Identification of A Novel Antibacterial Peptide from Atlantic Mackerel belonging to the GAPDH-Related Antimicrobial Family and Its In Vitro Digestibility.

The Atlantic mackerel, , is one of the most fished species in the world, but it is still largely used for low-value products, such as bait; mainly for crustacean fishery. This resource could be transformed into products of high value and may offer new opportunities for the discovery of bioactive molecules. Mackerel hydrolysate was investigated to discover antibacterial peptides with biotechnological potential.

Poly(ADP-ribosyl)ation-dependent Transient Chromatin Decondensation and Histone Displacement following Laser Microirradiation.

Chromatin undergoes a rapid ATP-dependent, ATM and H2AX-independent decondensation when DNA damage is introduced by laser microirradiation. Although the detailed mechanism of this decondensation remains to be determined, the kinetics of decondensation are similar to the kinetics of poly(ADP-ribosyl)ation. We used laser microirradiation to introduce DNA strand breaks into living cells expressing a photoactivatable GFP-tagged histone H2B.

Transgenic ω-3 PUFA enrichment alters morphology and gene expression profile in adipose tissue of obese mice: Potential role for protectins.

Objective: Dietary administration of ω-3 polyunsaturated fatty acids (PUFA) is often associated with altered adipose tissue (AT) morphology and/or function in obese mice. Yet, it is unclear whether this is an indirect consequence of reduced weight gain or results from direct actions of ω-3 PUFA. Here we studied the AT of high fat (HF)-fed fat-1 transgenic mice that convert endogenous ω-6 to ω-3 PUFA while maintaining equivalent fat accretion as their wild-type (WT) counterparts.

CXCL10 triggers early microglial activation in the cuprizone model.

A broad spectrum of diseases is characterized by myelin abnormalities and/or oligodendrocyte pathology. In most, if not all, of these diseases, early activation of microglia occurs. Our knowledge regarding the factors triggering early microglia activation is, however, incomplete.

Androgenic action of dehydroepiandrosterone (DHEA) on nerve density in the ovariectomized rat vagina.

Introduction: We have recently reported that dehydroepiandrosterone (DHEA) increases the density of nerve fibers in the ovariectomized (OVX) rat vagina.

Aim: To better define the mechanism of action of DHEA, we have examined the effect of DHEA, conjugated estrogens (premarin) and the potent blocker of estrogen action acolbifene on the innervation in the lamina propria in the OVX rat vagina.

Methods: Female Sprague-Dawley rats (10-12 weeks old) were used.

Determinants of pain, functional limitations and health-related quality of life six months after total knee arthroplasty: results from a prospective cohort study.

Background: Total knee arthroplasty (TKA) is an effective procedure. However, for some patients, the outcomes are not satisfactory. Identification of TKA determinants could help manage these patients more efficiently.

How do Midwives and Physicians Discuss Childhood Vaccination with Parents?

Even if vaccination is often described as one of the great achievements of public health, results of recent studies have shown that parental acceptance of vaccination is eroding. Health providers' knowledge and attitudes about vaccines are important determinants of their own vaccine uptake, their intention to recommend vaccines to patients and the vaccine uptake of their patients. The purpose of this article is to compare how midwives and physicians address vaccination with parents during pregnancy and in postpartum visits.

Specific transcriptional response of four blockers of estrogen receptors on estradiol-modulated genes in the mouse mammary gland.

Novel agents for the endocrine therapy of breast cancer are needed, especially in order to take advantage of the multiple consecutive responses observed in metastatic progressing breast cancer following previous hormone therapy, thus delaying the use of cytotoxic chemotherapy with its frequent poor tolerance and serious side effects. Acolbifene (ACOL) is a novel and unique antiestrogen which represents a unique opportunity to achieve the most potent and specific blockade of estrogen action in the mammary gland and uterus while exerting estrogen-like beneficial effects in other tissues, especially the bones. To better understand the specificity of action of ACOL, we have used Affymetrix GeneChips containing 45,000 probe sets to analyze 34,000 genes to determine the specificity of this compound compared to the pure antiestrogen fulvestrant, as well as to the mixed antagonists/agonists tamoxifen and raloxifene to block the effect of estradiol (E(2)) and to induce effects of their own on the genomic profile in the mouse mammary gland.

CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis.

Background: Granulocytes generally exert protective roles in the central nervous system (CNS), but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE), the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined.

Methods: CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and in situ hybridization.

Dietary supplementation with fish gelatine modifies nutrient intake and leads to sex-dependent responses in TAG and C-reactive protein levels of insulin-resistant subjects.

Previous studies have shown that fish protein, as well as marine n-3 PUFA, may have beneficial effects on cardiovascular risk profile. The objectives of this study were to investigate the combined effects of fish gelatine (FG) and n-3 PUFA supplementation on (1) energy intake and body weight, (2) lipid profile and (3) inflammatory and CVD markers in free-living insulin-resistant males and females. Subjects were asked to consume, in a crossover study design with two experimental periods of 8 weeks each, an n-3 PUFA supplement and n-3 PUFA supplement plus FG (n-3 PUFA + FG).

Resveratrol inhibition of inducible nitric oxide synthase in skeletal muscle involves AMPK but not SIRT1.

The plant-derived polyphenol resveratrol (RSV) modulates life span and metabolism, and it is thought that these effects are largely mediated by activating the deacetylase enzyme SIRT1. However, RSV also activates the cell energy sensor AMP-activated protein kinase (AMPK). We have previously reported that AMPK activators inhibit inducible nitric oxide synthase (iNOS), a key proinflammatory mediator of insulin resistance in endotoxemia and obesity.

Matrix metalloproteinase 2 attenuates brain tumour growth, while promoting macrophage recruitment and vascular repair.

Matrix metalloproteinase 2 (MMP2) is an extracellular protein-degrading enzyme widely believed to be involved in the invasion of brain tumour cells. However, this assumption is mainly based on in vitro studies. By characterizing the transcriptome and in vivo properties of 20 astrocytoma cell lines, we found that the levels of MMP2 were higher in GFAP(-) astrocytoma cells and correlated with their ability to induce vascular changes, a common complication of malignant tumours.

Crawling phagocytes recruited in the brain vasculature after pertussis toxin exposure through IL6, ICAM1 and ITGαM.

The cerebral vasculature is constantly patrolled by rod-shaped leukocytes crawling on the luminal endothelial surface. These cells are recruited in greater numbers after exposure to bacterial lipopolysaccharide (LPS) by a mechanism involving tumor necrosis factor (TNF), interleukin-1β (IL1β) and angiopoietin-2 (Angpt2). Here, we report that the population of crawling leukocytes, consisting mainly of granulocytes, is also increased in the brains of mice suffering from experimental autoimmune encephalomyelitis (EAE) or injected with pertussis toxin (PTX), which is commonly used to induce EAE.

Differential effects of various fish proteins in altering body weight, adiposity, inflammatory status, and insulin sensitivity in high-fat-fed rats.

Mounting evidence suggests that the benefits of fish consumption are not limited to the well-appreciated effects of omega-3 fatty acids. We previously demonstrated that cod protein protects against the development of diet-induced insulin resistance. The goal of this study was to determine whether other fish protein sources present similar beneficial effects.

Expression of 11β-hydroxysteroid dehydrogenase type 1 in breast cancer and adjacent non-malignant tissue. An immunocytochemical study.

Intratumoral biosynthesis of hormone steroids is thought to play a role in the pathogenesis and development of human breast cancer. There is evidence that glucocorticoids may inhibit the development and progression of breast cancer. 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 is the enzyme which converts inactive cortisone to active cortisol.

Skin responses to topical dehydroepiandrosterone: implications in antiageing treatment?

Background: Although low dehydroepiandrosterone (DHEA) is suspected to have a role in skin ageing, little information is available on the mechanisms potentially involved.

Objectives: To obtain information on androgen receptor (AR) and procollagen expression in ageing skin during DHEA treatment.

Methods: A placebo-controlled, randomized, prospective study was performed with 75 postmenopausal women aged 60-65 years.

Hormonal therapy of prostate cancer.

Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood.

DHEA, important source of sex steroids in men and even more in women.

A major achievement from 500 million years of evolution is the establishment of a high secretion rate of dehydroepiandrosterone (DHEA) by the human adrenal glands coupled with the indroduction of menopause which stops secretion of estrogens by the ovary. Cessation of estrogen secretion at menopause eliminates the risks of endometrial hyperplasia and cancer which would result from non-opposed estrogen stimulation during the post-menopausal years. In fact, from the time of menopause, DHEA becomes the exclusive and tissue-specific source of sex steroids for all tissues except the uterus.

The intracrine sex steroid biosynthesis pathways.

There is an increasing number of differences reported between the steroidogenesis pathways described in the traditional literature related to gonadal steroidogenesis and the more recent observations achieved using new technologies, especially molecular cloning, pangenomic expression studies, precise quantification of mRNA expression using real-time PCR, use of steroidogenic enzymes stably transfected in cells, detailed enzymatic activity analysis in cultured cell lines and mass spectrometry analysis of steroids. The objective of this chapter is to present steroidogenesis in the light of new findings that demonstrate pathways of biosynthesis of estradiol (E(2)) and dihydrotestosterone (DHT) from adrenal dehydroepiandrosterone (DHEA) in peripheral intracrine tissues which do not involve testosterone as intermediate as classically found in the testis and ovary. Steroidogenic enzymes different from those of the ovary and testis act in a tissue-specific manner to catalyze the transformation of DHEA into active sex steroids.

High internal consistency and efficacy of intravaginal DHEA for vaginal atrophy.

Following the compelling data obtained in a pivotal phase III clinical trial performed in 218 postmenopausal women suffering from vaginal atrophy who received daily intravaginal 0.25, 0.5 or 1.

Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue.

Objective: The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive.

Research Design And Methods: To assess the metabolic effects of chronic inhibition of the mTORC1/S6K1 pathway, rats were treated with rapamycin (2 mg/kg/day) or vehicle for 15 days before metabolic phenotyping.

Chronic inhibition of the mTORC1/S6K1 pathway increases insulin-induced PI3K activity but inhibits Akt2 and glucose transport stimulation in 3T3-L1 adipocytes.

The mammalian target of rapamycin complex 1 (mTORC)1 pathway has emerged as a critical signaling component in the modulation of insulin's metabolic action. This effect is triggered by a nutrient- and insulin-mediated negative feedback loop in which mTOR and S6 kinase (S6K)1 phosphorylate insulin receptor substrate (IRS)-1 on serine residues, which blunts phosphatidylinositol 3-kinase (PI3K) activation. Acute inhibition of mTORC1/S6K1 by rapamycin increases insulin signaling and glucose uptake in myocytes and adipocytes, but whether these effects can be maintained under chronic inhibition of mTORC1 or S6K1 remains unclear.

Immunocytochemical localization of sex steroid hormone receptors in normal human mammary gland.

The sex steroids, estrogens, progesterone, and androgens, all play a role in mammary development and function. To precisely identify the sites of action of these steroids, we studied the localization of the estrogen receptor alpha (ERalpha) and ERbeta, the progesterone receptor A (PRA) and PRB, and androgen receptors (AR) in the normal human mammary gland. Immunocytochemical localization of ERalpha, ERbeta, PRA, PRB, and AR was performed with reduction mammoplasty specimens from premenopausal women.

Construction of a ganciclovir-sensitive lentiviral vector to assess the influence of angiopoietin-3 and soluble Tie2 on glioma growth.

Malignant brain tumors grow by coopting the existing vasculature, a process involving the release of angiopoietin-2 (Angpt2) from endothelial cells and its binding to the Tie2 receptor. The first goal of this study was to examine the therapeutic potential of two proteins that could interfere with Angpt2, namely Angpt3 and the soluble extracellular domain of Tie2 (sTie2). The second goal was to develop a lentiviral vector capable of delivering such proteins while offering the possibility to identify and destroy the genetically modified cells.

Androgen receptor as a potential sign of prostate cancer metastasis.

Background: Androgen receptor (AR) expression and its modulation through the carcinogenesis process have been investigated in several studies with conflicting results.

Materials And Methods: In situ hybridization and immunocytochemistry were used to examine AR expression in prostatic needle core biopsies of benign, high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma.

Results: A significant increase in AR mRNA levels was found in the cancerous prostatic cells when compared with the benign tissue biopsies.