Fluorescent Water-Soluble Polycationic Chitosan Polymers as Markers for Biological 3D Imaging.

Over the last decades, various tissue-clearing techniques have broken the ground for the optical imaging of whole organs and whole-organisms, providing complete representative data sets of three-dimensional biological structures. Along with advancements in this field, the development of fluorescent markers for staining vessels and capillaries has offered insights into the complexity of vascular networks and their impact on disease progression. Here we describe the use of a modified water-soluble chitosan linked to cyanine dyes in combination with ethyl cinnamate-based optical tissue clearing for the 3D visualization of tissue vasculature in depth.

Endothelial cells drive organ fibrosis in mice by inducing expression of the transcription factor SOX9.

Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it is unclear to what extent endothelial cells also might contribute. We detected increased expression of the transcription factor in endothelial cells in several different mouse fibrosis models.

The crosstalk between glomerular endothelial cells and podocytes controls their responses to metabolic stimuli in diabetic nephropathy.

In diabetic nephropathy (DN), glomerular endothelial cells (GECs) and podocytes undergo pathological alterations, which are influenced by metabolic changes characteristic of diabetes, including hyperglycaemia (HG) and elevated methylglyoxal (MGO) levels. However, it remains insufficiently understood what effects these metabolic factors have on GEC and podocytes and to what extent the interactions between the two cell types can modulate these effects. To address these questions, we established a co-culture system in which GECs and podocytes were grown together in close proximity, and assessed transcriptional changes in each cell type after exposure to HG and MGO.

Microporous Polylactic Acid Scaffolds Enable Fluorescence-Based Perfusion Imaging of Intrinsic In Vivo Vascularization.

In vivo tissue engineering (TE) techniques like the AV loop model provide an isolated and well-defined microenvironment to study angiogenesis-related cell interactions. Functional visualization of the microvascular network within these artificial tissue constructs is crucial for the fundamental understanding of vessel network formation and to identify the underlying key regulatory mechanisms. To facilitate microvascular tracking advanced fluorescence imaging techniques are required.

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes.

Bone morphogenetic protein (BMP)-9, a member of the TGFβ-family of cytokines, is believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21.

Corrigendum: Sulforaphane promotes dendritic cell stimulatory capacity through modulation of regulatory molecules, JAK/STAT3- and microRNA-signaling.

[This corrects the article DOI: 10.3389/fimmu.2020.

Differences in junction-associated gene expression changes in three rat models of diabetic retinopathy with similar neurovascular phenotype.

Diabetic retinopathy, also defined as microvascular complication of diabetes mellitus, affects the entire neurovascular unit with specific aberrations in every compartment. Neurodegeneration, glial activation and vasoregression are observed consistently in models of diabetic retinopathy. However, the order and the severity of these aberrations varies in different models, which is also true in patients.

Influence of carnosine and carnosinase-1 on diabetes-induced afferent arteriole vasodilation: implications for glomerular hemodynamics.

Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy, and nephrin expression in diabetic BTBR mice.

Supplementation of Specific Collagen Peptides Following High-Load Resistance Exercise Upregulates Gene Expression in Pathways Involved in Skeletal Muscle Signal Transduction.

Previous evidence suggests that resistance training in combination with specific collagen peptides (CP) improves adaptive responses of the muscular apparatus. Although beneficial effects have been repeatedly demonstrated, the underlying mechanisms are not well understood. Therefore, the primary objective of the present randomized trial was to elucidate differences in gene expression pathways related to skeletal muscle signal transduction following acute high-load resistance exercise with and without CP intake.

Identification of liver-derived bone morphogenetic protein (BMP)-9 as a potential new candidate for treatment of colorectal cancer.

Colorectal cancer (CRC) is a high-incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)-9 and to find out whether the application of BMP-9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP-target gene ID1, especially in combination with low expression of the BMP-inhibitor noggin, is significantly associated with better patient survival.

A simple optical tissue clearing pipeline for 3D vasculature imaging of the mediastinal organs in mice.

Optical tissue clearing (OTC) methods render tissue transparent by matching the refractive index within a sample to enable three-dimensional (3D) imaging with advanced microscopes. The application of OTC method in mediastinal organs in mice remains poorly understand. Our aim was to establish a simple protocol pipeline for 3D imaging of the mediastinal organs in mice.

IER2-induced senescence drives melanoma invasion through osteopontin.

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner.

Biphasic Effects of Blue Light Irradiation on Human Umbilical Vein Endothelial Cells.

Blue light regulates biological function in various cells, such as proliferation, oxidative stress, and cell death. We employed blue light illumination on human umbilical vein endothelial cells utilizing a LED device at 453 nm wavelength and revealed a novel biphasic response on human umbilical vein endothelial cells (HUVECs). The results showed that low fluence blue light irradiation promoted the fundamental cell activities, including cell viability, migration and angiogenesis by activating the angiogenic pathways such as the VEGF signaling pathway.

Insulin Directly Regulates the Circadian Clock in Adipose Tissue.

Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a "zeitgeber" aligning the clock in AT with the external time, but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin directly entrain circadian clocks in AT and investigated a transcriptional-dependent mechanism of this regulation.

Role of Visible Light on Skin Melanocytes: A Systematic Review.

In the last few years, the focus of phototherapy has shifted toward the visible (400-700 nm) part of the electromagnetic spectrum of light. Lately, it has been demonstrated that visible light (VL) can have both beneficial and detrimental effects, especially on the skin. Previously and until now, the most harmful effects on the skin are associated with ultraviolet radiation (UVR).

Microglial Activation Is Associated With Vasoprotection in a Rat Model of Inflammatory Retinal Vasoregression.

Vascular dysfunction and vasoregression are hallmarks of a variety of inflammatory central nervous system disorders and inflammation-related retinal diseases like diabetic retinopathy. Activation of microglia and the humoral innate immune system are contributing factors. Anti-inflammatory approaches have been proposed as therapies for neurovascular diseases, which include the modulation of microglial activation.

Sulforaphane Promotes Dendritic Cell Stimulatory Capacity Through Modulation of Regulatory Molecules, JAK/STAT3- and MicroRNA-Signaling.

Introduction: The broccoli isothiocyanate sulforaphane was shown to inhibit inflammation and tumor progression, also in pancreatic cancer, while its effect on tumor immunity is poorly understood. We investigated the immunoregulatory effect of sulforaphane on human dendritic cells alone and in presence of pancreatic tumor antigens, as well as underlying molecular mechanisms.

Methods: Sulforaphane-treated human dendritic cells were matured with a cytokine cocktail, and the expression of regulatory molecules was examined by flow cytometry.

Compression Bioreactor-Based Mechanical Loading Induces Mobilization of Human Bone Marrow-Derived Mesenchymal Stromal Cells into Collagen Scaffolds In Vitro.

Articular cartilage (AC) is an avascular tissue composed of scattered chondrocytes embedded in a dense extracellular matrix, in which nourishment takes place via the synovial fluid at the surface. AC has a limited intrinsic healing capacity, and thus mainly surgical techniques have been used to relieve pain and improve function. Approaches to promote regeneration remain challenging.

A complementary study approach unravels novel players in the pathoetiology of Hirschsprung disease.

Hirschsprung disease (HSCR, OMIM 142623) involves congenital intestinal obstruction caused by dysfunction of neural crest cells and their progeny during enteric nervous system (ENS) development. HSCR is a multifactorial disorder; pathogenetic variants accounting for disease phenotype are identified only in a minority of cases, and the identification of novel disease-relevant genes remains challenging. In order to identify and to validate a potential disease-causing relevance of novel HSCR candidate genes, we established a complementary study approach, combining whole exome sequencing (WES) with transcriptome analysis of murine embryonic ENS-related tissues, literature and database searches, in silico network analyses, and functional readouts using candidate gene-specific genome-edited cell clones.

Yes-associated protein (YAP) induces a secretome phenotype and transcriptionally regulates plasminogen activator Inhibitor-1 (PAI-1) expression in hepatocarcinogenesis.

Background: Overexpression and nuclear enrichment of the oncogene yes-associated protein (YAP) cause tumor initiation and support tumor progression in human hepatocellular carcinoma (HCC) via cell autonomous mechanisms. However, how YAP expression in tumor cells affects intercellular communication within the tumor microenvironment is not well understood.

Methods: To investigate how tumor cell-derived YAP is changing the paracrine communication network between tumor cells and non-neoplastic cells in hepatocarcinogenesis, the expression and secretion of cytokines, growth factors and chemokines were analyzed in transgenic mice with liver-specific and inducible expression of constitutively active YAP (YAP).

YAP Orchestrates Heterotypic Endothelial Cell Communication via HGF/c-MET Signaling in Liver Tumorigenesis.

The oncogene yes-associated protein (YAP) controls liver tumor initiation and progression via cell extrinsic functions by creating a tumor-supporting environment in conjunction with cell autonomous mechanisms. However, how YAP controls organization of the microenvironment and in particular the vascular niche, which contributes to liver disease and hepatocarcinogenesis, is poorly understood. To investigate heterotypic cell communication, we dissected murine and human liver endothelial cell (EC) populations into liver sinusoidal endothelial cells (LSEC) and continuous endothelial cells (CEC) through histomorphological and molecular characterization.

Application of ethyl cinnamate based optical tissue clearing and expansion microscopy combined with retrograde perfusion for 3D lung imaging.

Purpose: 3 D imaging of the lung is not a trivial undertaking as during preparation the lung may collapse. Also serial sections and scans followed by 3 D reconstruction may lead to artifacts. The present study aims to figure out the best way to perform 3 D imaging in lung research.