JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2014
·
IF 3.107
Huan Rao,Li-Xin Ma,Ting-Ting Xu,Jing Li,Ze-Yuan Deng,Ya-Wei Fan,Hong-Yan Li
Our previous study showed that trans-fatty acids can cause apoptosis of endothelial cells through the caspase pathway and the mitochondrial pathway. The objective of this study was to explore how trans-fatty acids activate the caspase pathway, whether there exist specific receptors induced apoptosis by comparing normal cells and non-rafts cells treated with elaidic acid (9t18:1) and oleic acid (9c18:1), respectively. Compared to normal cells treated with 9t18:1, the cell viability increased by 13% and the number of apoptotic cells decreased by 3% in non-rafts cells treated with 9t18:1 (p < 0.05), and the expression levels of pro-apoptotic proteins such as caspase-3, -8, -9, Bax, and Bid decreased, and expression of antiapoptotic protein Bcl-2 increased (p < 0.05). In addition, Fas/FasL expression in cell membrane decreased significantly (p < 0.05). In conclusion, the lipid rafts and Fas/FasL pathway may involve in 9t18:1-induced apoptosis of human umbilical vein endothelial cells.
研究领域:
细胞生物学
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分子生物学
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心血管研究
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DOI
PubMed
高影响因子
ANDROLOGIA
·
2014
·Vol. 47
·期 9
·995-1003
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IF 1.172
J. Li,Y. Hu,Q. Zhang,B. Ma,Z. Wu,Y. Wang,J. Sun,J. Zhu,H. Ying,P. Ouyang
Summary This study investigated the treatment effects of a new compound, strontium fructose 1, 6-diphosphate (FDP-Sr), in cyclophosphamide (CP)-induced oligozoospermia. FDP-Sr, with extra high-energy supply, could reverse male hypogonadism in the testis. Male Wistar rats were randomly divided into three groups: control group (vehicle treated), CP group and CP + FDP-Sr group. Both CP group and CP + FDP-Sr groups were orally administered CP (20 mg kg −1 ) consecutively for the first 7 days to establish CP-induced testicular toxic models. Subsequently, CP group was given orally distilled water per day, whereas CP + FDP-Sr group was received FDP-Sr (200 mg kg −1 ) for 49 days. Compared to the CP group, the FDP-Sr group showed significantly increased levels of serum testosterone, testis relative weights and epididymal sperm counts in rats. In addition, rats treated by FDP-Sr showed the recuperative activities of testicular marker enzymes and normalised levels of antioxidants in tissue. Testicular protection of FDP-Sr was further demonstrated by enhancing expression of P450scc, reducing ability of FAS/FASL and generating cytoprotection in the histopathological study. FDP-Sr appeared to possess an ability to attenuate CP-induced reproduction toxicity via the activation of antioxidants and steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of testicular apoptosis by FAS/FASL pathway.
研究领域:
药理学
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生殖生物学
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毒理学
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Shuhan Wang,Yaqi Yang,Jiahong Lin,Weishan Zhang,Cuizhu Yang,Runheng Zhang,Chang Zhou,Li Zhang,Xin Wang,Jing Liu,Xiaobao Jin,Yuxin Ma
Alzheimer's disease (AD) as a common neurodegenerative disease, which characterized by amyloid Aβ deposition and neurofibrillary tangles. Astragalin (AST), a natural flavonoid, has anti-inflammatory, antioxidant, anti-cancer, and other pharmacological effects. Astrocytes can phagocytize and degrade Aβ in their vicinity. In this study, we used the AD mice model established by injecting the mixture of Aβ1-42 and Aβ25-35 into the CA1 region of the hippocampus, and C8D1A cells injured by Aβ1-42 to explore the neuroprotective effects of AST. Our findings showed that AST enhances learning and cognitive ability of AD mice, reduces Aβ deposition and neurofibrillary tangles in the brain, and improves the structural morphology of hippocampal nerve cells. Furthermore, AST promoted autophagy and suppressed apoptosis of astrocytes in the AD model. Additionally, AST inhibited the expression of proteins associated with the Fas/Fasl-VDAC1 signaling pathway, while autophagy inhibitor chloroquine (CQ) or apoptosis agonist phenoxodiol reversed above change. Interestingly, consistent with the action of pathway Fas inhibitor KR-33493, AST could activate autophagy of Aβ1-42 injured C8D1A cells while inhibit their apoptosis. In conclusion, AST activated autophagy and inhibited apoptosis of hippocampal astrocytes in AD mice, ameliorating animal cognitive deficits by down-regulating Fas/Fasl-VDAC1 signaling pathway. Thus, this study provided a new perspective and experimental foundation for developing AD treatment drugs.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
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IF 7.9
Shuai Chen,Jie Jin,Ziqing Xu,Huawei Han,Lan Wu,Zhiwei Li
Background Catalpol , a major active component of the Chinese herb Rehmannia glutinosa , possesses various pharmacological benefits, including anti-inflammatory, antidiabetic , and antitumor properties. Recent studies have reported that catalpol can attenuate bone loss and enhance bone formation. Nevertheless, the molecular mechanisms underlying its effects on osteoporosis pathogenesis remain unclear. Purpose We investigated whether catalpol had a protective effect against postmenopausal osteoporosis (PMOP) and explored its exact mechanism of action. Methods Seventy-two rats were randomly divided into six groups: sham, model, low-dose catalpol (5 mg/kg/day), medium-dose catalpol (10 mg/kg/day), high-dose catalpol (20 mg/kg/day), and positive control (alendronate, 2.5 mg/kg). In this experiment, a ovariectomy was performed to establish a female rat model of PMOP. After 12 weeks of gavage, micro-computed tomography (micro-CT) and histochemical staining were performed to evaluate bone mass, bone microstructure and histological parameters. Furthermore, RAW 264.7 cells were induced by RANKL to form mature osteoclasts to investigate the effect of catalpol on osteoclast differentiation and apoptosis in vitro . Additionally, the osteoclast apoptosis-related proteins of Sirt6 , ERα, FasL , NFATc1, cleaved-caspase 8, cleaved-caspase 3, and Bax were assessed using western blotting . The expressions of NFATc1, Ctsk, Oscar , and Trap were quantified using RT-qPCR. The apoptotic rate of the osteoclasts was determined using flow cytometry. Sirt6 knockdown was performed using siRNA gene silencing in experiments to investigate its role in catalpol-mediated osteoclast apoptosis. The deacetylation of ERα in osteoclasts was tested via co-immunoprecipitation. Results Catalpol (10 and 20 mg/kg) and alendronate (2.5 mg/kg) could significantly improve bone mineral density (BMD) and microstructure and decrease osteoclast density in ovariectomized (OVX) rats. In addition, catalpol (10 and 20 mg/kg) upregulated the expression of Sirt6, ERα, FasL, cleaved-caspase 8, cleaved-caspase 3, Bax, and downregulated the expression of NFATc1, Ctsk, Oscar, Trap both in vivo and in vitro . Catalpol also promoted ERα deacetylation and stabilized ERα protein to enhance the expression of FasL. In addition, Sirt6 knockdown by siRNA prevented ERα deacetylation and eliminated catalpol-mediated osteoclast apoptosis. Conclusions The present study demonstrated that catalpol prevents estrogen deficiency-induced osteoporosis by promoting osteoclast apoptosis via the Sirt6-ERα-FasL axis. These findings revealed a novel molecular mechanism underpinning the impact of catalpol in the progression of osteoporosis and provided novel insights into the treatment of osteoporosis.
研究领域:
药理学
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骨骼生物学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yao Huo,Wen-jie Ding,Yan-ru Liu,Zhen-tong Li,Ke-yao Dai,Chao Liu,Hai-yu Ji,An-jun Liu
An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro , whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO 3 -Na 2 SeO 3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV–visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.
研究领域:
药理学
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肿瘤学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Li Lin,Junyi He,Jiawei Li,Yan Xu,Jingxia Li,Yangzhe Wu
Background During the past few years, immune cell therapy for malignant cancer has benefited a considerable amount of patients worldwide. As one of several promising candidates for immunotherapy, Vγ9Vδ2 γδ T cells have many unique biological advantages, such as non-MHC restriction and have been noted as the earliest source of IFN-γ. However, potentiating anti-tumor functions of γδ T cells has become of particular interest to researchers studying γδ T cell applications.Purpose In this study, we proposed a nanotechnology-based methodology for strengthening γδ T cell functions.Methods As a type of reliable, biocompatible material, chitosan nanoparticles (CSNPs) were used to enhance anti-tumor immunity of γδ T cells.Results First, we found that the size of prepared CSNPs distributed 50 to 100 nm, and that CSNPs had optimal immunocompatibility. Then, we observed that CSNPs could induce α-tubulin cytoskeleton polarization and rearrangement, correlating with a higher killing ability of γδ T cells. Furthermore, we revealed that CSNPs could enhance Vγ9Vδ2 T cell anti-tumor functions by upregulating killing of related receptors, including NKG2D, CD56, FasL, and perforin secretion.Conclusion Our work provided evidence of application for CSNPs based bio-carrier in immunotherapy. More importantly, we proposed a new strategy for enhancing γδ T cell anti-tumor activity using nanobiomaterial, which could benefit future clinical applications of γδ T cells.
研究领域:
免疫学
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纳米技术
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肿瘤学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULES
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2019
·Vol. 24
·期 8
·1454
·
IF 3.06
Fang-Rong Cheng,Hong-Xin Cui,Ji-Li Fang,Ke Yuan,Ying Guo
Rheum palmatumL. is a traditional Chinese medicine with various pharmacological properties, including anti-inflammatory, antibacterial, and detoxification effects. In this study, the mechanism of the hypoglycemic effect of purified anthraquinone-Glycoside fromRheum palmatumL. (PAGR) in streptozotocin (STZ) and high-fat diet induced type 2 diabetes mellitus (T2DM) in rats was investigated. The rats were randomly divided into normal (NC), T2DM, metformin (Met), low, middle (Mid), and high (Hig) does of PAGR groups. After six weeks of continuous administration of PAGR, the serum indices and tissue protein expression were determined, and the pathological changes in liver, kidney, and pancreas tissues were observed. The results showed that compared with the type 2 diabetes mellitus group, the fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) levels in the serum of rats in the PAGR treatment groups were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels were noticeably increased. The expression of Fas ligand (FasL), cytochrome C (Cyt-c), and caspase-3 in pancreatic tissue was obviously decreased, and the pathological damage to the liver, kidney, and pancreas was improved. These indicate that PAGR can reduce oxidative stress in rats with diabetes mellitus by improving blood lipid metabolism and enhancing their antioxidant capacity, thereby regulating the mitochondrial apoptotic pathway to inhibitβ-cell apoptosis and improve β-cell function. Furthermore, it can regulate Fas/FasL-mediated apoptosis signaling pathway to inhibit β-cell apoptosis, thereby lowering blood glucose levels and improving T2DM.Keywords:Rheum palmatumL.;type 2 diabetes mellitus;oxidative stress;apoptosis
研究领域:
药理学
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内分泌学
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中医药学
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分子生物学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
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IF 26.8
Yaqing Kang,Xiaoqing Han,Shijie Zhou,Xingbo Wang,Yanjing Wang,Panpan Song,Xiaochen Su,Mengmeng Qin,Dongyang Qian,Huan Meng,Jiao Yan,Fang Pu,Haiyuan Zhang
Rheumatoid arthritis microenvironment (RAM) contains complex pathogenic mediators that interact dynamically to drive the progression of rheumatoid arthritis (RA). However, most current RA treatments are single-target interventions, exerting limited impact on RAM. Herein, apoptotic extracellular vesicles (ApoEV) are constructed for programmable regulation of the neutrophil-macrophage-ROS pathogenic axis, aiming to reconstruct RAM and improve RA therapy. Mesenchymal stem cells (MSCs) are pretreated with dexamethasone (Dex) and induced apoptosis to produce Dex-loaded and FasL-overexpressing ApoEV (D@ApoEV FasL ), which is further modified with low-molecular-weight heparin (LMWH) through a ROS-responsive cleavage linker to form D@ApoEV FasL ∩L. After intravenous injection into RA mice, D@ApoEV FasL ∩L targeted the inflamed joints based on their MSC-derived feature and blocked neutrophil recruitment through binding to P-selectin on vascular endothelial cells. In response to high ROS, D@ApoEV FasL ∩L shed LMWH and exposed FasL, inducing neutrophil apoptosis through the Fas/FasL signaling pathway. Subsequently, the apoptotic neutrophils triggered macrophage reprogramming from M1 to M2 phenotype, and the released Dex significantly reduced the oxidative damage. Various in vitro and in vivo assessments have confirmed that D@ApoEV FasL ∩L can effectively regulate neutrophils, macrophages, and ROS, trigger an immune cascade, and restore intra-articular immune homeostasis, exhibiting an effective RAM reconstruction ability and a promising therapeutic effect for RA.
研究领域:
免疫学
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风湿病学
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纳米医学
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细胞治疗
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转化医学
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炎症生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-13
·
IF 14.7
Wang Yuqian,Huang Renqi,Lu Yougong,Liu Mingqi,Mo Ran
The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can also cause severe adverse effects. Here, we report a local immuno-protective strategy to enhance post-transplant persistence of allografts using a mesenchymal stem cell membrane-derived vesicle (MMV)-crosslinked hydrogel (MMV-Gel). MMVs are engineered to upregulate expression of Fas ligand (FasL) and programmed death ligand 1 (PD-L1). The MMVs are retained within the hydrogel by crosslinking. The immuno-protective microenvironment of the hydrogel protects allografts by presenting FasL and PD-L1. The binding of these ligands to T effector cells, the dominant contributors to graft destruction and rejection, results in apoptosis of T effector cells and generation of regulatory T cells. We demonstrate that implantation with MMV-Gel prolongs the survival and function of grafts in mouse models of allogeneic pancreatic islet cells and skin transplantation.
研究领域:
免疫学
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移植医学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 29
·15906-15914
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IF 2.936
Zhaokun Yan,Qingtang Wang,Xiaolong Liu,Jun Peng,Qin Li,Ming Wu,Jiumao Lin
Ursolic acid (UA) has shown great potential in cancer therapy but their efficacy is seriously compromised by poor water-solubility and limited cellular uptake. In this paper, cationic nanomicelles self-assembled from Pluronic F127 with the cationic polymer of C18-polyethylenimine (C18-PEI) as a functional component are fabricated as delivery vehicles of Chinese herbal medicine active components of ursolic acid (UA) for colorectal cancer treatment. The inhibition effects of this drug loaded cationic nanomicelles (named as FUP) on cell viability and cell colony formation were more significant than the free UA, due to their cationic surface which can increase UA uptake by colorectal cancer cells. Cell cycle analysis showed that this inhibition effect was mediated by a cell cycle arrest at the G1 checkpoint, and the cell death induced by these nanomicelles occurred via apoptosis, which was detected by annexin V antibody and propidium iodide staining. Further western blot analysis demonstrated the apoptosis mechanism was associated with the regulation of Fas/FasL and activation of caspase-8 and caspase-3. Therefore, our cationic nanomicelles can potentially be used to enhance the therapeutic effect of UA for colorectal cancer treatment.
研究领域:
药学
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纳米技术
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肿瘤学
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中药
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
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IF 4.259
Yuhong Liu,Jiali Liang,Jiazhen Wu,Hanbin Chen,Zhenbiao Zhang,Hongmei Yang,Liping Chen,Haiming Chen,Ziren Su,Yucui Li
Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.
研究领域:
药理学
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胃肠病学
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生物化学
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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）