Page 12 - 北京京煤集团总医院第十一届·2023学术年会论文集
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北京京煤集团总医院                                                          第十一届·2023 学术年会论文集

                   commitment in T cells  [23] , and different subtypes of T cells influence immune responses in asthma
                   [24] . In addition, the Th17 cell lineage is subject to epigenetic plasticity through the remodeling of

                   its chromatin structure  [25] . A study found that genes associated with lysine levels may be also linked
                   to reduced inflammation and the degradation of air pollutants, and that these genes are less abundant
                   in asthmatics  [26] . Furthermore, there are differences in serum metabolites between children with
                   exacerbation-prone and non-exacerbation-prone asthma, with significant differences in those from

                   the lysine pathway  [27] .
                       B cells are a major component of the adaptive immune response to house dust mite allergens.
                   Depletion of B cells in house dust mite-sensitive mice prior to house dust mite stimulation results
                   in decreased allergic responses  [28] . Mast cells also play a role in asthma by secreting mediators with

                   pro-inflammatory  and  airway  constrictive  effects,  such  as  histamine  and  bioactive  lipids   [29] .
                   However, the role of NK cells in patients with asthma remains controversial. Studies have reported
                   that NK cells can promote the regression of inflammation by inducing eosinophil apoptosis  [30] .
                   Impaired cytotoxicity of peripheral blood NK cells has also been found in patients with severe

                   asthma, suggesting an impaired ability to manage severe asthmatic inflammation  [31, 32] . This study
                   revealed differences in multiple immune cells between patients with severe asthma and healthy
                   individuals.

                       To  further  investigate  the  relationship  between  CRs  and  prognosis  in  patients  with  severe
                   asthma, we constructed a prognostic prediction model using the four identified key CRs: SMARCC1,
                   CHD8, SETD2, and KMT2B. The model showed a good predictive performance for prognosis. It is
                   known  that  the  association  of  the  SWI/SNF  chromatin  remodeling  complex  with  cell  cycle

                   checkpoint genes controls cell proliferation and that SMARCC1 is an important member of the
                   SWI/SNF complex; SMARCC1 also plays an important role in development  [33] . The SWI/SNF
                   complex  has  been  observed  in  chronic  rhinosinusitis,  and  it  is  possibly  involved  in  the
                   pathophysiology of the disease  [34] . Patients with high blood eosinophil counts had lower levels of

                   expression of the BAF155 protein, whereas patients with high histopathological eosinophil counts
                   had lower expression of all SWI/SNF subunits  [34] .
                       SETD2 is a histone modifier responsible for the trimethylation of lysine 36 of histone H3
                   (H3K36)  [35] . Air pollution has been linked to several lung diseases, and particulate matter of 10 μm

                   in diameter (PM10) induces aneuploidy and leads to the generation of chromosomal instability in
                   A549 cells by downregulating SETD2  [36] . Our model also involved KMT2B, which encodes an
                   enzyme involved in histone H3 lysine 4 (H3K4) methylation  [37] , and CHD8, which encodes for a

                   member of the chromodomain-helicase-DNA binding protein family that has been reported to play
                   a role in transcriptional regulation, epigenetic remodeling, and other processes  [38] .
                       To further investigate the role of model genes in severe asthma, we constructed an miRNA-
                   mRNA regulatory network. The results showed that all genes, except KMT2B, were regulated by
                   multiple miRNAs, suggesting complex regulatory relationships. In addition, predicted drugs also

                   provide a basis for the future treatment of severe asthma.



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