Abstract: A method for filling a reservoir a filling assembly having a needle, and a fluid. The reservoir is in a disposable housing assembly with a septum fluidly connected to the reservoir, a septum access assembly having a first position covering the septum and a second position providing access to the septum, and a bias mechanism for biasing the septum access assembly to the first position. The method includes piercing the septum with the needle, inserting fluid to the reservoir through the needle, contacting the filling assembly to the septum access assembly, and removing the needle from the septum. Removing the needle from the septum allows the bias mechanism to move the septum access assembly from the second position to the first position. The disposable housing assembly is attached to a reusable housing assembly.

Abstract: The present disclosure provides an allosteric enhancing compound of GABAA receptors or a prodrug thereof, a method for preparing the same, and use thereof. The compound is represented by formula (1), wherein R1 and R2 are each independently selected from isopropyl or n-propyl; and when R1 is n-propyl, R2 is not isopropyl.

Abstract: This invention relates to a pharmaceutical composition comprising or consisting essentially of the phytocannabinoids cannabidivarin (CBDV) and cannabidiol (CBD). The composition is particularly safe and efficacious for use in the treatment of neurological conditions, characterized by hyper-excitability of the central nervous system, convulsions or seizures such as occur in epilepsy. Preferably the CBDV and the CBD are present with at least one non-cannabinoid component of cannabis such as one or more terpenes or a terpene fraction. More particularly the composition further comprises one or more cannabichromene type compounds. Particularly cannabichromene propyl variant (CBCV) and/or cannabichromene (CBC).

Abstract: The present disclosure provides inhibitors of bunyavirus of the formula: wherein the variables are defined herein. These inhibitors may be used to treat an infection of Rift Valley phlebovirus, hantavirus, and La Crosse virus, or Crimean-Congo Hemorrhagic fever.

Abstract: Disclosed here is a method of alleviating negative effects of cochlear implant surgery in a subject in need thereof comprising administering effective amounts of 2,4-disulfonyl ?-phenyl tertiary butyl nitrone (2,4-DSPBN) or a pharmaceutically acceptable salt thereof and N-acetylcysteine (NAC) or a pharmaceutically acceptable salt thereof to a subject prior to, during, and/or after undergoing cochlear implant surgery.

Abstract: D-serine is effective for inhibiting neuron loss due to an immune response by glial cells to a brain injury. An example of a method includes artificially administering a composition including D-serine to brain cells after an injury thereto, the composition including an amount of D-serine effective to inhibit death of neurons.

Abstract: The invention provides unit dosage forms, kits, and methods useful for treating viral infections.

Abstract: A method of using a truffle-derived biomass for producing 1,3-diolein includes obtaining a mycelial biomass from truffles, preparing an extract from the mycelial biomass, and isolating the 1,3-diolein from the extract. In an embodiment, isolating the 1,3-diolein from the extract can include using column chromatography for eluting a portion of a first extract with a mixture including chloroform and methanol into a plurality of fractions, and using column chromatography for eluting at least one of the fractions with methanol to provide 1,3-diolein.

Abstract: Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

Abstract: Disclosed herein are powders including a therapeutically effective amount of 4-oxo-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]1exadecane-10-yl]oxy]butanoic acid (artesunate) or a pharmaceutically acceptable salt thereof that can be easily manufactured, sterilized and packaged. Processes for producing these powders and pharmaceutical compositions containing these powders are also disclosed.

Abstract: A method for preparing a water-soluble curcumin liquid includes the following steps: A) dissolving curcumin, vitamin C and ascorbyl palmitate in an ethanol aqueous solution, evaporating ethanol under reduced pressure, and vacuum drying to obtain a curcumin-vitamin C-ascorbyl palmitate co-crystal; and B) high-speed emulsifying the curcumin-vitamin C-ascorbyl palmitate co-crystal and a water-soluble colloidal solution that includes an emulsifying additive under vacuum, sequentially conducting a two-stage wet grinding, a homogenization and a potential adjustment to obtain the water-soluble curcumin liquid.

Abstract: The disclosure herein provides combination therapies for the treatment of cancers such as Leukemia, lymphoma and triple negative breast cancer. The disclosure provides combination therapies of CDK inhibitors, e.g., a CDK inhibitor represented by Formula I: or a pharmaceutically acceptable salt thereof together with a BCL-2 inhibitor or proteasome inhibitor for the treatment of cancer.

Abstract: Provided herein are methods of improving kidney function in a subject in need thereof.

Abstract: The present invention generally relates to sensitizer compounds and their use to sensitize cancer and/or pre-cancerous cells of certain cancers to treatment with certain resistance-prone therapeutics used in cancer therapy. In embodiments, the conjugates of particular esters or amides of Near Infrared Dyes, are used as sensitizers to avoid or overcome therapeutic resistance once formed. In embodiments, the sensitizers include conjugates with Cisplatin, Simvastatin, Artemisinin, platin-based compounds or statins. In embodiments, the resistance prone cancer therapeutics include cisplatin, gemcitabine, doxorubicin, paclitaxel, docetaxel, and platin-based compounds. These may be administered in combination with the sensitizer, or the sensitizer itself may comprise an therapeutic-derived moiety conjugated to the sensitizer, for example as is the case for dye-CIS conjugated sensitizers. Alternatively, the sensitizer may be co-administered with one or more therapeutic.

Abstract: The present disclosure provides GLP-1R agonists, and compositions, methods, and kits thereof. Such compounds are generally useful for treating a GLP-1R mediated disease or condition.

Abstract: An object of the present invention is to provide an antifungal agent which is effective against cryptococcosis. The present invention provides an antifungal agent comprising ravuconazole as an active ingredient, wherein the agent is administered to an animal suffering from cryptococcosis. Further, the present invention provides an antifungal agent comprising ravuconazole as an active ingredient, wherein the agent is administered to an animal suffering from cryptococcus that is resistant to triazole-based antifungal agents selected from the group consisting of fluconazole, itraconazole and voriconazole.

Abstract: A first aspect of the invention relates to betahistine, or a pharmaceutically acceptable salt thereof, and a monoamine oxidase inhibitor, for use in the treatment or prevention of one or more symptoms of vertigo in a subject. A second aspect of the invention relates to a method of treating or preventing one or more symptoms of vertigo in a subject, said method comprising administering to the subject (i) betahistine, or a pharmaceutically acceptable salt thereof, and (ii) a monoamine oxidase inhibitor.

Abstract: This application relates to methods of treating attention deficit hyperactivity disorder (ADHD), 22q deletion and/or duplication syndrome, and co-morbidities with a nonselective activator of metabotropic glutamate receptors, such as fasoracetam, for example, in subjects having a genetic alteration in at least one metabotropic glutamate receptor (mGluR) network gene.

Abstract: Described herein are novel piperidine urea derived compounds and their pharmaceutical compositions for the treatment of conditions and diseases mediated by soluble epoxide hydrolase.

Abstract: The invention relates to aqueous pharmaceutical compositions comprising the compound 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl) acetamide; glycine; polysorbate 20; and an aqueous phosphate buffer, wherein the relative amounts are as described in the description, wherein the pH of said pharmaceutical composition is between about 7 and 8; to lyophilized pharmaceutical compositions prepared from said aqueous compositions, and to reconstituted aqueous compositions thereof which are suitable for i.v. administration. The invention further relates to processes for the preparation of said compositions, and to their use for the treatment of diseases and disorders which are related to IP receptor.

Abstract: The present disclosure relates to the endothelin receptor antagonist (ERA) zibotentan in combination with the sodium-dependent glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin for use in the treatment of certain endothelin related diseases.

Abstract: The invention is directed to roles for low doses of PARP-1 inhibitors and synergistic combinations thereof to treat disease.

Abstract: The present invention relates to a method for treating a tumor with a KRAS mutation. In the method, a compound 2-fluoro-5-methoxy-4-[(4-(2-methyl-3-oxo-2,3-dihydro-1H-isoindole-4-oxy)-5-trifluoromethyl-pyrimidine-2-yl)amino]-N-(1-methyl-piperidine-4-yl)benzamide or a pharmaceutically acceptable salt thereof is used, which can be administered alone or in combination with a KRAS inhibitor and/or an MEK inhibitor.

Abstract: The present invention relates to pharmaceutical formulations comprising metolazone, a lipid, and an emulsifier that provide a lipid formulation of metolazone that can be administered intravenously to patients, thereby enhancing the therapeutic delivery and improving patient care for acute heart failure and resistant edmitious states.

Abstract: The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF1R inhibitors.

Abstract: The present disclosure relates to methods for the treatment of diseases or disorders (e.g., cancer) with mTOR inhibitors. Specifically, the disclosure relates to methods of treating a subject having a cancer by administering a particular dosage of an mTOR inhibitor. In some embodiments this disclosure includes methods for delaying, preventing, or treating acquired resistance to RAS inhibitors using a dosage of an mTOR inhibitor. In some embodiments, this disclosure relates to methods of treating or preventing adverse events associated with administration of an mTOR inhibitor using tacrolimus.

Abstract: The invention comprises a method for treatment of ADHD or ADHD-related disorders by a pharmaceutical agent exhibiting combined serotonergic or noradrenergic reuptake transporters and monoamine receptor activity.

Abstract: The present invention relates to compounds useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various diseases, conditions, or disorders.

Abstract: We have discovered that administering anti-ceramide antibody treats and prevents an array of diseases mediated by cytolytic T lymphocyte (CTLs)-induced killing and by damage to endothelial microvasculture, including radiation-induced GI syndrome, Graft vs. Host diseases, inflammatory diseases and autoimmune diseases. We have also discovered new anti-ceramide monoclonal antibodies, that have therapeutic use preferably in humanized form to treat or prevent these diseases.

Abstract: The present invention concerns protection of an organ or tissue outside of the central nervous system following an ischemic episode. In particular aspects, the invention concerns organ preservation for transplantation, angina pectoris, kidney reperfusion injury, and so forth. In specific embodiments, the organ is subjected to an inhibitor of an NCCa-ATP channel that is regulated by SUR1. Exemplary inhibitors include sulfonylurea compounds, such as glibenclamide, for example.

Abstract: The present invention relates to antibody drug conjugates (ADCs) presenting improved properties of in vivo tolerability.

Abstract: The subject invention provides fluorophore-quencher nucleic acid molecules comprising relaxed or supercoiled DNA molecules, and their use in rapid and efficient high-throughput screening (HTS) assays to screen and identify compounds that inhibit DNA gyrases. These compounds can be used as antibiotics for treating bacterial infections, especially, multidrug resistant bacterial infections.

Abstract: Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Abstract: Described herein is are compositions and methods for treating an articulating joint disorders, comprising systemically administering to a subject a nucleoside reverse transcriptase inhibitor (NRTI).

Abstract: The invention relates generally to tRNA-based effector molecules having a non-naturally occurring modification and methods relating thereto.

Abstract: The present disclosure relates to modified antisense oligomers and related compositions and methods for increasing the expression of functional SMN protein and methods for treating spinal muscular atrophy and relates to inducing inclusion of exon 7 in SMN2 mRNA.

Abstract: An antiviral agent is provided, having a phosphorodiamidate morpholino oligomer with an antisense sequence to a portion of a genome of a strain of a coronavirus. The coronavirus may be SARS-CoV-2 or another ?CoV. The antiviral agent finds many uses, such as in a pharmaceutical composition, a method of treating coronavirus-mediated disease, a method of preventing coronavirus-mediated disease, a method of reducing or preventing the replication of coronavirus in a host cell, a method of controlling the spread of coronavirus in donated tissue, a treated tissue sample, and in the manufacture of a medicament for the treatment or prevention or coronavirus-mediated disease.

Abstract: It has been discovered that NAD+-dependent histone deacetylase SIRT6 is critical for suppression of PDAC by controlling the expression of Lin28b, which is a negative regulator of let-7 microRNA. Specifically, SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This invention relates generally to agents and methods of reducing expression or activity of Lin28b to treat (aggressive) PDAC in a subject.

Abstract: The object of the present invention is to find a pharmaceutical having strong cancer therapeutic effect. The present invention provides a pharmaceutical composition for cancer therapy comprising a transcription or processing product of a gene encoding a miRNA, wherein said miRNA is one or more miRNAs selected from the group consisting of miR-3140, miR-137, miR-631, and miR-657, pharmaceutical composition.

Abstract: Therapeutically-active compositions and formulations for treating pain, pruritus, irritation, inflammation, and tissue damage due to the irritation and inflammation, and therapeutically-active compositions and formulations for wound management, including wounds that are at high risk for infection. Strontium and beta hydroxybutyrate based compositions and formulations which can be topically applied.

Abstract: Compositions and methods for improving nitric oxide levels in a subject, comprising administering to a subject, a composition comprising dietary nitrate derived from potassium nitrate, beet root (whole plant, powder, plant extract), and/or nitrate-rich leafy green portions (whole plant, powder, plant extract) that improve functional nitric oxide levels in subjects as shown by increasing salivary bioconversion of nitrate to nitrite, a necessary a required step for nitric oxide mediated health benefits. The disclosed novel compositions improve cardiac health, lowers blood pressure, intraocular pressure, and LDL and restores nitric oxide mediated cardiovascular benefits, including but not limited, restoring endothelium function and improving flow mediated dilation.

Abstract: The present invention provides compositions comprising amorphous calcium carbonate (ACC), suitable to being administered by inhalation, and methods for their use in treating ACC-responsive diseases and conditions. Kits for preparing suspension compositions of the present invention are provided as well.

Abstract: The present invention relates to chimeric antigen receptors (CARs) directed to cells expressing a dysfunctional or non-functional P2X purinoceptor 7 receptor. Further provided are methods of targeting neoplastic cells and tumours expressing a dysfunctional or non-functional P2X purinoceptor 7 receptor and methods of treating and preventing cancer is a subject.

Abstract: Methods and compositions using novel Cbl inhibitors for supporting engraftment of immune cells to increase the efficacy of cell-based immunotherapeutics are disclosed. Also provided are cell-based immunotherapy methods and compositions using novel Cbl inhibitors for the propagation of cells desirable for use in cell-based immunotherapies.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: A chimeric antigen receptor (CAR) may be include: a BCMA binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain, wherein the BCMA binding domain includes heavy chain complementarity determining regions HCDR1-3, and the amino acid sequences of the HCDR1-3 are successively as shown in SEQ ID NO: 1-3.

Abstract: The present invention provides a method for producing platelets, including the step of culturing megakaryocyte cells in a culture solution in a culture vessel, wherein in the culturing step, the culture solution is stirred by a stirring blade moving reciprocally.

Abstract: Disclosed are methods of treating a subject following a small-volume ischemic stroke suffered by the subject and methods of treating a subject with a stroke-induced motor deficit. Disclosed also is a composition for treating small-volume ischemic stroke. In one aspect, the method of treating a subject following a small-volume ischemic stroke comprises administering, to a brain region surrounding a small-volume ischemic core of the subject, a therapeutically effective amount of cells, wherein the cells are descended from mesenchymal stem cells transiently-transfected by a polynucleotide encoding a Notch intracellular domain.

Abstract: A composition and a method for analyzing an anti-aging effect of the composition of a fecal derived sterilized postbiotic are disclosed. The method includes obtaining a baseline biomarker of aging measurement, wherein the baseline biomarker of aging measurement includes a biomarker of aging, selecting a dose schedule from a plurality of dose schedules of a composition for a fecal derived sterilized postbiotic as a function of the baseline biomarker of aging measurement, wherein the composition includes a plurality of biological macromolecules including at least a short chain fatty acid, wherein the short chain fatty acid includes acetic acid, propionic acid, and butyric acid and a plurality of agents, wherein the plurality of agents is configured to regulate the biomarker of aging and administering the composition to a subject.

Abstract: The invention is directed to methods for the treatment of diseases and conditions caused by increased vascular permeability. The invention is also directed to methods for returning vascular permeability that is a symptom of a disease or condition to a homeostatic state. Specifically, the invention is directed to methods for the treatment of diseases and conditions caused by increased vascular permeability or returning vascular permeability that is a symptom of a disease or condition to a homeostatic state by administering to a subject suffering from such diseases and conditions and symptoms novel cellular factor-containing solution compositions (referred to herein as “CFS” compositions), including novel sustained-release cellular factor-containing solution compositions (referred to herein as “SR-CFS” compositions).