Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective The study aimed to investigate whether montelukast sodium could alleviate airway inflammatory responses in asthmatic mice by affecting the PHD2/HIF-1α pathway.Methods An allergic asthma model was established by ovalbumin(OVA)induction,and 18 female BALB/c mice were randomly divided into a control group(Con group),an asthma group(OVA group),and an asthma group with montelukast sodium intervention(30 mg/kg montelukast sodium by oral administration 1 h before OVA challenge,Mon group).HE staining was used to analyze the pathological changes in the lungs of mice.Blood cell analyzer and kits were used to determine the number of inflammatory cells and the levels of cytokines,the content of lactic acid and pyruvic acid in the lungs,respectively.RT-PCR and Western blot were used to detect the mRNA and protein expression of HIF-1α,PHD2,E-cad and p120 in the lungs of mice.Results Compared with the Con group,there was a significant increase in the number of eosinophils,lymphocytes,neutrophils and monocytes,the levels of IL-5,IL-13,complement factor D(CFD)and contents of lactate and pyruvate in the lungs of mice in the OVA group.Lung HIF-1α,PHD2,p120 and E-cad mRNA levels were reduced,meanwhile HIF-1α and PHD2 protein expression were upregulated but E-cad and p120 protein expression were downregulated(all with P<0.05).After montelukast sodium intervention,the number of eosinophils and monocytes and CFD expression were significantly decreased in the lungs of Mon group,the contents of lactate and pyruvate were basically restored to normal,and the mRNA and protein expression of HIF-1α,PHD2,p120 and E-cad were effectively improved.Conclusion Montelukast sodium could alleviate the airway inflammatory responses in the lungs of asthmatic mice by regulating the PHD2/HIF-1α signaling pathway.

Objective To investigate the role of inosine monophosphate dehydrogenase(IMPDH)in the development of ovalbumin(OVA)-induced allergic asthma.Methods Thirty-six BALB/c female mice were randomly divided into a healthy con-trol group,an OVA asthma group,and an IMPDH inhibitor(ribavirin)intervention group,with 12 mice in each group.The bron-choalveolar lavage fluid(BALF),lung,peripheral blood and spleen were collected from each mouse.HE staining was used to an-alyze the pathological changes in the lung tissue,and immunohistochemistry was used to detect the expression of CD3 in the lung tissue.A hemocyte analyzer was used to determine the total number and classified counts of leukocytes in the BALF and peripheral blood.RT-PCR and Western blotting were used to detect IMPDH mRNA and protein levels,respectively,in the lung tissue.Immunofluorescence was used to detect IMPDH protein localization and expression in lung tissue,and flow cytometry was used to analyze lymphocyte subpopulations and their intracellular IMPDH protein levels in peripheral blood and spleen tis-sue.Results Compared with those in the healthy control group,the number of inflammatory cells around small airways and in alveolar spaces in the lungs of the OVA asthma group was greater,and the total number of leukocytes in both the BALF and pe-ripheral blood was significantly higher,with significant increases in the numbers of neutrophils,eosinophils,and monocytes(P＜0.05).There was also a significant increase in the level of IMPDH protein in lung tissue(P＜0.05),and immunostaining re-vealed increased expression of IMPDH protein in the cytoplasm of inflammatory cells in a dispersed pattern.Subsequently,lung inflammation was significantly reduced in OVA-induced asthmatic mice after ribavirin intervention,as characterized specifically by a significant reduction in eosinophils and neutrophils in the BALF(P＜0.05)and a decrease in the level of IMPDH protein in the lungs(P＜0.05).Furthermore,there was also a decrease in the expression of IMPDH in the cytoplasm of inflammatory cells,whereas an increased number of IMPDH-positive filamentous structures were observed in the nuclei of inflammatory cells.Additionally,the percentage of B cells in the spleens of the mice in the OVA asthma group was significantly greater than that in the control group(P＜0.05).After ribavirin intervention,the percentage of B cells in the spleens of asthmatic mice significantly decreased,whereas the percentages of NK,CD3+and CD8+T cells significantly increased(P＜0.05).Moreover,the IMPDH protein levels in NK cells increased,whereas the IMPDH protein levels in CD8+T cells decreased in the spleen.Conclusion Inhibition of IMPDH can effectively alleviate airway and systemic inflammation dominated by eosinophils.Moreover,it can also reduce the immune response of B cells and enhance the immune response effect of killer cells,such as NK and CD8 T cells,in the spleen.The underlying mechanism may be related to the level of IMPDH expression in inflammatory cells and the formation of filamentous structures.

Increasing prevalence of childhood obesity poses threats to the global health burden. Because this rising prevalence cannot be fully explained by traditional risk factors such as unhealthy diet and physical inactivity, early-life exposure to endocrine disrupting chemicals (EDCs) is recognized as emerging novel risk factors for childhood obesity. EDCs can disrupt the hormone-mediated metabolic pathways, affect children’s growth and mediate the development of childhood obesity. Many organic pollutants are recently classified to be EDCs. In this review, we summarized the epidemiological and laboratory evidence related to EDCs and childhood obesity, and discussed the possible mechanisms underpinning childhood obesity and early-life exposure to non-persistent organic pollutants (phthalates, bisphenol A, triclosan) and persistent organic pollutants (dichlorodiphenyltrichloroethane, polychlorinated biphenyls, polybrominated diphenyl ethers, per- and polyfluoroalkyl substances). Understanding the relationship between EDCs and childhood obesity helps to raise public awareness and formulate public health policy to protect the youth from exposure to the harmful effects of EDCs.
Adolescent ; Diet ; Endocrine Disruptors* ; Global Health ; Halogenated Diphenyl Ethers ; Humans ; Metabolic Networks and Pathways ; Pediatric Obesity* ; Polychlorinated Biphenyls ; Prevalence ; Public Health ; Risk Factors