PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes.

Neural stem cells (NSCs) are a small population of resident cells that can grow, migrate and differentiate into neuro-glial cells in the central nervous system (CNS). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor transcription factor that regulates cell growth and differentiation. In this study we analyzed the influence of PPARγ agonists on neural stem cell growth and differentiation in culture.

Differential regulation of CD4(+) T helper cell responses by curcumin in experimental autoimmune encephalomyelitis.

Nutraceuticals and phytochemicals are important regulators of human health and diseases. Curcumin is a polyphenolic phytochemical isolated from the rhizome of the plant Curcuma longa (turmeric) that has been traditionally used for the treatment of inflammation and wound healing for centuries. Systematic analyses have shown that curcumin exerts its beneficial effects through antioxidant, antiproliferative and anti-inflammatory properties.

Aptamers as a sensitive tool to detect subtle modifications in therapeutic proteins.

Therapeutic proteins are derived from complex expression/production systems, which can result in minor conformational changes due to preferential codon usage in different organisms, post-translational modifications, etc. Subtle conformational differences are often undetectable by bioanalytical methods but can sometimes profoundly impact the safety, efficacy and stability of products. Numerous bioanalytical methods exist to characterize the primary structure of proteins, post translational modifications; protein-substrate/protein/protein interactions and functional bioassays are available for most proteins that are developed as products.

Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis.

Multiple sclerosis (MS) is a neurological disorder that affects more than a million people world-wide. The aetiology of MS is not known and there is no medical treatment available that can cure MS. Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune disease model of MS.

Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus.

Vaccines against influenza viruses with pandemic potential, including H5N1, are under development. Because of a lack of preexisting immunity to these viruses, adjuvants (immune potentiators or enhancers) are needed to improve immune responses, to conserve scarce vaccine, and for cross-protection against strains that have drifted evolutionarily from the original. Aluminum-based adjuvants do not improve vaccine immunogenicity for influenza subunit vaccines, whereas oil-in-water adjuvants are effective, especially with H5N1-inactivated vaccines.

PPARgamma regulates LIF-induced growth and self-renewal of mouse ES cells through Tyk2-Stat3 pathway.

Embryonic stem (ES) cells are genetically normal, pluripotent cells, capable of self-renewal and multi-lineage differentiation. Leukemia inhibitory factor (LIF) is a growth factor that can maintain the pluripotency of mouse ES cells in culture. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor transcription factors that regulate growth and differentiation of many cell types.

Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model of multiple sclerosis. Signal transducer and activator of transcription 4 (Stat4) is a transcription factor activated by IL-12 and IL-23, two cytokines known to play important roles in the pathogenesis of EAE by inducing T cells to secrete IFN-gamma and IL-17, respectively. We and others have previously shown that therapeutic intervention or targeted disruption of Stat4 was effective in ameliorating EAE.

PPAR Regulation of Inflammatory Signaling in CNS Diseases.

Central nervous system (CNS) is an immune privileged site, nevertheless inflammation associates with many CNS diseases. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that regulate immune and inflammatory responses. Specific ligands for PPARalpha, gamma, and delta isoforms have proven effective in the animal models of multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, and trauma/stroke, suggesting their use in the treatment of neuroinflammatory diseases.

15-deoxy-Delta(12,14)-prostaglandin J(2) and curcumin modulate the expression of toll-like receptors 4 and 9 in autoimmune T lymphocyte.

Introduction: Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model for multiple sclerosis (MS). We have shown earlier that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and curcumin ameliorate EAE by modulating inflammatory signaling pathways in T lymphocytes. Toll-like receptors (TLRs), expressed primarily in innate immune cells, play critical roles in the pathogenesis of EAE.

Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin.

Many studies have been performed with the aim of developing effective resistance modulators to overcome the multidrug resistance (MDR) of human cancers. Potent MDR modulators are being investigated in clinical trials. Many current studies are focused on dietary herbs due to the fact that these have been used for centuries without producing any harmful side effects.

Modulation of the function of the multidrug resistance-linked ATP-binding cassette transporter ABCG2 by the cancer chemopreventive agent curcumin.

Curcumin (curcumin I), demethoxycurcumin (curcumin II), and bisdemethoxycurcumin (curcumin III) are the major forms of curcuminoids found in the turmeric powder, which exhibit anticancer, antioxidant, and anti-inflammatory activities. In this study, we evaluated the ability of purified curcuminoids to modulate the function of either the wild-type 482R or the mutant 482T ABCG2 transporter stably expressed in HEK293 cells and drug-selected MCF-7 FLV1000 and MCF-7 AdVp3000 cells. Curcuminoids inhibited the transport of mitoxantrone and pheophorbide a from ABCG2-expressing cells.

Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1).

Multidrug resistance is a major cause of chemotherapy failure in cancer patients. One of the resistance mechanisms is the overexpression of drug efflux pumps such as P-glycoprotein and multidrug resistance protein 1 (MRP1, (ABCC1)). In this study, curcumin mixture and three major curcuminoids purified from turmeric (curcumin I, II, and III) were tested for their ability to modulate the function of MRP1 using HEK293 cells stably transfected with MRP1-pcDNA3.