NNK, a highly carcinogenic nitrosamine found in tobacco, is implicated in the lung cancer-causing effects of cigarette smoke. Although NNK is known to mutate or activate certain oncogenes, its potential interaction with p27 in modulating these carcinogenic effects is currently unexplored. Recent studies have identified specific downregulation of p27 in human squamous cell carcinoma, in contrast to adenocarcinoma. Additionally, exposure to NNK significantly suppresses p27 expression in human bronchial epithelial cells. Subsequent studies indicates that the downregulation of p27 is pivotal in NNK-induced cell transformation. Mechanistic investigations have shown that reduced p27 expression leads to increased level of ITCH, which facilitates the degradation of Jun B protein. This degradation in turn, augments miR-494 expression and its direct regulation of JAK1 mRNA stability and protein expression, ultimately activating STAT3 and driving cell transformation. In summary, our findings reveal that: (1) the downregulation of p27 increases Jun B expression by upregulating Jun B E3 ligase ITCH, which then boosts miR-494 transcription; (2) Elevated miR-494 directly binds to 3'-UTR of JAK1 mRNA, enhancing its stability and protein expression; and (3) The JAK1/STAT3 pathway is a downstream effector of p27, mediating the oncogenic effect of NNK in lung cancer. These findings provide significant insight into understanding the participation of mechanisms underlying p27 inhibition of NNK induced lung squamous cell carcinogenic effect.


Assuntos
Brônquios , Carcinoma de Células Escamosas , Transformação Celular Neoplásica , Inibidor de Quinase Dependente de Ciclina p27 , Células Epiteliais , Neoplasias Pulmonares , Nitrosaminas , Humanos , Nitrosaminas/toxicidade , Brônquios/metabolismo , Brônquios/patologia , Brônquios/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para Baixo/efeitos dos fármacos , Carcinógenos/toxicidade
12.
Eur J Med Res ; 29(1): 406, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103884

RESUMO

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) is still challenging. We describe a novel method for sampling PPL without bronchial signs by creating invisible tunnel under electromagnetic navigation without the transbronchial access tool (TABT). METHODS: During electromagnetic navigation, we adjust the angle of the edge extended working channel catheter based on the real-time position of the lesion in relation to the locating guide rather than preset route. A biopsy brush or biopsy forceps is used to punch a hole in the bronchial wall. A locating guide is then re-inserted to real-time navigate through the lung parenchyma to the lesion. Safety and feasibility of this method was analyzed. RESULTS: A total of 32 patients who underwent electromagnetic navigation bronchoscopy were retrieved. The mean size of the lesion is 23.1 mm. The mean operative time of all patients was 12.4 min. Ten of the patients did not have a direct airway to the lesion, thus creating an invisible tunnel. For them, the length of the tunnel from the bronchial wall POE to the lesion was 11-30 mm, with a mean length of 16.9 mm and a mean operation time of 14.1 min. Adequate samples were obtained from 32 patients (100%), and the diagnostic yield was 87.5% (28/32). Diagnostic yield of with create the invisible tunnel TBAT was 90% (9/10), and one patient undergone pneumothorax after operation. CONCLUSIONS: This method is feasible and safe as a novel approach sampling pulmonary lesions without bronchial signs, and it further improves current tunnel technique.


Assuntos
Broncoscopia , Fenômenos Eletromagnéticos , Humanos , Broncoscopia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Brônquios/patologia , Brônquios/diagnóstico por imagem , Idoso de 80 Anos ou mais
13.
Am J Case Rep ; 25: e943957, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39126143

RESUMO

BACKGROUND Foreign body aspiration (FBA) is a common and serious problem in childhood that requires early recognition and treatment. Common complications include asphyxia, hemorrhage, infection, and pneumothorax. In severe cases of foreign body obstruction, death can result from asphyxia. We report an interesting case in which a forgotten cotton ball was inhaled into the lungs. CASE REPORT A 5-year-old boy presented to the local hospital with coughing for 6 days and fever for 4 days, without any information of foreign body aspiration upon admission. Laboratory findings indicated an elevated white blood cell; therefore, cefprozil was given as anti-infective treatment. However, the child's condition did not improve. A computed tomography scan showed left pulmonary atelectasis. Considering that the child's condition was serious, he was referred to our hospital for diagnosis and treatment. After referral, auscultation revealed decreased breath sounds over the left lung. After multidisciplinary discussion, combined with the results of auxiliary examination, the possibility of a foreign body was considered. He underwent rigid bronchoscopy, which confirmed a yellow-white foreign body in the left main bronchus that was later verified as a cotton ball. The operation was very successful. Eventually, his condition improved and he was discharged, without additional complications. CONCLUSIONS For children with unclear history of foreign body aspiration, bronchoscopy is recommended if there is recurrent pulmonary infection, low auscultation breath sounds, or abnormal imaging. The choice of surgical method depends on the location and type of foreign body and the experience of the surgeon, which is also very important.


Assuntos
Broncoscopia , Corpos Estranhos , Humanos , Masculino , Pré-Escolar , Corpos Estranhos/complicações , Aspiração Respiratória , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/diagnóstico por imagem , Fibra de Algodão , Tomografia Computadorizada por Raios X , Brônquios
14.
Kyobu Geka ; 77(8): 624-628, 2024 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-39205417

RESUMO

A 69-year-old man was diagnosed with an abnormal shadow on a chest X-ray during a routine check-up. Computed tomography (CT) showed a 36 mm solid nodule at left S1+2, and 3 dimentional (3D)-CT showed the left B1+2 branching from the left main bronchus. Bronchoscopy showed branching of B1+2, B3~5, and inferior lobar bronchus from the left main bronchus, and a biopsy from the peripheral area of B1+2 confirmed the diagnosis of lung adenocarcinoma. Subsequently, video-assisted thoracoscopic surgery was performed for the lung adenocarcinoma (cT2aN0M0, ⅠB). The dorsal pleura was incised and B1+2, which branches from the left main bronchus dorsal to the pulmonary artery, was identified. After dissecting B1+2, the fissure between the upper division and lower lobes was separated, followed by left upper lobectomy with ND2a-1. The preoperative understanding of the anatomical abnormalities obtained using 3D-CT allowed the surgery to be performed safely.


Assuntos
Brônquios , Neoplasias Pulmonares , Pneumonectomia , Humanos , Masculino , Idoso , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Brônquios/cirurgia , Brônquios/anormalidades , Brônquios/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adenocarcinoma/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem
15.
A A Pract ; 18(9): e01843, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39212333

RESUMO

An esophageal bronchus is a subtype of congenital bronchopulmonary foregut malformations in which a lobar bronchus arises directly from the esophagus, creating a communication between the esophagus and lung tissue. Early diagnosis is crucial to prevent worsening pulmonary sequelae but is challenging due to the rarity of the anomaly and nonspecific respiratory symptoms. We present a child whose esophageal bronchus was identified incidentally during preanesthetic assessment for craniosynostosis repair and discuss the role an anesthesiologist can play in identifying and managing this diagnosis.


Assuntos
Brônquios , Esôfago , Humanos , Brônquios/anormalidades , Esôfago/anormalidades , Esôfago/cirurgia , Lactente , Masculino , Craniossinostoses/cirurgia , Achados Incidentais
16.
Ecotoxicol Environ Saf ; 283: 116803, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39094460

RESUMO

Arsenic is a widespread carcinogen and an important etiological factor for lung cancer. Dysregulated miRNAs have been implicated in arsenic carcinogenesis and the mechanisms of arsenic-induced dysregulated miRNAs have not been fully elucidated. N6-methyladenosine (m6A) modification is known to modulate pri-miRNA processing. However, whether m6A-mediated pri-miRNA processing is involved in arsenic carcinogenesis is poorly understood. Here, we found that m6A modification was significantly increased in arsenite-transformed human bronchial epithelial BEAS-2B cells (0.5 µM arsenite, 16 weeks). Meanwhile, METTL3 was significantly upregulated at week 12 and 16 during cell transformation. The proliferation, migration, invasion, and anchorage-independent growth of arsenite-transformed cells were inhibited by the reduction of m6A levels through METTL3 knockdown. Further experiments suggest that the oncogene miR-106b-5p is a potentially essential m6A target mediating arsenic-induced lung cancer. miR-106b-5p was observed to be upregulated after exposure to arsenite for 12 and 16 weeks, and the reduction of m6A levels caused by METTL3 knockdown inhibited miR-106b-5p maturation in arsenite-transformed cells. What's more, miR-106b-5p overexpression successfully rescued METTL3 knockdown-induced inhibition of the neoplastic phenotypes of transformed cells. Additionally, Basonuclin 2 (BNC2) was uncovered as a potential target of miR-106b-5p and downregulated by METTL3 via enhancing miR-106b-5p maturation. Additionally, the METTL3 inhibitor STM2457 suppressed neoplastic phenotypes of arsenite-transformed BEAS-2B cells by blocking pri-miR-106b methylation. These results demonstrate that m6A modification promotes the neoplastic phenotypes of arsenite-transformed BEAS-2B cells through METTL3/miR-106b-5p/BNC2 pathway, providing a new prospective for understanding arsenic carcinogenesis.


Assuntos
Adenosina , Brônquios , Células Epiteliais , Metiltransferases , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Adenosina/análogos & derivados , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Metiltransferases/genética , Metiltransferases/metabolismo , Brônquios/efeitos dos fármacos , Brônquios/patologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Arsênio/toxicidade , Arsenitos/toxicidade , Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linhagem Celular , Fenótipo
17.
BMC Anesthesiol ; 24(1): 275, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103765

RESUMO

BACKGROUND: Double-lumen tubes (DLTs) and bronchial blockers (BBs) can be used to establish one-lung ventilation (OLV) for thoracic surgery. BBs are a good alternative when DLTs are not suitable or patients have difficult airways. However, BBs are more prone to malposition, leading to adverse events. CASE PRESENTATION: We present a 68-year-old male patient who was scheduled for thoracoscopic left lower lobectomy. The patient was not expected to have airway malformation preoperatively. When the DLT could not be inserted into the bronchus after general anesthesia induction, we used a BB to perform OLV. During surgery, malposition of the BB resulted in the development of an "incomplete balloon valve", leading to a cardiopulmonary crisis. CONCLUSIONS: Previewing chest computed tomography scans to assess the airway anatomy before thoracic surgery is essential. Three-dimensional reconstruction of the airway can provide a more intuitive assessment of airway anatomy. During OLV with BBs, we should pay attention to balloon malposition to prevent cardiopulmonary crises.


Assuntos
Intubação Intratraqueal , Ventilação Monopulmonar , Humanos , Masculino , Idoso , Ventilação Monopulmonar/métodos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Traqueia/diagnóstico por imagem , Traqueia/anormalidades , Brônquios/anormalidades , Brônquios/diagnóstico por imagem , Tomografia Computadorizada por Raios X
18.
Environ Int ; 191: 108978, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39197372

RESUMO

The shape of environmental aerosols contributes to the discrepancy in their dynamic behavior compared to spherical particles, which have received inadequate consideration. We reported deposition patterns of aerosols and aerosol-transmissible pathogens in real human respiratory systems, taking into account their actual shape, using a validated computational-based model. We found that the shape of the aerosols significantly influenced its deposits and accessibility within the respiratory system, significantly in the tracheobronchial region. As an example, we estimated that over 180 % of differences in deposits in the trachea and bronchi were attributable to pathogens shape, inferring the underlying pathogenicity difference of these regions. These findings, capturing the spatial heterogeneity of pathogens and aerosols deposition in human respiratory system, have major implication for understanding the evolution of aerosol-related disease.


Assuntos
Aerossóis , Humanos , Sistema Respiratório/microbiologia , Traqueia/microbiologia , Brônquios/microbiologia , Brônquios/patologia , Microbiologia do Ar
19.
BMC Pulm Med ; 24(1): 426, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210325

RESUMO

BACKGROUND: Lung cancer is the most common cause of cancer death worldwide and poses an immediate health threat. Despite decades of basic and clinical research, the 5-year survival rate for lung cancer patients is less than 10%.The most important drawbacks in efficient treatment of lung cancer are delayed diagnosis and absence of effective screening. Detection and study of precancerous lesions of the bronchial mucosa might be one of the turning points in understanding of neoplastic transformation. Therefore, it would be the most effective prevention and early treatment modality. We report a case of high-grade intraepithelial neoplasia of the bronchial mucosa in which a neoplastic growth in the lumen of intrinsic segment in the upper lobe of the left lung was detected on electronic bronchoscopy, and biopsy confirmed squamous papillary hyperplasia with high-grade intraepithelial neoplasia. CASE PRESENTATION: A 74-year-old male was admitted to the hospital due to a mass lesion in his left lung. After admission, computed tomography scan of the chest showed an intraluminal mass in the intrinsic segment of the upper lobe of the left lung and an enlarged left hilum. CONCLUSIONS: High-grade intraepithelial neoplasia of the bronchial mucosa is rare in the respiratory system. We report a case that can provide useful information for early diagnosis and treatment of the disease.


Assuntos
Broncoscopia , Carcinoma in Situ , Tomografia Computadorizada por Raios X , Idoso , Humanos , Masculino , Biópsia , Brônquios/patologia , Brônquios/diagnóstico por imagem , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Mucosa Respiratória/patologia , Carcinoma Broncogênico/diagnóstico , Carcinoma Broncogênico/patologia
20.
Biomolecules ; 14(8)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39199417

RESUMO

Extracellular vesicles (EVs) play a pivotal role in a variety of physiologically relevant processes, including lung inflammation. Recent attention has been directed toward EV-derived microRNAs (miRNAs), such as miR-191-5p, particularly in the context of inflammation. Here, we investigated the impact of miR-191-5p-enriched EVs on the activation of NF-κB and the expression of molecules associated with inflammation such as interleukin-8 (IL-8). To this aim, cells of bronchial epithelial origin, 16HBE, were transfected with miR-191-5p mimic and inhibitor and subsequently subjected to stimulations to generate EVs. Then, bronchial epithelial cells were exposed to the obtained EVs to evaluate the activation of NF-κB and IL-8 levels. Additionally, we conducted a preliminary investigation to analyze the expression profiles of miR-191-5p in EVs isolated from the plasma of patients diagnosed with chronic obstructive pulmonary disease (COPD). Our initial findings revealed two significant observations. First, the exposure of bronchial epithelial cells to miR-191-5p-enriched EVs activated the NF-kB signaling and increased the synthesis of IL-8. Second, we discovered the presence of miR-191-5p in peripheral blood-derived EVs from COPD patients and noted a correlation between miR-191-5p levels and inflammatory and functional parameters. Collectively, these data corroborate and further expand the proinflammatory role of EVs, with a specific emphasis on miR-191-5p as a key cargo involved in this process. Consequently, we propose a model in which miR-191-5p, carried by EVs, plays a role in airway inflammation and may contribute to the pathogenesis of COPD.


Assuntos
Vesículas Extracelulares , Interleucina-8 , MicroRNAs , NF-kappa B , Doença Pulmonar Obstrutiva Crônica , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Interleucina-8/metabolismo , Interleucina-8/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , NF-kappa B/metabolismo , Inflamação/metabolismo , Inflamação/genética , Células Epiteliais/metabolismo , Linhagem Celular , Transdução de Sinais , Masculino , Feminino , Brônquios/metabolismo , Brônquios/patologia , Pessoa de Meia-Idade , Idoso
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA