Significance Nanotechnology is a promising approach for improving cancer diagnosis and treatment with reduced side effects. A key question that has emerged is: What the ideal nanoparticle size, shape, or surface chemistry targeting tumors? Here, we show tumor pathophysiology volume can significantly impact targeting. This finding presents paradigm shift in nanomedicine away from identifying using universal design detection treatment. Rather, our results suggest future clinicians will be...

Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) patients with cardiovascular disease (CVD) by 44% diabetic CVD 57% on top statins. A III trial, BETonMACE, currently assessing apabetalone's ability to reduce MACE statin-treated post-acute coronary syndrome type 2 low high-density lipoprotein C. The leading cause atherosclerosis, driven dysfunctional lipid metabolism...

Nutritional characteristics of the hyperthermophilic archaeon Thermococcus litoralis have been investigated with emphasis on development a sulfur-free, defined growth medium, analysis an exocellular polysaccharide, and formation biofilm. An artificial-seawater-based containing 16 amino acids, adenine, uracil, vitamins, trace elements, allowed T. to attain rates cell densities similar those found complex media. Four acids (alanine, asparagine, glutamine, glutamate) were not included due their...

Hemodynamic factors drive nanoparticle distribution<italic>in vivo</italic>and<italic>in vitro</italic>in cell-based flow models.

Pluripotent embryonic stem cells (ESCs) have been used increasingly in research as primary material for various tissue-engineering applications. Pluripotency, or the ability to give rise all of body, is an important characteristic ESCs. Traditional methods use leukaemia inhibitory factor (LIF) maintain murine cell (mESC) pluripotency static and bioreactor cultures. When LIF removed from mESCs cultures, genes are downregulated cultures will spontaneously differentiate. Recently we shown...

The effect of surface PEGylation on nanoparticle transport through an extracellular matrix (ECM) is important determinant for tumor targeting success. Fluorescent stealth liposomes (base lipid DOPC) were prepared incorporating different proportions PEG-grafted lipids (2.5, 5 and 10% the total content) a series PEG molecular weights (1000, 2000 5000 Da). ECM was modelled using collagen matrix. kinetics PEGylated liposome adhesion to in matrices tracked fluorescence correlation spectroscopy...

Batch and continuous cultures were used to compare specific physiological features of the hyperthermophilic archaeon, Thermococcus litoralis (Topt 85° 88°C), another fermentative hyperthermophile that reduces S° facultatively, is, bacterium Thermotoga maritima 80° 85°C). Under nutritionally optimal conditions, these two hyperthermophiles had similar growth yields on maltose cell formula weights based elemental analysis: CH1.7O0.7N0.2S0.006 for T. CH1.6O0.6N0.2S0.005 maritima. However, they...

ABSTRACT Arteriovenous malformations (AVMs) develop where abnormal endothelial signalling allows direct connections between arteries and veins. Mutations in RASA1, a Ras GTPase activating protein, lead to AVMs humans and, as we show, zebrafish rasa1 mutants. mutants cavernous that subsume part of the dorsal aorta multiple veins caudal venous plexus (CVP) – vascular bed. The progressively enlarge fill with slow-flowing blood. We show AVM results both higher minimum maximum flow velocities,...

Nanoparticles are increasingly important in medical research for application to areas such as drug delivery and imaging. Understanding the interactions of nanoparticles with cells physiologically relevant environments is vital their acceptance, cell-particle likely vary based on design particle including its size, shape, surface chemistry. For this reason, kinetic fluorescent sizes 20, 100, 200, 500 nm human umbilical vein endothelial (HUVEC) were determined by (1) measuring per cell at 37...

Abstract Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles tumor delivery has been largely empirical, owing to a lack quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants into blood vessel determined. It is shown that dependent surface charge. Moreover, size dependency strongly suggests taken up by...

Young onset breast cancer (YOBC) is an increasing demographic with unique biology, limited screening, and poor outcomes. Further, women postpartum cancers (PPBCs), occurring up to 10 years after childbirth, have worse outcomes than other young patients matched for tumor stage subtype. Early-stage detection of YOBC critical improving However, most (under 45) do not meet current age guidelines routine mammographic screening are thus underserved population. Other challenges early in this...

Interactions involving hydrogen transfer were studied in a coculture of two hyperthermophilic microorganisms: Thermotoga maritima, an anaerobic heterotroph, and Methanococcus jannaschii, hydrogenotrophic methanogen. Cell densities T. maritima increased 10-fold when cocultured with M. jannaschii at 85°C, the methanogen was able to grow absence externally supplied H2 CO2. The could not be established if organisms physically separated by dialysis membrane, suggesting importance spatial...

Endothelial cells respond to fluid flow stimulation through transient and sustained signal pathway activation. Smad2 is a signaling molecule transcription factor in the Smad pathway, traditionally associated with TGF-β. Although phosphorylation of receptor-dependent COOH-terminal region most appreciated way activated affect gene expression, may also occur MH1-MH2 linker (L-psmad2). Here, we show that human aortic endothelial (HAEC), was both preferentially phosphorylated localized nucleus...

Abstract Background Mechanical interactions between tumor cells and microenvironments are frequent phenomena during breast cancer progression, however, it is not well understood how these affect Epithelial-to-Mesenchymal Transition (EMT). EMT associated with the progression of most carcinomas through induction new transcriptional programs within affected epithelial cells, resulting in becoming more motile adhesive to endothelial cells. Methods MDA-MB-231, SK-BR-3, BT-474, MCF-7 normal Human...

Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that targeted disassembly by many viruses. Kaposi's sarcoma-associated herpesvirus is the etiological agent of inflammatory endothelial cancer, sarcoma, and a PB-regulating virus. The virus encodes kaposin B (KapB), which induces actin stress fibers (SFs) cell spindling as well PB disassembly. We now show KapB-mediated requires rearrangements, RhoA effectors, mechanoresponsive transcription activator,...

A novel homomultimeric protease (&gt;669 kDa), based on 31 kDa subunits, was purified from cell extracts of the hyperthermophilic bacterium Thermotoga maritima . This exhibits activity toward chymotrypsin and trypsin substrates, optimally at 90°C pH 7.1, has a half‐life 36 min 95°C. Transmission electron microscopy established that consists large globular assembly which appears circular front view. The function this in T remains unclear, although putative homologs include 29 antigen...

Despite years of excellent individual studies, the impact nanoparticle (NP) cytotoxicity studies remains limited by inconsistent data collection and analysis. It is often unclear how exposure conditions can be used to determine quantitatively. Discrepancies due using different measurement conditions, readouts controls characterize NP interactions with cells lead further challenges. To examine which parameters are critical in we have chosen two types (liposomes quantum dots) at concentrations...

Abstract Crosstalk between tumor and non-tumor cells plays an important role in cancer progression metastasis often leading to a modification of non-malignant into pro-oncogenic phenotypes. Understanding this process is for diagnostic therapeutic advances. We previously reported clinical validation results new way detect early-stage breast using panel RNA biomarkers from whole blood machine learning software-powered testing system. Recently, we showed that immune undergo transcriptomic...

Fluid dynamics strongly influences endothelial cell function, and participates in the localization of atherosclerotic plaques at blood vessel branches. We investigated hypothesis that wild-type human aortic cells (HAEC) exposed to prolonged pulsatile flow stimulation have levels phosphorylated mitogen-activated protein kinases (MAPK) are significantly greater than those observed statically grown cultures. HAEC were laminar shear stress a parallel-plate chamber analyzed for ERK, JNK p38 1, 10...

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly prevalent pathogen capable of causing severe vascular infections. The goal this work was to investigate the role shear stress in early adhesion events. Methods Human umbilical vein endothelial cells (HUVEC) were exposed MRSA for 15-60 minutes and stresses 0-1.2 Pa a parallel plate flow chamber system. Confocal microscopy stacks captured analyzed assess number MRSA. Flow parameters validated using...

Introduction Current recommendations for surgical treatment of abdominal aortic aneurysms (AAA) rely on the assessment diameter as a marker risk rupture. The use size alone may overlook role that vessel heterogeneity plays in aneurysmal progression and rupture risk. aim current study was to investigate intra-patient mechanical fluid stresses wall tissue histopathology from collected at time repair. Methods Finite element analysis (FEA) computational dynamics (CFD) simulations were used...