The invention provides combination therapy using enantiopure deuterium-enriched pioglitazone, pharmaceutical compositions, and methods of treating nonalcoholic steatohepatitis, diabetes, fibrotic disorders, and other disorders using the combination therapy.

The invention provides combination therapy using enantiopure deuterium-enriched pioglitazone, pharmaceutical compositions, and methods of treating nonalcoholic steatohepatitis, diabetes, fibrotic disorders, and other disorders using the combination therapy.

The present invention relates to extracted plant lipid or microbial lipid comprising docosapentaenoic acid, and processes for producing the extracted lipid.

This disclosure describes compositions including cannabinoids and omega fatty acids and methods of using those compositions including, for example, to treat or prevent inflammation, as an immunosuppressant, and/or as an anti-cancer therapeutic. In some aspects, the cannabinoid is chosen from i) CBC, CBCA, CBD, CBDA, CBDV, CBDVA, CBG, CBGA, CBL, CBLA, CBN, CBNA, THCV, THCVA, and any combination thereof, and ii) an approximately 1:1 equimolar mixture of CBD:CBDA. In some aspects, the omega fatty acid is chosen from an omega-3 fatty acid (such as ALA, DHA, or EPA), an omega-7 fatty acid, or an omega-9 fatty acid.

This disclosure describes compositions including cannabinoids and omega fatty acids and methods of using those compositions including, for example, to treat or prevent inflammation, as an immunosuppressant, and/or as an anti-cancer therapeutic. In some aspects, the cannabinoid is chosen from i) CBC, CBCA, CBD, CBDA, CBDV, CBDVA, CBG, CBGA, CBL, CBLA, CBN, CBNA, THCV, THCVA, and any combination thereof, and ii) an approximately 1:1 equimolar mixture of CBD:CBDA. In some aspects, the omega fatty acid is chosen from an omega-3 fatty acid (such as ALA, DHA, or EPA), an omega-7 fatty acid, or an omega-9 fatty acid.

New host-protective molecules containing conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5) were produced in neutrophil-endothelial co-cultures, and they are present in human and mouse tissues after sterile inflammation or infection. These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. Atorvastatin and RvT were additive in E. coli infections in mice where they accelerated resolution of inflammation and increased survival >60%. Results documented novel host protective molecules in bacterial infections, namely RvT, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components to regulate key innate protective responses in the resolution of infectious-inflammation.

New host-protective molecules containing conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5) were produced in neutrophil-endothelial co-cultures, and they are present in human and mouse tissues after sterile inflammation or infection. These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. Atorvastatin and RvT were additive in E. coli infections in mice where they accelerated resolution of inflammation and increased survival >60%. Results documented novel host protective molecules in bacterial infections, namely RvT, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components to regulate key innate protective responses in the resolution of infectious-inflammation.

New host-protective molecules containing conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5) were produced in neutrophil-endothelial co-cultures, and they are present in human and mouse tissues after sterile inflammation or infection. These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. Atorvastatin and RvT were additive in E. coli infections in mice where they accelerated resolution of inflammation and increased survival >60%. Results documented novel host protective molecules in bacterial infections, namely RvT, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components to regulate key innate protective responses in the resolution of infectious-inflammation.

Aspects of the disclosure relate to methods and compositions for treatment of certain ocular diseases and disorders, for example age-related macular degeneration (AMD). In some embodiments, the methods comprise administering a subject having AMD one or more therapeutic agents that modulate the mTORCl pathway (or a component thereof). The disclosure is based, in part, on methods for treating AMD in a subject by administering one or more kinase inhibitors, for example one or more serine/threonine kinase inhibitors. In some embodiments, at least one of the serine/threonine kinase inhibitors is a Ribosomal protein S6 kinase beta-1 (S6K1) inhibitor.

Aspects of the disclosure relate to methods and compositions for treatment of certain ocular diseases and disorders, for example age-related macular degeneration (AMD). In some embodiments, the methods comprise administering a subject having AMD one or more therapeutic agents that modulate the mTORCl pathway (or a component thereof). The disclosure is based, in part, on methods for treating AMD in a subject by administering one or more kinase inhibitors, for example one or more serine/threonine kinase inhibitors. In some embodiments, at least one of the serine/threonine kinase inhibitors is a Ribosomal protein S6 kinase beta-1 (S6K1) inhibitor.