Beneficial effects of estrogens have been reported in Parkinson's disease (PD) for many years. We previously reported their neuroprotective and anti-inflammatory potentials in the enteric nervous ...system of the intestine, a region possibly affected during the early stages of the disease according to Braak’s hypothesis. Three different estrogen receptors have been characterized to date: the estrogen receptor alpha (ERα), the estrogen receptor beta (ERβ) and the G protein coupled estrogen receptor 1 (GPER1). The aim of the present study was to decipher the individual contribution of each estrogen receptor to the therapeutic properties of 17β-estradiol (E2) in the myenteric plexus of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Different agonists, 4,4',4''-(4-propyl-1H-pyrazole-1,3,5-triyl)trisphenol (PPT; ERα), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ERβ), G1 (GPER1), and antagonists, ICI 182,780 (ERα and ERβ), G15 (GPER1), were used to analyze the involvement of each receptor. We confirmed that G1 protects dopamine (DA) neurons to a similar extent as E2. An anti-inflammatory effect on proinflammatory macrophages and cultured human monocytes was also demonstrated with E2 and G1. The effects of PPT and DPN were less potent than G1 with only a partial neuroprotection of DA neurons by PPT and a partial reduction of interleukin (IL)− 1β production in monocytes by PPT and DPN. Overall, the present results indicate that the positive outcomes of estrogens are mainly through activation of GPER1. Therefore, this suggests that targeting GPER1 could be a promising approach for future estrogen-based hormone therapies during early PD.
•G1 protects enteric dopaminergic neurons against MPTP toxicity in vivo.•G1 has anti-inflammatory properties in MPP+-treated human monocytic THP cells in vitro.•G1 has more potent enteric neuroprotective effects than PPT and DPN in vivo.•Therapeutic effects of estrogens are mainly mediated by activation of GPER1.
An increasing number of clinical and empirical studies document the coping strategies used by partners of pathological gamblers (PGs). A postulate for this is that they may be useful for dealing with ...their partner’s problematic gambling behaviors. Despite a widespread endorsement of this postulate, no study has yet documented their effectiveness: does the use of these coping strategies impact the gambler’s behavior? To answer this question, semi-structured interviews were conducted with 19 participants (8 couples comprising one PG and his or her partner, one partner of a PG, and 2 PGs). Qualitative analysis of the interviews lead to a first main observation: via diverse coping strategies, partners of PGs can influence their spouse’s gambling behaviors. The impact of these strategies may occur as initially expected by partners, that is by a reduction of gambling behaviors. However, the use of certain strategies can also increase the PG’s gambling cravings, though this is not generally their partner’s intention.
Consequences experienced by the partners of individuals with a gambling disorder are well documented. However, little is known about the deleterious effects experienced by other people than partners ...of gamblers. A better understanding of these consequences could help improve clinical practices. The goal of this paper is to compare the consequences experienced by partners of gamblers with those experienced by their close family members (parents, adult children, siblings) by using the categorization method proposed by Langham et al. (BMC Public Health, 2016). To achieve this goal, 46 semi-structured interviews were conducted. Results indicate that the extent and intensity of the consequences experienced vary widely based on their level of emotional and financial involvement with the gambler. Considering the specific elements involved for each type of person in a gambler’s life, future research should distinguish participants based on the nature of their relationship with the gambler.
Gambling disorder (GD) is a major public health issue around the world. Even though prior studies have shown that the prevalence of problem gambling varies depending on certain sociodemographic ...factors, we know very little about gambling and sexual and gender minorities (i.e. LGBTQIA2S + populations). The objective of this scoping review was to summarize the available literature on gambling among LGBTQIA2S + populations and to underline future avenues of research. We conducted an electronic search using keywords related to gambling and sexual and gender minorities in 10 databases: Academic Search Complete, CINAHL Plus with Full Text, Education Source, ERIC, MEDLINE with Full Text, APA Psyc Articles, Psychology and Behavioral Sciences Collection, APA Psych Info, Social Work Abstracts, and SocINDEX. Studies eligible for this review had to meet the following criteria: discuss gambling and LGBTQIA2S + populations as the primary theme and be published in English in a peer-reviewed journal. After selecting the articles, the information was collated, analyzed, summarized, and reported using narrative synthesis. The search yielded 629 articles, and 476 remained following the removal of duplicates. Upon title and abstract review, 12 articles were retained for full-text reading, after which 6 articles were included in this review. We analyzed the data and revealed conflicting results on the associations between gambling and LGBTQIA2S + populations. Therefore, further research is needed on this population, which is known to be at risk for addictions.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
People living with pathological gamblers (PGs) have to endure the negative consequences of their problem gambling. It is known that the partners of PGs will develop adaptation strategies to cope with ...gambling behaviour. However, research conducted on the topic is still in its early stages. The goal of this study was to draw up a portrait of the strategies employed, their context, means, and main goals, and to examine the variation of these strategies over time and the viewpoints of the 2 members of the couple. Using 19 semi-structured interviews, we noted that the partners used some 30 strategies aiming primarily at modifying the gamblers’ pathological behaviour, and also at improving their own personal well-being. An analysis of the usage context illustrated the many possible interactions which occurred between individuals and their environment and which triggered a strategy’s use. Generally speaking, both members of the couple had a similar perception of the strategies used by the partners. When partners realized that they had not influenced the PGs’ habits, they sometimes changed adaptation strategies.RésuméLes partenaires de joueurs pathologiques (JP) vivent des conséquences négatives découlant des habitudes problématiques de jeux de hasard et d’argent (JHA) de leur conjoint.. Il est reconnu que les partenaires de JP mettront en place des stratégies d’adaptation pour faire face à ces comportements de JHA. Toutefois, les recherches effectuées sur le sujet en sont encore à leurs premiers balbutiements. L’objectif de cette étude vise à dresser un portrait des stratégies utilisées, leurs contextes d'utilisation, les moyens et les finalités recherchées, en plus de s’intéresser au point de vue des deux membres du couple et à la variation dans le temps de ces stratégies. À l'aide de dix-neuf entrevues semi-structurées, on remarque que les partenaires ont utilisé près d'une trentaine de stratégies visant principalement une modification des comportements de JHA du JP, mais aussi l'amélioration de leur bien-être personnel. L'analyse des contextes d’utilisation illustre les nombreuses interactions possibles entre l'individu et son environnement qui déclenchent l’utilisation d’une stratégie. De façon générale, les deux membres du couple ont une perception similaire des stratégies utilisées par l’autre partenaire. Enfin, lorsque les partenaires prennent conscience qu'elles n'ont pas influencé les habitudes de JHA du JP, elles changent parfois de stratégies d’adaptation.
Nck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been ...shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression.
Expression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2.
We found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate.
Collectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA) axis-related components, with proposed or described local regulatory ...systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production.
Expression of genes encoding for corticotropin-releasing hormone (CRH), CRH receptors (CRHR) 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC), melanocortin receptor 2 (MC2R), and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD) 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH) to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants.
We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1). Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1) on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed.
Temporal and spatial modulations of expression of HPA axis-related genes in late gestation are consistent with roles for these genes in lung development. Our data are likely to lead to valuable insights in relation to lung diseases originating from lung immaturity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accumulating evidences suggest that sex affects lung development. Indeed, a higher incidence of respiratory distress syndrome is observed in male compared to female preterm neonates at comparable ...developmental stage and experimental studies demonstrated an androgen-related delay in male lung maturation. However, the precise mechanisms underlying these deleterious effects of androgens in lung maturation are only partially understood.
To build up a better understanding of the effect of androgens on lung development, we analyzed by microarrays the expression of genes showing a sexual difference and those modulated by androgens. Lungs of murine fetuses resulting from a timely mating window of 1 hour were studied at gestational day 17 (GD17) and GD18, corresponding to the period of surge of surfactant production. Using injections of the antiandrogen flutamide to pregnant mice, we hunted for genes in fetal lungs which are transcriptionally modulated by androgens.
Results revealed that 1844 genes were expressed with a sexual difference at GD17 and 833 at GD18. Many genes were significantly modulated by flutamide: 1597 at GD17 and 1775 at GD18. Datasets were analyzed by using in silico tools for reconstruction of cellular pathways. Between GD17 and GD18, male lungs showed an intensive transcriptional activity of proliferative pathways along with the onset of lung differentiation. Among the genes showing a sex difference or an antiandrogen modulation of their expression, we specifically identified androgen receptor interacting genes, surfactant related genes in particularly those involved in the pathway leading to phospholipid synthesis, and several genes of lung development regulator pathways. Among these latter, some genes related to Shh, FGF, TGF-beta, BMP, and Wnt signaling are modulated by sex and/or antiandrogen treatment.
Our results show clearly that there is a real delay in lung maturation between male and female in this period, the latter pursuing already lung maturation while the proper is not yet fully engaged in the differentiation processes at GD17. In addition, this study provides a list of genes which are under the control of androgens within the lung at the moment of surge of surfactant production in murine fetal lung.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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