An association of boswellia, betaine and myo-inositol (Eumastós) in the treatment of mammographic breast density. A randomized, double-blind study

Mammographic breast density is a recognized risk factor for breast cancer. The causes that lead to the proliferation of the glandular breast tissue and, therefore, to an increase of breast density are still unclear. However, a treatment strategy to reduce the mammary density may bring about very relevant clinical outcomes in breast cancer prevention. Myo-inositol is a six-fold alcohol of cyclohexane, has already been proved to modulate different pathways: inflammatory, metabolic, oxidative and endocrine processes, in a wide array of human diseases, including cancer and the genesis of mammary gland and breast diseases, like fibrosis, as well as metabolic and endocrine cues. Similarly, boswellic acid and betaine (three-methyl glycine) both inhibit inflammation and exert protective effects on breast physiology. Based on this scientific background, we hypothesized that a combination including, boswellic acid, betaine and myo-inositol would be able to reduce breast density working on different pathways.OBJECTIVE: Mammographic breast density is a recognized risk factor for breast cancer. The causes that lead to the proliferation of the glandular breast tissue and, therefore, to an increase of breast density are still unclear. However, a treatment strategy to reduce the mammary density may bring about very relevant clinical outcomes in breast cancer prevention. Myo-inositol is a six-fold alcohol of cyclohexane, has already been proved to modulate different pathways: inflammatory, metabolic, oxidative and endocrine processes, in a wide array of human diseases, including cancer and the genesis of mammary gland and breast diseases, like fibrosis, as well as metabolic and endocrine cues. Similarly, boswellic acid and betaine (threemethyl glycine) both inhibit inflammation and exert protective effects on breast physiology. Based on this scientific background, we hypothesized that a combinat ion including, boswellic acid, betaine and myo-inositol would be able to reduce breast density working on different pathways. PATIENTS AND METHODS: In this study, seventy-six premenopausal women were randomly assigned to the placebo and the experimental drug arms (Eumastós®) for six months. RESULTS: After 6 months of treatment, statistically significant difference between the two groups was recorded on the breast density reduction (60% vs. 9%), using mammographic as well as ultrasound examination. CONCLUSIONS: Preliminary data collected here with support the starting assumptions,that the association comprising boswellic acid, betaine and myo-inositol significantly reduces mammary density, providing the first evidence for a new and safe approach for the management of mammographic density treatment

Quercetin directly promotes rabbit ovarian steroidogenesis

[EN] The bioflavonoid quercetin is a component of food with numerous biological effects, but its function in reproductive processes remains to be investigated. This study aimed to examine the direct action of quercetin on steroid hormone release in rabbit ovaries. We analysed the effect of quercetin (0, 1, 10, and 100 ng/mL) on cultured rabbit ovarian fragments. The release of progesterone (P4), testosterone (T) and estradiol (E2) were analysed by enzyme immunoassay. Quercetin promoted P4, T, and E2 release by rabbit ovarian fragments. These observations indicate that quercetin can directly stimulate rabbit ovarian steroidogenesis – an essential regulator of reproduction and fecundity. The application of dietary quercetin for control of rabbit reproduction is discussed.Sirotkin, A.; Štochmaľová, A.; Grossmann, R.; Alwasel, S.; Harrath, A. (2019). Quercetin directly promotes rabbit ovarian steroidogenesis. World Rabbit Science. 27(3):163-167. https://doi.org/10.4995/wrs.2019.11816163167273Anand D.A.V., Arulmoli R., Parasuraman S. 2016. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn. Rev., 10: 84-89. https://doi.org/10.4103/0973-7847.194044Beazley K.E., Nurminskaya M. 2016. Effects of dietary quercetin on female fertility in mice: implication of transglutaminase 2. Reprod. Fertil. Dev., 28: 974-981. https://doi.org/10.1071/RD14155Boots A.W., Haenen G.R.M.M., Bast A. 2008. Health effect of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol., 585: 325-337. https://doi.org/10.1016/j.ejphar.2008.03.008Chen C., Zhou, J.J., 2010a. Quercetin: A potential drug to reverse multidrug resistance. Life Sci., 87: 333-338. https://doi.org/10.1016/j.lfs.2010.07.004Chen Z.G., Luo L.L., Xu J.J., Zhuang X.L., Kong X.X., Fu Y.C., 2010b. Effects of plant polyphenols on ovarian follicular reserve in ageing rats. Biochem. Cell. Biol., 88: 737-45. https://doi.org/10.1139/O10-012Münster E. 1989. Entwicklung von enzymimmunologischen Messverfahren auf Mikrotitrationsplatten zur Bestimmung von Testosteron und Progesteron im Blutplasma. Doctoral Thesis. Institut for Animal Production and Breeding of the University of Hohemheim. 154.Naseer Z., Ahmad E., Epikmen E.T., Uçan U., Boyacioğlu M., İpek E., Akosy M. 2017. Quercetin supplemented diet improves follicular development, oocyte quality, and reduces ovarian apoptosis in rabbits during summer heat stress. Theriogenology, 96: 136-141. https://doi.org/10.1016/j.theriogenology.2017.03.029Nna V.U., Usman U.Z., Ofutet E.O., Owu D.U. 2017. Quercetin exerts preventive, ameliorative and prophylactic effects on cadmium chloride - induced oxidative stress in the uterus and ovaries of female Wistar rats. Food Chem. Toxicol., 102: 143-155. https://doi.org/10.1016/j.fct.2017.02.010Prakash B.S., Meyer H.H., Schallenberger E., van de Wiel D.F. 1987. Development of a sensitive enzyme immunoassay (EIA) for progesterone determination in unextracted bovine plasma using the second antibodytechnique. J. Steroid Biochem. Mol. Biol., 28: 623-627. https://doi.org/10.1016/0022-4731(87)90389-XRice S., Mason H.D., Whitehead S.A. 2006. Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells. J. Steroid Biochem. Mol. Biol., 101: 216-225. https://doi.org/10.1016/j.jsbmb.2006.06.021Santini S.E., Basini G., Bussolati S., Grasselli F. 2009. The phytoestrogen quercetin impairs steroidogenesis and angiogenesis in swine granulosa cells in vitro. J. Biomed. Biotechnol., 2009: 419891. https://doi.org/10.1155/2009/419891Sharma A., Kashyap D., Sak K., Tuli H.S., Sharma A.K. 2018. Therapeutic charm of quercetin and its derivatives: a review of research and patents. Pharm. Pat. Anal., 7: 15-32. https://doi.org/10.4155/ppa-2017-0030Shu X., Hu X.J., Zhou S.Y., Xu C.L., Qiu Q.Q., Nie S.P., Xie M.Y. 2011. [Effect of quercetin exposure during the prepubertal period on ovarian development and reproductive endocrinology of mice]. Yao Xue Xue Bao, 46: 1051-1057.Sirotkin A.V. 2014. Regulators of ovarian functions. New York: Nova Science Publishers Inc. 194, ISBN 978-1-62948-574-4.Sirotkin A.V., Harrath A.H. 2014. Phytoestrogens and their effects. Eur J Pharmacol., 741: 230-236. https://doi.org/10.1016/j. ejphar.2014.07.057Sirotkin A.V., Chrenek P., Kolesarová A., Parillo F., Zerani M., Boiti C. 2014. Novel regulators of rabbit reproductive functions. Anim. Reprod. Sci., 148: 188-196. https://doi.org/10.1016/j.anireprosci.2014.06.001Sirotkin A.V., Kadasi A., Stochmalova A., Balazi A., Földesiová M., Makovicky P., Chrenek P., Harrath A.H. 2017. Effect of turmeric on the viability, ovarian folliculogenesis, fecundity, ovarian hormones and response to luteinizing hormone of rabbits. Animal. 26: 1-8. https://doi.org/10.1017/S175173111700235Xvan Duursen M.B.M. 2017. Modulation of estrogen synthesis and metabolism by phytoestrogens in vitro and the implications for women's health. Toxicol Res (Camb)., 6: 772-794. https://doi.org/10.1039/C7TX00184CWalgren R.A., Lin J.T., Kinne R.K., Walle T. 2000. Cellular uptake of dietary flavonoid quercetin 4'-beta-glucoside by sodiumdependent glucose transporter SGLT1. J. Pharmacol. Exp. Ther., 294: 837-843.Whitehead S.A., Lacey M. 2003. Phytoestrogens inhibit aromatase but not 17beta-hydroxysteroid dehydrogenase (HSD) type 1 in human granulosa-luteal cells: evidence for FSH induction of 17beta-HSD. Hum. Reprod.,18: 487-494. https://doi.org/10.1093/humrep/deg12

Survival pathways are differently affected by microgravity in normal and cancerous breast cells

Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be paradoxically protected from programmed cell death during weightlessness. These controversial results can be explained by considering the notion that the behavior of adherent cells dramatically diverges in respect to that of detached cells, organized into organoids-like, floating structures. We investigated both normal (MCF10A) and cancerous (MCF-7) breast cells and found that appreciable apoptosis occurs only after 72 h in MCF-7 cells growing in organoid-like structures, in which major modifications of cytoskeleton components were observed. Indeed, preserving cell attachment to the substrate allows cells to upregulate distinct Akt- and ERK-dependent pathways in MCF-7 and MCF-10A cells, respectively. These findings show that survival strategies may differ between cell types but cannot provide sufficient protection against weightlessness-induced apoptosis alone if adhesion to the substrate is perturbed

Smart monitoring system of Najran dam

Najran city faces the flood situation every year due to intensive rain and climatic disturbances. Flooding also causes loss of money, along with loss of life and property and the destruction of agriculture and livestock. Thus, this project proposes a conceptual framework with three main phases: monitoring the water level inside the dam and level in water stream before and after the dam, controlling the opening and closing of the dam gate and measuring the water pressure at the dam barrier. In the case of high water level dam is monitored through water sensors placed at the top of the dam and then these sensors give a reference to the stepper motor and the flow of the stepper motor is controlled by the dam gate. The experimental results shows that the proposed system has the capability to reliably tackle the flood water. It can accurately measure the water level and control the gate of dam as soon as the level of the water reaches to danger level and water pressure at the barrier is measured by the sensor. The developed real-time monitoring system in Najran dam will help authorities to take preventive actions to deal with flood disaster

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

Microgravity impairs tissue organization and critical pathways involved in the cell– microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization

An Overview of Functional Food

Functional foods are responsible for the improvement of human health and can significantly reduce the probability of disease in the host body. Functional foods are directly or indirectly part of different food ingredients and can induce functional activities in the host biological system. Functional foods are present in fruits, vegetables, dairy, bakery, cereals and meat products. Functional foods are not additional food supplements, drugs or antibiotics, they are the main component of a normal human and animal diet. Functional foods are cost-effective and easily available in the market. Daily consumption of functional foods can prevent the gastrointestinal diseases and also provide ease against different acute and chronic diseases. Adequate administration of probiotics in a human food can convert a normal food into functional food. This chapter will highlight the effective role of functional food in an individual’s daily life

Metabolic Programming during Lactation Stimulates Renal Na+ Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways

BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Female rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na(+)+K(+))ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K(+). Programming doubled the ouabain-insensitive Na(+)-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT(1) and decreased the expression of AT(2) receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT(2) receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na(+) excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days. CONCLUSIONS/SIGNIFICANCE: Maternal protein restriction during lactation results in alterations in GFR, renal Na(+) handling and in components of the Ang II-linked regulatory pathway of renal Na(+) reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood