Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF. METHODS: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) staining. Mitochondrial morphology was detected by MitoTracker® Deep Red FM or transmission electron microscopy (TEM). Western blotting and immunofluorescence were used to determine the expression of protein. The migration ability of the cells was detected by the cell scratch test. Mitochondrial DNA (mtDNA) levels were assessed by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect cytokine levels. Superoxide dismutase (SOD) activity and the levels of glutathione (GSH) and malondialdehyde (MDA) were detected by chemichromatometry. RESULTS: PQ exposure caused EMT and PF in vivo and in vitro. PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1 (Drp1), which were accompanied by oxidative stress. Inhibiting mitochondrial fission using mitochondrial division inhibitor-1 (Mdivi-1), a selective inhibitor of Drp1, attenuated PQ-induced EMT and oxidative damage. Treatment with N-acetyl-L-cysteine (NAC), an antioxidant, reduced Drp1 expression, attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF. Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release, the expression of Toll-like receptor 9 (TLR9) and phosphorylation (P)-NF-κB p65 as well as cytokines (interleukin 6 [IL-6], interleukin-1ß [IL-1ß], and tumor necrosis factor-α [TNF-α]) production. CONCLUSION: Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF, which is associated with the mtDNA/TLR9/NF-κB pathway.

Effect of L3MBTL3/PTPN9 polymorphisms on risk to alcohol-induced ONFH in Chinese Han population.

PURPOSE: Alcohol-induced osteonecrosis femoral head necrosis (ONFH) is a disease that seriously affects human health. Abnormal expression of L3MBTL3/PTPN9 gene can cause a variety of human diseases. The purpose of this study is to investigate the effect of L3MBTL3/PTPN9 gene polymorphism on the susceptibility of alcohol-induced ONFH in Chinese Han population. METHODS: A total of 308 alcohol-induced ONFH patients and 425 healthy controls were enrolled in this case-control study. Alleles, genotypes, genetic models, haplotypes, and multifactor dimensionality reduction analyses (MDR) based on age-corrected by using odds ratio (OR) and 95% confidence interval (CI) were performed. RESULTS: Our result revealed rs2068957 in the L3MBTL3 gene increased the risk of alcohol ONFH under the recessive model after correction. Besides, we also found that rs75393192 in the PTPN9 gene was a protective site in stratification over 40 years of age and stage. In stratified analysis of necrotic sites, we only found that rs2068957 was associated with increased susceptibility of alcohol-induced ONFH under the co-dominant model and recessive model. Haplotype "GC" in the block (rs76107647|rs10851882 in PTPN9 gene) significantly decreased the susceptibility of alcoholic ONFH. CONCLUSIONS: Our results provide evidence that L3MBTL3/PTPN9 polymorphisms are associated with alcohol-induced ONFH risk in Chinese Han population.

Effects of polystyrene and triphenyl phosphate on growth, photosynthesis and oxidative stress of Chaetoceros meülleri.

The toxicity of microplastics to marine organisms has attracted much attention; however, studies of their effects on marine microalgae remain limited. Here, the effects of the single and combined toxicity of polystyrene (PS) and triphenyl phosphate (TPhP) on the cell growth, photosynthesis, and oxidative stress of Chaetoceros meülleri were investigated. PS inhibited growth of the algae cells and caused a dose-dependent effect on oxidative stress. The significantly high production of reactive oxygen species (ROS) induced severe cell membrane damage, as confirmed by high fluorescence polarization. However, there was no obvious decrease in chlorophyll a content, and 80 mg/L of PS significantly promoted chlorophyll a synthesis. The TPhP also inhibited cell growth, except at low concentrations (0.2-0.8 mg/L), which stimulated algae growth over 48 h. Moreover, no obvious decrease in chlorophyll a and maximal photochemical efficiency of PSII was found in the TPhP experimental groups except for 3.2 mg/L TPhP, where the rapid light curves showed a significantly reduced photosynthetic capacity of algae. In addition, TPhP caused high ROS levels at 96 h, resulting in cell membrane damage. Using the additive index and independent action methods, the combined toxic effects of PS and TPhP on the algae were evaluated as antagonistic; however, cell membrane damage caused by high ROS levels was still noticeable. This study has shown the potential toxicity of PS and TPhP to marine microalgae, and provided insights into the combined risk assessment of TPhP and microplastics in the marine environment.

Ultrasound for diagnosing new difficult laryngoscopy indicator: a prospective, self-controlled, assessor blinded, observational study.

BACKGROUND: Unpredictable difficult laryngoscopy (DL) remains a challenge for anesthesiologists, especially when difficult ventilation occurs during standard laryngoscopy. Accurate airway assessment should always be performed, but the common airway assessment methods only perform superficial screening. Thus, the deep laryngopharyngeal anatomy may not be evaluated. Ultrasound-based airway assessment has been recently proposed as a useful, simple, and non-invasive bedside tool as an adjunct to clinical methods, which may facilitate identification of DL. The present study aimed to determine the correlation between ultrasound-measured indicators and DL. METHODS: Patients undergoing elective surgery under general anesthesia with tracheal intubation were enrolled. Ultrasonic airway assessments were performed before anesthesia induction. Ultrasound diagnostic indicators included the thickness and width of the base of the tongue, the angle between the epiglottis and glottis, the length of the thyrohyoid membrane, and the thickness of the lateral pharyngeal wall. A score of ≥3 in the Modified Cormack-Lehane Scoring System was used as a standard of DL and was also applied to divide patients into DL and non-DL groups. The area under the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of various diagnostic indicators. RESULTS: A total of 499 patients were enrolled into non-DL and DL groups comprising 452 (452/499, 90.6%) and 47 (47/499, 9.4%) patients, respectively. One ultrasonic diagnoses indicator correlated with DL, namely, the angle between the epiglottis and glottis. When the angle between the epiglottis and glottis was 50°, the area under the ROC curve was maximum (0.902), and the best sensitivity (81%) and specificity (89%) were achieved. CONCLUSIONS: Airway ultrasounds should be considered to identify DL. The ultrasonic angle measured between the epiglottis and glottis is highly associated with DL, which may occur when the angle is less than 50°. CLINICAL TRIAL REGISTRATION: ChiCTR-DDT-13004102, http://www.chictr.org.cn/showproj.aspx?proj=5465.

Laryngotracheal closure and cricopharyngeal myotomy for intractable aspiration and dysphagia secondary to cerebrovascular accident.

OBJECTIVE: To investigate the clinical value, technique, indications and contraindications of laryngotracheal closure (LTC) and cricopharyngeal myotomy (CPM) for intractable aspiration and dysphagia secondary to a cerebrovascular accident (CVA). MATERIALS AND METHODS: Patients (n = 45) with intractable aspiration and dysphagia secondary to a CVA were treated with LTC and CPM. The LTC was performed by suturing the double cords, and packing the strap muscle flap into the subglottic tracheal cavity. RESULTS: Intractable aspiration was completely eradicated in all patients. The swallowing function was partially improved, and the patients' quality of life was greatly improved. It became easier to care for these patients after surgery. CONCLUSIONS: LTC and CPM are suitable for intractable aspiration and dysphagia secondary to a CVA.