scholarly journals Polydatin Inhibits Formation of Macrophage-Derived Foam Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Min Wu ◽  
Meixia Liu ◽  
Gang Guo ◽  
Wengao Zhang ◽  
Longtao Liu
Keyword(s):  
Gene Knockout ◽  
Foam Cells ◽  
Peritoneal Macrophages ◽  
Control Group ◽  
Group Model ◽  
Apolipoprotein E Gene ◽  
Long Time ◽  
Gene Knockout Mice ◽  
Underlying Mechanisms

Rhizoma Polygoni Cuspidati, a Chinese herbal medicine, has been widely used in traditional Chinese medicine for a long time. Polydatin, one of the major active ingredients inRhizoma Polygoni Cuspidati, has been recently shown to possess extensive cardiovascular pharmacological activities. In present study, we examined the effects of Polydatin on the formation of peritoneal macrophage-derived foam cells in Apolipoprotein E gene knockout mice (ApoE−/−) and explored the potential underlying mechanisms. Peritoneal macrophages were collected from ApoE−/−mice and culturedin vitro. These cells sequentially were divided into four groups: Control group, Model group, Lovastatin group, and Polydatin group. Our results demonstrated that Polydatin significantly inhibits the formation of foam cells derived from peritoneal macrophages. Further studies indicated that Polydatin regulates the metabolism of intracellular lipid and possesses anti-inflammatory effects, which may be regulated through the PPAR-γsignaling pathways.

scholarly journals Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice

2002 ◽  
Vol 43 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Brett Garner ◽  
David A. Priestman ◽  
Roland Stocker ◽  
David J. Harvey ◽  
Terry D. Butters ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Knockout Mice ◽  
Gene Knockout ◽  
E Gene ◽  
Apolipoprotein E Gene ◽  
Gene Knockout Mice

scholarly journals Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

2020 ◽  
Author(s):  
Guiqing Zhou ◽  
Jianhui Liu ◽  
Xiangyang Li ◽  
Yujian Sang ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Silica Nanoparticles ◽  
Caspase 3 ◽  
Reproductive Toxicity ◽  
Control Group ◽  
Caspase 9 ◽  
Protein Expressions ◽  
Underlying Mechanisms

Abstract Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

Abstract 5: Lipid Droplet Associated Hydrolase: A New Player in Cholesterol Mobilization From Foam Cells

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Younghwa Goo ◽  
Pradip Saha ◽  
Larry Chan ◽  
Antoni Paul
Keyword(s):  
Lipid Droplet ◽  
Cholesterol Efflux ◽  
Bone Marrow Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Peritoneal Macrophages ◽  
Cholesterol Homeostasis

Lipid laden macrophages/foam cells are a hallmark of atherosclerotic lesions from early to late stages of development. Macrophages take-up modified low-density lipoprotein (mLDL) particles and store surplus mLDL-derived cholesterol as cholesterol ester (CE) in cytoplasmic lipid droplets (LDs). Accelerating CE hydrolysis from the LDs is a plausible strategy to promote reverse cholesterol transport from the atheroma. However, the identity of the CE hydrolases that function on LDs remains unknown. Previously we identified lipid droplet-associated hydrolase (LDAH) in LDs purified from macrophages and reported that in vitro LDAH regulates CE levels by increasing CE hydrolysis. To determine the relevance of LDAH in atherogenesis, we have generated LDAH knockout (LDAH-/-) mice. Mouse peritoneal macrophages (MPM) isolated from LDAH-/- mice had increased cytoplasmic LDs, increased net CE content, and decreased cholesterol efflux. In atherosclerosis studies, both male and female LDAH-/- mice crossed with apolipoprotein E knockout (apoE-/-) mice fed a Western diet developed larger lesions. Lesions of LDAH-/-/ apoE-/- mice were characterized by increased areas of macrophages containing enlarged cytoplasms with large LDs. Supporting a direct atheroprotective role of LDAH in macrophages, lesions of apoE-/- mice that received bone marrows from LDAH-/-/apoE-/- mice progressed faster than those that received bone marrow cells from LDAH+/+/apoE-/- mice. In qPCR analyses of genes involved in cholesterol homeostasis in macrophages, we found that ABC binding cassette transporters ABCA1 and ABCG1, which mediate cholesterol efflux through the plasma membrane, were consistently decreased in LDAH-/- MPM. Further in vivo gene expression studies on macrophages selectively obtained from lesions using laser capture microdissection are underway. In conclusion, our study suggests that LDAH promotes LD CE hydrolysis and cholesterol efflux from foam cells within the atheroma, and uncovers a potential target to promote reverse cholesterol from arteries as a means of ameliorating atherosclerosis development.

Bioinformatics-based Prediction of the mechanism and targets for BushenjieduDecoction in preventing relapse of acute leukemia

2020 ◽  
Author(s):  
Weilong Sun ◽  
Fujun Yang ◽  
Weipeng Shi ◽  
Xia Tao ◽  
Zhiwei Xi ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Topological Analysis ◽  
Traditional Chinese Medicines ◽  
Potential Mechanism ◽  
Ppi Network ◽  
Chinese Medicines ◽  
Kegg Pathways ◽  
Long Time ◽  
Underlying Mechanisms

Abstract Background: Leukemia is a lethal myeloproliferative disorder, its’ relapse following chemotherapy is the major concern in clinical practice. For a long time, we found that traditional Chinese medicines such as Bushenjiedudecoction (BSJD) have significant effects on delaying relapse. However, the underlying mechanisms are not clear, which limits the clinical application of BSJD decoction. Methods: Therefore, we tried to make some explorations in this study. We isolated mesenchymal stem cells (MSC) after treated them with BSJD for proteomic analysis. And then 109 targets were screened out through analysis of the shared proteins of that affected by BSJD and those related to leukemia. Subsequently, the data were analyzed by GO functions, KEGG pathways, PPI network and topological analysis, and then some nodes were selected for animal experiment. Results: As a result, we demonstrated the effective targets of BSJD on MSC through bioinformatics analysis and explored the potential mechanism of BSJD from its influence on niches.These targets contains Hspb1、Dnmt1、Mmp2、Thbs1、Crebbp、Hmgb1、Acta2、Cdkn1b、Atg7、Tsc2 and Icam1. Afterwards, we confirmed BSJD reduced the gene expression of ICAM-1 through cultured MSC in vitro.Conclusions: We screened the potential targets of BSJD on MSC through proteomics and bioinformatics analysis, and selected some genes for experimental verification. These studies demonstrated the effect of BSJD on MSC. We hope that this research method could provide a new way of systematically studying the effects of traditional Chinese medicine on diseases.

Effect of Peritoneal Macrophages from Intermittent Peritoneal Dialysis Patients on Lymphocytes in Culture

1992 ◽  
Vol 12 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Wladyslaw Sulowicz ◽  
Zygmunt Hanicki ◽  
Wojciech Uracz ◽  
Barbara Hajto ◽  
Irena Ruggiero ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Lymphocyte Proliferation ◽  
Functional Expression ◽  
Suppressive Effect ◽  
Peritoneal Macrophages ◽  
Cardiac Insufficiency ◽  
Control Group ◽  
Nbt Reduction ◽  
End Stage

To investigate the biological activity of peritoneal macrophages, cells isolated from dialysate of 30 patients with end-stage kidney disease treated by intermittent peritoneal dialysis and from ascites of 6 patients with cardiac insufficiency (relative control group) were added to autologous, phytohemagglutinin (PHA)-stimulated lymphocyte cultures. Macrophages of dialyzed patients induced a dose-dependent increase in autologous lymphocyte proliferation, whereas macrophages obtained from control subjects exerted a suppressive effect on those cultures. The enhanced lymphocyte proliferation by macrophages from dialyzed patients was corroborated by the increased metabolic activity of macrophages as evaluated by the increased nitro blue tetrazolium (NBT) reduction test and increased functional expression of Fc receptors (FcR). The subpopulation of macrophages from patients with HLA -DR antigens as determined by HB55 monoclonal antibody, inhibited Iymphoproliferation in vitro. We conclude that peritoneal macrophages from dialyzed patients represent a heterogenous population of cells with different phenotypic and functional characteristics.

Protective effect of betulinic acid on early atherosclerosis in diabetic apolipoprotein-E gene knockout mice

2017 ◽  
Vol 796 ◽  
pp. 224-232 ◽  
Author(s):  
Jung Joo Yoon ◽  
Yun Jung Lee ◽  
Byung Hyuk Han ◽  
Eun Sik Choi ◽  
Min Chul Kho ◽  
...  
Keyword(s):  
Protective Effect ◽  
Apolipoprotein E ◽  
Knockout Mice ◽  
Betulinic Acid ◽  
Gene Knockout ◽  
E Gene ◽  
Apolipoprotein E Gene ◽  
Gene Knockout Mice ◽  
Early Atherosclerosis

scholarly journals Leptin Reduces Plin5 m6A Methylation through FTO to Regulate Lipolysis in Piglets

2021 ◽  
Vol 22 (19) ◽  
pp. 10610
Author(s):  
Dongqin Wei ◽  
Qian Sun ◽  
Yizhou Li ◽  
Chaowei Li ◽  
Xinjian Li ◽  
...  
Keyword(s):  
Treatment Group ◽  
Blood Lipid ◽  
Mitochondrial Respiratory Chain ◽  
Control Group ◽  
Fat Percentage ◽  
Lower Body Weight ◽  
Underlying Mechanisms ◽  
Porcine Adipocytes ◽  
Protein Treatment

Perilipin5 (Plin5) is a scaffold protein that plays an important role in lipid droplets (LD) formation, but the regulatory effect of leptin on it is unclear. Our study aimed to explore the underlying mechanisms by which leptin reduces the N6-methyladenosine (m6A) methylation of Plin5 through fat mass and obesity associated genes (FTO) and regulates the lipolysis. To this end, 24 Landrace male piglets (7.73 ± 0.38 kg) were randomly sorted into two groups, either a control group (Control, n = 12) or a 1 mg/kg leptin recombinant protein treatment group (Leptin, n = 12). After 4 weeks of treatment, the results showed that leptin treatment group had lower body weight, body fat percentage and blood lipid levels, but the levels of Plin5 mRNA and protein increased significantly in adipose tissue (p < 0.05). Leptin promotes the up-regulation of FTO expression level in vitro, which in turn leads to the decrease of Plin5 M6A methylation (p < 0.05). In in vitro porcine adipocytes, overexpression of FTO aggravated the decrease of M6A methylation and increased the expression of Plin5 protein, while the interference fragment of FTO reversed the decrease of m6A methylation (p < 0.05). Finally, the overexpression in vitro of Plin5 significantly reduces the size of LD, promotes the metabolism of triglycerides and the operation of the mitochondrial respiratory chain, and increases thermogenesis. This study clarified that leptin can regulate Plin5 M6A methylation by promoting FTO to affect the lipid metabolism and energy consumption, providing a theoretical basis for treating diseases related to obesity.

scholarly journals High-Survival Rate After Microinjection of Mouse Oocytes and Early Embryos With mRNA by Combining a Tip Pipette and Piezoelectric-Assisted Micromanipulator

2021 ◽  
Vol 9 ◽  
Author(s):  
Lei-Ning Chen ◽  
Xiao-Yan Fan ◽  
Yi-Tong Liu ◽  
Shao-Qing Chen ◽  
Feng-Yun Xie ◽  
...  
Keyword(s):  
Survival Rate ◽  
Gene Knockout ◽  
Germinal Vesicle ◽  
Early Embryo ◽  
High Rate ◽  
Laboratory Animals ◽  
High Survival ◽  
Early Embryos ◽  
Gene Knockout Mice

Utilizing microinjection to introduce biological molecules such as DNA, mRNA, siRNA, and proteins into the cell is well established to study oocyte maturation and early embryo development in vitro. However, microinjection is an empirical technology. The cellular survival after microinjection is mainly dependent on the operator, and an experienced operator should be trained for a long time, from several months to years. Optimizing the microinjection to be highly efficient and quickly learned should be helpful for new operators and some newly established laboratories. Here, we combined the tip pipette and piezo-assisted micromanipulator to microinject the oocyte and early embryos at different stages of mouse. The results showed that the survival rate after microinjection was more than 85% for cumulus–oocyte complex, germinal vesicle oocyte, two-cell, and four-cell embryos, and close to 100% for MII oocyte and zygotes. The high-rate survival of microinjection can save many experimental samples. Thus, it should be helpful in studying some rare animal models such as aging and conditional gene knockout mice. Furthermore, our protocol is much easier to learn for new operators, who can usually master the method proficiently after several training times. Therefore, we would like to publicly share this experience, which will help some novices master microinjection skillfully and save many laboratory animals.

scholarly journals Photodynamic Therapy Enhanced the Antitumor Effects of Berberine on HeLa Cells

2019 ◽  
Vol 17 (1) ◽  
pp. 413-421 ◽  
Author(s):  
Han-Qing Liu ◽  
Ya-Wen An ◽  
A-Zhen Hu ◽  
Ming-Hua Li ◽  
Guang-Hui Cui
Keyword(s):  
Photodynamic Therapy ◽  
Western Blot ◽  
Hela Cells ◽  
Mammalian Target Of Rapamycin ◽  
Control Group ◽  
Antitumor Effects ◽  
Underlying Mechanisms ◽  
And Control

AbstractIn this study we investigated the antineoplastic effects of Berberine (BBR)-mediated photodynamic therapy (PDT) on HeLa cells and its related mechanisms. The CCK-8 assay and flow cytometry were used to evaluate the proliferation and apoptosis of cells respectively. In addition, changes in protein expression levels were assessed using western blot. BBR at dose of 10 mg/kg was injected intraperitoneally to mice with tumors and PDT treatments were performed 24 hours later. In vivo imaging systems were used to evaluate the fluorescence of BBR. In vitro, PDT significantly enhanced the effects of BBR on inducing cell apoptosis and inhibiting proliferation. The in vivo results showed that the fluorescence intensity in the PDT group was decreased compared with that in the BBR group. Tumor weights and tumor size in the PDT group were less than those in the control group; however, when BBR was applied without PDT, no significant differences were observed between the BBR and control group. The results of western blot showed that PDT enhanced the inhibitory effects of BBR on the mammalian target of rapamycin (mTOR) signaling pathway, that may partly explain the potential underlying mechanisms.

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