The invention provides a novel class of orally and/or topically available, selective and potent JAK inhibitors as safe and effective therapeutics against various diseases and disorders. The invention also provides pharmaceutical composition of these compounds and methods of their preparation and use thereof.

Cannabidiol derivatives and medical use thereof, in particular to compounds represented by general formula (I), or stereoisomers, solvates, metabolites, pharmaceutically acceptable salts or cocrystals thereof, wherein the definitions of the substituents in general formula (I) are the same as those in the description.

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The present disclosure provides methods for the treatment of a mammal having a neurological condition, disease, or injury. The methods involve increasing the number of functional GABAergic interneurons at or near the site of the neurological disease, injury, or condition.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present disclosure is directed to a peptide of formula (I), or a pharmaceutically acceptable salt thereof, and uses thereof: R.sup.1—C—R—X.sup.1—X.sup.2—P—X.sup.3—X.sup.4—X.sup.5—X.sup.6—C—R.sup.2 (I) wherein X.sup.1, X.sup.3, X.sup.5, and X.sup.6 is an amino acid residue selected from the group consisting of serine, alanine, valine, leucine, isoleucine and glycine; X.sup.2 is alanine, arginine or lysine; X.sup.4 is glutamic acid or aspartic acid; R.sup.1 is selected from the group consisting of S, HS, GHS, PGHS, APGHS, EAPGHS, SEAPGHS, SSEAPGHS, PSSEAPGHS, DPSSEAPGHS and IDPSSEAPGHS, or R.sup.1 is absent; and R.sup.2 is selected from the group consisting of S, SS, SSK, SSKF, SSKFS, SSKFSW, SSKFSWD, SSKFSWDE, SSKFSWDEY, SSKFSWDEYE, SSKFSWDEYEQ, SSKFSWDEYEQY, SSKFSWDEYEQYK, SSKFSWDEYEQYKK, SSKFSWDEYEQYKKE, or R.sup.2 is absent; and wherein the peptide of formula (I), or the pharmaceutically acceptable salt thereof, is a cyclic peptide formed by a disulphide bond between the two cysteine residues.

Products, compositions, systems, and methods for modifying a target structure which mediates or is associated with a biological activity, including treatment of conditions, disorders, or diseases mediated by or associated with a target structure, such as a virus, cell, subcellular structure or extracellular structure. The methods may be performed in situ in a non-invasive manner by application of an initiation energy to a subject thus producing an effect on or change to the target structure directly or via a modulation agent. The methods may further be performed by application of an initiation energy to a subject in situ to activate a pharmaceutical agent directly or via an energy modulation agent, optionally in the presence of one or more plasmonics active agents, thus producing an effect on or change to the target structure. Kits containing products or compositions formulated or configured and systems for use in practicing these methods.

The present application relates to a method for inducing neurogenesis in an aganglionic or hypoganglionic segment of the distal colon of a human subject suffering from an enteric neuropathy such as Hirschsprung disease (HSCR) or intestinal hypoganglionosis through the administration of an effective dose of recombinant Glial cell line-Derived Neurotrophic Factor (GDNF) polypeptide into the distal colon of the subject. The method also permits to correct the imbalance of nitrergic and cholinergic neuron subtypes located upstream of the aganglionic or hypoganglionic segment and restore distal colon function (e.g., motility and epithelial barrier) in the subject.

Nanoparticles comprising resiniferatoxin (RTX) encapsulated in a poly(lactic-co-glycolic acid) (PLGA) polymer and compositions, especially topical compositions, comprising the nanoparticles. The compositions can be used as topical formulations for ameliorating pain, including for diabetic patients with peripheral neuropathy.

Nanoparticles comprising resiniferatoxin (RTX) encapsulated in a poly(lactic-co-glycolic acid) (PLGA) polymer and compositions, especially topical compositions, comprising the nanoparticles. The compositions can be used as topical formulations for ameliorating pain, including for diabetic patients with peripheral neuropathy.

Described herein are methods and pharmaceutical formulations for treating dry eye disease.