Disclosed herein are monomeric and oligomeric compound embodiments for use as contraceptive agents. Monomeric compound embodiments disclosed herein comprise substituents that facilitate the ability of the compounds to exhibit progestogenic, androgenic, and estrogenic activity, which can prevent or inhibit bone density loss in subjects. Oligomeric compound embodiments disclosed herein provide the ability to control receptor activation and/or treatment by incorporating a tunable linker group which couples steroidal-based compounds to one another or with therapeutic agents and facilitates selective cleavage of the monomeric components of the oligomeric compound.

The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.

A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX.sup.1X.sup.2rCrUrGrCrUrGrCrUrG (I), wherein X.sup.1 and X.sup.2 are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X.sup.1 and X.sup.2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.

A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX.sup.1X.sup.2rCrUrGrCrUrGrCrUrG (I), wherein X.sup.1 and X.sup.2 are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X.sup.1 and X.sup.2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.

Bromocriptine citrate administered to a vertebrate, animal or human, can be used for any purpose including, e.g., the long-term modification and regulation of metabolic disorders, including prediabetes, obesity, insulin resistance, hyperinsulinemia, hyperglycemia and type 2 diabetes mellitus (T2DM) and/or, e.g., the treatment of other medical disorder(s) including immune or endocrine disorders or diseases. Bromocriptine citrate is administered over a limited or extended period at a time of day dependent on re-establishing the normal circadian rhythm of central dopaminergic activity of healthy members of a similar species and sex. Insulin resistance, hyperinsulinemia and hyperglycemia, T2DM, prediabetes, MS or all, can be controlled in humans on a long term basis by such treatment inasmuch as the daily administration of bromocriptine citrate resets neuronal activity timing in the neural centers of the brain to produce long term effects.

This application provides a composition for preventing, alleviating and/or treating a heat illness, or cytotoxicity of cells such as vascular endothelial cells caused by load of heat stress and/or aberration associated with the production and release of a fever-inducing inflammatory cytokine(s) from blood cells caused by load of heat stress in a subject, comprising at least one substance selected from the group consisting of auraptene, tangeretin, and medium chain fatty acid as an active ingredient.

A compound of general formula (1) ##STR00001## [wherein: R.sub.1 and R.sub.2, which are the same or different, each represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower cycloalkyl group, a lower alkanoyl group, a halogen substituted lower alkyl group, a lower alkoxy group, a halogen substituted lower alkoxy group, a cyano group, a cross-linked methylenedioxy group, an ethylenedioxy group, a propylenedioxy group, a lower alkylthio group, a lower alkylsulfonyl group, a carboxyl group, a lower alkoxycarbonyl group, a lower alkylamide group, a lower alkylamino alkylene amide group, an amino group, an alkylamino group, a hydroxy group, a functional group represented by general formula (2), or a functional group represented by general formula (3)
—CONH(CH.sub.2).sub.p—R.sub.3  (2) [wherein R.sub.3 represents a di-lower alkylamino group, a morpholino group, a piperidino group, a 2-methyl-piperidino group, or a 2-oxo-pyrrolidinyl group; p represents an integer from 2 to 6]; ##STR00002## [wherein, R.sub.4 represents a lower alkyl group]; m and n each represent an integer from 0 to 3; the term lower represents a carbon number of 1 to 6; and the halogen atom represents a fluorine, chlorine or bromine atom] can inhibit endoplasmic reticulum stress to a greater extent as compared to known chemical chaperones. The compound thus can be used suitably as an agent for preventing, ameliorating or treating various diseases that are caused by endoplasmic reticulum stress.

The invention relates to variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of FGF19 and/or FGF21, and variants or fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics), having one or more activities, such as bile acid homeostasis modulating activity, and methods for and uses in treatment of bile acid and other disorders.

The present disclosure generally relates to viral-based expression systems suitable for the production of molecule of interests in recombinant host cells. The disclosure particularly relates to nucleic acid constructs, such as expression vectors, containing a modified arterivirus genome or replicon RNA in which at least some of its original viral sequence has been deleted. Also included in the disclosure are viral-based expression vectors including one or more expression cassettes encoding heterologous polypeptides. In some embodiments, the expression cassettes are configured and positioned at defined locations on the viral genome so as to enable expression of the heterologous polypeptides in a tunable manner.

A method of treating a disorder in a subject. The method comprises administering to said subject an effective amount of an agonist of the melanocortin-4 receptor (MC4R). The subject is a heterozygous carrier of an MC4R mutation, and the disorder results from an attenuated response of MC4R to α-melanocortin stimulating hormone (α-MSH).