Primary Active Seed Substances from Medicinal Plants as a Possible Supplement to Livestock Nutrition

Some of the active substances from the seeds of medicinal plants have a beneficial effect on human and animal health. The representatives of this group of plants, in addition to the secondary (biologically) active substances significant for their therapeutic properties and the flavours in the content of their seeds, have a high percentage of primary active substances (carbohydrates, oils, proteins and the like). These components are essential for plant growth and reproduction, but they are also very important as constituent substances. The objective of this study was to determine the effect of storage duration (from one to five years) on oil and protein content of the seeds of various medicinal plants. The seeds of 9 cultivated plant species namely: white mustard (Sinapis alba L.), flax (Linum usitatissimum L.), fenugreek (Trigonella foenum graecum L.), evening primrose (Oenothera biennis L.), marigold (Calendula officinalis L.), milk thistle (Silybum marianum Gaertn.), black cumin (Nigella sativa L.), borage (Borago officinalis L.) and castor oil plant (Ricinus communis L.) were analyzed. Laboratory studies have been performed in three replications in the course of 2014 according to accredited methods. On average, the highest oil content was obtained from castor seed (50.44%), whereas the lowest average oil content was recorded in fenugreek seed (5.35%). The greatest statistically significant variation of the oil content was observed in the seeds of white mustard. In spite of that, the highest number of medicinal plants had a statistically considerable reduction in oil contents between seeds of different ages. The highest protein content was recorded in the seeds of white mustard (31.96%), which was by about 2.3 times higher than the lowest protein content in seeds of evening primrose (13.80%). The largest statistically significant variation in protein content was observed with the seeds of white mustard, marigold and flax. The high content of oil and protein, with their beneficial effects, can positively affect the proper functioning of the immune system of bred animals, and can also work as an antioxidant, as a blood purifier, it destroys intestinal parasites, stops diarrhea, and cures foot-and-mouth disease, and the like

Onco-miR-155 targets SHIP1 to promote TNFalpha-dependent growth of B cell lymphomas.

Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro-inflammatory cytokine tumour necrosis factor a (TNFalpha). Anti-TNFalpha regimen such as eternacept or infliximab were sufficient to reduce miR-155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine-regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti-TNFalpha therapy as a novel and immediately accessible (co)treatment for DLBCL

Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells

Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of LGALS1, the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of LGALS1 into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that LGALS1 is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between LGALS1 transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle.publishedVersio

Evaluation of Staining-Dependent Colour Changes in Resin Composites Using Principal Component Analysis

Colour changes in Gradia Direct (TM) composite after immersion in tea, coffee, red wine, Coca-Cola, Colgate mouthwash, and distilled water were evaluated using principal component analysis (PCA) and the CIELAB colour coordinates. The reflection spectra of the composites were used as input data for the PCA. The output data (scores and loadings) provided information about the magnitude and origin of the surface reflection changes after exposure to the staining solutions. The reflection spectra of the stained samples generally exhibited lower reflection in the blue spectral range, which was manifested in the lower content of the blue shade for the samples. Both analyses demonstrated the high staining abilities of tea, coffee, and red wine, which produced total colour changes of 4.31, 6.61, and 6.22, respectively, according to the CIELAB analysis. PCA revealed subtle changes in the reflection spectra of composites immersed in Coca-Cola, demonstrating Coca-Colas ability to stain the composite to a small degree

Vav1/2/3-null mice define an essential role for vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells

The Vav family of Rho guanine nucleotide exchange factors is thought to orchestrate signaling events downstream of lymphocyte antigen receptors. Elucidation of Vav function has been obscured thus far by the expression of three highly related family members. We generated mice lacking all Vav family proteins and show that Vav-null mice produce no functional T or B cells and completely fail to mount both T-dependent and T-independent humoral responses. Whereas T cell development is blocked at an early stage in the thymus, immature B lineage cells accumulate in the periphery but arrest at a late “transitional” stage. Mechanistically, we show that the Vav family is crucial for both TCR and B cell receptor (BCR)–induced Ca(2+) signaling and, surprisingly, is only required for mitogen-activated protein kinase (MAPK) activation in developing and mature T cells but not in B cells. Thus, the abundance of immature B cells generated in Vav-null mice may be due to intact Ras/MAPK signaling in this lineage. Although the expression of Vav1 alone is sufficient for normal lymphocyte development, our data also reveal lineage-specific roles for Vav2 and Vav3, with the first demonstration that Vav3 plays a critical compensatory function in T cells. Together, we define an essential role for the entire Vav protein family in lymphocyte development and activation and establish the limits of functional redundancy both within this family and between Vav and other Rho–guanine nucleotide exchange factors

Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes

Melanoma has the highest propensity of all cancers to metastasize to the brain with a large percentage of late-stage patients developing metastases in the central nervous system (CNS). It is well known that metastasis establishment, cell survival, and progression are affected by tumour-host cell interactions where changes in the host cellular compartments likely play an important role. In this context, miRNAs transferred by tumour derived extracellular vesicles (EVs) have previously been shown to create a favourable tumour microenvironment. Here, we show that miR-146a-5p is highly expressed in human melanoma brain metastasis (MBM) EVs, both in MBM cell lines as well as in biopsies, thereby modulating the brain metastatic niche. Mechanistically, miR-146a-5p was transferred to astrocytes via EV delivery and inhibited NUMB in the Notch signalling pathway. This resulted in activation of tumour-promoting cytokines (IL-6, IL-8, MCP-1 and CXCL1). Brain metastases were significantly reduced following miR-146a-5p knockdown. Corroborating these findings, miR-146a-5p inhibition led to a reduction of IL-6, IL-8, MCP-1 and CXCL1 in astrocytes. Following molecular docking analysis, deserpidine was identified as a functional miR-146a-5p inhibitor, both in vitro and in vivo. Our results highlight the pro-metastatic function of miR-146a-5p in EVs and identifies deserpidine for targeted adjuvant treatment.publishedVersio

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

Indication for the disappearance of reactor electron antineutrinos in the Double Chooz experiment

The Double Chooz Experiment presents an indication of reactor electron antineutrino disappearance consistent with neutrino oscillations. A ratio of 0.944 $\pm$ 0.016 (stat) $\pm$ 0.040 (syst) observed to predicted events was obtained in 101 days of running at the Chooz Nuclear Power Plant in France, with two 4.25 GW$_{th}$ reactors. The results were obtained from a single 10 m$^3$ fiducial volume detector located 1050 m from the two reactor cores. The reactor antineutrino flux prediction used the Bugey4 measurement as an anchor point. The deficit can be interpreted as an indication of a non-zero value of the still unmeasured neutrino mixing parameter \sang. Analyzing both the rate of the prompt positrons and their energy spectrum we find \sang = 0.086 $\pm$ 0.041 (stat) $\pm$ 0.030 (syst), or, at 90% CL, 0.015 $<$ \sang $\ <$ 0.16.Comment: 7 pages, 4 figures, (new version after PRL referee's comments