RESUMO
BACKGROUND: Acute lung injury (ALI) can cause multiple organ dysfunction and a high mortality rate. Inflammatory responses, oxidative stress, and immune damage contribute to their pathogenic mechanisms. We studied the role of the newly discovered lncRNA, Lncmir155hg, in ALI. METHODS: The levels of Lncmir155hg and miR-450b-5p from mice with ALI were detected via polymerase chain reaction analysis (qRT-PCR) and Fluorescence in situ hybridization (FISH). Pathological changes of lung were detected by HE (hematoxylin and eosin) staining, and HIF-1α, NOD-like receptor 3 (NLRP3) and caspase-1 protein changes were detected by immunohistochemistry. MLE-12 cells proliferation was detected by Cell-Counting Kit 8 analysis, and reactive oxygen species (ROS) was detected via flow cytometry. NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were measured via western blotting, and enzyme-linked immunosorbent assays detected the expression of Inflammatory factors. Lncmir155hg, miR-450b-5p, miR-450b-5p, and HIF-1α targets were predicted using LncTar and miRWalk and confirmed in dual-luciferase reporter assays. RESULTS: In mice with ALI and MLE-12 cells induced by lipopolysaccharide (LPS), Lncmir155hg was high-expressed and miR-450b-5p was low-expressed. sh-Lncmir155hg reduced the damage of lung tissue, the production of inflammatory cytokines and oxidative stress reaction induced by LPSï¼miR-450b-5p reverses the effect of Lncmir155hg in mice. sh-Lncmir155hg decreased the protein levels of HIF-1α, NLRP3 and caspase-1 in LPS-induced lung tissues. sh-Lncmir155hg + miR-450b-5p inhibitor transfection reversed the effect of sh-Lncmir155hg on the expression of HIF-1α, NLRP3 and caspase-1. Lncmir155hg knockdown induced proliferation and inhibited NLRP3-inflammasome activation and oxidative stress in MLE-12 cells of ALI. miR-450b-5p was identified to have binding with Lncmir155hg, and inhibition of miR-450b-5p eliminated the effect of si-Lncmir155hg in MLE-12 cells of ALI. More importantly, miR-450b-5p was directly combined with HIF-1α, miR-450b-5p mimic promoted proliferation and inhibited activation of inflammasome associated proteins and reaction of oxidative stress, and HIF-1α overexpression abolished these effects. CONCLUSION: Lncmir155hg aggravated ALI via the miR-450b-5p/HIF-1α axis.
RESUMO
BACKGROUND: Studies have reported the relationship between functional constipation and obesity in pediatric population. However, the results are contradictory. The purpose of this study is to evaluate the possible association between these two disorders in pediatric population. METHODS: Four databases including PubMed, Embase, CENTRAL, and Web of Science were searched until 30 September 2022. The review was done in accordance with PRISMA guidelines and registered in PROSPERO (CRD42022328992) RESULTS: Nine studies met the eligibility criteria, including 7444 participants. Studies showed the risk of obesity was significantly increased in boys with functional constipation (CI: 1.12, 3.07; P = 0.016). Such an association was also observed in girls (CI: 1.42-4.47; P = 0.00). A statistically significant association was observed between overweight/obesity and increased risk of functional constipation in children and adolescents (CI: 1.14-3.97; P = 0.02). Especially in developed countries (CI: 1.49-3.46; P = 0.00); however, no significant association was observed in developing countries (CI: 0.81-5.3; P = 0.13). CONCLUSIONS: There is a risk of obesity in either boys or girls with functional constipation. An association exists between the risk of functional constipation and children/adolescents with obesity, especially in developed countries, but not in developing countries. IMPACT: Our study encourages further research in this field because early detection and intervention are crucial for both functional constipation and overweight/obesity in children, to better identify its complex biology and possibly optimize the treatment approaches.