RNA mA modification and its function in diseases / 医学前沿

N-methyladenosine (mA) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism. mA modification could be installed by mA "writers" composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by mA "erasers" (FTO and ALKBH5). The function of mA is executed by mA "readers" that bind to mA directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in mA modulators ("writers," "erasers," and "readers") have remarkably renewed our understanding of the function and regulation of mA in different cells under normal or disease conditions. However, the mechanism and the regulatory network of mA are still largely unknown. Moreover, investigations of the mA physiological roles in human diseases are limited. In this review, we summarize the recent advances in mA research and highlight the functional relevance and importance of mA modification in in vitro cell lines, in physiological contexts, and in cancers.

Effects of budesonide on HIF-1α and VEGF expression and airway remodeling in an asthmatic mouse model / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model.</p><p><b>METHODS</b>Thirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 μg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated.</p><p><b>RESULTS</b>Vessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF.</p><p><b>CONCLUSIONS</b>Budesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.</p>

Mechanism of conditioned immune response in curing bronchial asthma in mice / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the mechanism of effect of conditioned immune response in curing bronchial asthma.</p><p><b>METHODS</b>An experimental asthma modal was produced on healthy BALB/C mice (female, 4 - 6 weeks old) by sensitization and stimulation with ovalbumin (OV A). Totally 105 mice were divided into 7 groups randomly with 15 in each and treated differently: in group CIR(1), noise was used as conditioned stimulus (CS) and budesonide and salbutamol as unconditioned stimulus (UCS) respectively, a conditioned immune response model of mice with asthma was established by the combination of CS and UCS 7 times (7 days), then the mice were given CS only, and the combination were given once a week for 20 weeks. In group CIR(2) saccharin (SAC) was taken as CS, and the other treatments were the same as the group CIR(1). In the group of conventional therapy, the mice were given inhalation of nebulized budesonide and salbutamol only for 20 weeks. In the group of lower dose conventional therapy, the mice were given nebulized inhalation of budesonide and salbutamol for the first 7 days, then once a week for 20 weeks. In the noise group the mice were given noise only everyday for 20 weeks. In SAC group the mice were treated with SAC only everyday for 20 weeks. In the blank control group the mice were treated with placebo for 20 weeks. The mice in all the groups were stimulated with OVA once a day. The mice in the healthy control group were given PBS inhalation for 20 weeks. After 20 weeks therapy, the bronchoalveolar lavage fluid (BALF) was taken for eosinophils (EOS) counting. The spleens were taken to obtain CD4(+)T lymphocytes and the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7), IL-4, IFN-gamma and IL-17 were detected by flow cytometry.</p><p><b>RESULTS</b>(1) The percent of EOS of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that of blank control (P < 0.01), and there was no significant difference among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). (2) The expression of nAChRalpha7, IL-4 and IL-17 of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that in blank control group, IFN-gamma was much higher (P < 0.01), and no significant difference was found among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). There was a positive correlation between nAChRalpha7 and IL-4 (r = 0.76, P < 0.01), nAChRalpha7 and IL-17 (r = 0.46, P < 0.01). There was a negative correlation between nAChRalpha7 and IFN-gamma (r = 0.69, P < 0.01). (3) In the groups treated with lower dose of conventional therapy, noise, SAC and blank control, the epithelial tissue of airway were much thicker, the lumens were much narrower, and inflammatory cells and collagen fibers were much more than in the healthy control group, and after therapy, the inflammation in groups CIR(1), CIR(2) and conventional therapy was significantly improved.</p><p><b>CONCLUSION</b>The conditioned immune response models established by both noise and SAC as CS and budesonide and salbutamol as UCS can downregulate nAChRalpha7 on CD4(+)T lymphocytes, regulate the function of CD4(+)T lymphocytes, and achieve the same therapeutic efficacy in treatment of asthma.</p>

Mechanisms of Stimulating Vagus Nerve on CD4~+ T Lymphocytes Activation in Experimental Arthritis Rats / 实用儿科临床杂志

Objective To explore the effects of stimulating vagus nerve with pulse current on peripheral blood CD4+T lymphocyte of rats with collagen induced arthritis and its mechanism.Methods To duplicate model rats of experimental arthritis(EA)by intradermal injection of Ⅱtype collagen,divide the rats into 2 groups:vagus nerve stimulation(VNS)group and sham operated group.Rats in VNS group were stimulated at the left cervical vagus nerves for 30 minutes a day with constant square wave,pulse current with intra train of 16 Hz,pulse duration of 1.0 ms,train duration of 10 s,interstimulus interval of 1.5 min and intensities of 3.0 mA.Then flow cytometry and immunofluorescence methods were used to detect the activation of CD4+T lymphocytes(expressing CD71)and the expression of nicotinic acetylcholine receptors alpha 7(nAChR?7)and choline acetyltransferase(ChAT)in peripheral blood CD4+T lymphocytes.Results In VNS group,the expression of nAChR?7 and ChAT were significantly raised in CD4+ T cells at 1st weekend(Pa