Experimental biology and medicine (Maywood, N.J.)最新文献

{"title":"Effects of hydrogen as adjuvant treatment for unstable angina.","authors":"Yanhong Si,&nbsp;Hua Tian,&nbsp;Bingqing Dong,&nbsp;Ying Zhang,&nbsp;Yuanyuan Wen,&nbsp;Xiubin Jia,&nbsp;Ying Li,&nbsp;Aihua Zhang,&nbsp;Shucun Qin","doi":"10.1177/15353702211009138","DOIUrl":"https://doi.org/10.1177/15353702211009138","url":null,"abstract":"<p><p>Oxidative stress and inflammation are closely related to atherosclerotic cardiovascular disease. It is established that hydrogen has significant protective effects on many diseases as a potential antioxidative and anti-inflammatory agent. The purpose of this study is to evaluate the effect of hydrogen on unstable angina <i>in vitro and in vivo.</i> An atherosclerosis model <i>in vitro</i> was constructed by ox-LDL-induced injury of human umbilical vein endothelial cells and <i>in vitro</i> testing indicated hydrogen inhibited ox-LDL-induced oxidative stress and inflammatory response by down-regulating LOX-1/NF-kB signaling pathway. Subsequently, the attenuating effect of hydrogen-rich water intake on unstable angina was further confirmed in clinic. Forty hospitalized subjects with unstable angina were enrolled and consumed either 1000-1200 mL/d hydrogen-rich water or the same amount of placebo pure water in addition to conventional drugs for three months. Clinical analysis showed hydrogen-rich water intake relieved angina symptoms in unstable angina patients. Serum analysis showed that hydrogen-rich water addition resulted in more effective reductions of total-cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B levels compared with conventional treatment. These results support that hydrogen as adjuvant treatment has a beneficial effect on unstable angina.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1981-1989"},"PeriodicalIF":3.2,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211009138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38907626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel single-tube multiplex real-time PCR assay for genotyping of thiopurine intolerance-causing variant <i>NUDT15</i> c.415C>T.","authors":"Xiaoyun Lian,&nbsp;Yanwei Li,&nbsp;Lan Li,&nbsp;Kaicheng U,&nbsp;Wenxia Wang,&nbsp;Yinmin Shi,&nbsp;Jiying Ma,&nbsp;Huijuan Wang","doi":"10.1177/15353702211026579","DOIUrl":"https://doi.org/10.1177/15353702211026579","url":null,"abstract":"<p><p>Thiopurines are commonly used in the treatment of acute lymphoblastic leukaemia and autoimmune conditions, can be limited by myelosuppression. The <i>NUDT15</i> c.415C>T variant is strongly associated with thiopurine-induced myelosuppression, especially in Asians. The purpose of this study was to develop a fast and reliable genotyping method for <i>NUDT15</i> c.415C>T and investigate the polymorphic distribution among different races in China. A single-tube multiplex real-time PCR assay for <i>NUDT15</i> c.415C>T genotyping was established using allele-specific TaqMan probes. In 229 samples, the genotyping results obtained through the established method were completely concordant with those obtained by Sanger sequencing. The distributions of <i>NUDT15</i> c.415C>T among 173 Han Chinese, 48 Miaos, 40 Kazakhs, and 40 Kirghiz were different, with allelic frequencies of 0.06, 0.02, 0.07, and 0, respectively. This method will provide a powerful tool for the implementation of the genotyping-based personalized prescription of thiopurines in clinical settings.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1961-1967"},"PeriodicalIF":3.2,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474986/pdf/10.1177_15353702211026579.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39125186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins.","authors":"Mingfei Xu,&nbsp;Chaoyue Liu,&nbsp;Lulan Pu,&nbsp;Jinrong Lai,&nbsp;Jingjia Li,&nbsp;Qianwen Ning,&nbsp;Xin Liu,&nbsp;Shishan Deng","doi":"10.1177/15353702211010417","DOIUrl":"https://doi.org/10.1177/15353702211010417","url":null,"abstract":"<p><p>Cadherins form connection between cells, facilitate communication, and serve as essential agents in the progression of multiple cancers. Over 100 cadherins have been identified and they are mainly divided into four groups: classical cadherins (CDHs), protocadherins (PCDHs), desmosomal (DSC), and cadherin-related proteins. Accumulating evidence has indicated that several members of the cadherins are involved in breast cancer development. Nevertheless, the expression profiles and corresponding prognostic outcomes of these breast cancer-related cadherins are yet to be analyzed. Here, we examined the expression levels and prognostic potential of these breast cancer-related cadherins from the specific databases viz. oncomine, gene expression profiling interactive analysis, human protein atlas, UALCAN, Kaplan-Meier Plotter, and cBioPortal. We found that the CDH2/11 levels were higher in breast cancer tissues, compared to healthy breast tissues, whereas with CDH3-5, PCDH8/10, and DSC3, the levels were lower in the former than in the latter. Additionally, for CDH1/6/13/17/23, PCDH7, and FAT4, trancript level alterations between breast cancer and healthy tissues varied across different databases. The CDH1 protein levels were elevated in breast cancer tissues versus healthy breast tissues, whereas the protein levels of CDH3/11 and PCDH8/10 were reduced in breast cancer, compared to healthy breast tissues. For CDH15 and CDH23, the expression levels paralleled tumor stage. Survival analysis, using the Kaplan-Meier Plotter database, demonstrated that elevated CDH1-3 levels correlated with diminished relapse-free survival in breast cancer patients. Alternately, enhanced CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 levels estimated a rise in relapse-free survival of breast cancer patients. These data suggest CDH1-3 to be a promising target for breast cancer precision therapy and CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 to be novel biomarkers for breast cancer prognosis.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1706-1720"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211010417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38907628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of plasma acylcarnitines with insulin sensitivity, insulin secretion, and prediabetes in a biracial cohort.","authors":"Ibiye Owei,&nbsp;Nkiru Umekwe,&nbsp;Frankie Stentz,&nbsp;Jim Wan,&nbsp;Sam Dagogo-Jack","doi":"10.1177/15353702211009493","DOIUrl":"https://doi.org/10.1177/15353702211009493","url":null,"abstract":"<p><p>The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1698-1705"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211009493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 variants: A double-edged sword?","authors":"Manasi P Jogalekar,&nbsp;Anurag Veerabathini,&nbsp;Prakash Gangadaran","doi":"10.1177/15353702211014146","DOIUrl":"https://doi.org/10.1177/15353702211014146","url":null,"abstract":"<p><p>Since the worldwide emergence of the COVID-19 outbreak, there have been international concerns about the possible viral evolution into variants with underlying mutations that may contribute to their increased transmissibility, disease severity, risk of death, and their potential escape from the immune response or may even lead to its extinction. Rigorous surveillance has revealed the variants harboring mutations in the spike protein, the main target of neutralizing antibodies generated through vaccination or herd immunity. In this review, we have highlighted major SARS-CoV-2 variants as well as other local strains along with their specific mutations, suspected changes in their characteristics, and their impact on the current pandemic and vaccine efficacy. We have also emphasized the need to develop widely protective interventions to curb further transmission of variants.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1721-1726"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211014146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38927273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutant U2AF1-induced differential alternative splicing causes an oxidative stress in bone marrow stromal cells.","authors":"Zhe Liu,&nbsp;Xuanjia Dong,&nbsp;Zhijie Cao,&nbsp;Shaowei Qiu,&nbsp;Yihui Li,&nbsp;Mengjun Zhong,&nbsp;Zhenya Xue,&nbsp;Yingxi Xu,&nbsp;Haiyan Xing,&nbsp;Kejing Tang,&nbsp;Zheng Tian,&nbsp;Min Wang,&nbsp;Qing Rao,&nbsp;Jianxiang Wang","doi":"10.1177/15353702211010130","DOIUrl":"https://doi.org/10.1177/15353702211010130","url":null,"abstract":"<p><p>Alternative splicing (AS) is a critical regulatory process of gene expression. In bone marrow microenvironment, AS plays a critical role in mesenchymal stem cells fate determination by forming distinct isoforms of important regulators. As a spliceosome factor, U2AF1 is essential for the catalysis of pre-mRNA splicing, and its mutation can cause differential AS events. In the present study, by forced expression of mutant U2AF1 (U2AF1S34F) in the mouse bone marrow stroma OP9 cells, we determine AS changes in U2AF1S34F transduced OP9 cells and investigate their role in stroma cell biological functions. We find that abundant differential RNA splicing events are induced by U2AF1S34F in OP9 cells. U2AF1S34F causes increased generation of hydrogen peroxide, promotes production of cytokines and chemokines. U2AF1S34F transduced OP9 cells also exhibit dysfunction of mitochondria. RNA-seq data, gene ontology (GO), and gene set enrichment analysis reveal that differentially expressed genes downregulated in response to U2AF1S34F are enriched in peroxisome component and function. U2AF1S34F can also cause release of hydrogen peroxide from OP9 cells. Furthermore, we investigate the influence of U2AF1S34F-induced oxidative stress in stromal cells on hematopoietic cells. When co-culturing mouse bone marrow mononuclear cells with OP9 cells, the U2AF1S34F expressing OP9 cells induce phosphorylation of histone H2AX in hematopoietic cells. Collectively, our results reveal that mutant U2AF1-induced differential AS events cause oxidative stress in bone marrow stromal cells and can further lead to DNA damage and genomic instability in hematopoietic cells.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1750-1759"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211010130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39031218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleated red blood cells participate in myocardial regeneration in the toad <i>Bufo Gargarizan Gargarizan</i>.","authors":"Shu-Qin Liu,&nbsp;Xiao-Ye Hou,&nbsp;Feng Zhao,&nbsp;Xiao-Ge Zhao","doi":"10.1177/15353702211013297","DOIUrl":"https://doi.org/10.1177/15353702211013297","url":null,"abstract":"<p><p>Heart regeneration is negligible in humans and mammals but remarkable in some ectotherms. Humans and mammals lack nucleated red blood cells (NRBCs), while ectotherms have sufficient NRBCs. This study used <i>Bufo gargarizan gargarizan</i>, a Chinese toad subspecies, as a model animal to verify our hypothesis that NRBCs participate in myocardial regeneration. NRBC infiltration into myocardium was seen in the healthy toad hearts. Heart needle-injury was used as an enlarged model of physiological cardiomyocyte loss. It recovered quickly and scarlessly. NRBC infiltration increased during the recovery. Transwell assay was done to <i>in vitro</i> explore effects of myocardial injury on NRBCs. In the transwell system, NRBCs could infiltrate into cardiac pieces and could transdifferentiate toward cardiomyocytes. Heart apex cautery caused approximately 5% of the ventricle to be injured to varying degrees. In the mildly to moderately injured regions, NRBC infiltration increased and myocardial regeneration started soon after the inflammatory response; the severely damaged region underwent inflammation, scarring, and vascularity before NRBC infiltration and myocardial regeneration, and recovered scarlessly in four months. NRBCs were seen in the newly formed myocardium. Enzyme-linked immunosorbent assay and Western blotting showed that the levels of tumor necrosis factor-α, interleukin- 1β, 6, and11, cardiotrophin-1, vascular endothelial growth factor, erythropoietin, matrix metalloproteinase- 2 and 9 in the serum and/or cardiac tissues fluctuated in different patterns during the cardiac injury-regeneration. Cardiotrophin-1 could induce toad NRBC transdifferentiation toward cardiomyocytes <i>in vitro</i>. Taken together, the results suggest that the NRBC is a cell source for cardiomyocyte renewal/regeneration in the toad; cardiomyocyte loss triggers a series of biological processes, facilitating NRBC infiltration and transition to cardiomyocytes. This finding may guide a new direction for improving human myocardial regeneration.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1760-1775"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211013297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39009841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia.","authors":"Qinzhi Li,&nbsp;Yang Liu,&nbsp;Xiujuan Wang,&nbsp;Mingling Sun,&nbsp;Lei Wang,&nbsp;Xinyou Wang,&nbsp;Ying Liu,&nbsp;Wenxia Fan,&nbsp;Kaile Zhang,&nbsp;Xiao Sui,&nbsp;Xinhong Guo","doi":"10.1177/15353702211009787","DOIUrl":"https://doi.org/10.1177/15353702211009787","url":null,"abstract":"<p><p>This study investigates the regulatory effect of plasmacytoid dendritic cells (pDC)/myeloid dendritic cells (mDC) imbalance on balance of Th1/Th2 and Th17/Treg in primary immune thrombocytopenia (ITP). A total of 30 untreated ITP patients and 20 healthy controls were recruited. Compared with healthy control, the pDC proportion of ITP patients was significantly reduced (<i>P</i> = 0.004), while the mDC proportion was not significantly changed (<i>P</i> = 0.681), resulting in a decrease in the pDC/mDC ratio (<i>P</i> = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients (<i>P</i> < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased (<i>P</i> =0.014, <i>P</i> = 0.043, <i>P</i> < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased (<i>P</i> = 0.001, <i>P</i> = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased (<i>P</i> = 0.025, <i>P</i> = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients (<i>P</i> = 0.018, <i>P</i> < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased (<i>P</i> = 0.007, <i>P</i> < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-β) (<i>P</i> = 0.028, <i>P</i> = 0.042), and an increase in GATA-3 mRNA (<i>P</i> < 0.001). However, there was no significant difference in Foxp3 mRNA levels (<i>P</i> = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 (<i>r</i> = 0.526, <i>P</i> = 0.003) and IL-23 (<i>r </i>= 0.501, <i>P</i> = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts (<i>r</i> = -0.494, <i>P</i> = 0.009; <i>r</i> = -0.415, <i>P</i> = 0.028; <i>r</i> = -0.492, <i>P</i> = 0.032). However, IL-23 was positively correlated with IL-17 (<i>r </i>= 0.489, <i>P</i> = 0.006) and negatively correlated with platelet count (<i>r</i> = -0.564, <i>P</i> = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count (<i>r</i> = -0.443, <i>P</i> = 0.014; <i>r</i> = -0.471, <i>P</i> = 0.011). The imbalance of pDC/mDC and the increase of IL-6, IL-12, and IL-23 lead to the increased differentiation of CD4+ T cells into Th1 and Th17 cells, which might be the important mechanisms underlying the imbalance of Th1/Th2 and Th17/Treg in ITP patients.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"1688-1697"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/15353702211009787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38861859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergence of human pluripotent stem cell, organoid, and genome editing technologies.","authors":"Lin Wang,&nbsp;Zhaohui Ye,&nbsp;Yoon-Young Jang","doi":"10.1177/1535370220985808","DOIUrl":"https://doi.org/10.1177/1535370220985808","url":null,"abstract":"<p><p>The last decade has seen many exciting technological breakthroughs that greatly expanded the toolboxes for biological and biomedical research, yet few have had more impact than induced pluripotent stem cells and modern-day genome editing. These technologies are providing unprecedented opportunities to improve physiological relevance of experimental models, further our understanding of developmental processes, and develop novel therapies. One of the research areas that benefit greatly from these technological advances is the three-dimensional human organoid culture systems that resemble human tissues morphologically and physiologically. Here we summarize the development of human pluripotent stem cells and their differentiation through organoid formation. We further discuss how genetic modifications, genome editing in particular, were applied to answer basic biological and biomedical questions using organoid cultures of both somatic and pluripotent stem cell origins. Finally, we discuss the potential challenges of applying human pluripotent stem cell and organoid technologies for safety and efficiency evaluation of emerging genome editing tools.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"861-875"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1535370220985808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38840592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of histone acetylation in a murine model of allergic asthma by proteomic analysis.","authors":"Yuan Ren, Menglu Li, Shiyao Bai, Lingfei Kong, Xinming Su","doi":"10.1177/1535370220980345","DOIUrl":"10.1177/1535370220980345","url":null,"abstract":"<p><p>The pathogenesis of asthma is closely related to histone acetylation modification, but the specific acetylation sites related to this process remain indistinct. Herein, our study sought to identify differentially modified acetylation sites and their expression distribution in cells involved in asthma in lung tissues. The airway hyper-responsiveness, inflammation, and remodeling were assessed by non-invasive whole-body plethysmography, ELISA, and hematoxylin-eosin staining to confirm the successful establishment of the allergic asthma model. Afterward, the differentially modified acetylation sites in asthmatic lung tissues were identified and validated by using proteomics and western blotting, respectively. The immunohistochemistry analysis was applied to reveal the distribution of identified acetylation sites in asthmatic lung tissues. A total of 15 differentially modified acetylation sites, including 13 upregulated (H3K9ac, H3K14ac, H3K18ac, H3K23ac,H3K27ac, H3K36ac, H2B1KK120ac, H2B2BK20ac, H2BK16ac, H2BK20ac, H2BK108ac, H2BK116ac, and H2BK120ac) and 2 downregulated (H2BK5ac and H2BK11ac) sites were identified and validated. Furthermore, immunohistochemical staining of lung tissues showed that nine of the identified histone acetylation sites (H2BK5, H2BK11, H3K18, H2BK116, H2BK20, H2BK120, H3K9, H3K36, and H3K27) were differentially expressed in airway epithelial cells, and the acetylation of identified H3 histones were observed in both eosinophil and perivascular inflammatory cells. Additionally, differential expression of histone acetylation sites was also observed in nucleus of airway epithelial cells, vascular smooth muscle cells, perivascular inflammatory cells, and airway smooth muscle cells. In conclusion, we identified potential acetylation sites associated with asthma pathogenesis. These findings may contribute greatly in the search for therapeutic approaches for allergic asthma.</p>","PeriodicalId":520623,"journal":{"name":"Experimental biology and medicine (Maywood, N.J.)","volume":" ","pages":"929-939"},"PeriodicalIF":2.7,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024510/pdf/10.1177_1535370220980345.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38721246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}