Described are peptides and peptide conjugates comprising CN binding motifs (CNBM) which inhibit the CN-NFAT interaction. In some embodiments, the peptides comprise: (i) CNBM; (ii) a hydrophobic, non-peptidic moiety (RH) which interacts with the hydrophobic pocket on a CN protein; (iii) a sequence -AAU1-AAU2-AAU3-AAU4-AAU5-AAU6-, wherein each of AAU2, AAU3, AAU4, AAU5, and AAU6, is, independently, optional, and each of AAU1, AAU2, AAU3, AAU4, AAU5, and AAU6 when present is independently an amino acid as defined herein; or (iv) combinations thereof. In some embodiments, RH is conjugated to the N- or C-terminus of the CNBM. In some embodiments, the sequence -AAU1-AAU2-AAU3-AAU4-AAU5-AAU6- is conjugated to the N- or C terminus of the CNBM. In some embodiments, the peptides comprise: CNBM and RH. In some embodiments. In some embodiments, the peptides comprise: CNBM and AAU1-AAU2-AAU3-AAU4-AAU5-AAU6-. In some embodiments, the peptides of the disclosure CNBM and RH.

Described are peptides and peptide conjugates comprising CN binding motifs (CNBM) which inhibit the CN-NFAT interaction. In some embodiments, the peptides comprise: (i) CNBM; (ii) a hydrophobic, non-peptidic moiety (RH) which interacts with the hydrophobic pocket on a CN protein; (iii) a sequence -AAU1-AAU2-AAU3-AAU4-AAU5-AAU6-, wherein each of AAU2, AAU3, AAU4, AAU5, and AAU6, is, independently, optional, and each of AAU1, AAU2, AAU3, AAU4, AAU5, and AAU6 when present is independently an amino acid as defined herein; or (iv) combinations thereof. In some embodiments, RH is conjugated to the N- or C-terminus of the CNBM. In some embodiments, the sequence -AAU1-AAU2-AAU3-AAU4-AAU5-AAU6- is conjugated to the N- or C terminus of the CNBM. In some embodiments, the peptides comprise: CNBM and RH. In some embodiments. In some embodiments, the peptides comprise: CNBM and AAU1-AAU2-AAU3-AAU4-AAU5-AAU6-. In some embodiments, the peptides of the disclosure CNBM and RH.

This invention relates to thienopyrimidinones and their use as inhibitors of TRPA1 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of fibrotic diseases, inflammatory and auto-immune diseases and CNS-related diseases.

The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. The antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of the antibodies in medicine are also described.

The present disclosure provides compositions and methods for promoting stem cell and/or progenitor cell proliferation and/or differentiation. The provided compositions may be useful in treating a disease or condition that is related to mucosal barrier function, e.g., wound healing, treating skin conditions (e.g., atopic dermatitis, psoriasis, bed sores, or condition related to the aging of skin), treating a lung disorders (e.g., asthma), a condition related to improving mucosal barrier function, and/or treating injury to GI mucosa in a subject in need thereof. The present disclosure also provides methods for promoting the proliferation and/or differentiation of stem cells and/or the progenitor cells in a subject in need of such treatment by administering a composition. The ability to stimulate the proliferation and/or differentiation of stem cells and/or the progenitor cells in vivo, ex vivo and/or in vitro provides tremendous benefit. The present disclosure can be used to increase stem cell populations in in vivo, ex vivo and/or in vitro. Stem cell transplantation provides treatments and/or cures of many disease states, degeneration and/or injury.

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

The technology described herein is directed to methods of treating and diagnosing bronchial premalignant lesions, e.g. by determining the lesion subtype using one or more biomarkers described herein.

The present invention relates to the compound of the formula: ##STR00001##
or pharmaceutically acceptable salts thereof, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, acute and chronic bronchitis, cystic fibrosis, emphysema, and pneumonia.

Methods for the reversal of hemorrhagic shock or hemorrhagic trauma. Methods for restoring mean arterial pressure to a normal range and reducing trauma adverse risks in a patient through the administration of oxygen reduced blood compositions.

The present invention relates to sustained-release formulations and dosage forms of ruxolitinib, or a pharmaceutically acceptable salt thereof, which are useful in the treatment of Janus kinase-associated diseases such as myeloproliferative disorders.