Stearic acid, beeswax and carnauba wax as green raw materials for the loading of carvacrol into nanostructured lipid carriers

The use of lipid nanoparticles as drug delivery systems has been growing over recent decades. Their biodegradable and biocompatible profile, capacity to prevent chemical degradation of loaded drugs/actives and controlled release for several administration routes are some of their advantages. Lipid nanoparticles are of particular interest for the loading of lipophilic compounds, as happens with essential oils. Several interesting properties, e.g., anti-microbial, antitumoral and antioxidant activities, are attributed to carvacrol, a monoterpenoid phenol present in the composition of essential oils of several species, including Origanum vulgare, Thymus vulgaris, Nigellasativa and Origanum majorana. As these essential oils have been proposed as the liquid lipid in the composition of nanostructured lipid carriers (NLCs), we aimed at evaluating the influence of carvacrol on the crystallinity profile of solid lipids commonly in use in the production of NLCs. Different ratios of solid lipid (stearic acid, beeswax or carnauba wax) and carvacrol were prepared, which were then subjected to thermal treatment to mimic the production of NLCs. The obtained binary mixtures were then characterized by thermogravimetry (TG), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS) and polarized light microscopy (PLM). The increased concentration of monoterpenoid in the mixtures resulted in an increase in the mass loss recorded by TG, together with a shift of the melting point recorded by DSC to lower temperatures, and the decrease in the enthalpy in comparison to the bulk solid lipids. The miscibility of carvacrol with the melted solid lipids was also confirmed by DSC in the tested concentration range. The increase in carvacrol content in the mixtures resulted in a decrease in the crystallinity of the solid bulks, as shown by SAXS and PLM. The decrease in the crystallinity of lipid matrices is postulated as an advantage to increase the loading capacity of these carriers. Carvacrol may thus be further exploited as liquid lipid in the composition of green NLCs for a range of pharmaceutical applications.This work was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil, FinanceCode 001), by the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) under the projects M-ERA-NET/0004/2015 and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

The androgen receptor can signal through Wnt/β-Catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens

<p>Abstract</p> <p>Background</p> <p>A crucial event in Prostate Cancer progression is the conversion from a hormone-sensitive to a hormone-refractory disease state. Correlating with this transition, androgen receptor (AR) amplification and mutations are often observed in patients failing hormonal ablation therapies. β-Catenin, an essential component of the canonical Wnt signaling pathway, was shown to be a coactivator of the AR signaling in the presence of androgens. However, it is not yet clear what effect the increased levels of the AR could have on the Wnt signaling pathway in these hormone-refractory prostate cells.</p> <p>Results</p> <p>Transient transfections of several human prostate cancer cell lines with the AR and multiple components of the Wnt signaling pathway demonstrate that the AR overexpression can potentiate the transcriptional activities of Wnt/β-Catenin signaling. In addition, the simultaneous activation of the Wnt signaling pathway and overexpression of the AR promote prostate cancer cell growth and transformation at castration levels of androgens. Interestingly, the presence of physiological levels of androgen or other AR agonists inhibits these effects. These observations are consistent with the nuclear co-localization of the AR and β-Catenin shown by immunohistochemistry in human prostate cancer samples. Furthermore, chromatin immunoprecipitation assays showed that Wnt3A can recruit the AR to the promoter regions of Myc and Cyclin D1, which are well-characterized downstream targets of the Wnt signalling pathway. The same assays demonstrated that the AR and β-Catenin can be recruited to the promoter and enhancer regions of a known AR target gene PSA upon Wnt signaling. These results suggest that the AR is promoting Wnt signaling at the chromatin level.</p> <p>Conclusion</p> <p>Our findings suggest that the AR signaling through the Wnt/β-Catenin pathway should be added to the well established functional interactions between both pathways. Moreover, our data show that via this interaction the AR could promote prostate cell malignancy in a ligand-independent manner.</p

Investigation of protective effects of erythrina velutina extract against MMS induced damages in the root meristem cells of allium cepa

Erythrina velutina Willd., Fabaceae, is a medicinal plant that can be found in the tropics and subtropics, including in the semi-arid northeastern Brazil. It is commonly used in folk medicine to treat anxiety, agitation and insomnia. E. velutina has been known to present analgesic, anti-infl ammatory and antibacterial activities, however, it is unknown if this plant present a protective effect on DNA. We assessed the antigenotoxic effect of E. velutina against the genotoxic effects induced by MMS in the root meristem cells of Allium cepa. Three concentrations of the aqueous extract (100, 200 and 400 mg/L) of this medicinal plant were used in three different types of treatment (pre-, post- and simultaneous). The effects of the extracts on the root meristem cells of A. cepa were analyzed at both macroscopic and microscopic levels. Protective effects were observed at higher concentrations in pre-treatment and in simultaneous treatment. The results suggest that E. velutina may present antigenotoxic properties and demonstrate its chemopreventive potential

Myeloid Sirtuin 2 expression does not impact long-term Mycobacterium tuberculosis control

Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-?, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis.Fundação para a Ciência e Tecnologia, Portugal and cofunded by Programa Operacional Regional do Norte (ON.2–O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER). Project grants: PTDC/SAU-MII/101977/2008 (to AGC) and PTDC/BIA-BCM/102776/2008 (to MS). LMT was supported by FCT Grant SFRH/BPD/77399/20

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Evolutionary dynamics of the karyotype of the wasp Trypoxylon (Trypargilum) nitidum (Hymenoptera, Sphecidae) from the Rio Doce State Park, Minas Gerais, Brazil

Cytogenetic analysis based on the distribution of C-bands showed two groups of karyotypes in a Trypoxylon nitidum population from the Rio Doce Park, State of Minas Gerais, Brazil. One of these groups, that was identical to a previously described karyotype (n = 15; 2n = 30), had a stable chromosome number and was rich in acrocentric chromosomes, whereas the other had a variable chromosome number (n = 12 to 14; 2n = 25 to 28) and was rich in pseudo-acrocentric chromosomes. We propose a hypothesis explaining the dynamics of the modifications which occurred in the karyotype of this species, based on the minimum interaction theory of Imai et al. (1986, 1988, 1994) and on the chromosome rearrangements and heteromorphisms observed by us

THE EFFECT OF DIFFERENT VOLUMES OF ACUTE RESISTANCE EXERCISE ON ELDERLY INDIVIDUALS WITH TREATED HYPERTENSION

Scher, LML, Ferriolli, E, Moriguti, JC, Scher, R, and Lima, NKC. The effect of different volumes of acute resistance exercise on elderly individuals with treated hypertension. J Strength Cond Res 25(4): 1016-1023, 2011-Acute resistance exercise can reduce the blood pressure (BP) of hypertensive subjects. The aim of this study was to evaluate the effect of different volumes of acute low-intensity resistance exercise over the magnitude and the extent of BP changes in treated hypertensive elderly individuals. Sixteen participants (7 men, 9 women), with mean age of 68 6 5 years, performed 3 independent randomized sessions: Control (C: 40 minutes of rest), Exercise 1 (E1: 20 minutes, 1 lap in the circuit), and Exercise 2 (E2: 40 minutes, 2 laps in the circuit) with the intensity of 40% of 1 repetition maximum. Blood pressure was measured before (during 20 minutes) and after each session (every 5 minutes during 60 minutes) using both a mercury sphygmomanometer and a semiautomatic device (Omrom-HEM-431). After that, 24-hour ambulatory blood pressure monitoring was performed (Dyna-MAPA). Blood pressure decreased during the first 60 minutes (systolic: p < 0.01, diastolic: p < 0.05) after all exercise sessions. Only the highest volume session promoted a reduction of mean systolic 24-hour BP and awake BP (p, 0.05) after exercise, with higher diastolic BP during sleep (p, 0.05). Diastolic 24-hour BP and both systolic and diastolic BP during sleep were higher after E1 (p, 0.05). Concluding, acute resistive exercise sessions in a circuit with different volumes reduced BP during the first 60 minutes after exercise in elderly individuals with treated hypertension. However, only the highest volume promoted a reduction of mean 24-hour and awake systolic BP.National Council for Scientific and Technological Development (CNPq)Foundation for the Support to Education, Research, and Assistance of the University Hospital, Ribeirao Preto School of Medicine (FAEPA