The obese inflammatory microenvironment may promote breast DCIS progression.

Introduction: Ductal carcinoma in situ (DCIS), characterized by a proliferation of neoplastic cells confined within the mammary ducts, is distinctly isolated from the surrounding stroma by an almost uninterrupted layer of myoepithelial cells (MECs) and by the basement membrane. Heightened interactions within the adipose microenvironment, particularly in obese patients, may play a key role in the transition from DCIS to invasive ductal carcinoma (IDC), which is attracting growing interest in scientific research. Adipose tissue undergoes metabolic changes in obesity, impacting adipokine secretion and promoting chronic inflammation. This study aimed to assess the interactions between DCIS, including in situ cancer cells and MECs, and the various components of its inflammatory adipose microenvironment (adipocytes and macrophages). Methods: To this end, a 3D co-culture model was developed using bicellular bi-fluorescent DCIS-like tumoroids, adipose cells, and macrophages to investigate the influence of the inflammatory adipose microenvironment on DCIS progression. Results: The 3D co-culture model demonstrated an inhibition of the expression of genes involved in apoptosis (BAX, BAG1, BCL2, CASP3, CASP8, and CASP9), and an increase in genes related to cell survival (TP53, JUN, and TGFB1), inflammation (TNF-α, PTGS2, IL-6R), invasion and metastasis (TIMP1 and MMP-9) in cancer cells of the tumoroids under inflammatory conditions versus a non-inflammatory microenvironment. On the contrary, it confirmed the compromised functionality of MECs, resulting in the loss of their protective effects against cancer cells. Adipocytes from obese women showed a significant increase in the expression of all studied myofibroblast-associated genes (myoCAFs), such as FAP and α-SMA. In contrast, adipocytes from normal-weight women expressed markers of inflammatory fibroblast phenotypes (iCAF) characterized by a significant increase in the expression of LIF and inflammatory cytokines such as TNF-α, IL-1ß, IL-8, and CXCL-10. These changes also influenced macrophage polarization, leading to a pro-inflammatory M1 phenotype. In contrast, myoCAF-associated adipocytes, and the cancer-promoting microenvironment polarized macrophages towards an M2 phenotype, characterized by high CD163 receptor expression and IL-10 and TGF-ß secretion. Discussion: Reciprocal interactions between the tumoroid and its microenvironment, particularly in obesity, led to transcriptomic changes in adipocytes and macrophages, may participate in breast cancer progression while disrupting the integrity of the MEC layer. These results underlined the importance of adipose tissue in cancer progression.

Long-Term High-Fat Diet Limits the Protective Effect of Spontaneous Physical Activity on Mammary Carcinogenesis.

Breast cancer is influenced by factors such as diet, a sedentary lifestyle, obesity, and postmenopausal status, which are all linked to prolonged hormonal and inflammatory exposure. Physical activity offers protection against breast cancer by modulating hormones, immune responses, and oxidative defenses. This study aimed to assess how a prolonged high-fat diet (HFD) affects the effectiveness of physical activity in preventing and managing mammary tumorigenesis. Ovariectomised C57BL/6 mice were provided with an enriched environment to induce spontaneous physical activity while being fed HFD. After 44 days (short-term, ST HFD) or 88 days (long-term, LT HFD), syngenic EO771 cells were implanted into mammary glands, and tumour growth was monitored until sacrifice. Despite similar physical activity and food intake, the LT HFD group exhibited higher visceral adipose tissue mass and reduced skeletal muscle mass. In the tumour microenvironment, the LT HFD group showed decreased NK cells and TCD8+ cells, with a trend toward increased T regulatory cells, leading to a collapse of the T8/Treg ratio. Additionally, the LT HFD group displayed decreased tumour triglyceride content and altered enzyme activities indicative of oxidative stress. Prolonged exposure to HFD was associated with tumour growth despite elevated physical activity, promoting a tolerogenic tumour microenvironment. Future studies should explore inter-organ exchanges between tumour and tissues.

[Affirming one's gender: supporting and accompanying trans young people and their families]. / Affirmer son genre : soutenir et accompagner les jeunes trans et leur famille.

Support for trans teenagers and young adults is based on a comprehensive approach to care, taking into account the needs and desires of the individual and his or her environment. It involves welcoming their requests and listening to their questions, in order to help them assert themselves. The aim is to be particularly attentive to these young people, sometimes in vulnerable psychological, social and educational situations, as well as to their families, by welcoming them, listening to them and taking charge of them through multidisciplinary networks.

[Ethical implications of supporting trans or questioning children and adolescents: Articulation with reproductive health]. / Enjeux éthiques de l'accompagnement des enfants et des adolescents et adolescentes trans ou en questionnement : articulation à la santé reproductive.

Supporting children and adolescents who are trans or who are questioning cannot be done without an ethical reflection on one's own practice as a health professional. It is important to consider the young person as a whole, including reproductive health issues. This article proposes, through the principles of Beauchamps and Childress, an ethical reflection on the issues of beneficence - not maleficence, and of autonomy and justice for adolescents, young adults, and future trans or questioning parents. For adolescents, concerning the possibilities of medical treatment of gender affirmation, we need to propose information in terms of impact on fertility and, if necessary, proposals for the possibilities of preserving their reproductive capacities. These issues require to question the state of scientific knowledge in terms of parenthood of trans people and questioning. We propose here a state of knowledge of these realities, put in perspectives of the axes of ethical reflections inherent to guidance. In fine, it appears that the major ethical stake concerns the child to be born. Finally, it is necessary to consider the quality of life of the future parents and the impact of their medical follow-up.

Title: Enjeux éthiques de l'accompagnement des enfants et des adolescents et adolescentes trans ou en questionnement : articulation à la santé reproductive. Abstract: L'accompagnement des enfants et des adolescents et adolescentes trans ou en questionnement ne peut faire l'économie d'une pensée éthique réflexive de sa propre pratique en tant que professionnel de santé. Il est important de considérer le jeune dans sa globalité, et cela également en ce qui concerne les enjeux en santé reproductive. Cet article propose, au travers des principes de Tom Beauchamps et James Childress1, une réflexion éthique des enjeux de bienfaisance/non nuisance, d'autonomie et de justice, pour les adolescents, jeunes adultes, et futurs parents trans ou en questionnement. Pour les adolescents et les adolescentes, autour des possibilités de traitement médical d'affirmation de genre, il est nécessaire de proposer des informations, en termes d'impact sur la fertilité et, le cas échéant, des propositions de possibilités de conservation de ses capacités reproductives. Ces enjeux nécessitent d'interroger l'état des connaissances scientifiques en termes de parentalité des personnes trans et en questionnement. Nous proposons ici un état des lieux des connaissances de ces réalités, mises en perspective des axes de réflexions éthiques inhérentes aux accompagnements. In fine, il apparaît que l'enjeu éthique majeur porte sur l'enfant à naître. À cela, il est nécessaire de considérer la qualité de vie des futurs parents et l'impact des accompagnements médicaux des personnes.

[Fertility preservation in transgender people]. / Préservation de la fertilité chez les personnes transgenres.

Most of transgender people plan to have a family but their fertility may be affected by gender affirmation. Hormone therapy can permanently affect gamete production, especially in trans women. Sex reassignment surgery leads to permanent sterility. In France, networks of health professionals have been organized and recommend access to fertility preservation for trans people. However, gamete collection is often difficult due to hormonal incongruence for trans women or to the invasive nature of the procedure for trans men. Future studies are required to assess the use of self-preserved gametes by trans people.

Title: Préservation de la fertilité chez les personnes transgenres. Abstract: La majorité des personnes transgenres envisage de fonder une famille, mais leur fertilité peut être altérée par l'affirmation du genre. L'hormonothérapie peut affecter durablement la production de gamètes, notamment chez les femmes trans. La chirurgie de réassignation sexuelle entraîne une stérilité définitive. En France, des réseaux de professionnels de santé se sont organisés. Ils recommandent l'accès à la préservation de la fertilité dans le cadre de la transidentité. Cependant, le recueil de gamètes reste souvent difficile en raison de l'incongruence hormonale pour les femmes trans, ou du caractère invasif de la procédure pour les hommes trans. De futures études permettront de statuer sur l'utilisation des gamètes autoconservés.

25-Hydroxyvitamin D potentializes extracellular cathelicidin release from human PBMC stimulated ex vivo with either bacterial (LPS) or viral (P: IC) mimetics

Human cathelicidin refers to the cationic antimicrobial peptide hCAP18/LL-37. LL-37 is formed by cleavage of the propeptide hCAP18 coded by the CAMP gene. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)D), has been shown to induce the CAMP gene expression through promoter activation. We previously failed to demonstrate in a clinical trial that supplementation of 25-hydroxyvitamin D (25(OH)D) improves LL-37 serum levels. The aim of this work was to evaluate the impact of 25(OH)D supplementation on intracellular expression of CAMP and secretion of LL-37 in an ex vivo model using the peripheral blood mononuclear cells (PBMC). PBMC collected from healthy donors and incubated with different concentrations of 25(OH)D (0 ng/ml: control (D0); 25 ng/ml: deficient (D25); 75 ng/ml: physiological (D75); 125 ng/ml: supraphysiological (D125)) were stimulated or not with lipopolysaccharide (LPS, 100 ng/ml) or synthetic double-stranded RNA Poly (I: C) (PIC, 10 µg/ml). The intracellular expressions of the CAMP gene and the hCAP18 peptide were measured respectively after 24-h and 48-h incubation periods. The concentration of LL-37 was determined in the culture medium after 48-h incubation. 25(OH)D significantly induced CAMP gene expression at 24 h with a maximum effect at a dose of D125 in either unstimulated (tenfold expression) or stimulated (LPS: 100-fold expression; PIC: 15-fold expression) conditions. Intracellular hCAP18 peptide was overexpressed at 48 h under unstimulated (1.5-fold, D125) and stimulated conditions, LPS (twofold, D125) and PIC (2.5-fold, D125). The secretion of LL-37 in the culture medium was significantly induced by 25(OH)D only in both stimulated (LPS and PIC) conditions in a dose-dependent manner. (AU)

25-Hydroxyvitamin D potentializes extracellular cathelicidin release from human PBMC stimulated ex vivo with either bacterial (LPS) or viral (P: IC) mimetics.

Human cathelicidin refers to the cationic antimicrobial peptide hCAP18/LL-37. LL-37 is formed by cleavage of the propeptide hCAP18 coded by the CAMP gene. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)D), has been shown to induce the CAMP gene expression through promoter activation. We previously failed to demonstrate in a clinical trial that supplementation of 25-hydroxyvitamin D (25(OH)D) improves LL-37 serum levels. The aim of this work was to evaluate the impact of 25(OH)D supplementation on intracellular expression of CAMP and secretion of LL-37 in an ex vivo model using the peripheral blood mononuclear cells (PBMC). PBMC collected from healthy donors and incubated with different concentrations of 25(OH)D (0 ng/ml: control (D0); 25 ng/ml: deficient (D25); 75 ng/ml: physiological (D75); 125 ng/ml: supraphysiological (D125)) were stimulated or not with lipopolysaccharide (LPS, 100 ng/ml) or synthetic double-stranded RNA Poly (I: C) (PIC, 10 µg/ml). The intracellular expressions of the CAMP gene and the hCAP18 peptide were measured respectively after 24-h and 48-h incubation periods. The concentration of LL-37 was determined in the culture medium after 48-h incubation. 25(OH)D significantly induced CAMP gene expression at 24 h with a maximum effect at a dose of D125 in either unstimulated (tenfold expression) or stimulated (LPS: 100-fold expression; PIC: 15-fold expression) conditions. Intracellular hCAP18 peptide was overexpressed at 48 h under unstimulated (1.5-fold, D125) and stimulated conditions, LPS (twofold, D125) and PIC (2.5-fold, D125). The secretion of LL-37 in the culture medium was significantly induced by 25(OH)D only in both stimulated (LPS and PIC) conditions in a dose-dependent manner. Our results demonstrate that 25(OH)D incubation increases intracellular expression of CAMP and hCAP18, but extracellular secretion of LL-37 antimicrobial peptide is increased by 25(OH)D only when PBMC from healthy donors were stimulated with bacterial or viral immune mimetic.

Characteristics and intentions of heterosexual couples comprising a transgender man awaiting sperm donation to conceive a child.

BACKGROUND: More than half of transgender (TG) men wish to have children. Until recently, TG people in France were rarely offered gamete donation, mainly because the Bioethics Law allows the use of assisted reproductive technologies (ART) only in infertile couples. The only option currently available for heterosexual couples with a TG man is ART with sperm donation. The Center for Study and Preservation of Eggs and Sperm (CECOS) of the Cochin Hospital is the first French center to propose sperm donation to such couples, and has done so since 1999. OBJECTIVES: To determine the main characteristics and intentions of 43 couples, including a TG man and his cisgender female partner awaiting sperm donation. MATERIALS AND METHODS: A retrospective analysis was carried out on the records from October 2010 to December 2019, of 43 couples with a TG man who applied for sperm donation at the CECOS of the Cochin Hospital (Paris, France). RESULTS: The mean age of TG men and cisgender women was 32 ± 6.6 and 29.7 ± 4.6 years, respectively. In 77% of cases, the couple met before the man's transition. Eighty-one percent of the couples were in a stable relationship for at least 3 years, and 94% wished to have a child for no more than 5 years. Almost all of the couples (95%) intended to inform their child of their conception by sperm donation and the father's transidentity (92%). DISCUSSION: Due to restrictive French legislation, the profile of our couples probably does not reflect that of all couples consisting of a TG man and a cisgender woman. The study took place over a long period of time and the characteristics of the couples could probably change over time. CONCLUSION: The couples often met before the man's transition, cohabited for several years, intended to inform their child of sperm donation and the father's transidentity.

Fertility preservation and sperm donation in transgender individuals: The current situation within the French CECOS network.

BACKGROUND: Many studies reported that reproductive desire could be high among transgender individuals. In France, fertility preservation and sperm donation were very little proposed to transgender individuals until recently, mainly because the Bioethics Law allows the use of assisted reproductive technologies only in infertile couples and prohibits surrogacy. OBJECTIVES: To evaluate the distribution of care on the French territory concerning fertility preservation and sperm donation in transgender individuals. MATERIALS AND METHODS: A multicentric national survey was carried out between January 2019 and October 2020 in 28 assisted reproductive technology centres of the French CECOS (Centres d'Etudes et de Conservation des Oeufs et du Sperme) network. Each centre was questioned to find out how many transgender individuals came, were informed and cared for fertility preservation and sperm donation. RESULTS: Concerning fertility preservation, 71.4% of centres received transgender individuals and performed gamete cryopreservation; 581 transgender individuals consulted for fertility preservation. Transgender women were more likely to desire (p < 0.0001) and achieve (p < 0.0001) fertility preservation than transgender men. Concerning sperm donation in couples including a transgender man, 68% of centres offer the complete course from the first consultation to the completion of the assisted reproductive technology cycles; 122 offsprings have been conceived with sperm donation in couples including a transgender man since 1999. DISCUSSION: Our results showed that even if all centres do not propose fertility preservation or sperm donation in transgender individuals, these assisted reproductive technologies are present throughout the French territory. The major point is that both fertility preservation and sperm donation in transgender individuals have grown significantly and that the care of these patients is improving year after year. CONCLUSION: In France, most of CECOS centres can take care of transgender individuals for fertility preservation and sperm donation. The French Bioethics Law allows these latter, and transgender individuals can benefit from a financial support of the national health care insurance for fertility preservation and sperm donation.

[Accessing parenthood in a transgender context]. / Accéder à la parentalité en contexte de transidentité.

Becoming a father is a process that covers different situations. In addition to the well-known situations of traditional conception and sperm donation, there are others that need to be considered. These situations concern in particular access to parenthood for transgender men who have made a social transition.

Vitamin D supplementation associated with physical exercise promotes a tolerogenic immune environment without effect on mammary tumour growth in C57BL/6 mice.

PURPOSE: High plasma vitamin D (VitD) level and regular exercise (Ex) are known to have anti-cancer and immunomodulatory effects. This study aimed to evaluate the impact of VitD supplementation and imposed physical Ex on mammary tumour growth and immune response in ovariectomised mice fed high-fat (HF) diet. METHODS: Ovariectomised 33-week-old mice C57BL/6 (n = 60), housed in enriched environment (EE), were fed HF diet (450 kcal/100 g) supplemented or not with VitD (HF/HF + D: 125/1225 IU/100 g) for 12 weeks and submitted or not to Ex (HF + Ex; HF + D + Ex) on treadmill (45 min/day, 5 days/week). At w8, syngeneic tumour cells EO771 were orthotopically injected into the 4th mammary gland. Spontaneous activity (SPA), maximal speed (MS) and forelimb grip strength (GS) were measured. Tumour immune cells infiltrate was phenotyped by FACS. Data (mean ± SEM) were analysed by two-way ANOVA + Tukey post-test. RESULTS: Ex (p = 0.01) and VitD (p = 0.05) reduced body weight gain. Exercise decreased visceral fat mass [g: 1.5 ± 0.8 (HF); 1.2 ± 0.65 (HF + Ex); 0.9 ± 0.6 (HF + D + Ex); p = 0.03]. SPA (p < 0.0001) and GS (p = 0.01) were higher in HF + D + Ex mice vs others. No effect of Ex or VitD on tumour growth was detected. In tumour, VitD decreased the proportion of NK (p = 0.03), while Ex increased it (p = 0.03). The Th1/Th2 ratio is lowered by VitD (p = 0.05), while Tc/Treg ratio was not affected either by Exercise or VitD. CONCLUSION: In our experimental conditions, VitD supplementation and physical exercise have synergetic effects reducing the weight gain under HF diet and improving the physical capacities of mice. VitD coupled with exercise induces an immunosuppressive response without effect on tumour growth.

Transgender fathering: Children's psychological and family outcomes.

Medical advances in assisted reproductive technology have created new ways for transgender persons to become parents outside the context of adoption. The limited empirical data does not support the idea that trans-parenthood negatively impacts children's development. However, the question has led to lively societal debates making the need for evidence-based studies urgent. We aimed to compare cognitive development, mental health, gender identity, quality of life and family dynamics using standardized instruments and experimental protocols in 32 children who were conceived by donor sperm insemination (DSI) in French couples with a cisgender woman and a transgender man, the transition occurring before conception. We constituted two control groups matched for age, gender and family status. We found no significant difference between groups regarding cognitive development, mental health, and gender identity, meaning that neither the transgender fatherhood nor the use of DSI had any impact on these characteristics. The results of the descriptive analysis showed positive psycho-emotional development. Additionally, when we asked raters to differentiate the family drawings of the group of children of trans-fathers from those who were naturally conceived, no rater was able to differentiate the groups above chance levels, meaning that what children expressed through family drawing did not indicate cues related to trans-fatherhood. However, when we assessed mothers and fathers with the Five-Minute Speech Sample, we found that the emotions expressed by transgender fathers were higher than those of cisgender fathers who conceived by sex or by DSI. We conclude that the first empirical data regarding child development in the context of trans-parenthood are reassuring. We believe that this research will also improve transgender couple care and that of their children in a society where access to care remains difficult in this population. However, further research is needed with adolescents and young adults.

EO771, the first luminal B mammary cancer cell line from C57BL/6 mice.

BACKGROUND: Despite decades of therapeutic trials, effective diagnosis, many drugs available and numerous studies on breast cancer, it remains the deadliest cancer in women. In order to choose the most appropriate treatment and to understand the prognosis of the patients, breast cancer is divided into different subtypes using a molecular classification. Just as there remains a need to discover new effective therapies, models to test them are also required. METHODS: The EO771 (also named E0771 or EO 771) murine mammary cancer cell line was originally isolated from a spontaneous tumour in C57BL/6 mouse. Although frequently used, this cell line remains poorly characterized. Therefore, the EO771 phenotype was investigated. The phenotype was compared to that of MCF-7 cells, known to be of luminal A subtype and to express estrogen receptors, as well as MDA-MB-231 cells, which are triple negative. Their sensitivity to hormonal treatment was evaluated by viability tests. RESULTS: The EO771 were estrogen receptor α negative, estrogen receptor ß positive, progesterone receptor positive and ErbB2 positive. This phenotype was associated with a sensitivity to anti-estrogen treatments such as tamoxifen, 4-hydroxy-tamoxifen, endoxifen and fulvestrant. CONCLUSIONS: On account of the numerous results published with the EO771 cell line, it is important to know its classification, to facilitate comparisons with corresponding types of tumours in patients. Transcriptomic and protein analysis of the EO771 cell line classified it within the luminal B subtype. Luminal B cancers correspond to one of the subtypes most frequently encountered in patients and associated with a poor prognosis.

The Developmental Implications of the Use of Reproductive Technologies for Transgender People: A Comparative Cross-Section Protocol.

BACKGROUND: Today, individuals and couples with fertility issues can use advances in biomedical technologies to conceive. Transgender persons also benefit from these advances and can not only actualize their self-identified gender identities but also experience parenthood. These strategies for persons to self-actualize and to access parenthood have improved the condition of transgender persons. However, some may question the welfare of the offspring because such transfamily forms are often confusing to many. The sparse research on the psychological well-being of children of transgender people is reassuring. However, the limited empirical research justifies more studies to be conducted with an evidence-based methodology to assess whether these new methods of parenting have any adverse impact on children. AIMS: The current report details the protocol we built to compare cognitive development, mental health, gender identity, quality of life, and family dynamics in children of transgender fathers and donor sperm insemination (DSI) and two control groups matched for age and gende typically developing (TD) children and children from cisgender parents and DSI. HYPOTHESIS: To calculate sample sizes, we hypothesize no significant difference between groups. SUBJECTS AND METHODS: Since 2008, married couples that include a transgender father have been able to access DSI and have started conceiving children in France. They are always invited to participate in research to assess their children's well-being. To date, the cohort includes 53 children in 37 families. We propose to carry out a cross-sectional comparative study exploring cognitive development with the Brunet-Lézine Psychomotor Development Scale or Wechsler's Intelligence Scales according to age; mental health with the Child Behaviour Checklist; gender identity with the Gender Identity Interview for Children; quality of life with the KIDSCREEN and the Adolescent Coping Questionnaire; and family dynamics with the Parental Bonding Instrument, the Inventory of Parent and Peer Attachment, the Five-Minute Speech Sample, and Corman's Family Drawing Test. To assess possible subtle differences between children's family drawings, we will use a generalization of the "lady-tasting-tea" procedure to link qualitative and quantitative approaches in psychiatric research. Twenty raters [four child and family psychoanalysts (CHILDPSY), four adult psychiatrists (ADUPSY), four biologists working in assistive reproduction technology (BIOL), four endocrinologists working with transgender individuals (ENDOC), and four students (STUD)] will be randomly shown the drawings and asked to blindly classify them using a Likert scale according to whether the child has a transgender father. STATISTICAL ANALYSIS: After testing normality, comparisons between the three groups will be performed with appropriate statistical tests (Kruskal-Wallis, ANOVA, Chi2 or Fisher's exact test). For the "lady-tasting-tea" procedure, we will use a permutation test. ETHICS: The study protocol has been approved by the CERES (Comité d'Ethique de Recherche en Santé) of Paris 5 University. Registration number is 2015/31.

Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.

Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGß (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFß plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.

Biotechnologies that empower transgender persons to self-actualize as individuals, partners, spouses, and parents are defining new ways to conceive a child: psychological considerations and ethical issues.

Today, thanks to biomedical technologies advances, some persons with fertility issues can conceive. Transgender persons benefit also from these advances and can not only actualize their self-identified sexual identities but also experience parenthood. Based on clinical multidisciplinary seminars that gathered child psychiatrists and psychoanalysts interested in the fields of assisted reproduction technology (ART) and gender dysphoria, philosophers interested in bioethics, biologists interested in ART, and endocrinologists interested in pubertal suppression, we explore how new biotechnical advances, whether in gender transition or procreation, could create new ways to conceive a child possible. After reviewing the various medical/surgical techniques for physical gender transition and the current ART options, we discuss how these new ways for persons to self-actualize and to experience parenthood can not only improve the condition of transgender persons (and the human condition as a whole through greater equity) but also introduce some elements of change in the habitual patterns of thinking especially in France. Finally, we discuss the ethical issues that accompany the arrival of these children and provide creative solutions to help society handle, accept, and support the advances made in this area.

Supernatants of Adipocytes From Obese Versus Normal Weight Women and Breast Cancer Cells: In Vitro Impact on Angiogenesis.

Breast cancer is correlated with a higher risk of metastasis in obese postmenopausal women. Adipokines, whose plasma concentrations are modulated in obese subjects and adipocytes surround mammary cells, suggesting that adipocyte secretome affect mammary tumorogenesis. We hypothesize that mature adipocyte secretions from obese women conditioned or not by breast neoplasic cells, increase changes on the angiogenesis stages. Supernatants of human mature adipocytes, differentiated from stem cells of either adipose tissue of normal weight (MA20) or obese (MA30) women or obtained from co-cultures between MA20 and MA30 and breast cancer cell line MCF-7, were collected. The impact of these supernatants was investigated on proliferation, migration, and tube formation by endothelial cells (HUVEC). MA20 and MA30 showed a preservation of their "metabolic memory" (increase of Leptin, ObR, VEGF, CYP19A1, and a decrease of Adiponectin expression in MA30 compared to MA20). Supernatants from obese-adipocytes increased HUVEC proliferation, migration, and sprouting like with supernatants obtained from co-cultures of MA/MCF-7 regardless the women's BMI. Additional analyses such as the use of neutralizing antibodies, analysis of supernatants (Milliplex®) and variations in gene expression (qRT-PCR), strongly suggest an implication of IL-6, or a synergistic action among adipokines, probably associated with that of VEGF or IL-6. As a conclusion, supernatants from co-cultures of MA30 and MCF-7 cells increase proliferation, migration, and sprouting of HUVEC cells. These results provide insights into the interaction between adipocytes and epithelial cancer cells, particularly in case of obesity. The identification of synergistic action of adipokines would therefore be a great interest in developing preventive strategies. J. Cell. Physiol. 232: 1808-1816, 2017. © 2016 Wiley Periodicals, Inc.

Polyphenol-rich grape pomace extracts protect against dextran sulfate sodium-induced colitis in rats.

BACKGROUND: Several studies have reported that polyphenols may exert beneficial effects on inflammatory bowel disease. This study aimed to evaluate the effects of preventive consumption of polyphenol-rich red grape pomace extracts (GPEs) on dextran sulfate sodium (DSS)-induced colitis in rats. Rats were fed for 21 days with a semi-synthetic diet enriched with a GPE (Alicante-S, Alicante-P or Pinot-S) and colitis was induced by DSS administration in drinking water (40 g L(-1) ) during the last 7 days of experimentation. RESULTS: GPEs attenuated clinical signs and colon shortening and Alicante GPEs limited histological lesions induced by DSS. GPEs curbed the increase in myeloperoxidase activity and modulated antioxidant enzyme activities. Moreover, GPEs prevented the DSS-induced increase in pro-inflammatory cytokine levels and the up-regulation of various genes implicated in colitis such as intercellular adhesion molecule 1 (ICAM-1) and matrix metalloproteinase 9 (MMP-9). CONCLUSION: These results suggest that polyphenol-rich red GPEs could provide prevention against colon inflammation.