Authentication of the species identity of squid rings using UHPLC-Q-Orbitrap MS/MS-based lipidome fingerprinting and chemoinformatics.

Species mislabeling of commercial loliginidae squid can undermine important conservation efforts and prevent consumers from making informed decisions. A comprehensive lipidomic fingerprint of Uroteuthis singhalensis, Uroteuthis edulis, and Uroteuthis duvauceli rings was established using high-resolution mass spectrometry-based lipidomics and chemoinformatics analysis. The principal component analysis showed a clear separation of sample groups, with RX and Q values of 0.

Human visceral adipose tissue microvascular endothelial cell isolation and establishment of co-culture with white adipocytes to analyze cell-cell communication.

Communication between adipocytes and endothelial cells (EC) is suggested to play an important role in the metabolic function of white adipose tissue. In order to generate tools to investigate in detail the physiology and communication of EC and adipocytes, a method for isolation of adipose microvascular EC from visceral adipose tissue (VAT) biopsies of subjects with obesity was developed. Moreover, mature white adipocytes were isolated from the VAT biopsies by a method adapted from a previously published Membrane aggregate adipocytes culture (MAAC) protocol.

Insulin-inducible THRSP maintains mitochondrial function and regulates sphingolipid metabolism in human adipocytes.

Background: Thyroid hormone responsive protein (THRSP) is a lipogenic nuclear protein that is highly expressed in murine adipose tissue, but its role in humans remains unknown.

Methods: We characterized the insulin regulation of THRSP in vivo in human adipose tissue biopsies and in vitro in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. To this end, we measured whole-body insulin sensitivity using the euglycemic insulin clamp technique in 36 subjects [age 40 ± 9 years, body mass index (BMI) 27.

Angiopoietin-like protein 3, an emerging cardiometabolic therapy target with systemic and cell-autonomous functions.

Angiopoietin like protein 3 (ANGPTL3) is best known for its function as an inhibitor of lipoprotein and endothelial lipases. Due to the capacity of genetic or pharmacologic ANGPTL3 suppression to markedly reduce circulating lipoproteins, and the documented cardioprotection upon such suppression, ANGPTL3 has become an emerging therapy target for which both antibody and antisense oligonucleotide (ASO) therapeutics are being clinically tested. While the antibody is relatively selective for circulating ANGPTL3, the ASO also depletes the intra-hepatocellular protein, and there is emerging evidence for cell-autonomous functions of ANGPTL3 in the liver.

Hydroxysteroid 17-β dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease.

Carriers of the hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk of NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, and transcriptome using ultra performance liquid chromatography-mass spectrometry and RNA-seq. In carriers and noncarriers of the gene variant, we also measured pathways of hepatic fatty acids (de novo lipogenesis [DNL] and adipose tissue lipolysis [ATL] using 2H2O and 2H-glycerol) and insulin sensitivity using 3H-glucose and euglycemic-hyperinsulinemic clamp) and plasma cytokines.

ANGPTL3 deficiency alters the lipid profile and metabolism of cultured hepatocytes and human lipoproteins.

Loss-of-function (LOF) mutations in ANGPTL3, an inhibitor of lipoprotein lipase (LPL), cause a drastic reduction of serum lipoproteins and protect against the development of atherosclerotic cardiovascular disease. Therefore, ANGPTL3 is a promising therapy target. We characterized the impacts of ANGPTL3 depletion on the immortalized human hepatocyte (IHH) transcriptome, lipidome and human plasma lipoprotein lipidome.

Short-Term Cooling Increases Plasma ANGPTL3 and ANGPTL8 in Young Healthy Lean Men but Not in Middle-Aged Men with Overweight and Prediabetes.

Angiopoietin-like proteins (ANGPTLs) regulate triglyceride (TG)-rich lipoprotein distribution via inhibiting TG hydrolysis by lipoprotein lipase in metabolic tissues. Brown adipose tissue combusts TG-derived fatty acids to enhance thermogenesis during cold exposure. It has been shown that cold exposure regulates ANGPTL4, but its effects on ANGPTL3 and ANGPTL8 in humans have not been elucidated.

Improving skin integration around long-term percutaneous devices using fibrous scaffolds in a reconstructed human skin equivalent model.

The interface between synthetic percutaneous devices and skin is a common area for bacterial infection, which may ultimately result in failure of the device. Better integration of percutaneous devices with skin may help reduce infection rates due to the creation of a dermal seal. However, the mismatch in material and chemical properties of devices and skin presents a challenge for closing the dermal gap at the skin-device interface.

A Bayesian Sequential Learning Framework to Parameterise Continuum Models of Melanoma Invasion into Human Skin.

We present a novel framework to parameterise a mathematical model of cell invasion that describes how a population of melanoma cells invades into human skin tissue. Using simple experimental data extracted from complex experimental images, we estimate three model parameters: (i) the melanoma cell proliferation rate, [Formula: see text]; (ii) the melanoma cell diffusivity, D; and (iii) [Formula: see text], a constant that determines the rate that melanoma cells degrade the skin tissue. The Bayesian sequential learning framework involves a sequence of increasingly sophisticated experimental data from: (i) a spatially uniform cell proliferation assay; (ii) a two-dimensional circular barrier assay; and (iii) a three-dimensional invasion assay.

miR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes.

MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling.

Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue.

Background: Melanoma can be diagnosed by identifying nests of cells on the skin surface. Understanding the processes that drive nest formation is important as these processes could be potential targets for new cancer drugs. Cell proliferation and cell migration are two potential mechanisms that could conceivably drive melanoma nest formation.

MicroRNA-221-3p Regulates Angiopoietin-Like 8 (ANGPTL8) Expression in Adipocytes.

Context: Angiopoietin-like 8 (ANGPTL8) has been identified as a key regulator of lipid metabolism.

Design: We addressed the correlation between ANGPTL8 messenger RNA (mRNA) with hallmark insulin-regulated and lipogenic genes in human adipose tissue (AT). The regulation of ANGPTL8 expression in adipocytes was studied after inflammatory challenge, and the role of microRNA (miRNA)-221-3p therein was investigated.

Quantitative comparison of the spreading and invasion of radial growth phase and metastatic melanoma cells in a three-dimensional human skin equivalent model.

Background: Standard two-dimensional (2D) cell migration assays do not provide information about vertical invasion processes, which are critical for melanoma progression. We provide information about three-dimensional (3D) melanoma cell migration, proliferation and invasion in a 3D melanoma skin equivalent (MSE) model. In particular, we pay careful attention to compare the structure of the tissues in the MSE with similarly-prepared 3D human skin equivalent (HSE) models.

Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion.

Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro.

Standard melanoma-associated markers do not identify the MM127 metastatic melanoma cell line.

Reliable identification of different melanoma cell lines is important for many aspects of melanoma research. Common markers used to identify melanoma cell lines include: S100; HMB-45; and Melan-A. We explore the expression of these three markers in four different melanoma cell lines: WM35; WM793; SK-MEL-28; and MM127.

Quantifying the effect of experimental design choices for in vitro scratch assays.

Scratch assays are often used to investigate potential drug treatments for chronic wounds and cancer. Interpreting these experiments with a mathematical model allows us to estimate the cell diffusivity, D, and the cell proliferation rate, λ. However, the influence of the experimental design on the estimates of D and λ is unclear.

Spatial structure arising from neighbour-dependent bias in collective cell movement.

Mathematical models of collective cell movement often neglect the effects of spatial structure, such as clustering, on the population dynamics. Typically, they assume that individuals interact with one another in proportion to their average density (the mean-field assumption) which means that cell-cell interactions occurring over short spatial ranges are not accounted for. However, in vitro cell culture studies have shown that spatial correlations can play an important role in determining collective behaviour.

Fatal fungal infection: the living dead.

Necrotizing fasciitis is an uncommon infection mainly caused by Streptococcus pyogenes, which is also known as flesh-eating bacteria. It is often caused by bacteria, but can also be caused and complicated by fungus. We report a case of bacterial necrotizing fasciitis that was complicated by a fatal fungal infection, a rare clinical presentation affecting the upper limbs, head and neck, in a young diabetic female patient.

Spinal Epidural Varices, a great Mimic of Intervertebral Disc Prolapse - A Case Series.

Introduction: Epidural venous plexus enlargement, presenting with low back pain and radiculopathy, is an uncommon cause of nerve roots impingement. This condition commonly mimics a herniated nucleus pulposus radiologically. The radiological diagnosis is often missed and the diagnosis is made during the surgery.

Do pioneer cells exist?

Most mathematical models of collective cell spreading make the standard assumption that the cell diffusivity and cell proliferation rate are constants that do not vary across the cell population. Here we present a combined experimental and mathematical modeling study which aims to investigate how differences in the cell diffusivity and cell proliferation rate amongst a population of cells can impact the collective behavior of the population. We present data from a three-dimensional transwell migration assay that suggests that the cell diffusivity of some groups of cells within the population can be as much as three times higher than the cell diffusivity of other groups of cells within the population.

Aspirin and clopidogrel resistance using the cone and plate(let) analyser in Indian patients with coronary artery disease.

Background: Resistance to antiplatelet drugs is a well-known entity. However, data for aspirin and clopidogrel resistance, and its clinical significance, in Indian patients are meagre.

Aims And Objectives: We sought to determine the prevalence of resistance to aspirin and clopidogrel in Indian patients with stable coronary heart disease (CHD), using the cone and plate(let) analyser (CPA) technology.

Multiple types of data are required to identify the mechanisms influencing the spatial expansion of melanoma cell colonies.

Background: The expansion of cell colonies is driven by a delicate balance of several mechanisms including cell motility, cell-to-cell adhesion and cell proliferation. New approaches that can be used to independently identify and quantify the role of each mechanism will help us understand how each mechanism contributes to the expansion process. Standard mathematical modelling approaches to describe such cell colony expansion typically neglect cell-to-cell adhesion, despite the fact that cell-to-cell adhesion is thought to play an important role.

Experimental and modelling investigation of monolayer development with clustering.

Standard differential equation-based models of collective cell behaviour, such as the logistic growth model, invoke a mean-field assumption which is equivalent to assuming that individuals within the population interact with each other in proportion to the average population density. Implementing such assumptions implies that the dynamics of the system are unaffected by spatial structure, such as the formation of patches or clusters within the population. Recent theoretical developments have introduced a class of models, known as moment dynamics models, which aim to account for the dynamics of individuals, pairs of individuals, triplets of individuals, and so on.