Abstract: The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: Peptides are provided consisting of L- and/or D-amino acids and combinations thereof, which affect myeloid cells by action on the triggering receptors expressed on myeloid cells (TREMs), including TREM-1 and TREM-2. The peptides act on the TREM/DAP-12 signaling complex. Also provided are lipid and sugar conjugated peptides comprising L- or D-amino acids. A method is provided of designing the peptides and lipid- and/or sugar-conjugated peptides comprising L- or D-amino acids. The disclosure relates to the therapy of various myeloid cell-related disease states involving the use of these peptides and compounds. The peptides and compounds are useful in the treatment and/or prevention of a disease or condition where myeloid cells are involved or recruited. The peptides of the present invention also are useful in the production of medical devices comprising peptide matrices (for example, medical implants and implantable devices).

Abstract: Provided herein are compositions and methods for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival. This in turn reduces or prevents tissue necrosis and death.

Abstract: The present invention provides peptide-based peroxidase inhibitors having the formula AA1-AA2-AA3, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AA2 is a redox active amino acid, and AA3 is an amino acid possessing a reducing potential such that AA3 is capable of undergoing a redox reaction with a radical of amino acid AA2 or a retro or retro-inverso analog thereof. The result of such a combination is a highly effective inhibitor of peroxidase activity that has potent anti-inflammatory properties in widely diverse models of vascular disease and injury. Exemplary tripeptides effectively inhibit peroxidase mediated LDL oxidation, increase vasodilation in SCD mice, inhibit eosinophil infiltration and collagen deposition in asthma mice, inhibit acute lung injury, and decrease ischemic injury of the heart.

Abstract: A method of reducing damage to cells and tissue caused by an ischemic or hypoxic event is disclosed. The method includes administering to the cell or tissue, either in vivo or ex vivo, ??RACK peptide. The peptide can be administered before, during or after the ischemic or hypoxic event.

Abstract: The present invention provides an HDL comprising an agent selected from the group consisting of antiproteases, antixoxidants, antimitotics, anti-apoptotic agents and agents involved in the iron metabolism for use as a medicament.

Abstract: Disclosed are methods of reducing the incidence of oxidative stress in infants, toddlers, and children using nutritional compositions including human milk oligosaccharides. The nutritional compositions including the human milk oligosaccharides are effective at reducing inflammation and the incidence of inflammatory diseases.

Abstract: A method of inducing a protective response against ischemic tissue damage is carried out by administering to subject a composition comprising an HASF polypeptide. The composition is administered prior to an ischemic event such as myocardial infarction to reduce tissue damage associated with such an event.

Abstract: A conjugate which comprises a cyclosporin moiety of formula (I) linked to one or more mitochondrial targeting groups, or a pharmaceutically acceptable salt thereof: wherein: A represents or, B represents methyl or ethyl, one Of R1 and R1 represents hydrogen and the other represents methyl, R2 represents ethyl or isopropyl, R3 represents hydrogen or methyl, and R4 represents —CH2CH(CH3)CH3, —CH2CH(CH3)CH2CH3, —CH(CH3)CH3 or —CH(CH3)CH2CH3.

Abstract: The present invention relates, in some embodiments, to compositions comprising a substantially pure compound represented by Structural Formula (I) and methods of using such compounds to activate cytoprotective kinases. In additional embodiments, the invention relates to methods for treating an ischemia or an ischemia-reperfusion injury in a subject, comprising administering to the subject an effective amount of a compound of the invention (e.g., in multiple doses). The values and preferred values of the variables in Structural Formula (I) are defined herein.

Abstract: Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Abstract: Apoptosis inducing factor (“AIF”) contains a PAR-binding motif (“PBM”) that binds to Poly(ADP-ribose) (“PAR”). Binding of PAR to AIF via the PBM is required for AIF release from the mitochondria to occur, and that this PAR-related release is a key step in the programmed cell death process known as parthanatos, both in vitro and in vivo. Preventing or disrupting this release can inhibit parthanatos and thus be the basis for treatments for patients suffering from diseases or medical conditions during which parthanatos commonly occurs, including Parkinson's disease or diabetes, or patients who have had and are recovering from heart attack, stroke and other ischemia reperfusion-related injuries. Alternatively, agents could be identified that enhance the release of AIF, thereby promoting parthanatos and serving as potential anti-tumor chemotherapeutic agents.

Abstract: Use of polypeptide micromolecule MLIF in preparing medicine for preventing and treating myocardial ischmia, where amino acid sequence of the polypeptide micromolecule MLIF is Met-Gln-Cys-Asn-Ser (SEQ ID NO:1).

Abstract: Compositions and methods for inhibiting the interaction between eNOS and ?-actin are provided for use in inhibiting or reducing lung injury from oxygen toxicity. One embodiment provides a synthetic or recombinant polypeptide having the ?-actin binding domain of eNOS, wherein the polypeptide inhibits or reduces eNOS activity in lung endothelial cells.

Abstract: The method of the invention relates to a modified OmCI polypeptide or a polynucleotide encoding a modified OmCI polypeptide which lacks LK/E binding activity and the use of such polypeptides and polynucleotides for the treatment of a disease or condition mediated by complement.

Abstract: Provided are methods to enhance healing of wounds and tissue, especially during or pursuant to psychological and/or physical stress and to protect tissue from deleterious effects associated with oxidative, psychological and/or physical stress, including but not limited to extreme exertion, ischemia, infarct, and damage associated with reperfusion of ischemic or transplanted tissues.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The present invention relates to the therapeutic and prophylactic use of C1 inhibitor for preventing, reducing and treating ischemia and reperfusion injury. The C1 inhibitor of the present invention is still therapeutically effective when administered after an ischemic period and reperfusion and therefore particularly useful for unforeseen occurrences of ischemic reperfusion such as e.g. a stroke.

Abstract: The present invention relates to novel serine rich peptides capable of exhibiting antioxidative properties and that can be used to protect a cell, tissues, organs or a multi-cellular organism, such as animals, against oxidative stress. In aspects of the invention, the peptides may be derived from egg yolk proteins utilizing only generally recognized as safe (GRAS) compounds. The invention also relates to cosmetics, functional foods, food supplements or pharmaceutical formulations comprising the peptides of the present invention having antioxidative properties. The cosmetics, functional food or pharmaceutical products are particularly suitable for the care of the skin in protecting against oxidative stress and ageing phenomena.

Abstract: The invention relates to polypeptides of amino acid sequence SEQ ID NO: 1 according to formula (1), the use thereof for producing a medicament, and medicaments for the treatment of diseases related to monocyte recruitment.

Abstract: Novel mutants of human monocyte chemoattractant protein 1 (MCP-1) with increased glycosaminoglycan (GAG) binding affinity and knocked-out or reduced GPCR activity compared to wild type MCP-1, and their use for therapeutic treatment of inflammatory diseases.

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: A method of treatment of inflamed, pre-cancerous or cancerous tissue or polyps in a mammalian subject is disclosed. The treatment involves administration of a composition of at least one peptide agonist of a guanylate cyclase receptor and/or other small molecules that enhance intracellular production of cGMP. The at least one peptide agonist of a guanylate cyclase receptor may be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The inhibitor may be a small molecule, peptide, protein or other compound that inhibits the degradation of cGMP. Without requiring a particular mechanism of action, this treatment may restore a healthy balance between proliferation and apoptosis in the subject's population of epithelial cells, and also suppress carcinogenesis.

Abstract: The present invention provides a compound including a peptidomimetic which interacts sterically with the binding site of a F11R molecule, the peptidomimetic including a peptidomimetic having the SEQ ID NO: 4D. The present invention also provides a method for treating a disorder comprising administering peptide 4D to a mammal.

Abstract: The present disclosure relates to peptides having a core sequence as described herein as well as application of the disclosed technology as inhibitors of caspase-2 and/or -6 activity.

Abstract: A highly purified and heat stable ?-? cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin and the plasma proteins impurities effectively. Addition of N-acetyl cysteine to the heat stable a-a cross-linked tetrameric hemoglobin maintains a low level of met-hemoglobin. The heat stable a-a cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart.

Abstract: The instant invention provides a method of treating an animal suffering a disease characterized by excessive apoptosis by administering a therapeutically effective amount of at least one serine protease inhibitor and thereafter monitoring a decrease in apoptosis. The inhibitor of the invention includes ?1-antitrypsin or an ?1-antitrypsin-like agent, including, but not limited to oxidation-resistant variants of ?1-antitrypsin, and peptoids with antitrypsin activity. The diseases treatable by the invention include cancer, autoimmune disease, sepsis neurodegenerative disease, myocardial infarction, stroke, ischemia-reperfusion injury, toxin induced liver injury and AIDS. The method of the invention is also suitable for the prevention or amelioration of diseases characterized by excessive apoptosis.

Abstract: A method heat treatment of cross-linked hemoglobin solutions including polymeric hemoglobin is disclosed. The method involves contacting the hemoglobin solution with a high temperature short time heat treatment apparatus. The high temperature short time process thermally denatures unmodified tetrameric hemoglobin (hemoglobin dimer form), protein impurities (e.g. immunoglobin-G, serum albumin), bacteria, and viruses so that renal injury, vascular detrimental effects and other toxicity reactions can be avoided.

Abstract: A high temperature-stable and highly purified ?-? cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells obtained from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents the lysis of white blood cells. Nucleic acids from white blood cells and the phospholipids impurities are not detected. The blocking of reactive sulfhydryl groups in hemoglobin by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography is used to remove different plasma protein impurities. N-acetyl cysteine is added to the ?-? cross-linked tetrameric hemoglobin solution to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion.

Abstract: An isolated polypeptide inhibitor of SuIfIa having a sequence which is a variant of Sulf1a, and which lacks sulfatase activity and lacks the ability to bind to the surface of a cell. The polypeptide inhibitor of SuIf1a may be the alternatively spliced isoform SuIf1b. An isolated polypeptide inhibitor of Sulf2a having a sequence which is a variant of Sulf2a, and which lacks sulfatase activity and lacks the ability to bind to the surface of a cell. The polypeptide inhibitor of Sulf2a may be the alternatively spliced isoform Sulf2b. A method of combating a cancer in which Wnt signalling is upregulated or of treating ischaemia in a patient, the method comprising administering to the patient a polypeptide inhibitor of Sulf1a and/or Sulf2a. A method of combating a cancer in which Wnt signalling is not upregulated, the method comprising administering to the patient an inhibitor of Sulf1b and/or Sulf2b.

Abstract: Methods are described for preventing or reducing ischemia, e.g., cerebral ischemia, and/or reperfusion injury, e.g., reperfusion injury associated with cerebral ischemia, in a patient.

Abstract: The present invention provides methods of treating heart failure and improving renal function, and/or preventing the advancement of heart failure into advanced stages, and methods of counteracting ischemia due to a myocardial infarction by providing improved methods of administering a therapeutically effective amount CGRP as a controlled release formulation. The therapies can be administered on an outpatient or inpatient basis and can further be used as maintenance therapies.

Abstract: Provided are methods to enhance healing of wounds and tissue, especially during or pursuant to psychological and/or physical stress and to protect tissue from deleterious effects associated with oxidative, psychological and/or physical stress, including but not limited to extreme exertion, ischemia, infarct, and damage associated with reperfusion of ischemic or transplanted tissues.

Abstract: A high temperature-stable and highly purified cross-linked (optionally ?70% ?-? linked) tetrameric hemoglobin with high efficiency of oxygen delivery suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents lysis of white blood cells. Nucleic acids from white blood cells and phospholipids impurities are not detected. Blocking of reactive sulfhydryl groups by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography removes different plasma protein impurities. N-acetyl cysteine is added to the cross-linked tetrameric hemoglobin to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion.

Abstract: The present invention provides zinc complexes for use in methods of providing zinc to subjects in need of treatment. The invention further provides improved dietary supplement formulations for improving and maintaining ocular nutrition. In particular, the improved dietary supplement formulations comprise the zinc complexes described herein, antioxidant vitamins, minerals and excipients.

Abstract: The present invention relates to a method of protecting cells against damage caused at least in part by apoptosis, comprising administering to subjects a therapeutic dose of leumorphin having cytoprotective activity, and a pharmaceutical composition comprising an effective amount of leumorphin having a cytoprotective activity.

Abstract: Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Abstract: A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart.

Abstract: The present invention relates to pharmaceutical compositions for treating diseases and conditions caused by ischemia. The pharmaceutical compositions contain a conjugate of a phospholipase (PL) polypeptide and a protein transduction domain (PTD). PLC-? plays a major role in the regulation of cytosolic calcium levels. During myocardial ischemia, cytosolic calcium accumulation mediates pathogenic changes. According to the present invention, ischemic diseases or conditions leading to hypoxia in tissues, such as the heart and the brain, can be prevented or alleviated by administration of a PTD-PL conjugate.

Abstract: Disclosed are Lipids, Annexin, and Lipid-Annexin Complexes for Use in the Prevention and/or Treatment of Ischemia-Reperfusion injury and reperfusion injury associated with a variety of diseases and conditions. Also disclosed are therapeutic targets and compositions for the prevention and treatment of ischemia-reperfusion injury and diseases and conditions associated with ischemia-reperfusion injury.

Abstract: Described herein is the finding that a mutant form of human neuroglobin (H64L) with a stable five-coordinate geometry reduces nitrite to nitric oxide approximately 2000-times faster than the wild type neuroglobin. Five-coordinate neuroglobin is also capable of binding and releasing oxygen. Based on these findings, the use of five-coordinate neuroglobin as a blood substitute is described herein. Particularly provided is a method of replacing blood and/or increasing oxygen delivery to tissues in a subject by administering to the subject a therapeutically effective amount of neuroglobin with a stable five-coordinate geometry. In some cases, five-coordinate neuroglobin is administered in combination with another therapeutic agent or composition, such as a second blood replacement product (for example, a hemoglobin-based oxygen carrier), a blood product (such as red blood cells, serum or plasma) or whole blood.

Abstract: H-NOX proteins are mutated to exhibit improved or optimal kinetic and thermodynamic properties for blood gas O2 delivery. The engineered H-NOX proteins comprise mutations that impart altered O2 or NO ligand-binding relative to the corresponding wild-type H-NOX domain, and are operative as physiologically compatible mammalian blood O2 gas carriers. The invention also provides pharmaceutical compositions, kits, and methods that use wild-type or mutant H-NOX proteins for the treatment of any condition for which delivery of O2 is beneficial.

Abstract: The present invention relates to biologically active polypeptides linked to one or more accessory polypeptides. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: The present invention is directed to the use of the peptide compound Glu-Ala-Leu-Glu-Leu-Ala-Arg-Gly-Ala-Ile-Phe-Gln-Ala-NH2 as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilisate or liquid buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Glu-Ala-Leu-Glu-Leu-Ala-Arg-Gly-Ala-Ile-Phe-Gln-Ala-NH2 optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.

Abstract: The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.