• Title/Summary/Keyword: apolipoprotein

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Clinical significance of APOB inactivation in hepatocellular carcinoma

  • Lee, Gena;Jeong, Yun Seong;Kim, Do Won;Kwak, Min Jun;Koh, Jiwon;Joo, Eun Wook;Lee, Ju-Seog;Kah, Susie;Sim, Yeong-Eun;Yim, Sun Young
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.7.1-7.12
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    • 2018
  • Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model

  • Zhang, Zhidong;Zou, Gangqiang;Chen, Xiaosan;Lu, Wei;Liu, Jianyang;Zhai, Shuiting;Qiao, Gang
    • Molecules and Cells
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    • v.42 no.3
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    • pp.218-227
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    • 2019
  • This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial

  • Hwang, Hyo-Jeong;Liu, Yanan;Kim, Hyun-Sook;Lee, Heeseung;Lim, Yunsook;Park, Hyunjin
    • Nutrition Research and Practice
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    • v.13 no.2
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    • pp.105-114
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    • 2019
  • BACKGROUND/OBJECTIVES: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. SUBJECTS/METHODS: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6 week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. RESULTS: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. CONCLUSION: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS. This trial is registered at ClinicalTrials.gov as NCT03267901.

The Relationship between Coronary Risk Factors and Coronary Calcium Score Detected by Computed Tomography Coronary Angiography in Korean Middle Aged Men (다중절편 방사선단층촬영 결과에 기반한 한국 중년 남성에서의 관상동맥 석회화와 심혈관질환 위험인자와의 연관성)

  • Park, Seung-Hyun;Kim, Young-Wook;Chae, Chang-Ho;Kim, Ja-Hyun;Kang, Yune-Sik;Park, Yong Whi;Jeong, Baek Geun
    • Journal of agricultural medicine and community health
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    • v.39 no.1
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    • pp.25-36
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    • 2014
  • Objectives: The objective of this study was to investigate the relationship between coronary artery calcification and risk factors of cardiovascular disease with multidetector computed tomography. Methods: Data were collected from 5,899 males between 30 and 59 years old by interview, survey, physical examination, blood test, and multidetector computed tomography in the university hospital from January 2010 to December 2011. We confirmed the coronary artery calcium scores of subjects by multidetector computed tomography and identified risk factors of cardiovascular disorders. We investigated the relationship between coronary artery calcification and risk factors of cardiovascular disorders. Results: Mean calcium score of the coronary arteries in 5,899 participants was 8.20, and 773 participants (13.1%) exhibited coronary artery calcification. The presence of coronary artery calcification was correlated to risk factors of cardiovascular disease (age, blood pressure, triglyceride, HDL cholesterol, LDL cholesterol, glucose, Apolipoprotein A-1, Apolipoprotein B, body mass index, waist circumference) and risk assessment tools of cardiovascular disorders. Significant predicted factors of coronary artery calcification had different patterns in each age group (30-39, 40-49, 50-59 years old). Conclusions: We confirmed the relationship between coronary artery calcification and either typical risk factors of cardiovascular disease or risk assessment tools of cardiovascular disease. In addition, we also observed that the pattern of these factors varied according to age. Therefore, age-related variation needs to be considered in management strategies to prevent cardiovascular disease.

Analysis of Serum proteom before and after Intravenous Injection of wild ginseng herbal acupuncture (자연산 산삼 증류약침의 혈맥주입 전.후 혈장의 Proteom 분석)

  • Kang, Tae-Sik;Lee, Sun-Gu;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.7 no.3
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    • pp.5-25
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    • 2004
  • Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensionl electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as Transferrin, 9001 as(Alpha-Oxy, Beta-(C112g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803), which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5. Immunoglobulin lambda chain(3105), Alpha-Oxy, Beta-(C112g)deoxy T-State Human Hemoglobin(9001), and human hemoglobin(9003) were increased by more than two-times after the administration of herbal acupuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of herbal acupuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of herbal acupuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial aimyloid polyneuropathy(FAP), was decreased after the administration of herbal acupuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of herbal acupuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of herbal acupuncture. 11. Transferrin(8101), T-State Human Hemoblobin(9001), and Human Hemoblobin(9003) which balances the iron level in the body, were increased after the administration of herbal acupuncture. Conousion : Above results support the notion that intravenous injection of cultivated wild ginseng herbal acupuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

Association of Clusterin Polymorphisms (-4453T<G, 5608T<C) with Coronary Heart Disease in Korean Population (한국인에서의 Clusterin의 유전자다형성(-4453T<G, 5608T<C)과 관상동맥질환과의 연관성)

  • Kim, Su-Won;Yoo, Min
    • Journal of Life Science
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    • v.20 no.4
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    • pp.584-588
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    • 2010
  • Clusterin is an 80 kDa heterodimetric glycosylated protein which plays diverse biological roles in various tissues and organs. Clusterin is reported to be associated with the pathogenesis of coronary artery disease and atherosclerosis. Therefore, we investigated the genotype for the T

Root bark extract of Cudrania tricuspidata reduces LPS-induced inflammation in macrophages of atherogenic mice

  • Lee, Mi-Ran
    • Journal of the Korea Society of Computer and Information
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    • v.25 no.10
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    • pp.115-123
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    • 2020
  • In this paper, we propose to evaluate the potential anti-inflammatory properties of root bark extract of Cudrania (C.) tricuspidata on lipopolysaccharide (LPS)-induced inflammation in macrophages of apolipoprotein E (ApoE) knockout (ApoE-/-) mice, murine model of atherosclerosis. Atherosclerosis is a chronic vascular inflammatory disease. C. tricuspidata is a small tree of the Moraceae family and its extract has anti-inflammatory activities. However, its role in the progress of atherosclerosis is not yet clear. To determine anti-inflammatory effects of C. tricuspidata in atherogenesis, we applied LPS in peritoneal macrophages of ApoE-/- mice and measured cell viability by CCK-8 and expression of pro-inflammatory cytokines by qRT-PCR following treatment with root bark extract of C. tricuspidata. Research data was expressed as differences between the cells treated with LPS and root bark extract and the cells treated with LPS alone (control) by a two-tailed non-parametric Mann-Whitney U-test using GraphPad Instat program. No cytotoxic effect was observed when the cells were treated with the extract at concentrations ≤ 100 ㎍/mL. The expression of inflammatory cytokines, including MCP-1, IL-1β, IFN-γ, TNF-α, and IL-6 were inhibited by the extract. These results indicated that the extract has an anti-inflammatory effect and therefore a possible role in the treatment of atherosclerosis.

Development of Low Density Lipoprotein Receptor-Related Protein 5 (LRP5) Gene Targeted Mouse (저밀도 리포단백질 수용체 관련 단백질 5(LRP5) 유전자 적중 생쥐의 개발)

  • Park H. Y.;Kim C. M.;Lee S. M.;Jeoung Y. H.;Moon S. J.;Kang M. J.
    • Reproductive and Developmental Biology
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    • v.29 no.1
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    • pp.19-24
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    • 2005
  • The low density lipoprotein receptor-related protein 5 (LRP5) highly expressed in many tissues, including hepatocytes and pancreatic beta cells, can bind to apolipoprotein E. To evaluate in vivo roles of LRP5, we generated LRP5-deficient mice. LRP5 genomic DNA was isolated from TT2 embryonic stem (ES) cells. Targeting vector was constructed to disrupt an exon 18 of the mouse LRP5 gene and transfected into ES cells. Three homologous recombinants at LRP5 locus were identified from 178 G418-resistant clones. Chimeric males generated by morula aggregation technique were mated to C57BL/6 female mice. After achieving germ-line transmission, LRP5+/- females were crossed with LRP5+/- males to obtain LRP5-deficient mice. One line of mice lacking LRP5 gene was confirmed by Southern blotting. Such knock-out mice may serve as an effective animal model to study in vivo function of LRP5 gene.

Effects of Aerobic Training Plus Diet on Blood Lipids and Apolipoproteins in Obese Children (유산소 트레이닝과 식사조절 병행이 비만아동의 혈중지질과 아포지단백에 미치는 효과)

  • Park, Tae-Gon
    • Journal of Life Science
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    • v.18 no.10
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    • pp.1384-1389
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    • 2008
  • The purpose of this study was to find out the effects of aerobic training plus diet on blood lipids and apolipoproteins (Apo) in obese children. Sixteen healthy obese boys (ages 10.9; body mass index (BMI) $\geq$95th percentiles for age and sex) participated in this study. The aerobic training program consisted of 40 minutes hiking on a mountain, 60 minute of basketball and football dribbling at an intensity of 60-70% of HRmax, and was performed 5 days a week for 9 weeks. The diet prescription was 2,100 kal/day according to the recommended dietary allowance for 10-12 year old Koreans. All subjects stayed in a training camp for 9 weeks. The results of this study were as follows; Blood lipid profiles including total cholesterol (TC), triglyceride (TG) high density lipoprotein cholesterol (HDL-C) and TC/HDL-C ratio were significantly improved after the 9 week program, but there was no significant change in low density lipoprotein (LDL-C). Apolipoprotein profiles, Apo AI, AII, B, CII and CⅢ were all significantly decreased after the 9 week program, but there were no significant difference in Apo AI/AII ratio and Apo B/AI ratio. These results indicate that aerobic training together with a healthy diet can induce positive changes on blood lipid profiles, Apo AII, B and CII in obese children.

Inhibitory Activity of Edible Mushrooms on the Tissue Thromboplastin (Tissue Factor) (조직 혈액응고인자에 대한 식용버섯류의 저해활성)

  • Hwang, Keum-Hee;Kim, Hyun-Ku;Han, Yong-Nam
    • Korean Journal of Food Science and Technology
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    • v.29 no.1
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    • pp.161-166
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    • 1997
  • Tissue thromboplastin (tissue factor), a membrane bound glycoprotein is an important initiating factor in blood coagulation cascade, which leads to the formation of thrombin by activating both factor X and IX. Activation of blood coagulation by TF is essential for blood injury, and stimulates the blood coagulation in myocardial infarction, cancer and blood coagulatory diseases. High density lipoprotein, apolipoprotein A-II were known to be biological TF inhibitors. Recently, studies on search for TF inhibitors from natural products have been active in Korea. Among the edible mushrooms screened for inhibitory activities on the TF, Lentinus edodes showed the most strong activity, followd by Agaricus bisporus and Ganoderma lucidium. And the fractionation of the above mushrooms with the chloroform ($CHCl_3$) and ethylacetate (EtOAc) was done and evaluated for the inhibitory activities on TF. In Ganoderma lucidium, $CHCl_3$ fraction and $H_2O$ layer were not active, but EtOAc fraction exhibited a strong inhibitory activity on TF and the $IC_{50}$ value was $1.07{\times}10^{-4}\;g$. In the case of Agaricus bisporus, there were no inhibitory activities on the TF in all of the fractions. $CHCl_3$ fraction and $H_2O$ layer of Lentinus edodes did not show inhibition on the TF but EtOAc fraction showed strong inhibition on the TF, and the $IC_{50}$ value was $7.70{\times}10^{-4}\;g$.

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