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

Zebrafish embryo extracts enhance 5-FU anti-cancer effects upon breast cancer cells

– OBJECTIVE: The inhibition of the metastatic capability of cancer cells is a pivotal aim of current anticancer strategies. We investigated herein the anti-migrating and anti-invasive properties of Zebrafish embryo extracts (SL) – an integrative formula comprising morphogenetic factors extracted from zebrafish embryos – alone or in association with 5-Fluoro-Uracil (5-FU), when added to metastatic breast cancer cells (MDA-MB-231) and in normal epithelial breast cells (MCF10A) committed toward an inflammatory phenotype upon TGF-β1 stimulation. MATERIALS AND METHODS: Invasiveness, migrating capability, cytoskeleton architecture and related molecular factors involved in the epithelial-mesenchymal transition were studied after treatment with 5-FU, with and without SL. RESULTS: Remarkably, in both circumstances, embryo extracts amplify the migratory inhibition triggered by the anticancer drug 5-Fu. The fact that such an effect is noticed in normal as well as in cancerous cells suggests that the critical target of embryo extracts is specifically represented by the migrating/invasive phenotype. However, while 5-FU was unable in antagonizing the invasiveness of cancerous cells, the association with SL can significantly impair the invasive capability of tumor cells. These findings are noticeably associated with the reversion of the EMT phenotype in SL-treated cells, as documented by the contemporary downregulation of TCTP and some EMT-related molecular effectors, like α-SMA and Vimentin. CONCLUSIONS: Embryo fish extracts significantly counteract the migrating and invasive phenotype of cancerous and inflammatory breast cells treated with the chemotherapeutic drug 5-FU. The availability of a compound able to amplify 5-Fu activity while significantly hampering the invasive phenotype of breast cancer should provide invaluable benefits, namely if we consider that this compound is substantially deprived of side-effects

Zebrafish embryo extracts enhance 5-FU anti-cancer effects upon breast cancer cells

OBJECTIVE: The inhibition of the metastatic capability of cancer cells is a pivotal aim of current anticancer strategies. We investigated herein the anti-migrating and anti-invasive properties of Zebrafish embryo extracts (SL) - an integrative formula comprising morphogenetic factors extracted from zebrafish embryos - alone or in association with 5-Fluoro-Uracil (5-FU), when added to metastatic breast cancer cells (MDA-MB-231) and in normal epithelial breast cells (MCF10A) committed toward an inflammatory phenotype upon TGF-beta 1 stimulation.MATERIALS AND METHODS: Invasiveness, migrating capability, cytoskeleton architecture and related molecular factors involved in the epithelial-mesenchymal transition were studied after treatment with 5-FU, with and without SL.RESULTS: Remarkably, in both circumstances, embryo extracts amplify the migratory inhibition triggered by the anticancer drug 5-Fu. The fact that such an effect is noticed in normal as well as in cancerous cells suggests that the critical target of embryo extracts is specifically represented by the migrating/invasive phenotype. However, while 5-FU was unable in antagonizing the invasiveness of cancerous cells, the association with SL can significantly impair the invasive capability of tumor cells. These findings are noticeably associated with the reversion of the EMT phenotype in SL-treated cells, as documented by the contemporary downregulation of TCTP and some EMT-related molecular effectors, like alpha-SMA and Vimentin.CONCLUSIONS: Embryo fish extracts significantly counteract the migrating and invasive phenotype of cancerous and inflammatory breast cells treated with the chemotherapeutic drug 5-FU. The availability of a compound able to amplify 5-Fu activity while significantly hampering the invasive phenotype of breast cancer should provide invaluable benefits, namely if we consider that this compound is substantially deprived of side-effects

Shear stress influences the release of platelet derived growth factor and basic fibroblast growth factor by arterial smooth muscle cells

Objectives: To determine the correlation between haemodynamic forces and the release of two mitogens for smooth muscle cells (SMC): Platelet Derived Growth Factor (PDGF) and basic Fibroblast Growth Factor (bFGF). Methodology: Bovine aortic smooth muscle cells were seeded on fibronectin coated polystyrene cylinders and allowed to reach confluence. The cells were subjected to a laminar flow of 50 cc/min (3 dyne/cm2), 100 cc/min (6 dyne/cm2) and 150 cc/min (9 dyne/cm2) in an in vitro system. Control cells were subjected to similar incubation conditions without flow. Principal results: Shear stress increased the release of mitogens by SMC. The release of mitogens was proportional to the level of shear stress and was still evident 24 hours after flow cessation. Conditioned serum-free medium from SMC subjected to shear stress increased tritiated thymidine uptake in Swiss 3T3 fibroblasts 13-fold as compared to conditioned serum-free medium from control SMC and not subjected to shear stress (p < 0.01) and threefold as compared to standard control (p < 0.001). Addition of an excess of anti-PDGF antibody reduced the mitogenic activity of the conditioned medium by 30% (p < 0.01). Addition of an excess of anti-bFGF antibody reduced the mitogenic activity of the conditioned medium by 60% (p < 0.01). Conclusions: Increasing shear stress promotes the release of both PDGF and bFGF from arterial SMC in culture and is a possible explanation for atherosclerosis formation

Before Kukulkán

This volume illuminates human lifeways in the northern Maya lowlands prior to the rise of Chichén Itzá. This period and area have been poorly understood on their own terms, obscured by scholarly focus on the central lowland Maya kingdoms. "Before Kukulkán" is anchored in three decades of interdisciplinary research at the Classic Maya capital of Yaxuná, located at a contentious crossroads of the northern Maya lowlands. Using bioarchaeology, mortuary archaeology, and culturally sensitive mainstream archaeology, the authors create an in-depth regional understanding while also laying out broader ways of learning about the Maya past. Part 1 examines ancient lifeways among the Maya at Yaxuná, while part 2 explores different meanings of dying and cycling at the settlement and beyond: ancestral practices, royal entombment and desecration, and human sacrifice. The authors close with a discussion of the last years of occupation at Yaxuná and the role of Chichén Itzá in the abandonment of this urban center. "Before Kukulkán" provides a cohesive synthesis of the evolving roles and collective identities of locals and foreigners at the settlement and their involvement in the region’s trajectory. Theoretically informed and contextualized discussions offer unique glimpses of everyday life and death in the socially fluid Maya city. These findings, in conjunction with other documented series of skeletal remains from this region, provide a nuanced picture of the social and biocultural dynamics that operated successfully for centuries before the arrival of the Itzá

Article microgravity induces transient emt in human keratinocytes by early down-regulation of e-cadherin and cell-adhesion remodeling

Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial– mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotype

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

Comparison of two ancient DNA extraction protocols for skeletal remains from tropical environments

Objectives The tropics harbor a large part of the world\u27s biodiversity and have a long history of human habitation. However, paleogenomics research in these climates has been constrained so far by poor ancient DNA yields. Here we compare the performance of two DNA extraction methods on ancient samples of teeth and petrous portions excavated from tropical and semi‐tropical sites in Tanzania, Mexico, and Puerto Rico (N = 12). Materials and Methods All samples were extracted twice, built into double‐stranded sequencing libraries, and shotgun sequenced on the Illumina HiSeq 2500. The first extraction protocol, Method D, was previously designed for recovery of ultrashort DNA fragments from skeletal remains. The second, Method H, modifies the first by adding an initial EDTA wash and an extended digestion and decalcification step. Results No significant difference was found in overall ancient DNA yields or post‐mortem damage patterns recovered from samples extracted with either method, irrespective of tissue type. However, Method H samples had higher endogenous content and more mapped reads after quality‐filtering, but also higher clonality. In contrast, samples extracted with Method D had shorter average DNA fragments. Discussion Both methods successfully recovered endogenous ancient DNA. But, since surviving DNA in ancient or historic remains from tropical contexts is extremely fragmented, our results suggest that Method D is the optimal choice for working with samples from warm and humid environments. Additional optimization of extraction conditions and further testing of Method H with different types of samples may allow for improvement of this protocol in the future

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