Abstract: The present invention relates to methods for diagnosing and treating Myhre Syndrome. The invention provides a method for diagnosing or predicting Myhre Syndrome, or a risk of Myhre Syndrome, in a subject, which method comprises detecting a mutation in SMAD4 gene, as compared to a control population, wherein the presence of said mutation is indicative of Myhre Syndrome or of a risk of Myhre Syndrome. The present invention also relates to an inhibitor of the SMAD4-mediated TGF?/BMP signalling pathway for use in the treatment of Myhre Syndrome.

Abstract: The present invention relates to a new combination for the treatment of renal damage, in particular of acute renal failure and acute kidney injury, the pharmaceutical compositions and the kits containing it and their use in therapy.

Abstract: The present invention provides methods for treating disorders arising from hypogonadism by administering myostatin antagonists to subjects suffering from such disorders.

Abstract: This disclosure relates to compounds, compositions and methods of epigenetically transforming cells. In certain embodiments, the disclosure relates to methods of generating epigenetically altered cells comprising mixing isolated cells with compositions disclosed herein under conditions such that epigenetically altered cells are formed. In certain embodiments, the disclosure contemplates inducing cells, such as adult somatic cells or cells that are not naturally pluripotent, into cells with chemically induce pluripotency. In certain embodiments, the disclosure contemplates certain compounds disclosed herein, compounds disclosed herein optionally substituted with one or more substituents, derivatives, or salts thereof, for these purposes.

Abstract: The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (Treg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound Treg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.

Abstract: Metallo-proteins including but not limited to lactoferrin (LF), transferrin (TF) and ovotransferrin (OTF) (all members of transferrin family), ceruloplasmin (CP) and metallo-thionein (MT) were found to stabilize and enhance the bio-functional activity of tocotrienol (T3), T3 mixtures or derivates. The synergism between MP and T3 also promote the intestinal transfer and the ultimate bio-availability of T3 and T3-derivatives for physiological functions. Such functional synergism includes hypocholesterolemic, anti-thrombotic, antioxidant, anti-athermogenic, anti-inflammatory and immuno-regulatory activities of T3 agents. Addition of a non-protein-type metal chelator provided further improvement in the action of the bio-functional activity of T3. These T3 compositions are useful as pharmaceuticals, in cosmetics, in foods and as nutritional supplements.

Abstract: Methods of stimulating collagen production, including stimulation of chondrocyte production, at the site of a defect. Methods include administering to the site of a defect at least two proteins from the group IL-1ra, sTNF-RI, sTNF-RII, IGF-I, EGF, HGF, PDGF-AB, PDGF-BB, VEGF, TGF-?1, and sIL-1RII.

Abstract: A skin care composition comprising an isolated Asteroidea body fluid or extract thereof is described. Uses and methods of use of the composition for the prevention and/or treatment of a skin disorder or condition, such as skin-aging signs, are also described.

Abstract: This document relates to compositions containing cardiogenic factors, to methods to obtain cells by culturing initial cells in the presence of such factors; and methods of administering the obtained cells to heart tissue.

Abstract: The present invention relates to pharmaceutical compositions for a combination therapy with a cytokine antagonist and a corticosteroid. By means of the combination therapy diseases such as osteoarthritis, tendon injuries and/or degenerative spinal diseases can be treated.

Abstract: The invention is directed to novel cellular factor-containing solution compositions (referred to herein as “CFS” compositions), including novel sustained-release cellular factor-containing solution compositions (referred to herein as “SR-CFS” compositions), methods of making such novel compositions and uses thereof.

Abstract: Disclosed are in situ-forming injectable hydrogel and medical uses thereof. In the in situ-forming injectable hydrogel two or more homogeneous or heterogeneous polymers are bonded to each other by a dehydrogenation reaction between phenol or aniline moieties on adjacent polymers, wherein a polymer backbone is grafted with a phenol or aniline moiety using a linker. In contrast to conventional hydrogel, the in situ-forming injectable hydrogel is superior in terms of in vivo stability and mechanical strength thanks to the introduction of a water-soluble polymer as a linker which leads to an improvement in the reactivity of phenol or aniline moieties. Having the advantage of superior bio stability and mechanical strength, the hydrogel finds a variety of applications in the biomedical field.

Abstract: Endoglin has now been shown to be an important target of therapy to reduce disease symptoms associated with heart failure, particularly cardiac fibrosis. Soluble Endoglin is identified as an anatogonist to TGF?1 activity, while membrane-bound Endoglin is identified as a necessary component to promote TGF?1 activity in heart failure. The present invention therefore features methods and kits for treatment of subject having heart failure or a related disorder by administering a composition that decreases TGF?1 signaling through either direct inhibition of membrane-bound Endoglin or promoting expression of soluble Endoglin.

Abstract: The present invention relates to an isocyanate-free multi-component system, in particular for medical uses such as foamable wound coverings, with at least two separate components, wherein the first component comprises at least one alkoxysilane-terminated prepolymer and the second component comprises an aqueous component, wherein the aqueous component is a polyurethane dispersion.

Abstract: Compositions and methods are provided for a post-procedure care following the treatment of skin with cosmetic skin resurfacing treatments, which include without limitation a variety of laser treatments, chemical peeling and dermabrasion, by applying a silicone-based gel formulation in combination with therapeutic peptides. Peptides of interest include one or more of transforming growth factor, epidermal growth factor, and basic fibroblast growth factor. The formulation may further comprise an effective dose of one or more acylated peptides, which peptides are active in remodeling of the skin.

Abstract: The present invention relates to devices and related methods for treating fistulas such as anal or recto-vaginal fistulas, in particular by the use of a seton to secure a tissue growth promoter such as a growth factor and/or fibrin. The various devices are particularly suitable for positioning tissue growth promoters securely within a fistula. Thus, one device comprises a seton and a tissue growth promoter. Further related aspects of the invention included devices comprising an enclosure provided in between portions of a seton, devices comprising a seton and a plurality of holes for enabling the device to be sutured to tissue, devices comprising a probe and a seton that are releasably connectable end-to-end, devices comprising an attachment device to secure the ends of a seton, and devices comprising a fistula plug adapted to be secured to a section.

Abstract: Endosseous implant to be applied to a human or animal bone, wherein the surface of the implant is made from titanium or a titanium alloy, said implant having a smooth or rough surface texture, which is characterized in that said surface has been treated with at least one selected organic phosphonate compound or a pharmaceutically acceptable salt or ester or an amide thereof; process for producing said implants.

Abstract: Described herein is a cell tissue gel cross-linked with a cross-linking agent, and a quenching agent bound to a reactive group of the cross-linking agent.

Abstract: The present invention relates to a method of implanting a sterile, active agent-coated material comprising contacting a sterile implant with a sterile active agent or active agent solution to form a sterile, active agent-coated implant and, at most a relatively short time after forming the active agent-loaded sterile implant, implanting the active agent-loaded sterile implant into a subject such as a mammal or a human.

Abstract: Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Abstract: The present invention relates to compositions of bone morphogenetic proteins, particularly solid and liquid formulations of such proteins comprising one or more stabilizing excipients. The invention further provides methods of producing the compositions, kits comprising the compositions and methods of using the compositions in the treatment of diseases of skeletal and non-skeletal tissues.

Abstract: The present invention relates to injecting a high specificity cytokine antagonist into a diseased intervertebral disc.

Abstract: A system for growing tissue based upon layers of an inorganic extracellular matrix, wherein each layer of the inorganic matrix is designed to dissolve at a separate rate and result in sequential growth factor delivery upon its dissolution.

Abstract: The present invention provides variant activin IIB soluble receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the variant polypeptides and proteins. Compositions and methods for treating muscle-wasting and other diseases and disorders are also provided.

Abstract: The present invention provides a peptide represented by formula (I) of X1-Leu-X2-Leu-X3 wherein X1 represents Glu or Asp, X2 represents His, Lys or Arg, X3 represents Asp or Glu, with Glu, Asp, Leu, His, Lys and Arg being respectively glutamic acid, aspartic acid, leucine, histidine, lysine and arginine; or a pharmaceutically acceptable salt thereof; a composition for the treatment or prevention of at least one selected from cartilage damage and arthritis, containing the same peptide or a pharmaceutically acceptable salt thereof as an active ingredient; and a composition containing the same peptide or a pharmaceutically acceptable salt thereof and TGF?1.

Abstract: The present invention is directed to methods and compositions for accomplishing systemic delivery of minimally-soluble bioactive agents such as, but not limited to, proteins of the TGF-? superfamily via a peripheral mode of administration. According to the invention, an exemplary bioactive agent is BMP-7. The invention further provides for minimally-invasive systemic treatment of skeletal disorders such as osteoporosis as well as minimally-invasive systemic treatment of injured or diseased non-mineralized tissues and organs such kidneys. Practice of the invention eliminates adverse side effects at the peripheral site of intravenous administration of the bioactive agent.

Abstract: In certain aspects, the present invention provides compositions and methods for regulating body weight, in particular, for treating obesity and obesity-associate disorders. The present invention also provides methods of screening compounds that modulate activity of GDF3. The compositions and methods provided herein are also useful in treating diseases associated with abnormal activity of GDF3.

Abstract: Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.

Abstract: Methods for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of cerebral hemorrhage and subarachnoid hemorrhage. Therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). An effective amount of DFO may be administered to the upper third of the nasal cavity of a patient at risk for, or diagnosed with, cerebral hemorrhage and subarachnoid hemorrhage. The effective amount of DFO is delivered directly to the patient's central nervous system for preconditioning, preventing and/or treating the cerebral hemorrhage and subarachnoid hemorrhage.

Abstract: A cyclized peptide designated BMP Binding Peptide (BBP) is a synthetic peptide that avidly binds rhBMP-2. BBP increases the overall osteogenic activity of rhBMP-2, increases the rate at which rhBMP-2 induces bone formation, and BBP induces calcification alone. Compositions and substrates including BBP, and methods of using BBP are useful in therapeutic, diagnostic and clinical applications requiring calcification and osteogenesis.

Abstract: The invention provides compositions, methods, and kits for increasing transport of GDNF across the blood brain barrier while allowing its activity to remain substantially intact. The GDNF is transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems.

Abstract: A synthetic, flexible tissue matrix and methods for repairing hyaline cartilage defects in a joint using the flexible tissue matrix are described. The flexible tissue matrix includes a high molecular weight polycaprolactone polymer entangled with a polysaccharide such as hyaluronic acid. In the methods, autologous bone mesenchymal stem cells are introduced to a joint by a microfracturing technique, and a membrane made of the flexible matrix is applied to the joint. Cartilage which forms in the joint is hyaline cartilage rather than fibrocartilage.

Abstract: Methods and compositions are provided for the persistent modification of cell membranes with exogenous proteins so as to alter the function of the cell to achieve effects similar to those of gene therapy, without the introduction of exogenous DNA. DNA sequences, the proteins and polypeptides embodying these sequences are disclosed for modulating the immune system. The modulations include down-regulation, up-regulation and apoptosis.

Abstract: Provided herein are methods for treating pain and for reducing the excitability of nociceptors, comprising administering a TGF-? antagonist. In some embodiments, a TGF-? antagonist is a monoclonal TGF-f3 neutralizing antibody or a fusion product comprising a monoclonal TGF-? neutralizing antibody, a soluble receptor, an antisense oligodeoxynucleotides (ODNs), a ribozymes, a small inhibitory RNA (siRNA), Smad 6, Smad7, or a small molecule that blocks TGF-? signaling.

Abstract: A method for promoting bone formation is provided. More specifically, a method for promoting bone formation by promoting osteoclast formation is provided. In one embodiment, an implant comprising an implantable material and an osteoclast stimulating substance is provided.

Abstract: Disclosed are a novel therapeutic agent and a novel treatment method for cancer. Specifically disclosed are: a targeting agent for a cell selected from the group consisting of a cancer cell and a cancer-associated fibroblast, which comprises a retinoid; a substance delivery carrier for the cell, which comprises the targeting agent; an anti-cancer composition utilizing the targeting agent or the carrier; an anti cancer-associated fibroblast composition; and a method for treatment of cancer.

Abstract: Disclosed is a method of promoting neuronal growth by administering IGFBPL-1, or an agent that increases or stabilizes IGFBPL-1 activity to a subject in need thereof, e.g., a subject in need of treating optic nerve degeneration.

Abstract: The present invention provides compounds for disrupting the binding of a matrix metalloprotease (MMP) protein to a substrate protein at an interaction site other than the protease catalytic site. In particular the inventive compounds inhibit the MMP's ability to cleave a substrate protein. In some cases the compound may prevent activation of transforming growth factor beta (TGF?). The compounds are preferably polypeptide fragments of the hemopexin-like domain of the MMP, but may be mimetics thereof or peptides or mimetics of the portion of the MMP substrate protein to which the MMP interacts.

Abstract: The present invention relates to a method for preparing a cartilage product comprising a protein hydrolysate with a degree of hydrolysis comprised between 0.5% and 3.0%, at least one glycosaminoglycan and at least one growth factor. The present invention also relates to the cartilage product obtainable through said method. Said cartilage product is useful in the treatment or prevention of wounds, ulcers, burns, psoriasis, osteoarthritis, synovitis, osteoporosis, osteopenia, diseases of the tendons and ligaments, periodontal diseases, signs of skin aging, the harmful effects of ultraviolet radiation exposure or stretch marks.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: The present invention discloses methods and compositions for treating or ameliorating a condition associated with increased or decreased myofibroblast activities and use thereof

Abstract: A flowable biomedical implant for application to a bone defect to promote bone growth is provided. The flowable biomedical implant comprises a carrier matrix including a biodegradable polysaccharide and ceramic material. An impermeable membrane can be integrally formed at the surface of the carrier matrix by applying a crosslinking agent to the biodegradable polysaccharide mixed with ceramic materials.

Abstract: A system for multiphasic delivery of at least one growth factor at a treatment site comprises a delivery vehicle for releasing at least one growth factor in an initial release profile and a carrier for releasing at least one growth factor in a sustained release profile. The initial release profile releases at least one growth factor over a period of hours to days, wherein the growth factor is released in a large amount initially, with the remainder being released in progressively lower amounts. The sustained release profile releases at least one growth factor over a period of days to weeks, wherein the growth factor is released at a generally constant amount over such period. The system of the invention is particularly suited for applications on bioimplants. The invention also comprises methods and kits for multiphasic delivery of at least one growth factor.

Abstract: The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.

Abstract: Provided are proteins and polynucleotides, complexes and compositions containing the proteins, and methods for their use in administration to subjects and for disease treatment. Among the provided proteins and complexes are complexes containing a TGF-beta associated with immunoglobulins (such as IgGs) or functional portions thereof including Fc portions, such as by non-covalent bonds. The provided complexes include those in which the immunoglobulin portion binds to inhibitory Fc? receptors to a greater degree than to activating Fc? receptors. The provided complexes further include those in which the immunoglobulin portion bind to activating Fc? receptors to a greater degree than to inhibitory Fc? receptors. The complexes and compositions can be used for administration to subjects, such as for increasing immunity or decreasing inflammation, such as for treating diseases including autoimmune diseases and cancer.

Abstract: Dermatological and cosmetic compositions and methods are provided to reduce the appearance of biological and/or environmentally-caused aging.

Abstract: The invention provides a particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, including i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 70 weight percent based on the total weight of the particulate composition; ii) a monocalcium phosphate monohydrate powder; and iii) a ?-tricalcium phosphate powder having a median particle size of less than about 20 microns. Bone graft substitute cements made therefrom, a bone graft substitute kit comprising the particulate composition, methods of making and using the particulate composition, and articles made from the bone graft substitute cement are also provided.

Abstract: Provided herein are compositions and methods for forming fibrochondrocytes or fibrochondrocyte-like cells from progenitor cells, such as mesenchymal stem cells. One aspect provides a fibrochondrocyte culture medium including CTGF and TGF?3, optionally encapsulated by microspheres having different release profiles. Another aspect provides a method for forming fibrochondrocytes or fibrochondrocyte-like cells from progenitor cells by culturing with CTGF and TGF?3.

Abstract: In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density.

Abstract: The described invention provides compositions, dressings and methods for treating a cutaneous scar in a subject. The compositions of the derived invention contains a pharmaceutical composition comprising a therapeutic amount of a Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) inhibitor comprising an MK2 polypeptide inhibitor or a functional equivalent thereof, and a pharmaceutically acceptable carrier.