LncRNA-AK007111 affects airway inflammation in asthma via the regulation of mast cell function.

Long noncoding RNAs (lncRNAs) are involved in gene transcription and pathophysiological processes of human diseases. Multiple lncRNAs have been shown to play important roles in the occurrence and development of asthma. This study aimed to explore the role of a novel lncRNA, lncRNA-AK007111, in asthma. Overexpression of lncRNA-AK007111 was induced in a mouse model of asthma via viral transfection, followed by the collection of alveolar lavage fluid and lung tissue for the detection of relevant inflammatory factors and pathological analysis of lung sections. Pulmonary resistance and respiratory dynamic compliance were measured using an animal pulmonary function analyzer. The number of mast cells sensitized by immunofluorescence was detected at the cellular level. The degree of degranulation of lncRNA-AK007111 after its knockdown was determined by detecting the level of ß-hexosaminidase that was released and quantifying IL-6 and TNF-α using ELISA in a model of RBL-2H3 cells activated by immunoglobulin E plus antigen. Finally, we observed the migration ability of mast cells under a microscope. The results showed that in ovalbumin-sensitized mice, the upregulation of lncRNA-AK007111 promoted the infiltration of inflammatory cells in lung tissue, increased the number of total cells, eosinophils, and mast cells, upregulated IL-5 and IL-6 levels, and increased airway hyper-reactivity. Downregulation of lncRNA-AK007111 decreased the degranulation ability of IgE/Ag-activated mast cells and inhibited the expression of IL-6 and TNF-α; moreover, the migration ability of mast cells was significantly weakened. In conclusion, our study revealed that lncRNA-AK007111 plays an important role in asthma by modulating mast cell-related functions.

Toll-Like Receptor 2 Modulates Pulmonary Inflammation and TNF-α Release Mediated by Mycoplasma pneumoniae.

Objectives: To investigate the roles that Toll-like receptors (TLRs) play in lung inflammation mediated by Mycoplasma pneumoniae (MP). Methods: The changes in TLRs and tumor necrosis factor alpha (TNF-α) in peripheral blood of children with M. pneumoniae pneumonia (MPP) were monitored, and the interactions of signaling molecules regulating TNF-α release in A549 cells and neutrophils after M. pneumoniae stimulation were investigated. In TLR2 knockout (TLR2-/-) mice, the levels of TNF-α in bronchial alveolar lavage fluid (BALF) and peripheral blood after mycoplasma infection and the pathological changes in the lung tissue of mice were detected. Results: TNF-α levels in peripheral blood of children with MPP were higher than those in non-infected children, and children with refractory MPP had the highest levels of TNF-α and TLR2. TNF-α secretion and TLR2, myeloid differentiation primary response 88 (MyD88) and phospho-p65(p-p65) levels were increased in stimulated cells. TNF-α secretion was suppressed upon siRNA-mediated TLR2 silencing. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) and MyD88 effectively reduced TNF-α expression. Compared with wild-type mice, the TNF-α in serum and BALF decreased, and lung pro-inflammatory response was partially suppressed in TLR2-/- mice. Conclusion: We concluded that TLR2 regulates M. pneumoniae-mediated lung inflammation and TNF-α release through the TLR2-MyD88-NF-κB signaling pathway.

Development of a scale for early prediction of refractory Mycoplasma pneumoniae pneumonia in hospitalized children.

Now there is no clinical scale for early prediction of refractory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study is to identify indicators and develop an early predictive scale for RMPP in hospitalized children. First we conducted a retrospective cohort study of children with M. pneumoniae pneumonia admitted to Children's Hospital of Nanjing Medical University, China in 2016. Children were divided into two groups, according to whether their pneumonia were refractory and the results were used to develop an early predictive scale. Second we conducted a prospective study to validate the predictive scale for RMPP in children in 2018. 618 children were included in the retrospective study, of which 73 with RMPP. Six prognostic indicators were identified and included in the prognostic assessment scale. The sensitivity of the prognostic assessment scale was 74.0% (54/73), and the specificity was 88.3% (481/545) in the retrospective study. 944 children were included in the prospective cohort, including 92 with RMPP, the sensitivity of the prognostic assessment scale was 78.3% (72/92) and the specificity was 86.2% (734/852). The prognostic assessment scale for RMPP has high diagnostic accuracy and is suitable for use in standard clinical practice.

Influence of different delivery modes on the clinical characteristics of Chlamydia trachomatis pneumonia.

We analyzed the effects of delivery methods on Chlamydia trachomatis pneumonia in infants. Three hundred forty-four children hospitalized with Chlamydia trachomatis pneumonia were enrolled. They were divided into the vaginal delivery group and the cesarean delivery group. We compared and analyzed their age of onset, peripheral blood white blood cell count, liver enzymes, chlamydia trachomatis titers, and chest radiograph scores. Seventy-eight (22.7%) were delivered by a cesarean, and 266 (77.3%) were delivered vaginally. There were no statistically significant differences between groups when compared by sex and age (P > 0.05). Copy numbers and white blood cell counts in the peripheral blood of children with Chlamydia trachomatis in respiratory secretions of the vaginal delivery group were significantly higher than those of the cesarean delivery group (P < 0.05). The alanine aminotransferase and aspartate aminotransferase levels between groups were not statistically significant. Comparisons of admission chest radiography scores, discharge radiography scores, and score differences showed no statistical differences (P > 0.05). CONCLUSION: Infants delivered by cesarean comprise approximately one-fifth of those affected. The Chlamydia trachomatis titers and peripheral blood leukocyte counts of the vaginal delivery group were higher than those of the cesarean delivery group. Age of onset, liver enzymes, pulmonary inflammation, and pneumonia absorption were not different between groups. What is Known: • Chlamydia trachomatis is an important pathogen that causes lower respiratory tract infections in infants. • C. trachomatis is primarily transmitted to infants through the infected mother, resulting in Chlamydia trachomatis pneumonia subsequently. What is New: • Vaginal delivery and cesarean delivery can result in Chlamydia trachomatis pneumonia transmission; however, cesarean delivery accounts for ~ 20% of cases. • C. trachomatis volume in the respiratory tract and the number of peripheral blood leukocytes in infants delivered vaginally were higher than those in infants delivered by cesarean.

Biochemical and behavioral characterization of the double transgenic mouse model (APPswe/PS1dE9) of Alzheimer's disease.

OBJECTIVE The double transgenic mouse model (APPswe/PS1dE9) of Alzheimer's disease (AD) has been widely used in experimental studies. ß-Amyloid (Aß) peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. METHODS Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels of Aß1-40, Aß1-42 and 8-hydroxydeoxyguanosine (8-OHdG) in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. RESULTS The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aß(1-40) and Aß(1-42) were detected in these dead mice brains with a ratio of 1:10. The level of blood-borne Aß at 6-month age was similar with that at 12-month age. Besides, Aß(1-40) level in the blood was significantly higher than Aß(1-42) level at the ages of 6 and 12 months (ratio 2.37:1). In contrast, the level of Aß(1-42) in the brain (160.6 ng/mg protein) was higher than that of Aß(1-40) (74 ng/mg protein) (ratio 2.17:1). In addition, the levels of Aß(1-40) and Aß(1-42) varied markedly among different brain regions. Aß(1-42) level was significantly higher than Aß(1-40) level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher γ-secretase activity but was more efficient in producing Aß(1-42) peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. CONCLUSION These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.