Abstract: The present invention relates to compositions and methods for treating cancer, particularly to agents that inhibit the expression and/or activity of the protein second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (SMAC/Diablo). The inhibiting agents include RNA interference molecules silencing the expression of SMAC/Diablo and peptides modulating its interactions within the cell nucleus and mitochondria. The methods and agents of the present invention are useful in treating cancers associated with overexpression of SMAC/Diablo.

Abstract: An aspect of the present disclosure pertains to a novel long-acting fatty acid-conjugated gonadotrophin-releasing hormone (GnRH) derivative and a pharmaceutical composition containing the same. A GnRH derivative of the present invention is expected to greatly contribute, through excellent bioavailability, increased half-life in blood, and remarkably high therapeutic effects on sex hormone-dependent disease, to the reduction in drug dosing frequency and dosage and the like in the treatment of sex hormone-dependent diseases. Particularly, the GnRH derivative can overcome the disadvantages of existing GnRH sustained-release preparations, which have the side effects of residual feeling and pain at the injection site.

Abstract: Agents, kits, and methods that utilize oxygenation to treat Inflammatory Bowel Disease (IBD) and/or provide prophylaxis against exacerbation of IBD are provided. In several embodiments, the agents, kits, and methods according to several embodiments generate in, or carry to, oxygen in the intestinal lumen to treat IBD and provide prophylaxis against exacerbation of IBD, including those caused by the presence of anaerobic bacteria in the intestine. The agents, kits, and methods provided herein generate an aerobic environment within the intestine to alleviate intestinal inflammation.

Abstract: An application of a skeletal muscle secreted factor Thbs4 in a preparation of a drug for improving systemic glucose and lipid metabolism is provided. According to the present invention, it is found through experiments that Thbs4 increases a body's metabolic rate by activating a beige-like change of white adipose, relieves the metabolic disorder caused by high-fat diet, and reveals its application value in the treatment of the metabolic disorder.

Abstract: The method includes the steps of performing in-vitro liver, intestinal and/or expressed enzyme assays with selected ethnobotanical substances, for both humans and a variety of animal species, to produce an array of resulting chemical entities, such as metabolites, for the human and the animals. Comparisons are then made between the chemical entities from the human in-vitro studies and the animal in-vitro studies to determine the closest match. The animal with the closest match is then used for an in-vivo study. If a match is present between the animal in-vivo results and the human in-vitro results, the matched chemical entity is isolated or synthesized and then further tested to determine the suitability of the matched chemical entity as a treatment drug.

Abstract: The present invention provides modulators of complement activity. Also provided are methods of utilizing such modulators as therapeutics.

Abstract: Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: The present application provides compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein D is a residue of a GLP-polypeptide or an analog thereof, which underdo hydrolysis under physiological conditions to release the GLP-polypeptide or analog thereof and which are useful in the treatment of disorders that could be beneficially treated with the GLP-polypeptide or analog thereof.

Abstract: The present invention provides means and methods for equipping a polypeptide of interest at its C-terminus with a versatile adaptor amino acid that allows the functionalization of the polypeptide of interest.

Abstract: Agents, kits, and methods that utilize oxygenation to treat Inflammatory Bowel Disease (IBD) and/or provide prophylaxis against exacerbation of IBD are provided. In several embodiments, the agents, kits, and methods according to several embodiments generate in, or carry to, oxygen in the intestinal lumen to treat IBD and provide prophylaxis against exacerbation of IBD, including those caused by the presence of anaerobic bacteria in the intestine. The agents, kits, and methods provided herein generate an aerobic environment within the intestine to alleviate intestinal inflammation.

Abstract: The invention provides compositions and methods of treating cancer in a patient with a combination therapy comprising a fusion protein of SEQ ID NO: 1 in combination with an immune checkpoint inhibitor. Preferably the patient has failed to achieve complete or partial response with prior or ongoing treatment with an immune checkpoint inhibitor.

Abstract: An antifungal peptide targeting P4-ATPase function is synthesized based on Cdc50 loop region to identify peptides sensitize caspofungin by blocking flippase function. It was found that myristylated peptides based on “AS15 sequence” was effective at high concentrations. A modified peptide, “AW9-Ma” showed minimum inhibitory concentration (MIC) of 64 ?g/mL against H99 wild type and fractional inhibitory concentration (FIC) index value of 0.5 when used with caspofungin. With the AW9-Ma peptide, C. neoformans wild type was highly sensitive to caspofungin with a MIC of 4 ?g/mL, the same as cdc50? mutant. Further assays with flow cytometry showed inhibition of lipid flippase enzyme activity and significant accumulation of phosphatidylserine on the cell surface. It was confirmed that the peptide co-localized with mCherry-tagged P4-ATPase protein Apt1 in C. neoformans.

Abstract: Therapeutic compositions and an associated method for improving a Toll-like receptor (TLR)-related condition, including determining a set of peptide sequences associated with a microorganism-related modulator of a TLR, determining a first set of binding parameters for the set of peptide sequences in relation to the TLR, selecting a target subset of peptide sequences from the set of peptide sequences based on the first set of binding parameters, reengineering the target subset of peptide sequences based on mutating amino acid residues of the target subset of peptide sequences, determining a second set of binding parameters for the reengineered target subset of peptide sequences in relation to the TLR, and identifying a first peptide for use in a therapeutic composition for improving the TLR-related condition, based on the second set of binding parameters for the reengineered target subset of peptide sequences.

Abstract: The present invention relates to fusion proteins comprising variant IL-15 proteins, fusion proteins comprising variant anti-PD-1 antigen binding domains, and fusion proteins comprising variant IL-15 proteins and variant anti-PD-1 antigen binding domains. The present invention also relates to nucleic acid molecules, expression vectors, host cells and methods for making such fusion proteins and the use of such fusion proteins in the treatment of cancer.

Abstract: Disclosed are a novel therapeutic means effective and practical against cancer, and a novel substance useful as such a therapeutic means. Provided are novel peptides derived from a partial region of HMGN1, HMGN2, HMGN4 or HMGN5, and anti-cancer agents and anti-cancer effect enhancers containing the peptide as an active ingredient. The peptide of the present invention has an anti-tumor effect even independently, and exerts a remarkably excellent anti-tumor effect particularly when used in combination with an immune checkpoint regulator, or an anti-CD4 antibody or antigen-binding fragment thereof.

Abstract: Disclosed are methods of treating obesity or an obesity-related condition comprising administering an effective amount of soluble (pro)renin receptor (sPRR) to a subject that is obese or having an obesity-related condition. In some instances, obesity-related conditions can be, but are not limited to, steatosis, hyperglycemia, insulin resistance, chronic renal disease. Disclosed are methods of reducing body weight comprising administering an effective amount of sPRR to a subject in need thereof. Disclosed are methods of treating fatty liver in a subject comprising administering an effective amount of sPRR to a subject in need thereof. Disclosed are methods of treating a fluid and electrolyte disorder comprising administering an effective amount of sPRR to a subject diagnosed with a fluid and electrolyte disorder.

Abstract: The invention provides novel antibacterial compounds of formulae IA, IB and IC as defined herein. Optionally, the antibacterial compounds can be bonded to a delivery agent that is capable of bonding to one or more structures on a bacterial cell membrane. The invention also provides the use of such compounds in treating or preventing bacterial infections, and processes for their synthesis.

Abstract: Conjugates for delivering an anti-cancer agent to nerve cells are provided. Conjugate compounds of the present disclosure according to certain embodiments include a compound having a protein, peptide or pepetidomimetic that binds selectively to a neurotrophin receptor, an anti-cancer agent and a linker that covalently bonds the anti-cancer agent to the protein, peptide or pepetidomimetic binds selectively to the neurotrophin receptor. Compositions and methods for delivering an anti-cancer agent selectively into nerve cells (e.g., in the treatment of optic pathway glioma) as well as indications such as perineural invasion and skin cancers are also described. Also provided are methods of making the anti-cancer conjugate compounds.

Abstract: Antibody molecule-drug conjugates (ADCs) that specifically bind to lipopolysaccharides (LPS) are disclosed. The antibody molecule-drug conjugates can be used to treat, prevent, and/or diagnose bacterial infections and related disorders.

Abstract: Agents, kits, and methods that utilize oxygenation to prevent and/or treat infections caused by anaerobic microorganisms are provided. The agents, kits, and methods according to several embodiments utilize oxygenation in the intestinal lumen to prevent and/or treat infections caused by anaerobic bacteria. The agents, kits, and methods can be utilized to prevent and/or treat anaerobic bacterial infections of the intestinal lumen by enteric aerobization therapy.