Abstract: The present disclosure described herein provides compositions with a membrane-penetrating properties and methods for allowing translocation across a membrane without disruption.

Abstract: Described herein are bioactive peptides that are modified at one or more positions with a PEG moiety. An example of such a PEGylated bioactive peptide is a GHRH analog that is modified at one or more positions with a PEG moiety. Also described are pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising such analogs or salts thereof, as well as methods, kits and uses thereof, for example for inducing or stimulating growth hormone secretion in a subject and for diagnosing, preventing or treating GH-deficient conditions in a subject.

Abstract: The present invention concerns compositions comprising and methods of identification and use of imaging agents. The imaging agents comprise a growth hormone secretagogues having a conjugated fluoride. The imaging agents of the present invention may be used for detection, diagnosis and/or staging of prostate or other forms of cancer, and may also be used for cardiac disease.

Abstract: Disclosed herein are bacterial proteins that increase pancreatic beta (?) cell number and/or proliferation, methods of increasing ? cell number and/or proliferation using such proteins, and methods of treating or inhibiting diabetes in a subject by administering such proteins to the subject. In some embodiments, the protein has at least 80% sequence identity to the amino acid sequence set forth as any one of SEQ ID NOs: 1-7, or fragments thereof. Recombinant vectors including a nucleic acid encoding the protein (such as a nucleic acid encoding a protein with at least 80% sequence identity to any one of SEQ ID NOs: 1-7 or fragments thereof) operably linked to a heterologous promoter are also disclosed. Also disclosed are methods of identifying compounds that increase ? cell number and/or proliferation by determining the effect of test compounds on ? cell number or proliferation in zebrafish pancreas.

Abstract: The present invention relates to a method for suppressing or treating cancer, in particular to a method for suppressing or treating one or more of colorectal cancer, breast cancer, prostate cancer and/or lung cancer. The therapy employs use of a non-cytotoxic protease, which is targeted to a growth hormone-secreting cell such as to a pituitary cell. When so delivered, the protease is internalised and inhibits secretion/transmission of growth hormone from said cell. The present invention also relates to polypeptides and nucleic acids for use in said methods.

Abstract: Disclosed are peptide and peptidomimetic compounds generally according to formula (I) that are useful as GHRP analogs: R1-A1-A2-A3-A4-A5-R2?? (I) wherein: A1 is Aib, Apc or Inp; A2 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A3 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A4 is 2Fua, Orn, 2Pal, 3Pal, 4Pal, Pff, Phe, Pim, Taz, 2Thi, 3Thi, Thr(Bzl); A5 is Apc, Dab, Dap, Lys, Orn, or deleted; R1 is hydrogen, (C1-6)alkyl, (C5-14)aryl, (C1-6)alkyl(C5-14)aryl, (C3-8)cycloakyl, or (C2-10)acyl; and R2 is OH or NH2; and pharmaceutical compositions and methods of use thereof.

Abstract: The present invention provides peptidomimetic macrocycles capable of modulating growth hormone levels and methods of using such macrocycles for the treatment of disease.

Abstract: There are provided a novel series of peptide analogs of hGH-RH(1-29)NH2 and hGH-RH(1-30)NH2 which show high activities in stimulating the release of pituitary GH in animals. They retain their physiological activity in solution for extended periods of time and resist enzymic degradation in the body. These novel and useful properties appear to be due to novel substitution patterns ant at the 1, 15, 27 and 29 positions on the peptide.

Abstract: Agonists of growth hormone releasing hormone promote islet graft growth and proliferation in patients. Methods of treating patients comprise the use of these agonists.

Abstract: Disclosed herein are an in situ-forming, bioadhesive hydrogel and the medical uses thereof. Being formed by in situ crosslinking through an enzymatic reaction, the hydrogel has an advantage over conventional bioadhesive hydrogels in terms of biocompatibility. In addition, the in situ-forming bioadhesive hydrogel has excellent biocompatibility and mechanical strength and has excellent tissue adhesiveness thanks to modification with/without dopa derivatives. The hydrogel finds a variety of applications in the biomedical field, including bioadhesives or hemostats, implant substances for tissue regeneration and augmentation, carriers for delivering biologically active materials or drugs, etc.

Abstract: Disclosed are peptide and peptidomimetic compounds generally according to formula (I) that are useful as GHRP analogs: R1-A1-A2-A3-A4-A5-R2??(I) wherein: A1 is Aib, Apc or Inp; A2 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A3 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A4 is 2Fua, Orn, 2Pal, 3Pal, 4Pal, Pff, Phe, Pim, Taz, 2Thi, 3Thi, Thr(Bzl); A5 is Apc, Dab, Dap, Lys, Orn, or deleted; R1 is hydrogen, (C1-6)alkyl, (C5-14)aryl, (C1-6)alkyl(C5-14)aryl, (C3-8)cycloakyl, or (C2-10)acyl; and R2 is OH or NH2; and pharmaceutical compositions and methods of use thereof.

Abstract: A method for preventing cognitive decline, comprises the steps of identifying, in an individual, a first stage of cognitive decline corresponding to Subjective Cognitive Impairment and administering a predetermined treatment to the individual to inhibit a progression of the individual to a second predetermined stage of cognitive decline or to inhibit progression of cognitive decline within the first stage.

Abstract: The present invention relates to methods for protecting a subject, tissues and/or organs from a subject against oxidative stress-induced damage, such as but not limited to, oxidative stress-induced tissue damage. The method comprises administering an effective amount of unacylated ghrelin, a fragment thereof, an analog thereof and/or pharmaceutically acceptable salts thereof to the subject.

Abstract: The present invention relates to water-soluble protein carrier-linked prodrugs wherein the protein carrier comprises an amino acid sequence consisting of at least 100 amino acid residues forming random coil conformation and comprising alanine, serine and proline residues. It further relates to pharmaceutical compositions comprising said water-soluble protein carrier-linked prodrugs, their use as a medicament as well as methods of treatment and administration.

Abstract: Stabilized solid and liquid pharmaceutical formulations comprising a GRF molecule as active ingredient, such as GRF analogs including those comprising an N-terminal-attached hydrophobic moiety, such as [trans-3-hexenoyl]hGHRH (1-44) amide, are disclosed. The formulation comprises a GRF molecule or a pharmaceutically acceptable salt thereof and a ?-cyclodextrin which is not conjugated to the GRF molecule or salt thereof. Also disclosed is the use of the formulation for the treatment of various conditions, methods of preparing the formulation, as well as kits containing it. Methods of stabilizing (e.g., with respect to chemical stability) such GRF molecules, as well as methods of inhibiting their deamidation at Asn8, are also disclosed.

Abstract: Disclosed herein are compositions of GHRH agonists and peptides, and methods to treat diabetes. In one embodiment, a method of promoting survival of grafted cells and/or tissues may involve exposing the cells and/or tissues to an effective amount of at least one agonist of GHRH. In some embodiments, the grafted cells and/or tissues may be pancreatic cells. In some embodiments, the grafted cells may be islet cells co-cultured with non-pancreatic cells. In a further embodiment, a method of treating a patient diagnosed with diabetes involves transplanting and/or grafting the islet cells and/or tissues comprising islet cells into a patient, and administering a therapeutically effective amount of at least one agonist of GHRH to the patient. In some embodiments, the islet cells and/or tissues comprising islet cells may be optionally exposed to GHRH and/or at least one agonist of GHRH prior to transplantation into a patient.

Abstract: Disclosed herein are compositions of GHRH agonists and peptides, and methods to treat disorders, such as ischemia and reperfusion injury. In one embodiment, a method of treating a reperfusion injury in a subject in need may involve administering a therapeutically effective amount of at least one GHRH agonist peptide to the subject. In additional embodiment, a method of promoting vasculogenesis in a mammal may involve administering a therapeutically effective amount of at least one GHRH agonist peptide to the subject. In a further embodiment, a method of promoting differentiation of mesenchymal stem cells into endothelial cells may involve contacting mesenchymal stem cells with at least one GHRH agonist peptide.

Abstract: There is provided a novel series of synthetic analogs of hGH-RH(1-29)NH2 (SEQ ID NO: 1) and hGH-RH(1-30)NH2. Of particular interest are those carrying PhAc, N-Me-Aib, Dca, Ac-Ada, Fer, Ac-Amc, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, or CH3—(CH2)10—CO-Ada, at the N-Terminus and ?-Ala, Amc, Apa, Ada, AE2A, AE4P, ?-Lys(?-NH2), Agm, Lys(Oct) or Ahx, at the C-terminus. These analogs inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers, and inhibit the hyperplastic and benign proliferative disorders of various organs, through a direct effect on the cancerous and non-malignant cells. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, result from replacement of various amino acids.

Abstract: Disclosed herein are methods demonstrating that growth-hormone releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-I independent fashion. Following experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4 week period, either placebo (n=14), rat recombinant GH (rrGH, n=8) or JI-38 (n=8; 50 ?g/Kg/day), a potent GHRH-agonist. JI-38 did not elevate serum levels of GH or IGF-I, but markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, circulating GH and IGF-I, but did not offset the decline in cardiac structure and function. Whereas, both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased anti-apoptotic gene expression. Collectively, these findings demonstrate that within the heart, GHRH-agonists can activate cardiac repair following MI.

Abstract: The invention comprises peptidyl analogs that possess agonist or antagonist ghrelin activity, along with therapeutic and non-therapeutic uses thereof.

Abstract: There is provided a novel series of synthetic analogs of hGH-RH(1-29)NH2 (SEQ ID NO: 96) and hGH-RH(1-30)NH2. Of particular interest are those carrying PhAc, N-Me-Aib, Dca, Ac-Ada, Fer, Ac-Amc, Me-NH-Sub, PhAc-Ada, Ac-Ada-D-Phe, Ac-Ada-Phe, Dca-Ada, Dca-Amc, Nac-Ada, Ada-Ada, or CH3—(CH2)10—CO-Ada, at the N-Terminus and ?-Ala, Amc, Apa, Ada, AE2A, AE4P, ?-Lys(?-NH2), Agm, Lys(Oct) or Ahx, at the C-terminus. These analogs inhibit the release of growth hormone from the pituitary in mammals as well as inhibit the proliferation of human cancers, and inhibit the hyperplastic and benign proliferative disorders of various organs, through a direct effect on the cancerous and non-malignant cells. The stronger inhibitory potencies of the new analogs, as compared to previously described ones, result from replacement of various amino acids.

Abstract: Agonists of growth hormone releasing hormone promote islet graft growth and proliferation in patients. Methods of treating patients comprise the use of these agonists.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: Whether the growth hormone (GH)/Insulin-like growth factor 1(IGF-I) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we tested the hypothesis that growth-hormone releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-I independent fashion. Following experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4 week period, either placebo (n=14), rat recombinant GH (rrGH, n=8) or JI-38 (n=8; 50 ?g/Kg/day), a potent GHRH-agonist. JI-38 did not elevate serum levels of GH or IGF-I, but markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, circulating GH and IGF-I, but did not offset the decline in cardiac structure and function.

Abstract: Agonists of growth hormone releasing hormone promote islet graft growth and proliferation in patients. Methods of treating patients comprise the use of these agonists.

Abstract: The invention relates to use of a GH secretagogue (e.g. GRF or an analog thereof) for (1) altering a lipid parameter in a subject; (2) altering a body composition parameter in a subject, (3) treating a condition characterized by deficient or decreased bone formation in a subject (4) improving daytime vigilance and/or cognitive function in a subject, (5) improving a metabolic condition in a subject, (6) improving anabolism in a catabolic condition in a subject, and/or (7) improving and/or reconstituting immune function in a subject.

Abstract: The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Abstract: Disclosed are peptide and peptidomimetic compounds generally according to formula (I) that are useful as GHRP analogs: R1-A1-A2-A3-A4-A5-R2??(I) wherein: A1 is Aib, Apc or Inp; A2 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A3 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A4 is 2Fua, Orn, 2Pal, 3Pal, 4Pal, Pff, Phe, Pim, Taz, 2Thi, 3Thi, Thr(Bzl); A5 is Apc, Dab, Dap, Lys, Orn, or deleted; R1 is hydrogen, (C1-6)alkyl, (C5-14)aryl, (C1-6)alkyl(C5-14)aryl, (C3-8)cycloakyl, or (C2-10)acyl; and R2 is OH or NH2; and pharmaceutical compositions and methods of use thereof.

Abstract: The present invention provides peptidomimetic macrocycles capable of modulating growth hormone levels and methods of using such macrocycles for the treatment of disease.

Abstract: The invention relates to use of a GH secretagogue (e.g. GRF or an analog thereof) for (1) altering a lipid parameter in a subject; (2) altering a body composition parameter in a subject, (3) treating a condition characterized by deficient or decreased bone formation in a subject (4) improving daytime vigilance and/or cognitive function in a subject, (5) improving a metabolic condition in a subject, (6) improving anabolism in a catabolic condition in a subject, and/or (7) improving and/or reconstituting immune function in a subject.

Abstract: Human growth hormone factor (GFR) containing pharmaceutical compositions are described, and more precisely, lyophilized compositions of hGRF stabilized by means of saccharose.

Abstract: Activated fatty acids, pharmaceutical composition compositions including activated fatty acids, methods for using activated fatty acids to treat nephropathy, and methods for preparing activated fatty acids are provided herein.

Abstract: A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: Novel GRF analogs having GRF activity are described herein, as well as uses thereof for example as a GRF receptor agonist, e.g., to induce growth hormone secretion in a subject or biological system.

Abstract: The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Abstract: A method for treating obesity and more particularly a method for treating diet-induced obesity in a subject comprising administering to said subject an isolated unacylated ghrelin peptide as set forth in SEQ ID NO: 1, a fragment thereof or a cyclic fragment thereof such as a cyclic unacylated ghrelin fragment. The method being achievable without affecting the food intake of the subject.

Abstract: The invention relates to use of a GH secretagogue (e.g. GRF or an analog thereof) for (1) altering a lipid parameter in a subject; (2) altering a body composition parameter in a subject, (3) treating a condition characterized by deficient or decreased bone formation in a subject (4) improving daytime vigilance and/or cognitive function in a subject, (5) improving a metabolic condition in a subject, (6) improving anabolism in a catabolic condition in a subject, and/or (7) improving and/or reconstituting immune function in a subject.

Abstract: Novel GRF analogs having GRF activity are described herein, as well as uses thereof for example as a GRF receptor agonist, e.g., to induce growth hormone secretion in a subject or biological system.

Abstract: Disclosed herein are an in situ-forming, bioadhesive hydrogel and the medical uses thereof. Being formed by in situ crosslinking through an enzymatic reaction, the hydrogel has an advantage over conventional bioadhesive hydrogels in terms of biocompatibility. In addition, the in situ-forming bioadhesive hydrogel has excellent biocompatibility and mechanical strength and has excellent tissue adhesiveness thanks to modification with/without dopa derivatives. The hydrogel finds a variety of applications in the biomedical field, including bioadhesives or hemostats, implant substances for tissue regeneration and augmentation, carriers for delivering biologically active materials or drugs, etc.

Abstract: The present invention relates to the use of inclusion bodies as vehicles for therapeutic protein delivery. This method is applicable to the delivery of therapeutic proteins to intracellular locations. In addition, the invention also relates to the administration of a cell or a pharmaceutical composition comprising inclusion bodies formed by therapeutic proteins. These inclusion bodies formed by therapeutic proteins could be used for the treatment of different diseases.

Abstract: One aspect of the current invention is a method of preventing and/or treating arthritis and/or preventing or treating lameness in a subject. Additionally, subject quality of life and welfare, and body condition scores are improved by utilizing methodology that administers the nucleic acid expression construct encoding a GHRH or functional biological equivalent to a subject through a parenteral route of administration. Following a single dose of nucleic acid expression vector, subjects are healthier and effects are demonstrated long term without additional administration(s) of the expression construct.

Abstract: The invention provides methods of extracting a biodegradable polyester with a supercritical fluid effective to obtain a purified biodegradable polyester, such as a purified biodegradable poly(lactide-glycolide) (PLG). The supercritical fluid can be carbon dioxide at an elevated pressure, or can be carbon dioxide with one or more cosolvents. Methods for carrying out stepwise purification of the biodegradable polyester at multiple pressures or multiple temperatures, or both, are also provided. When the polyester is PLG, a purified PLG copolymer is obtained having a narrowed molecular weight distribution with respect to the unpurified polyester. The purified PLG copolymer can have a polydispersity index of less than about 1.7, less than about 2% monomers, and less than about 10% oligomers. The purified PLG copolymer can exhibit a reduced initial burst effect when incorporated into a controlled release formulation such as a flowable implant adapted to be injected into body tissues.

Abstract: The present invention relates to a biopolymer-modified nanocarrier in which chitosan is bound to a water-soluble biocompatible polymer that has been crosslinked via a photo-crosslinkable functional group; wherein the chitosan-modified nanocarrier has a diameter which changes in accordance with changes in temperature, has enhanced skin permeability or cellular uptake and selective delivery to cancer tissue as compared with a bare nanocarrier to which chitosan has not been bound, and exhibits characteristics that are advantageous in photothermal therapy. The chitosan-modified nanocarrier of the present invention exhibits highly superior efficacy as a transdermal carrier, since the skin permeability is enhanced to a significant level as compared with a bare nanocarrier that has no chitosan.

Abstract: The present invention relates biomedically useful compositions containing bioactive agents and biodegradable carbohydrate polyethers that exhibit reverse thermogelation properties in aqueous media. The microstructure structure and properties of the carbohydrate polyethers can be conveniently controlled with respect to functionality, molecular weight, polydispersity index, microstructure and tertiary structure, they can be customized for use in a variety of biomedical applications including drug delivery, cell delivery, surgical procedures and the like.

Abstract: Various nucleic acid-based matrixes are provided, comprising nucleic acid monomers as building blocks, as well as nucleic acids encoding proteins, so as to produce novel biomaterials. The nucleic acids are used to form dendrimers that are useful as supports, vectors, carriers or delivery vehicles for a variety of compounds in biomedical and biotechnological applications. In particular, the macromolecules may be used for the delivery of drugs, genetic material, imaging components or other functional molecule to which they can be conjugated. An additional feature of the macromolecules is their ability to be targeted for certain organs, tumors, or types of tissues. Methods of utilizing such biomaterials include delivery of functional molecules to cells.

Abstract: Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, active compound, and optional flavoring agent; formulation II: aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation III: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

Abstract: The invention relates to use of a GH secretagogue (e.g. GRF or an analog thereof) for (1) altering a lipid parameter in a subject; (2) altering a body composition parameter in a subject, (3) treating a condition characterized by deficient or decreased bone formation in a subject (4) improving daytime vigilance and/or cognitive function in a subject, (5) improving a metabolic condition in a subject, (6) improving anabolism in a catabolic condition in a subject, and/or (7) improving and/or reconstituting immune function in a subject.

Abstract: A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Abstract: A transmembrane fusion protein including ubiquitin or a ubiquitin-like protein, a membrane translocation sequence linked to the C-terminus of the ubiquitin or ubiquitin-like protein, and a biologically active molecule linked to the C-terminus of the membrane translocation sequence is disclosed herein. A polynucleotide encoding the transmembrane fusion protein, a recombinant expression vector including the polynucleotide sequence, a cell transformed by the recombinant expression vector, and a method of delivering the biologically active molecule into a cell using the transmembrane fusion protein are also disclosed.

Abstract: Compositions and methods for mucosal delivery of agents are provided. The compositions are intended for administration to mucosal surface, such as oral, gastrointestinal and nasal mucosa. The compositions provided contain one or more mucoadhesive proteins and an agent to be delivered. Methods for delivery of agents using the compositions provided herein are also provided.