Curbing Breast Cancer by Altering V-ATPase Action on F-Actin, Heterochromatin, ETV7 and mTORC2 Signaling.

Background/aims: Motivated by the vacuolar proton pump's importance in cancer, we investigate the effects of proton pump inhibition on breast cancer cell migration and proliferation, F-actin polymerization, lamin A/C, heterochromatin, and ETV7 expressions, nuclear size and shape, and AKT/mTOR signaling.

Methods: Lowly metastatic MCF7 and highly metastatic MDA-MB-231 breast cancer cells were treated with 120 nM of proton pump inhibitor Bafilomycin A1 for 24 hours. Cell migration was studied with wound- scratch assays, ATP levels with a chemiluminescent assay; cell proliferation was quantified by a cell area expansion assay.

Mitigation of Breast Cancer Cells' Invasiveness via Down Regulation of ETV7, Hippo, and PI3K/mTOR Pathways by Vitamin D3 Gold-Nanoparticles.

Metastasis in breast cancer is the major cause of death in females (about 30%). Based on our earlier observation that Vitamin D3 downregulates mTOR, we hypothesized that Vitamin D3 conjugated to gold nanoparticles (VD3-GNPs) reduces breast cancer aggressiveness by downregulating the key cancer controller PI3K/AKT/mTOR. Western blots, migration/invasion assays, and other cell-based, biophysical, and bioinformatics studies are used to study breast cancer cell aggressiveness and nanoparticle characterization.

A High Dose of Calcitriol Inhibits Glycolysis and M2 Macrophage Polarization in the Tumor Microenvironment by Repressing mTOR Activation: in vitro and Molecular Docking Studies.

Background/aims: Macrophages interact with tumor cells within the tumor microenvironment (TME), which plays a crucial role in tumor progression. Cancer cells also can instruct macrophages to facilitate the spread of cancer and the growth of tumors. Thus, modulating macrophages-cancer cells interaction in the TME may be therapeutically beneficial.

Modeling the change in European and US COVID-19 death rates.

Motivated by several possible differences in Covid-19 virus strains, age demographics, and face mask wearing between continents and countries, we focussed on changes in Covid death rates in 2020. We have extended our Covid-19 multicompartment model (Khan et al., 2020) to fit cumulative case and death data for 49 European countries and 52 US states and territories during the recent pandemic, and found that the case mortality rate had decreased by at least 80% in most of the US and at least 90% in most of Europe.

Parthenolide reverses the epithelial to mesenchymal transition process in breast cancer by targeting TGFbeta1: In vitro and in silico studies.

Aims: Breast cancer metastasis is the leading cause of mortality among breast cancer patients. Epithelial to mesenchymal transition (EMT) is a biological process that plays a fundamental role in facilitating breast cancer metastasis. The present study assessed the efficacy of parthenolide (PTL Tanacetum parthenium) on EMT and its underlying mechanisms in both lowly metastatic, estrogen-receptor positive, MCF-7 cells and highly metastatic, triple-negative MDA-MB-231 cells.

Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth.

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages (TAMs) are the major components of the breast cancer microenvironment.

Shear Stress Increases V-H -ATPase and Acidic Vesicle Number Density, and p-mTORC2 Activation in Prostate Cancer Cells.

Introduction: Cells in the tumor microenvironment experience mechanical stresses, such as compression generated by uncontrolled cell growth within a tissue, increased substrate stiffness due to tumor cell extracellular matrix (ECM) remodeling, and leaky angiogenic vessels which involve low fluid shear stress. With our hypothesis that shear stress increases V-H -ATPase number density in prostate cancer cells activation of the mTORC1 and mTORC2 pathways, we demonstrated and quantified such a mechanism in prostate cancer cells.

Methods: Moderately metastatic DU145 and highly metastatic PC3 prostate cancer cells were subjected to 0.

VD and LXR agonist (T0901317) combination demonstrated greater potency in inhibiting cholesterol accumulation and inducing apoptosis via ABCA1-CHOP-BCL-2 cascade in MCF-7 breast cancer cells.

Obesity is associated with hypercholesterolemia and is a global epidemic. Epidemiological and animal studies revealed cholesterol is an essential regulator of estrogen receptor positive (ER+) breast cancer progression while inhibition of cholesterol accumulation was found to prevent breast tumor growth. Individually, vitamin D and LXR agonist T0901317 showed anticancer properties.

Higher Glucose Enhances Breast Cancer Cell Aggressiveness.

Cancer cells overexpress several transcription factors and motor proteins, such as NFkB and kinesin, to accommodate their high energy demand as well as migratory needs via enhanced glycolysis. We hypothesize that high glucose drives cancer progression and cell aggressiveness by decreasing actin expression, increasing NFkB, and kinesin expressions, and by activating Epithelial Mesenchymal Transition (EMT). Using lowly metastatic MCF-7 and highly metastatic MDA-MB231 (MB231) breast cancer cells - highly incident cancer types - we establish how glucose metabolism regulates actin and the biochemical changes that lead to alterations of cell mechanical properties.

Enhanced blebbing as a marker for metastatic prostate cancer.

Highly metastatic prostate cancer cells flowing through a microfluidic channel form plasma membrane blebs: they form 27% more than normal cells and have a lower stiffness (about 50%). Hypo-osmotic stress assays (with osmolarity) show 22% more blebbing of highly metastatic than moderately metastatic and 30% more than normal cells. Plasma membrane blebbing is known to provide important metastatic capabilities to cancer cells by aiding cell detachment from the primary tumor site and increasing cell deformability to promote cell migration through the extracellular matrix.

VD mitigates breast cancer aggressiveness by targeting V-H-ATPase.

Low vitamin D levels increase the risk of developing several cancer types including breast cancer. Breast cancer is the most incident cancer among women worldwide and in the United States. Our previous study showed that vitamin D (VD) decreases breast cancer aggressiveness by inhibiting mammalian target of rapamycin (mTOR).

Aggressive prostate cancer cell nuclei have reduced stiffness.

It has been hypothesized that highly metastatic cancer cells have softer nuclei and hence would travel faster through confining environments. Our goal was to prove this untested hypothesis for prostate cells. Our nuclear creep experiments using a microfluidic channel with a narrow constriction show that stiffness of aggressive immortalized prostate cancer nuclei is significantly lower than that of immortalized normal cell nuclei and hence can be a convenient malignancy marker.

Vitamin D decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells.

Breast cancer is one of the major causes of death in the USA. Cancer cells, including breast, have high glycolysis rates to meet their energy demands for survival and growth. Vitamin D (VD) is important for many important physiological processes such as bone mineralization, but its anticancer role is yet to be proven.

Gramicidin Peptides Alter Global Lipid Compositions and Bilayer Thicknesses of Coexisting Liquid-Ordered and Liquid-Disordered Membrane Domains.

Effects of adding 1 mol % of gramicidin-A on the biochemical properties of coexisting liquid-ordered and liquid-disordered (L + L) membrane domains were investigated. Quaternary giant unilamellar vesicles (GUV) of di18:1PC(DOPC)/di18:0PC(DSPC)/cholesterol/gramicidin-A were prepared using our recently developed damp-film method. The phase boundary of L + L coexisting region was determined using video fluorescence microscopy.

Vacuolar H+-ATPase in the nuclear membranes regulates nucleo-cytosolic proton gradients.

The regulation of the luminal pH of each organelle is crucial for its function and must be controlled tightly. Nevertheless, it has been assumed that the nuclear pH is regulated by the cytoplasmic proton transporters via the diffusion of H across the nuclear pores because of their large diameter. However, it has been demonstrated that ion gradients exist between cytosol and nucleus, suggesting that the permeability of ions across the nuclear pores is restricted.

Anomalous dissipation and kinetic-energy distribution in pipes at very high Reynolds numbers.

A symmetry-based theory is developed for the description of (streamwise) kinetic energy K in turbulent pipes at extremely high Reynolds numbers (Re's). The theory assumes a mesolayer with continual deformation of wall-attached eddies which introduce an anomalous dissipation, breaking the exact balance between production and dissipation. An outer peak of K is predicted above a critical Re of 10^{4}, in good agreement with experimental data.

Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains.

Diacylglycerols (DAGs) with unsaturated acyl chains play many important roles in biomembranes, such as a second messenger and activator for protein kinase C. In this study, three DAGs of distinctly different chain unsaturations (i.e.

Gelatin Nanofiber Matrices Derived from Schiff Base Derivative for Tissue Engineering Applications.

Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of 2-nitrobenzyl-gelatin (N-Gelatin)--a novel gelatin Schiff base derivative--and the resulting electrospun nanofiber matrices.

Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.

We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1), a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM) and correlated to microfluidic platform.

A dynamical systems approach to the control of chaotic dynamics in a spatiotemporal jet flow.

We present a strategy for control of chaos in open flows and provide its experimental validation in the near field of a transitional jet flow system. The low-dimensional chaotic dynamics studied here results from vortex ring formation and their pairings over a spatially extended region of the flow that was excited by low level periodic forcing of the primary instability. The control method utilizes unstable periodic orbits (UPO) embedded within the chaotic attractor.

Role of differential adhesion in cell cluster evolution: from vasculogenesis to cancer metastasis.

Cell-cell and cell-matrix adhesions are fundamental to numerous physiological processes, including angiogenesis, tumourigenesis, metastatic spreading and wound healing. We use cellular potts model to computationally predict the organisation of cells within a 3D matrix. The energy potentials regulating cell-cell (JCC) and cell-matrix (JMC) adhesive interactions are systematically varied to represent different, biologically relevant adhesive conditions.

In silico vascular modeling for personalized nanoparticle delivery.

Aims: To predict the deposition of nanoparticles in a patient-specific arterial tree as a function of the vascular architecture, flow conditions, receptor surface density and nanoparticle properties.

Materials & Methods: The patient-specific vascular geometry is reconstructed from computed tomography angiography images. The isogeometric analysis framework integrated with a special boundary condition for the firm wall adhesion of nanoparticles is implemented.

Mach-number-invariant mean-velocity profile of compressible turbulent boundary layers.

A series of Mach-number- (M) invariant scalings is derived for compressible turbulent boundary layers (CTBLs), leading to a viscosity weighted transformation for the mean-velocity profile that is superior to van Driest transformation. The theory is validated by direct numerical simulation of spatially developing CTBLs with M up to 6. A boundary layer edge is introduced to compare different M flows and is shown to better present the M-invariant multilayer structure of CTBLs.

The preferential targeting of the diseased microvasculature by disk-like particles.

Different classes of nanoparticles (NPs) have been developed for controlling and improving the systemic administration of therapeutic and contrast agents. Particle shape has been shown to be crucial in the vascular transport and adhesion of NPs. Here, we use mesoporous silicon non-spherical particles, of disk and rod shapes, ranging in size from 200nm to 1800nm.

Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution.

Nanoparticles for cancer therapy and imaging are designed to accumulate in the diseased tissue by exploiting the Enhanced Permeability and Retention (EPR) effect. This limits their size to about 100nm. Here, using intravital microscopy and elemental analysis, we compare the in vivo localization of particles with different geometries and demonstrate that plateloid particles preferentially accumulate within the tumor vasculature at unprecedented levels, independent of the EPR effect.