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: Method and peptide for regulating cellular activity includes a panel of synthesized peptides that have biological effects on inhibiting or enhancing cellular activity. Selected peptides can be used as therapy to reduce and/or inhibit, or initiate and/or enhance, an inflammatory response in a subject.

Abstract: The present invention provides methods and materials for use in increasing HSP20 activation in a biological system, for example by increasing phosphorylation of Ser16 of HSP20. In one aspect, the invention provides a method for increasing HSP20 activation in a biological system, comprising contacting the system with an antagonist capable of inhibiting PDE4 binding to HSP20, the antagonist comprising or consisting essentially of a fragment of PDE4 or an analogue thereof. In a further aspect the invention provides a method of screening for an agent able to increase activation of HSP20. A preferred antagonist has a C-terminal lysine residue.

Abstract: The present invention provides methods of identifying candidate compounds for the treatment of type I diabetes comprising contacting pancreatic ? cells with an amount of apolipoprotein CIII (“apoCIII”) effective to increase intracellular calcium concentration, in the presence of one or more test compounds, and identifying those test compounds that inhibit an apoCIII-induced increase in intracellular calcium concentration in the pancreatic ? cells. The present invention also provides methods for treating patients with type I diabetes comprising administering to the patient an amount effective of an inhibitor of apoCIII to reduce apoCIII-induced increase in intracellular calcium concentration in pancreatic ? cells.

Abstract: The present disclosure elucidates that 34-mer PEDF suppresses hepatic stellate cells (HSCs) from activation by diminishing the levels of alpha-smooth muscle actin (?-SMC), collagen type 1, and monocyte chemoattractant protein-1 (MCP-1); and 44-mer PEDF promotes liver regeneration process by enhancing the replication of liver-derived progenitor cells (LDPCs). Accordingly, methods and compositions directing to the new use of the 34-mer PEDF or 44-mer PEDF in patients suffering from liver cirrhosis are provided herein.

Abstract: The present invention concerns compositions comprising and methods of identification and use of targeting peptides selective for cancer tissue, particularly prostate or ovarian cancer tissue. The method may comprise identifying endogenous mimeotopes of such peptides, such as GRP78, IL-11R? and hsp90. Antibodies against such targeting peptides or their mimeotopes may be used for detection, diagnosis and/or staging of prostate or ovarian cancer. In other embodiments, the compositions and methods concern a novel type of gene therapy vector, known as adeno-associated phage (AAP). AAP are of use for targeted delivery of therapeutic agents to particular tissues, organs or cell types, such as prostate or ovarian cancer. In still other embodiments, targeting peptides selective for low-grade lipomas may be used for detection, diagnosis and targeted delivery of therapeutic agents.

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: The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2Lz4 wherein z2 is an amino acid residue and z4 is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae (SEQ?ID?NO:?100) a1a2a3CDa6La8a9a10Ca12a13a14, (SEQ?ID?NO:?104) b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ?ID?NO:?105) c1c2c3Cc5DC7Lc9c10c11c12c13c14Cc16c17c18 (SEQ?ID?NO:?106) d1d2d3Cd5d6d7WDd10Ld13d14d15Ld16d17d18 (SEQ?ID?NO:?107) e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18 (SEQ?ID?NO:?109) f1f2f3Kf5Df7Lf9f10Qf12f13f14 wherein the substituents are as defined in the specification.

Abstract: Peptides for the treatment of inflammation, and therapeutic uses and methods of using the same are disclosed. Peptides including a transducing sequence are effective for inhibiting cytokine activity and TNF-? secretion through interaction with toll-like receptors.

Abstract: TIR-domain decoy peptides and TIR domain peptides are disclosed, as well as methods of using the peptides in the regulation of toll-like receptor (TLR) activation and signaling.

Abstract: The use of monoclonal antibodies to the angiotensin-II type-I receptor is provided for the treatment of cancer and vascular smooth muscle cell proliferation. Specifically, use is provided of a monoclonal antibody or a fragment thereof to a peptide comprising the N-terminal portion of the angiotensin-II type-1 receptor defined by the sequence (SEQ?ID?NO:?1) MILNSSTEDG?IKRIQDDCPK?AGRHNYIFVM?IPTLYSIIFV?VGIFG in the preparation of a medicament for the treatment of cancer or in the preparation of a medicament for the treatment of vascular smooth muscle (VSM) cell proliferation.

Abstract: The present invention provides embodiments which involve methods of providing a predetermined concentration of thymosin beta 4 (TB4) at a predetermined time, t, in a body portion of a live human patient. The methods can include determining a thymosin beta 4 treatment dosage (D) using Formula I: C=(A)D.t?B, wherein C is the predetermined concentration at time t, in ng/mL, D is the dosage of thymosin beta 4 administered in mg, t is the time elapsed after administration of dosage D in hours, A is about 30 to about 38, and B is about 0.5 to about 1; and administering the dosage (D) of thymosin beta 4 to the patient. Formula I may be, for example, C=(35.6)D.t?0.754??(Formula II).

Abstract: The present invention relates to isolated polypeptides comprising the amino acid sequence of residues 378-413 of Mus musculus ?-1-antitrypsyn (serpina1c), and active fragments thereof, and to pharmaceutical compositions comprising same. The compositions of the invention are useful for treating burns, inflammatory, autoimmune and degenerative diseases.

Abstract: Peptides for the treatment of inflammation, and therapeutic uses and methods of using the same are disclosed. Peptides including a transducing sequence are effective for inhibiting cytokine activity and TNF-? secretion through interaction with toll-like receptors.

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: The present disclosure is generally related to methods of using the secretory protein SCGB3A2 for promoting lung development and treating lung disease. Some embodiments are, for example, methods for treating and inhibiting the development of neonatal respiratory distress. Other embodiments are methods of promoting lung development in damaged or diseased lungs. Also disclosed are methods for inhibiting lung damage due to anti-cancer agents.

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: The present invention provides isolated splice variants of Bnip3 and isolated polynucleotides encoding the splice variants. Also provided are isolated polypeptides present at the carboxy-terminus of Bnip3 splice variants, and antibody that specifically binds Bnip3 splice variants and/or the carboxy-terminus of Bnip3 splice variants. The present invention further provides methods of altering cellular apoptosis, cellular necrosis, cellular autophagy, or the combination thereof. For instance, the methods may include changing the amount of a Bnip3 splice variant or a carboxy-terminal region of a Bnip3 splice variant in a cell. Also provided herein are methods for determining whether death of cells in a tissue can be altered, methods for evaluating treatment options for a subject, and methods for identifying a compound that alters the amount or activity of a Bnip3 splice variant in a cell.

Abstract: The invention provides agents, compositions, pharmaceutical compositions and method for inhibiting tumor cell proliferation by inhibiting FoxM1B activity, expression, or nuclear localization in a tumor cell.

Abstract: The present invention relates to novel isolated peptides which induce analgesia and which inhibit ASIC channels (Acid Sensing Ion Channels), to the polynucleotides encoding said peptides, and also to the pharmaceutical compositions, host cells and vectors comprising same. In particular, said peptides are isolated from the venom of the snake Dendroaspis polylepis. The present invention also relates to the use thereof as a diagnostic tool or as medicament, and in particular as an analgesic, or for identifying analgesic molecules or molecules which inhibit ASIC channels.

Abstract: The present invention provides peptides and pharmaceutical compositions thereof for appetite suppression and weight control. Preferred peptides are calcitonin analogs, preferably with specific amino acid changes to make the peptide more amylin-like.

Abstract: A method for treating disorders involving deregulation of cell proliferation and/or angiogenesis comprising the administration of an effective amount of a multivalent synthetic compound comprising a support on which at least 3 pseudopeptide units are grafted, said compound being of formula (I).

Abstract: The present invention relates generally to novel GIP analogs and GIP hybrid polypeptides with selectable properties, useful as agents for the treatment and prevention of metabolic diseases and disorders, for example those which can be alleviated by control plasma glucose levels, insulin levels, and/or insulin secretion, positive inotropic effects, reduction of catabolic effects, slowing of gastric emptying. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, critical care, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

Abstract: Polypeptides which bind to the helical transmembrane region of membrane proteins are disclosed, as are methods for the design of polypeptides that bind to the transmembrane region of membrane proteins. Also provided are methods for the use of the disclosed polypeptides in various applications, as well as products made through the practice of the instant methods.

Abstract: A number of human beta-glucuronidase variants having higher enzymatic activity at physiological pH as compared with wild-type beta-glucuronidase and uses thereof in prodrug therapy. Also disclosed herein is a method for identifying enzyme variants having elevated enzymatic activity using a mammalian surface display system.

Abstract: Methods of increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided. The method for increasing blood flow in such a mammalian brain blood vessel includes administering to a patient in need thereof a therapeutically effective amount of an inhibitor of ? protein kinase C. In certain embodiments, the inhibitor can be chronically administered without causing desensitization of the patient to the inhibitor. Kits for increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.

Abstract: A method is provided for increasing trafficking of endothelial progenitor cells to an ischemic myocardium in a subject's heart comprising administering to the subject's heart an amount of Stromal-Derived Factor-1 (SDF-1).

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present invention is directed to a method of treating hypophosphatemia in a subject. This method involves selecting a subject with hypophosphatemia associated with elevated or normal FGF23 and administering to the selected subject an inhibitor of FGF23-Klotho-FGF receptor complex formation under conditions effective to treat the hypophosphatemia. The present invention is also directed to a method of screening for compounds suitable for treatment of hypophosphatemia associated with elevated or normal FGF23. This method involves providing FGF23, FGFR-Klotho complex, and one or more candidate compounds. The FGF23, the FGFR-Klotho complex, and the candidate compounds are combined under conditions effective for the FGF23 and the binary FGFR-Klotho complex to form a ternary complex if present by themselves.

Abstract: An isolated protein is provided for use in treatment of a condition selected from the group consisting of Alzheimer's disease, familial Danish dementia and familial British dementia in a mammal, including man. The isolated protein is selected from the group consisting of proteins comprising an amino acid sequence having at least 70% identity to residues 90-236 of Bri2 from human; and proteins comprising an amino acid sequence having at least 70% identity to any one of the Brichos domains of Bri2 from human, chimpanzee, bovine, pig, mouse and rat.

Abstract: The present invention provides novel peptides that can modulate the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and sub-types, isoforms and variants thereof). These peptides are useful as antagonists of the ghrelin receptor as well as inverse agonist, partial agonist or a combination of these activities 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, diabetes, central nervous system disorders, genetic disorders, and hyperproliferative disorders.

Abstract: The present invention relates to the identification and functional characterization of human cell-penetrating peptides (CPPs) and their use; in particular as transfection vehicles.

Abstract: The present invention includes compositions, methods and kits for directing an agent across the nuclear membrane of a cell. The present invention includes a Karyopherin beta2 translocation motif in a polypeptide having a slightly positively charged region or a slightly hydrophobic region and one or more R/K/H-X(2-5)-P-Y motifs. The polypeptide targets the agent into the cell nucleus.

Abstract: The invention relates to conjugates that bind to Her2/neu, methods of using conjugates that bind to Her2/neu and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies that express Her2/neu.

Abstract: A method including advancing a delivery device through a lumen of a blood vessel to a particular region in the blood vessel; and introducing a synthetic apolipoprotein A-1 (Apo A-I) mimetic peptide into a wall of the blood vessel at the particular region, wherein the peptide has a property that renders the peptide effective in reverse cholesterol transport. A composition including a synthetic apolipoprotein A-I (Apo A-I) mimetic peptide, or combination of an Apo A-I synthetic peptide and an Acyl CoA cholesterol: acyltransferase (ACAT) inhibitor in a form suitable for delivery into a blood vessel, the peptide including an amino acid sequence in an order reverse to an order of an endogenous Apo A-I related peptide. A composition including an apolipoprotein A-1 (Apo A-I) synthetic peptide in a form suitable for delivery into a blood vessel, the peptide including an amino acid backbone that has less amino acid residues relative to endogenous Apo A-I and a chimera of helix 1 and helix 9 of Apo A-I.

Abstract: The present application relates to methods of producing exosomes. The application also provides a method for preparing a protein composition comprising culturing an exosome-producing cell expressing a Nef-fusion protein comprising a Nef-derived peptide fused to a protein of interest; isolating exosomes from the exosome-producing cell culture; and purifying the protein of interest from the isolated exosomes. The application further discloses compositions that comprise exosomes containing the Nef-fusion protein, as well as methods of using the Nef-fusion protein and exosomes containing the Nef-fusion protein.

Abstract: Disclosed are exendin-3 or exendin-4 derivatives modified with biotin, a preparation method thereof and a pharmaceutical composition containing the same. More specifically, disclosed are exendin-3 or exendin-4 derivatives in which the lysine residue of exedin is modified with biotin. The disclosed exendin-3 or exendin-4 derivatives modified with biotin show biological activity similar to that of native exendin and at the same time, have increased in vivo stability and are easily absorbed through the mucosa. Thus, biotin-modified exendin-3 or exendin-4 derivatives are useful for treating diseases, which can be caused by the excessive secretion of insulin, the lowering of plasma glucose, the inhibition of gastric or intestinal motility, the inhibition of gastric or intestinal emptying or the inhibition of food intake. Particularly, the biotin-modified exendin-3 or exendin-4 derivatives are useful for the treatment of diabetes, obesity and irritable bowel syndromes.

Abstract: The present invention relates to parstatin peptides, compositions comprising parstatin peptides and their use in the treatment of various disorders, including angiogenesis-related diseases, ocular neovascularisation and related disease states, ischemia-reperfusion injury and myocardial-related disease states, and renal disorders.

Abstract: The present invention identified a high affinity binding sequence in collagen type III for the collagen-binding integrin I domains. Provided herein are the methods used to characterize the sequence, the peptides comprising this novel sequence and the use of the peptides in enabling cell adhesion. Also provided herein are methods to identify specific integrin inhibitors, sequences of these inhibitors and their use in inhibiting pathophysiological conditions that may arise due to integrin-collagen interaction.

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: The invention relates to a peptide of 8-50 amino acids comprising the sequence of KAHKKRAD or KARKKHAD, or a cyclic peptide of 8-50 amino acids comprising the sequence of HKKR or RKKH. Also disclosed are methods of using the peptide for detecting, monitoring, or treating cancer.

Abstract: Lytic peptides, including fusion peptides of lytic peptides conjugated with luteinizing hormone-releasing hormone or modified versions thereof to target luteinizing hormone-releasing hormone receptors, are disclosed. The lytic peptides show anti-proliferative activity against human prostate cancer cell lines, but are nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. The lytic peptides have specificity for and anti-proliferative activity against prostate cancer tumor cells, and low toxicity for normal prostate cells, making the peptides useful in therapies for prostate cancer.

Abstract: A nucleic acid sequence is provided, encoding at least one of a precursor of a lariat peptide, a processing factor of a lariat peptide, and an export factor of a lariat peptide, wherein the lariat peptide is a non-MccJ25 lariat peptide according to general structural formula (I) Also provided are biosynthesis systems useful for the synthesis of peptides according to formula (I), and methods of detecting and identifying nucleic acid sequences encoding the disclosed proteins.

Abstract: The present invention relates, inter alia, to certain peptide conjugates, and to the use of the conjugates in the treatment of a variety of diseases or disorders, including diabetes (type 1 and/or type 2) and diabetes-related diseases or disorders.

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: Provided are compounds and methods of making compounds containing two or three groups derived from a peptide, such as enfuvirtide or exenatide, covalently bound to a linker. The compounds may contain polyethylene glycol groups to enhance solubility and pharmacokinetic properties. The compounds are useful for the treatment of diseases or conditions subject to treatment with the parent peptide, such as HIV and AIDS in the case of enfuvirtide, or diabetes in the case of exenatide.

Abstract: Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented.

Abstract: The invention relates to lipopeptide building blocks consisting of a peptide chain comprising a coiled-coil domain, linked covalently to a lipid moiety comprising long alkyl or alkenyl chains, and optionally linked to an antigen; and to helical lipopeptide bundles and synthetic virus-like particles formed by aggregation. The nanometer size and shape of these bundles and particles, their stability under aqueous physiological conditions, their chemical composition, the possibility to incorporate B- and T-cell epitopes, and their production by chemical synthesis, make them highly suitable as vaccine delivery vehicles.

Abstract: The present invention is based on the identification of synaptic vessel glycoprotein SV2 as the BoNT/A receptor and the further identification of various BoNT/A-binding fragments of SV2. The disclosure here provides new tools for diagnosing and treating botulism.