A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion.

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions.

Urine exosome mRNA-based test for monitoring kidney allograft rejection: Effects of sample transportation and storage, and interference substances.

Background: Exosomes are 30-150 nm nanovesicles with sophisticated nucleic acids cargo, actively secreted by all cells within human body, and found in abundance in all body fluids, including urine. These extracellular vesicles have tremendous potential for next generation diagnostics, theoretically enabling noninvasive assessment of organ and tissue function liquid biopsy analysis.

Aim: Recently, feasibility of an exosomal molecular test was demonstrated for post-organ transplant monitoring: Analysis of urine-derived exosomal mRNA cargo allowed early detection of kidney allograft rejection.

Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic β-cell failure.

Objective: Disturbances in NAD metabolism have been described as a hallmark for multiple metabolic and age-related diseases, including type 2 diabetes. While alterations in pancreatic β-cell function are critical determinants of whole-body glucose homeostasis, the role of NAD metabolism in the endocrine pancreas remains poorly explored. Here, we aimed to evaluate the role of nicotinamide riboside (NR) metabolism in maintaining NAD levels and pancreatic β-cell function in pathophysiological conditions.

Developing an Online Dashboard to Visualize Performance Data-Tennessee Newborn Screening Experience.

Newborn screening (NBS) is a vital public health program and delays in the screening process can lead to catastrophic outcomes for infants and their families. Efforts to improve screening quality in Tennessee are proactive and ongoing. From these efforts, an open-access dashboard has been developed to address a need for methods to better visualize performance data, promote data transparency, and drive quality improvement.

Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD by Generating Dihydronicotinamide Riboside.

Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD precursors influence intracellular NAD levels.

High-throughput roll-to-roll production of polymer biochips for multiplexed DNA detection in point-of-care diagnostics.

Roll-to-roll UV nanoimprint lithography has superior advantages for high-throughput manufacturing of micro- or nano-structures on flexible polymer foils with various geometries and configurations. Our pilot line provides large-scale structure imprinting for cost-effective polymer biochips (4500 biochips/hour), enabling rapid and multiplexed detections. A complete high-volume process chain of the technology for producing structures like μ-sized, triangular optical out-couplers or capillary channels (width: from 1 μm to 2 mm, height: from 200 nm up to 100 μm) to obtain biochips (width: 25 mm, length: 75 mm, height: 100 μm to 1.

Monitoring tissue oxygen heterogeneities and their influence on optical glucose measurements in an animal model.

The purpose of this study was to characterize the heterogeneity of oxygen partial pressure in different adipose tissue zones and to assess the possibility of compensating these heterogeneities during optical glucose measurements. In this proof of concept study, the heterogeneity of oxygen partial pressure was determined in the adipose tissue of a pig by using 48 oxygen sensors in 3 zones of the abdominal region at two different blood oxygen levels. Sensor oxygen values correlated well with reference blood oxygen values and we identified heterogeneities in oxygen partial pressure among the defined zones of the abdominal region.

Evaluation of subcutaneous glucose monitoring systems under routine environmental conditions in patients with type 1 diabetes.

Continuous and flash glucose monitoring (GM) systems have been established in diabetes care. We compared the sensor performance of 3 commercially available GM systems. A total of 12 patients with type 1 diabetes were included in a single-centre, open-label study in which the sensor performance of the Abbott FreeStyle libre (Abbott), Dexcom G4 Platinum (Dexcom) and Medtronic MiniMed 640G (Medtronic) systems over 12 hours was compared during mimicked real-life conditions (meals, exercise, hypo- and hyperglycaemia).

First application of a transcutaneous optical single-port glucose monitoring device in patients with type 1 diabetes mellitus.

The combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion can be used to improve the treatment of patients with diabetes. The aim of this study was to advance an existing preclinical single-port system for clinical application by integrating the sensors of a phosphorescence based CGM system into a standard insulin infusion set. The extracorporeal optical phase fluorimeter was miniaturised and is now comparable with commercial CGM systems regarding size, weight and wear comfort.

Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate.

Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2,Col1a1,Bglap2,Sp7,Atf4, andAlpl).

Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis.

Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria.

Quantitative analysis of 11-nor-9-carboxy-tetrahydrocannbinol (THC-COOH) in urine by LC-MS/MS following a simple filtration.

Quantification methods utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS) are common in clinical and forensic toxicology laboratories and the efficiency and rapidity of such methods continues to evolve. In most cases, urine drug confirmation does not require a drug extraction and can quickly and easily be accomplished with a dilution followed by sample filtration. The report describes the validation of a simple confirmation method for 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) and compared two types of filter extraction columns for sample clean-up.

The pharmacokinetics of glycopyrrolate in Standardbred horses.

The disposition of plasma glycopyrrolate (GLY) is characterized by a three-compartment pharmacokinetic model after a 1-mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V1 ), volume of distribution at steady-state (Vss), and area under the plasma concentration-time curve (AUC0-inf ) were 16.7 (13.

Osteoclasts on bone and dentin in vitro: mechanism of trail formation and comparison of resorption behavior.

The main function of osteoclasts in vivo is the resorption of bone matrix, leaving behind typical resorption traces consisting of pits and trails. The mechanism of pit formation is well described, but less is known about trail formation. Pit-forming osteoclasts possess round actin rings.

Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous-rate infusion in the horse.

Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2-h constant-rate intravenous infusion (4 μg/kg/h) and evaluate potential PK-PD models for cardiac stimulation in adult horses.

The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.

A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model.

Geometry as a factor for tissue growth: towards shape optimization of tissue engineering scaffolds.

Scaffolds for tissue engineering are usually designed to support cell viability with large adhesion surfaces and high permeability to nutrients and oxygen. Recent experiments support the idea that, in addition to surface roughness, elasticity and chemistry, the macroscopic geometry of the substrate also contributes to control the kinetics of tissue deposition. In this study, a previously proposed model for the behavior of osteoblasts on curved surfaces is used to predict the growth of bone matrix tissue in pores of different shapes.

Mitogen-activated protein kinase 2 regulates physiological and pathological bone turnover.

The objective of this study was to investigate the role of the serine-threonine kinase mitogen-activated protein kinase 2 (MK2) in bone homeostasis. Primary bone cell cultures from MK2(+/+) and MK2(-/-) mice were assessed for osteoclast and osteoblast differentiation, bone resorption, and gene expression. Bone architecture of MK2(+/+) and MK2(-/-) mice was investigated by micro-computed tomography and histomorphometry.

How linear tension converts to curvature: geometric control of bone tissue growth.

This study investigated how substrate geometry influences in-vitro tissue formation at length scales much larger than a single cell. Two-millimetre thick hydroxyapatite plates containing circular pores and semi-circular channels of 0.5 mm radius, mimicking osteons and hemi-osteons respectively, were incubated with MC3T3-E1 cells for 4 weeks.

Regulatory control of glycopyrrolate in performance horses using validated UHPLC/MS-MS methods.

We describe a validated, rapid, sensitive, and specific UHPLC-MS/MS method to detect and quantify glycopyrrolate in 0.5 mL of horse urine. Further, we investigated the elimination of glycopyrrolate in urine after both intravenous and oral administration of clinically relevant doses to Thoroughbred horses.

Microcracks and osteoclast resorption activity in vitro.

During bone remodeling osteoclasts resorb bone, thus removing material, e.g., damaged by microcracks, which arises as a result of physiological loading and could reduce bone strength.