Abstract: The invention provides methods for treating inflammatory diseases by administering to the subject an effective amount of an agent that provides alpha B-crystallin activity, where the dose is effective to suppress or prevent initiation, progression, or relapses of disease, including the progression of established disease. In some embodiments, the methods of the invention comprise administering to a subject having a pre-existing inflammatory disease condition, an effective amount of alpha B-crystallin protein, to suppress or prevent relapses of the disease.

Abstract: Nitration shielding peptides that reduce or prevent nitration of a protein of interest are disclosed. The peptide can serve as molecular sink for nitrating agents, block access of the nitrating agents to the target tyrosine on the protein of interest, serve as substrate for the nitrating agent (i.e., provide an alternative nitratable tyrosine residue), provide a nitrating agent neutralizing moiety such as antioxidant, or a combination thereof. The nitration shielding peptide can be a fusion protein that includes one or more additional domains such a protein transduction domain, a targeting signal, a purification tag, or any combination thereof. Exemplary nitration shielding peptides for reducing nitration of RhoA and PKG-1?, and methods of use thereof for treating pathologies, disease, and disorders associated with nitration of RhoA and PKG-1?, respectively are also provided.

Abstract: An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3?UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B/X)R)2XB, where R is arginine; B is ?-alanine; and each X is —C(O)—(CH2)n—NH—, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and/or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.

Abstract: According to a first aspect the invention relates to the use of fumaric acid derivatives selected from the group consisting of dialkyl fumarates, monoalkyl hydrogen fumarates, fumaric acid monoalkyl ester salts, fumaric acid monoamides, monoamido fumaric acid salts, fumaric acid diamides, monoalkyl monoamido fumarates, carbocyclic and oxacarbocyclic oligomers of these compounds and mixtures thereof for preparing a drug for the treatment or prevention of cardiac insufficiency, in particular left ventricular insufficiency, myocardial infarction and angina pectoris.

Abstract: This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a WAP domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.

Abstract: The invention is in the field of molecular medicine. It provides antagonistic compounds for frizzled-1 and/or frizzled-2 receptors, which may be useful in molecular imaging of the wound healing process after myocardial infarction and in therapeutic intervention into wound healing after remodeling of the heart, thereby ameliorating the consequences of myocardial infarction. The invention provides a method for antagonizing frizzled-1 or frizzled-2 receptors, wherein the receptor is contacted with a composition comprising a linear fragment of Wnt3(a) or Wnt5a or a functional analogue thereof, which comprises at least one cysteine residue, one threonine residue, one aspartic acid residue and one glycine residue.

Abstract: Described herein are methods and compositions related to the discovery that the Follistatin-like 1 protein (Fstl-1) has metabolic and cardioprotective effects in vivo. Fstl-1 and portions and derivatives or variants thereof can be used to treat or prevent metabolic diseases or disorders and to treat or prevent cardiac damage caused by interrupted cardiac muscle blood supply.

Abstract: Methods of treating atrial arrhythmia include administering an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof, such that the at least one antiarrhythmic pharmaceutical agent first enters the heart through the pulmonary vein to the left atrium. Other methods of treating atrial arrhythmia include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. An amount of the at least one antiarrhythmic pharmaceutical agent may peak in the coronary sinus of the heart at a time ranging from 10 seconds to 30 minutes from initiation of the administering. Unit doses, aerosols, and kits are also contemplated.

Abstract: The invention relates to composition comprising a pharmaceutically effective amount of one or more functional vasoactive intestinal peptide (VIP) fragments, and the use of those compositions in the treatment of fibrosis, hypertension and other disorder.

Abstract: This invention provides a method of treating a disorder of a subject's heart involving loss of cardiomyocytes which comprises administering to the subject a composition comprising an amount of a human stromal derived factor-1 and an amount of a human granulocyte-colony stimulating factor, the composition being administered in an amount effective to cause proliferation of cardiomyocytes within the subject's heart so as to thereby treat the disorder. This invention also provides a method of treating a subject suffering from a disorder of a tissue involving loss and/or apoptosis of cells of the tissue which comprises administering to the subject a composition comprising an amount of an agent which induces phosphorylation and/or activation of protein kinase B, or an agent which induces phosphorylation and/or activation of an extracellular signal-regulated protein kinase, or an agent which induces activation of CXCR4.

Abstract: Maternal adaptive immunity conveys temporary humoral immune protection to neonates. The disclosure demonstrates the influence of the in utero environment on adult atherosclerosis and provides evidence for persistent effects of maternal immunization on adult immune responses. The disclosure provides methods and compositions useful for immunization and more particularly for actively modulating the fetal programming of the immune system for the purpose of preventing or treating immune-modulated diseases. The disclosure also provides interventions to protect offspring and immunized subjects against insulin resistance.

Abstract: A method is provided for treatment of a condition mediated by Nox2 in a patient. The method comprises administering to the patient by inhalation a polypeptide as described herein, able to inhibit superoxide production by Nox2. Conditions treatable in this manner include, without limitation, one or more of: right ventricular hypertrophy; pulmonary hypertension; acute lung injury; obstructive sleep apnea; ischemia/reperfusion injury in the lung; pulmonary fibrosis; an obstructive lung disorder such as Chronic Obstructive Pulmonary Disease (COPD), asthma, cystic fibrosis and emphysema; and atherosclerosis.

Abstract: The present invention provides novel PAR lderived cytoprotective oligopeptides or polypeptides which typically contain at least the first 4 N-terminal residues that are substantially identical to the corresponding N-terminal residues of Met1-Arg46 deleted human PAR 1 sequence. These cytoprotective oligopeptides or polypeptides are capable of activating PAR 1 and promoting PAR 1 cytoprotective signaling activities. The invention also provides engineered cells or transgenic non-human animals which harbor in their genome an altered PAR 1 gene that is resistant to cleavage at Arg41 and/or Arg46 residues. Additionally provided in the invention are methods of screening candidate compounds to identity additional cytoprotective compounds or cytoprotective proteases. The invention further provides therapeutic use or methods of employing a PAR 1 derived cytoprotective oligopeptide or polypeptide to treat conditions associated with tissue injuries or undesired apoptosis.

Abstract: The present inventors investigated the effects of anti-IL-6 receptor antibodies on improving the condition of infarcted areas in myocardial infarction, and on suppressing left ventricular remodeling after myocardial infarction. As a result, the administration of anti-IL-6 receptor antibodies significantly suppressed the increase of MPO activity in the infarcted area and suppressed myocardial MCP-1 expression in both the infarcted area and the non-infarcted area. Furthermore, echocardiography and histological examinations revealed that cardiac hypertrophy is also suppressed.

Abstract: This application describes compounds acting as, for example, ?-arrestin effectors and uses thereof, in, for example, the treatment of chronic and acute cardiovascular diseases.

Abstract: The present invention relates generally to the novel use of cardioprotective incretin compounds (CICs) such as GLP-1 and exendin and agonists thereof, including analogs and derivatives to prevent, delay, attenuate, or ameliorate cardiac remodeling. The present invention relates to methods for using CICs for the treatment of conditions associated with cardiac remodeling. The present invention further relates to methods for using CICs for the reduction of the risk or severity of congestive heart failure.

Abstract: The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13??I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor.

Abstract: The present invention relates to an inhibitor of the Rho guanine nucleotide exchange factor 12 (RhoGEF12) or an inhibitor of an activator of RhoGEF12 for use in the prevention and/or treatment of heart failure associated with cardiac hypertrophy and/or cardiac fibrosis and diseases associated therewith. Further, it relates also a method of treatment and methods for identifying inhibitors of Rho guanine nucleotide exchange factor 12 (RhoGEF12) or inhibitors of an activator of RhoGEF12.

Abstract: The present invention provides a method of treating, ameliorating or preventing myocardial ischemia/reperfusion injury in a subject in need thereof, by administering to the subject a therapeutically effective amount of an annexin A1 short peptide (ANXA1sp).

Abstract: Disclosed are methods of treating kidney disease, infectious or inflammatory diseases, acute kidney injury and hypertension by administering a (pro)renin receptor (PRR) antagonist. In some instances the PRR antagonist is a polypeptide. The PRR antagonist can be a polypeptide having at least 70% identity to the amino acid sequence set forth in SEQ ID NO:2. Also disclosed are methods of decreasing proteinuria and methods of promoting wound healing by administering a PRR antagonist.

Abstract: The present invention relates to C5 binding polypeptides, comprising a C5 binding motif, BM, which motif consists of an amino acid sequence selected from i) EX2X3X4A X6X7EID X11LPNL X16X17X18QW X21AFIX23X26LX28D, and ii) an amino acid sequence which has at least 86% identity to the sequence defined in i), wherein the polypeptide binds to C5. The present invention moreover relates to C5 binding polypeptides for use in therapy, such as for use in treatment of a C5 related condition, and to methods of treatments.

Abstract: The present invention relates to novel peptidic inhibitors of signal transmission from G?s- to G?i-coupled receptor cascades and methods for their use.

Abstract: The present invention relates to nociceptin peptide mimetics that have ?-helical structures and bind to and modulate the opioid receptor-like-1 (ORL-1) receptor. The peptide mimetics are constrained cyclic nociceptin analogs which have either agonist or antagonist activity. Pharmaceutical compositions comprising the nociceptin peptide mimetics and methods of treating or preventing a disease or condition ameliorated by modulating the ORL-1 receptor are also described.

Abstract: Provided herein are pharmaceutically acceptable sodium nitrite and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-volatile organic carbon in a sodium nitrite-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium nitrite. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium nitrite.

Abstract: An apolipoprotein formulation is provided at a fixed dosage that is efficacious in the prophylactic and/or therapeutic treatment of diseases or conditions including, but not limited to cardiovascular disease, acute coronary syndrome, atherosclerosis, unstable angina pectoris, and myocardial infarction. More particularly, the fixed dosage apolipoprotein formulation displays relatively reduced inter-patient variability compared to weight-adjusted dosages. Typically, the apolipoprotein formulation is a reconstituted high density lipoprotein formulation comprising ApoA1, one or more lipids such as phosphatidylcholine, sphingomyelin and/or phosphatidylglycerol and, optionally, a detergent such as cholate at a level that does not induce liver toxicity.

Abstract: This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents.

Abstract: The invention relates to composition comprising a pharmaceutically effective amount of one or more functional vasoactive intestinal peptide (VIP) fragments, and the use of those compositions in the treatment of fibrosis, hypertension and other disorder.

Abstract: The invention relates to the use of a cyclic undecapeptide, with the structure in formula (I), for the preparation of a medicament for administration during a myocardial ischaemic event.

Abstract: The present invention provides methods, compositions, and systems for treating a subject at risk for, with, or suspected of having, myocardial ischemia using hepatocyte secretory factors (e.g., AGP2, BMPER, FGF21, NRG4, and/or TFF3) or using factors that promote liver cell migration to ischemic myocardial tissue (e.g., IL-6 and/or MMP-2).

Abstract: This application describes a family of compounds acting as ?-arrestin effectors. Such compounds may provide significant therapeutic benefit in the treatment of chronic and acute cardiovascular diseases.

Abstract: The present invention provides the use of formulation with surfactant protein-D (SP-D) in the modulation of activity of human eosinophils derived from hypereosinophilic patients to an increased activation state and increased apoptosis. Accordingly the utility of the invention can be extended in human subjects in resolution of eosinophilic inflammations in related diseases and disorders like neuromuscular and respiratory diseases with eosinophilia other than airway-hyperresponsiveness, allergy and asthma, hypereosinophilic leukemias, hypereosinophilc syndromes (rare hematological diseases), skin diseases like eosinophilia-Myalgia syndrome, eosinophilic fascitis, capillary leak syndromes (IL-2), Churg-Strauss syndrome, toxic oil syndrome, parasitosis, etc., where a large number of stimulated eosinophils accumulate and release a series of growth factors, cytokines, chemokines, bioactive lipid mediators, toxic oxygen metabolites.

Abstract: This invention provides a composition for heart disease comprising extracts from raw herbs of 80.0-97.0% Radix Salviae Miltorrhizae, 1.0-19.0% Panax Notoginseng and 0.1-1.0% Borneol and its active ingredients. This invention also provides a method for preparing said composition and the active ingredients of the composition. Finally, this invention provides various uses of said compositions and the active ingredients.

Abstract: The present invention relates to method of treating arrhythmias or heart failure comprising co-administration of a late INa inhibitor and a CAMK II inhibitor.

Abstract: Therapeutic peptides having guanylyl cyclase C agonist activity are disclosed. The therapeutic peptides are analogues of the E. coli STa peptide with non-natural amino acid, isosteric or D-amino acid substituents. The therapeutic peptides are useful in the treatment of chronic ideopathic constipation, inflammatory bowel disease, and other diseases. Pharmaceutical compositions comprising the therapeutic peptides are also disclosed.

Abstract: A peptide composition is provi'deo!which specifically inhibits the ability of ? protein kinase C (?PKC) to phosphor/late pyruvate dehydrogenase kinase (PDK) under ischemic conditions. The peptide composition is useful for treating or reducing tissue damage resulting from ischemia and/or reperfusion.

Abstract: The present invention relates to veterinary decorin compositions and methods of their production.

Abstract: Potent compounds having combined antioxidant, anti-inflammatory, anti-radiation and metal chelating properties are described. Short peptides having these properties, and methods and uses of such short peptides in clinical and cosmetic applications are described.

Abstract: The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-related diseases, metabolic diseases, coagulation disorders, and growth hormone-related disorders and conditions.

Abstract: The present disclosure provides method of generating cardiomyocytes from post-natal fibroblasts. The present disclosure further provides cells and compositions for use in generating cardiomyocytes.

Abstract: This invention provides novel peptides and methods to prevent, control, and treat an inflammation, cancer and other disorders, particularly of the gastrointestinal tract and the lung by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound selected from i) 5-aminosalicyclic acid (5-ASA) or a derivative or a pharmaceutically acceptable salt thereof; ii) mercaptopurine; or iii) an anti-TNF therapy.

Abstract: The present disclosure provides peptides and constructs that inhibit mitochondrial fission, and compositions comprising the peptides or constructs. The present disclosure provides methods of reducing abnormal mitochondrial fission in a cell. Also provided are methods for designing and validating mitochondrial fission inhibitor constructs and peptides, including but not limited to, evaluating the effects of the constructs and peptides on Drp1 GTPase activity, binding of Drp1 to Fis1, reduction of mitochondrial damage, reduction in cell death, inhibition of mitochondrial fragmentation in a cell under pathological conditions, and reduced loss of neurites in primary dopaminergic neurons in a Parkinsonism cell culture.

Abstract: This application relates to methods of predicting susceptibility or likelihood of a clinically-relevant mannose-binding lectin (MBL)-deficient subject to develop a cardiovascular disease and/or cardiodiabetes. The methods include measuring MBL mass or concentration and, optionally, measuring MBL activity, at least one other biomarker and/or genotyping of MBL gene and its promoters; combining the information obtained into a calculated MBL-inclusive index score that involves mathematical transformation; and assigning a risk of cardiadiabetic status and clinical endpoints based on the determination and comparison of the MBL inclusive index to reference values from a population.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with myocardial infarction. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: Bioscaffoldings formed of hydrogels that are crosslinked in situ in an infarcted region of the heart (myocardium) by a Michael's addition reaction or by a disulfide bond formed by an oxidative process are described. Each of the bioscaffoldings described includes hyaluronan as one of the hydrogel components and the other component is selected from collagen, collagen-laminin, poly-1-lysine, and fibrin. The bioscaffolding may further include an alginate component. The bioscaffoldings may have biofunctional groups such as angiogenic factors and stem cell homing factors bound to the collagen, collagen-laminin, poly-1-lysine, or fibrinogen hydrogel component. In particular, the biofunctional groups may be PR11, PR39, VEGF, bFGF, a polyarginine/DNA plasmid complex, or a DNA/polyethyleneimine (PEI) complex. Additionally, the hydrogel components may be injected into the infarct region along with stem cells and microspheres containing stem cell homing factors.

Abstract: According to the embodiments described herein, a series of biological materials for treatment/therapy of DMD and/or BMD through the recovery of sarcolemmal nNOS is provided. The biological material comprises the complete dystrophin repeats R16 and R17 or certain domains, sections, or fragments of the dystrophin repeats R16 and R17. In some aspects, such domains, sections, or fragments may be selected from sequence motifs including dystrophin R17 ?1 helix, ?2 and ?3 helices of both R16 and R17, or a combination thereof.

Abstract: This application describes a family of compounds acting as ?-arrestin effectors. Such compounds may provide significant therapeutic benefit in the treatment of chronic and acute cardiovascular diseases.

Abstract: The present invention provides an agent capable of inhibiting MMP-2 specifically. Disclosed is a fusion molecule composed of a ?-amyloid precursor protein molecule-derived domain having an activity of selectively inhibiting matrix metalloproteinase-2 and a tissue inhibitor of metalloproteinase capable of binding to latent matrix metalloproteinase. Also disclosed are a pharmaceutical composition, a cancer metastasis and/or angiogenesis inhibitor, a therapeutic and/or prophylactic for cardiovascular diseases, and a matrix metalloproteinase-2 inhibitor, each of which comprises the fusion molecule.

Abstract: The invention relates to methods of promoting the expression of pro-angiogenic factors and decreasing the expression of anti-angiogenic and fibrotic factors in a cell, as well as the treatment of cardiomyopathy and wounds.

Abstract: Potent compounds having combined antioxidant, anti-inflammatory, anti-radiation and metal chelating properties are described. Short peptides having these properties, and methods and uses of such short peptides in clinical and cosmetic applications are described.

Abstract: Provided are methods for the treatment of disease and promotion of healing that include providing a therapeutically effective amount of a mammalian antimicrobial peptide (AMP) or analog thereof, in particular a cathelicidin or cathelicidin fragment or cathelicidin analog, thereby treating the disease in the subject in need thereof. Also provided are specific analogs or fragments of cathelicidin that function as agonists, as do endogenous cathelicidins, or as either dominant negatives or as inhibitors to endogenous cathelicidin or to other endogenous AMPs or that compete with pro-inflammatory agents or fragments of AMPs on cognate receptors without inducing disease.