RESUMEN
BACKGROUND: Pathology is considered the gold standard for the diagnosis of lung lesions, but the pathological result is relatively lagging and cannot provide real-time guidance for the biopsy procedure. OBJECTIVE: To investigate the potential application of rapid on-site evaluation (ROSE) during flexible bronchoscopy (FB) in the evaluation and diagnosis of lung lesions. PATIENTS AND METHODS: Consecutive patients who underwent FB for the diagnosis of lung lesions between August 2022 and February 2023 were included in this retrospective study. 294 patients underwent FB with ROSE, while 304 patients underwent FB without ROSE. The final pathological results and the number of patients undergoing repeat biopsies were recorded in both groups. Specifically, we conducted separate statistical analysis for patients undergoing different biopsy methods, including the endobronchial biopsy (EBB), radial probe endobronchial ultrasound transbronchial lung biopsy with guide sheath (r-EBUS-GS-TBLB), and the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to study the detailed roles that ROSE plays under different biopsy methods. RESULTS: The adequacy rate of biopsy specimens from the non-ROSE group was significantly lower than that of the ROSE group (259/281 = 92.17 % vs. 263/268 = 98.13 %, p = 0.001). Meanwhile, fewer patients underwent repeat biopsies in the ROSE group compared to the non-ROSE group (2/294 = 0.68 % vs. 10/304 = 3.29 %, p = 0.023). For the ROSE group, the consistency between ROSE diagnoses and final pathological diagnoses was 94.40 % (κ = 0.886), with 95.58 % for benign diseases and 93.55 % for malignant diseases. CONCLUSION: The utility of ROSE during FB increases the adequacy rate of biopsy specimens and thus decreases the need for repeat biopsies in patients with lung lesions to get a definite diagnosis. Moreover, the high consistency between ROSE diagnoses and final pathological diagnoses suggests that ROSE is a reliable tool for optimizing the diagnosis of lung lesions.
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Broncoscopía , Neoplasias Pulmonares , Humanos , Broncoscopía/métodos , Evaluación in Situ Rápida , Estudios Retrospectivos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologíaRESUMEN
Epidemiological studies suggested that PM2.5 (particle matters with an aerodynamic diameter ≤2.5 µm) exposure is associated with atherosclerosis. Extracellular vesicles (EVs) are messengers between intracellular communications which are important in diseases procession. At present, whether EVs derived from PM2.5-exposed alveolar epithelial cells (P-EVs) involve in atherosclerosis has not been clearly understood. This study is performed to investigate the effects of P-EVs on the development of endothelium adhesion and atherosclerosis. Here, ApoE-/- mice were randomized into different groups receiving one of the following treatments, filtered air (FA), PM2.5, PBS, PBS-treated alveolar epithelial cells-derived EVs (EVs), or P-EVs. Then the atherosclerosis level in aortas or aorta sections was evaluated by oil red O staining. The results indicated that ApoE-/- mice treated with P-EVs or PM2.5 showed more obvious atherosclerosis plaques in aortas and aortic arches than those treated with EVs or PBS. Endothelial cells (ECs) were treated with PBS, EVs, P-EVs, or PM2.5. The adhesion property, miRNAs level and expressions of IκBα, phosphorylated IκBα, NF-κB p65, phosphorylated NF-κB p65, and VCAM1 in ECs were determined. It was found that P-EVs activated IκBα-NF-κB-VCAM1 signaling and increased adhesion of ECs, and such effects could be reversed by adalimumab (the TNF-α inhibitor) or miR-326-3p inhibitor. Further study suggested that P-EVs induced upregulation of TNF-α and miR-326-3p in recipient ECs and contributed to the phosphorylation of NF-κB p65. Collectively, EVs derived from PM2.5-exposed alveolar epithelial cells played an important role in the development of atherosclerosis via activating IκBα-NF-κB-VCAM1 signaling.
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Células Epiteliales Alveolares/patología , Apolipoproteínas E/metabolismo , Aterosclerosis/patología , Adhesión Celular/efectos de los fármacos , Endotelio/patología , Vesículas Extracelulares/patología , Material Particulado/efectos adversos , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/metabolismo , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/fisiología , Aterosclerosis/metabolismo , Endotelio/efectos de los fármacos , Endotelio/metabolismo , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/metabolismo , Ratones , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Environmental pollution, especially particulate matter in the air, is a serious threat to human health. Long-term inhalation of particulate matter with a diameter < 2.5 µm (PM2.5) induced irreversible respiratory and lung injury. However, it is not clear whether temporary exposure to massive PM2.5 would result in epithelial damage and lung injury. More importantly, it is urgent to clarify the mechanisms of PM2.5 cytotoxicity and develop a defensive and therapeutic approach. In this study, we demonstrated that temporary exposure with PM2.5 induced lung epithelial cell apoptosis via promoting cytokines expression and inflammatory factors secretion. The cytotoxicity of PM2.5 could be alleviated by tussilagone (TSL), which is a natural compound isolated from the flower buds of Tussilago farfara. The mechanism study indicated that PM2.5 promoted the protein level of Hif-1α by reducing its degradation mediated by PHD2 binding, which furtherly activated NF-κB signaling and inflammatory response. Meanwhile, TSL administration facilitated the interaction of the Hif-1α/PHD2 complex and restored the Hif-1α protein level increased by PM2.5. When PHD2 was inhibited in epithelial cells, the protective function of TSL on PM2.5 cytotoxicity was attenuated and the expression of cytokines was retrieved. Expectedly, the in vivo study also suggested that temporary PM2.5 exposure led to acute lung injury. TSL treatment could effectively relieve the damage and decrease the expression of inflammatory cytokines by repressing Hif-1α level and NF-κB activation. Our findings provide a new therapeutic strategy for air pollution-related respiratory diseases, and TSL would be a potential preventive medicine for PM2.5 cytotoxicity.
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Lesión Pulmonar Aguda , Lesión Pulmonar , Sesquiterpenos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/prevención & control , Humanos , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/prevención & control , FN-kappa B/metabolismo , Material Particulado/toxicidadRESUMEN
AIM OF THE STUDY: Acute lung injury (ALI) exhibits the features of noncardiogenic pulmonary edema and acute inflammatory process, and it also displays significant morbidity and mortality rates. This work focused on identifying how overexpression of PPARγ coactivator 1α (PGC-1α) positively regulated TFEB and mitophagy for resisting the lipopolysaccharide (LPS)-mediated ALI. MATERIALS AND METHODS: The levels of autophagic proteins and inflammatory factors in LPS-induced ALI rats and primary type II alveolar epithelial cells were measured, respectively. Lung wet/dry ratios were calculated. Protein co-immunoprecipitation of PGC-1α and TFEB was detected. To explore the interaction between TFEB and PGC-1α, a luciferase reporter assay was conducted. RESULTS: The results showed that overexpression of PGC-1α decreases IL-1 and IL-6 but increases IL-10 in LPS-mediated ALI rats and type II alveolar epithelial cells (P < 0.05). Overexpression of PGC-1α can reduce lung edema in LPS-mediated ALI rats (P < 0.05). Overexpression of PGC-1α upregulates mitophagy-related proteins, such as TFEB, LC3B, Beclin, and LAMP1, and improves mitophagy in LPS-induced ALI. Protein immunoprecipitation indicated that TFEB and PGC-1α are interacting proteins. The luciferase reporter assay demonstrated that PGC-1α positively regulated TFEB in the LPS-induced primary type II alveolar epithelial cells. CONCLUSION: PGC-1α protects LPS-induced ALI by decreasing inflammation and alleviating lung edema. The mechanism might be positive regulation of TFEB directly and then upregulation of mitophagy in LPS-induced ALI.
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Lesión Pulmonar Aguda/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Pulmón/metabolismo , Mitofagia , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Células Epiteliales Alveolares/metabolismo , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos , Pulmón/patología , Masculino , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Unión Proteica , Interferencia de ARN , Ratas Sprague-DawleyRESUMEN
BACKGROUND Exposure to PM2.5 (fine particulate matter ≤2.5 µm in aerodynamic diameter) in air increases the risk of lung injury and pulmonary fibrosis (PF). Extracellular vesicles (EVs) derived from adipose mesenchymal stem cells (ADSCs) have been identified as a potential treatment based on the proteins or RNAs delivery and immunomodulatory properties. Here, we assessed the protective effects and mechanisms of ADSCs-EVs on PM2.5-induced lung injury or PF. MATERIAL AND METHODS Rats (male, 6 weeks old) were exposed to PBS or PM2.5 (1.5 mg/kg/day) for 3 days a week for 4 weeks. ADSCs-EVs were extracted by ultracentrifugation. PBS and ADSCs-EVs were administrated through intratracheal instillation. After the end of exposure, the rats were anesthetized and killed. Lung tissues with different treatments were collected for Western blot analysis and HE, IHC, and IF staining analysis. Cells exposed to PM2.5 or "PM2.5+ADSCs-EVs" in vitro were also collected for further Western blotting, qRT-PCR, and IF staining evaluation. RESULTS The results indicated that the initial response of lungs exposed to PM2.5 was lung injury with oxidative stress and inflammation. Long-term PM2.5 exposure resulted in obvious PF in rats. Treatment with ADSCs-EVs decreased PM2.5-induced apoptosis and necrosis in type II alveolar epithelial cells and alleviated lung injury and PF in rats. ADSCs-EVs suppressed reactive oxygen species (ROS) levels and inflammation induced by PM2.5. Furthermore, ADSCs-EVs inhibited TGF-ßRI by transferring let-7d-5p and further mitigated PF. CONCLUSIONS Our results suggest that EVs derived from ADSCs can alleviate PM2.5-induced lung injury and PF.
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Vesículas Extracelulares/metabolismo , Lesión Pulmonar/terapia , Células Madre Mesenquimatosas/fisiología , Tejido Adiposo/metabolismo , Animales , Citocinas/metabolismo , Inflamación/metabolismo , Pulmón/metabolismo , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Estrés Oxidativo , Tamaño de la Partícula , Material Particulado/efectos adversos , Fibrosis Pulmonar/terapia , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Massive hemoptysis is one of emergency and critical diseases of the respiratory system. The definition of massive hemoptysis has always been different in the literature, which often depends on the quantitative estimation of the amount of hemoptysis, such as the amount of hemoptysis being in the range of 300-600 mL within 24 h, or hemoptysis more than 3 times within 1 week. Each amount of hemoptysis that is greater than 100 mL can be considered as massive hemoptysis, but the amount of hemoptysis is difficult to accurately estimate. Therefore, massive hemoptysis can be defined as any life-threatening hemoptysis and any hemoptysis that may cause airway obstruction and asphyxia. Massive hemoptysis accounts for approximately 5% of all hemoptysis cases and usually indicates the presence of a potentially severe respiratory or systemic disease. The mortality rate of massive hemoptysis is about 6.5-38%. The cause of death is generally shock caused by airway obstruction or excessive bleeding, and asphyxia is the main cause of death. At present, due to insufficient understanding of massive hemoptysis, there are limited technical means in the etiological diagnosis and untimely or improper treatment, resulting in high mortality of massive hemoptysis. Therefore, the diagnosis and treatment of massive hemoptysis needs to be standardized.
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Hemoptisis/diagnóstico , Hemoptisis/terapia , Guías de Práctica Clínica como Asunto , Manejo de la Vía Aérea , Obstrucción de las Vías Aéreas , Asfixia , Enfermedades Autoinmunes/complicaciones , Trastornos de la Coagulación Sanguínea/complicaciones , Bronquiectasia/complicaciones , Broncoscopía , Enfermedades Cardiovasculares/complicaciones , China , Hemoptisis/etiología , Hemostasis Endoscópica , Humanos , Enfermedad Iatrogénica , Enfermedades Pulmonares Fúngicas/complicaciones , Neoplasias Pulmonares/complicaciones , Embolia Pulmonar/complicaciones , Infecciones del Sistema Respiratorio/complicaciones , Índice de Severidad de la Enfermedad , Vasculitis Sistémica/complicaciones , Tomografía Computarizada por Rayos X , Tuberculosis Pulmonar/complicacionesRESUMEN
RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.
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Ventilación no Invasiva/efectos adversos , Síndrome de Dificultad Respiratoria/complicaciones , Lesión Pulmonar Inducida por Ventilación Mecánica/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ventilación no Invasiva/métodos , Proyectos Piloto , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Lesión Pulmonar Inducida por Ventilación Mecánica/terapiaRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a leading cause of morbidity and mortality in China, with tobacco smoke, air pollution, and occupational biohazards being the major risk factors. OBJECTIVES: The REACH trial is a multicenter, prospective, randomized controlled trial undertaken in China to assess the safety and effectiveness of the Spiration® Valve System (SVS) compared to standard medical care in COPD patients with severe emphysema. METHODS: Patients with severe airflow obstruction, hyperinflation, and severe dyspnea with interlobar fissure integrity were evaluated for enrollment. A total of 107 subjects were randomized in a 2: 1 allocation ratio to either the treatment group (SVS valves and medical management) or the control group (medical management alone). RESULTS: The 3-month primary endpoint showed statistically significant improvement in forced expiratory volume in 1 s in the treatment group compared to the control group (0.104 ± 0.18 vs. 0.003 ± 0.15 L, p = 0.001), with the difference being durable through 6 months. Statistically significant target lobe volume reduction was achieved at 3 months (mean change 684.4 ± 686.7 mL) and through 6 months (757.0 ± 665.3 mL). Exercise function and quality of life measures improved in the treatment group, but showed a deterioration in the control group. The serious adverse event (SAE) rate was 33% in the treatment group and 24.2% in the control group. The predominance of SAEs were acute exacerbations of COPD in both groups. There was 1 death in the control group and no deaths in the treatment group. CONCLUSION: The SVS represents a novel approach for the treatment of severe emphysema with a clinically acceptable risk-benefit profile.
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Broncoscopía/métodos , Disnea , Neumonectomía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfisema Pulmonar , Calidad de Vida , Progresión de la Enfermedad , Disnea/etiología , Disnea/psicología , Tolerancia al Ejercicio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonectomía/efectos adversos , Neumonectomía/instrumentación , Neumonectomía/métodos , Diseño de Prótesis , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/prevención & control , Enfisema Pulmonar/terapia , Pruebas de Función Respiratoria/métodos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Optimal management of persistent air leaks (PALs) in patients with secondary spontaneous pneumothorax (SSP) remains controversial. OBJECTIVE: To evaluate the efficacy and safety of endobronchial autologous blood plus thrombin patch (ABP) and bronchial occlusion using silicone spigots (BOS) in patients with SSP accompanied by alveolar-pleural fistula (APF) and PALs. METHODS: This prospective multicentre randomized controlled trial compared chest tube-attached water-seal drainage (CTD), ABP, and BOS that were performed between February 2015 and June 2017 in one of six tertiary care hospitals in China. Patients diagnosed with APF experiencing PALs (despite 7 days of CTD) and inoperable patients were included. Outcome measures included success rate of pneumothorax resolution at the end of the observation period (further 14 days), duration of air leak stop, lung expansion, hospital stay, and complications. RESULTS: In total, 150 subjects were analysed in three groups (CTD, ABP, BOS) of 50 each. At 14 days, 60, 82, and 84% of CTD, ABP, and BOS subjects, respectively, experienced full resolution of pneumothorax (p = 0.008). All duration outcome measures were significantly better in the ABP and BOS groups than in the CTD group (p < 0.016 for all). The incidence of adverse events, including chest pain, cough, and fever, was not significantly different. All subjects in the ABP and BOS groups experienced temporary haemoptysis. Spigot displacement occurred in 8% of BOS subjects. CONCLUSION: ABP and BOS resulted in clinically meaningful outcomes, including higher success rate, duration of air leak stop, lung expansion, and hospital stay, with an acceptable safety profile.
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Broncoscopía/métodos , Neumotórax , Complicaciones Posoperatorias , Fístula del Sistema Respiratorio , Toracocentesis , Anciano , Bioprótesis , Tubos Torácicos/efectos adversos , Drenaje/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Pleurales/complicaciones , Neumotórax/diagnóstico , Neumotórax/etiología , Neumotórax/fisiopatología , Neumotórax/terapia , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Fístula del Sistema Respiratorio/etiología , Fístula del Sistema Respiratorio/terapia , Toracocentesis/efectos adversos , Toracocentesis/instrumentación , Toracocentesis/métodos , Resultado del TratamientoRESUMEN
Malignant central airway stenosis refers to airway stenosis caused by primary or metastatic malignant tumors which may lead to different levels of dyspnea or asphyxia in patients. With the rapid development of interventional pulmonology, therapeutic bronchoscopy has become one of the main methods for the diagnosis and treatment of malignant central airway stenosis. However, the level of diagnosis and treatment of respiratory intervention techniques in China is uneven at present, the treatment methods are not uniform, the treatment effects vary greatly, and some treatments even lead to serious complications. The interventional treatment technology for malignant central airway stenosis in China needs to be standardized. Therefore, the relevant experts of the Beijing Health Promotion Association Respiratory and Oncology Intervention and Treatment Alliance have formulated this consensus after several rounds of full discussion.
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Técnicas de Ablación , Obstrucción de las Vías Aéreas , Broncoscopía , Disección , Neoplasias Pulmonares , Técnicas de Ablación/instrumentación , Técnicas de Ablación/métodos , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/terapia , Broncoscopía/instrumentación , Broncoscopía/métodos , China , Dilatación/instrumentación , Dilatación/métodos , Disección/instrumentación , Disección/métodos , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Índice de Severidad de la Enfermedad , Stents/clasificación , Tiempo de TratamientoRESUMEN
BACKGROUND: Female genital tuberculosis (FGTB) is one of the major causes of infertility. However, nonspecific manifestations and the lack of easy access to gold-standard diagnostic test render a diagnostic difficult for FGTB. The objective of this study was to determine T-SPOT.TB (an interferon-γ release assay, IGRA) performance in patients with FGTB. METHODS: A total of 213 female patients with validated T-SPOT.TB results were recruited in this retrospective study. Among which, 103 were confirmed FGTB, and 110 were excluded from tuberculosis (control). Of the confirmed FGTB patients, 52 were confirmed by microbiologically/histopathologically examination, while the remaining 51 were clinically confirmed (successfully responsive to anti-tuberculosis treatment). T-SPOT.TB test was performed in both FGTB and control group during the diagnostic procedure. RESULTS: The overall sensitivity and specificity of T-SPOT.TB were 86.41% and 75.45% respectively. Sensitivity of T-SPOT.TB was significantly higher when compared with conventional tuberculosis diagnostic tests. Moreover, T-SPOT.TB test using pelvic effusion (PE) showed higher sensitivity than using corresponding peripheral blood (PB) (94.44% vs 72.22%, P < 0.001). Mean value of spot forming cells (SFCs) of T-SPOT.TB using PE was significantly higher than that of PB in FGTB group (193 (IQR 105-280) SFCs/2.5 × 105 PEMCs vs 71 (IQR 36-107) SFCs/2.5 × 105 PBMCs, P = 0.01), while this was not detected in control group (11 (IQR 0-22) SFCs/2.5 × 105 PEMCs vs 9 (IQR 0-18) SFCs/2.5 × 105 PBMCs, P = 0.77). CONCLUSION: These results demonstrated that T-SPOT.TB, especially PE T-SPOT.TB, is an useful adjunct in FGTB diagnosis.
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Ensayos de Liberación de Interferón gamma/métodos , Ensayos de Liberación de Interferón gamma/normas , Tuberculosis de los Genitales Femeninos/diagnóstico , Adulto , China , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
A fundamental element of acute lung injury (ALI) is the inflammatory response, which can affect the entire respiratory system, including the respiratory tract and alveoli. Berberine has gained attention because of its anti-inflammatory effects. Nuclear factor-erythroid 2-related factor 2 (Nrf2) and endoplasmic reticulum (ER) stress are involved in lung injury. Nrf2 also acts as a protein kinase-like ER kinase (PERK) substrate in heart disease. Therefore, this study investigated the effect of berberine against lipopolysaccharide (LPS)-induced ALI and the role of the PERK-mediated Nrf2/HO-1 signaling axis. Berberine promoted Nrf2 nuclear translocation and phosphorylation in vitro. After LPS stimulation, this effect was further enhanced, whereas inflammatory factor (IL-6 and IL-8) release and reactive oxygen species generation were significantly decreased. Berberine effectively alleviated lung injury by reducing lung edema and neutrophil infiltration. Berberine also significantly reduced histopathological inflammatory changes via inhibition of ER stress and activation of Nrf2 signaling. Thapsigargin-induced ER stress and small interference RNA (siRNA)-mediated Nrf2 inhibition abrogated the protective effects of berberine in vitro, whereas siRNA-mediated suppression of ER stress and sulforaphane-induced Nrf2 activation further improved those effects. Importantly, ER stress induction led to Nrf2 activation, whereas PERK depletion partly reduced the level of Nrf2 phosphorylation and translocation in LPS-induced cells. Therefore, berberine inhibits LPS-induced ALI through the PERK-mediated Nrf2/HO-1 signaling axis.
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Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Berberina/uso terapéutico , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Berberina/farmacología , Humanos , Lipopolisacáridos , Masculino , Transducción de SeñalRESUMEN
Previous studies have shown that apoptosis of alveolar cells can be regulated by autocrine of angiotensin (ANG)II and its counter regulatory ACE-2/ANG1-7 axis. Our earlier study has shown that endoplasmic reticulum (ER) stress in response to seawater aspiration eventually led to apoptosis in lung tissue. In this study, we examined the hypothesis that ER stress-induced apoptosis in seawater aspiration-induced acute lung injury (ALI) might also be regulated by the ANGII/ANG1-7 system. ER stress was induced by seawater stimulation and proteasome inhibitor MG132 (an ER stress inductor). Moreover, ER stress in seawater-stimulated lung tissues and rat pulmonary microvascular endothelial cells (RPMVECs) promoted ANGII expression and decreased ACE-2/ANG1-7 expression. ER stress induced by seawater stimulation also led to apoptosis. Apoptosis induced by seawater stimulation and MG132 were inhibited by ANGII receptor blocker and abrogated by the addition of ANG1-7. These results suggest that apoptosis induced by ER stress in seawater aspiration-induced ALI is regulated by ANG II/ANG1-7 in lung tissues and RPMVECs. In addition, the active form of X-box binding protein 1 (XBP1), spliced XBP1 (XBP1s), a transcription factor that regulates ER-associated degradation genes during ER stress was significantly activated in seawater stimulated cells. Based on this phenomenon we designed a tandem gene, Wfs1 promoter (a target gene promoter of XBP1s)- ACE2 and ANG1-7 and transfected this tandem gene into seawater-stimulated cells. ACE-2/ANG1-7 expression were significantly promoted and apoptosis was inhibited in cells transfected with the tandem gene. These results suggest that stimulation of ACE-2/ANG1-7 may be a therapeutic target of ER stress-induced apoptosis in seawater aspiration-induced ALI.
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Lesión Pulmonar Aguda/metabolismo , Angiotensina I/metabolismo , Apoptosis/fisiología , Estrés del Retículo Endoplásmico/fisiología , Pulmón/metabolismo , Fragmentos de Péptidos/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Células Epiteliales Alveolares/metabolismo , Enzima Convertidora de Angiotensina 2 , Animales , Células Cultivadas , Células Endoteliales/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratas , Ratas Sprague-Dawley , Agua de Mar , Proteína 1 de Unión a la X-Box/metabolismoRESUMEN
The cell cycle-related and expression-elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non-small-cell lung cancer (NSCLC) remains unclear. In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western blot analysis, and RT-PCR. The correlation between CREPT expression and clinicopathologic features was analyzed in 271 NSCLC patients. The prognostic value of CREPT expression was evaluated by Kaplan-Meier analysis and Cox regression analysis. CREPT was overexpressed in Calu-1 cell lines by using plasmid vector and its biological function was explored both in vitro and in vivo. We found that CREPT was significantly overexpressed in NSCLC compared with paired adjacent non-tumor tissues, and the expression level of CREPT was correlated with tumor differentiation, lymph node metastasis, and clinical stage. Kaplan-Meier analysis showed that the recurrence-free survival and overall survival of high CREPT expression groups were significantly shorter than those of the low CREPT expression group. Multivariate analysis identified that CREPT might be an independent biomarker for the prediction of NSCLC prognosis. Overexpression of CREPT increased cell proliferation and enhanced the migration and invasion ability of Calu-1 cells (a human NSCLC cell line with relative low CRPET expression) in vitro. Moreover, CREPT overexpression promoted tumor growth in a nude mice model. These results suggest that CREPT is closely relevant to the proliferation of NSCLC cells and it might be a potential prognostic marker in NSCLC patients.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiología , Proliferación Celular/fisiología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/metabolismo , Células A549 , Animales , Biomarcadores de Tumor/metabolismo , Diferenciación Celular/fisiología , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Electrocautery needle knives can largely reduce scar and granulation tissue hyperplasia and play an important role in treating patients with benign stricture. OBJECTIVE: The aim of this retrospective study was to evaluate the efficacy and safety of electrocautery needle knife combined with balloon dilatation versus balloon dilatation alone in the treatment of tracheal stenosis caused by tracheal intubation or tracheotomy. METHODS: We retrospectively analysed the clinical data of 43 patients with tracheal stenosis caused by tracheotomy or tracheal intubation in our department from January 2013 to January 2016. Among these 43 patients, 23 had simple web-like stenosis and 20 had complex steno sis. All patients were treated under general anaesthesia, and the treatment methods were (1) balloon dilatation alone, (2) needle knife excision of fibrotic tissue combined with balloon dilatation, and (3) needle knife radial incision of fibrotic tissue combined with balloon dilatation. RESULTS: After treatment the symptoms, such as shortness of breath, were markedly improved immediately in all cases. The stenosis degree of patients who were treated with the elec-trocautery needle knife combined with balloon dilatation had better improvement compared with that of those treated with balloon dilatation treatment alone after 3 months (0.45 ± 0.04 vs. 0.67 ± 0.05, p < 0.01), and the proportion of restenosis occurrence that required further treatment was decreased at 6 months (46.9 vs. 81.8%), especially for the web-like stenosis patients, as most of their stenoses dilated with no obvious restenosis and achieved clinical cure. CONCLUSION: Electrocautery needle knife combined with balloon dilatation is an effective and safe treatment for tracheal fibrotic stenosis compared with balloon dilatation alone.
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Electrocoagulación , Estenosis Traqueal/cirugía , Adulto , Cicatriz/complicaciones , Dilatación/métodos , Femenino , Fibrosis , Humanos , Intubación Intratraqueal/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estenosis Traqueal/etiología , Adulto JovenRESUMEN
Losartan is a selective antagonist of Angâ type (AT1) receptor of Angiotensin â ¡ (Ang â ¡), which is widely used as a clinical medicine for the hypertension. Recent studies have shown that losartan was shown to protect from acute lung injury (ALI). However, the underlying mechanism remains unclear. The aim of this research was to clarify whether Ang â ¡ participated in the inflammatory response of ALI induced by seawater inhalation, and whether losartan had the protective effects on ALI by blocking the combination of Ang â ¡ and AT1 receptor. In the current study, the severity of lung injury and the inflammatory reactions during seawater drowning induced ALI were assessed. Besides, we also detected the activation of relative pathways such as NF-κB, JAK2/STATs and apoptosis. The results showed that seawater inhalation could up-regulate the expression of Ang â ¡ and AT1. While pretreatment of losartan (especially 15 mg/kg and 30 mg/kg) alleviated lung injury by inhibiting Ang-â ¡ and AT1 receptor combination and in turn decreased the expression of p-NF-κB and activation of JAK2/STATs pathway. We also confirmed that losartan could reduce the apoptotic ratio of cells in the lung by modulating the phosphorylation of JNK and leak of cytochrome C to cytosol. Taken together, these findings demonstrate that losartan might have a therapeutic potential as an anti-inflammatory agent for treating SWI-ALI.
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Lesión Pulmonar Aguda/prevención & control , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Apoptosis/efectos de los fármacos , Losartán/farmacología , Lesión Pulmonar Aguda/etiología , Animales , Antiinflamatorios/farmacología , Citocromos c/metabolismo , Janus Quinasa 2/metabolismo , Masculino , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores de Transcripción STAT/metabolismo , Agua de Mar/efectos adversosRESUMEN
Heat-labile enterotoxin (LT), the major virulence factor of enterotoxigenic Escherichia coli (ETEC), can lead to severe diarrhea and promotes ETEC adherence to intestinal epithelial cells. Most previous in vitro studies focused on ETEC pathogenesis were conducted under aerobic conditions, which do not reflect the real situation of ETEC infection because the intestine is anoxic. In this study, the expression and secretion of LT under anaerobic or microaerobic conditions were determined; LT was not efficiently secreted into the supernatant under anaerobic or microaerobic conditions unless terminal electron acceptors (trimethylamine N-oxide dihydrate [TMAO] or nitrate) were available. Furthermore, we found that the restoration effects of TMAO and nitrate on LT secretion could be inhibited by amytal or ΔtorCAD and ΔnarG E. coli strains, indicating that LT secretion under anaerobic conditions was dependent on the integrity of the respiratory chain. At the same time, electron acceptors increase the ATP level of ETEC, but this increase was not the main reason for LT secretion. Subsequently, the relationship between the integrity of the respiratory chain and the function of the type II secretion system was determined. The GspD protein, the secretin of ETEC, was assembled under anaerobic conditions and was accompanied by LT secretion when TMAO or nitrate was added. Our data also demonstrated that TMAO and nitrate could not induce the GspD assembly and LT secretion in ΔtorCAD and ΔnarG strains, respectively. Moreover, GspD assembly under anaerobic conditions was assisted by the pilot protein YghG.
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Anaerobiosis/fisiología , Toxinas Bacterianas/metabolismo , Escherichia coli Enterotoxigénica/fisiología , Enterotoxinas/metabolismo , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/metabolismo , Oxidantes/fisiología , Porinas/metabolismo , Adenosina Trifosfato/metabolismo , Escherichia coli Enterotoxigénica/metabolismo , Escherichia coli Enterotoxigénica/patogenicidad , Infecciones por Escherichia coli/metabolismo , Calor , Humanos , Metilaminas/metabolismo , Nitratos/metabolismo , VirulenciaRESUMEN
BACKGROUND AND OBJECTIVE: Although massive bleeding is the most life-threatening complication caused by flexible bronchoscopy, data on flexible bronchoscopy-induced massive bleeding are scarce, and the associated clinical characteristics and prognostic factors are unknown. METHODS: This was a multicentre retrospective cohort study of all patients who underwent flexible bronchoscopy in 33 tertiary hospitals from January 2001 to June 2013. The clinical characteristics and outcomes were collected and analysed. RESULTS: A total of 194 patients with massive bleeding were identified among 520 343 patients who underwent flexible bronchoscopy. The average blood loss reached up to 378 mL. The overall incidence and mortality were 0.037% and 0.004%, respectively, and the overall fatality was 10.8%. The risk of massive bleeding induced by therapeutic bronchoscopies was significantly higher than that induced by diagnostic bronchoscopies (incidence: 0.059% vs 0.031%, P < 0.001; mortality: 0.012% vs 0.003%, P < 0.001; fatality: 20% vs 8.4%, P = 0.068). Multivariate analysis showed that age ≥65 years, tracheal bleeding, blood loss ≥500 mL and occurrence of shock were independent factors predicting poor outcome, while emergency surgery was an independent protective factor. Re-bleeding occurred in six patients, resulting in three deaths within a month. CONCLUSION: Flexible bronchoscopy-induced massive bleeding is rare but life-threatening. Age, bleeding location, bleeding volume, circulation condition and emergency surgery were independent prognostic factors.
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Pérdida de Sangre Quirúrgica , Broncoscopía/efectos adversos , Choque Hemorrágico , Adulto , Anciano , Pérdida de Sangre Quirúrgica/mortalidad , Pérdida de Sangre Quirúrgica/fisiopatología , Volumen Sanguíneo , Broncoscopía/métodos , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Choque Hemorrágico/etiología , Choque Hemorrágico/mortalidad , Choque Hemorrágico/cirugíaRESUMEN
The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy.
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Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Acuaporina 5/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Factores de Transcripción/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad NeoplásicaRESUMEN
Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH.