Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark.

AIMS/HYPOTHESIS: Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model. METHODS: miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic-hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue. RESULTS: The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased Perk (also known as Eif2ak3) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased Xbp1, spliced Xbp1, Chop (also known as Ddit3) and Perk mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance. CONCLUSIONS/INTERPRETATION: Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target.

Hypercaloric Diet-Induced Obesity and Obesity-Related Metabolic Disorders in Experimental Models.

Overnutrition and obesity have developed into a major public health problem across different parts of the world. Epidemiological studies have shown that excessive intake of dietary components, such as fatty acids and/or sugars, can promote obesity. In this context, the use of dietary intervention in animal models that respond to a diet similar to humans is useful to understand this preventable, multifactorial disease. The aim of this chapter is to aid researchers in choosing specific nutritional interventions and animal strains to induce obesity and obesity-related morbidities in experimental models.

Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the Evaluation of Head and Neck Cancer.

OBJECTIVE: Dual-energy computed tomography high energy virtual monochromatic images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing tumor. We investigated this trade-off to identify VMI(s) that strike the best balance between iodine detection and artifact reduction. METHODS: The study was performed using an Alderson radiation therapy phantom. Different iodine solutions (based on estimated tumor iodine content in situ using dual-energy computed tomography material decomposition) and different dental fillings were investigated. Spectral attenuation curves and quality index (QI: 1/SD) were evaluated. RESULTS: The relationship between iodine attenuation and QI depends on artifact severity and iodine concentration. For low to average concentration solutions degraded by mild to moderate artifact, the iodine attenuation and QI curves crossed at 95 keV. CONCLUSIONS: High energy VMIs less than 100 keV can achieve modest artifact reduction while preserving sufficient iodine attenuation and could represent a useful additional reconstruction for evaluation of head and neck cancer.

Low-Energy Virtual Monochromatic Dual-Energy Computed Tomography Images for the Evaluation of Head and Neck Squamous Cell Carcinoma: A Study of Tumor Visibility Compared With Single-Energy Computed Tomography and User Acceptance.

OBJECTIVE: Dual-energy computed tomography (CT) 40-keV virtual monochromatic images (VMIs) have been reported to improve visualization of head and neck squamous cell carcinoma, but a direct comparison to single-energy CT (SECT) is lacking, and there is debate regarding subjective user preference. We compared 40-keV VMIs with SECT and performed a subjective evaluation of their utility and acceptability for clinical use. METHODS: A total of 60 dual-energy CT and 60 SECT scans from 2 different institutions were evaluated. Tumor conspicuity was evaluated objectively using absolute and relative attenuation and subjectively by 3 head and neck specialists and 3 general radiologists. RESULTS: Tumors had significantly higher absolute and relative attenuation on 40-keV VMIs (P < 0.0001). Subjectively, the 40-keV VMIs improved visualization, with substantial (κ, 0.61-0.80) to almost perfect (κ, 0.81-1) interrater agreements. CONCLUSIONS: The 40-keV VMIs improve tumor visibility objectively and subjectively both by head and neck specialists and general radiologists.

SILAC Mass Spectrometry Profiling: A Psychiatric Disorder Perspective.

Stable isotope labelling by amino acids in cell culture (SILAC) is a technique that allows proteomic profiling of cells. In this chapter we describe a protocol for the identification and quantification of newly synthesised proteins. The methodology can be applied to any cultured cell system with relevance to schizophrenia, affective disorders and autism spectrum conditions including those addressing responses to pharmacological stimuli.

Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets.

BACKGROUND: Although males contribute half of the embryo's genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter's breast cancer risk has been examined in few studies. METHODS: Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis. RESULTS: Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers' sperm and their daughters' mammary glands, and to modifications in breast cancer-related protein expression in this tissue. CONCLUSIONS: Our findings highlight the importance of paternal nutrition in affecting future generations' risk of developing breast cancer.

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring.

Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.

Developmental programming of type 2 diabetes: early nutrition and epigenetic mechanisms.

PURPOSE OF REVIEW: The environment experienced during critical windows of development can 'programme' long-term health and risk of metabolic diseases such as type 2 diabetes in the offspring. The purpose of this review is to discuss potential epigenetic mechanisms involved in the developmental programming of type 2 diabetes by early nutrition. RECENT FINDINGS: Maternal and more recently paternal nutrition have been shown to play key roles in metabolic programming of the offspring. Although the exact mechanisms are still not clear, epigenetic processes have emerged as playing a plausible role. Epigenetic dysregulation is associated with several components that contribute to type 2 diabetes risk, including altered feeding behaviour, insulin secretion and insulin action. It may also contribute to transgenerational risk transmission. SUMMARY: Epigenetic processes may represent a central underlying mechanism of developmental programming of type 2 diabetes. During embryonic and foetal development, extensive epigenetic remodelling takes place not only in somatic but also in primordial germ cells. Therefore, concerns have been raised that epigenetic dysregulation induced by a suboptimal early environment could programme altered phenotypes not only in the first generation but also in the subsequent ones. Characterizing these altered epigenetic marks has great implications for identifying individuals at an increased disease risk as well as potentially leading to novel preventive and treatment strategies.

ß-ionone inhibits persistent preneoplastic lesions during the early promotion phase of rat hepatocarcinogenesis: TGF-α, NF-κB, and p53 as cellular targets.

Dietary isoprenic derivatives such as ß-ionone (ßI) are a promising class of chemopreventive agents. In this study, cellular aspects of ßI protective activities during early hepatocarcinogenesis were evaluated. Male Wistar rats were submitted to "resistant hepatocyte" model and then received daily 16 mg/100 g body weight (b.w.) of ßI (ßI group) or only 0.25 mL/100 g b.w. of corn oil (vehicle, control group [CO]) during 4 wk, specifically during early promotion phase. Compared to controls, ßI inhibited (P < 0.05) the development of persistent preneoplastic lesions (pPNL), considered to be potential hepatocellular carcinoma (HCC) progression sites, and increased remodeling PNL (rPNL) (P < 0.05) that tend to regress to a normal phenotype. Increased ßI hepatic levels (P < 0.05), in the ßI group, were associated with its chemopreventive actions. Compared to control rats, ßI reduced the frequency of both pPNL and rPNL positive for tumor growth factor (TGF)-α (P < 0.05), reduced the frequency of pPNL stained for p65 (nuclear factor-kappaB; NF-κB) (P < 0.05), and reduced the frequency of pPNL positive for cytoplasmic p53 (P < 0.05). Our data demonstrated that ßI targets TGF-α, NF-κB, and p53 in initial phases of hepatocarcinogenesis and specifically inhibits PNL with increased probability to progress to HCC. This isoprenoid may represent a chemopreventive agent of choice for HCC control.

Universal vaginal applicator for the uniform distribution of vaginal gel and cream formulations: a magnetic resonance imaging study.

OBJECTIVE: Conventional vaginal applicators with a single apical hole do not distribute vaginal formulations homogenously and do not cover the entire vaginal and cervical mucosa. To overcome this problem and offer women further protection against vaginal infections, we designed a unique vaginal applicator with multiple apical and lateral holes. We have previously shown that the new applicator distributes an investigational vaginal gel homogenously over the entire vaginal and cervical mucosa. In this study, we investigated (using MRI) whether the new applicator works as well with marketed vaginal gels and creams. METHODS: Eighteen women participated in the study and six vaginal gels and creams were tested. Each woman used a marketed vaginal product with its own commercial applicator (CA) once and with our universal vaginal applicator (UVA) once to deliver the same product. The applications were separated by a one-week period. Pelvic MRI was performed immediately after vaginal application to evaluate the product's distribution and mucosal coverage. RESULTS: Immediately after application of the vaginal product, the UVA homogenously distributed the six products (3 gels and 3 creams) over the entire vaginal and cervical mucosa. On the other hand, the tested CA delivered four products (3 gels and 1 cream) mainly to the cervix and the upper vagina, but not to the mid and lower vagina; for the other two creams, the distribution was similar to that of UVA. Furthermore, the UVA received the highest acceptability score. CONCLUSION: The UVA can be used to deliver different vaginal gel and cream products homogenously throughout the vagina. This was the first time the UVA had been tested with marketed vaginal gels and creams. This applicator, giving uniform mucosal coverage and being highly acceptable, may help women to better protect themselves against sexually transmitted infections.

Objectif : Les applicateurs vaginaux conventionnels dotés d'un seul orifice apical ne permettent pas de distribuer les formulations vaginales de façon homogène et ne couvrent pas l'intégralité de la muqueuse vaginale et cervicale. Pour surmonter ce problème et offrir aux femmes davantage de protection contre les infections vaginales, nous avons conçu un applicateur vaginal unique en son genre doté de multiples orifices apicaux et latéraux. Nous avons déjà démontré que ce nouvel applicateur permettait de distribuer un gel vaginal expérimental de façon homogène sur l'intégralité de la muqueuse vaginale et cervicale. Dans le cadre de cette étude, nous nous sommes penchés (en ayant recours à l'IRM) sur la question de savoir si ce nouvel applicateur fonctionnait tout aussi bien dans le cas des crèmes et des gels vaginaux offerts sur le marché. Méthodes : Dix-huit femmes ont participé à l'étude et six crèmes et gels vaginaux ont été mis à l'essai. Chacune de ces femmes a utilisé à deux reprises un même produit vaginal offert sur le marché : une fois au moyen de l'applicateur commercial fourni par le fabricant (AC) et une autre fois au moyen de notre applicateur vaginal universel (AVU). Une période d'une semaine séparait ces deux applications. Une IRM pelvienne a été menée immédiatement à la suite de chacune de ces applications vaginales afin d'évaluer la distribution du produit et l'aire couverte en ce qui concerne la muqueuse. Résultats : Immédiatement à la suite de l'application du produit vaginal, nous avons constaté que l'utilisation de l'AVU permettait la distribution homogène des six produits (trois gels et trois crèmes) sur l'intégralité de la muqueuse vaginale et cervicale. En revanche, dans le cas de quatre des produits en question (trois gels et une crème), l'AC mis à l'essai a donné lieu à une distribution ayant principalement atteint le col utérin et la partie supérieure du vagin (excluant ainsi les parties intermédiaire et inférieure du vagin); pour ce qui est des deux autres crèmes, la distribution obtenue était semblable à celle qu'a permise l'AVU. De surcroît, l'AVU a obtenu le score d'acceptabilité le plus élevé. Conclusion : L'AVU peut être utilisé pour assurer l'administration de divers produits vaginaux en gel et en crème de façon homogène dans tout le vagin. Il s'agissait de la première mise à l'essai de l'AVU au moyen de crèmes et de gels vaginaux offerts sur le marché. Cet applicateur, qui permet de couvrir l'aire muqueuse de façon uniforme et qui compte une acceptabilité élevée, pourrait aider les femmes à mieux se protéger contre les infections transmissibles sexuellement.

Assessing nutrition-related knowledge, attitudes, and practices towards breast cancer prevention among female students at the Federal University of Oye-Ekiti, Nigeria.

BACKGROUND: Breast cancer remains a complex disease and leading cause of cancer-related death in Nigerian women. Recently, the role of nutrition has been highlighted in the etiology of breast cancer. METHODS: The aim of this research was to evaluate the nutrition-related knowledge, attitude, and practices of female university students. We also investigated the correlation between their demographic characteristics and their knowledge and attitudes of the survey participants. A descriptive cross-sectional study was carried out among female students at the Federal University of Oye (FUOYE), Nigeria. Participants completed self-administered questionnaires designed to assess their knowledge, attitude, and practices concerning cancer prevention. Statistical analysis was performed using SPSS 20, and significance was set at p < 0.05. RESULTS: Out of the 402 students who received the questionnaire, 300 completed it. The average age of the participants was 21.26 years with a standard deviation of 2.68. There was generally limited knowledge regarding breast cancer risk factors, with 45% of participants citing family history as the most recognized risk factor. Overall, knowledge level was influenced by the participants' permanent place of residence and course of study. Attitudes towards the impact of maternal and paternal nutrition on breast cancer prevention were notably low. Additionally, less than half of the participants demonstrated good dietary practices. CONCLUSION: This study revealed low levels of nutrition-related knowledge concerning cancer prevention, accompanied by poor dietary habits among the participants. These results suggest a possible link between inadequate knowledge about breast cancer prevention and the observed poor dietary practices among the participants. The frequent consumption of unhealthy foods among the participants may be a pointer to higher risk of breast cancer in the future, emphasizing a need for health education targeted at this group.

Essential Oils: Chemistry and Pharmacological Activities-Part II.

The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.

The chemopreventive activity of the butyric acid prodrug tributyrin in experimental rat hepatocarcinogenesis is associated with p53 acetylation and activation of the p53 apoptotic signaling pathway.

The reversibility of non-genotoxic phenotypic alterations has been explored in order to develop novel preventive and therapeutic approaches for cancer control. Previously, it has been demonstrated that histone deacetylase (HDAC) inhibitor tributyrin, a butyric acid prodrug, to have chemopreventive effects on rat hepatocarcinogenesis. The goal of this study was to determine molecular mechanisms associated with the chemopreventive activity of tributyrin. Male Wistar rats were allocated randomly to untreated control group and two experimental groups. Rats in the experimental group 1 were treated with maltodextrin (3g/kg body wt), and rats in experimental group 2 were treated with tributyrin (2g/kg body wt) daily for 8 weeks. Two weeks after treatment initiation, rats from experimental groups were subjected to a 'resistant hepatocyte' model of hepatocarcinogenesis. Treatment with tributyrin resulted in lower HDAC activity and Hdac3 and Hdac4 gene expression, and an increase of histone H3 lysine 9 and 18 and histone H4 lysine 16 acetylation as compared with the experimental group 1. In addition to the increase in histone acetylation, tributyrin caused an increase in the acetylation of the nuclear p53 protein. These changes were accompanied by a normalization of the p53-signaling network, particularly by the upregulation of pro-apoptotic genes, and a consequent increase of apoptosis and autophagy in the livers of tributyrin-treated rats. These results indicate that the chemopreventive activity of tributyrin may be related to an increase of histone and p53 acetylation, which could lead to the induction of the p53 apoptotic pathway.

Anthocyanins Reduce Cell Invasion and Migration through Akt/mTOR Downregulation and Apoptosis Activation in Triple-Negative Breast Cancer Cells: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies have suggested the chemopreventive effects of anthocyanins on breast cancer carcinogenesis. This systematic review and meta-analysis aimed to evaluate the effect of anthocyanins on triple-negative breast cancer cells (TNBC) cultured in vitro. METHODS: We searched for all relevant studies that evaluated the mechanisms of migration, invasion, Akt/mTOR and MAPK pathways, and apoptosis, using PubMed and Scopus. Means and standard deviation were used, and a randomized effects model was applied, with a confidence interval of 95%. Statistical heterogeneity between studies was assessed using the Chi2 test and I2 statistics. All analyses were performed using RevMan software (version 5.4). RESULTS: Eleven studies were included in the systematic review and ten in the meta-analysis, where the roles of anthocyanin-enriched extract or cyanidin-3-O-glucoside (C-3-O-G) on MDA-MB-231 and MDA-MB-453 cells were investigated. DISCUSSION: There was a significant reduction in invasion (mean difference: -98.64; 95% CI: -153.98, -43.3; p ˂ 0.00001) and migration (mean difference: -90.13; 95% CI: -130.57, -49.68; p ˂ 0.00001) in TNBC cells after anthocyanins treatment. Anthocyanins also downregulated Akt (mean difference: -0.63; 95% CI: -0.70, -0.57; p ˂ 0.00001) and mTOR (mean difference: -0.93; 95% CI: -1.58, -0.29; p = 0.005), while JNK (mean difference: -0.06; 95% CI: -1.21, 1.09; p = 0.92) and p38 (mean difference: 0.05; 95% CI: -1.32, 1.41; p = 0.95) were not modulated. There was also an increase in cleaved caspase-3 (mean difference: 1.13; 95% CI: 0.11, 2.16; p = 0.03), cleaved caspase-8 (mean difference: 1.64; 95% CI: 0.05, 3.22; p = 0.04), and cleaved PARP (mean difference: 0.93; 95% CI: 0.54, 1.32). Although the difference between control and anthocyanin groups was not significant regarding apoptosis rate (mean difference: 3.63; 95% CI: -2.88, 10.14; p = 0.27), the analysis between subgroups showed that anthocyanins are more favorable in inducing overall apoptosis (p ˂ 0.00001). CONCLUSION: The results show that anthocyanins hold promise in fighting against TNBC, but their effects should not be generalized. In addition, further primary studies should be conducted so that more accurate conclusions can be drawn.

Suppression of hypoxia-inducible factor-1α contributes to the antiangiogenic activity of red propolis polyphenols in human endothelial cells.

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1α (HIF1α) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent manner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1α protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1α protein half-life from ~58 min to 38 min under hypoxic conditions. The reduced HIF1α protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1α. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1α. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1α protein accumulation and signaling.

Effect of Paternal Diet on Spermatogenesis and Offspring Health: Focus on Epigenetics and Interventions with Food Bioactive Compounds.

Infertility is a growing public health problem. Consumption of antioxidant bioactive food compounds (BFCs) that include micronutrients and non-nutrients has been highlighted as a potential strategy to protect against oxidative and inflammatory damage in the male reproductive system induced by obesity, alcohol, and toxicants and, thus, improve spermatogenesis and the fertility parameters. Paternal consumption of such dietary compounds could not only benefit the fathers but their offspring as well. Studies in the new field of paternal origins of health and disease show that paternal malnutrition can alter sperm epigenome, and this can alter fetal development and program an increased risk of metabolic diseases and breast cancer in adulthood. BFCs, such as ascorbic acid, α-tocopherol, polyunsaturated fatty acids, trace elements, carnitines, N-acetylcysteine, and coenzyme Q10, have been shown to improve male gametogenesis, modulate epigenetics of germ cells, and the epigenetic signature of the offspring, restoring offspring metabolic health induced by stressors during early life. This indicates that, from a father's perspective, preconception is a valuable window of opportunity to start potential nutritional interventions with these BFCs to maximize sperm epigenetic integrity and promote adequate fetal growth and development, thus preventing chronic disease in adulthood.

Selenium Supplementation during Puberty and Young Adulthood Mitigates Obesity-Induced Metabolic, Cellular and Epigenetic Alterations in Male Rat Physiology.

Selenium (Se) role in obesity is not clear. In addition, information on Se's role in male physiology, specifically in obesity, is scarce. We conducted this study to evaluate the efficacy of Se supplementation, specifically during puberty until young adulthood, against obesity-induced deregulation of metabolic, cellular, and epigenetic parameters in epididymal fat and/or sperm cells in a rat model. High-fat-diet consumption by male rats during puberty and young adulthood significantly increased body weight, adipocyte size, oxidative stress, deregulated expression of genes associated with inflammation (Adiponectin, IL-6, TNF-α), adipogenesis (CEBPα), estrogen biosynthesis (CYP19) and epigenetic processes in epididymal adipose tissue (Dnmt3a), as well as altered microRNA expression vital for spermatogenesis in sperm cells (miR-15b and miR-497). On the other hand, Se supplementation significantly decreased oxidative stress and mitigated these molecular/epigenetic alterations in epididymal adipose tissue or sperm cells. Our results indicate that selenium supplementation during puberty/young adulthood could improve male physiology in the context of obesity. In addition, it suggests that Se could potentially positively affect offspring health.

Multidisciplinary management of chronic atopic dermatitis in children and adolescents: a prospective pilot study.

BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic disorder affecting 10-20% of children and is associated with psychological issues and impaired quality of life (QoL). The role of psychosocial support in the treatment of AD is increasingly important. We studied the impact of a multidisciplinary clinic (MDC) in the management of AD in a tertiary children's hospital in Singapore. METHODS: We performed a prospective pilot interventional study on 34 pediatric patients with AD and concomitant psychosocial impairment. Patients were recruited into an MDC, comprising a dermatologist, clinical psychologist and medical social worker. AD severity was scored using Scoring Atopic Dermatitis (SCORAD), while QoL was assessed using the Children's Dermatology Life Quality Index Questionnaire (CDLQI) and Family Dermatology Life Quality Index Questionnaire (FDLQI). Biopsychosocial assessments and interventions were also performed. Eighty-three percent of patients received cognitive behavioral therapy, while 40% received social work intervention. RESULTS: There was an overall improvement in mean SCORAD, CDLQI, and FDLQI scores across MDC visits. A correlation between AD severity and QoL was established. A patient satisfaction survey showed improvement in severity, understanding, and control of the disease. CONCLUSION: Our study suggests the effectiveness of a multidisciplinary approach in managing pediatric AD patients with psychosocial co-morbidities.

Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects.

Folic acid (FA) supplementation during carcinogenesis is controversial. Considering the impact of liver cancer as a public health problem and mandatory FA fortification in several countries, the role of FA supplementation in hepatocarcinogenesis should be elucidated. We evaluated FA supplementation during early hepatocarcinogenesis. Rats received daily 0.08 mg (FA8 group) or 0.16 mg (FA16 group) of FA/100 g body weight or water (CO group, controls). After a 2-week treatment, animals were subjected to the "resistant hepatocyte" model of hepatocarcinogenesis (initiation with diethylnitrosamine, selection/promotion with 2-acetylaminofluorene and partial hepatectomy) and euthanized after 8 weeks of treatment. Compared to the CO group, the FA16 group presented: reduced (p < 0.05) number of persistent and increased (p < 0.05) number of remodeling glutathione S-transferase (GST-P) positive preneoplastic lesions (PNL); reduced (p < 0.05) cell proliferation in persistent GST-P positive PNL; decreased (p < 0.05) hepatic DNA damage; and a tendency (p < 0.10) for decreased c-myc expression in microdissected PNL. Regarding all these parameters, no differences (p > 0.05) were observed between CO and FA8 groups. FA-treated groups presented increased hepatic levels of S-adenosylmethionine but only FA16 group presented increased S-adenosylmethionine/S-adenosylhomocysteine ratio. No differences (p > 0.05) were observed between experimental groups regarding apoptosis in persistent and remodeling GST-P positive PNL, and global DNA methylation pattern in microdissected PNL. Altogether, the FA16 group, but not the FA8 group, presented chemopreventive activity. Reversion of PNL phenotype and inhibition of DNA damage and of c-myc expression represent relevant FA cellular and molecular effects.