RESUMO
This study investigated the molecular mechanism by which bronchoalveolar lavage fluid exosomes (BALF-exo) alleviated acute lung injury (ALI). BALF-exo was isolated from mice. LPS was used to induce inflammation in rat alveolar macrophages (NR8383). NR8383 cell models were treated with BALF-exo or BALF-exo loaded with miR-223-3p mimics/inhibitors, or STK39 was overexpressed in NR8383 cells before LPS and BALF-exo treatment. These cells were subjected to apoptosis, autophagy, and inflammation assays. RNA immunoprecipitation and dual-luciferase reporter assay were conducted to verify the binding between miR-223-3p and STK39. LPS-induced ALI mouse models were treated with BALF-exo loaded with miR-223-3p mimics. miR-223-3p was lowly expressed in BALF-exo from LPS-treated mice. BALF-exo loaded with miR-223-3p mimics increased viability and autophagy and decreased apoptosis and inflammation in NR8383 cell models. Inhibition of miR-223-3p in BALF-exo or overexpression of STK39 in NR8383 cells repressed the therapeutic effect of BALF-exo in LPS-treated NR8383 cells. STK39 was a target gene of miR-223-3p. miR-223-3p shuttled by BALF-exo negatively regulated the expression of STK39 in NR8383 cells. BALF-exo loaded with miR-223-3p mimics also reduced lung injuries in ALI mice. In conclusion, miR-223-3p loaded in BALF-exo alleviates ALI by targeting STK39 in alveolar macrophages.
Assuntos
Lesão Pulmonar Aguda , Exossomos , MicroRNAs , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/terapia , Animais , Autofagia/genética , Líquido da Lavagem Broncoalveolar , Exossomos/genética , Inflamação , Lipopolissacarídeos/efeitos adversos , Macrófagos Alveolares/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RatosRESUMO
Lung is colonized by a diverse array of microbes and the lung microbiota is profoundly involved in the development of respiratory diseases. There is little knowledge about the role of lung microbiota dysbiosis in lung cancer. In this study, we performed metagenomic sequencing on bronchoalveolar lavage (BAL) from two different sampling methods in non-small cell lung cancer (NSCLC) patients and non-cancer controls. We found the obvious variation between bronchoscopy samples and lobectomy samples. Oral taxa can be found in both bronchoscopy and lobectomy samples and higher abundance of oral taxa can be found in bronchoscopy samples. Although the NSCLC patients had similar microbial communities with non-cancer controls, rare species such as Lactobacillus rossiae, Bacteroides pyogenes, Paenibacillus odorifer, Pseudomonas entomophila, Magnetospirillum gryphiswaldense, fungus Chaetomium globosum et al. showed obvious difference between NSCLC patients and non-cancer controls. Age-, gender-, and smoking-specific species and EGFR expression-related species in NSCLC patients were detected. There results implicated that different lung segments have differential lung microbiome composition. The oral taxa are found in the lobectomy samples suggesting that oral microbiota are the true members of lung microbiota, rather than contamination during bronchoscopy. Lung cancer does not obviously alter the global microbial composition, while rare species are altered more than common species. Certain microbes may be associated with lung cancer progression.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Disbiose , Neoplasias Pulmonares/complicações , Pulmão/microbiologia , Microbiota , Pneumonia/etiologia , Adulto , Idoso , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Metagenoma , Metagenômica/métodos , Pessoa de Meia-Idade , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: To discuss the treatment strategy for outpatient diminutive colorectal polyps.â© Methods: Diminutive colonic polyps (≤5 mm in size) patients detected at the initial screening colonoscopy between January 2012 to December 2014 at outpatient endoscopy center of the Second Xiangya Hospital were retrospectively studied. The linear growth rate of the natural history cases without polypectomy (Group A, n=31) and the recurrence rate after polypectomy (Group B, n=212) were analyzed. Then the adenoma detection rate, the incidence of advanced adenoma and cancer were compared between the 2 groups.â© Results: Patients were followed up for 1.5-57.6 months. In the Group A, 61.2% patients' linear diameter remained stable and 19.4% patients were progressed. The growth rate in 12.1-24.0 months were the highest (25.0%). In the Group B, overall recurrence rate was 16% after polypectomy in the Group B. The highest recurrence rate for the first follow-up was 12.1-24.0 months, accounting for 14.3%. The adenoma detection rates in the Group A and the Group B were 38.7% and 54.2%, respectively. In the Group A, 3.2% of patients naturally progressed to advanced adenoma, and 1.4% of patients in the Group B relapsed into advanced adenoma. No cancerous patients were found in either group.â© Conclusion: Outpatient diminutive colorectal polyps can be temporarily unremoved for colonoscopy screening. It is advisable to perform colonoscopy within 12-24 months.