Abstract: Provided is a method to identify subjects with inflammatory diseases, such as inflammatory bowel disease, for their suitability for treatment with antifungal compounds. The method comprises identification of loss-of-function in the gene CX3CR1.

Abstract: Described herein are novel compounds that block the activity of LOX family members having good IC50 values, no cellular toxicity below 10 ?M, induce sensitization of the cells to doxorubicin, strong activity in a recombinant LOX/LOXL2 activity, and a chemical structure that is drug-like and does not have a PAINS flag, as well as, methods of treatment using the compounds with respect to cancer, organ fibrosis, neurodegenerative and cardiovascular diseases.

Abstract: The present invention relates to phenyl derivatives of formula (I) wherein (R1)n, R3, R4a, R4b, R5a, R5b and Ar1 are as described in the description and their use in the treatment of cancer by modulating an immune response comprising a reactivation of the immune system in the tumor. The invention further relates to novel benzofurane and benzothiophene derivatives of formula (III) and their use as pharmaceuticals, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as modulators of the prostaglandin 2 receptors EP2 and/or EP4.

Abstract: This document provides methods and materials involved in identifying and treating mammals having a cancer resistant to BET inhibitors. For example, methods and materials for administering one or more AKT inhibitors in combination with one or more BET inhibitors to mammals identified as having a cancer resistant to treatment with one or more BET inhibitors in the absence of AKT inhibitors are provided.

Abstract: The present invention covers an ATR kinase inhibitor, particularly 2-[(3R)-3-methylmorpholin-4-yl]-4-(1-methyl-1H-pyrazol-5-yl)-8-(H-pyrazol-5-yl)-1,7-naphthyridine (“Compound A”), for use in the treatment of a hyper-proliferative disease in a subject, wherein the hyper-proliferative disease or the subject is or has been characterized by one or more biomarker(s), wherein the biomarker(s) comprise(s) a) one or more functional mutations in one or more gene(s)/protein(s) selected from RBBP8, APOBEC3A, APOBEC3B, CLSPN, ERCC, HUS1, MAD2L2, PGBD5, POLD1, RAD1, TIMELESS and/or TIPIN; and/or b) the expression of a fusion gene encoding a fusion protein selected from EWSR-ERG, EWSR1-FLI1, SS18-SSX and/or SS18-SSX2 gene/protein.

Abstract: Disclosed herein are compositions comprising an NSAID such as meloxicam and/or rizatriptan in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.

Abstract: A dry powder inhalation treatment for pulmonary arterial hypertension includes a dose of dry particles comprising greater than 25 micrograms of treprostinil enclosed in a capsule. The dry particles can include treprostinil, a wetting agent, a hydrophobicity modifying agent, a pH modifying agent and a buffer. A method of treating a patient having pulmonary arterial hypertension includes providing a patient a dry powder inhaler, providing the patient at least one capsule for use in the dry powder inhaler, the capsule including at least 25 micrograms of treprostinil.

Abstract: The present invention relates to certain cortexolone derivatives of formula (I) and the use of the same as antitumor active ingredients for the curative or adjuvant, or neoadjuvant or palliative treatment of precancerous lesions, dysplasias, metaplasias and tumor diseases, including malignant neoplasias and metastasis. The present invention also relates to pharmaceutical compositions comprising cortexolone derivatives of formula (I) as active ingredients and at least one physiologically acceptable excipient, and to the use of the pharmaceutical compositions as antitumor medicinal products.

Abstract: The present invention features methods and composition directed to treating neuronal injury, CNS lesion, and/or promoting axon regeneration using a phosphine sulfide-stabilized phosphine.

Abstract: The present disclosure relates generally to compositions and methods for improving the consistency and regularity of a subject's bowel movements. Additionally, the compositions and methods are useful for also improving deficiencies in nutrition, deficiencies in hemoglobin, and reducing inflammation.

Abstract: Methods are disclosed for the mobilization of marrow infiltrating cells (MILs) using E-selectin antagonists for the treatment of disorders such as cancer. Methods for treating or preventing cancers using MILs mobilized by E-selectin antagonists are further disclosed.

Abstract: A method of manufacturing a high molecular weight heparin (HMWH) compound is disclosed. The method comprises dissolving heparin to form a heparin solution and fractionating the heparin solution via tangential flow filtration (TFF) using a membrane with a molecular weight cut off (MWCO) between about 8 kDa and about 12 kDa. The TFF yields a retentate comprising fractionated heparin with a weight average molecular weight of about 20 kDa or greater, i.e., a high molecular weight heparin compound. A substantial proportion of heparin chains in the fractionated heparin may have a high molecular weight, e.g., 50% of the heparin chains or greater may have a molecular weight of 20 kDa or greater.

Abstract: The disclosure relates to an alginate oligomer of 2 to 75 monomer residues, wherein said monomer residues do not carry a sulphate group, for use as a blood anticoagulant in clinical and non-clinical applications, including in vivo, ex vivo and in vitro contexts. The invention further provides for the use of such an alginate oligomer in preparing a product or device having a reduced capacity to promote blood coagulation, wherein said alginate oligomer is provided at or on a surface of said product or device. Such products and devices form a further aspect of the invention.

Abstract: The present disclosure relates to methods and complexes for ingestion of an elemental magnesium complex as inverted micellar nanodroplets designed to enhance uptake and cell delivery of active constituents. The complex and methods associated with delivery of the elemental magnesium complex disclosed improves many magnesium deficiencies that include cardiovascular, metabolic, neurohormonal, immune defense and repair systems, digestive, behavioral, and community risks.

Abstract: The present invention is directed to a method and a composition for producing and using a plant-based biocidal solution. The plant-based biocidal solution contains a bioactive material and a plant-based substance formed from the cellular material of a plant. The plant-based substance is capable of binding to the bioactive material. In some embodiments, the bioactive material is hydrogen peroxide. The hydrogen peroxide can be added exogenously or generated endogenously. In accordance with further embodiments, the plant-based biocidal solution can be applied to a target, thereby impairing the target. In some embodiments, the target can be a pathogen. In accordance with another embodiment, the plant-based substance of the plant-based biocidal solution can form a microscopic cluster, a complex, or an aggregate for providing sufficient bioactive material to overcome the defense mechanism of the target.

Abstract: An object of the present invention is to provide, for example, a more practical wound healing accelerator that more effectively accelerates wound healing. More specifically, a feature of the present invention is to provide, for example, a more practical wound healing accelerator that is easily obtained in a larger amount than that of peripheral blood platelet and has a better wound healing effect than that of peripheral blood platelet. The present invention employs a platelet-like cell population coexpressing one or more platelet surface markers and one or more mesenchymal cell surface markers. A wound healing accelerator containing the platelet-like cell population is a more practical wound healing accelerator that more effectively accelerates wound healing. The platelet-like cell population is easily obtained in a larger amount than that of peripheral blood platelet and has a better wound healing effect than that of peripheral blood platelet.

Abstract: The present disclosure relates to methods for treating or preventing heart failure in subjects with elevated left ventricular end systolic volume (LVESV). In particular, the present disclosure relates to methods for treating or preventing heart failure in subjects with a LVESV of greater than 70 ml (>70 ml).

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 invention extends the utility of apparatus used to extract medicinal cannabis compounds into an eluate by separating a portion of medicinal cannabis compounds contained within a portion of eluate at a first extraction target level providing enough clean solvent to continue extraction operations. A high efficiency concentrator such as a rotary evaporator or a wiped film evaporator processes eluate from one or more tanks or extraction vessels creating clean solvent when extraction targets are met or when clean solvent is exhausted. This manages eluate concentration levels and limits the quantity of concentrated medicinal cannabis compounds on site at any moment in time. The invention enables a business model for keeping medicinal cannabis compounds within a legal system, and reduces pollution because law enforcement would no longer have to burn large quantities of cannabis plant matter.

Abstract: The present disclosure relates to methods of treating pain in veterinary subjects using pharmaceutical compositions and dosage forms comprising hemp extract.

Abstract: A Syringa microphylla seed extract includes the following components by weight based on a total weight of the Syringa microphylla seed extract: 0.4944-0.7142 mg/g of echinacoside, 6.624-7.617 mg/g of oleuropein, 0.4276-0.6309 mg/g of verbascoside, 3.927-4.684 mg/g of syringin, and 4.505-5.250 mg/g of forsythiaside B. A method of preparing the Syringa microphylla seed extract is disclosed. A composition for treating antibiotic-resistant infections that includes the Syringa microphylla seed extract is also disclosed.

Abstract: The present application provides bifunctional compounds of Formula X or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.

Abstract: The disclosure features pharmaceutical compositions, methods, and kits featuring dosing regimens and CD101, or a pharmaceutical acceptable salt or neutral form thereof (e.g., CD101 acetate).

Abstract: In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.

Abstract: A polypeptide composition for treating atrial fibrillation includes a polypeptide that has a sequence: fADNYTRLRKQMAVKKYLNSILN-NH2 (SEQ ID NO: 1), From an N-terminus of the polypeptide, a first amino acid (f) is a D-Phe, a second amino acid is Ala, and a third amino acid is Asp; and the peptide is linear in a solution and forms an ?-helix structure after encountering a lipid bilayer.

Abstract: A method of treating systemic lupus erythematosus in a subject is provided in which a therapeutically effective amount of PIC1 is administered to the subject. A method of treating transfusion-related acute lung injury is also provided where a therapeutically effective amount of PIC1 is administered to the subject. PIC1 can modulate immune complex activation of the complement system and NET formation in the subject. PIC1 can also inhibit myeloperoxidase (MPO) activity in the subject.

Abstract: The present invention provides, among other things, methods of treating Pompe disease, including administering to a subject in need of treatment a composition comprising an mRNA encoding acid alpha-glucosidase (GAA) at an effective dose and an administration interval such that at least one symptom or feature of Pompe disease is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Abstract: A device for interventions within the body, the device comprising: an end piece 6 for insertion into the body at a distal end thereof, the end piece 6 including a rigid lumen for holding an instrument 10 and guiding the instrument 10 to the distal end of the end piece; and a body section 4 supporting the lumen and being rigidly connected thereto, the body section including a navigation array 14 for guidance of the device using a surgical navigation system and/or including an anchor point 20 for a standard navigation array.

Abstract: The present invention relates to cancer immunotherapy, in particular to sequence variants of tumor-related antigenic epitope sequences. Namely, the present invention provides a method for identification of microbiota sequence variants of tumor-related antigenic epitope sequences. Such microbiota sequence variants are useful for the preparation of anticancer medicaments, since they differ from self-antigens and, thus, they may elicit a strong immune response. Accordingly, medicaments comprising microbiota sequence variants, methods of preparing such medicaments and uses of such medicaments are provided.

Abstract: The present invention provides a vaccine composition for treating or preventing cancer expressing VASH2, containing a peptide including an amino acid sequence represented by SEQ ID NO: 4.

Abstract: Provided herein are methods for rational design of nicotine haptens. More particularly, provided herein are methods for designing, selecting, and synthesizing nicotine haptens and nicotine hapten conjugates. Also provided herein are novel nicotine haptens and methods for using nicotine haptens to treat nicotine addiction.

Abstract: The present invention provides combinations and methods using same for the treatment of malignancy, particularly a myeloid malignancy such as acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), chronic myeloid leukemia (CML), and chronic myelomonocytic leukemia (CMML). The combination may comprise an antibody or antigen-binding fragment thereof that binds to CD70, and an inhibitor of BCL-2. In certain embodiments, the antibody is ARGX-110 (cusatuzumab). In certain embodiments, the BCL-2 inhibitor is venetoclax. In certain embodiments, the combination provides synergistic treatment of AML. The combination may additionally comprise at least one additional anti-cancer agent.

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: The present invention discloses an antibody specifically binding to a human endothelin receptor and uses thereof, where the antibody can inhibit the functions of the human endothelin receptor. The present invention includes the preparation, cloning, expression, and characterization of the antibody. The present invention can be used to effectively treat pulmonary arterial hypertension, a disease associated with pulmonary arterial hypertension, and a reproductive organ cancer in a human.

Abstract: The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, an acetate buffering agent/system such as sodium acetate/acetic acid, and a sugar stabiliser such as trehalose. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.

Abstract: Provided is a stable pharmaceutical composition, comprising an anti-human TSLP receptor antibody, capable of inhibiting the generation of chemically modified substances, such as deamidated forms and oxidized forms, or degradants or multimers. The pharmaceutical composition comprises an anti-human TSLP receptor antibody, a pharmaceutically acceptable buffer, arginine or a pharmaceutically acceptable salt thereof, and a surfactant.

Abstract: The present invention relates to a sensitizer-peptide conjugate for use in the treatment of cancer. In particular, the present invention relates to a sensitizer-peptide conjugate for use in the treatment of melanoma. The use of such sensitizer-peptide conjugate in photodynamic therapy or sonodynamic therapy is also disclosed. According to the present invention, there is provided a sensitizer-peptide conjugate for use in the treatment of cancer; wherein the sensitizer-peptide conjugate comprises at least one sensitizer and at least one peptide.

Abstract: Disclosed are means of stimulating systemic immunity and reduction of post-surgery tumor metastasis through the concurrent intralymphatic inhibition of NR2F6 and treatment with cannabidiol. In some embodiments NR2F6 is inhibited by high pressure transient delivery of short interfering RNA into tumor draining lymph nodes concurrent with systemic administration of cannabidiol. This combination may be performed together with means that induce immunogenic tumor cell death. Through the combination of immunogenic cell death and immune stimulation, the invention provides a means of enhancing the abscopal effect and in some embodiments to cause immunological mediated destruction primary and secondary neoplasia.

Abstract: The present invention relates to a risperidone sustained release delivery system for treatment of medical conditions relating to delusional psychosis, schizophrenia, bipolar disorder, psychotic depression, obsessive-compulsion disorder, Tourette syndrome, and autistic spectrum disorders. The sustained release delivery system includes a flowable composition containing risperidone, a metabolite, or a prodrug thereof and an implant containing risperidone, a metabolite, or a prodrug thereof. The flowable composition may be infected into tissue whereupon it coagulates to become a solid or gel, monolithic implant. The flowable composition includes a biodegradable, thermoplastic polymer, an organic liquid, and risperidone, a metabolite or a prodrug thereof.

Abstract: The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

Abstract: The present invention provides compositions and methods for immunotherapy, which include shelf-stable pharmaceutical compositions for inducing antigen-specific T cells. Such compositions are employed as components of an artificial antigen presenting cell (aAPC), to provide a patient with complexes for presentation of an antigen (e.g., a tumor antigen) and/or a T cell co-stimulatory molecule.

Abstract: Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

Abstract: The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R1, R2, Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drug conjugates, and the resulting antibody drug conjugates made with components having heteroaryl sulfone-based conjugation handles.

Abstract: Improved formulations of lipid nanoparticles are provided. Use of the lipid nanoparticles for delivery of a therapeutic agent and methods for their preparation are also provided.

Abstract: Provided herein is a pharmaceutical composition comprising an effective amount of cypate-Cyclo(Cys-Gly-Arg-Asp-Ser-Pro-Cys)-Lys-OH (LS301), cypate-Cyclo(Cys-Gly-Arg-Asp-Ser-Pro-Cys)-Tyr-OH (LS838) or pharmaceutically acceptable salts thereof, wherein each amino acid residue is independently in a D or L configuration; a divalent metal ion; and a pharmaceutically acceptable carrier. Further provided are lyophilized products comprising a dye-conjugate and m methods for identifying compromised and for binding phosphorylated annexin A2 (pANXA2) protein in a biological sample using a composition described herein.

Abstract: The present disclosure provides activatable and detectable membrane-interacting peptides that, following activation, can interact with phospholipid bilayers, such as cell membranes. The present disclosure also provides methods of use of such compounds. The compounds of the present disclosure are of the general structure X1a-A-X2—Z—X1b, where A is a membrane-interacting peptide region having a plurality of nonpolar hydrophobic amino acid residues that, following separation from portions Z, is capable of interaction with a phospholipid bilayer; Z is an inhibitory peptide region that can inhibit the activity of portion A; X2 is a cleavable linker that can be cleaved to release cleavage products from the compound; and X1a and X1b are optionally-present chemical handles that facilitate conjugation of various cargo moieties to the compound. Prior to cleavage of the composition at X2, the composition acts as a promolecule that does not associate with cellular membranes to a significant or detectable level.

Abstract: A method for generating vapour bubbles in an object comprises introducing a composition into the object, the composition comprising carbon-based nano- or microparticles that can couple with a photon wave of electromagnetic radiation. The method also comprises irradiating said object using electromagnetic radiation. The irradiation thereby is adapted for using a set of carbon-based nano- or microparticles for subsequently forming first vapour bubbles and at least second vapour bubbles using the same carbon-based nano- or microparticles.

Abstract: Metal complexes including a radionuclide and a compound of Formula I and Formula II are potent inhibitors of PSMA.

Abstract: The present invention relates to a conjugated compound comprising a marker M pharmaceutically acceptable, and a peptide or pseudo-peptide P having at most 30 amino acid residues and able to bind the Low-Density Lipoprotein Receptor (LDLR) and to its use in a method of labelling and/or detecting and/or treating cancerous cells in a subject by administration of the conjugated compound to the subject an analysis of the presence and/or the amount of marker.

Abstract: The present invention relates to compositions and methods for imaging and treating various diseases and disorders, including cancers. The composition of the invention can include a plurality of biodegradable micro-beads, each embedding a plurality of nano-beads, further including a polymer, a radionuclide, a radionuclide chelator, a radioligand, a chemotherapeutic agent, and a cell-penetrating peptide. Upon injection into a blood vessel supplying a cancer tumor, the micro-beads lodge into the tumor and degrade, releasing the nano-beads with a therapeutic or diagnostic agent. The compositions and methods of the invention provide a more homogeneous and deeper distribution of radiation or chemotherapeutic agents throughout the target tumor. The micro-beads provide a local, sustained, and controlled delivery nano-beads including therapeutic or diagnostic agents.