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Lam Wai Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 124-148). / Abstracts in English and Chinese. / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1 --- Lipoproteins --- p.1 / Chapter 1.1.1 --- General structure --- p.1 / Chapter 1.1.2 --- Chylomicrons --- p.2 / Chapter 1.1.3 --- Very-low-density lipoprotein (VLDL) --- p.3 / Chapter 1.1.4 --- Low-density lipoprotein (LDL) --- p.4 / Chapter 1.1.5 --- High-density lipoprotein (HDL) --- p.4 / Chapter 1.1.6 --- Lipoprotein metabolism --- p.5 / Chapter 1.1.6.1 --- Exogenous pathway --- p.5 / Chapter 1.1.6.2 --- LDL receptor pathway --- p.6 / Chapter 1.1.6.3 --- Reverse cholesterol transport --- p.6 / Chapter 1.2 --- Cholesterol homeostasis --- p.8 / Chapter 1.2.1 --- Role of Acyl-CoA: Cholesterol Acyltransferase (ACAT) in intracellular cholesterol regulation --- p.8 / Chapter 1.2.2 --- Cholesterol biosynthesis --- p.9 / Chapter 1.2.3 --- Bile acid metabolism --- p.10 / Chapter 1.3 --- Coronary heart disease (CHD) --- p.14 / Chapter 1.3.1 --- Risk factors of CHD --- p.16 / Chapter 1.3.2 --- Lipoprotein cholesterol and CHD --- p.18 / Chapter 1.4 --- Animal models for hypercholesterolemic study --- p.20 / Chapter 1.5 --- Physico-chemical properties of water-soluble dietary fiber (SDF) --- p.22 / Chapter 1.5.1 --- Water-holding capacity --- p.23 / Chapter 1.5.2 --- Viscosity --- p.24 / Chapter 1.5.3 --- Adsorption or entrapment of organic molecules --- p.25 / Chapter 1.5.4 --- Fermentability --- p.25 / Chapter 1.6 --- Hypocholesterolemic effect of SDF and proposed mechanisms --- p.26 / Chapter 1.7 --- Medicinal properties of edible mushrooms --- p.28 / Chapter 1.7.1 --- Background information --- p.28 / Chapter 1.7.2 --- Hypocholesterolemic effect of edible mushrooms --- p.29 / Chapter 1.7.3 --- Previous studies on edible jelly mushrooms --- p.31 / Chapter 1.8 --- Objectives / Chapter Chapter 2: --- Materials and Methods --- p.34 / Chapter 2.1 --- Materials --- p.34 / Chapter 2.1.1 --- Sample preparation --- p.34 / Chapter 2.1.2 --- Animal model --- p.35 / Chapter 2.2 --- Methods --- p.35 / Chapter 2.2.1 --- Extraction scheme of mushroom water-soluble non-starch polysaccharides (SNSPs) --- p.35 / Chapter 2.2.2 --- Proximate analyses of samples --- p.36 / Chapter 2.2.2.1 --- Crude protein --- p.36 / Chapter 2.2.2.2 --- Fat --- p.37 / Chapter 2.2.2.3 --- Total dietary fiber --- p.38 / Chapter 2.2.2.4 --- Soluble and insoluble dietary fiber --- p.39 / Chapter 2.2.2.5 --- Ash --- p.40 / Chapter 2.2.2.6 --- Moisture --- p.41 / Chapter 2.2.3 --- Chemical characterization of mushroom SNSPs --- p.41 / Chapter 2.2.3.1 --- Monosaccharide composition by gas chromatography --- p.41 / Chapter 2.2.3.2 --- Total carbohydrate content --- p.44 / Chapter 2.2.3.3 --- Uronic acid content --- p.44 / Chapter 2.2.3.4 --- Soluble protein content --- p.45 / Chapter 2.2.4 --- Rheological study of mushroom SNSPs --- p.46 / Chapter 2.2.4.1 --- Determination of intrinsic viscosity [ η] of mushroom SNSPs --- p.46 / Chapter 2.2.4.2 --- Determination of apparent viscosity [ηap] of mushroom SNSPs --- p.48 / Chapter 2.2.5 --- In vivo study --- p.50 / Chapter 2.2.5.1 --- Animal diets --- p.50 / Chapter 2.2.5.1.1 --- Study for hypocholesterolemic potential of mushroom SNSPs --- p.50 / Chapter 2.2.5.1.2 --- Study for dose-dependent effect on hypocholesteolemic potential of Auricularia polytricha (AP) SNSP --- p.50 / Chapter 2.2.5.2 --- Feeding experiments --- p.51 / Chapter 2.2.5.2.1 --- Screening for hypocholesterolemic potential of mushroom SNSPs --- p.51 / Chapter 2.2.5.2.2 --- Dose-dependent effect on hypocholesterolemic potential of AP SNSP --- p.52 / Chapter 2.2.5.3 --- Blood samples collection --- p.52 / Chapter 2.2.5.4 --- Plasma preparation --- p.53 / Chapter 2.2.5.5 --- Liver samples collection and preparation --- p.53 / Chapter 2.2.5.6 --- Fecal samples collection and preparation --- p.53 / Chapter 2.2.5.7 --- Determination of plasma lipid profiles --- p.54 / Chapter 2.2.5.7.1 --- Plasma total cholesterol (TC) analysis --- p.54 / Chapter 2.2.5.7.2 --- Plasma high-density lipoprotein cholesterol (HDL-C) analysis --- p.54 / Chapter 2.2.5.7.3 --- Plasma triglycerides (TG) analysis --- p.55 / Chapter 2.2.5.8 --- Determination of hepatic cholesterol profile by gas chromatography --- p.56 / Chapter 2.2.5.9 --- Determination of hepatic enzymes activity --- p.58 / Chapter 2.2.5.9.1 --- Preparation of hepatic microsomes --- p.58 / Chapter 2.2.5.9.2 --- Determination of 3-hydroxy-3-methyl- glutaryl-Coenzyme A reductase (HMG-CoA reductase) activity --- p.58 / Chapter 2.2.5.10 --- Determination of fecal lipid profiles by gas chromatography --- p.61 / Chapter 2.2.5.10.1 --- Separation of fecal neutral and acidic sterols --- p.61 / Chapter 2.2.5.10.2 --- Fecal neutral sterol analysis --- p.61 / Chapter 2.2.5.10.3 --- Fecal acidic sterol analysis --- p.62 / Chapter 2.2.6 --- Statistical analysis --- p.63 / Chapter Chapter 3: --- Results and Discussion --- p.65 / Chapter 3.1 --- Proximate analysis of edible jelly mushrooms --- p.65 / Chapter 3.2 --- Yield of mushroom SNSP crude extracts --- p.67 / Chapter 3.3 --- Chemical characterization of mushroom SNSPs --- p.68 / Chapter 3.3.1 --- Total carbohydrate content --- p.68 / Chapter 3.3.2 --- Uronic acid content --- p.68 / Chapter 3.3.3 --- Soluble protein content --- p.68 / Chapter 3.3.4 --- Monosaccharide composition --- p.69 / Chapter 3.4 --- Rheological behavior of mushroom SNSPs --- p.71 / Chapter 3.4.1 --- Intrinsic viscosity [η] --- p.71 / Chapter 3.4.2 --- Apparent viscosity [ηap] --- p.75 / Chapter 3.5 --- In vivo hypocholesterolemic potential of mushroom SNSPs --- p.78 / Chapter 3.5.1 --- Effect on body weight and diet intake --- p.79 / Chapter 3.5.2 --- Effect on plasma TC concentration --- p.81 / Chapter 3.5.3 --- Effect on plasma HDL-C concentration --- p.84 / Chapter 3.5.4 --- Effect on plasma TG concentration --- p.86 / Chapter 3.5.5 --- Effect on hepatic cholesterol profile --- p.89 / Chapter 3.5.6 --- Effect on HMG-CoA reductase activity by AA and AP SNSPs --- p.92 / Chapter 3.5.7 --- Effect on neutral and acidic sterols excretion by AA and AP SNSPs --- p.93 / Chapter 3.5.8 --- Correlation between hypocholesterolemic potential and viscosity of mushroom SNSPs --- p.97 / Chapter 3.6 --- In vivo dose-dependent effect on hypocholesterolemic potential of AP SNSP --- p.99 / Chapter 3.6.1 --- Effect on body weight and diet intake --- p.100 / Chapter 3.6.2 --- Effect on plasma TC concentration --- p.102 / Chapter 3.6.3 --- Effect on plasma HDL-C concentration --- p.105 / Chapter 3.6.4 --- Effect on plasma TG concentration --- p.107 / Chapter 3.6.5 --- Effect on hepatic cholesterol profile --- p.110 / Chapter 3.6.6 --- Effect on HMG-CoA reductase activity --- p.113 / Chapter 3.6.7 --- Effect on neutral and acidic sterols excretion --- p.114 / Chapter 3.6.8 --- Correlation between dosage and hypocholesterolemic effect of AP SNSP --- p.119 / Chapter Chapter 4: --- Conclusions and Future works --- p.121 / List of References --- p.124 / Related Publications --- p.149

Chin, Chi Hou. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves [165]-178). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese (摘要） --- p.iv / Acknowledgements --- p.vi / Abbreviations --- p.vii / List of Figures and Tables --- p.xi / Publications --- p.xv / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Hematopoiesis and Leukemia --- p.2 / Chapter 1.1.1. --- Hematopoiesis --- p.2 / Chapter 1.1.2. --- Leukemia --- p.8 / Chapter 1.1.2.1. --- Overview of leukemia --- p.8 / Chapter 1.1.2.2. --- Symptoms and diagnosis of leukemia --- p.9 / Chapter 1.1.2.3. --- Classification of leukemia --- p.9 / Chapter 1.1.2.4. --- Epidemiology of leukemia --- p.13 / Chapter 1.1.2.5. --- Conventional treatments for leukemia --- p.15 / Chapter 1.1.2.6. --- Novel approaches to leukemia treatment --- p.18 / Chapter 1.2. --- Statins --- p.22 / Chapter 1.2.1. --- Overview of statins --- p.22 / Chapter 1.2.2. --- Chemical structures of statins --- p.24 / Chapter 1.2.3. --- Pharmacokinetics of statins --- p.26 / Chapter 1.2.4. --- Pleiotropic effects of statins --- p.29 / Chapter 1.2.4.1. --- Anti-inflammatory and immunomodulatory effects of statins --- p.29 / Chapter 1.2.4.2. --- Anti-angiogenic effects of statins --- p.30 / Chapter 1.2.4.3. --- Anti-tumor effects of statins --- p.31 / Chapter 1.3. --- Objectives and scope of the present study --- p.33 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1. --- Materials --- p.36 / Chapter 2.1.1. --- Animals --- p.36 / Chapter 2.1.2. --- Cell lines --- p.36 / Chapter 2.1.3. --- "Cell culture media, buffers and other reagents" --- p.37 / Chapter 2.1.3.1. --- Cell culture media and reagents --- p.37 / Chapter 2.1.3.2. --- Drugs and chemicals --- p.40 / Chapter 2.1.3.3. --- Reagents and buffers for primary culture --- p.42 / Chapter 2.1.3.4. --- Dye solutions --- p.43 / Chapter 2.1.3.5. --- Reagents for cell proliferation assays --- p.44 / Chapter 2.1.3.6. --- Reagents and buffers for flow cytometry --- p.44 / Chapter 2.1.3.7. --- Reagents for Hoechst staining --- p.45 / Chapter 2.1.3.8. --- Reagents and buffers for DNA isolation --- p.46 / Chapter 2.1.3.9. --- Reagents and buffers for DNA agarose gel electrophoresis --- p.48 / Chapter 2.1.3.10. --- Reagents and buffers for Cell Death ELISA --- p.50 / Chapter 2.1.3.11. --- Reagents and buffers for measuring caspase activity --- p.51 / Chapter 2.1.3.12. --- Reagents and buffers for Western blotting --- p.55 / Chapter 2.1.3.13. --- Reagents for determining nitric oxide production --- p.63 / Chapter 2.2. --- Methods --- p.64 / Chapter 2.2.1. --- Culture of tumor cell lines --- p.64 / Chapter 2.2.2. --- "Isolation, preparation and culture of murine peritoneal macrophages" --- p.64 / Chapter 2.2.3. --- Cell proliferation and cytotoxicity studies --- p.66 / Chapter 2.2.4. --- In vivo tumorigenicity study --- p.68 / Chapter 2.2.5. --- Cell cycle profile and flow cytometric analysis --- p.69 / Chapter 2.2.6. --- Hoechst staining --- p.69 / Chapter 2.2.7. --- DNA fragmentation analysis --- p.70 / Chapter 2.2.8. --- Cell Death ELISA --- p.71 / Chapter 2.2.9. --- Mitochondrial membrane potential analysis --- p.73 / Chapter 2.2.10. --- Measurement of caspase activity --- p.73 / Chapter 2.2.11. --- Protein expression study --- p.75 / Chapter 2.2.12. --- Cell morphological staining --- p.80 / Chapter 2.2.13. --- Cell size and granularity analysis by flow cytometry --- p.81 / Chapter 2.2.14. --- Determination of nitric oxide production by macrophages --- p.81 / Chapter 2.2.15. --- Statistical analysis --- p.82 / Chapter Chapter 3 --- Anti-Proliferative Effect of Statins on Myeloid Leukemia Cells / Chapter 3.1. --- Introduction --- p.84 / Chapter 3.2. --- Results --- p.86 / Chapter 3.2.1. --- Anti-proliferative effect of statins on various murine and human myeloid leukemia cells --- p.86 / Chapter 3.2.2. --- Cytotoxicity of fluvastatin on murine myelomonocytic leukemia WEHI-3B JCS cells --- p.93 / Chapter 3.2.3. --- Cytotoxicity of fluvastatin on primary murine myeloid cells --- p.96 / Chapter 3.2.4. --- Kinetic and reversibility studies on the anti-proliferative effect of fluvastatin on WEHI-3B JCS cells --- p.98 / Chapter 3.2.5. --- Relationship between the anti-proliferative effect of fluvastatin and the cholesterol biosynthesis pathway in WEHI-3B JCS cells --- p.102 / Chapter 3.2.6. --- Effect of fluvastatin on the in vivo tumorigenicity of WEHI-3B JCS cells --- p.106 / Chapter 3.2.7. --- Effect of fluvastatin on the cell cycle profile of WEHI-3B JCS cells --- p.108 / Chapter 3.2.8. --- Effect of fluvastatin on the expression of cell cycle regulatory proteins inWEHI-3B JCS cells --- p.113 / Chapter 3.3. --- Discussion --- p.116 / Chapter Chapter 4 --- Apoptosis- and Differentiation-inducing Effects of Fluvastatin on Murine Myelomonocytic Leukemia WEHI-3B JCS Cells / Chapter 4.1. --- Introduction --- p.124 / Chapter 4.2. --- Results --- p.128 / Chapter 4.2.1. --- Induction of chromatin condensation in WEHI-3B JCS cells by fluvastatin --- p.128 / Chapter 4.2.2. --- Induction of DNA fragmentation in WEHI-3B JCS cells by fluvastatin --- p.130 / Chapter 4.2.3. --- Effect of fluvastatin on the mitochondrial membrane potential in WEHI-3B JCS cells --- p.134 / Chapter 4.2.4. --- Effect of fluvastatin on the caspase activities in WEHI-3B JCS cells --- p.138 / Chapter 4.2.5. --- Effect of fluvastatin on the expression of pro-apoptotic protein AIF in WEHI-3B JCS cells --- p.144 / Chapter 4.2.6. --- Effect of fluvastatin on the morphology of WEHI-3B JCS cells --- p.147 / Chapter 4.2.7. --- Effect of fluvastatin on the cell size and granularity of WEHI-3B JCS cells --- p.149 / Chapter 4.2.8. --- Immunomodulation of murine peritoneal macrophages by fluvastatin --- p.151 / Chapter 4.3. --- Discussion --- p.153 / Chapter Chapter 5 --- Conclusions and Future Perspectives --- p.160 / References --- p.165

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 53-59).

Plant sterols (PS) are effective in reducing plasma lipid concentrations, however, few studies have examined their cholesterol lowering effects in type 2 diabetics. The objective was to assess whether PS consumption alters blood lipid profile in hypercholesterolemic subjects with and without type 2 diabetes. Fifteen control subjects (age = 55.1 +/- 8.5 yr and BMI = 26.9 +/- 3.0kg/m2) and fourteen diabetic subjects (age = 54.5 +/- 6.7 yr and BMI = 30.2 +/- 3.0kg/m2) participated in a double-blinded, randomized, crossover, placebo-controlled feeding trial. The Western diet included either 1.8g/d of PS or cornstarch placebo each provided over 21 d separated by a 28 d washout period. Subjects consumed only foods prepared in Mary Emily Clinical Nutrition Research Unit of McGill University. Total cholesterol (TC) decreased (p < 0.05) from baseline with PS for control and diabetic subjects by 9.7% and 13.6%, respectively. TC decreased (P < 0.05) from baseline with placebo for control and diabetic subjects by 10.9% and 11.6%, respectively. Non high density lipoprotein cholesterol (non-HDL-C) decreased (p < 0.05) from baseline with PS for diabetic subjects by 18.5%. Low density lipoprotein cholesterol (LDL-C) levels were reduced (p < 0.05) from baseline with PS for control and diabetic subjects by 14.9% and 29.8%, respectively. The reduction of LDL-C due to PS alone is greater with type 2 diabetics. There were no significant changes in HDL-C and TG across diets or treatments. It is thus concluded that PS consumption with diet enhances non-HDL-C and LDL-C reduction compared with diet alone in hypercholesterolemic individuals with and without type 2 diabetes. Demonstration for the first time that PS alone are more efficacious in lowering LDL-C and non-HDL-C in diabetic individuals compared to non-diabetics confirm the beneficial effects of PS to help prevent cardiovascular disease (CVD) for this high risk population.

The objective of this research was to examine the effects of plant sterols and glucomannan on lipid profiles, plasma plant sterol levels and glycemic control in mildly hypercholesterolemic subjects. Thirteen type 2 diabetic and sixteen non-diabetic individuals participated in a randomized crossover trial consisting of 4 phases, of 21 days each. During the study period, subjects were supplemented with plant sterols and/or glucomannan. Overall reductions of total cholesterol and low-density lipoprotein (LDL) cholesterol concentrations were greater after consumption of plant sterols and glucomannan compared to plant sterol or glucomannan supplementation alone. Plasma lathosterol levels, indicators of cholesterol biosynthesis, were decreased after combination treatment. The results suggest that a combination of glucomannan and plant sterols substantially improve plasma lipids by reducing cholesterol absorption and synthesis simultaneously. Supplementation of plant sterols and glucomannan can thus be used as an effective treatment for management of circulating cholesterol levels and prevention of cardiovascular disease.

The objective of this study was to compare the effect of phytosterols (PS) on lipid profiles and cholesterol kinetics of hypercholesterolemic individuals with or without type 2 diabetes. It was hypothesised that the response to PS would differ between both groups due to different lipid metabolism. During this randomised, double blind, crossover trial, participants consumed a controlled diet with placebo or PS for 21 days. / Plasma total cholesterol (TC) decreased with placebo and PS (10.9% and 9.7% in non-diabetic versus 11.6% and 13.6% in diabetic participants, p < 0.05). Plasma low-density lipoprotein cholesterol (LDL) significantly decreased with PS in both groups. The reduction in LDL with PS was greater in diabetic compared to non-diabetic individuals (29.8% versus 14.9%, p < 0.05). Cholesterol absorption decreased on average (p = 0.06) by 26.5% with PS compared with placebo in the diabetic group only. Therefore, a controlled heart healthy diet reduced TC and LDL concentrations in non-diabetic and diabetic individuals. Adding PS as adjuncts to a hypocholesterolemic dietary treatment was associated with lower LDL concentrations and cholesterol absorption in hypercholesterolemic participants with type 2 diabetes.

The objective of this study was to examine the effects of plant sterols and/or glucomannan on lipid profiles and cholesterol kinetics in hyperlipidemic individuals with or without type 2 diabetes. It was hypothesized that plant sterols and glucomannan reduce circulating cholesterol levels and may have an additive or synergistic effect when combined by reducing cholesterol absorption. Thirteen type 2 diabetics and sixteen non-diabetics all mildly hypercholesterolemic free living subjects participated in a randomized crossover trial consisting of 4 phases, 21 days each. Subjects consumed plant sterols and glucomannan during the trial. Overall reductions in total and LDL-cholesterol levels were greater (P<0.05) after consumption of the combination supplement. Effects of supplements were not different between diabetics and non-diabetics. No significant changes were observed in cholesterol absorption or synthesis in both diabetics and non-diabetics. The intake of plant sterols and glucomannan together may be an alternative approach in reducing blood cholesterol levels.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.