Retinoic acid, or an analogue thereof, is delivered within an oil-in-water emulsion to provide an improved immunological adjuvant.

Retinoic acid, or an analogue thereof, is delivered within an oil-in-water emulsion to provide an improved immunological adjuvant.

The present invention relates to ophthalmic compositions and methods for the treatment of dry eye and other inflammatory ocular conditions. In particular, the present invention relates to a composition comprising an esterified anti-inflammatory lipid mediator, which is an ester of an anti-inflammatory lipid mediator that is a reaction product of the anti-inflammatory lipid mediator and a monohydric alcohol or an amide wherein the majority of the anti-inflammatory lipid mediator is present in an ester form. In this way, the compositions are substantially free of an acid form of the anti-inflammatory lipid mediators. Anti-inflammatory lipid mediators can be selected from the group consisting of polyunsaturated fatty acids (e.g., omega-three and omega-six fatty acids), resolvins or a metabolically stable analog, protectins or a metabolically stable analog, lipoxins or a metabolically stable analog, prostaglandins or a metabolically stable analog, retinoic acids, endocannabinoids, metabolites thereof, and mixtures thereof. This composition can be topically delivered to the ocular surface via a preparation, solution, gel, ointment, and/or strip and/or a contact lens.

The present invention relates to ophthalmic compositions and methods for the treatment of dry eye and other inflammatory ocular conditions. In particular, the present invention relates to a composition comprising an esterified anti-inflammatory lipid mediator, which is an ester of an anti-inflammatory lipid mediator that is a reaction product of the anti-inflammatory lipid mediator and a monohydric alcohol or an amide wherein the majority of the anti-inflammatory lipid mediator is present in an ester form. In this way, the compositions are substantially free of an acid form of the anti-inflammatory lipid mediators. Anti-inflammatory lipid mediators can be selected from the group consisting of polyunsaturated fatty acids (e.g., omega-three and omega-six fatty acids), resolvins or a metabolically stable analog, protectins or a metabolically stable analog, lipoxins or a metabolically stable analog, prostaglandins or a metabolically stable analog, retinoic acids, endocannabinoids, metabolites thereof, and mixtures thereof. This composition can be topically delivered to the ocular surface via a preparation, solution, gel, ointment, and/or strip and/or a contact lens.

The present invention provides methods and kits a) for preventing and/or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and/or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and/or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylornithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and/or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.

The present invention provides methods and kits a) for preventing and/or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and/or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and/or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylornithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and/or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.

The present invention provides methods and kits a) for preventing and/or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and/or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and/or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylornithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and/or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.

Transgenic mice (Crym tg) overexpressing Crym protein in skeletal muscle were studied. Muscular functions, Ca.sup.2+ transients, contractile force, fatigue, and running on treadmills or wheels were not significantly altered and serum T.sub.3 and thyroid stimulating hormone levels were unaffected although T.sub.3 levels in tibialis anterior (TA) muscle were elevated and serum T.sub.4 was decreased. Crym tg mice had a decreased respiratory exchange ratio, corresponding to a 13.7% increase in fat utilization. Female Crym tg mice gained weight more rapidly than controls on high fat or high simple carbohydrate diets. Machine learning algorithms revealed morphological differences between Crym tg and control soleus fibers. RNA-seq and gene ontology enrichment analysis showed a shift towards genes associated with slower muscle function and β-oxidation. Therefore, high levels of μ-crystallin are associated with greater fat metabolism. These data indicate that Crym and μ-crystallin can be used as a treatment modality for diabetes and obesity.

Transgenic mice (Crym tg) overexpressing Crym protein in skeletal muscle were studied. Muscular functions, Ca.sup.2+ transients, contractile force, fatigue, and running on treadmills or wheels were not significantly altered and serum T.sub.3 and thyroid stimulating hormone levels were unaffected although T.sub.3 levels in tibialis anterior (TA) muscle were elevated and serum T.sub.4 was decreased. Crym tg mice had a decreased respiratory exchange ratio, corresponding to a 13.7% increase in fat utilization. Female Crym tg mice gained weight more rapidly than controls on high fat or high simple carbohydrate diets. Machine learning algorithms revealed morphological differences between Crym tg and control soleus fibers. RNA-seq and gene ontology enrichment analysis showed a shift towards genes associated with slower muscle function and β-oxidation. Therefore, high levels of μ-crystallin are associated with greater fat metabolism. These data indicate that Crym and μ-crystallin can be used as a treatment modality for diabetes and obesity.

A porous silica particles according to an embodiment of the present disclosure includes a plurality of pores with a diameter of 5 nm to 100 nm. The porous silica particles have particular physical properties, can deliver all various drugs by a supported amount in a sustained manner, and can be parenterally administered.