Cancer cells with stem or progenitor properties play a pivotal role in the initiation, recurrence and metastatic potential of solid tumors, including those of the human prostate. Cancer stem cells are generally more resistant to conventional therapies thus requiring the characterization of key pathways involved in the formation and/or maintenance of this malignant cellular subpopulation. To thi...

Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT) is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β) is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played b...

Two new epoxy steroids, 5α,8α-epidioxy-22β,23β-epoxyergosta-6-en-3β-ol (1) and 5α,8α-epidioxy-22α,23α-epoxyergosta-6-en-3β-ol (2), and ten known steroids including (24R)-5α,8α-epidioxyergosta-6-en-3β-ol (3), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (4), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3β-ol (5), β-sitosterol (6), sitost-5-en-3β-ol acetate (7), 7α-hydroxysitosterol (8), s...

Purpose: To determine the effect of dexmedetomidine on sepsis-mediated acute kidney injury (SAKI) in rats.
 Methods: Twenty-four SD rats were randomly divided into blank untreated control group, model group given lipopolysaccharide at a dose 10 mg/kg, (Dex) and glycogen synthase kinase-3 beta (GSK-3β) inhibitor sb216763. In addition, Dex groups received same as group. There each Pathologic...

Organic matter in soils and sediments derives from a mixture of biological origins, often making it difficult to determine inputs individual sources. Complicating the determination source soil sedimentary organic (OM) is fact that physical microbial processes have likely modified initial composition these This study focused on identifying watershed-derived OM better understand inland waters imp...

In this research, dried acetone:chloroform extract of aerial parts of E. denticulata as one of the endemic plants to Iran, afforded a number of triterpenes and steroids including: betulin, 24-methylene-cycloart-3-ol, cycloart-23Z-ene-3β,25-diol, cycloart-23Z-ene-3β,25-diol, ergosta-8,24-dien-3-ol (obtusifoliol) and beta-sitosterol which were reported for the first time from this plant. The stru...

Glycogen synthase kinase-3 beta (GSK-3β) has been investigated as a therapeutic target for numerous human diseases including cancer because of their diverse cellular functions. Although GSK-3β inhibitors have been investigated as anticancer reagents, precise biological mechanisms remain to be determined. In this study, we investigated the anticancer effects of GSK-3β inhibitors on cancer cell l...

BACKGROUND Myocardial infarction-induced remodeling includes chamber dilatation, contractile dysfunction, and fibrosis. Of these, fibrosis is the least understood. After myocardial infarction, activated cardiac fibroblasts deposit extracellular matrix. Current therapies to prevent fibrosis are inadequate, and new molecular targets are needed. METHODS AND RESULTS Herein we report that glycogen...

Abnormal hyperphosphorylation of tau is pivotally involved in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Glycogen synthase kinase 3β (GSK-3β) is a primary tau kinase that is most implicated in tau pathology in AD. However, the exact molecular nature of GSK-3β involved in AD is unclear. In the present study, we found that GSK-3β was truncated at C-terminus and correlat...

A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC₅₀ value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ...