Syndecan-1 and heparanase as novel regulators of colon cancer stem cell function

Proteoglykane, Glykosaminoglykane und ihre degradierenden Enzyme spielen eine große Rolle innerhalb der Homeostase im normalen Gewebe als auch bei Krebs. Das Transmembran Heparansulfat Proteoglykan Syndekan-1 ist ein wesentliches Bestandteil des strukturellen Gerüsts im Darmgewebe. Das Ziel dieser Arbeit war es herauszufinden, ob die Expression von Syndekan-1 und HPSE Tumorstammzell-Eigenschaften und ihre Invasivität im Darmkrebs beeinflusst. Unsere Ergebnisse haben deutlich gezeigt, dass Syndekan-1 und HPSE innerhalb der Stammzellnische durch die Signalwege EGR1, pFAK und Wnt dynamisch miteinander interagieren. Das Targeting dieser Signalkaskaden könnte einen neuen therapeutischen Ansatz darstellen, um Darmkrebs künftig zu behandeln.Proteoglycans and glycosaminoglycans and their degradative enzymes are involved in normal tissue homeostasis and cancer. The transmembrane heparan sulfate proteoglycan Syndecan1 provides a structural framework for proper tissue organization in the intestinal tract. The aim of this thesis was to investigate whether expression of Sdc1 and HPSE influences cancer stem cell properties and invasiveness in colon cancer cell lines (Caco2 and HT29). Taken together, our results report for the first time showed the dynamic interplay between Sdc1 and HPSE in stemness associated colon cancer properties via  signaling axis involving EGR1, pFAK and Wnt. These findings could form a conceptual framework for establishing novel therapeutic approaches to treat colon cancer

Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia.

Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing to microglia activation for synapse elimination in pathology are not fully understood. Here, using in vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) in genetically engineered mice in vivo, we report that at 24 hours after ischemia, microglia release brain-derived neurotrophic factor (BDNF) to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the cornu ammonis 1 (CA1) in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75 neurotrophin receptor (p75 <sup>NTR</sup> ) and tropomyosin receptor kinase B (TrkB) receptors, respectively. After MCAO, we report that in the peri-infarct area and in the corresponding contralateral hemisphere, similar neuroplasticity occurs through microglia activation and gephyrin phosphorylation at serine-268 and serine-270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point mutations protects against ischemic brain damage, neuroinflammation, and synapse downregulation after MCAO

Effect of supercritical-CO2 interaction time on the alterations in coal pore structure

International audienc

Hippo/MST blocks breast cancer by downregulating WBP2 oncogene expression via miRNA processor Dicer

10.1038/s41419-020-02901-3Cell Death and Disease11866

The Heparan Sulfate Sulfotransferases HS2ST1 and HS3ST2 Are Novel Regulators of Breast Cancer Stem-Cell Properties

Heparan sulfate (HS) is a glycosaminoglycan found mainly in its protein-conjugated form at the cell surface and the extracellular matrix. Its high sulfation degree mediates functional interactions with positively charged amino acids in proteins. 2-O sulfation of iduronic acid and 3-O sulfation of glucosamine in HS are mediated by the sulfotransferases HS2ST and HS3ST, respectively, which are dysregulated in several cancers. Both sulfotransferases regulate breast cancer cell viability and invasion, but their role in cancer stem cells (CSCs) is unknown. Breast CSCs express characteristic markers such as CD44+/CD24−/low, CD133 and ALDH1 and are involved in tumor initiation, formation, and recurrence. We studied the influence of HS2ST1 and HS3ST2 overexpression on the CSC phenotype in breast cancer cell lines representative of the triple-negative (MDA-MB-231) and hormone-receptor positive subtype (MCF-7). The CD44+/CD24−/low phenotype was significantly reduced in MDA-MB-231 cells after overexpression of both enzymes, remaining unaltered in MCF-7 cells. ALDH1 activity was increased after HS2ST1 and HS3ST2 overexpression in MDA-MB-231 cells and reduced after HS2ST1 overexpression in MCF-7 cells. Colony and spheroid formation were increased after HS2ST1 and HS3ST2 overexpression in MCF-7 cells. Moreover, MDA-MB-231 cells overexpressing HS2ST1 formed more colonies and could not generate spheres. The phenotypic changes were associated with complex changes in the expression of the stemness-associated notch and Wnt-signaling pathways constituents, syndecans, heparanase and Sulf1. The results improve our understanding of breast CSC function and mark a subtype-specific impact of HS modifications on the CSC phenotype of triple-negative and hormone receptor positive breast cancer model cell lines

Unlocking nature's potential: Green synthesis of ZnO nanoparticles and their multifaceted applications – A concise overview

In recent years, zinc oxide nanoparticles (ZNPs) have gained tremendous attention attributed to their unique properties. It is the most desirable group of nanostructures as far as both structure and properties are concerned. It is an adaptable material that has distinctive properties, such as high sensitivity, large specific area, non-toxicity, good compatibility, and a high isoelectric point, which favors it to be considered with a few exceptions. They are utilized in an expanding number of mechanical items, for example, elastic, paint, coating, cosmetics, supercapacitors, Lithium batteries, color-sensitized sun-powered cells, photocatalysis, biosensors, biomedical and characteristic applications. They have brought a promising potential up in biomedicine, especially in the fields of anticancer and antibacterial fields, which are locked in with their solid ability to trigger plenitude reactive oxygen species (ROS) creation, discharge zinc particles, and instigate cell apoptosis. ZNPs have also been successfully utilized to transport and load drugs to target locations as drug carriers, reducing undesirable toxicity and non-target effects and increasing the synergistic effects. In addition, ZNPs display outstanding light assets and this property has made them one of the chief bioimaging applicants Thus, this paper reviews the biological synthesis of ZNPs by the microbes, the mechanisms of the biological synthesis, parameters for the optimization process and their potential application as an antimicrobial agent and feed supplement in the animal industry as well as their toxicological hazards on animals. Here, we summarize the synthesis and recent advances of ZNPs in the biomedical fields, which will be helpful for facilitating their future research progress and focusing on biomedical fields