雷公藤红素通过靶向核受体Nur77促进损伤线粒体自噬而抑制炎症反应

文章简介线粒体在细胞死亡、自噬、免疫和炎症中起着不可或缺的作用。前期研究发现,孤儿核受体Nur77通过靶向线粒体诱导细胞凋亡。本文报道了Nur77作为具有抗炎作用的雷公藤红素的直接靶点,介导雷公藤红素通过自噬清除损伤线粒体,抑制炎症反应而达到治疗炎症疾病包括肥胖症的功能。研究人员发现,雷公藤红素的结合

Review of Structural Fire Hazards, Challenges, and Prevention Strategies

Reducing the occurrence of structural fires is the common goal of all countries. However, the development level of different countries determines the degree of perfection of local fire management regulations. Developed countries have a more rational urban layout, sufficient firefighting resources, and the ability to guarantee fire safety. In contrast, haphazardly built residential areas in developing and underdeveloped countries have more safety hazards, which increases the challenges of local fire management. This study provides an overview of the causes and impacts of fires in different countries and identifies gaps in fire safety between developed and developing countries, as well as corresponding strategies to deal with fires. It is worth mentioning that the development and evolution of artificial intelligence (AI) has made it possible to predict fires, thereby greatly reducing damage and losses caused by fires. In addition, the development of new fire-resistant building materials, etc., provides more means to reduce the possibility of fire

Impacts of temperature on evolution of char structure during pyrolysis of lignin

This study investigated the pyrolysis of lignin pyrolysis in a temperature region from 200 to 800 °C, aiming to understand influence of pyrolysis temperature on evolution of structures of the resulting char. The results showed that fusion of the ring structure initiated at 200 °C, where the C/H ratio in the char was equal to that in naphthalene (two fused rings). The C/H ratio in the char obtained at 350 °C corresponded to that in pyrene (four fused rings), while the char produced at 550 °C was equivalent to 20 fused benzene rings in terms of C/H ratio. The increasing pyrolysis temperature also shifted the oxygen-containing functionalities such as the carbonyl, esters, ketones in the bio-oil to the ether functionality that had a higher thermal stability. The DRIFTS study of pyrolysis of lignin showed that drastic changes of the functionalities and the internal structure of the char occurred in a narrow temperature region from 520 to 530 °C. The carbonyl functionality and the aliphatic structure were eliminated, and new conjugated π-bond systems formed

Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model

Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.National Key R&D Program of China [2016YFC0903700]; National Natural Science Foundation of China [81520108001, 81220108001, 81770043]; 973 Key Scheme of China [2015CB553406]; Guangzhou Science and Technology Programs for Science Study [201607020030]; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme; Guangzhou Department of Science and Technology programs [201607020030]; Guangzhou Department of Education grant [1201620007]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Pharmacological activation of PPARγ inhibits hypoxia-induced proliferation through a caveolin-1-targeted and -dependent mechanism in PASMCs

Previously, we and others have demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPAR gamma are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1. However, other than the caveolin-1 targeted mechanism, in this study, we further uncovered a caveolin-1 dependent mechanism within the activation of PPAR gamma by the specific agonist GW1929. First, effective knockdown of caveolin-1 by small-interfering RNA (siRNA) markedly abolished the upregulation of GW1929 on PPAR gamma expression at both mRNA and protein levels; Then, in HEK293T, which has previously been reported with low endogenous caveolin-1 expression, exogenous expression of caveolin-1 significantly enhanced the upregulation of GW1929 on PPAR gamma expression compared with nontransfection control. In addition, inhibition of PPAR gamma by either siRNA or pharmacological inhibitor T0070907 led to increased phosphorylation of cellular mitogen-activated protein kinases ERK1/2 and p38. In parallel. GW 1929 dramatically decreased the expression of the proliferative regulators (cyclin D1 and PCNA), whereas it increased the apoptotic factors (p21, p53, and mdm2) in hypoxic PASMCs. Furthermore, these effects of GW1929 could be partially reversed by recovery of the drug treatment. In combination, PPAR gamma activation by GW1929 reversibly drove the cell toward an antiproliferative and proapoptotic phenotype in a caveolin-1-dependent and -targeted mechanism.National Heart, Lung, and Blood Institute [R01-HL-093020]; National Natural Science Foundation of China [81173112, 81470246, 81170052, 81220108001]; Guangzhou Department of Education Yangcheng Scholarship [12A001S]; Guangzhou Department of Natural Science [2014Y2-00167]; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2014)12 month embargo; published online: 1 April 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]