Abstract: A first aspect of the invention relates to a polypeptide compound of formula (I): A-C-B??(I) wherein: A is the A chain of insulin or a functional derivative or variant thereof; B is the B chain of insulin or a functional derivative or variant thereof; C is a peptide of the formula: (X1)p-(X2)n-(X3)q wherein: each X1 and X3 is independently a basic amino acid; each X2 is independently a natural or unnatural amino acid; p is 1 or 2; q is 0, 1 or 2; n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising said polypeptide compound, and therapeutic uses thereof. Another aspect relates to the use of said polypeptide compounds in the preparation of insulin and derivatives thereof.

Abstract: Disclosed are a bifunctional peptide having the capability to permeate cells and the capability to regenerate muscles and the use thereof. Advantageously, the bifunctional peptide has a function of regenerating muscle cells and thus is useful for the prevention or treatment of diseases affecting muscle regeneration, and additionally has the capability to permeate cells and thus eliminates the necessity to adhere an additional peptide or add other agent or drug for cell permeation of the peptide, thereby finally exerting an efficient muscle generation effect. Thus, the bifunctional peptide can be easily applied to various surgical regenerative treatments and can shorten the treatment period.

Abstract: The present disclosure describes analog conotoxin peptides of the ?-contoxin peptide RgIA. These analog conotoxin peptides block the ?9?10 subtype of the nicotinic acetylcholine receptor (nAChR) and can be used for treating pain, inflammatory conditions, inflammation, and/or cancer.

Abstract: The present invention relates to Pyrazolopyrimidinone compounds as PDE5 inhibitors with better IC50 value, good in vivo efficacy and PK profile and a process for the preparation thereof. The present invention covers the pyrazolo pyrimidinone based compounds that have been designed, synthesized and screened for PDE5 inhibitory activity and its PDE5 inhibitory potential is provided in this invention. These designer compounds have shown nanomolar potency when screened for PDE5 inhibitory activity and also shown better in vivo efficacy. These compounds can be used in the treatment of male erectile dysfunction or in the treatment of impotence.

Abstract: A method is described for treating a subject having acute heart failure (AHF) by measuring PERLECAN levels in the subject. The PERLECAN level in the subject is used to determine risk of mortality within one year for the subject. Treatment is selected on the basis of the outcome of the assay.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: Isolated polypeptides are disclosed comprising an amino acid sequence encoding a monomer of a fibrous polypeptide attached to a heterologous polysaccharide binding domain. Composites comprising same, methods of generating same and uses thereof are all disclosed.

Abstract: The present invention relates to the use of obestatin, or to the nucleotide sequence that codes for same, as an in vitro myogenic agent, and for the production of a drug for muscle regeneration, preferably for musculoskeletal regeneration, thus being useful in the treatment and/or prevention of degenerative or genetic diseases or of lesions that present with muscle damage.

Abstract: Methods of regulating uterine contractions using light are described. An exemplary method of regulating uterine contractions comprises suppressing a nocturnal endogenous melatonin level of a pregnant female experiencing uterine contractions by exposing the pregnant female during nighttime to a light source emitting visible light.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: A method for treating prostate related diseases in a subject, the method comprising i) optionally administering to subject an initial boost dose of one or more active substances and/or prodrugs, and ii) administering locally into the prostate a controlled release pharmaceutical composition comprising one or more active substances in a biodegradable ceramic carrier. The biodegradable hydrating ceramic may be selected from the group consisting of non-hydrated or hydrated calcium sulphate, calcium phosphate, calcium carbonate, calcium fluoride, calcium silicate, magnesium sulphate, magnesium phosphate, magnesium carbonate, magnesium fluoride, magnesium silicate, barium sulphate, barium phosphate, barium carbonate, barium fluoride, barium silicate, or mixtures thereof. In a specific embodiment, the biodegradable hydrating ceramic is non-hydrated or hydrated calcium sulphate.

Abstract: The invention provides a method for treating or preventing preterm labor in pregnant female subjects. The method comprises the step of administering a therapeutically effective amount of a Toll-like Receptor 9 antagonist sufficient to prevent the activation of Toll-like Receptor 9 by fetal DNA. The invention further provides compositions comprising a Toll-like Receptor 9 antagonist for use in the methods of the invention. The compositions and methods of the present invention enhance gestation and therefore improve neonatal morbidity and mortality.

Abstract: The present invention relates generally to compositions and methods comprising histidyl-tRNA synthetase polypeptides or other specific blocking agents for the treatment autoimmune diseases and other inflammatory diseases, including those related to Jo-1 antibodies.

Abstract: The invention discloses use of a pharmaceutical composition for slow-release delivery of a bioactive agent, comprising mixing the bioactive agent with a partially hydrophobic chitosan solution at a low pH and delivering the hydrogel at a physiological pH to transform the hydrogel to a solid complex for releasing the bioactive agent. The partially hydrophobic chitosan is characterized by presence of alternating charges of protonated amine groups and hydrophobic side groups.

Abstract: A process for producing an insulin type peptide, for example a relaxin, involving oxidizing a methionine residue on a B-chain having cysteine residues and combining the B chain with an A chain having cysteine residues to form a peptide having intermolecular disulphide links and biological activity. Novel synthetic relaxin 1 and methionine oxidized relaxins and Met(O) B-chains having enhanced solubility are disclosed.

Abstract: The invention relates to relatively short peptides (termed ?-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.

Abstract: An enriched conglutin-? protein extract from lupin seeds having a % by weight of conglutin-? between 10 and 30%, or a conglutin-? protein, or functional derivatives thereof for use as a medicament, as food integrator or diet supplement or integrator.

Abstract: The present invention relates to the use of three-dimensional microrod scaffolds for the temporal release of growth factors useful in tissue regeneration, engineering and treatment of disorders.

Abstract: The present invention provides a humanized recombinant uricase and mutants thereof, wherein the humanized recombinant uricase is a chimeric protein which comprises amino acids of non-human mammal uricase and amino acids of human uricase. The humanized recombinant unease and mutants thereof have reduced immunogenicity in human, and can be used for the treatment of hyperuricemia and gout.

Abstract: A biologic intervention method and apparatus generates a persistent modification to an AV node that is physiologically stable after the agent has matured but is alterable with subsequent application of an agent. Specifically, the generic agent is used to modulate a node in a cardiac conduction system including rate control using one and a combination of a family of K+ channel or equivalent. Specifically, the channel is implemented to slow conduction by generating an outward current during optimization of action potential and repolarization phase thus decreasing the current that is available to excite downstream cells. A Kv 1.3 channel, for example, may be used as the biologic channel. The invention enables reversal of the modulation or adjustment for various heart rates (BPM) based on medical and patient-specific needs.

Abstract: The present invention relates to compositions and methods for treating and preventing cocaine addiction. In particular, the present invention provides mutated cocaine esterase proteins for use in treating and preventing cocaine addiction.

Abstract: Systems and methods of tissue remodeling or altering a surface of a skin of a patient are provided. A method includes increasing myostatin activity in a target tissue. Methods can include increasing myostatin activity in a target tissue in addition to various tissue remodeling techniques, including cryogenic cooling of target tissue for tissue remodeling.

Abstract: The present invention provides splice variants of myostatin that promote muscle growth, and include polynucleotides and polypeptide sequences, constructs comprising the sequences and compositions for regulating muscle growth and treating diseases associated with muscle tissue. The splice variants include the consensus sequence X1 I F L E X2 X3 X4 Q X5 C S I L X6 X7 X8 X9 X10 wherein X1 is I or L, X2 is V or L, X3 is Y, C, G or S, X4 is I or F, X5 is F or L, X6 is G or E, X7 is E or V, X8 is A or T, X9 is A or V and X10 is absent, F or L. The present invention also provides for the use of the present sequences in identifying animals with altered muscle mass, and for use in selective breeding programs to produce animals with altered muscle mass.

Abstract: A fusion protein comprising at least one IGF1 variant component and a fusion component (F), and, optionally, a signal sequence, exhibits improved stability relative to the native IGF1 or IGF2 polypeptide. The fusion component (F) may be a multimerizing component, such as an immunoglobulin domain, in particular, the Fc domain of IgG or a heavy chain of IgG. IGF1 variants were shown to have improved ability to increase muscle mass in a subject suffering from muscle atrophy caused by cachexia, immobilization, aging, chronic disease, cancer, hereditary condition, an atrophy-causing agent, and the like. IGF1 variants are also effective in decreasing blood glucose in a subject suffering from diabetes or hyperglycemia.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: Described are methods of treating and preventing conditions associated with a loss of elastic fibers. Also provided herein are methods of screening for agents useful in treating such conditions, and animal models of conditions associated with a loss of elastic fibers.

Abstract: The invention pertains to a method of reducing scar formation during wound healing by administering a phosphatidylserine-binding compound, in particular an annexin, to a subject in need thereof. The healing wound may be a skin damage, but it may also be a myocardium e.g. which is at risk of suffering or is recovering from a heart failure.

Abstract: Provided herein are methods of decreasing glial fibrillary acidic protein (GFAP) levels in a cell. Such methods include administering an effective amount of a GFAP lowering compound to the cell. Also provided are compounds useful for the treatment of Alexander disease in subjects at risk of or diagnosed with Alexander disease and methods for the identification of such compounds.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a bioactive agent for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for drug delivery.

Abstract: Calcium channels can be regulated by natural gamma proteins. Herein we disclose embodiments of compositions and methods, particularly involving short peptides which are capable of regulating calcium channel function. Certain short peptides which can inhibit calcium current have structural features from the first transmembrane domain of gamma6 such as a GxxxA motif and adjoining aliphatic residues. In embodiments the peptide compositions and methods are capable of selective efficacy for low voltage-activated calcium channels, such as LVA channel Cav3.1, versus high voltage-activated channels.

Abstract: The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.

Abstract: Botulinum toxin, a well know systemic poison, produces favorable therapeutic effect by virtue of regionally attaching to nerves within the myoneural junction and possibly other tissues in a target region of a particular tissue. The present invention provides compositions of botulinum toxin and a sequestration agent that increase sequestration and delivery of the botulinum toxin to neural and associated tissues, as compared with available formulations of botulinum toxins, and thereby produce a beneficial clinical effect. The sequestration agents of the present invention include proteins, lipids and carbohydrates. A preferred composition of the present invention comprises a botulinum toxin and an albumin. The present invention also provides methods of treating neuromuscular diseases and pain using the disclosed compositions and methods of making the disclosed compositions.

Abstract: The present invention relates to a modified plasminogen activator inhibitor type-1 (PAI-1) molecule that displays an increased in vivo half-life of the active form of PAI-1, but is deficient in one or more functional activities as compared to the wild-type PAI-1 protein. The modified PAI-1 molecule that displays an increased half-life further displays at least one of the following functional characteristics: (i) decreased binding activity to at least one of the following molecules: urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and vitronectin (Vn); and (ii) decreased specific activity against at least one of the following molecules: uPA, tPA and Vn. The invention further relates to pharmaceutical compositions comprising modified PAI-1 molecules and methods of using these pharmaceutical compositions for treatment.

Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

Abstract: The invention discloses bioactive nanoparticles composed of chitosan, poly-glutamic acid, and diethylenetriaminepentaacetic acid for use in radionuclide decorporation during radiological emergency. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.

Abstract: Described are methods of treating and preventing conditions associated with a loss of elastic fibers. Also provided herein are methods of screening for agents useful in treating such conditions, and animal models of conditions associated with a loss of elastic fibers.

Abstract: Disclosed is a method for removing endotoxin from proteins. Also disclosed are products made by using the method. The method may be used, for example, to produce endotoxin-free lactoferrin. Bovine milk-derived lactoferrin may be produced in commercial quantities by the method, and endotoxin-free bovine lactoferrin may be used for a variety of therapeutic uses, including improving wound healing.

Abstract: The invention relates to the transdermal application of oligopeptides for reducing synaptic transmission in tissues of an animal. In one aspect, this invention relates to compositions comprising an oligopeptide and optionally a carrier comprising a positively charged “backbone” having positively charged branching or “efficiency” groups, as described herein. Most preferably the positively charged carrier is a long-chain positively charged polypeptide or a positively charged nonpeptidyl polymer, for example, a polyalkyleneimine. The invention further relates methods for producing a biologic effect of reducing synaptic transmission in a tissue by topically applying an effective amount of such a composition, preferably to the skin, of a subject or patient in need of such treatment.

Abstract: A nonaqueous, single-phase vehicle that is capable of suspending an active agent. The nonaqueous, single-phase vehicle includes at least one solvent and at least one polymer and is formulated to exhibit phase separation upon contact with an aqueous environment. The at least one solvent may be selected from the group consisting of benzyl benzoate, decanol, ethyl hexyl lactate, and mixtures thereof and the at least one polymer may be selected from the group consisting of a polyester, pyrrolidone, ester of an unsaturated alcohol, ether of an unsaturated alcohol, polyoxyethylenepolyoxypropylene block copolymer, and mixtures thereof. In one embodiment, the at least one solvent is benzyl benzoate and the at least one polymer is polyvinylpyrrolidone. A stable, nonaqueous suspension formulation that includes the nonaqueous, single-phase vehicle and an active agent, and a method of forming the same, are also disclosed.

Abstract: The invention relates to relatively short peptides (termed ?-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.

Abstract: The invention relates to novel conopeptides and/or novel uses of conopeptides. The conopeptides of the invention are analogs of ?-Conotoxin MII that are selective for ?6-containing nAChRs as described herein.

Abstract: A method for treating uterine disorders, including hyperplasic, hypertonic, cystic and/or neoplastic uterine gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted uterine tissue.

Abstract: The disclosure pertains to methods of reducing decompensation through acute intervention including in subjects afflicted with acute decompensated heart failure. Particularly, the disclosure provides methods for treating acute cardiac decompensation by administering a pharmaceutically effective amount of relaxin.

Abstract: A polypeptide having the amino acid sequence as set forth in SEQ ID NO: 2, 4, or 6, a DNA encoding the same, and an antibody against said polypeptide, and the use thereof. The above amino acid sequence has a homology with chondromodulin-I that has an effect of controlling the growth and differentiation of chondrocytes and inhibiting angiogenesis.

Abstract: Calcium channels in a variety of tissues may contain different subunits, including several different ? (gamma) subunits. We report studies regarding structural features of certain gamma subunits, for example the N-terminal first transmembrane domain (TM1) of the subunit ?6. We disclose that certain structural motifs, for example a GxxxG-like structural motif as described herein, can mediate subunit function for calcium channels. A particular peptide motif that has been identified as significant for the ability to mediate a decrease in calcium current is GxxxA. Compositions and methods are disclosed which are useful in modifying calcium regulation in mammalian cells. In various embodiments, calcium current is modified.

Abstract: Nanoparticulate compositions comprising at least one poorly soluble MAP kinase inhibitor and at least one surface stabilizer are described. The nanoparticulate compositions have an average particle size of less than about 2000 nm. The invention also describes methods of making and using such compositions.

Abstract: A composition of matter for an analgesia and its method of use is disclosed. The method of use is for the treatment of chronic pain, especially to the treatment of heretofore intractable pain as associated with advanced cancer. The pain associated with neurological conditions, rheumatoid arthritis, viral infections and lesions is also contemplated. The method includes administering to a host an alpha-neurotoxin that is characterized by its ability to blocking of the action of acetylcholine at nicotinic acetylcholine receptors.