RESUMO
BACKGROUND: Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. RESEARCH QUESTION: Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection? STUDY DESIGN AND METHODS: This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29. RESULTS: The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35; P < .001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P < .001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. INTERPRETATION: TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection. TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT03715322; URL: www. CLINICALTRIALS: gov.
Assuntos
Bronquiectasia , Infecções por Pseudomonas , Humanos , Adulto , Tobramicina , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Antibacterianos/uso terapêutico , Qualidade de Vida , Administração por Inalação , Bronquiectasia/complicações , Bronquiectasia/tratamento farmacológico , Método Duplo-Cego , Pseudomonas aeruginosaRESUMO
Three new ester glycosides, named as Caesateroside A (1), Caesateroside B (2) and Caesateroside C (3) were obtained from the seeds of Caesalpinia sappan. The new structures of compounds 1-3 were elucidated by analyzing their 1 D NMR, 2 D NMR and HR-ESI-MS spectra. Compounds 1-3 showed weak-moderate cytotoxicity against Hela and HepG-2 human cancer cell lines.
Assuntos
Caesalpinia , Diterpenos , Ésteres , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , SementesRESUMO
Bronchial asthma poses a serious threat to human health. Previous studies have documented the role of long noncoding RNAs (lncRNAs) in asthma. However, the molecular mechanism underlying bronchial asthma remains unclear. The aim of the present study was to evaluate the role of the lncRNA Opainteracting protein 5 antisense RNA1 (OIP5AS1) in the house dust miteinduced inflammatory response in human bronchial epithelial cells. BEAS2B cells were treated with Dermatophagoides pteronyssinus peptidase 1 (Der p1) to establish an in vitro model of asthma. OIP5AS1 expression levels increased in BEAS2B cells following Der p1 treatment, while microRNA (miR)1433p was downregulated. Additionally, the levels of the proinflammatory factors tumor necrosis factorα, interleukin (IL)6 and IL8 were measured, and apoptosis was evaluated following OIP5 silencing. OIP5AS1 knockdown reduced the inflammatory response and apoptosis in BEAS2B cells. Furthermore, using dual luciferase reporter assays and cotransfection experiments, it was demonstrated that the function of OIP5AS1 was mediated by miR1433p. miR1433p overexpression attenuated the Der p1induced inflammatory response and apoptosis of BEAS2B cells by targeting high mobility group box 1 (HMGB1). In summary, OIP5AS1 exacerbated Der p1induced inflammation and apoptosis in BEAS2B cells by targeting miR1433p via HMGB1.
Assuntos
Asma/genética , Brônquios/metabolismo , RNA Longo não Codificante/genética , Células Epiteliais Alveolares/metabolismo , Animais , Apoptose/genética , Asma/patologia , Brônquios/imunologia , Linhagem Celular , Células Epiteliais/metabolismo , Proteína HMGB1/metabolismo , Humanos , Inflamação/genética , MicroRNAs/genética , Pyroglyphidae/patogenicidade , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genéticaRESUMO
A critical pathogenic factor in the development of lethal liver failure is cell death induced by the accumulation of lipid reactive oxygen species. In this study, we discovered and illuminated a new mechanism that led to alcoholic liver disease via ferroptosis, an iron-dependent regulated cell death. Study in vitro showed that both necroptosis inhibitor and ferroptosis inhibitors performed significantly protective effect on alcohol-induced cell death, while apoptosis inhibitor and autophagy inhibitor had no such effect. Our data also indicated that alcohol caused the accumulation of lipid peroxides and the mRNA expression of prostaglandin-endoperoxide synthase 2, reduced the protein expression of the specific light-chain subunit of the cystine/glutamate antiporter and glutathione peroxidase 4. Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.