Hsa_circ_0008833 promotes COPD progression via inducing pyroptosis in bronchial epithelial cells

Purpose: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder. Pyroptosis represents a distinctive form of inflammatory cell death that is mediated through the activation of Caspase-1 and inflammasomes. CircRNAs have emerged as a novel class of biomolecules with implications in various human diseases. This study aims to investigate the circRNAs profile of in COPD progression and identify pivotal circRNAs associated with the development of this disease. Methods: he expression profiles of circRNAs in peripheral blood mononuclear cells of COPD patients were assessed by circRNA microarray. Furthermore, flag-labeled vectors were constructed to assess the potential protein-coding capacity of has-circ-0008833. 16HBE cells were stably transfected with lentivirus approach, and cell proliferation and death were assessed to clarify the functional roles of has-circ-0008833 and its encoded protein circ-0008833aa. Additionally, western blot analysis was furthered performed to determine the level of Caspase-1, IL-18, IL-1β, NLRP3, ASC, and cleaved GSDMD regulated by has-circ-0008833 and circ-0008833-57aa. Results: Initially, we screened the expression profiles of human circRNAs in peripheral blood mononuclear cells of COPD patients, and found that has-circ-0008833 exhibited a significant increase in COPD mononuclear cells. Subsequently, we demonstrated that has-circ-0008833 carried an open reading frame (ORF), which encoded a functional protein, referred to as circ-0008833-57aa. By employing gain-of-function approaches, our results suggested that both circ-0008833 and circ-0008833-57aa inhibited proliferation, but accelerated the rate of 16HBE cell death. Finally, we discovered that circ-0008833 and circ-0008833-57aa promoted the expression of Caspase-1, IL-18, IL-1β, NLRP3, ASC, and cleaved GSDMD in 16HBE cells. Conclusions: Upregulation of circ-0008833 might promote COPD progression by inducing pyroptosis of bronchial epithelial cells through the encoding of a 57-amino acid peptide.</p

Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report

Hypervirulent Klebsiella pneumoniae (hvKp) causes increasing infections in healthy individuals from the community. In severe cases, it can cause multiple organ infection with invasive metastasis of blood sources, seriously threatening the patients’ life. Rapid and accurate diagnosis of the pathogen becomes the key to timely antibiotic treatment to improve the prognosis. This article reports a case of liver abscess complicated with multiple organ invasive infection caused by hematogenous-disseminated hvKp. K. pneumoniae was identified by culture and metagenomic next-generation sequencing (mNGS) using blood and liver abscess drainage fluid. The isolates from the two samples were subsequently identified with high homology (99.999%) by whole genome sequencing. In addition, multiple virulence genes were detected in the two isolates and the string test was positive, indicating hvKp with hypermucoviscosity phenotype. Multiple antibiotic treatments were given. The conditions of the patient were stable but the temperature remained high. Surgical drainage treatment was performed, and the patient’s body temperature immediately dropped to normal. He finally recovered after 6 months of follow-up. mNGS using body fluids can facilitate the rapid diagnosis of pathogens. For hvKp infection, choosing a better antibiotic therapy and receiving surgical drainage can significantly improve the prognosis of the patient