Effects of resistance training on cardiovascular health in non-obese active adolescents

AIM:To determine the benefits of a 10-wk resistance training programme on cardiovascular health in nonobese and active adolescents.METHODS:This is a pragmatic randomised controlled intervention.The study was carried out in a Hong Kong Government secondary school.Thirty-eight lean and active boys and girls were randomised to either the resistance training group or the control group.Students in the resistance training group received in-school 10-wk supervised resistance training twice per week,with each session lasting 70 min.Main outcome measures taken before and after training included brachial endothelial dependent flow-mediated dilation,body composition,fasting serum lipids,fasting glucose and insulin,high sensitive C-reactive protein,24-h ambulatory blood pressure and aerobic fitness.RESULTS:The only training related change was in endothelial dependent flow-mediated dilation which increased from 8.5%to 9.8%.A main effect of time and an interaction(P<0.005) indicated that this improvement was a result of the 10-wk resistance training.Main effects for time(P<0.05) in a number of anthropometric,metabolic and vascular variables were noted;however,there were no significant interactions indicating the change was more likely an outcome of normal growth and development as opposed to a training effect.CONCLUSION:Ten weeks of resistance training in school appears to have some vascular benefit in active,lean children.

MTBSTFA derivatization-LC-MS/MS approach for the quantitative analysis of endogenous nucleotides in human colorectal carcinoma cells

Endogenous ribonucleotides(RNs)and deoxyribonucleotides(dRNs)are important metabolites related to the pathogenesis of many diseases.In light of their physiological and pathological significances,a novel and sensitive pre-column derivatization method with N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide(MTBSTFA)was developed to determine RNs and dRNs in human cells using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A one-step extraction of cells with 85%methanol followed by a simple derivatization reaction within 5 min at room temperature contributed to shortened analysis time.The derivatives of 22 nucleoside mono-,di-and tri-phosphates were retained on the typical C;column and eluted by ammonium acetate and acetonitrile in 9 min.Under these optimal conditions,good linearity was achieved in the tested calibration ranges.The lower limit of quantitation(LLOQ)was determined to be 0.1-0.4μM for the tested RNs and 0.001-0.1μM for dRNs.In addition,the precision(CV)was<15%and the RSD of stability was lower than 10.4%.Furthermore,this method was applied to quantify the endogenous nucleotides in human colorectal carcinoma cell lines HCT 116 exposed to 10-hydroxycamptothecin.In conclusion,our method has proven to be simple,rapid,sensitive,and reliable.It may be used for specific expanded studies on intracellular pharmacology in vitro.

Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

We elucidated the anti-inflammatory mechanisms of IL-38 in allergic asthma.Human bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly(I:C)/LyoVec or infection-related cytokine TNF-αto induce expression of cytokines/chemokines/adhesion molecules.House dust mite(HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in vivo.IL-38 significantly inhibited induced proinflammatory IL-6,IL-1β,CCL5,and CXCL10 production,and antiviral interferon-βand intercellular adhesion molecule-1 expression in the coculture system.Mass cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1,STAT3,p38 MAPK,ERK1/2,and NF-κB pathways,and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene RGS13.Intraperitoneal injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4,IL-5,and IL-13 in the bronchoalveolar lavage fluid(BALF)and lung homogenates.Histological examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia,together with reduced Th2,Th17,and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs,spleen,and lymph nodes.IL-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice,together with significantly decreased CCR3^(+) eosinophil numbers in the BALF and lungs,and a reduced percentage of human CD4^(+)CRTH2^(+)Th2 cells in the lungs and mediastinal lymph nodes.Together,our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic asthma.

Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma

We sought to examine the regulatory effect of Meteorin-β(Metrnβ)/Meteorin like(Metrnl)/IL-41 on lung inflammation in allergic asthma.We found that Metrnβwas elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite(HDM)extract.Upon exposure to HDM,Metrnβwas secreted predominantly by airway epithelial cells and inflammatory cells,including macrophages and eosinophils.The increased Metrnβeffectively blocked the development of airway hyperreactivity(AHR)and decreased inflammatory cell airway infiltration and type 2 cytokine production,which was associated with downregulated DC-mediated adaptive immune responses.Moreover,Metrnβimpaired the maturation and function of bone marrow-derived dendritic cells in vitro.Asthmatic mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR,airway inflammation,and lung injury.Metrnβalso displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models.Moreover,blockade of Metrnβby anti-Metrnβantibody treatment promoted the development of allergic asthma.These results revealed the unappreciated protective roles of Metrnβin alleviating DC-mediated Th2 inflammation in allergic asthma,providing the novel treatment strategy of therapeutic targeting of Metrnβin allergic asthma.

Novel insights into the role of anti-inflammatory IL-38 in immunity against infection

Since the identification and cloning of interleukin(IL)-38 in 2001,a plethora of studies have focused on its essential roles as a novel IL-1 family cytokine in both innate and acquired immunity.Based on the shared traits with IL-36 receptor antagonist(IL-36Ra)and IL-1 receptor antagonist(IL-1Ra),IL-38 constitutes one of the most important anti-inflammatory cytokines within the IL-36 subfamily and thus elicits its antagonistic effects through binding to IL-36 receptor(IL-36R)and to IL-R1 with a relatively low affinity[1,2].IL-38 has been proven to bind to X-linked interleukin-1 receptor accessory protein-like 1(IL1RAPL1)[1],and IL1RAPL1 therefore serves as a novel receptor of IL-38.

NOD2 和 TLR2 ligands 由在遗传性过敏症的像皮炎的皮肤发炎与真皮的成纤维细胞交往触发 basophils 和嗜曙红血球的激活

The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.