The present invention relates to compounds of formula (I) that are capable of modulating, e.g., inhibiting or activating, one or more kinases, especially LRRK2 and/or NUAK1 and/or TYK2 or mutants thereof. The compounds are useful for treating diseases, such as autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, Alzheimer's disease, Parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 40 to 146; examples 1 to 63; compounds 1 to 248; tables 1 to 3). Preferred compounds are e.g. 1,4-dihydrobenzo[d]pyrazolo[3,4-f] [1,3]diazepine derivatives and related compounds. An exemplary compound is e.g. 5-(2,6-difluorophenyl)-8-methoxy-1,4-dihydrobenzo[d]pyrazolo[3,4-f] [1,3]diazepine (example 49). (Formula (II)).

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Provided herein are genetically engineered mammalian stem and progenitor cells that have increased potential to differentiate into regulatory T cells. Also provided are methods of making and use thereof.

The present disclosure provides 6-hydrazinoadenosine represented by the general Formula (I) and its derivatives with A.sub.2A adenosine receptor agonist activity, and pharmaceutical compositions containing them. The compound and composition can be used as A.sub.2A adenosine receptor agonists and used as medicament.

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Some embodiments of the invention include methods for treating an animal for a disease comprising one or more administrations of one or more compositions comprising (a) a TNF signaling inhibitor, (b) a CD40 inhibitor, a FAS signaling inhibitor, or both, and (c) optionally, a caspase 8 inhibitor. Other embodiments include methods for treating the disease comprising one or h more administrations of one or more compositions comprising (a) the TNF signaling inhibitor and (b) the CD40 inhibitor. Certain embodiments include methods for treating the disease comprising one or more administrations of one or more compositions comprising (a) the TNF signaling inhibitor, (b) the FAS signaling inhibitor, and (c) optionally, the caspase 8 inhibitor. Still other embodiments include methods for treating a human for autoimmune disease, T cell mediated autoimmune disease, IL-1β mediated autoimmune disease, or cytokine release syndrome. Additional embodiments of the invention are also discussed herein.

Some embodiments of the invention include methods for treating an animal for a disease comprising one or more administrations of one or more compositions comprising (a) a TNF signaling inhibitor, (b) a CD40 inhibitor, a FAS signaling inhibitor, or both, and (c) optionally, a caspase 8 inhibitor. Other embodiments include methods for treating the disease comprising one or h more administrations of one or more compositions comprising (a) the TNF signaling inhibitor and (b) the CD40 inhibitor. Certain embodiments include methods for treating the disease comprising one or more administrations of one or more compositions comprising (a) the TNF signaling inhibitor, (b) the FAS signaling inhibitor, and (c) optionally, the caspase 8 inhibitor. Still other embodiments include methods for treating a human for autoimmune disease, T cell mediated autoimmune disease, IL-1β mediated autoimmune disease, or cytokine release syndrome. Additional embodiments of the invention are also discussed herein.

Novel compounds, in particular novel peroxisome proliferator-activated receptor (PPAR) agonist compounds, are provided. Pharmaceutical formulations for treating PPAR mediated disorder or condition are also provided. The formulations may be a combination of cannabinoids and the PPAR agonist compounds. The PPAR mediated disorder or condition may include inflammation related diseases such as psoriasis, psoriatic arthritis and atopic dermatitis.

Novel compounds, in particular novel peroxisome proliferator-activated receptor (PPAR) agonist compounds, are provided. Pharmaceutical formulations for treating PPAR mediated disorder or condition are also provided. The formulations may be a combination of cannabinoids and the PPAR agonist compounds. The PPAR mediated disorder or condition may include inflammation related diseases such as psoriasis, psoriatic arthritis and atopic dermatitis.

The present invention provides a composition comprising dendritic cells loaded with hHsp60sp, which dendritic cells are from a subject and have been fixed with paraformaldehyde (PFA). The subject may suffer from an autoimmune disease. Also provided are a method for preparing the composition; recombinant human cells comprising a heterologous gene encoding a fusion protein of HLA-E and hHsp60sp or B7sp, and expressing the fusion protein on the surface of the cells; a method for determining a percentage of maximum inhibition of testing the function of the HLA-E restricted CD8+ Treg cells from a subject, determining whether HLA-E restricted CD8+ Treg cells freshly isolated from a subject are defective, or determining whether defective HLA-E restricted CD8+ Treg cells from a subject are correctable; and a method for correcting defective HLA-E restricted CD8+ Treg cells, treating type 1 diabetes (T1D), or treating multiple sclerosis (MS).

The present invention is directed to carrier systems comprising ether-lipids conjugated to one or more bioactive ligands and exposed on the surface of the carrier system for use in targeted delivery and/or antigen display systems. Optionally one or more further bioactive agents may be encapsulated or embedded within or attached to or adsorbed onto the carrier system. The present invention is further directed to methods of their preparation and their uses in medical applications, such as targeted delivery of bioactive agents to specific tissues or cells and antigen display systems for the study, diagnosis, and treatment of traits, diseases and conditions that respond to said bioactive agents.

Compound of formula (I) or a pharmaceutically acceptable salt, or N-oxide thereof, that are inhibitors of SSAO activity: ##STR00001##
where V, W, X, Y, Z, R.sup.1, and R.sup.3 are as defined herein.