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Acinetobacter baumannii (A. baumannii) is characterized by a high prevalence of drug resistance; how to effectively treat it is still a major clinical challenge. Our previous experiments confirmed that ompA, which is one of the most well-characterized virulence factors, may be dependent on the caspase-1 pathway-stimulated expression of NLRP3 inflammasome to enhance inflammation. TLRs (i.e., TLR2, etc.) is the initiating signal for NLRP3 inflammasome activation; how it relates to ompA in its underlying pathogenic mechanism is not clear. In this study, we proofed that ompA promoted NLRP3 inflammasome activation while the TLR2-NF-κB pathway was also activated after A. baumannii infection. Additionally, the expression of NLRP3 inflammasome-associated proteins and genes was inhibited by silencing TLR2 and NLRP3. This indicated that ompA might depend on the TLR2-NF-κB pathway to assemble and activate the NLRP3 inflammasome. OmpA promoted the assembly of the NLRP3 inflammasome through the TLR2-NF-κB pathway and inhibited the degradation of caspase-1 by the proteasome so that a large number of mature IL-1β/IL-18 and other proinflammatory factors were released extracellularly to enhance the body's inflammatory response. Taken together, the results of the joint pre-study confirmed a novel TLR2-NF-κB/NLRP3/caspase-1-modulated mechanism underpinning ompA activity, the NLRP3 inflammasome pathway may be as a potential immunomodulatory target against A. baumannii infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing fnancial interests or personal relationships that could have appeared to infuence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of caspase-1 degradation by proteasome inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pneumonia accounts for ~1.3 million mortalities in children per year worldwide. MicroRNAs are implicated in several diseases, including cancer and pneumonia; however, the role of let7f‑5p in pneumonia is not completely understood. In the present study, lipopolysaccharide (LPS) was used to establish an in vitro pneumonia model in A549 and WI‑38 cells. The reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting results demonstrated that let7f‑5p expression levels were significantly decreased, whereas MAPK6 expression levels were significantly increased in the peripheral venous blood of patients with pneumonia and in LPS‑induced A549 and WI‑38 cells compared with healthy volunteers and control cells, respectively. Furthermore, the dual‑luciferase reporter assay demonstrated that let7f‑5p targeted the 3'‑untranslated region of MAPK6. The ELISA and RT‑qPCR results demonstrated that let7f‑5p mimic ameliorated LPS‑induced inflammatory injury in A549 and WI‑38 cells, as demonstrated by decreased expression levels of proinflammatory cytokines, including TNF‑α and IL‑6. In addition, the Cell Counting Kit‑8 assay results indicated that let7f‑5p mimic ameliorated LPS‑induced reductions in cell viability, and the western blotting results demonstrated that let7f‑5p mimic reversed LPS‑induced activation of the STAT3 signaling pathway. Notably, the aforementioned let7f‑5p‑mediated effects were reversed by MAPK6 overexpression. Collectively, the results of the present study suggested that let7f‑5p inhibited inflammation by targeting MAPK6 in the in vitro pneumonia model, thus let7f‑5p may serve as a potential novel therapeutic target for pneumonia.

Background: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were mainly based on information from adult populations. Limited data are available for children with COVID-19, especially for infected infants., Methods: We report a 55-day-old case with COVID-19 confirmed in China and describe the identification, diagnosis, clinical course, and treatment of the patient, including the disease progression from day 7 to day 11 of illness., Results: This case highlights that children with COVID-19 can also present with multiple organ damage and rapid disease changes., Conclusions: When managing such infant patients with COVID-19, frequent and careful clinical monitoring is essential., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Asthma is a common chronic airway disease worldwide. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of asthma. We therefore aimed to estimate the national prevalence of asthma in a representative sample of the Chinese population., Methods: A representative sample of 57 779 adults aged 20 years or older was recruited for the national cross-sectional China Pulmonary Health (CPH) study using a multi-stage stratified sampling method with parameters derived from the 2010 census. Ten Chinese provinces, representative of all socioeconomic settings, from six geographical regions were selected, and all assessments were done in local health centres. Exclusion criteria were temporary residence, inability to take a spirometry test, hospital treatment of cardiovascular conditions or tuberculosis, and pregnancy and breastfeeding. Asthma was determined on the basis of a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. All participants were assessed with a standard asthma questionnaire and were classed as having or not having airflow limitation through pulmonary function tests before and after the use of a bronchodilator (400 μg of salbutamol). Risk factors for asthma were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was assessed by the self-reported history of physician diagnosis, treatments, and hospital visits in people with asthma., Findings: Between June 22, 2012, and May 25, 2015, 57 779 participants were recruited into the CPH study. 50 991 (21 446 men and 29 545 women) completed the questionnaire survey and had reliable post-bronchodilator pulmonary function test results and were thus included in the final analysis. The overall prevalence of asthma in our sample was 4·2% (95% CI 3·1-5·6), representing 45·7 million Chinese adults. The prevalence of asthma with airflow limitation was 1·1% (0·9-1·4), representing 13·1 million adults. Cigarette smoking (odds ratio [OR] 1·89, 95% CI 1·26-2·84; p=0·004), allergic rhinitis (3·06, 2·26-4·15; p<0·0001), childhood pneumonia or bronchitis (2·43, 1·44-4·10; p=0·002), parental history of respiratory disease (1·44, 1·02-2·04; p=0·040), and low education attainment (p=0·045) were associated with prevalent asthma. In 2032 people with asthma, only 28·8% (95% CI 19·7-40·0) reported ever being diagnosed by a physician, 23·4% (13·9-36·6) had a previous pulmonary function test, and 5·6% (3·1-9·9) had been treated with inhaled corticosteroids. Furthermore, 15·5% (11·4-20·8) people with asthma reported at least one emergency room visit and 7·2% (4·9-10·5) at least one hospital admission due to exacerbation of respiratory symptoms within the preceding year., Interpretation: Asthma is prevalent but largely undiagnosed and undertreated in China. It is crucial to increase the awareness of asthma and disseminate standardised treatment in clinical settings to reduce the disease burden., Funding: National Key R&D Program of China, Ministry of Science and Technology of China; the Special Research Foundation for Public Welfare of Health, Ministry of Health of China; the Chinese National Research Program for Key Issues in Air Pollution Control; and the National Natural Science Foundation of China., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Interleukin (IL)-33 treatment has been reported to reduce mortality in a rat model of sepsis, and the present study aimed to determine whether this effect of IL-33 is achieved through a reduction in the systemic inflammatory response in Acinetobacter baumannii pneumonia. After induction of pneumonia, rats were treated with normal saline or IL-33, and mortality over 5 days was recorded. Inflammation within lung tissues was evaluated by hematoxylin and eosin staining as well as measurement of the concentrations of IL-8 and tumor necrosis factor alpha (TNF-α) in the bronchoalveolar lavage fluid (BALF) and plasma by enzyme-linked immunosorbent assay. In addition, the expression of Toll-like receptor 4 (TLR4), ST2, and nuclear factor kappa B (NF-κB) in rat lung tissues was assessed by western blotting. The result showed that the mortality rate and systemic inflammation were significantly increased in rats upon infection with A. baumannii, as evidenced by significant increases in the IL-8 and TNF-α levels in BALF and plasma as well as increased NF-κB activity and TLR4 expression in rat lung tissues. Importantly, IL-33 (1 μg/kg) treatment significantly decreased mortality and pulmonary inflammation in A. baumannii-infected rats. Moreover, IL-33 treatment suppressed the elevation of IL-8 and TNF-α levels and inhibited TLR4 expression and NF-κB activation. Overall, these results suggest that IL-33 may decrease the mortality and inhibit the systematic inflammatory response associated with A. baumannii pneumonia by suppressing TLR4/NF-κB signaling. [ABSTRACT FROM AUTHOR]

Pneumonia accounts for ~1.3 million mortalities in children per year worldwide. MicroRNAs are implicated in several diseases, including cancer and pneumonia; however, the role of let7f-5p in pneumonia is not completely understood. In the present study, lipopolysaccharide (LPS) was used to establish an in vitro pneumonia model in A549 and WI-38 cells. The reverse transcription-quantitative PCR (RT-qPCR) and western blotting results demonstrated that let7f-5p expression levels were significantly decreased, whereas MAPK6 expression levels were significantly increased in the peripheral venous blood of patients with pneumonia and in LPS-induced A549 and WI-38 cells compared with healthy volunteers and control cells, respectively. Furthermore, the dual-luciferase reporter assay demonstrated that let7f-5p targeted the 3′-untranslated region of MAPK6. The ELISA and RT-qPCR results demonstrated that let7f-5p mimic ameliorated LPS-induced inflammatory injury in A549 and WI-38 cells, as demonstrated by decreased expression levels of proinflammatory cytokines, including TNF-α and IL-6. In addition, the Cell Counting Kit-8 assay results indicated that let7f-5p mimic ameliorated LPS-induced reductions in cell viability, and the western blotting results demonstrated that let7f-5p mimic reversed LPS-induced activation of the STAT3 signaling pathway. Notably, the aforementioned let7f-5p-mediated effects were reversed by MAPK6 overexpression. Collectively, the results of the present study suggested that let7f-5p inhibited inflammation by targeting MAPK6 in the in vitro pneumonia model, thus let7f-5p may serve as a potential novel therapeutic target for pneumonia. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (SP) is a major cause of community-acquired pneumonia. Ferroptosis pitches in pneumonia. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) regulates ferroptosis in various cells. Therefore, this study probed the mechanism of lncRNA NEAT1 on SP-induced ferroptosis in AECs. Serum lncRNA NEAT1 level in 36 streptococcus pneumonia patients were retrospectively detected, with its correlations with inflammatory factor (TNF-α/IL-1β/IL-6) levels analyzed. Human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with sh-NEAT1 and induced by SP. Cell viability was evaluated by CCK-8. Lactate dehydrogenase (LDH) activity was assessed. Iron content, and levels of TNF-α/IL-1β/IL-6/IL-10/lncRNA NEAT1/lipid peroxidation products [malondialdehyde (MDA)/glutathione (GSH)/reactive oxygen species/(ROS)]/ferroptosis-related proteins [Cyclooxgenase 2 (COX2)/recombinant solute carrier family 7 member 11 (SLC7A11)/total nuclear factor erythroid 2-related factor 2 (Nrf2)/cytoplasmic Nrf2 (C-Nrf2)/nuclear Nrf2 (N-Nrf2)/GPX4)] were determined by kit/ELISA/RT-qPCR/kits/Western blot. Nrf2 nuclear translocation was detected by immunofluorescence assay. On top of lncRNA NEAT1 knockdown, SP-induced HPAEpiC were treated with ML385. Serum lncRNA NEAT1 level was elevated in streptococcus pneumonia patients, and were positively interrelated with TNF-α/IL-1β/IL-6 levels. SP promoted cell HPAEpiC injury and inflammatory response, and up-regulated lncRNA NEAT1 level. LncRNA NEAT1 knockdown suppressed HPAEpiC injury/inflammatory response (reduced LDH activity and TNF-α/IL-1β/IL-6 levels, elevated IL-10) and suppressed ferroptosis (decreased iron/MDA/ROS contents and COX2 level, increased GSH/SLC7A11), facilitated Nrf2 nuclear translocation, and up-regulated GPX4. Nrf2-GPX4 pathway inhibition annulled NEAT1 knockdown-mediated improvement on SP-induced HPAEpiC ferroptosis/injury/inflammatory response. LncRNA NEAT1 knockdown suppressed SP-induced HPAEpiC ferroptosis by activating Nrf2-GPX4 pathway, thereby alleviating cell injury and inflammatory response. [Display omitted] • LncRNA NEAT1 level in Streptococcus pneumoniae pneumonia patients is positively linked with TNF-α, IL-1β, and IL-6 levels. • LncRNA NEAT1 knockout reduces streptococcus pneumoniae-led human pulmonary alveolar epithelial cell injury and inflammation. • LncRNA NEAT1 knockdown represses streptococcus pneumoniae-induced ferroptosis in human pulmonary alveolar epithelial cells. • Silencing lncRNA NEAT1 promotes Nrf2 nuclear translocation and up-regulates GPX4. • Nrf2-GPX4 ferroptosis inhibition annuls the effects of NEAT1 knockout in human pulmonary alveolar epithelial cells. [ABSTRACT FROM AUTHOR]