ABSTRACT
Objective:To investigate the effect of ionizing radiation on the N 6-methyladenine (m 6A) modification profile of circular RNA (circRNA) in mouse bone marrow cells and provide scientific basis for revealing the relationship between RNA epigenetic modification and hematopoietic radiation injury. Methods:A total of twenty four C57BL/6 J mice were randomly divided into two groups: the healthy control group ( n=12), and ionizing radiation group ( n=12) irradiated in total body with 4 Gy of 137Cs γ-rays. At 5 min after irradiation, mice were killed and bone marrow cells were collected from the femur. Total RNAs were extracted and the changes in circRNA m6A modification profiles were investigated by RNA immunoprecipitation-high-throughput sequencing (MeRIP-Seq) technology and bioinformatics analysis. The representative alterations of m 6A peaks were validated by MeRIP-PCR assay. Results:325 and 455 m 6A sites were identified on circRNAs in the healthy control group and ionizing radiation group (178 common sites, 147 specific sites in the healthy control group and 277 specific sites in ionizing radiation group), respectively. 1 275 and 1 017 deriving genes of m 6A-circRNAs were identified in the healthy control group and ionizing radiation group (767 common genes, 508 specific genes in the healthy control group and 250 specific genes in ionizing radiation group), respectively. Compared with the control healthy group, 414 (178) m 6A peaks was significantly up- (down-) regulated in the ionizing radiation group( P < 10 -10; fold-change cut-off > 5). Moreover, Gene Ontology (GO) assay revealed that the deriving genes of circRNAs with differentially methylated m 6A sites between two groups involves various functions including chromatin regulation, ciliary transition fiber and poly (A)-specific ribonuclease activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) assay revealed that the deriving genes of circRNAs with differentially methylated m 6A sites between two groups included numerous pathways such as platelet activation, Fc γ R-mediated phagocytosis and B cell receptor signaling pathway. Conclusions:Ionizing radiation triggers rapid alterations in the m 6A modification profile of circRNA in mouse bone marrow cells. The deriving genes of differentially methylated circRNAs are associated with a variety of functions and signaling pathways of hematopoietic radiobiology.
ABSTRACT
Objective:To study the effect of emulsifier Tween-80 on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy.Methods:Male C57BL/6 J mice were randomly divided into healthy control group, radiation-only group, radiation + Tween-80 group and radiation + Tween-80 + butyric acid group. The mice were exposed to total abdominal irradiation (TAI) using a specific steel lead chamber and γ-ray irradiator was used throughout the experiments. Mice in radiation+ Tween-80 group and radiation+ Tween-80+ butyric acid group were intragastrically administrated with Tween-80 for 7 d before irradiation, while healthy control group and radiation-only group were treated with sterile water. After irradiation, butyric acid was administrated to mice in radiation+ Tween-80+ butyric acid group until euthanasia, while healthy control group, radiation-only group and radiation+ Tween-80 group were treated with sterile water until euthanasia. Small intestine and fecal particles were collected 21 d after irradiation. The concentrations of bile acid in small intestinal and fecal samples were measured using enzyme linked immunosorbent assay (ELISA), the expression of TGR5 and JAM-A, as well as the ratio of IL-10/IL-12 in intestine were detected by quantitative real-time PCR (qRT-PCR). The expression levels of GPR43 in the colon were compared using immunohistochemistry (IHC).Results:Tween-80 pretreated mice exhibited lower concentration of bile acid in small intestine and higher level of bile acid in fecal sample after irradiation (7.92%, 7.99%, t=3.93, 2.94, P<0.05), the expression of TGR5, which mediating the biological function of bile acid, and it′s downstream JAM-A gene were down-regulated (20.93%, 9.91%, t=4.85, 5.14, P<0.05), the ratio of IL-10/IL-12 (indicator related to inhibition of inflammation) (4.59%, t=3.39, P<0.05) as well as the expression of GPR43 protein, a G-protein-coupled receptor for butyric acid, decreased in the colon of Tween-80-pretreated mice compared with the radiation-only group. ELISA assay revealed that butyric acid administration elevated bile acid level in small intestines (8.06%, t=9.25, P<0.05), but reduced that in feces (14.41%, t=4.71, P<0.05). In addition, TGR5 and JAM-A showed higher expression in the intestine of butyric acid-treated mice (19.35%, 32.71%, t=7.69, 19.23, P<0.05), as well as the ratio of IL-10/IL-12 (2.39%, 4.05%, t=3.38, 5.92, P<0.05) and the content of GPR43 protein in colon. Conclusions:Tween-80 deteriorates the disturbance of bile acid enterohepatic circulation induced by ionizing radiation in mice. Butyric acid administration erases the adverse effects of Tween-80.
ABSTRACT
Congenital adrenal hyperplasia(CAH)is a family of autosomal recessive disorders caused by the loss or severe decrense in activitv in one of the steroidogenie enzymes involved in cortisol biosynthesis.The cortisol synthetic block leads to corticotropin stimulation of the adrenal cortex.with accumulatiOn of cortisol precursors that are diverted to sex hormone biosynthesis.The most common CAH is 21-OHD due to deficiency of the enzyme 21-hydroxylase.It is distinguished in classical(C-CAH)and non-classical form(NC-CAH),and it is also one of the most eomnon autosomal recessive inherited disorders in human.The goal of therapy in CAH is to replace the missing glucocorticoids and mineralocorticoids,thereby suppressing eorticotropin concentrations and normalizing adrenal androgens, a8 well as to enable normal growth and skeletal maturation.Nonetheless.growth is a key problem in CAH because patients often fail to reach their target height,and the average heights are shorter than the general population,relating both to the underlying disease and its treatment.This paper review the literature on growth and final height outcome,considering the factors related tO diagnosis and treatment which are known to affect height outcome.Current strategies to optimize height outcome are indicated and future treatment strategies as well.