다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

mTOR Signaling in Growth Control and Disease

mTOR signaling in growth control and disease.

Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.

/pdf/ampk-and-mtor-regulate-autophagy-through-direct-14wqsz16ke.pdf

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Identifying Codium fragile extract components and their effects on muscle weight and exercise endurance.

SIRT1 plays a key role in regulating metabolism, and SIRT1 activation may be a promising strategy to treat metabolic syndrome. This study investigated whether zerumbone ameliorated diet-induced obe...

Effect of a new dietary SIRT1 activator on high fat diet-induced obesity and the involvement of microRNAs

Soluble glucan, which was obtained from action of glucosyltransferases (GTFs) of Streptococcus mutans on sucrose, was partially hydrolyzed by acetic acid and examined for human T lymphoblast (MOLT-4) stimulating activity. Addition of the partially hydrolyzed glucan (15-60 microg/ml) stimulated human T cell (39-65%) in a dose dependant manner according to MTT assay. Production of interleukine-2 (IL-2) and interleukine-2 receptor (IL-2R) from T cell was increased by 44.5 and 25%, respectively, by addition of partially hydrolyzed glucan (15 microg/ml). These results indicate that stimulation of human T cells by hydrolyzed glucan is probably caused by its effects on stimulating gene expression of IL-2 and IL-2R of human T cell.

Effect of partially hydrolyzed soluble glucan produced by glucosyltrasferases of Streptococcus mutans on stimulating human T cell

2,6-Dimethoxy-1,4-benzoquinone increases skeletal muscle mass and performance by regulating AKT/mTOR signaling and mitochondrial function.

This study was conducted to investigate the physicochemical properties of the ethanol extracts and soluble dietary fiber from Cassia tora L. seed. The proximate composition of Cassia tora, soluble solid contents, color intensity and contents of emodin and rhein of Cassia tora extract, molecular mass distribution, sugar contents and viscosity of soluble fiber from Cassia tora were analyzed. Cassia tora contains 12.6% of moisture, 5.2% of ash, 13.4% of crude protein, 7.2% of crude fat, 8.8% of insoluble fiber and 48.3% of soluble fiber. The effects of extract condition on soluble solid contents, color intensity and contents of emodin and rhein of Cassia tora extract were investigated. The soluble solid contents were higher in 70% or 50% ethanol extracts than those in 100% ethanol extracts and showed highest value in grind sample extracts. In Hunter's color value, 100% ethanol extracts and whole Cassia tora sample extracts were higher in L and b value, but on the contrary, were lower in a value, than those of the other. The highest emodin and rhein contents were observed in 70% and 50% ethanol extracts, respectively, and showed higher value in room temperature extracts than in heating extracts. The molecular mass of soluble fiber from Cassia tora seed was estimated by gel filtration chromatography. Most soluble fiber(80%) exhibited a molecular mass range of between 50~2000 kDa. The major sugars of soluble fiber from Cassia tora seed were identified as xylose, mannose and galactose. The apparent viscosity of 0.5% soluble fiber from Cassia tora seed was 33 mPas showing a higher value than pectin or xanthan gum.

/pdf/physicochemical-properties-of-ethanol-extracts-and-dietary-215gn3lym9.pdf

Chang Hwa Jung

Papers

Identifying Codium fragile extract components and their effects on muscle weight and exercise endurance.

Effect of a new dietary SIRT1 activator on high fat diet-induced obesity and the involvement of microRNAs

Effect of partially hydrolyzed soluble glucan produced by glucosyltrasferases of Streptococcus mutans on stimulating human T cell

2,6-Dimethoxy-1,4-benzoquinone increases skeletal muscle mass and performance by regulating AKT/mTOR signaling and mitochondrial function.

Physicochemical Properties of Ethanol Extracts and Dietary Fiber from Cassia tora L. Seed