| 1. |
- Chen, Lujun, et al.
(författare)
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Immunochemical Staining of MT2-MMP Correlates Positively to Angiogenesis of Human Esophageal Cancer
- 2010
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Ingår i: Anticancer research. - 1791-7530. ; 30:10, s. 4363-4368
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) play an important role in the pathological processes of degradation of extracellular matrix and destruction of basement membrane, which leads to tumor invasion and metastasis. In the present study, we investigated membrane-type 2 MMP (MT2-MMP) expression pattern in esophageal cancer tissues collected from 103 patients, and explored MT2-MMP expression pattern in correlation to patients' clinicopathological features, intratumoral angiogenesis and postoperative prognoses. The intensity of immunochemical staining of MT2-MMP was significantly positively correlated to the intratumoral angiogenesis of esophageal cancer tissues. Positive MT2-MMP immunoreactions were found in 85.4% of total tumor sections, whereas none or very weak MT2-MMP staining occurred in normal esophageal tissues. In addition, MT2-MMP immunochemical intensities were significantly correlated to tumor size, but not to patient's gender, age, invasion depth, lymph node metastasis and distant metastasis. Moreover, MT2-MMP levels could not be applied for predicting patients' survival rate although the H-score cut-off value showed the overall survival rate of patients with low MT2-MMP protein level to be better than those with high MT2-MMP protein level.
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| 2. |
- Chen, Lujun, et al.
(författare)
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Immunolocalisation of tissue factor in esophageal cancer is correlated with intratumoral angiogenesis and prognosis of the patient
- 2010
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Ingår i: Acta Histochemica. - : Elsevier BV. - 0065-1281. ; 112:3, s. 233-239
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Tidskriftsartikel (refereegranskat)abstract
- It has been demonstrated that tissue factor (TF) may be involved in the tumor-derived procoagulatory status and angiogenic modulation in certain solid tumors. In the present study, we examined immunohistochemical localisation of TF in esophageal squamous cell carcinomas (ESCC) from 103 patients. TF immunopositivity was found in 91.3% of all tumor sections, while normal esophageal tissues were immunonegative. Patients were divided into a low TF immunoreactivity group (9 cases of negative and 48 cases of weak positive) and a high TF immunoreactivity group (35 cases of moderate positive and 11 cases of strong positive). TF immunoreactivity was significantly correlated to the presence of distant metastasis (P = 0.0014), while it was not correlated to patient's gender, age, tumor size, depth of tumor invasion or lymph node metastasis. Survival analysis revealed that the overall survival rate in the patients that had high TF immunoreactivity was significantly poorer than those with low TF immunoreactivity (P = 0.0094). Univariate analysis demonstrated that tumor size (P = 0.0095), depth of tumor invasion (P = 0.0050), lymph node metastasis (P = 0.0045) and distant metastasis (P < 0.0001) were effective predictors of prognosis in patients. However, only distant metastasis could independently predict patients' outcomes by the analysis of multivariate proportional hazards regression (P = 0.0043). Furthermore, the intratumoral microvessel density (MVD), evaluated by CD34 immunolabeling, indicated that MVD was positively correlated to the TF immunoreactivity (P = 0.0056). It is concluded that TF immunopositivity in ESCC tissues is strongly correlated to the intratumoral angiogenesis and to poor patient prognosis. (C) 2009 Elsevier GmbH. All rights reserved.
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| 3. |
- Jiang, Jingting, et al.
(författare)
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Expression of apolipoprotein M in human hepatocellular carcinoma tissues
- 2011
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Ingår i: Acta Histochemica. - : Elsevier BV. - 0065-1281. ; 113:1, s. 53-57
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined mRNA levels and protein mass of apolipoprotein M (apoM) in human hepatocellular carcinoma (HCC) tissues and in the adjacent tissues. Plasma apoM levels in these HCC patients were also determined and compared to the normal subjects. The mean level of plasma apoM in the HCC patients was 0.61 +/- 0.30 OD mm(-2), which was significantly higher than that in the normal subjects 0.37 +/- 0.07 OD mm(-2) (P < 0.01). However, both apoM mRNA levels and apoM protein mass in the HCC tissues were significantly lower than in the adjacent tissues (P < 0.05). It is concluded that human hepatocellular carcinoma tissues had a reduced capacity to produce apoM than the adjacent non-tumor tissues. However, the plasma apoM levels were higher in the HCC patients than in normal subjects, which suggested that tissues adjacent to the tumors or extra-hepatic apoM production in the HCC patients may contribute to the higher plasma apoM levels in these patients. The clinical significance of apoM in relation to HCC still needs further investigation. (C) 2009 Published by Elsevier GmbH.
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| 4. |
- Jiang, Jingting, et al.
(författare)
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Increased plasma apoM levels in the patients suffered from hepatocellular carcinoma and other chronic liver diseases
- 2008
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine plasma apolipoprotein M ( apoM) levels and other lipid profiles in hepatocellular carcinoma ( HCC) patients compared to other chronic liver diseases and normal subjects. Materials and methods: 36 HCC, 68 chronic hepatitis, 29 liver cirrhosis patients and 64 normal controls were subjected in the present study. Serum lipids, lipoproteins, apolipoprotein AI ( apoAI) and apoB were determined by the conventional methods. Plasma apoM levels were semiquantitatively determined by both dot- blotting and western blotting analysis. Results: Serum levels of triglycerides ( TG), HDL- cholesterol, apoAI and lipoprotein ( a) ( Lp( a)) were significantly lower in the HCC patients than in the normal subjects, whereas there were no obvious differences on serum total cholesterol, LDL- cholesterol and apoB between HCC patients and normal subjects. However, plasma apoM levels in HCC patients were significantly increased than those in the normal subjects, but lower than those in the chronic hepatitis and cirrhosis patients. Conclusion: It is concluded that serum TG, apoAI, HDL- C and Lp( a) were significantly decreased in HCC patients than in controls, whereas plasma apoM levels were significantly increased in the HCC patients. Decreased serum TG, apoAI, HDL- C and Lp( a) may reflect the liver damage in HCC patients, whereas the clinical significance of increased plasma apoM levels in relation to HCC is not clear.
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| 5. |
- Liu, Bokai, et al.
(författare)
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Al-DeMat: A web-based expert system platform for computationally expensive models in materials design
- 2023
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Ingår i: Advances in Engineering Software. - : Elsevier. - 0965-9978 .- 1873-5339. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- We present a web-based framework based on the R shiny package with functional back-end server in machine learning methods. A 4-tiers architecture is programmed to achieve users’ interactive design and visualization via a web browser. Many data-driven methods are integrated into this framework, namely Random Forest, Gradient Boosting Machine, Artificial and Deep neural networks. Moreover, a robust gradient-free optimization technique, the Particle Swarm Optimization, is used to search optimal values in hyper-parameters tuning. K-fold Cross Validation is applied to avoid over-fitting. R2 and RMSE are considered as two key factors to evaluate the trained models. The contributions to the expert system in materials design are: (1) A systematic framework that can be applied in materials prediction with machine learning approaches, (2) A user-friendly web-based platform that is easy and flexible to use and (3) integrated optimization and visualization into the framework with pre set algorithms. This computational framework is designed for researchers and materials engineers who would like to do the preliminary designs before experimental studies. Finally, we demonstrate the performance of the web-based framework through 2 case studies.
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| 6. |
- Liu, Bokai, et al.
(författare)
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Stochastic interpretable machine learning based multiscale modeling in thermal conductivity of Polymeric graphene-enhanced composites
- 2024
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Ingår i: Composite structures. - : Elsevier. - 0263-8223 .- 1879-1085. ; 327
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Tidskriftsartikel (refereegranskat)abstract
- We introduce an interpretable stochastic integrated machine learning based multiscale approach for the prediction of the macroscopic thermal conductivity in Polymeric graphene-enhanced composites (PGECs). This method encompasses the propagation of uncertain input parameters from the meso to macro scale, implemented through a foundational bottom-up multi-scale framework. In this context, Representative Volume Elements in Finite Element Modeling (RVE-FEM) are employed to derive the homogenized thermal conductivity. Besides, we employ two sets of techniques: Regression-tree-based methods (Random Forest and Gradient Boosting Machine) and Neural networks-based approaches (Artificial Neural Networks and Deep Neural Networks). To ascertain the relative influence of factors on output estimations, the SHapley Additive exPlanations (SHAP) algorithm is integrated. This interpretable machine learning methodology demonstrates strong alignment with published experimental data. It holds promise as an efficient and versatile tool for designing new composite materials tailored to applications involving thermal management.
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| 7. |
- Lundström, Linda, et al.
(författare)
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Important pharmacophores for binding to galanin receptor 2
- 2005
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Ingår i: Neuropeptides. - 0143-4179 .- 1532-2785. ; 39:3, s. 169-171
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Tidskriftsartikel (refereegranskat)abstract
- Galanin(2–11) has been introduced as a receptor subtype selective ligand for the GalR2 subtype of the galanin receptors, and has gained use in pharmacological studies of galaninergic signaling in the past two years. By introducing l-Ala substitutions in the galanin(2–11) sequence, we have examined the amino acid residues which are of importance for binding to the GalR2 receptor. Our study shows that Trp2, Asn5, Gly8 and Tyr9 are of great importance for high affinity binding. When placed in an α-helical conformation, the side chains of these residues are, with the exception of Tyr9, displayed on the same “side” of the peptide. This information is useful in the rational design of non-peptide type GalR2 receptor ligands.
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| 8. |
- Luo, Guanghua, et al.
(författare)
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Expression and localization of apolipoprotein M in human colorectal tissues
- 2010
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been well documented that apolipoprotein M (apoM) is principally expressed in the liver and kidney. However we found that there was weak apoM expression in other tissues or organs too, which could not be ignored. In the present study, we therefore examined apoM expression in human colorectal tissues including cancer tissues, cancer adjacent normal tissues, polyp tissues and normal mucosa as well as inflammatory mucosa. Methods: Tissue samples were collected from patients who underwent surgical resection or endoscopic examination. ApoM mRNA levels were determined by the real-time RT-PCR and apoM protein mass were examined by the immunohistochemistry. Results: ApoM protein can be detected in all colorectal tissues. However, apoM protein mass were significantly lower in the cancer tissues than its matched adjacent normal tissues, polyp tissues, normal mucosa and inflammatory mucosa. In parallel, apoM mRNA levels in the colorectal cancer tissues (0.0536 +/- 0.0131) were also significantly lower than those in their adjacent normal tissues (0.1907 +/- 0.0563) (P = 0.033). Interestingly, apoM mRNA levels in colorectal cancer tissues were statistic significant higher in the patients with lymph node metastasis than the patients without lymph node metastasis (P = 0.008). Patients under Dukes' C and D stages had much higher apoM mRNA levels than patients under Dukes' A and B stages (P = 0.034). Conclusion: It is concluded that apoM could also be expressed in human colorectal tissues besides liver and kidney. ApoM mRNA levels in the colorectal cancer tissues were significantly increased in the patients with lymph node metastasis. Whether increased apoM expression in the patients with lymph node metastasis being related to patients' prognosis and the physiopathological importance of apoM expression in colorectal tissues need further investigation.
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| 9. |
- Luo, Guanghua, et al.
(författare)
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Genotyping of single nucleotide polymorphisms using base-quenched probe: A method does not invariably depend on the deoxyguanosine nucleotide
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 1096-0309 .- 0003-2697. ; 386:2, s. 161-166
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Tidskriftsartikel (refereegranskat)abstract
- Most available methods for detecting single nucleotide polymorphisms (SNPs) are based principally on the system that can produce an increased fluorescence signal during hybridization. In the current study, we demonstrate a method of base-quenched probe for polymerase chain reaction (PCR) genotyping that requires only a pair of primers and one fluorescent probe and does not invariably depend on the deoxyguanosine nucleotide. This method further exploits the phenomenon of fluorescence quenching of fluorescent-labeled probe during hybridization to its complementary target gene's sequence. 6-Carboxyfluorescein (FAM) can be directly conjugated to a base of either adenine (A), thymine (T), cytosine (C), or guanine (G), referred to as A-, T-, C-, or G-quenched probe, respectively, at either the 5' or 3' end. For describing the method in detail, we chose apolipoprotein M (apoM) as a target gene in the current study. DNA sequencing analyses validated that all four types of base-quenched probes could provide unbiased genotyping results (K = 1, P = 0.000), although the maximum speed of fluorescence increase, max(dF/dT), when using the G-quenched probe method, was approximately twofold lower than the others (P < 0.0001). Moreover, we applied this method to detect another seven SNPs in the genomes of phospholipase A2, monocyte chemoattractant protein I (MCP1), and L-ficolin, further confirming our method. It is concluded that this method is precise, simple, and economic as well as suitable for large-scale genotyping Studies. (C) 2008 Elsevier Inc. All rights reserved.
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| 10. |
- Luo, Guanghua, et al.
(författare)
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Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPARβ/δ in HepG2 cells.
- 2014
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 445:1, s. 203-207
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Tidskriftsartikel (refereegranskat)abstract
- It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPARβ/δ pathway.
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| 11. |
- Luo, Guanghua, et al.
(författare)
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Rosiglitazone Enhances Apolipoprotein M (Apom) Expression in Rat's Liver.
- 2014
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 11:10, s. 1015-1021
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of high density lipoprotein (HDL), which plays a crucial role behind the mechanism of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin resistance could associate with decreased APOM expressions. In agreement with our previous reports, here, we further confirmed that the insulin sensitivity was also reduced in rats treated with high concentrations of glucose; such effect could be reversed by administration of rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ). The present study shows that Apom expression is significantly affected by either rosiglitazone or hyperglycemia alone without cross interaction with each other, which indicates that the pathway of Apom expression regulating by hyperglycemia might be differed from that by rosiglitazone. Further study indicated that hyperglycemia could significantly inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1) (P<0.0001), liver receptor homologue-1 (Lrh1) (P=0.0012), ATP-binding cassette transporter 1 (Abca1) (P=0.0012) and Pparb/d (P=0.0043). Two-way ANOVA analysis demonstrated that the interactions between rosiglitazone and infusion of 25% glucose solution on Shp1 (P=0.0054) and Abca1 (4E, P=0.0004) mRNA expression was statistically significant. It is concluded that rosiglitazone could increase Apom expression, of which the detailed mechanism needs to be further investigated. The downregulation of Apom by hyperglycemia might be mainly through decreasing expression of Pparg and followed by inhibiting Lxrb in rats.
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| 12. |
- Shi, Yuanping, et al.
(författare)
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Comprehensive lipidomics in apoM−/− mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation
- 2020
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Ingår i: Journal of Genetics and Genomics. - : Elsevier BV. - 1673-8527. ; 47:9, s. 523-534
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apoM affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apoM on liver and plasma lipidomes and how apoM participates in lipid cycling, via apoM knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry–based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters (CEs), in apoM−/− mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apoM−/− mice; while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of ApoB-100 was dramatically increased in the liver, whereas significant reductions in both ApoB-100 and low-density lipoprotein (LDL) cholesterol were observed in the serum of apoM−/− mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apoM−/− leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apoM knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.
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| 13. |
- Tang, Xiaojie, et al.
(författare)
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Orbital hydroclimate variability revealed by grain-size evidence in the tropical Pacific Islands since 140 ka
- 2024
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Ingår i: Global and Planetary Change. - 0921-8181. ; 236
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Tidskriftsartikel (refereegranskat)abstract
- The past evolution of precipitation and atmospheric convection in the Western Pacific Warm Pool (WPWP) is critical for global climate changes but is under debate because of its forcing mechanisms. Here, we present a high temporal resolution (∼156 years) grain-size record of core MD01–2385 over the last 140 kyr, in offshore northern New Guinea to reveal sediment dynamics as a proxy for precipitation changes. End-member analysis revealed that a two-endmember model was optimal. The end-member 1/end-member 2 (EM1/EM2) ratio could represent the variation in grain size and exhibited significant precessional cycles changes in phase with modelled Niño 3 SST anomaly from a global climate model transient simulation. From these data, we inferred orbital fluctuations in precipitation from tropical western Pacific islands, with general precipitation peaks during the time of perihelion at the boreal autumnal equinox (midpoint from a low to high precession index), corresponding to La Niña-like conditions and vice versa. Comparisons of our new record with published precipitation records showed that orbital precipitation changes in the WPWP are mainly dominated by El Niño-Southern Oscillation-like (ENSO-like) oscillations in the precession band, while the Intertropical Convergence Zone (ITCZ) mainly controls the distribution of precipitation over a larger spatial area.
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| 14. |
- Wang, Zhigang, et al.
(författare)
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Decreased Splenic CD4(+) T-Lymphocytes in Apolipoprotein M Gene Deficient Mice
- 2015
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Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- Spleen T-lymphocytes, especially CD4(+) T-cells, have been demonstrated to be involved in broad immunomodulation and host-defense activity in vivo. Apolipoprotein M gene (apoM) may have an important role in the regulation of immunoprocess and inflammation, which could be hypothesized to the apoM containing sphingosine-1-phosphate (S1P). In the present study we demonstrate that the splenic CD4(+) T-lymphocytes were obviously decreased in the apoM gene deficient (apoM(-/-)) mice compared to the wild type (apoM(+/+)). Moreover, these mice were treated with lipopolysaccharide (LPS) and it was found that even more pronounced decreasing CD4(+) T-lymphocytes occurred in the spleen compared to the apoM(+/+) mice. The similar phenomena were found in the ratio of CD4(+)/CD8(+) T-lymphocytes. After administration of LPS, the hepatic mRNA levels of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemotactic protein-1 (MCP-1) were markedly increased; however, there were no statistical differences observed between apoM(+/+) mice and apoM(-/-) mice. The present study demonstrated that apoM might facilitate the maintenance of CD4(+) T-lymphocytes or could modify the T-lymphocytes subgroups in murine spleen, which may further explore the importance of apoM in the regulation of the host immunomodulation, although the detailed mechanism needs continuing investigation.
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| 15. |
- Zhang, Xiaoying, et al.
(författare)
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Expression of MMP-10 in lung cancer
- 2007
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Ingår i: Anticancer research. - 1791-7530. ; 27:4C, s. 2791-2795
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix is a key point in tumor development and expansion. MMP-10 is one of the most important and well-characterized members of the MMP family. In the present study, we examined MMP-10 mRNA and protein levels in non-small cell lung cancer (NSCLC). Patients and Methods: Three endogenous reference genes including GAPDH, beta-actin and 18S rRNA, and MMP-10 mRNA levels were determined using real-time RT-PCR. Immunohistochemical staining was applied to examine MMP-10 protein levels. Both tumor and adjacent normal lung tissues were collected from 32 NSCLC patients. The mRNA levels of GAPDH, beta-actin and 18S rRNA exhibited great differences in tumor tissues and in the adjacent normal tissues. The ratio of mRNA levels in the tumor tissues compared to the adjacent normal tissues followed the pattern GAPDH > beta-actin > 18S rRNA. Thereafter, we chose 18S rRNA as the reference gene for MMP-10 mRNA level determinations. MMP-10 mRNA levels in tumor tissues were significantly lower than those in the adjacent normal tissues (p = 0.0423). However, the MMP- 10 protein levels were higher in the tumor tissues than in the adjacent normal tissues (p=0.0055). The MMP-10 mRNA level was positively-correlated to the MMP-10 protein level in tumor tissues (r=0.4672, p=0.0161), but this correlation was not seen in the adjacent normal tissues (r=-0.0030, p=0.9891). Conclusion: There were no statistical differences in MMP-10 mRNA levels and protein levels in relation to patient's gender, age, tumor stages, tumor size, lymph node metastasis or tumor histological type.
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| 16. |
- Zhang, Xiaoying, et al.
(författare)
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IL-6 Regulates MMP-10 Expression via JAK2/STAT3 Signaling Pathway in a Human Lung Adenocarcinoma Cell Line
- 2009
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Ingår i: Anticancer research. - 1791-7530. ; 29:11, s. 4497-4501
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that matrix metalloproteinase (MMP)-10 mRNA levels were significantly lower in tumor tissues than in adjacent normal tissues in human non-small cell lung cancer (NSCLC), whereas protein levels of MMP-10 were higher in the tumor tissues than the adjacent tissues. The mechanism of this divergence is still unknown. In the present stud), the role of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) on interleukin (IL)-6 mediated regulation of MMP-10 expression was investigated in a human lung adenocarcinoma cell line (A549 cells) and the molecular regulatory mechanism of MMP-10 expression was explored. A549 cells were stimulated by different concentrations of IL-6 with or without AG490, a specific JAK2 inhibitor. It was demonstrated that IL-6 moderately reduced the MMP-10 mRNA levels, whereas it significantly enhanced the MMP-10 protein mass in the A549 cells. This phenomenon mimicked the divergence of mRNA level and protein mass of MMP-10 in human NSCLC. Moreover, the present study indicated that IL-6 regulation of MMP-10 expression was via the JAK2/STAT3 pathway. STAT3 mRNA levels were significantly increased when the cells were treated with IL-6, whereas when AG490 (50 mu M) was added to the cell cultures, IL-6-induced increase of STAT3 mRNA levels was abolished. Meanwhile, AG490 blocked the IL-6-induced inhibition of MMP-10 mRNA as well as blocking the IL-6-induced increase of MMP-10 protein mass in the A549 cells. Neither IL-6 nor AG490 influenced JAK2 mRNA levels in the A549 cell cultures. It is concluded that the JAK2/STAT3 pathway is involved in the IL-6-mediated regulation of MMP-10, and IL-6 can moderately reduce MMP-10 mRNA levels and strongly increase MMP-10 protein mass in human lung adenocarcinoma A549 cells. Contrasting effects of IL-6 on MMP-10 mRNA level and protein concentration in A549 cells may partially explain the divergence of MMP-10 mRNA level and protein mass in human NSCLC.
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| 17. |
- Zhang, Xiaoying, et al.
(författare)
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Liver X receptor agonist downregulates hepatic apoM expression in vivo and in vitro
- 2008
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 371:1, s. 114-117
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Tidskriftsartikel (refereegranskat)abstract
- It has been demonstrated that apolipoprotein M (apoM), a recently discovered HDL apolipoprotein, has antiatherosclerotic properties, which may be mediated by the enhancement of reversed cholesterol transportation and/or hepatic cholesterol catabolism. The detailed mechanisms are unknown yet. Liver X receptor (LXR) belongs to the nuclear receptor superfamily and is a ligand-activated transcription factor involved in the regulation of lipid metabolism and inflammation. Activation of LXR in the cell cultures results in an enhancement of cholesterol efflux to apoAl. In the present study, we investigated effects of the LXR agonist, T0901317 on hepatic apoM expression in vivo and in vitro. Serum apoM levels in mice given T0901317 at 10 mg or 100 mg/kg for 7 days were reduced by 12-17% (P < 0.05). In HepG2 cell cultures, apoM mRNA levels were significantly lower in presence of 25 mu M T0901317 (37.1%) than in control cells (P < 0.001). A similar reduction was found by the addition of 9-cis retinoic acid (RA). Twenty-five micromolar T0901317 together with 100 nM RA decreased apoM mRNA expression by 65% (P < 0.001). Thus, the LXR agonist T0901317 significantly downregulates apoM mRNA expression in vivo and in vitro, which indicates that apoM is another novel target gene regulated by the LXR. The combination of RA and T0901317 showed additive effects, which suggests that apoM expression can be modulated by LXR/RXR pathway.
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| 18. |
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| 19. |
- Zheng, Lu, et al.
(författare)
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Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.
- 2014
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 11:4, s. 365-372
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.
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| 20. |
- Zheng, Lu, et al.
(författare)
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Intralipid decreases apolipoprotein m levels and insulin sensitivity in rats.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (ApoM) is a constituent of high-density lipoproteins (HDL). It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels.
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