Interactions among insulin resistance, epigenetics, and donor sex in gene expression regulation of iPSC-derived myoblasts.

About 25% of people in the general population are insulin resistant, increasing the risk for type 2 diabetes (T2D) and metabolic disease. Transcriptomic analysis of induced pluripotent stem cells differentiated into myoblasts (iMyos) from insulin-resistant (I-Res) versus insulin-sensitive (I-Sen) nondiabetic individuals revealed that 306 genes increased and 271 genes decreased in expression in iMyos from I-Res donors with differences of 2-fold or more. Over 30 of the genes changed in I-Res iMyos were associated with T2D by SNPs and were functionally linked to insulin action and control of metabolism.

Effect of Preoperative Duloxetine Hydrochloride on Reducing Postoperative Morphine Requirement after Open Radical Cholecystectomy in Cancer Patients: A Randomized Controlled Study.

Background: Recently, opoids are linked with cancer recurrence. Duloxetine hydrochloride (DH), an anxiolytic may reduce total opoid requirement after cancer surgery.

Aims: We assessed the efficacy of a single dose of DH in reducing the total morphine requirement after open radical cholecystectomy.

Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex.

Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro.

Defining the underlying defect in insulin action in type 2 diabetes.

Insulin resistance is one of the earliest defects in the pathogenesis of type 2 diabetes. Over the past 50 years, elucidation of the insulin signalling network has provided important mechanistic insights into the abnormalities of glucose, lipid and protein metabolism that underlie insulin resistance. In classical target tissues (liver, muscle and adipose tissue), insulin binding to its receptor initiates a broad signalling cascade mediated by changes in phosphorylation, gene expression and vesicular trafficking that result in increased nutrient utilisation and storage, and suppression of catabolic processes.

Activation of the PDGFRα-Nrf2 pathway mediates impaired adipocyte differentiation in bone marrow mesenchymal stem cells lacking Nck1.

Background: The limited options to treat obesity and its complications result from an incomplete understanding of the underlying molecular mechanisms regulating white adipose tissue development, including adipocyte hypertrophy (increase in size) and hyperplasia (increase in number through adipogenesis). We recently demonstrated that lack of the adaptor protein Nck1 in mice is associated with reduced adiposity and impaired adipocyte differentiation. In agreement, Nck1 depletion in 3 T3-L1 cells also attenuates adipocyte differentiation by enhancing PDGFRα activation and signaling.

Disconnect between the developing eye and craniofacial prominences in the avian embryo.

In the amniote embryo, the upper jaw and nasal cavities form through coordinated outgrowth and fusion of craniofacial prominences. Adjacent to the embryonic prominences are the developing eyes, which abut the maxillary and lateral nasal prominences. The embryos of extant sauropsids (birds and nonavian reptiles) develop particularly large eyes in comparison to mammals, leading researchers to propose that the developing eye may facilitate outgrowth of prominences towards the midline in order to aid prominence fusion.

Comparative evaluation of effect of chlorhexidine, (neem), and () on resin-dentin bond stabilization using shear bond testing: An study.

Introduction: Cavity disinfectants help to remove the microbial remnants; hence, its use prior to any restoration is valuable, and a search for alternative to chlorhexidine (CHX) is required which may be more efficacious and can overcome the drawbacks of CHX.

Objective: The aim of this study was to evaluate the effect of application of three different cavity disinfectants in a clinically relevant time period on the immediate and delayed shear bond strengths (SBSs) of an etch-and-rinse adhesive system to dentin.

Materials And Methods: For SBS testing, flat coronal dentin surfaces were prepared in two hundred extracted human molars.

Harnessing adipogenesis to prevent obesity.

Obesity and associated metabolic complications, including diabetes, cardiovascular and hepatic diseases, and certain types of cancers, create a major socioeconomic burden. Obesity is characterized by excessive expansion of white adipose tissue resulting from increased adipocyte size, and enhanced adipocyte precursor cells proliferation and differentiation into mature adipocytes, a process well-defined as adipogenesis. Efforts to develop therapeutically potent strategies to circumvent obesity are impacted by our limited understanding of molecular mechanisms regulating adipogenesis.

Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRα in Preadipocytes.

Obesity results from an excessive expansion of white adipose tissue (WAT), which is still poorly understood from an etiologic-mechanistic perspective. Here, we report that Nck1, a Src homology domain-containing adaptor, is upregulated during WAT expansion and in vitro adipogenesis. In agreement, Nck1 mRNA correlates positively with peroxisome proliferator-activated receptor (PPAR) γ and adiponectin mRNAs in the WAT of obese humans, whereas Nck1-deficient mice display smaller WAT depots with reduced number of adipocyte precursors and accumulation of extracellular matrix.

Nck2 Deficiency in Mice Results in Increased Adiposity Associated With Adipocyte Hypertrophy and Enhanced Adipogenesis.

Obesity results from an excessive expansion of white adipose tissue (WAT) from hypertrophy of preexisting adipocytes and enhancement of precursor differentiation into mature adipocytes. We report that Nck2-deficient mice display progressive increased adiposity associated with adipocyte hypertrophy. A negative relationship between the expression of Nck2 and WAT expansion was recapitulated in humans such that reduced Nck2 protein and mRNA levels in human visceral WAT significantly correlate with the degree of obesity.