Synephrine and Its Derivative Compound A: Common and Specific Biological Effects.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models.

Roles Played by Stress-Induced Pathways in Driving Ethnic Heterogeneity for Inflammatory Skin Diseases.

Immune-mediated skin conditions (IMSCs) are a diverse group of autoimmune diseases associated with significant disease burden. Atopic dermatitis and psoriasis are among the most common IMSCs in the United States and have disproportionate impact on racial and ethnic minorities. African American patients are more likely to develop atopic dermatitis compared to their European American counterparts; and despite lower prevalence of psoriasis among this group, African American patients can suffer from more extensive disease involvement, significant post-inflammatory changes, and a decreased quality of life.

The long winding road to the safer glucocorticoid receptor (GR) targeting therapies.

Glucocorticoids (Gcs) are widely used to treat inflammatory diseases and hematological malignancies, and despite the introduction of novel anti-inflammatory and anti-cancer biologics, the use of inexpensive and effective Gcs is expected to grow. Unfortunately, chronic treatment with Gcs results in multiple atrophic and metabolic side effects. Thus, the search for safer glucocorticoid receptor (GR)-targeted therapies that preserve therapeutic potential of Gcs but result in fewer adverse effects remains highly relevant.

Targeting transcription factor NFkappaB: comparative analysis of proteasome and IKK inhibitors.

Nuclear factorkappaB (NFkappaB) plays a critical role in cancer development and progression. Thus, the NFkappaB signaling pathway provides important targets for cancer chemoprevention and anticancer chemotherapy. The central steps in NFkappaB activation are phosphorylation and proteasome-dependent degradation of its inhibitory proteins termed IkappaBs.

Epithelial cells in the hair follicle bulge do not contribute to epidermal regeneration after glucocorticoid-induced cutaneous atrophy.

One of the major adverse effects of glucocorticoid therapy is cutaneous atrophy, often followed by the development of resistance to steroids. It is accepted that epithelial stem cells (SCs) located in the hair follicle bulge divide during times of epidermal proliferative need. We determined whether follicular epithelial SCs and their transit amplifying progeny were stimulated to proliferate in response to the chronic application of glucocorticoid fluocinolone acetonide (FA).

Glucocorticoid receptor functions as a potent suppressor of mouse skin carcinogenesis.

Glucocorticoids are effective inhibitors of epidermal proliferation and skin tumorigenesis. Glucocorticoids affect cellular functions via glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated skin-targeted transgenic mice overexpressing GR under control of the keratin5 promoter (K5-GR mice).

Selenium compounds inhibit I kappa B kinase (IKK) and nuclear factor-kappa B (NF-kappa B) in prostate cancer cells.

Selenium compounds are potential chemopreventive agents for prostate cancer. There are several proposed mechanisms for their anticancer effect, including enhanced apoptosis of transformed cells. Because the transcription factor nuclear factor-kappa B (NF-kappa B) is often constitutively activated in tumors and is a key antiapoptotic factor in mammalian cells, we tested whether selenium inhibited NF-kappa B activity in prostate cancer cells.

The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells.

Rel/NF-kappaB transcription factors are implicated in the control of cell proliferation, apoptosis and transformation. The key to NF-kappaB regulation is the inhibitory IkappaB proteins. During response to diverse stimuli, IkappaBs are rapidly phosphorylated by IkappaB kinases (IKKs), ubiquitinated and undergo degradation.

Functional roles of Akt signaling in mouse skin tumorigenesis.

The mouse skin carcinogenesis protocol is a unique model for understanding the molecular events leading to oncogenic transformation. Mutations in the Ha-ras gene, and the presence of functional cyclin D1 and the EGF receptor, have proven to be important in this system. However, the signal transduction pathways connecting these elements during mouse skin carcinogenesis are poorly understood.