The liver is a major site for the metabolism of xenobiotic compounds due to its abundant level phase I/II metabolic enzymes. With cost drug development escalating over $400 million/drug there an urgent need rigorous models hepatic preclinical screening clearance and hepatotoxicity. Here, we present microenvironment in which primary human rat hepatocytes maintain high competence without long adaptation period. We demonstrate that co-cultures endothelial cells serum-free media seeded under 95%...

// Stephen L. Hayward 1 , Christina Wilson Srivatsan Kidambi 1, 2, 3, 4, 5 Department of Chemical and Biomolecular Engineering, University Nebraska-Lincoln, Lincoln, NE, 68588, USA 2 Nebraska Center for Materials Nanoscience, 3 the Prevention Obesity Diseases, 68583, 4 Mary Dick Holland Regenerative Medicine Program, Medical Center, Omaha, 68198, Fred Pamela Buffett Cancer Omaha Correspondence to: Kidambi, email: skidambi2@unl.edu Keywords: glioblastoma, nanomedicine, CD44 targeting, lipid...

Liver fibrosis occurs as a consequence of chronic injuries from viral infections, metabolic disorders, and alcohol abuse. Fibrotic liver microenvironment (LME) is characterized by excessive deposition aberrant turnover extracellular matrix proteins, which leads to increased tissue stiffness. stiffness acts vital cue in the regulation hepatic responses both healthy diseased states; however, effect varying on cells not well understood. There critical need engineer vitro models that mimic...

Titanium dioxide (TiO2) nanoparticles are one of the most highly manufactured and employed nanomaterials in world with applications copious industrial consumer products. The liver is a major accumulation site for many nanoparticles, including TiO2, directly through intentional exposure or indirectly unintentional ingestion via water, food animals increased environmental contamination. Growing concerns over current usage TiO2 coupled lack mechanistic understanding its potential health risk...

TiO₂nanoparticle exposure to primary astrocytes induced concentration dependent loss in glutamate uptake, morphological changes mitochondria (tabulation or fragmentation) and damage mitochondrial dynamics.

Glioblastoma (GBM), the most aggressive brain tumor, is associated with a median survival at diagnosis of 16-20 months and limited treatment options. The key hallmark GBM altered tumor metabolism marked increase in rate glycolysis. Aerobic glycolysis along elevated glucose consumption lactate production supports rapid cell proliferation growth. In this study, we examined gene expression profile metabolic targets samples from patients lower grade glioma (LGG) GBM. We found that glycolytic...

Abstract This paper describes the formation of patterned cell co‐cultures using layer‐by‐layer deposition synthetic ionic polymers and without aid adhesive proteins/ligands such as collagen or fibronectin. In this study, we used polymers, namely poly(diallyldimethylammonium chloride) (PDAC) sulfonated polystyrene (SPS) polycation polyanion, respectively, to build multilayer films. We formed SPS patterns on polyelectrolyte (PEM) surfaces either by microcontact printing PDAC onto vice‐versa....

Glioblastoma Multiforme (GBM) is the most abundant and fatal malignant brain cancer. There are more than 13,000 cases projected in United States 2020 2021. GBM tumors often arise from astrocytes characterized by their invasive nature, recruiting healthy tissues into tumor tissue. Understanding communication between glioblastoma cells vital for molecular understanding of progression. This protocol demonstrates a novel patterned co-culture method to investigate contact-mediated effects on...

This article demonstrates that the micro-topography of surface with respect to pattern size and pitch influences cell adhesion proliferation. Extensive research has shown dependence proliferation on substrate chemistry, but influence topography attachment only recently been appreciated. To evaluate effect physical properties (i.e., periodic microstructures) morphology, we compared response several types (fibroblasts, HeLa, primary hepatocytes) cultured various polydimethylsiloxane (PDMS)...

Abstract The development of resistance to trastuzumab is a major obstacle for lasting effective treatment patients with ErbB2-overexpressing tumors. Here, we demonstrate that the physical contact breast cancer cells mesenchymal stem (MSCs) potential modulator response by activation nonreceptor tyrosine kinase c-Src and down regulation phosphatase tensin homolog (PTEN). Using an in vitro patterned cancer/MSC co-culture model, find presence MSCs results Src missing monoculture, transwell...

Mechanical properties of the cellular microenvironment induces astrogliosis<italic>in vitro</italic>in primary rat astrocytes.

The development of new methods for fabricating thin films that provide precise control the three-dimensional topography and cell adhesion could lead to significant advances in fields tissue engineering biosensors. This Communication describes successful attachment spreading primary hepatocytes on polyelectrolyte multilayer (PEM) without use adhesive proteins such as collagen or fibronectin. We demonstrate can be controlled using this layer-by-layer deposition ionic polymers. In our study, we...

We engineered patterned co-cultures of primary neurons and astrocytes on polyelectrolyte multilayer (PEM) films without the aid adhesive proteins/ligands to study oxidative stress mediated by neuronal cells. A number studies have explored engineering co-culture predominantly using cell lines rather than cells owing difficulties involved in attaching onto synthetic surfaces. To our knowledge this is first demonstration for studying metabolism. In study, we used polymers, namely...

Propofol is a commonly used intravenous anesthetic agent, which produce rapid induction of and recovery from general anesthesia. Numerous clinical studies reported that propofol can potentially cause amnesia memory loss in human subjects. The underlying mechanism for this unclear but may be related to the memory-associated genes such as c-Fos Egr-1 by propofol. This study explored effects on expression rat hippocampal slices.Hippocampal brain slices were exposed varying concentrations at...

MicroRNAs (miRNAs) are endogenous regulators of gene expression that play a pivotal role in biological processes spanning from global homeostasis to disease onset and progression. The ability manipulate induce cellular reequilibrium deregulated miRNA profiles by inhibition oncogenic or overexpression tumor suppressor is promising cancer strategy, but currently hindered application the lack nonviral delivery systems. Here we present lipid nanoparticle (LNP) platform surface coated with...

In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause morbidity and mortality, resulting in death 15–17% human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated damage promotes the progression advanced fibrosis cirrhosis. However, mechanisms behind these events are uncertain. Here, we hypothesize that ethanol metabolism potentiates accumulation HIV hepatocytes, causing oxidative stress intensive apoptotic cell...

This article reports the synthesis of manganese ferrite nano-assemblies (MNAs) encapsulated with fluorescent silica and demonstrates their applicability for magnetic hyperthermia, optical <italic>T</italic>₂ contrast MRI imaging HeLa cancer cells.

Abstract There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of TICs required for drug discovery and development. In this paper we report a new method encapsulates patient-derived primary grows them 3 dimension thermoreversible hydrogels. Our allows long-term (~50 days, 10 passages tested, accumulative ~&gt;10 -fold expansion) with both high...

Abstract The ability to control the spatial distribution and temporal release of a therapeutic remains central challenge for biomedical research. Here, we report development optimization novel substrate mediated delivery system comprising hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. PEM was constructed from sequential deposition Poly-L-Lysine (PLL) Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)...

Glioblastoma Multiforme (GBM) is known to be by far the most aggressive brain tumor affect adults. The median survival rate of GBM patient's < 15 months, while cells aggressively develop resistance chemo- and radiotherapy with their self-renewal capacity which suggests pressing need novel preventative measures. We have recently proved that GPR17 -an orphan G protein-coupled receptor- highly expressed on cell surface it has a vital role play in disease progression. Despite progress made...

Autotaxin (ATX) is an extracellular secretory enzyme (lysophospholipase D) that catalyzes the hydrolysis of lysophosphatidyl choline to lysophosphatidic acid (LPA). The ATX–LPA axis a well-known pathological mediator liver fibrosis, metastasis in cancer, pulmonary atherosclerosis, and neurodegenerative diseases. Additionally, it believed LPA may cause vascular permeability. In ischemic stroke, permeability leading hemorrhagic transformation major limitation for therapies obstacle stroke...

This paper describes the fabrication of self-assembled monolayer (SAM) patterns m-d-poly(ethylene glycol) (m-dPEG) acid molecules onto polyelectrolyte multilayers (PEMs). The patterned SAMs on PEMs were created by ionic interactions using microcontact printing (μCP) technique. m-dPEG act as resistive templates, and thus further depositions consecutive poly(anion)/poly(cation) pairs charged particles result in formation three-dimensional (3-D) PEM films or selective particle atop original...