Ultrasound-assisted enzymatic synthesis of galacto-oligosaccharides using native whey with two commercial β-galactosidases: Aspergillus oryzae and Kluyveromyces var lactis.

Native whey obtained during casein micelle microfiltration was used as a novel source to produce galacto-oligosaccharides (GOS). Since the presence of macromolecules and other interferers reduces biocatalyst performance, this work evaluated the effect of different ultrasound processing conditions on GOS synthesis using concentrated native whey. Ultrasonic intensities (UI) below 11 W/cm tended to increase the activity in the enzyme from Aspergillus oryzae for several minutes but accelerated the inactivation in that from Kluyveromyces lactis.

Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties.

Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule, we synthesized and characterized the non-purine XO inhibitor caffeic acid phenethylester (CAPE) and 19 derivatives using a convenient microwave-assisted Knoevenagel condensation protocol.

Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle.

Cancer is defined as an uncontrolled proliferation of malignant cells in a host and it is one of the main causes of death worldwide. Genetic and environmental factors play an important role in its development, and the involvement of microbial communities has also recently been recognized. The close relationship that characterizes the colonization by human commensal communities involves health risks, particularly when the homeostasis is disturbed.

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells.

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance.

Cis-regulatory elements involved in species-specific transcriptional regulation of the SVCT1 gene in rat and human hepatoma cells.

Ascorbic acid is transported into cells by the sodium-coupled vitamin C transporters (SVCTs). Recently, we obtained evidence of differential regulation of SVCT expression in response to acute oxidative stress in cells from species that differ in their capacity to synthesize vitamin C, with a marked decrease in SVCT1 mRNA and protein levels in rat hepatoma cells that was not observed in human hepatoma cells. To better understand the regulatory aspects involved, we performed a structural and functional analysis of the proximal promoter of the SVCT1 rat gene.

A snapshot of cancer in Chile: analytical frameworks for developing a cancer policy.

Introduction: The South American country Chile now boasts a life expectancy of over 80 years. As a consequence, Chile now faces the increasing social and economic burden of cancer and must implement political policy to deliver equitable cancer care. Hindering the development of a national cancer policy is the lack of comprehensive analysis of cancer infrastructure and economic impact.

Lectin-like oxidized LDL receptor-1 is an enhancer of tumor angiogenesis in human prostate cancer cells.

Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas.

Altered corepressor SMRT expression and recruitment to target genes as a mechanism that change the response to androgens in prostate cancer progression.

Androgen receptor (AR) is required for the development and progression of prostate cancer (CaP) from androgen-dependence to androgen-resistance. Both corepressors and coactivators regulate AR-mediated transcriptional activity, and aberrant expression or activity due to mutation(s) contributes to changes in AR function in the progression to androgen resistance acquired during hormonal ablation therapies. Primary culture of epithelial cells from androgen-dependent CWR22 and androgen-resistant CWR22R xenograft tumors were used to evaluate the effect of androgens on AR function, and the association with coactivators (SRC-1 and TIF-2) and corepressors (SMRT and NCoR).

Biochemical characterization of nuclear receptors for vitamin D3 and glucocorticoids in prostate stroma cell microenvironment.

The disruption of stromal cell signals in prostate tissue microenvironment influences the development of prostate cancer to androgen independence. 1α,25-Dihydroxyvitamin D(3) (1,25D(3)) and glucocorticoids, either alone or in combination, have been investigated as alternatives for the treatment of advanced prostate cancers that fails androgen therapies. The effects of glucocorticoids are mediated by the intracellular glucocorticoid receptor (GR).

Prx1 enhances androgen receptor function in prostate cancer cells by increasing receptor affinity to dihydrotestosterone.

Androgen receptor (AR) signaling plays a critical role in the development and progression of prostate cancer. It has been reported previously that peroxiredoxin-1 (Prx1), a member of a novel family of peroxidases, interacts physically with AR to enhance AR transactivation of target genes. In the present study, we evaluated the biological significance of Prx1 in modulating dihydrotestosterone (DHT)-stimulated growth and AR target gene expression of prostate cancer cells.

Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell.

Androgen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. The acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. However, rat prostate endothelial cells were reported not to express androgen receptor (AR), and the role of the androgen axis in human prostate endothelial cell (HPEC) homeostasis was poorly characterized.

1alpha,25-dihydroxy vitamin D3-enhanced expression of the osteocalcin gene involves increased promoter occupancy of basal transcription regulators and gradual recruitment of the 1alpha,25-dihydroxy vitamin D3 receptor-SRC-1 coactivator complex.

Binding of 1alpha,25-dihydroxy vitamin D(3) to the C-terminal ligand-binding domain (LBD) of its receptor (VDR) induces a conformational change that enables interaction of VDR with transcriptional coactivators such as members of the p160/SRC family or the DRIP (vitamin D receptor-interacting complex)/Mediator complex. These interactions are critical for VDR-mediated transcriptional enhancement of target genes. The p160/SRC members contain intrinsic histone acetyl transferase (HAT) activities that remodel chromatin at promoter regulatory regions, and the DRIP/Mediator complex may establish a molecular bridge between the VDR complex and the basal transcription machinery.

[Differences in the synthesis pattern of vasoactive factors in gestational hypertension and preeclampsia].

Background And Objective: The gestational hypertension -HG- and preeclampsia -P- are hypertensive diseases whose pathogenic mechanism has not been determined yet. The aim of this work is to define some patterns of vasoactive factors release that allow to explain the origin of the differences between both entities.

Design: Prospective case-control study.

Altered VDR-mediated transcriptional activity in prostate cancer stroma.

The 1alpha,25-dihydroxy-vitamin D(3) (1alpha,25(OH)(2)D(3)) mediated gene transcription in primary cultures of human prostate cells was analyzed using an adenoviral luciferase expression reporter under the control of the 25-hydroxy-vitamin D(3)-24-hydroxylase (CYP24) gene promoter. Stromal cells isolated from benign and malignant associated stroma (BAS and CAS) of a human clinical sample have been determined to contain similar levels of functional 1alpha,25(OH)(2)D(3) receptor (VDR). However, VDR-mediated reporter activity of the luciferase reporter has been found to be limited 7-9-fold in CAS compared to 14-16-fold in BAS.

Phosphorylation at serine 208 of the 1alpha,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators.

Upon ligand binding the 1alpha,25-dihydroxy Vitamin D3 receptor (VDR) undergoes a conformational change that allows interaction with coactivator proteins including p160/SRC family members and the multimeric DRIP complex through the DRIP205 subunit. Casein kinase II (CKII) phosphorylates VDR both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of VDR to bind DNA, but increases its ability to transactivate target promoters.

Stromal-epithelial cell interactions and androgen receptor-coregulator recruitment is altered in the tissue microenvironment of prostate cancer.

Tissue recombination experiments show that prostate mesenchyma directs prostate epithelial cell growth and development in an androgen-dependent manner, and that functional differentiation of prostate epithelium requires androgen-driven processes in both epithelia and stroma. The androgen induction of target genes in primary cultures of prostate stromal and epithelial cells was determined using an adenoviral expression system, which employed the MMTV-enhancer driven luciferase reporter as an androgen receptor (AR)-mediated transcription assay. These studies indicate that both cell types contain functional AR.

The 1alpha,25-dihydroxy Vitamin D3 receptor preferentially recruits the coactivator SRC-1 during up-regulation of the osteocalcin gene.

Binding of 1alpha,25-dihydroxy Vitamin D3 to the C-terminal domain (LBD) of its receptor (VDR), induces a conformational change that enables interaction of VDR with transcriptional coactivators such as the members of the p160/SRC family or the DRIP (Vitamin D interacting complex)/Mediator complex. These interactions are critical for VDR-mediated transcriptional enhancement of target genes. Recent reports indicate that nuclear receptors, including VDR, interact with p160/SRC members and the DRIP/Mediator complex in a sequential, cyclical, and mutually exclusive manner when bound to a target promoter, exhibiting also a high exchange rate.

Mechanistic insights and functional determinants of the transport cycle of the ascorbic acid transporter SVCT2. Activation by sodium and absolute dependence on bivalent cations.

We characterized the human Na(+)-ascorbic acid transporter SVCT2 and developed a basic model for the transport cycle that challenges the current view that it functions as a Na(+)-dependent transporter. The properties of SVCT2 are modulated by Ca(2+)/Mg(2+) and a reciprocal functional interaction between Na(+) and ascorbic acid that defines the substrate binding order and the transport stoichiometry. Na(+) increased the ascorbic acid transport rate in a cooperative manner, decreasing the transport K(m) without affecting the V(max), thus converting a low affinity form of the transporter into a high affinity transporter.

Hypoxia increases androgen receptor activity in prostate cancer cells.

Recent studies show that prostate cancer cells are able to survive in a hypoxic tumor environment, and the extent of tumor hypoxia correlates with poor clinical outcome. Androgen deprivation, the most common form of prostate cancer therapy, was itself shown to induce a state of transient hypoxia at the microenvironmental level. Because androgen receptor (AR) signaling plays a critical role in prostate cancer, we investigated the effect of hypoxia in regulating AR function.

Mechanisms of selenium down-regulation of androgen receptor signaling in prostate cancer.

Prevention trials showed that selenium reduced prostate cancer incidence by 50%, establishing selenium as a promising chemopreventive agent for prostate cancer. Selenium inhibited human prostate cancer cell growth, blocked cell cycle progression at multiple transition points, and induced apoptotic cell death. Previous studies showed a novel mechanism of selenium anticancer action in which selenium markedly reduces androgen signaling and androgen receptor (AR)-mediated gene expression, including prostate-specific antigen (PSA), in human prostate cancer cells.

Selenium disrupts estrogen signaling by altering estrogen receptor expression and ligand binding in human breast cancer cells.

Cancer prevention studies suggest that selenium is effective in reducing the incidence of cancers including prostate, colon, and lung cancers. Previous reports showed that selenium inhibits premalignant human breast MCF-10AT1 and MCF10AT3B cell growth in vitro and reduces mammary tumor incidence after exposure to carcinogens in tumor models. Because estrogen is critical to the development and differentiation of estrogen target tissues, including the breast, the present study was designed to examine the effect of selenium on estrogen receptor (ER) expression and activation using methylseleninic acid (MSA), an active form of selenium in vitro.

Ikappab kinase-beta (ikkbeta) modulation of epithelial sodium channel activity.

Using the yeast two-hybrid system, we identified a number of proteins that interacted with the carboxyl termini of murine epithelial sodium channel (ENaC) subunits. Initial screens indicated an interaction between the carboxyl terminus of beta-ENaC and IkappaB kinase-beta (IKKbeta), the kinase that phosphorylates Ikappabeta and results in nuclear targeting of NF-kappaB. A true two-hybrid reaction employing full-length IKKbeta and the carboxyl termini of all three subunits confirmed a strong interaction with beta-ENaC, a weak interaction with gamma-ENaC, and no interaction with alpha-ENaC.

Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway.

Androgen receptor (AR) plays an important role in the development and progression of prostate cancer upon the action of androgen through the binding of the androgen-responsive elements (AREs) on the target genes. Abnormal activation of the AR by nonandrogen has been implicated in the progression of androgen-independent prostate cancer. The levels of interleukin-4 (IL-4) are significantly elevated in sera of patients with hormone refractory prostate cancer.