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Taurine can ameliorate hypercholesterolemia by facilitating cholesterol efflux and increasing cytochrome P450 7A1 (CYP7A1) without clear underlying molecular mechanisms. This study aims to elucidate the molecular action of taurine in diet-induced hypercholesterolemia. Male Wistar rats were fed a high cholesterol diet containing 5% taurine for 14 days. Three-dimensional primary hepatocytes from rats were exposed to 10 mM taurine for 24 h. Transcriptome analyses of both the liver and hepatocytes were performed using DNA microarray. Taurine significantly decreased serum cholesterol levels and increased hepatic CYP7A1 mRNA levels and transcription rates in rats. Taurine altered the expression of seventy-seven genes in the liver, involving lipid, drug, amino acid metabolism, and gluconeogenesis pathways. The small heterodimer partner (SHP), a transcription factor regulated by taurine, was suppressed. "Network analysis" revealed a negative correlation between the SHP and induction of CYP7A1 and cytochrome P450 8B1 (CYP8B1). However, CYP7A1 and CYP8B1 levels were not altered by taurine in 3D-primary hepatocytes. Venn diagram analyses of the transcriptomes in both hepatocytes and the liver indicated a consistent upregulation of organic anion transporting polypeptide 2 (OATP2) and betaine homocysteine methyltransferase (BHMT). Taurine ameliorated hypercholesterolemia in rats fed a high cholesterol diet by directly enhancing the hepatic expression of BHMT and OATP2, which modulated the SHP and induced CYP7A1 and CYP8B1, thereby promoting cholesterol catabolism and lowering blood cholesterol levels. [ABSTRACT FROM AUTHOR]

Drug bioavailability refers to the fraction of administered drug that reaches systemic circulation after ingestion by mouth and absorption in the gastrointestinal tract. Bioavailability is influenced by various routes or dosage forms. Bioavailability is impacted by absorption, distribution, metabolism, and excretion of drugs by an organism. In medicine and other fields, nanoscale drug delivery systems offer effective methods for improving the bioavailability of bioactives. Pharmaceuticals need to be released from these carriers to be fully absorbed and exert their therapeutic effects. In bioactive molecule research and development, in vitro models and in vivo animal models can be used to simulate delivery of drugs into the body and assess parameters that allow prediction of their bioavailability. To date, common bioavailability models include in vitro simulated drug release models, in vitro simulated digestion models, cellular models, and in vivo pharmacokinetic models. This paper summarizes the establishment and application of representative bioavailability models to provide a reference for future research and development of in vitro and in vivo bioavailabilitymodels for nanoscale drug delivery systems. [ABSTRACT FROM AUTHOR]

It is known that plasma lipid levels are controlled not only by dietary fat and carbohydrate but also by dietary protein and amino acids. Although it used to be thought that the source of protein was important, it is known that amino acid composition, amino acids themselves, and peptides from digested protein are more important than the protein source. Sulfur-containing amino acids (SAAs) are recognized to be some of the most potent modulators of lipid metabolism among amino acids. It has been demonstrated that SAAs have an increasing effect on HDL (high-density lipoprotein)-cholesterol and a decreasing effect on VLDL (very low-density lipoprotein)-cholesterol. These data lead us to propose that SAAs have some beneficial functions against atherosclerotic diseases and metabolic syndrome. Relative availability of SAAs (RASAA) as well as the amount of SAAs in dietary protein would determine lipid metabolism. Therefore, we propose RASAA as a feasible index for improvement of lipid metabolism by amino acids. Although it is not clear how SAAs influence gene expression and lipid metabolism at a molecular level, SAAs change the metabolic pathway through transcriptional stimulation and posttranslational modification of regulatory proteins. KEY WORDS: * sulfur-containing amino acids * methionine * cystine * taurine * cholesterol

The effect of taurine on hypercholesterolemia induced by feeding a high-cholesterol (HC) diet (10g/kg) to rats was examined. When various amounts of taurine (0.25, 0.5, 1,2.5, 5, 10, 20, 30, 40 or 50 g/kg diet) were supplemented to HC for 2 wk, serum total cholesterol gradually and significantly decreased in a dose-dependent manner and normalized at the dose of 10 g taurine/kg, compared with the control (cholesterol free) diet group. By contrast, serum HDL-cholesterol was elevated by taurine supplementation. The HC diet caused a significant decrease in the concentration of taurine in serum, liver and heart compared to that in the control group, and the effective dose of supplemental taurine to improve its reduction was 2.5 g/kg diet. In the hypercholesterolemic rats fed the HC diet, the excretion of fecal bile acids and hepatic cholesterol 7 [Alpha]-hydroxylase (CYP7A1) activity and its mRNA level increased significantly, and the supplementation of taurine further enhanced these indexes, indicating an increase in cholesterol degradation. The abundance of mRNA for Apo A-I, one of the main components of HDL, was reduced by HC and recovered by taurine supplementation. Agarose gel electrophoresis revealed that, in hypercholesterolemic rats fed the HC diet, the serum level of the heavier VLDL increased significantly, but taurine repressed this increase and normalized this pattern. Significant correlations were observed between the time- and dose-dependent increases of CYP7A1 gene expression and the decrease of blood cholesterol concentration in rats fed the HC diet supplemented with taurine (time, r = -0.538, P < 0.01, n = 32; dose, r = -0.738, P < 0.001, n = 20). These results suggest that the hypocholesterolemic effects of taurine observed in the hypocholesterolemic rats fed the HC diet were mainly due to the enhancement of cholesterol degradation and the excretion of bile acid. KEY WORDS: taurine; cholesterol; hypocholesterolemia; cholesterol 7-hydroxylase (CYP7A1); rat

Many reports have shown the therapeutic efficacy of LDL apheresis (LDL‐A) in drug‐resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long‐Term Effects of the LDL‐Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m2), moderately impaired (M) (≥30 to <60 ml/min/1.73 m2), and severely impaired (S) (<30 ml/min/1.73 m2) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end‐stage renal disease at 2 years after LDL‐A treatment. These results suggest that LDL‐A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor-6 (HNF-6) is a liver-enriched transcription factor that contains a single cut domain and a novel type of homeodomain. Here we have studied the developmental expression pattern of HNF-6 in the mouse. In situ hybridization experiments showed that HNF-6 mRNA is detected in the liver at embryonic day (E) 9, at the onset of liver differentiation. HNF-6 mRNA disappeared transiently from the liver between E12.5 and E15. In transfection experiments HNF-6 stimulated the expression of HNF-4 and of HNF-3[Beta], two transcription factors known to be involved in liver development and differentiation. HNF-6 was detected in the pancreas from E10.5 onward, where it was restricted to the exocrine cells. HNF-6 was also detected in the developing nervous system. Both the brain and the spinal cord started to express HNF-6 at E9-9.5 in postmitotic neuroblasts. Later on, HNF-6 was restricted to brain nuclei, to the retina, to the ventral horn of the spinal cord, and to dorsal root ganglia. Our observations that HNF-6 contributes to the control of the expression of transcription factors and is expressed at early stages of liver, pancreas, and neuronal differentiation suggest that HNF-6 regulates several developmental programs.