The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer.

BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity.

Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer.

Silencing of androgen receptor (AR) signaling is a specific and effective mechanism to cure cancer of the prostate (CaP). In this study, the isolation and characterization of a compound from the aromatic berries of Pimenta dioica (allspice) that silences AR is presented. Potential antitumor activities of an aqueous allspice extract (AAE) and a compound purified from the extract were tested on CaP cells.

Chlamydial infection in vitamin D receptor knockout mice is more intense and prolonged than in wild-type mice.

Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection.

Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase.

Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E₂ (PGE₂).

Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.

Eplerenone suppresses aldosterone/ salt-induced expression of NOX-4.

Introduction: Salt-induced hypertension in the Dahl rat is associated with increases in angiotensin II, aldosterone, free radical generation and endothelial dysfunction. However, little is known about the specific mechanism(s) associated with the end-organ damage effects of aldosterone. We hypothesised that eplerenone reduces kidney damage by blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.

CXC receptor-1 silencing inhibits androgen-independent prostate cancer.

The CXC receptor-1 (CXCR1) is a coreceptor for interleukin-8 (IL-8) and is expressed on both normal and tumor cells. The function of CXCR1 in prostate cancer was investigated by silencing its expression, using RNA interference. We established stable cell colonies of PC-3 cells, depleted of CXCR1, using lentiviral plasmids (pLK0.

Role of T lymphocytes in the pathogenesis of Chlamydia disease.

Vaccines are needed to prevent the oculogenital diseases of Chlamydia trachomatis. Infected hosts develop immunity, although temporary, and experimental vaccines have yielded significant protective immunity in animal models, fueling the impetus for a vaccine. Because infections cause sequelae, the functional relationship between infection- and vaccine-induced immunity is unclear.

A Vibrio cholerae ghost-based subunit vaccine induces cross-protective chlamydial immunity that is enhanced by CTA2B, the nontoxic derivative of cholera toxin.

The Vibrio cholerae ghost (rVCG) platform is an effective carrier and delivery system for designing efficacious Chlamydia vaccines. We investigated whether CTA2B, the nontoxic derivative of cholera toxin, can augment protective immunity conferred by an rVCG-based chlamydial vaccine and enhance cross-protection against heterologous chlamydial strains. An rVCG vaccine coexpressing chlamydial major outer membrane protein and CTA2B was genetically constructed and antigens were targeted to the inner membrane of V.

Involvement of LEK1 in dendritic cell regulation of T cell immunity against Chlamydia.

We investigated the hypothesis that the enhanced Ag-presenting function of IL-10-deficient dendritic cells (DCs) is related to specific immunoregulatory cytoskeletal molecules expressed when exposed to Ags. We analyzed the role of a prominent cytoskeletal protein, LEK1, in the immunoregulation of DC functions; specifically cytokine secretion, costimulatory molecule expression, and T cell activation against Chlamydia. Targeted knockdown of LEK1 expression using specific antisense oligonucleotides resulted in the rapid maturation of Chlamydia-exposed DCs as measured by FACS analysis of key activation markers (i.

Immunogenicity and protection against genital Chlamydia infection and its complications by a multisubunit candidate vaccine.

Background And Purpose: Genital infections due to Chlamydia trachomatis pose a considerable public health challenge worldwide and a vaccine is urgently needed to protect against these infections. We examined whether a vaccine composed of a combination of the major outer membrane protein (MOMP) and porin B protein (PorB) of C. trachomatis would have a protective advantage over a single subunit construct.

Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer.

The proinflammatory chemokine interleukin-8 (IL-8) is undetectable in androgen-responsive prostate cancer cells (e.g., LNCaP and LAPC-4), but it is highly expressed in androgen-independent metastatic cells, such as PC-3.

Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines.

Effective delivery systems are needed to design efficacious vaccines against the obligate intracellular bacterial pathogen, Chlamydia trachomatis. Potentially effective delivery vehicles should promote the induction of adequate levels of mucosal T-cell and antibody responses that mediate long-term protective immunity. Antigen targeting to the nasal-associated lymphoid tissue (NALT) is effective for inducing high levels of specific immune effectors in the genital mucosa, and therefore suitable for vaccine delivery against genital chlamydial infection.

Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion.

T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development.

Molecular basis for the potency of IL-10-deficient dendritic cells as a highly efficient APC system for activating Th1 response.

Identification and targeting of novel immunobiological factors that regulate the induction of Th1 cells are crucial for designing effective vaccines against certain intracellular pathogens, including Chlamydia. IL-10-deficient dendritic cells (DC) are potent APCs and effective cellular vaccines that activate a high frequency of specific Th1 cells. To elucidate the molecular basis for the potency of the IL-10-deficient APC system, we tested the hypothesis that Chlamydia Ag-primed IL-10 knockout (IL-10KO) DC are quantitatively and qualitatively distinct in their metabolic characteristics relating to T cell activation.

The 894T allele of endothelial nitric oxide synthase gene is related to left ventricular mass in African Americans with high-normal blood pressure.

Background And Objectives: The 894T allele in exon 7 of the endothelial nitric oxide synthase (eNOS) gene has been inconsistently associated with hypertension in different racial groups. Because high-normal blood pressure (BP) confers an increased risk for the development of hypertension and other cardiovascular disorders, including left ventricular hypertrophy (LVH), we tested the hypothesis that the allelic variation (894T) in the eNOS gene would directly correlate with alterations in LV mass (LVM) in individuals with high-normal BP.

Methods: Genotype distribution of G894T was compared between 20 African Americans (10 females/10 males) with high-normal BP (systolic BP of 130-139 and/or diastolic BP of 85-89 mmHg) and 64 counterparts (37 females/27 males) with normal BP (<130/85 mmHg).

A novel recombinant multisubunit vaccine against Chlamydia.

The administration of an efficacious vaccine is the most effective long-term measure to control the oculogenital infections caused by Chlamydia trachomatis in humans. Chlamydia genome sequencing has identified a number of potential vaccine candidates, and the current challenge is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. Vibrio cholerae ghosts (VCG) are nontoxic, effective delivery vehicles with potent adjuvant properties, and are capable of inducing both T cell and Ab responses in mucosal tissues.

Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans.

Background: The role of eNOS gene polymorphisms on plasma nitrite or nitrate (NOx) level, endothelial function, and blood pressure (BP) remains unclear.

Methods: We estimated the relationship of eNOS polymorphisms (the T(-786)C in the 5'-flanking promoter region, T(-786)C; 27-bp repeat in intron 4, eNOS4; and Glu298Asp in exon 7, G894T) with plasma NOx level, brachial endothelial function assessed by ultrasound measure of brachial artery flow-mediated dilation (FMD), and BP in 60 healthy African Americans, 30 men and 30 women aged 18 to 73 years.

Results: Among them, 73.

Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens.

Immunity to intracellular microbial pathogens, including Chlamydia species, is controlled primarily by cell-mediated effector mechanisms, yet, the absence of antibodies results in inefficient microbial clearance. We investigated the hypothesis that certain Fc receptor functions promote the rapid induction of elevated T helper type 1 (Th1) response, which effectively clears chlamydiae. FcR(-/-) mice exhibited a delayed and reduced frequency of Chlamydia-specific Th1 cells, compared to FcR(+/+) mice.

Ischemia elicits a coordinated expression of pro-survival proteins in mouse myocardium.

Cardiomyocytes are post-mitotic, long-lived cells until disruptions to pro-survival factors occur after myocardial ischemia. To gain an understanding of the factors involved with ischemic injury, we examined expression changes in pro-survival and opposing pro-apoptotic signals at early and chronic periods of ischemia using an in vivo murine model. Alterations of pro-survival proteins such as the inhibitor of apoptosis protein on chromosome X (xIAP) and the apoptotic repressor protein (ARC) have not been evaluated in a murine model of cardiac ischemia.

Recombinant Vibrio cholerae ghosts as a delivery vehicle for vaccinating against Chlamydia trachomatis.

An efficacious vaccine is needed to control the morbidity and burden of rising healthcare costs associated with genital Chlamydia trachomatis infection. Despite considerable efforts, the development of reliable chlamydial vaccines using conventional strategies has proven to be elusive. The 40kDa major outer membrane protein (MOMP) of C.

TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins.

Recent studies have shown that in vitro steady-state expression of the tumor susceptibility gene TSG101 is important for maintenance of genomic stability and cell cycle regulation. To determine the contribution of TSG101 expression in neoplastic formation, expression of TSG101 protein levels were evaluated in primary ovarian and endometrial adenocarcinoma tumors. Expression of TSG101 was also examined in various tumor cell lines (PA-1, AN3CA, HeLa, HS578T, HCT116).

Chemokine and chemokine receptor dynamics during genital chlamydial infection.

Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection.

Sequence analysis of HIV-1 insertion sites in peripheral blood lymphocytes.

An essential component of the HIV-1 life cycle involves insertion in the genome of an infected cell. The site of HIV-1 integration has the potential to disrupt a gene and perturb a normal cellular function. To begin to address whether disease pathogenesis may correlate with the site of insertion, flanking cellular sequences at these HIV integrated regions were directly amplified from peripheral blood mononuclear cells DNA from a broad range of infected individuals using an inverse polymerase chain reaction strategy.

Trypanosoma brucei infection induces apoptosis and up-regulates neuroleukin expression in the cerebellum.

Human infection with Trypanosoma brucei may result in meningo-encephalitis, neuronal demyelination, blood-brain-barrier dysfunction, peri-vascular infiltration, astrocytosis and neuronal apoptosis. Prevention of the short- or long-term, parasite-induced, neuronal assault requires a better understanding of the host's responses to the infection at the molecular level. Northern analysis, cDNA micro-arrays, reverse-transcriptase-PCR (RT-PCR), SDS-PAGE and immunohistology were therefore used to investigate global gene and protein expression in the brains of mice infected with T.