FREE RADICAL BIOLOGY AND MEDICINE
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2019
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IF 5.657
Xueming Cao,Na Zhu,Li Li,Yuwei Zhang,Yan Chen,Jing Zhang,Jiang Li,Chuanyu Gao
Aims Y-box protein 1 (YB1) is a key regulator of inflammatory mediators . However, the roles of YB1 in oxidized low-density lipoprotein (ox-LDL)-induced macrophage inflammation and lipid uptake remain less understood. Thus, we explored the roles of YB1 in ox-LDL-induced macrophage inflammation and lipid uptake and its underlying molecular mechanisms. Methods An ox-LDL-induced atherosclerosis (AS) model was used in this study. Western blotting , RT-PCR, immunofluorescence, ELISA, dil-ox-LDL staining, a dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and in vivo experiments were used to detect each target. Results ox-LDL downregulates YB1 expression in THP-1-derived macrophages and human monocyte-derived macrophages (hMDMs) via the NF-κB pathway. Downregulation of YB1 is facilitated by lipid uptake in macrophages, and CD36 is involved in this process. Furthermore, YB1 suppresses CD36 protein levels by directly binding to the coding sequence of the CD36 gene to promote CD36 mRNA decay but does not affect its mRNA transcription. Additionally, YB1 knockdown enhances the inflammatory response and lipid deposition via the NF-κB pathway in vivo. Conclusion ox-LDL decreases YB1 expression in macrophages, resulting in enhanced inflammatory responses by affecting NF-κB and facilitating lipid uptake by promoting scavenger receptor CD36 mRNA decay.
研究领域:
免疫学
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2018
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IF 3.831
Jiao Shihong,Tang Binghua,Wang Yong,Li Chun,Zeng Zifan,Cui Lixia,Zhang Xuefeng,Shao Mingyan,Guo Dongqing,Wang Qiyan
Coronary artery disease (CAD) is one of the leading causes of deaths worldwide. Energy metabolism disorders, including a reduction in fatty acids oxidation and upregulation of glycolysis pathway, are involved in the process of CAD. Therapeutic angiogenesis has become a promising treatment for CAD. Traditional Chinese medicines, such as Danqi Pill (DQP), have been proven to be effective in treating CAD in China for many years. However, the pro-angiogenic effects of DQP based on fatty acids oxidation are still unknown and the mechanism is worthy of investigation. In this study, left anterior descending (LAD) coronary artery was ligated to induce the CAD models in vivo, and cardiac functions were examined using echocardiography. Human umbilical vein endothelial cells (HUVEC) were subjected to H2O2-induced oxidative stress in vitro. The effects of DQP on CAD rat models and in vitro HUVEC were detected. Our results showed that DQP had cardio-protective effects in rat model. The intensity of capillaries in the marginal area of infarction of the rat heart was increased remarkably in DQP group, and the expression of PPARα and VEGF-2 were increased. The key enzymes involved in the transportation and intake of fatty acids, including CPT1A and CD36, both increased. In H2O2-induced endothelial cells injury models, DQP also showed protective roles and promoted capillary-like tube formation. DQP up-regulated key enzymes in fatty acids oxidation in H2O2-treated HUVEC. In addition, inhibition of CPT1A compromised the pro-angiogenic effects of DQP. In conclusion, fatty acids oxidation axis PPARα-CD36-CPT1A was involved in the pro-angiogenic roles of DQP against CAD. Cardiac CPT1A may serve as a target in therapeutic angiogenesis in clinics.
研究领域:
心脏病学
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药理学
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分子生物学
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中医
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DOI
PubMed
高影响因子
Redox Biology
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2026
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IF 16.2
Jiani Gao,Ke Zhou,Yijiu Ren,Fengjing Yang,Minjue Shan,Yubing Fang,Changbo Sun,Weili Han,Chang Chen,Xuefei Hu
Transfusion-related acute lung injury (TRALI) remains a life-threatening complication of blood transfusion, yet the macrophage-neutrophil-NETosis inflammatory amplification mechanism and effective interventions are still incompletely defined. Here, we examined a CD36/Fyn-CXCL-related axis in TRALI and evaluated a ROS-responsive platelet extracellular vesicle biomimetic nanosystem (PEV@SP@EG) as a targeted delivery strategy. In a murine TRALI model, exploratory single-cell transcriptomic analysis showed immune-cell remodeling and linked CD36 expression to M1-like macrophage features. CD36 knockdown or pharmacological inhibition of Fyn/NF-kappaB reduced M1 polarization markers, CXCL production, and ROS generation. Conditioned medium from CD36-overexpressing BMDMs promoted neutrophil migration and NETosis, whereas CXCL-CXCR2 blockade or CD36/Fyn inhibition weakened these responses. PEV@SP@EG showed ROS-triggered drug release and preferential lung enrichment. In vivo , PEV@SP@EG attenuated CD36/Fyn-NF-kappaB-CXCL-related inflammatory signaling, NET formation, and oxidative stress in TRALI lung tissue, with concomitant improvement in lung architecture and gas exchange. These findings support a role for macrophage CD36/Fyn signaling in TRALI-associated macrophage-neutrophil inflammatory crosstalk and suggest that PEV@SP@EG may provide a targeted nanotherapeutic delivery platform for TRALI intervention.
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DOI
高影响因子
Cell Metabolism
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2024
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IF 27.7
Hui Lin,Chuanshun Ma,Xiao Zhuang,Shuo Liu,Dong Liu,Mingxiang Zhang,Yan Lu,Guangjian Zhou,Chao Zhang,Tengwei Wang,Zihao Zhang,Lin Lv,Daolai Zhang,Xiong-Zhong Ruan,Yunfei Xu,Renjie Chai,Xiao Yu,Jin-Peng Sun,Bo Chu
G protein-coupled receptors (GPCRs) mediate most cellular responses to hormones, neurotransmitters, and environmental stimulants. However, whether GPCRs participate in tissue homeostasis through ferroptosis remains unclear. Here we identify that GPR56/ADGRG1 renders cells resistant to ferroptosis and deficiency of GPR56 exacerbates ferroptosis-mediated liver injury induced by doxorubicin (DOX) or ischemia-reperfusion (IR). Mechanistically, GPR56 decreases the abundance of phospholipids containing free polyunsaturated fatty acids (PUFAs) by promoting endocytosis-lysosomal degradation of CD36. By screening a panel of steroid hormones, we identified that 17α-hydroxypregnenolone (17-OH PREG) acts as an agonist of GPR56 to antagonize ferroptosis and efficiently attenuates liver injury before or after insult. Moreover, disease-associated GPR56 mutants were unresponsive to 17-OH PREG activation and insufficient to defend against ferroptosis. Together, our findings uncover that 17-OH PREG-GPR56 axis-mediated signal transduction works as a new anti-ferroptotic pathway to maintain liver homeostasis, providing novel insights into the potential therapy for liver injury.
研究领域:
药理学
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细胞生物学
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分子生物学
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肝病学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-21
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IF 12.6
Wei Min,Jiang Qiaoji,Bian Shuang,Chang Pengzhao,Li Bangbang,Shi Changzhou,Zhu Yangang,Wang Yanchen,Hou Pingfu,Li Jingjing
With the progress of atherosclerosis (AS), the arterial lumen stenosis and compact plaque structure, the thickening intima and the narrow gaps between endothelial cells significantly limit the penetration efficiency of nanoprobe to plaque, weakening the imaging sensitivity and therapy efficiency. Thus, in this study, a H 2 O 2 -NIR dual-mode nanomotor, Gd-doped mesoporous carbon nanoparticles/Pt with rapamycin (RAPA) loading and AntiCD36 modification (Gd-MCNs/Pt-RAPA-AC) was constructed. The asymmetric deposition of Pt on Gd-MCNs catalyzed H 2 O 2 at the inflammatory site to produce O 2 , which could promote the self-motion of the nanomotor and ease inflammation microenvironment of AS plaque. Near-infrared (NIR) laser irradiation promoted the photothermal conversion of Gd-MCNs to generate the thermal propulsion of nanomotor and photothermal ablation of inflammatory macrophages. Meanwhile, the modification of AntiCD36 to bind with inflammatory macrophages further promotes the targeting effect. The released RAPA could inhibit the inflammatory side effects caused by photothermal effects, and promote macrophage autophagy to hinder the development of AS. The dual-mode propulsion nanomotors combining with the synergistic therapy of photothermal treatment, anti-inflammatory and pro-autophagy provided improved theranositc effect of AS. Graphical abstract
研究领域:
医学影像学
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纳米医学
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心血管疾病
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2024
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IF 10.7
Ting Yang,Zihan Liu,Zixuan Fu,Xiaojie Zhang,Yongjin Cao,Qiangwei Liang,Jiale Miao,Hao Yang,Tong Zhang,Jing Hei,Weiqing Ni,Yanhua Liu
Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer (TNBC) therapy. However, the ferroptosis accompanied with down-regulation of glutathione peroxidase 4 (GPX4) lead to CD36-mediated tumor-infiltrating CD8 + T cells uptaking fatty acids, resulting in the negative action on immunotherapeutic efficacy. Herein, the albumin nanoparticles, abbreviated as LHS NPs, were designed by co-assembly of hemin, linoleic acid-cystamine, and a CD36 inhibitor sulfosuccinimide oleate, to bi-directionally manipulated ferroptosis in tumor and CD8 + T cells for TNBC therapy. LHS NPs exerted more efficient reactive oxygen species generation, glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes, which amplified the positive action on ferroptosis in tumor cells. Meanwhile, LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8 + T cells, thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death, proliferation of CD4 + CD8 + T cells and natural killer cells, alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and repolarization of the M2- to M1-phenotype tumor-associated macrophages. Thus, LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lung metastasis of 4T1-tumor mice. Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8 + T cells on TNBC chemoimmunotherapy.
研究领域:
癌症治疗
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纳米医学
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免疫学
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肿瘤学
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产品关联
DOI
高影响因子
Food Bioscience
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2025
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IF 5.9
Xi Lu,Xirui Cheng,Guohua Li
Hyperlipidemia impose a substantial burden on human health. Recent studies have demonstrated that probiotics can regulate lipid metabolism by modulating gut microbiota composition or producing bioactive metabolites, with human-derived strains potentially exhibiting superior host colonization capacity. This study isolated Lactobacillus gasseri LG 2361 from 84 healthy infant fecal samples. Safety assessments confirmed non-hemolytic activity, antibiotic susceptibility (except natural resistance), and gastrointestinal adaption (81 % survival at pH 3.0; 60 % survival at 0.1 % bile). The strain demonstrated lipid-lowering capacity in vitro , degrading 43.0 % cholesterol and 34.6 % triglycerides. In high-fat diet mice, LG 2361 reduced hepatic lipid accumulation (11.6 % total cholesterol, p < 0.05), attenuated abdominal adiposity (32.9 % subcutaneous fat reduction, p < 0.01), and may enhance antioxidant status (22.5 % glutathione peroxidase increase, p < 0.01). Synergy with L . acidophilus ATCC 43121 amplified efficacy, achieving 61.6 % abdominal fat reduction (p < 0.01) while suppressing TNF-α (0.46-fold) and IL-1β (0.29-fold, p < 0.001). Mechanistically, LG 2361 downregulated PPARγ (0.59-fold, p < 0.01) and modulated FAT/CD36 pathways, indicating dual regulation of lipogenesis and lipid transport. These findings suggest that LG 2361 may be a probiotic candidate for hyperlipidemia management.
研究领域:
微生物学
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益生菌研究
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代谢紊乱
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胃肠健康
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免疫学
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产品关联
DOI
高影响因子
Journal of Animal Science and Biotechnology
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2022
·Vol. 13
·期 1
·1-13
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IF 6.175
Zhou Xiaoge,Mo Zhaoyi,Li Yankun,Huang Liang,Yu Sihai,Ge Lan,Hu Yamei,Shi Shengjie,Zhang Lutong,Wang Liguang,Gao Lei,Yang Gongshe,Chu Guiyan
Background Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state, and it may have detrimental effects on female reproduction and fertility. Oleic acid induces lipid accumulation in bovine granulosa cells, which leads to a foam cell-like morphology and reduced steroidogenesis. However, why oleic acid increases lipid accumulation but decreases steroidogenesis remains unclear. This study focused on oleic acid’s effects on lipid type and steroidogenesis. Results Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester level. Oleic acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in vitro. In addition, oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2, but down-regulated the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2, as well as steroidogenesis-related genes, including cytochrome P450 family 11 subfamily A member 1, cytochrome P450 family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein levels. An oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice, which resulted in lower estradiol levels than in control-fed mice. Compared with the control, decreases in estrus days and the numbers of antral follicles and corpora lutea, as well as an increase in the numbers of the atretic follicles, were found in the oleic acid-fed female mice. Conclusions Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells, and led to a decrease in steroidogenesis. These results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.
研究领域:
生殖生物学
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内分泌学
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动物科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Shan Li,Ronghua Guo,Xiang Gao,Yin Wang,Jiaxin Wen,Ting Zhao,Xiaofei Guo,Junhui Li,Shiguo Chen,Duo Li
Fucosylated chondroitin sulfate from Pearsonothuria graeffei (FCS- Pg ), a natural macromolecular polysaccharide, has been proven to prevent obesity, but its underlying molecular mechanism is still unclear. C57BL/6 J mice fed on high fat diet (HFD) were administered FCS- Pg lasting for ten weeks. The results demonstrated that FCS- Pg supplementation reduced body weight with dosage manner compared with HFD group. The expressions of intestinal lipid synthesis related proteins such as cluster of differentiation 36 (CD36) in FCS- Pg group were lower than those in the HFD group. Compared with the normal group, HFD caused gut microbiota disorder in the colon. FCS- Pg supplementation at high dosage restored the gut microbiota composition with higher abundance of Alistipes and Bacteroidetes and lower abundance of Colidextribacter , Bilophila and Firmicutes compared with HFD group. Moreover, FCS- Pg decreased the expression of proteins involved in triglyceride synthesis such as glycerol 3-phosphate dehydrogenase 1 (GPD1) and increased the expression of proteins involved in lipolysis and thermogenesis such as adipose triglyceride lipase (ATGL) and uncoupling protein 1 (UCP1) in the white adipose tissue (WAT) compared with HFD group. In conclusion, our study suggested that FCS- Pg significantly prevented obesity and improved WAT function in HFD-fed mice by regulating intestinal lipid metabolism and microflora composition.
研究领域:
营养学
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分子生物学
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微生物学
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肥胖研究
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代谢学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2022
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IF 5.168
Xueyun Liu,Man Hu,Chen Ye,Lihong Liao,Chang Ding,Lijuan Sun,Jichao Liang,Yong Chen
It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid , 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting . Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas , as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor , compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.
研究领域:
分子生物学
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细胞生物学
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药理学
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代谢紊乱
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
研究领域:
药理学
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代谢学
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2021
·
IF 7.963
Cuiyuan Jin,You Weng,Yi Zhang,Zhiwei Bao,Guiling Yang,Zhengwei Fu,Yuanxiang Jin
Propamocarb is a systemic carbamate fungicide used to fight diseases. The effect of propamocarb on the formation of atherosclerosis was evaluated in wild-type (WT) and ApoE knockout (ApoE −/− ) mice. C57BL/6 J WT mice were fed control diet or high-fat diet (HFD) with 20 mg/L propamocarb in drinking water for 24 weeks. Propamocarb significantly increased the serum levels of triglyceride, cholesterol and low-density lipoprotein cholesterol while decreasing high-density lipoprotein cholesterol. Simultaneously, propamocarb facilitated lipid accumulation in the liver and increased the expression of cholesterol synthesis and transport genes in the liver and ileum. Lipid accumulation was observed in the aortic roots of the propamocarb-treated mice fed HFD, and similar results were also observed with whole aorta staining. In addition, propamocarb exposure significantly increased the mRNA levels of IL-1β , TNF-α , ICAM-1 , and VCAM-1 in the aorta and the serum IL-1β, IL-6, and TNF-α levels in HFD groups treated with propamocarb. In ApoE −/− mice, the results were consistent with those obtained in WT mice after exposure to 20 mg/L propamocarb for 10 weeks. Meanwhile, propamocarb significantly increased the levels of CD36, NF-κB, VCAM-1 and ICAM-1 proteins in the aortas of ApoE −/− mice. Propamocarb further disrupted cholesterol metabolism and enhanced atherosclerosis and inflammatory responses much more substantially, indicating that propamocarb has the potential to accelerate the formation of atherosclerosis. An analysis of gut microbiota revealed that propamocarb altered the composition of gut microbiota in both WT and ApoE −/− mice. Interestingly, propamocarb increased the abundance of Peptostreptococcaceae, Ruminococcaceae, and Clostridiales_VadinBB60_group , which are related to atherosclerosis at the family level. The abundance of Paeniclostridium, Allobaculum, and Clostridioides , which are closely related to atherosclerosis, was also increased by propamocarb exposure. Our findings indicate that propamocarb exposure may promote atherosclerosis by disrupting lipid metabolism, increasing the inflammatory response, and altering the structure of gut microbiota.
研究领域:
药理学
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心血管疾病
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免疫学
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微生物学
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代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）