Aaenweber3637
SIRT6, a member of the silencing information regulatory protein family, is a nicotinamide adenine dinucleotide-dependent histone deacetylase and an ADP-ribose transferase enzyme. It plays an important role in fundamental physiological and pathological processes, including lipid metabolism, inflammation, oxidative stress and fibrosis, and is considered as a potential therapeutic target for metabolic syndrome. SIRT6 knockout mice displayed severe fatty liver, and the expression of SIRT6 in the liver of nonalcoholic steatohepatitis (NASH) mice was significantly lower than that of normal mice. Overexpression of SIRT6 significantly ameliorated NASH-induced liver damage. It is suggested that SIRT6 may play a key role in protecting against NASH. In this paper, we review the important regulatory functions of SIRT6 in the occurrence and development of NASH.Circadian clock is an internal autonomous time-keeping system, including central clocks located in the suprachiasmatic nucleus (SCN) and peripheral clocks. The molecular circadian clock consists of a set of interlocking transcriptional-translational feedback loops that take the clock-controlled genes 24 h to oscillate. Y-27632 The core mechanism of molecular circadian clock is that CLOCK/BMAL1 dimer activates the transcription of cryptochromes (CRYs) and Periods (PERs), which act as transcriptional repressors of further CLOCK/BMAL1-mediated transcription. In addition to this basic clock, there is an additional sub-loop of REV-ERBα and RORα regulating the transcription of BMAL1. Approximately 80% protein-coding genes demonstrate significant rhythmicity. The earth rotation is responsible for the generation of the daily circadian rhythms. To coordinate metabolic balance and energy availability, almost all organisms adapt to the rhythm. Studies have shown that circadian clock integrating with metabolic homeostasis increases the efficiency of energy usage and coordinates with different organs in order to adapt to internal physiology and external environment soon. As the central organ of metabolism, the liver performs various physiological activities nearly all controlled by the circadian clock. There are multiple interactive regulation mechanisms between the circadian clock and the regulation of liver metabolism. The misalignment of metabolism with tissue circadian is identified as a high-risk factor of metabolic diseases. This article reviews the recent studies on circadian physiological regulation of liver glucose, lipid and protein metabolism and emphasizes oscillation of mitochondrial function. We also take an outlook for new methods and application of circadian clock research in the future.Amino acids are essential nutrients for humans and have a wide range of biological functions. They are the constituent units of protein and energy metabolites. In addition, they are also widely involved in the maintenance and regulation of various physiological functions, and play a role in transcription, translation, post-translational modification and other levels. The liver is a key metabolic organ, and it acts as a hub that connects the metabolism of various tissues. Amino acid sensing plays a very important role in the regulation of hepatic glucose and lipid metabolism. Therefore, accurately sensing the levels of intracellular and extracellular amino acids is the key to maintaining cell homeostasis. There are several well-known amino acid sensors in eukaryotic cells, such as general control non-derepressible-2 (GCN2), mammalian target of rapamycin (mTOR) and taste receptors, which play an important role in maintaining metabolic homeostasis. This article gives a detailed introduction to the role and mechanism of amino acids in regulating hepatic glucose and lipid metabolism, laying a foundation for further exploration of amino acid sensing mechanism and treatment of hepatic glucose and lipid metabolism disorders.Glucose and lipid metabolism is the most fundamental metabolic activity of higher organisms. This process is affected by both genetic polymorphisms and environmental factors. Excessive uptake and accumulation of lipids lead to obesity and disorder of glucose metabolic homeostasis characterized by insulin resistance and hyperglycemia, suggesting that the cross-regulation between lipid and glucose metabolism happens precisely at organ, cellular and molecular levels by known mechanisms. Adenine nucleotides and their metabolites have emerged as mediators in the mutual regulation of glucose and lipid metabolism. This review summarizes the roles of purinergic signaling induced by fatty acids in glucose metabolism and the development of type 2 diabetes.The high failure rate of the new drug development has been well recognized. Relying on the pre-clinical data obtained from animal experiments will inevitably cause a low concordance with human clinical trials, which will eventually lead to new drug development failure. Employing human induced pluripotent stem cells (iPSCs) or adult stem cells to simulate disease models can not only provide an unlimited cell materials, but also faithfully represent the genetic background of a certain disease, when iPSCs or adult stem cells derived from patients with a specific disease genetic variation are applied. In addition, gene editing methods can be used to introduce genetic variants of interest into stem cells to generate disease models. Furthermore, by establishing a cell bank with a population of iPSCs in petri dish, in vitro human genetic studies can be carried out in these cells, with GWAS and QTL studies applied to identify genetic variants that are associated with drug sensitivity or cytotoxicity. These efforts may offer valuable information for the recruitment of suitable patients for clinical trials. Therefore, stem cell-derived disease models can provide valuable resources for the pathophysiological studies of diseases as well as the drug development. In this review, we will briefly introduce the development of the liver disease models derived from stem cells and their applications in disease study and drug development.TBS-protected or NH-sulfonimidamides react with β-alkoxyvinyl trifluoromethylketones under solvent-free mechanochemical conditions to give 3-trifluoromethyl-substituted three-dimensional 1,2,6-thiadiazine 1-oxides. C4-Functionalized products can be obtained by starting from cyclic enones and brominations of the initially formed heterocycles. The stability of the products was investigated by varying the pH value and storage under aerobic conditions.Glycolipids are a group of sugar-containing lipids with versatile functions. In this study, a natural glycolipid product was obtained from soy lecithin, and its emulsifying, oil-gelling, antibacterial and antiviral properties were investigated. A silica-based extraction method on a preparative scale was used to recover the glycolipid product (GLP) from soy lecithin. The GLP consisted of three different glycolipid classes acylated sterol glucoside (64.16%), sterol glucoside (25.57%) and cerebroside (6.71%). As an emulsifier, the GLP was able to form a stable water-in-oil emulsion. The GLP exhibited a good oil-gelling property, capable of gelling rapeseed oil at a concentration of 6%. For the investigated microorganisms (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus), the GLP did not show any antibacterial effects. The GLP exerted antiviral activity against lentivirus, but not adenovirus. The results of this study help in enriching the knowledge on the properties of naturally occurring glycolipids, which may find potential applications in the food, pharmaceutical and related industries.It is generally assumed that listeners with normal audiograms have relatively symmetric hearing, and more specifically that diotic stimuli (having zero interaural differences) are heard as centered in the head. While measuring intracranial lateralization with a visual pointing task for tones and 50-Hz-wide narrowband noises from 300 to 700 Hz, examples of systematic and large (>50% from midline to the ear) lateralization biases were found. In a group of ten listeners, five showed consistent lateralization bias to the right or left side at all or a subset of frequencies. Asymmetries in hearing, not apparent in audiometric thresholds, may explain these lateralization biases.
Some trans people want to create families in a variety of ways that include pregnancy, but often face obstacles in doing so.
This paper explores how trans pregnancy is treated as exceptional and out of the ordinary by reproductive institutions.
Analysis of case studies demonstrates the ubiquity of institutional obstacles to trans pregnancy and how reproductive institutions unnecessarily render trans pregnancy exceptional.
Reproductive institutions shape the kinds of people for whom achieving pregnancy is made easier, and often fail to imagine the possibility of trans parents. This failure of imagination is not rooted in biological fact, but rather in social logics that ought to be the site for transformations that expand access and shift provider attitudes.
Trans parents are unexceptional in the sense that, even though they may experience relatively more concentrated forms of adversity, they share many reproductive capabilities and obstacles with cis parents. In light of that concentrated adversity and the epistemic insights it might generate, how might prospective trans parents engage with new reproductive technologies? How might these engagements render them moral pioneers called to make decisions about the sorts of people created using reproductive biotechnologies?
Trans parents are unexceptional in the sense that, even though they may experience relatively more concentrated forms of adversity, they share many reproductive capabilities and obstacles with cis parents. In light of that concentrated adversity and the epistemic insights it might generate, how might prospective trans parents engage with new reproductive technologies? How might these engagements render them moral pioneers called to make decisions about the sorts of people created using reproductive biotechnologies?
The primary aims of the present study were to assess the relationships of early (0-50 ms) and late (100-200 ms) knee extensor rate of force development (RFD) with maximal voluntary force (MVF) and sit-to-stand (STS) performance in participants with chronic kidney disease (CKD) not requiring dialysis.
Thirteen men with CKD (eGFR = 35.17 ±.5 ml/min per 1.73 m
, age = 70.56 ±.4 years) and 12 non-CKD men (REF) (eGFR = 80.31 ± 4.8 ml/min per 1.73 m
, age = 70.22 ±.9 years) performed maximal voluntary isometric contractions to determine MVF and RFD of the knee extensors. RFD was measured at time intervals 0-50 ms (RFD
) and 100-200 ms (RFD
). STS was measured as the time to complete five repetitions. Measures of rectus femoris grayscale (RF GSL) and muscle thickness (RF MT) were obtained via ultrasonography in the CKD group only. Standardized mean differences (SMD) were used to examine differences between groups. Bivariate relationships were assessed by Pearson's product moment correlation.
Knee extensor .
ClinicalTrials.gov, identifier NCT03160326 and NCT02277236.
