Synergistic activation of RARβ and RARγ nuclear receptors restores cell specialization during stem cell differentiation by hijacking RARα-controlled programs.

How cells respond to different external cues to develop along defined cell lineages to form complex tissues is a major question in systems biology. Here, we investigated the potential of retinoic acid receptor (RAR)-selective synthetic agonists to activate the gene regulatory programs driving cell specialization during nervous tissue formation from embryonic carcinoma (P19) and mouse embryonic (E14) stem cells. Specifically, we found that the synergistic activation of the RARβ and RARγ by selective ligands (BMS641 or BMS961) induces cell maturation to specialized neuronal subtypes, and to astrocytes and oligodendrocyte precursors.

A Core Transcription Regulatory Circuitry Defining Microglia Cell Identity Inferred from the Reanalysis of Multiple Human Microglia Differentiation Protocols.

Microglia, the immune cells in the brain involved in both homeostasis and injury/infection control, play a predominant role in neurodegenerative diseases. In vivo studies on microglia are limited due to the requirement of surgical intervention, which can lead to the destruction of the tissues. Over the last few years, multiple protocols-presenting a variety of strategies-have described microglia differentiation issued from human pluripotent stem cells.

Inferring biologically relevant molecular tissue substructures by agglomerative clustering of digitized spatial transcriptomes with multilayer.

Spatially resolved transcriptomics (SrT) can investigate organ or tissue architecture from the angle of gene programs that define their molecular complexity. However, computational methods to analyze SrT data underexploit their spatial signature. Inspired by contextual pixel classification strategies applied to image analysis, we developed MULTILAYER to stratify maps into functionally relevant molecular substructures.

Biosensor-based enzyme engineering approach applied to psicose biosynthesis.

Bioproduction of chemical compounds is of great interest for modern industries, as it reduces their production costs and ecological impact. With the use of synthetic biology, metabolic engineering and enzyme engineering tools, the yield of production can be improved to reach mass production and cost-effectiveness expectations. In this study, we explore the bioproduction of D-psicose, also known as D-allulose, a rare non-toxic sugar and a sweetener present in nature in low amounts.

Regulatory T-cell development and function are impaired in mice lacking membrane expression of full length intercellular adhesion molecule-1.

To further investigate the contribution of intercellular adhesion molecule-1 (ICAM-1) to adaptive immune responses, we analysed T-cell development and function in mice lacking full-length ICAM-1 (ICAM-1(tm1Jcgr) ). Compared with wild-type (ICAM-1(WT) ) mice, ICAM-1(tm1Jcgr) mice have impaired thymocyte development. Proportions and numbers of double negative, double positive, mature CD4(+) and CD8(+) thymocytes, as well as of regulatory T (Treg) cells were also significantly decreased.

Microbiota and mucosal immunity in amphibians.

We know that animals live in a world dominated by bacteria. In the last 20 years, we have learned that microbes are essential regulators of mucosal immunity. Bacteria, archeas, and viruses influence different aspects of mucosal development and function.

Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms.

A current target of cancer gene therapy is tumour vasculature. We present a gene-directed enzyme prodrug therapy (GDEPT) approach to target tumours in vivo by modifying endothelial cells (ECs) with the Escherichia coli nitroreductase (ntr) gene. Firstly, we isolated two ntr-transfected clones of the human umbilical vein endothelial cell line (HUV-EC-C/ntr+) that showed a differential sensitivity in vitro to the prodrug, dinitroaziridinylbenzamide (CB1954), with respect to untransfected HUV-EC-C cells (HUV-EC-C/ntr-).

Anti-angiogenic strategies for cancer therapy (Review).

Acquired drug resistance to chemotherapy is a major problem in the treatment of cancer. After primary surgical intervention, followed by chemotherapy treatments, the majority of patients develop disease recurrence. This is due to tumor cell heterogeneity and genetic instability.

Bystander cell killing spreading from endothelial to tumor cells in a three-dimensional multicellular nodule model after Escherichia coli nitroreductase gene delivery.

Tumor cells are elusive targets for standard anticancer chemotherapy due to their heterogeneity and genetic instability. On the other hand, proliferating host endothelial cells (ECs) are genetically stable and have a low mutational rate. Thus, antiangiogenic therapy directed against tumor's ECs should, in principle, improve the efficacy of antitumor therapy by inducing little or no drug resistance.

Similar immune responses and antitumor effects of murine dendritic cells loaded with either exogenous or endogenous-synthesized protein.

Conceptually, dendritic cells (DCs) take up and process exogenous antigens that are presented on MHC (major histocompatibility complex) class II molecules to stimulate CD4+ T cells, and present endogenously-produced proteins to CD8+ T cells through an MHC class I-dependent pathway. In this study, we compared the antitumor effects generated in vivo after vaccinations with DCs either loaded with exogenous protein (DCs-exo) or presenting antigens derived from endogenous-synthesized protein (DCs-endo). We used the murine MC26SC31 colon carcinoma cell line expressing on the cell surface the human CD4 (hCD4) molecule as a model tumor-associated antigen (TAA).

A new phenylacetate-bisphosphonate inhibits breast cancer cell growth by proapoptotic and antiangiogenic effects.

Sodium phenylacetate (NaPa) and some bisphosphonates demonstrated antiproliferative and proapoptotic properties against cancer. We have previously shown that NaPa inhibited cell proliferation of MCF7-ras tumor breast cells both in vitro and in vivo. On the other hand, bisphosphonate activities have only been demonstrated in vitro.

Aponecrotic, antiangiogenic and antiproliferative effects of a novel dextran derivative on breast cancer growth in vitro and in vivo.

1. Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory effect of carboxymethyl benzylamide dextran (CMDB) on the breast cancer growth, we performed the esterification of CMDB with NaPa to obtain a new drug carrying the characteristics of these two components. A new molecule, phenylacetate carboxymethyl benzylamide dextran, was named NaPaC.