RESUMO
PURPOSE: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), compromises immune surveillance through the upregulation of programmed cell death-1 ligand (PD-L1). Tumor-released extracellular vesicles (EVs) have been reported to modulate immunosuppressive activities. We investigated whether or not EVs derived from intermittent hypoxic lung cancer cells can alter the expression of PD-L1 in macrophages. METHODS: The expression of PD-L1+monocytes from 40 patients with newly diagnosed non-small-cell lung cancer (NSCLC) and with (n=21) or without (n=19) OSA were detected. Plasma EVs isolated from NSCLC patients with moderate-severe OSA (n=4) and without OSA (n=4) were co-cultured with macrophages. A549 cells were exposed to normoxia or IH (48 cycles of 5 min of 1% O2 hypoxia, followed by 5 min of normoxia). EVs were isolated from cell supernatant and were co-cultured with macrophages differentiated from THP-1. PD-L1 and hypoxia-inducible factor-1 α (HIF-1α) expressions were measured by flow cytometry, immunofluorescence, and Western blot analysis. RESULTS: PD-L1+monocytes were elevated in NSCLC patients with OSA and increased with the severity of OSA and nocturnal desaturation. PD-L1+ macrophages were induced by EVs from NSCLC patients with OSA and positively correlated with HIF-1α expressions. EVs from IH-treated A549 can promote PD-L1 and HIF-1α expression in macrophages and the upregulation of PD-L1 expression was reversed by specific HIF-1α inhibitor. CONCLUSION: IH can enhance the function of EVs derived from lung cancer cells to aggravate immunosuppressive status in macrophages. HIF-1α may play an important role in this process.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Apneia Obstrutiva do Sono , Antígeno B7-H1/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Pulmonares/metabolismo , Macrófagos/metabolismoRESUMO
BACKGROUND: Most patients with comorbid sleep apnea (OSA), cardiovascular (CV) disease, and/or cerebrovascular (CeV) disease simultaneously take medications. Whether OSA and continuous positive airway pressure (CPAP) interact with CV/CeV medications remains unknown. This study aimed to determine the interaction among OSA, CPAP, and CV/CeV medications; the effects of medications on major adverse cardiac and cerebrovascular events, and survival in patients with comorbid OSA and CV/CeV. METHODS: This was a post hoc analysis of the data from one center of the Sleep Apnea Cardiovascular Endpoints Study. Participants (aged 45-75 years) with comorbid OSA and CV/CeV were randomized to receive usual care with or without CPAP from December 2008 to November 2013. The primary endpoint was death and the secondary endpoint was a composite of death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, and transient ischemic attack. RESULTS: In total, 131 patients were analyzed. Sixty-three were in the CPAP group and 68 were in the usual care group, 41 had good adherence to CPAP (65.1%), and the median follow-up time was 43.0 (35.0, 54.0) months. In Cox regression analysis, ACE inhibitors and nitrates were independent factors for decreased survival in patients with comorbid OSA and CV/CeV (chi-square = 22.932, P = 0.003; ACE inhibitors: OR 7.241, P = 0.048, 95% CI 1.016-51.628; nitrates: OR 18.012, P = 0.011, 95% CI 1.923-168.750). ACE inhibitors increased mortality and secondary endpoints in the CPAP group (chi-square = 4.134, P = 0.042) but not in patients with good CPAP adherence. Clopidogrel and nitrates decreased survival in usual care group (clopidogrel: chi-square = 5.312, P = 0.021; nitrates: chi-square = 6.417, P = 0.011), but not in CPAP group. CONCLUSIONS: OSA may predispose patients with CV/CeV and CV/CeV medications to a negative effect. CPAP treatment may neutralize the negative effects of OSA by relieving chronic intermittent hypoxia. Trial registration ClinicalTrials.gov (NCT00738179, first registration date: 20/08/2008).
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/mortalidade , Comorbidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nitratos/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Análise de SobrevidaRESUMO
BACKGROUND: Endobronchial electrocautery is a common and safe therapeutic endoscopic treatment for malignant airway obstruction. Cerebral arterial air embolism (CAAE) is a rare but potentially fatal complication of endobronchial electrocautery. CASE PRESENTATION: We present the first case of cerebral arterial air embolism after endobronchial electrocautery. A 56-year-old male with a pulmonary tumour in the right upper lobe received repeated endobronchial electrocautery. During the procedure, he experienced unresponsiveness, hypoxemia and bradycardia, and he developed tetraplegia. Brain computed tomography showed several cerebral arterial air emboli with low-density spots in the right frontal lobe. He received hyperbaric oxygen therapy with almost full recovery, except for residual left-sided weakness. CONCLUSIONS: General physicians should realize that CAAE may be a possible complication of endobronchial electrocautery. Several measures, including avoiding positive pressure, lowering ventilatory pressures if possible, avoiding advancing the bronchoscope to occlude the bronchus and using the non-contact technique, should be used to prevent this devastating complication.
Assuntos
Broncoscopia/efeitos adversos , Artérias Cerebrais/diagnóstico por imagem , Eletrocoagulação/efeitos adversos , Embolia Aérea/etiologia , Embolia Aérea/diagnóstico por imagem , Embolia Aérea/terapia , Humanos , Oxigenoterapia Hiperbárica , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: COVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission. METHODS: COVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson's χ2-test or Fisher's exact test, and continuous variables were analyzed using Student's t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method. RESULTS: A total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P < 0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P < 0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P = 0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P = 0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P < 0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P < 0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P < 0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973). CONCLUSIONS: A nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary.
Assuntos
COVID-19/epidemiologia , COVID-19/mortalidade , Cardiopatias/epidemiologia , Nomogramas , Pandemias , Admissão do Paciente , SARS-CoV-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/virologia , China/epidemiologia , Doença Crônica/epidemiologia , Comorbidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Small peripheral pulmonary nodules, which are usually deep-seated with no visual markers on the pleural surface, are often difficult to locate during surgery. At present, CT-guided percutaneous techniques are used to locate pulmonary nodules, but this method has many limitations. Thus, we aimed to evaluate the accuracy and feasibility of electromagnetic navigational bronchoscopy (ENB) with pleural dye to locate small peripheral pulmonary nodules before video-associated thoracic surgery (VATS). METHODS: The ENB localisation procedure was performed under general anaesthesia in an operating room. Once the locatable guide wire, covered with a sheath, reached the ideal location, it was withdrawn and 0.2-1.0 mL of methylene blue/indocyanine green was injected through the guide sheath. Thereafter, 20-60 mL of air was instilled to disperse the dye to the pleura near the nodules. VATS was then performed immediately. RESULTS: Study subjects included 25 patients with 28 nodules. The mean largest diameter of the pulmonary nodules was 11.8 mm (range, 6.0-24.0 mm), and the mean distance from the nearest pleural surface was 13.4 mm (range, 2.5-34.9 mm). After the ENB-guided localisation procedure was completed, the dye was visualised in 23 nodules (82.1%) using VATS. The average duration of the ENB-guided pleural dye marking procedure was 12.6 min (range, 4-30 min). The resection margins were negative in all malignant nodules. Complications unrelated to the ENB-guided localisation procedure occurred in two patients, including one case of haemorrhage and one case of slow intraoperative heart rate. CONCLUSION: ENB can be used to safely and accurately locate small peripheral pulmonary nodules and guide surgical resection. TRIAL REGISTRATION NUMBER: ChiCTR1900021963.
Assuntos
Broncoscopia , Magnetometria/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Cirurgia Torácica Vídeoassistida/métodos , Broncoscopia/instrumentação , Broncoscopia/métodos , Corantes/farmacologia , Precisão da Medição Dimensional , Campos Eletromagnéticos , Feminino , Humanos , Índigo Carmim/farmacologia , Masculino , Azul de Metileno/farmacologia , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/cirurgia , Cuidados Pré-Operatórios/métodos , Reprodutibilidade dos Testes , Nódulo Pulmonar Solitário/cirurgiaRESUMO
BACKGROUND: Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical fields, we attempt to integrate a well-trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images. MATERIALS AND METHODS: Open-source data sets and multicenter data sets have been used in this study. A three-dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results. RESULTS: The sensitivity and specificity of this well-trained model were found to be 84.4% (95% confidence interval [CI], 80.5%-88.3%) and 83.0% (95% CI, 79.5%-86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10-30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three-dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment. CONCLUSION: Under the companion diagnostics, the three-dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices. IMPLICATIONS FOR PRACTICE: The three-dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice.
Assuntos
Aprendizado Profundo , Neoplasias Pulmonares/diagnóstico , Redes Neurais de Computação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Algoritmos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
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.
Assuntos
Broncoscopia/métodos , Dispneia , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar , Qualidade de Vida , Progressão da Doença , Dispneia/etiologia , Dispneia/psicologia , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/instrumentação , Pneumonectomia/métodos , Desenho de Prótese , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/prevenção & controle , Enfisema Pulmonar/terapia , Testes de Função Respiratória/métodos , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000ï¼with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.
Assuntos
Biomarcadores Tumorais , Neoplasias Pulmonares , Derrame Pleural Maligno , Derrame Pleural , Proteômica , Humanos , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Proteômica/métodos , Feminino , Masculino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Derrame Pleural/metabolismo , Derrame Pleural/diagnóstico , Diagnóstico Diferencial , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Idoso , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/diagnósticoRESUMO
Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), which mostly occurs in the immunocompromised host. The clinical condition is critical, especially to those who develop bronchopleural fistula. This study aimed to assess the characteristics and the prognosis of aspergillus pleurisy. Clinical data from 13 patients diagnosed with aspergillus pleurisy in our hospital from January 2000 to December 2022 were retrospectively studied. Thirteen patients with Aspergillus pleurisy were included. There were 10 males and 3 females, with a median age of 65 (range: 18-79) years. Bronchopleural fistula was present in eight patients. A proven diagnosis of Aspergillus pleurisy was based on positive pleural fluid culture in seven cases and histopathological examination of pleural biopsies in six cases. Four patients refused further treatment and were discharged from the hospital against medical advice. Nine cases recovered and were discharged after multiple antifungal treatments (systemic and topical antifungal therapies, pleural drainage and irrigation, and surgical repair). During follow-up, one patient, who suffered underlying bronchiectasis, died of massive hemoptysis 2 years after discharge. The remaining eight cases are still under close follow-up, with a median follow-up of 5.4 (range: 1.3-18.9) years. The prognosis of aspergillus pleurisy complicated with bronchopleural fistula is poor. Thoracic surgery, especially lung resection, is a risk factor associated with the incidence of Aspergillus pleurisy. Systemic antifungal therapy and adequate pleural irrigation could improve the prognosis. IMPORTANCE: Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), associated with a poor prognosis. The morbidity and mortality of this condition have not been thoroughly studied, and recent research on this topic is limited. The current study included 13 patients diagnosed with Aspergillus pleurisy, with the majority presenting concomitantly with a bronchopleural fistula. Among these patients, nine had a history of thoracic surgery, including lung transplantation and lobectomy. Four patients refused further treatment and were discharged against medical advice, while one patient succumbed to massive hemoptysis 2 years after discharge. This case series provides essential insights into Aspergillus pleurisy and evaluates the therapeutic strategy based on a limited cohort.
Assuntos
Fístula , Aspergilose Pulmonar Invasiva , Pleurisia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antifúngicos/uso terapêutico , Aspergillus , Fístula/tratamento farmacológico , Hemoptise/tratamento farmacológico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Pleurisia/tratamento farmacológico , Estudos RetrospectivosRESUMO
Arsenic has been shown to be highly toxic and can cause liver damage. Previous studies have shown that arsenic causes severe liver damage and induces accumulation of reactive oxygen species (ROS). This study aimed to investigate the effects of ferroptosis on the liver in arsenic trioxide (ATO) and to explore the underlying mechanisms. We confirmed the hepatotoxic effects of arsenic by in vivo and in vitro experiments. After 28 days of administration of arsenic trioxide (4-mg/kg, 8-mg/kg) by gavage, chickens exhibited body weight loss and liver damage in a dose-dependent manner. In addition, in vivo and in vitro western blot and real-time fluorescence quantitative PCR analyses simultaneously indicated that ferroptosis might be the main pathway of arsenic-induced liver injury. Finally, Mito-TEMPO effectively eliminated the ROS accumulation in mitochondria, significantly attenuating the process of cellular ferroptosis. In summary, the hepatotoxic effects of arsenic are related to ferroptosis, and the hepatic ferroptosis process of arsenic is regulated by mitochondrial ROS (MtROS). Our study reveals new mechanisms of arsenic toxicity to the liver, which may deepen our understanding of arsenic toxicology.
Assuntos
Trióxido de Arsênio , Galinhas , Ferroptose , Hepatócitos , Mitocôndrias , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Ferroptose/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Trióxido de Arsênio/toxicidade , Trióxido de Arsênio/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Arsênio/toxicidade , Relação Dose-Resposta a DrogaRESUMO
Conclusion: These findings indicate that EVs obtained from lung adenocarcinoma cells cultured under IH deliver miR-20a-5p to promote M2 macrophage polarization by targeting PTEN.
Assuntos
Adenocarcinoma de Pulmão , Vesículas Extracelulares , MicroRNAs , Humanos , MicroRNAs/genética , Macrófagos , Hipóxia , Adenocarcinoma de Pulmão/genéticaRESUMO
Aflatoxin B1 (AFB1), as the most toxic secondary metabolite produced by Aspergillus flavus, is a serious threat to human and animal health. Curcumin, a polyphenol from the plant turmeric, has demonstrated unique anti-damage properties in several studies. But, its ability to alleviate AFB1-induced liver damage in ducks and the underlying mechanisms are not completely elucidated. In this study, we investigated the intervention of curcumin on AFB1-induced hepatotoxicity in ducks. Research data showed that the combination of curcumin and AFB1 alleviated oxidative stress, reduced malondialdehyde (MDA) accumulation and relieved hepatotoxicity after 28 days of treatment, compared with AFB1. Also, curcumin upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzymes (SOD, HO-1), which enhanced the antioxidant capacity of the liver. In addition, curcumin inhibited AFB1-induced lysosomal damage in the liver, with the character of reduced lysosomal membrane permeabilization, restored autophagic flux, and promoted lysosomal biogenesis, thereby enhancing the self-protective capacity of the liver. In conclusion, our results suggest that curcumin alleviates AFB1-induced duck hepatotoxicity by inhibiting oxidative stress and lysosomal damage.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Curcumina , Animais , Aflatoxina B1/toxicidade , Aflatoxina B1/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Curcumina/farmacologia , Curcumina/metabolismo , Patos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Estresse OxidativoRESUMO
Aflatoxin B1 (AFB1), an extremely toxic mycotoxin that extensively contaminates feed and food worldwide, poses a major hazard to poultry and human health. Curcumin, a polyphenol derived from turmeric, has attracted great attention due to its wonderful antioxidant properties. Nevertheless, effects of curcumin on the kidneys of ducks exposed to AFB1 remain unclear. Additionally, the underlying mechanism between AFB1 and ferroptosis (based on excessive lipid peroxidation) has not been sufficiently elucidated. This study aimed to investigate the protective effects and potential mechanisms of curcumin against AFB1-induced nephrotoxicity in ducklings. The results indicated that curcumin alleviated AFB1-induced growth retardation and renal distorted structure in ducklings. Concurrently, curcumin inhibited AFB1-induced mitochondrial-mediated oxidative stress by reducing the expression levels of oxidative damage markers malondialdehyde (MDA) and 8-hydroxy-2 deoxyguanosine (8-OHdG) and improved the expression of mitochondria-related antioxidant enzymes and the Nrf2 pathway. Notably, curcumin attenuated iron accumulation in the kidney, inhibited ferritinophagy via the NCOA4 pathway, and balanced iron homeostasis, thereby alleviating AFB1-induced ferroptosis in the kidney. Collectively, our results suggest that curcumin alleviates AFB1-induced nephrotoxicity in ducks by inhibiting mitochondrial-mediated oxidative stress, ferritinophagy, and ferroptosis and provide new evidence for the mechanism of AFB1-induced nephrotoxicity in ducklings treated with curcumin.
Assuntos
Curcumina , Ferroptose , Animais , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Aflatoxina B1/toxicidade , Aflatoxina B1/metabolismo , Patos/metabolismo , Curcumina/farmacologia , Estresse Oxidativo , Ferro/farmacologiaRESUMO
Primary pulmonary venous malformation is rare and usually presents as single or multiple round masses or nodules. Here, we present the first report of a case of venous malformation presenting as Mauritia arabica-like bronchial wall thickness that was initially misdiagnosed as bronchiectasis. A Chinese man in his late 20s presented complaining of hemoptysis for 10 days. Computed tomography demonstrated bronchiectasis and M. arabica-like bronchial wall thickening in the left lower lobe. He was unresponsive to medical treatment for bronchiectasis and underwent thoracoscopic left lower lobectomy. Histopathological examination revealed venous malformation around the bronchial walls with no bronchiectasis. Venous malformation should be considered in the differential diagnosis of bronchiectasis, especially in patients with the following triad of signs: no response to antibiotics, M. arabica-like bronchial wall thickness, and normal accompanying arteries.
Assuntos
Brônquios , Bronquiectasia , Masculino , Humanos , Traqueia , Hemoptise , ArtériasRESUMO
The incidence of severe Chlamydia psittaci (C. psittaci) pneumonia and coinfections is increasing. Early detection of this condition is needed to prevent negative outcomes, along with detailed descriptions of its associated clinical characteristics. Our study contributes by undertaking etiological analysis of patients with C. psittaci pneumonia based on metagenomic next-generation sequencing (mNGS). A retrospective analysis of 30 patients with C. psittaci pneumonia was undertaken and confirmed by mNGS or polymerase chain reaction (PCR). Clinical manifestations of the severe and non-severe C. psittaci pneumonia groups were compared for clinical reference. Etiological analyses were also performed to comprehensively understand pathogeny and coinfection with other respiratory pathogens in C. psittaci patients. The absolute value of lymphocytes (LYM) in the severe group was lower than in the non-severe group. At the same time, neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), alanine aminotransferase (ALT), D-II polymer, brain natriuretic peptide (BNP), myoglobin (MYO), and cardiac troponin I (cTnI) were significantly higher (P < 0.05) in the severe group. mNGS has a broader pathogen spectrum and can more sensitively detect C. psittaci and other low-abundance pathogens with a higher positive detection rate (100%, 13/13 vs. 46%, 6/13, P <0.05) than conventional culture methods. mNGS detected the following dominant species associated with C. psittaci in patients: bacteria (53.2%, 39% gram-positive, 61% gram-negative), fungi (12.9%), and viruses (33.9%). A total of 73.3% (11/15) of patients had suspected coinfections, with a coinfection rate of 91.7% (11/12) in the severe group. No coinfection or death occurred in the non-severe group. Prognosis in the severe group was poor, with a mortality rate of 27.3% (3/11) for patients with coinfection. Eight of 11 patients with coinfections (72.7%) recovered. In conclusion, the clinical symptoms of severe C. psittaci pneumonia manifested as abnormal inflammatory indicators, impaired liver function, myocardial injury, coagulation, and relatively low immune responses. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia. Simultaneous early identification of coinfections would further improve the clinical treatment of these patients.
Assuntos
Chlamydophila psittaci , Coinfecção , Pneumonia , Humanos , Chlamydophila psittaci/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Metagenômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pneumonia/diagnóstico , Pneumonia/microbiologia , Coinfecção/microbiologiaRESUMO
Background: Skeletal muscle dysfunction (SMD) is one of the most prominent extrapulmonary effects of chronic obstructive pulmonary disease (COPD). Myostatin negatively regulates the growth of skeletal muscle. We confirmed that myostatin expression is significantly increased in the quadriceps femoris muscle tissue of rats with COPD and is involved in the development of SMD in COPD, but the mechanism by which this occurs has yet to be uncovered. Dynamin-related protein 1 (Drp-1) has been shown to promote apoptosis and affect cellular energy metabolism by mediating enhanced mitochondrial division. Preliminary findings from our group illustrated that mitochondrial division and Drp-1 expression were increased in COPD quadriceps femoris cells. However, it is not yet clear whether mitochondrial dynamics are affected by myostatin in COPD quadriceps myocytes. Methods: The study sought to explore the effects and potential mechanisms of myostatin on skeletal muscle atrophy, mitochondrial dynamics, apoptosis, and the links between related processes in COPD. Results: Our findings showed that cigarette smoke exposure stimulated an increase in myostatin, increased superoxide production, decreased mitochondrial membrane potential, significantly promoted Drp-1-mediated mitochondrial fission, and promoted apoptosis. Conclusions: In summary, our study demonstrated that cigarette smoke led to increased Drp-1 expression and enhanced mitochondrial division by upregulating myostatin, which in turn promoted apoptosis and affected cellular energy metabolism, leading to the development of SMD in COPD. This study extends understandings of skeletal muscle function in COPD and provides a basis for the use of myostatin and Drp-1 as novel therapeutic targets for SMD in COPD.
RESUMO
Background: Because of the high incidence and poor prognoses of lung adenocarcinoma (LUAD), it is essential to identify cost-effective treatment options and accurate and reliable prognostic biomarkers. CDCA4 upregulation has been identified in many cancers. However, the prognostic importance of CDCA4 and its role in LUAD remain unknown. Methods: CDCA4 expression was assessed through IHC, Western blotting (WB) and RT-PCR. The Cancer Genome Atlas (TCGA) provided data from 513 patients to study the expression and prognostic relevance of CDCA4 in LUAD. This study used gene set enrichment analyses (GSEA), gene ontology and KEGG pathway analyses for elucidating potential mechanisms underpinning the function of CDCA4 in LUAD. We also investigated correlations between immune infiltration and CDCA4 expression with single specimen GSEA (ssGSEA). Results: According to database analysis and identification of patient tissue samples, CDCA4 expression in tumour tissues surpassed that in normal tissues (P< 0.001). Increased CDCA4 expression was positively correlated with a higher T, N, pathologic stage and poor primary therapy outcome. In addition, the Kaplan-Meier plotter exhibited that an elevated CDCA4 expression was related to worse disease-specific survival(DSS) and overall survival (OS) (DSS HR= 5.145, 95% CI=3.413-7.758, P<0.001; OS HR=3.570, 95% CI=2.472-5.155, P<0.001). Then multivariate COX regression analyses indicated that the CDCA4 gene was an independent risk consideration for prognoses. GO and KEGG results showed that CDCA4 and its neighbouring genes were enriched in the cell cycle and DNA replication. As determined by GSEA, CDCA4 was related to various immune-related signalling pathways (SPs), Homologous recombination, DNA replication and the cell cycle. SsGSEA analysis showed a significant association between CDCA4 expression and Th2 cells, mast cells, eosinophils and Th17 cells. Conclusions: CDCA4 expression is increased in LUAD and is a potential predictive biomarker and therapeutic target.
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BACKGROUND: To observe the effect of cigarette smoke extract (CSE) on mitochondrial division in mouse quadriceps femoris cells and to explore the potential molecular mechanism of skeletal muscle dysfunction (SMD) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Quadriceps femoris were cultured, passaged, and stimulated with different concentrations of CSE. We divided cells into four groups (Control, 2.5%, 5%, 10%). The growth of cells, the expression of Dynamin related protein 1 (Drp-1), and apoptosis were observed and evaluated by fluorescence microscopy, RT-PCR, Western blot, and flow cytometry. RESULTS: The longer the intervention time, the more obvious the decrease in cell number. In the 5% and 10% groups, the cells became round with gaps. Under an inverted fluorescence microscope, the green fluorescence of cells in 5% and 10% stained with Mito-Tracker Green was significantly less than that of the Control and 2.5%. Red fluorescence was reduced and the green fluorescence was increased in the 5% and 10% stained with JC-1. Flow cytometry analysis showed that reactive oxygen species (ROS) and apoptosis were increased in the CSE intervention groups. In the Control, 2.5%, 5%, and 10%, the levels of ROS were 0.052±0.015, 0.170±0.030, 5.340±0.500, and 24.400±1.900, respectively. The apoptotic rates (%) were 0.270±0.009, 2.650±0.060, 11.850±0.020, and 31.820±1.260, respectively. The relative expression levels were, 0.900±0.093, 1.141±0.099, 1.361±0.034, 2.155±0.092 for DNM1L mRNA, and 0.509±0.008, 0.569±0.028, 0.792±0.048, 0.940±0.062 for Drp-1. There were significant differences in the apoptotic rate, and Drp-1 expression between 5% and 10% compared with the Control and 2.5% (P<0.05). CONCLUSIONS: CSE may enhance mitochondrial division of quadriceps femoris cells by up-regulating the expression of Drp-1, affecting cellular energy metabolism and promoting quadriceps femoris apoptosis, ultimately leading to the occurrence and development of skeletal muscle dysfunction in COPD.