Abstract:
A multi-functional broad-spectrum antiviral and anti-inflammatory nanosystem and methods of treating, including prophylactically, coronavirus infections, such as those caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by administering such nanosystem to a patient is presented. The nanosystem may be comprised of a combination of therapeutic agents directed to the particular coronavirus encapsulated in a nanoparticle that is surface coated with a targeting moiety. For CoV-2 infections, an antiviral such as the PPAR-γ agonist leriglitazone (LG) and an siRNA targeting a conserved sequence of the virus can be encapsulated within a nanoparticle surface coated with a fatty acid such as linoleic acid, as the targeting moiety. Administration can occur intranasally prior to infection for prophylactic treatment or post-infection for treatment of the viral infection.
Abstract:
A 4D-perfused tumoroid-on-a-chip platform used in personalized cancer treatment. The platform includes a plate with a plurality of bottomless wells that resides atop a microfluidic channel layer, which in turn resides atop a surface acoustic wave (SAW) based sensor layer that is capable of measuring potential pH values of fluids disposed within the platform. The microfluidic channel layer includes a plurality of bioreactors, with each bioreactor including an inlet well, a culture well, and an outlet well. The inlet well, culture well, and outlet well form a closed system via fluid conduits spanning from the inlet well to the culture well, as well as from the culture well to the outlet well. Due to the fluid flow from the plate to the chip, and from the inlet well to the outlet well on the chip through the culture well, target cell (tumoroid) growth is promoted within the culture well.
Abstract:
An in vitro microfluidic device includes a device configured to model a blood-brain barrier. The device includes a center well in fluidic communication with each of an inlet and an outlet. Each of the center well, inlet, and outlet includes a porous membrane that separates a “blood” portion (a fluid flow portion) from a “brain” portion (a fluid containing portion). The porous membrane is seeded with endothelial cells such as the human venule endothelial cells (HUVECs) on the blood side, and with astrocytes on the brain side, to accurately model the blood-brain barrier. Fluid flows between the inlet, the center well, and the outlet to test the permeability of the porous membrane, thereby providing an accurate in vitro model of a blood-brain barrier.
Abstract:
A multifunctional dendrimer nanoparticle and method of treating diseases of the posterior segment of the eye is presented. The functionalized polyamidoamine (PAMAM) dendrimer effectively delivers drugs and/or genes to the posterior eye, thereby providing for the effective, non-invasive, and topical treatment of diseased in the posterior eye. The multifunctional dendrimer nanoparticle has shRNA-encoding DNA and small molecule drug encapsulated cyclodextrin complexed to the outer surface of the dendrimer for delivery to the posterior segment of the eye.
Abstract:
The present application is related to methods of treating ARDS in a subject in need thereof, by administering (a) pioglitazone, or a pharmaceutically acceptable salt thereof, and (b) mesenchymal stromal cells to the subject. Also disclosed herein are methods of treating one or more symptoms of ARDS in a subject in need thereof.
Abstract:
Disclosed herein are compositions and methods for treating cancer. Further provided herein are compositions and methods for reducing, inhibiting, or preventing resistance of cancer to tyrosine kinase inhibitors. The methods may include administering an anti-resistance agent such as a CYP51A1 inhibitor or an agonist of miRNA-764 (SEQ ID NO: 4) to a subject. A tyrosine kinase inhibitor may also be administered to the subject in addition to the anti-resistance agent.
Abstract:
Provided herein is a method of transfecting a brain cell of a subject with a polynucleotide comprising systemically administering to the subject a composition comprising a micelle having a hydrophobic superparamagnetic iron oxide nanoparticle (SPION) core, a first coating comprising a cationic polymer, and a second coating comprising the polynucleotide, wherein the subject has a mild traumatic brain injury.
Abstract:
Described herein are compositions and methods of forming multi-cellular tumoroids. Also described herein are methods of using the multi-cellular tumoroids.
Abstract:
This invention pertains to polynucleotides, such as small interfering RNA (siRNA), useful for reducing the expression of respiratory syncytial virus (RSV) genes within a subject; and methods for treating a patient suffering from, or at risk of developing, an RSV infection by administering such polynucleotides to the subject.
Abstract:
A method of treating or preventing Alzheimer's disease or related dementias in patients previously infected with a respiratory virus such as SARS CoV2 is presented. Brain gene expression profiles of severe COVID-19 patients show increased expression of several innate immune response genes and genes implicated in Alzheimer's disease pathogenesis. The gene expression signature includes genes involved in inflammation, protein folding/trafficking, complement activation, calcium homeostasis, and amyloid/tau processing. The gene expression signature is correlated with tau pathology, α-synuclein, and demyelination with neuroinflammation being increased in old versus young CoV-2 infected mice.