关键词：
Fibroblast activation;High-mobility group box protein 1 (HMGB1);MIR155 host gene (MIR155HG);Nuclear factor kappa beta (NF-κB);Pulmonary fibrosis (PF);miR-627
摘要：
Nature Reviews' clinical content is written by internationally renowned clinical academics and researchers and targeted towards readers in the medical sciences, from postgraduate level upwards. While intended to be read by practicing doctors, researchers and academics within a specialty, we aim to make all our articles accessible to readers working in any medical discipline. In-depth Reviews present authoritative, up-to-date information on a topic, placing it in the context of a field's history and development. Topical discussion and opinions are proffered in Perspectives and News & Views articles, and in the Research Highlights section we filter primary research from a range of specialty and general medical journals. Finally, Case Studies enable authors to present novel and interesting cases and discuss the most useful features to bear in mind for treating future cases.Subjects coveredRheumatoid arthritisOsteoarthritisMetabolic bone disease (including osteoporosis, osteonecrosis, Paget disease of bone)Connective tissue diseases (including systemic lupus erythematosus, scleroderma (systemic sclerosis), antiphospholipid antibody disease, S�gren disease, Raynaud phenomenon, Cogan keratitis syndrome, relapsing polychondritis) Spondyloarthropathies (including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis of inflammatory bowel disease)Acute inflammatory arthritis (including monoarthritis, oligoarthritis, polyarthritis, infectious/septic arthritis, crystal deposition diseases, Lyme disease)The idiopathic inflammatory myopathies (including polymyositis, dermatomyositis, juvenile dermatomyositis, inclusion body myositis)FibromyalgiaPolymyalgia RheumaticaVasculitis syndromes (including systemic vasculitides, large, medium and small vessel vasculitides, vasculitis of small vessels)Periarticular rheumatic disease (including bursitis, tendonitis)Pediatric rheumatic diseaseMiscellaneous rheumatic diseasesTherapy (including pharmacotherapy, physical therapy [exercise and rest], surgery, splinting, complementary and alternative treatments)Pain managementRehabilitationEpidemiologyGeneticsImmunologyInflammationHealth services, economics and outcomes research
摘要：
There are two well-characterized cannabinoid receptors (CB1R and CB2R and other candidates): the central nervous system (CNS) enriched CB1R and peripheral tissue enriched CB2R with a wide dynamic range of expression levels in different cell types of human tissues. Hepatocytes and neurons express low baseline CB1R and CB2R, respectively, and their cell-type-specific functions are not well defined. Here we report inducible expression of CB1R in the liver by high-fat and high sugar diet and CB2R in cortical neurons by methamphetamine. While there is less controversy about hepatocyte CB1R, the presence of functional neuronal CB2R is still debated to date. We found that neuron CB2R basal expression was higher than that of hepatocyte CB1R by measuring mRNA levels of specific isoform CB2A in neurons isolated by fluorescence-activated cell sorting (FACS) and CB1A in hepatocytes isolated by collagenase perfusion of liver. For in vivo studies, we generated hepatocyte, dopaminergic neuron, and microglia-specific conditional knockout mice (Abl-Cnr1(Delta), Dat-Cnr2(Delta), and Cx3cr1-Cnr2(Delta)) of CB1R and CB2R by crossing Cnr1(f/f) and Cnr2(f/f) strains to Abl-Cre, Dat-Cre, and Cx3cr1-Cre deleter mouse strains, respectively. Our data reveals that neuron and microglia CB2Rs are involved in the "tetrad" effects of the mixed agonist WIN 55212-2, CB1R selective agonist arachidonyl-2 '-chloroethylamide (ACEA), and CB2R selective agonist JWH133. Dat-Cnr2(Delta) and Cx3cr1-Cnr2(Delta) mice showed genotypic differences in hypomobility, hypothermia, analgesia, and catalepsy induced by the synthetic cannabinoids. Alcohol conditioned place preference was abolished in DAT-Cnr2(Delta) mice and remained intact in Cx3cr1-Cnr2(Delta) mice in comparison to WT mice. These Cre-loxP recombinant mouse lines provide unique approaches in cannabinoid research for dissecting the complex endocannabinoid system that is implicated in many chronic disorders.
摘要：
This study investigated the effects of a physiologically active peptide derived from rice bran (KF-8) on oxidative stress in D-galactose (D-gal)-induced aging mice and the underlying molecular mechanisms. The aging model was developed by subcutaneously injecting Institute of Cancer Research mice with 250 mg/kg D-gal daily for 12 weeks and simultaneously treating them with 30 mg/kg KF-8. The relative expression levels of Nrf2 and NF-kappa B in the liver were determined by the western blot. The regulation of Nrf2 and NF-kappa Bp65 by KF-8 was further validated in NIH/3T3 cells. Compared with the control mice, the aging mice had significantly decreased body weights as well as superoxide dismutase and GSH-Px levels (p < 0.05); however, they had increased serum reactive oxygen species and malondialdehyde and 8-hydroxydeoxyguanosine levels accompanied by aortic and brain injuries. They also had elevated RAGE, TLR4, I kappa B, Box, and caspase-8 expressions and NF-kappa B/p65 phosphorylation but reduced BcL-2 expression in the liver. Moreover, in vitro experiments demonstrated that the pretreatment of H2O2 -treated NIH/3T3 cells with KF8 significantly mitigated the NF-kappa B signaling and attenuated the Nrf2 nuclear transport (both p < 0.05). In conclusion, KF-8 treatment inhibited aging-induced oxidative stress-related organ injury in mice by attenuating NF-kappa B/p38 signaling and preserving Nrf2 activity.
摘要：
Epithelial-mesenchymal transition (EMT) is a biological process through which epithelial cells differentiate into mesenchymal cells. EMT plays an important role in embryonic development and wound healing; however, EMT also contributes to some pathological processes, such as tumor metastasis and fibrosis. EMT mechanisms, including gene mutation and transcription factor regulation, are complicated and not yet well understood. In this review, we introduce some herbal active substances that exert antitumor activity through inhibiting EMT that is induced by hypoxia, high blood glucose level, lipopolysaccharide, or other factors.
期刊：
JOURNAL OF CELLULAR BIOCHEMISTRY,2019年120(3):2983-2993 ISSN：0730-2312
通讯作者：
Zhang, Wei;Liang, Ying
作者机构：
[Zhang, Zhihui; Li, Jie; Song, Junfu; Liao, Wenjian] Jiangxi Prov Chest Hosp, Dept Internal Med, Nanchang, Jiangxi, Peoples R China.;[Kong, Xinyi] Nanchang Univ, Dept Cardiol, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China.;[Jiang, Shanshan] Peoples Hosp Anyang City, Dept Digest Syst, Anyang, Henan, Peoples R China.;[Liang, Ying] Cent South Univ Forestry & Technol, Mol Nutr Branch, Natl Engn Lab Rice & By Prod Deep Proc, Changsha, Hunan, Peoples R China.;[Liang, Ying] Cent South Univ Forestry & Technol, Coll Food Sci & Engn, Changsha, Hunan, Peoples R China.
通讯机构：
[Zhang, Wei] N;[Liang, Ying] C;Nanchang Univ, Dept Respirat, Affiliated Hosp 1, Nanchang 330006, Jiangxi, Peoples R China.;Cent South Univ Forestry & Technol, Dept Food Sci & Engn, 498 Shaoshan South Rd, Changsha 410004, Hunan, Peoples R China.
关键词：
RAGE/NF-kappaB signaling;high-mobility group box protein 1 (HMGB1);miR-627;normal human lung fibroblast (NHLF);pulmonary fibrosis (PF);regulatory loop
摘要：
Pulmonary fibrosis (PF) is a fibroproliferative disease that can eventually lead to fatal lung failure. It is characterized by abnormal proliferation of fibroblasts, dysregulated fibroblast differentiation to myofibroblast, and disorganized collagen and extracellular matrix production, deposition and degradation. There is still a lack of effective treatment strategies for PF. Extracellular high-mobility group box protein 1 (HMGB1) induces PF through NF-kappaB-mediated TGF-beta1 release. Herein, we first validate the suppressive effect of HMGB1 knockdown on TGF-beta1-induced alpha-smooth muscle actin (alpha-SMA) and collagen I protein expression. In PF, miRNAs exert different effects through targeting various downstream target messenger RNAs. We searched an online database for dysregulated miRNAs in PF tissues; among them, miR-627 was predicted by online tools to target HMGB1 to inhibit its expression. miR-627 overexpression could partially reverse TGF-beta1-induced normal human lung fibroblast proliferation, as well as alpha-SMA and collagen I protein expression. miR-627 inhibition could partially reverse the suppressive effect of HMGB1 knockdown on TGF-beta1-induced alpha-SMA and collagen I protein expression through direct binding to the 3'-untranslated region of HMGB1. Moreover, miR-627/HMGB1 affected TGF-beta1 release through RAGE/NF-kappaB signaling; miR-627/HMGB1 and RAGE/NF-kappaB signaling formed a regulatory loop to modulate TGF-beta1-induced PF in vitro. In conclusion, miR-627 may be a potential agent that targets HMGB1 to inhibit its expression, thereby improving TGF-beta1-induced PF in vitro.
作者机构：
[林亲录; 梁盈; 马酉初; 黄萍; 李佳佳; 刘一超] National Engineering Laboratory for Rice and By-Product Deep Processing, Central South University of Forestry and Technology, Changsha, 410004, China
作者机构：
[梁盈; 林亲录; 黄萍; 朱凤霞; 王玉倩; 崔校基] National Engineering Laboratory for Rice and By-Product Deep Processing, Central South University of Forestry and Technology, Changsha, 410004, China
作者机构：
[黄萍; 袁丹; 崔校基; 王玉倩; 梁盈; 周欣雨] National Engineering Laboratory for Rice and By-product Deep Processing, Central South University of Forestry & Technology, Changsha 410004, China
期刊：
CELL DEATH & DISEASE,2017年8(10):e3096 ISSN：2041-4889
通讯作者：
Yao, Hongliang;Liang, Ying
作者机构：
[Liu, Kuijie; Lei, Zhendong; Xiong, Li; Zhou, Nanjiang; Chen, Weidong; Yao, Hongliang; Lei, Sanlin; Zhao, Hua] Cent S Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China.;[Liang, Dong] Zhengzhou Univ, Peoples Hosp, Henan Prov Peoples Hosp, Zhengzhou 450003, Henan, Peoples R China.;[Liang, Ying] Cent South Univ Forestry & Technol, Dept Food Sci & Engn, Shaoshan South Rd 498, Changsha 410004, Hunan, Peoples R China.
通讯机构：
[Yao, Hongliang; Liang, Ying] C;Cent S Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China.;Cent South Univ Forestry & Technol, Dept Food Sci & Engn, Shaoshan South Rd 498, Changsha 410004, Hunan, Peoples R China.
摘要：
Colorectal cancer (CRC) is a most common digestive system malignant tumor. p53 mutation has essential role in cancers and is frequently observed in CRC and presents a huge challenge. p53 mutation has been reported to attenuate the inhibitory effect of photofrin-based photodynamic therapy (PDT). p53 mutation-induced gain of function brings up the dysfunction of carcinogenic factors, including miRNAs. Our research found that PDT suppressed CRC cell viability, reduced the tumor size and prolonged the survival time, all of which could be attenuated by p53 mutation or deletion. After p53 mutation or deletion, several miRNA expression levels were downregulated, among which miR-124 was the most strongly downregulated, whereas iASPP expression was upregulated. p53 binds to the promoter of miR-124 to promote its expression and then inhibited iASPP expression, so as to amplify the inhibitory effect of PDT on wild-type p53 cells. In p53-mutant or -deleted cells, this binding no longer worked to promote miR-124 expression, and iASPP expression increased, finally resulted in promoted CRC cell viability upon PDT. The interactive modulation among miR and iASPP in p53-mutant or -deleted cells may serve as a crucial pathway, which mediates therapy resistance when p53 is mutated or deleted, in the process of PDT treatment of CRC.
摘要：
In our previous study, we revealed that Cyclosporin A (CsA) could inhibit miR-144 expression to regulate proliferation and invasion of human trophoblast (HT) cells through miR-144 targeting titin. This partially demonstrated the mechanism by which CsA promotes titin expression to increase the vitality of HT cells. However, the mechanism by which CsA inhibits miR-144 expression remains to be investigated. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes. In the present study, online tools were used to figure out that X-inactive specific transcript (XIST) could interact with miR-144. XIST and miR-144 reciprocally inhibited each other in HT cells; as exhibited by luciferase reporter gene assays, miR-144 bind to XIST by direct targeting. XIST suppressed miR-144 expression to promote titin expression. As exhibited by the Spearman's correlation analysis, in CsA treated HT cells, miR-144 was inversely correlated with titin and XIST, respectively; XIST was positively correlated with titin. Moreover, CsA could promote the proliferation and invasion of HT cells through XIST and the downstream MAPK and MMPs pathway. Taken together, these findings will shed light to the role and mechanism of CsA/XIST/miR-144/titin in regulating HT cells proliferation and invasion. XIST may serve as a potential therapeutic target in HT in the future. J. Cell. Biochem. 118: 2208-2218, 2017. (c) 2017 Wiley Periodicals, Inc.
