This disclosure relates to compositions and methods for recruiting brown adipocytes in vitro and in vivo from brown adipocyte progenitor cells found in human skeletal muscle. Methods for treating metabolic disease are also provided. Additionally, methods for treating hypothermia are provided. In some embodiments, the brown adipocyte recruiter is a human protein or peptide. In other embodiments the brown adipocyte recruiter may be a non-human protein or peptide. In still other embodiments, the brown adipocyte recruiter is a small molecule or natural product.

Disclosed are the preparing method of a pentacyclic triterpenoid saponin compound and a drug composition, and in particular the method of the pentacyclic triterpenoid saponin compounds as shown in formulae (I) to (XVI) in the preparation of a drug for preventing or treating a disease mediated by AMPK and/or ERRα, comprising the preparation of a drug for preventing or treating diseases such as a liver disease, respiratory system disease, metabolic disease, autoimmune disease, cardiovascular and cerebrovascular disease, kidney disease, central nervous system disease or muscular dystrophy. The definition of formulae (I) to (XVI) is the same as the definition in the specification.

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An insulin degludec derivative and a preparation method therefor are provided. Specifically, a fusion protein has a green fluorescent protein folding unit and an insulin degludec precursor or an active fragment thereof are provided. The fusion protein has a significantly increased expression level, and the insulin degludec precursor protein in the fusion protein is folded correctly, and has biological activity. Moreover, the green fluorescent protein folding unit in the fusion protein can be digested into small fragments by a protease, which have a great difference in molecular weight in comparison to a target protein, and are easy to separate. A method for using the fusion protein to prepare insulin degludec and prepare an intermediate thereof are also provided.

This invention is in the field of protein conjugates. More specifically the invention relates to oligomer extended insulins with covalently attached Fc monomer polypeptides, for use in the treatment of a metabolic disorder or condition, and to methods of producing such oligomer extended insulin-Fc conjugates. The invention also relates to novel Fc fragments, to intermediate products, and to the use of such intermediate products in processes for the synthesis of the oligomer extended insulin-Fc conjugates of the invention. Finally the invention provides pharmaceutical compositions comprising the oligomer extended insulin-Fc conjugates of the invention, and relates to the use of such compositions for the treatment or prevention of medical conditions relating to metabolic disorders or conditions.

The present disclosure provides binding proteins, such as antibodies and binding fragments thereof, that bind beta klotho, including human beta klotho, and methods of their use, including in the treatment of nonalcoholic steatohepatitis. The present disclosure also provides exemplary specific sequences of complementarity determining regions, variable regions, heavy chains, and light chains of the antibodies and/or binding fragments thereof.

The present invention is directed to a cargo-loaded cholesteryl ester nanoparticle with a hollow compartment (“cholestosome”) consisting essentially of at least one non-ionic cholesteryl ester and one or more encapsulated active molecules which cannot appreciably pass through an enterocyte membrane in the absence of said molecule being loaded into said cholestosome, the cholestosome having a neutral surface and having the ability to pass into enterocytes in the manner of orally absorbed nutrient lipids using cell pathways to reach the golgi apparatus. Pursuant to the present invention, the novel cargo loaded cholestosomes according to the present invention are capable of depositing active molecules within cells of a patient or subject and effecting therapy or diagnosis of the patient or subject.

Embodiments provide swallowable devices, preparations and methods for delivering viable cells (VC) into the GI tract including GI wall tissue or other tissue site. Particular embodiments provide a swallowable device such as a capsule for delivering VC into an intestinal wall or other site. The VC can be contained within a tissue-penetrating shell disposed in the capsule that protects the VC as they pass through the GI tract until they are inserted into GI tract tissue or other location. The shell desirably has shape, size and material consistency to be contained in a swallowable capsule, delivered from the capsule into solid tissue by the application of force on the shell and biodegrade within the solid tissue to release the VC into the tissue. Within the shell or other structure the VC can be maintained in a viability-sustaining gel that preserves the viability of the VC for selected time periods.

Compositions for promoting intestinal health are disclosed and described. In one example, the composition can include a combination of cyanidins and delphinidins, in an amount sufficient to treat intestinal hyperpermeability. In a further example, the composition can further comprise a prebiotic blend and fructooligosaccharides. Further presented herein, is a method of treating a condition or disorder related to gastrointestinal health in a subject. In one example, the method can include maximizing tight junction integrity in epithelial cells of gastrointestinal tract of the subject.

Compositions for promoting intestinal health are disclosed and described. In one example, the composition can include a combination of cyanidins and delphinidins, in an amount sufficient to treat intestinal hyperpermeability. In a further example, the composition can further comprise a prebiotic blend and fructooligosaccharides. Further presented herein, is a method of treating a condition or disorder related to gastrointestinal health in a subject. In one example, the method can include maximizing tight junction integrity in epithelial cells of gastrointestinal tract of the subject.

The present invention relates to a cryopreserved in vitro cell culture comprising human pancreatic progenitor cells that co-express pancreatic-duodenal homeobox factor-1 (PDX1) and NK6 homeobox 1 (NKX6.1) and are chromogranin negative. The present invention also relates to a method for cryopreserving an in vitro population of human pancreatic progenitor cells that co-express PDX1 and NKX6.1 and are chromogranin negative.