Biomaterials Advances
·
2022
·
IF 0
Tianshu Chu,Chun Dai,Xiang Li,Lei Gao,Hongyan Yin,Jianjun Ge
Following vein grafting, the vein must adapt to arterial hemodynamics, which can lead to intimal hyperplasia (IH) and restenosis. Moreover, endothelial-to-mesenchymal transition (EndMT) components are highly associated with IH. Therefore, in this study, we aimed to design an extravascular film loaded with rapamycin (extravascular rapamycin film [ERF]) to limit vein graft stenosis. The film exhibited stable physicochemical properties as well as in vivo and in vitro biocompatibility. In vivo , the film inhibited the EndMT by activating the autophagy pathway. Moreover, rapamycin enhanced this biological effect. Collectively, these findings highlighted the applicability of ERF as a new therapeutic target for preventing vein graft restenosis.
研究领域:
心血管医学
·
药理学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
Journal of Animal Science and Biotechnology
·
2023
·Vol. 14
·期 1
·1-17
·
IF 7
He Zhaoqi,Zhao Caijun,He Yuhong,Liu Zhuoyu,Fan Guyue,Zhu Kun,Wang Yiqi,Zhang Naisheng,Fu Yunhe,Hu Xiaoyu
Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.Results First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusion sIn conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
研究领域:
兽医学
·
微生物学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Di Kang,Guorui Zhang,Zhonghui Zhang,Zhancheng Tian,Shandian Gao,Guangyuan Liu,Guiquan Guan,Jianxun Luo,Hong Yin,Junzheng Du
Bluetongue virus (BTV) infection effectively activates the innate immune response, followed by the expression of interferon (IFN) and multiple interferon-stimulated genes (ISGs). ISG15 is one of the most induced ISGs, and often plays a role in inhibiting virus replication. This study aims to explore the role and specific mechanisms of ovine ISG15 (oISG15) in BTV infection. We found that the transcription level of oISG15 was upregulated in a time-dependent and BTV multiplicity of infection-dependent manner. The overexpression of exogenous oISG15 enhances BTV replication, whereas the knockdown of endogenous oISG15 inhibits BTV replication. The viral protein in wild-type oISG15-overexpressed cells and ISGylation defective oISG15-overexpressed cells have no significant differences, which indicated that oISG15 promoted BTV replication in an ISGylation-independent manner. A co-immunoprecipitation assay showed that four viral BTV proteins—VP3, VP4, VP5, and NS1—interacted with oISG15. We also found that the VP4 and NS1 proteins associated with ubiquitin via co-immunoprecipitation, and that oISG15 overexpression improved the stability of both proteins. Further results showed that the degradation of NS1 was involved in lysine 63-linked polyubiquitin. This suggested that oISG15 may interfere with NS1 degradation via the autophagy pathway. This study provides new insights on the interaction between BTV and ISG15, and enriches our understanding of the regulation and biological function of ISG15 with virus replication.
研究领域:
病毒学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Autophagy
·
2020
·
IF 9.77
Zu-Guo Zheng,Si-Tong Zhu,Hui-Min Cheng,Xin Zhang,Gang Cheng,Pyone Myat Thu,Supeng Perry Wang,Hui-Jun Li,Ming Ding,Lei Qiang,Xiao-Wei Chen,Qing Zhong,Ping Li,Xiaojun Xu
SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases.Abbreviation: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1
研究领域:
药理学
·
代谢
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Lianghua Xie,Xin Hao,Jiahong Xie,Jianling Mo,Changzheng Yuan,Wei Chen
Nonalcoholic fatty liver disease (NAFLD) is a worldwide public health issue, but a widely accepted therapy is still lacking until now. Anthocyanins are natural flavonoid compounds that possess various bioactivities, but their applications are limited due to their low bioavailability and stability. Acylated anthocyanins are reported to show higher stability, whereas their effects on NAFLD are still unclear. Herein, pelargonidin-3-O-(6′′-acetyl)-glucoside (Ace Pg3G) was found to dose-dependently reduce intracellular lipid droplets and triglycerides, and improve cellular oxidative stress that accompanied lipid deposition. Besides, Ace Pg3G was proved to activate AMPK phosphorylation, thus stimulating AMPK-mediated lysosome-autophagy pathway to eliminate overloaded lipid. Further study unveiled that Ace Pg3G regulated genes related to lipid metabolism downstream of AMPK to inhibit lipid synthesis and accelerate lipid oxidation. Overall, this study provided the first evidence, to our best knowledge, that Ace Pg3G ameliorated free fatty acid-induced lipid deposition in hepatocytes through regulating AMPK-mediated autophagy pathways and redox state.
研究领域:
营养学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ZOOLOGICAL RESEARCH
·
2021
·
IF 4.56
Huan Wang,Tian-Xiu Qiu,Jian-Fei Lu,Han-Wei Liu,Ling Hu,Lei Liu,Jiong Chen
Chronic pollution in aquatic ecosystems can lead to many adverse effects, including a greater susceptibility to pathogens among resident biota. Trifloxystrobin (TFS) is a strobilurin fungicide widely used in Asia to control soybean rust. However, it has the potential to enter aquatic ecosystems, where it may impair fish resistance to viral infections. To explore the potential environmental risks of TFS, we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus (SVCV). Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge, SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini (EPC) cells and zebrafish exposed to 25 μg/L TFS. Results showed that the highest viral load was more than 100-fold that of the controls. Intracellular biochemical assays indicated that autophagy was induced by TFS, and associated changes included an increase in autophagosomes, conversion of LC3-II, accumulation of Beclin-1, and degradation of P62 in EPC cells and zebrafish. In addition, TFS markedly decreased the expression and phosphorylation of mTOR, indicating that activation of TFS may be associated with the mTOR-mediated autophagy pathway. This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.
研究领域:
环境毒理学
·
水生生物学
·
病毒学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2023
·
IF 4.1
Tianze Li,Min Lv,Houpeng Wen,Jiawei Du,Zhen Wang,Shaoyong Zhang,Hui Xu
Background Phytopathogenic fungi can cause a direct loss in economic value of agriculture. Especially Valsa mali Miyabe et Yamada, a devastating phytopathogenic disease especially threatening global apple production, is very difficult to control and manage. To discover new potential antifungal agents, a series of thiosemicarbazone derivatives of 3-acetyl- N -benzylindoles were prepared. Their antifungal activities were first tested against six typically phytopathogenic fungi including Curvularia lunata , Valsa mali , Alternaria alternate , Fusarium graminearum , Botrytis cinerea and Fusarium solani . Then their mechanism of action against V. mali was investigated. Results Derivatives displayed potent antifungal activity against V. mali . Notably, 3-acetyl- N -benzylindole thiosemicarbazone (IV-1: EC 50 : 0.59 μ g mL −1 ), whose activity was comparable to that of a commercial fungicide carbendazim (EC 50 : 0.33 μ g mL −1 ), showed greater than 98-fold antifungal activity of the precursor indole. Moreover, compound IV-1 displayed good protective and therapeutic effects on apple Valsa canker disease. By scanning electron microscope (SEM) and RNA-Seq analysis, it was demonstrated that compound IV-1 can destroy the hyphal structure and regulate the homeostasis of metabolism of V. mali via the ergosterol biosynthesis and autophagy pathways. Conclusion 3-Acetyl- N -(un)substituted benzylindoles thiosemicarbazones (IV-1–IV-5) can be studied as leads for further structural modification as antifungal agents against V. mali . Particularly, these ergosterol biosynthesis and autophagy pathways can be used as target receptors for design of novel green pesticides for management of congeneric phytopathogenic fungi. © 2023 Society of Chemical Industry.
研究领域:
农业科学
·
植物病理学
·
化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Hongzhou Lin,Huihui Chen,Rengcheng Qian,Guoqi Tang,Yinjuan Ding,Yalan Jiang,Congde Chen,Dexuan Wang,Maoping Chu,Xiaoling Guo
Background Nephrotic syndrome (NS) is a chronic kidney disease mainly caused by impaired podocytes, ultimately resulting in massive proteinuria or even end-stage renal disease (ESRD). Methods The objective of this study was to explore the potential pathogenesis of NS caused by podocyte injury, and further explore the underlying mechanism through data mining , bioinformatics analysis, and experimental verification. The integrated analyses including Seurat, CellChat, gene ontology (GO), and molecular docking were performed based on the single-cell RNA-seq data (scRNA-seq). The adriamycin (ADR)-induced podocyte injury model in vitro was established to conduct the experimental verification for bioinformatics analysis results through western blot and real-time quantitative PCR (RT-qPCR). Results The results of bioinformatics analysis revealed that the bone morphogenetic protein (BMP) signaling pathway was involved in the podocyte-to-podocyte communication, which plays a crucial role in podocyte injury. The expression of BMP7 was significantly increased in ADR-induced podocytes through activating the Adenosine-monophosphate activated-protein kinase/Mammalian target of rapamycin (AMPK/mTOR) mediated autophagy pathway, and these findings were confirmed by in vitro experiments. Conclusion This study first demonstrated that BMP7 participated in ADR-induced podocyte injury. The BMP7/AMPK/mTOR mediated autophagy pathway may play a crucial role in podocyte injury, which may be the potential therapeutic target for NS patients.
研究领域:
肾病学
·
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Luoyijun Xie,Li Wang,Ling Li,Chutong Liu,Lihao Guo,Yingying Liao,Shuyi Zhou,Weiwei Wu,Yanhong Duo,Leilei Shi,Miaomiao Yuan
Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Wan-Ying Li,Jun-Yang Liu,Zi-Xian Wang,Ke-Ying Wang,Chun-Xiang Huang,Wen He,Jia-Le Song
Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1β. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.
研究领域:
药理学
·
胃肠病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2023
·
IF 4
Yuanlei Huang,Mengdi Lv,Binglian Guo,Guojing Hu,Yong Qian,Zhi Su,Xuling Xue,Hong-Ke Liu
Breast cancer (BC) is one of the most common malignant tumors and often accompanied by inflammatory processes. Inflammation is an essential component of the tumor microenvironment, which might influence tumor proliferation and metastasis. Herein, three metal–arene complexes MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru were prepared by tethering the non-steroidal anti-inflammatory drug meclofenamic acid (MA). Among them, MA-bip-Ru and MA-bpy-Ir showed lower cytotoxicity towards cancer cells, but MA-bpy-Ru showed significantly high selectivity and cytotoxicity towards MCF-7 cells through the autophagic pathway and exhibited no toxicity against normal HLF cells, showing potential for selective treatment of tumor cells. MA-bpy-Ru could also effectively destroy the 3D multicellular tumor spheroids, demonstrating its potential for clinical application. Besides, MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru exhibited anti-inflammatory properties superior to MA, notably downregulating the expression of cyclooxygenase-2 (COX-2) and inhibiting the secretion of prostaglandin E2 in vitro. These findings demonstrated that MA-bpy-Ru was capable of intervening in inflammatory processes and showed the potential of MA-bpy-Ru to act as a selective anticancer agent, thus presenting a new mechanism of action for metal–arene complexes.
研究领域:
肿瘤学
·
药物化学
·
无机化学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·
IF 6.1
Dekun Cheng,Zhangtie Wang,Xin Guo,Yiwen Guo,Yu Zhang,Yuanhui Zhao,Ruijie Liu,Ming Chang
Dietary nutritional support for special populations is an effective and feasible method to improve quality of life of patients and reduce medical pressure. The effects of ATSO on chemotherapy population were evaluated by a zebrafish model of demyelination. The results showed that 100 μg/mL ATSO reversed tail morphology damage, axon degeneration, touch response delay, ROS level upregulation and the expression of myelin basic protein decrease in chemotherapy-induced zebrafish. In addition, the expression of myelin markers (including sox10, krox20, pmp22) in oxaliplatin-induced cells was markedly reversed by ATSO and its active components (gondoic acid, erucic acid, nervonic acid). ATSO and its active components could reverse demyelination by ameliorating mitochondrial dysfunction. Conversely, linoleic acid and linolenic acid promoted demyelination by exacerbating mitochondrial dysfunction. Moreover, the Pink1/Parkin pathway was recognized as the main reason for ATSO and its active components to improve mitochondrial function by activating mitophagy and restoring autophagic flow. Taken together, this study demonstrated that ATSO and its active components could be further developed as novel functional food ingredients to antagonize demyelination.
研究领域:
神经科学
·
药理学
·
营养学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）