Abstract: A pharmaceutically acceptable small molecule which inhibits GSK-3 activity, such as BIO, CHIR99021 or tideglusib; are used in the repair or regeneration of dentine. Combinations with matrix materials forming dental implants are also described and claimed.

Abstract: Disclosed herein are compositions comprising a combination of at least one Pol I inhibitor, and at least one autophagy inhibiting compound, and/or at least one ACAT1 inhibiting compound, and/or at least one PARP inhibiting compound and their use in treating cancers and other related neoplastic diseases and which may also include additional chemotherapeutic agents.

Abstract: The present application in some embodiments provides a pharmaceutical composition comprising: and a compounding agent. Further provided herein are methods of making and methods of using the pharmaceutical compositions, for example, in the treatment of cancer.

Abstract: The present disclosure provides methods and kits for treating or slowing the progression of a hematological malignancy, by administering to a subject in need thereof a therapeutically effective amount of: (i) at least one inhibitor of PI3 kinase (PI3K)-delta (e.g., TGR-1202); (ii) at least one anti-CD20 antibody (e.g., ublituximab); and (iii) at least one anti-PD-1 antibody (e.g., pembrolizumab) or anti-PD-Ll antibody (e.g., atezolizumab). Treatment regimens are also provided.

Abstract: The present disclosure relates to methods for treating an ANCA associated vasculitis, for example, granulomatosis with polyangiitis (GPA), with compositions comprising an effective amount of certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds of Formula (I), including pharmaceutically acceptable salts thereof, that inhibit dipeptidyl peptidase 1 (DPP1) activity. In one embodiment, the compound of Formula (I) is (2S)-N-{(1S)-1-cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide (INS1007).

Abstract: Pharmaceutical compositions for co-administering estradiol and progesterone to a human subject having vasomotor symptoms associated with estrogen deficiency are provided. In some embodiments, the pharmaceutical composition produces certain pharmacokinetic parameters when the composition is administered to the subject.

Abstract: Formulations of comprising a neuroactive steroid, e.g., allopregnanolone; and optionally a cyclodextrin, e.g., a ?-cyclodextrin, e.g., a sulfo butyl ether ?-cyclodextrin, e.g., a ?-cyclodextrin, e.g., a sulfo butyl ether ?-cyclodextrin, e.g., CAPTISOL®; and methods of use in treating CNS disorders.

Abstract: The present application discloses methods for treating an IL-6-mediated disorder such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic JIA (sJIA), polyarticular course JIA (pcJIA), systemic sclerosis, or giant cell arteritis (GCA), with subcutaneously administered antibody that binds interleukin-6 receptor (anti-IL-6R antibody). In particular, it relates to identification of a fixed dose of anti-IL-6R antibody, e.g. tocilizumab, which is safe and effective for subcutaneous administration in patients with IL-6-mediated disorders. In addition, formulations and devices useful for subcutaneous administration of an anti-IL-6R antibody are disclosed.

Abstract: The present invention provides an NASH therapeutic agent including: an FXR agonist, preferably obeticholic acid or a pharmaceutically acceptable salt thereof; and an ARB or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to olesoxime for use in the treatment of spinal muscular atrophy (SMA), its pharmaceutical composition to be used in the treatment of SMA, its methods of treatment thereof.

Abstract: The present invention relates to a composition for preventing, treating, or alleviating ischemia-reperfusion injury, containing bile acid. According to the present invention, bile acid increases intranuclear beta-catenin levels, interferes with the opening of a mitochondria permeable transition pore (mPTP), and has excellent effects, in ischemia-reperfusion injury animal models, of alleviating tissue injury and reducing the size of infarcts, thereby being usable in the prevention, treatment, or alleviation of ischemia-reperfusion injury.

Abstract: A nanodevice composition including N-acetyl cysteine linked to a dendrimer, such as a PAMAM dendrimer or a multiarm PEG polymer, is provided. Also provided is a nanodevice for targeted delivery of a compound to a location in need of treatment. The nanodevice includes a PAMAM dendrimer or multiarm PEG polymer, linked to the compound via a disulfide bond. There is provided a nanodevice composition for localizing and delivering therapeutically active agents, the nanodevice includes a PAMAM dendrimer or multiarm PEG polymer and at least one therapeutically active agent attached to the PAMAM dendrimer or multiarm PEG polymer.

Abstract: The present invention relates to agents and methods for treating autism spectrum disorders, such as Rett Syndrome.

Abstract: A method of producing sialyloligosaccharides a sialyloligosaccharides-containing source that also contains carbohydrates and minerals. The process includes subjecting the source to a temperature of from about 67° C. and (i) filtration with a heat-resistant filter at a temperature of about 35 to about 95° C. to produce a first retentate and first permeate, or (ii) centrifugal separation to produce a light phase and a heavy phase and filtration of the light phase at a temperature of about 50 to about 70° C. to produce a first retentate and first permeate, (b) nanofiltration of the first permeate, or nanofiltration and diafiltration of the first permeate, to produce a second retentate and second permeate, and (c) concentration of the second retentate, to produce a sialyloligosaccharide-containing extract.

Abstract: Described herein are compositions comprising shortened fibers of poly-N-acetylglucosamine and/or a derivative thereof (“sNAG nanofibers”) and anti-bacterial applications of such compositions. The sNAG nanofibers may be formulated into compositions for the prevention and/or treatment of bacterial infections and diseases associated with such infections. Regimens employing such compositions are also described.

Abstract: The invention provides a method of treating heterotopic ossification in a subject in need thereof. The method comprises administering a hypoxia inducible factor-1? (Hif-1?) inhibitor to the subject. In various embodiments, the Hif-1? inhibitor is PX-478, rapamycin, or digoxin.

Abstract: HAT-Pi chemotherapy arrests uncontrolled replication and metastatic migration of neoplastic cells by inhibiting enzymatic activity of poly(ADP-ribose) polymerase 1 (PARP 1) through administration of one or more halogenated analogs of thymidine (HAT). A full HAT-Pi treatment regimen, involving repeated HAT-Pi courses over extended periods (24 weeks), may lead to tumor regression through HAT-Pi-induced neoplastic cell death and disintegration. Pain related to neoplastic disease may be reduced during HAT-Pi treatment and for extended periods thereafter. Myelosuppression is a potentially life-threatening but manageable HAT-Pi toxicity and other HAT-Pi side-effects may be tolerated by most patients. Acquired patient resistance to HAT-Pi has not been observed. HAT-Pi is potentially teratogenic and is restricted to post-reproductive adults with advanced neoplastic disease. Modified HAT-Pi treatment regimens may allow for broader application to treat additional individuals and/or conditions.

Abstract: In alternative embodiment, provided are methods and compositions for treating, ameliorating or preventing diseases and conditions, such as cancer, including cancers associated with stem cells such as, without limitation, myelodysplastic syndrome (MDS) and a myeloproliferative neoplasm like chronic myeloid leukemia (CML) or acute myeloid leukemia (AML), and ablating or killing cancer stem cells. In alternative embodiment, provided are a new set of biomarkers to detect leukemia stem cell reprogramming and CML progression. In alternative embodiment, provided are therapeutic targets for treating myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML) by targeting edited let-7 transcripts.

Abstract: The present invention provides a composition and a method for efficiently delivering a nucleic acid agent to the central nervous system and/or the retina and bringing about antisense effects. Provided is a composition for reducing the expression level of a target transcription product in the central nervous system and/or retina of a subject, the composition including a nucleic acid complex that includes a first nucleic acid strand and a second nucleic acid strand, wherein: the first nucleic acid strand comprises a base sequence capable of hybridizing with at least part of the target transcription product and has an antisense effect on the target transcription product; the second nucleic acid strand comprises a base sequence complementary to the first nucleic acid strand and is conjugated to tocopherol, cholesterol, or an analog thereof; and the first nucleic acid strand is annealed to the second nucleic acid strand.

Abstract: This document provides methods and materials for activating muscle remodeling. For example, methods and materials for using GAR1 inhibitors to activate muscle remodeling are provided.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA ? 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by improved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

Abstract: The methods and assays described herein relate to detection, diagnosis, and treatment of lung cancer, e.g., by detecting the level of expression of certain miRNAs described herein and/or by therapeutically increasing the level of those miRNAs.

Abstract: The present invention relates to ophthalmic compositions and methods useful to treat dry eye, or to diagnose, cure, mitigate, treat, or prevent dry eye syndrome in man or other animals.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 mRNA in a cell or animal, and in certain instances reducing the amount of Ataxin-3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to prevent or ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include ataxia, neuropathy, and aggregate formation. Such neurodegenerative diseases include SCA3.

Abstract: The present disclosure relates to a method which allows direct formation of gel-like solutions of polyglucosamine at neutral pH?7 to 8, eliminating the need of prior dissolution of polyglucosamine in acidic environment; and to a homogeneous liquid combination of polyglucosamine-glyoxylate with hyaluronan.

Abstract: It is an objective of the present invention to provide a composition that is sufficiently safe to allow daily ingestion and that has an ability to promote the secretion of s-IgA into saliva in a continuous and age-independent manner. The above objective is achieved by the composition for promoting secretion of secretory IgA, comprising as an active ingredient Okinawa mozuku-derived fucoidan with a recommended daily intake of 1,000 mg or more. The composition has the mucosal immunostimulatory effect, anti-infection effect or anti-allergy effect and is expected to be used for ameliorating, mitigating, suppressing, treating or preventing diseases or symptoms on which these effects are expected to work, such as bacterial infection, viral infection, protozoan infection, food allergy, pollenosis, gastritis, enteritis, diarrhea, ulcerative colitis, rhinitis, bronchitis, bronchial asthma, Löffler's syndrome and stomatitis, as well as any symptoms resulting therefrom.

Abstract: The disclosure provides products and methods of treating diseases and disorders involving microbial pathogens, such as intestinal microbial pathogens, e.g., Pseudomonas aeruginosa, by administering an effective amount of a phosphorylated polyethylene glycol compound of defined structural organization. Those diseases and disorders characterized by an epithelium attacked by a microbial pathogen are contemplated, including gastrointestinal infections and inflammation, e.g., treatment of intestinal or esophageal anastomosis or treatment or suppression of anastomotic leakage.

Abstract: In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method of promoting bone growth described herein comprises promoting cell differentiation or phenotype progression in a population of bone cells by providing a citrate-presenting composition to the population of bone cells. In some embodiments, the citrate-presenting composition is provided to the bone cells at a first stage of cell development selected to obtain a first cell differentiation or phenotype progression. Additionally, in some cases, a second citrate-presenting composition is further provided to the bone cells at a second stage of cell development selected to obtain a second cell differentiation or phenotype progression.

Abstract: Provided are a RUNX inhibitor which binds to a RUNX-binding sequence on DNA and thus inhibits the binding of a RUNX family member to the sequence; an antitumor agent comprising the RUNX inhibitor; and an antiallergic agent comprising the RUNX inhibitor.

Abstract: The invention relates to method of treating chronic inflammatory diseases in subjects in need thereof by administering calcium lactate as an active agent. The calcium lactate can be provided in a pharmaceutical, food, or nutrient composition.

Abstract: A method for treating or preventing a disease or condition that operates by calcium transport through the mitochondrial calcium uniporter (MCU), the method comprising administering to a subject a therapeutically effective amount of an MCU inhibitor having the following structure: wherein L1, L2, L3, L4, L5, L6, L7, L8, X1, and X2 are independently selected from halide, amine groups —NR1R2R3, phosphine groups —PR5R6R7, carboxylate groups R4C(O)O—, and solvent molecules, and provided that at least one of L1, L2, L3, L4, L5, L6, L7, L8, X1, and X2 is selected from amine or phosphine groups; wherein R1, R2, R3, and R4 are independently selected from hydrogen atoms and hydrocarbon groups having up to six carbon atoms, wherein two of R1, R2, and R3 within a —NR1R2R3 group are optionally interconnected to form an N-containing ring; and R groups in adjacent amino or phosphine groups may optionally interconnect.

Abstract: The invention relates to compositions for administering zinc, including nutritional supplement compositions, comprising ?-polyglutamic acid, a zinc salt, and a gastro-resistant material for use as a dietary supplement to provide zinc to persons desiring or in need thereof, and methods for preparing such compositions as solid dosage forms such as tablets and capsules, and as liquid dosage forms.

Abstract: The present invention is in the field of medicinal technologies, and provides a nano-material composition DG-5 for use as a medicament against drug-resistant bacteria. The composition showed a strong inhibitory effect against several super drug-resistant bacteria (superbugs), and thus can be used for manufacture of novel effective antibacterial drugs. The mediocament can be administered externally, orally, subcutaneously, or via intravenous or intramuscular injection.

Abstract: The present invention relates to cells engineered to express at least one cytokine and at least one antigen which induces the self differentiation of dendritic cell (DC) progenitor cells into functional antigen-presenting induced DC (iDC). Moreover, therapeutic uses of said iDC for regenerating the immune system after transplantation of hematopoietic stem cells are disclosed. Said iDC are also useful for generating mice with a functional endogenously regenerated humanized immune system producing antigen-specific T and B cell responses which can be used as animal models for the study of the human adaptive immune responses.

Abstract: Provided herein are methods for the production of activated CD26high T cells by co-stimulation with inducible coactivator (ICOS). Further provided are methods for treatment of cancer by administration of the of activated CD26high T cells as an adoptive T cell therapy.

Abstract: The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g. PD-1 or TIM-3) is downregulated.

Abstract: The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.

Abstract: Control Devices are disclosed including RNA destabilizing elements (RDE), and RNA control devices, combined with transgenes, including Chimeric Antigen Receptors (CARs) in eukaryotic cells. RDEs can be combined with RNA control devices to make RDEs that include ligand mediated control. These smart RDEs and other RDEs can be used to optimize expression of transgenes, e.g., CARs, in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered at desired times from the eukaryotic cell.

Abstract: Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have observed the emergence of acquired resistance in non-small cell lung cancer patients that were initially responsive to immune checkpoint blockade. Resistance occurred 4-11 months after the initiation of immunotherapy and both clinical response and therapeutic resistance were associated with changes in T cell clonality but not with changes in expression of PD-L1. Genomic analyses of responsive and resistant tumors from the same patients identified loss of 7 to 18 mutation-associated putative neoantigens in resistant clones that were predicted to have high MHC binding affinity. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations. These analyses provide insights into the mechanisms of evasion to immune checkpoint blockade and immune therapies that target tumor neoantigens.

Abstract: Compositions and methods concern the sequence modification of an endogenous genomic DNA region. Certain aspects relate to a method for site-specific sequence modification of a target genomic DNA region in cells comprising: transfecting the cells by electroporation with a composition comprising (a) a DNA oligo; (b) a DNA digesting agent; and (c) a targeting RNA, wherein the targeting RNA is capped and/or polyadenylated; wherein the donor DNA comprises: (i) a homologous region comprising nucleic acid sequence homologous to the target genomic DNA region and (ii) a sequence modification region; and wherein the genomic DNA sequence is modified specifically at the target genomic DNA region.

Abstract: The present inventions provides systems and methods to manufacture genetically modified lymphocyte cells via the use of linear DNA expression amplicons, and uses of such genetically modified lymphocyte cells to treat disease. The present invention also provides for the composition of genetically modified lymphocyte cells.

Abstract: The present disclosure provides compositions and methods for targeted delivery of therapeutic agents. The present disclosure further provides methods for treating or preventing the metastasis or recurrence of a cancer using platelets loaded with a therapeutic agent (for example, an immunotherapeutic agent).

Abstract: Provided herein are methods and compositions for the treatment of musculoskeletal disorders, including disorders of a joint.

Abstract: Provided are cells containing exogenous antigen and uses thereof.

Abstract: The present disclosure relates to a novel musculoskeletal stem cell (MSSC) differentiated from an ESC (embryonic stem cell) or an iPSC (induced pluripotent stem cell). The musculoskeletal stem cell of the present disclosure can be easily induced from a human embryonic stem cell or a human-derived pluripotent stem cell and can be effectively differentiated not only into bone but also into cartilage, tendon and muscle. Accordingly, it can be usefully used for prevention or treatment of various musculoskeletal diseases.

Abstract: A cognitive decline inhibitor or a learning ability improver is provided, which comprises, as an active ingredient, a liver hydrolysate having a lipid content of less than 2 mass % or a phosphatidylcholine content of less than 1 mass %.

Abstract: Disclosed are methods of making a genetically cell that expressed FOXP3 and methods of treatment. In some embodiments, the method can providing a first nucleotide sequence, wherein the first nucleotide sequence comprises a coding strand, the coding strand comprising one or more regulatory elements and a FOXP3 gene or portion thereof providing a nuclease and performing a gene editing process on the first nucleotide sequence, which edits said one or more regulatory elements, and optionally edits the FOXP3 gene or portion thereof. Methods of treating a subject suffering from an autoimmune disease and subjects suffering the effects of organ transplantation are also provided.

Abstract: The present technology relates generally to formulations comprising egg white protein, methods of manufacturing egg protein formulations and uses for egg protein formulations. In particular, several embodiments are directed to egg protein formulations for oral administration in immunotherapy of subjects affected by egg allergies.

Abstract: The present disclosure provides compositions and methods for treating Clostridium difficile infection (CDI) including primary and recurrent CDI. In particular, the compositions and methods described herein are capable of achieving a CDI clearance rate of at least 80% through a single oral dose of a pharmaceutical composition comprising a freeze-dried fecal microbiota preparation.