Paving the way for adequate myelination: The contribution of galectin-3, transferrin and iron

AbstractConsidering the worldwide incidence of well characterized demyelinating disorders such as Multiple Sclerosis (MS) and the increasing number of pathologies recently found to involve hypomyelinating factors such as micronutrient deficits, elucidating the molecular basis of central nervous system (CNS) demyelination, remyelination and hypomyelination becomes essential to the development of future neuroregenerative therapies. In this context, this review discusses novel findings on the contribution of galectin-3 (Gal-3), transferrin (Tf) and iron to the processes of myelination and remyelination and their potentially positive regulation of oligodendroglial precursor cell (OPC) differentiation. Studies were conducted in cuprizone (CPZ)-induced demyelination and iron deficiency (ID)-induced hypomyelination, and the participation of glial and neural stem cells (NSC) in the remyelination process was evaluated by means of both in vivo and in vitro assays on primary cell cultures

Uncommon Trimethoxylated Flavonol Obtained From Rubus Rosaefolius Leaves And Its Antiproliferative Activity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)This study shows the evaluation the antiproliferative effect of the extract, fractions, and uncommon compounds isolated from R. rosaefolius leaves. The compounds were identified by conventional spectroscopic methods such as NMR-H-1 and C-13 and identified as 5,7-dihydroxy-6,8,4'-trimethoxyflavonol (1), 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (2), and tormentic acid (3). Both hexane and dichloromethane fractions showed selectivity formultidrug-resistant ovary cancer cell line (NCI-ADR/RES) with total growth inhibition values of 11.1 and 12.6 mu g/ml, respectively. Compound 1 also showed selective activity against the same cell line (18.8 mu g/ml); however, it was especially effective against glioma cells (2.8 mu g/ml), suggesting that this compound may be involved with the in vitro antiproliferative action.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)ProPPEC/UNIVALICoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CNPq [212RT0464

A Central Limit Theorem for intransitive dice

Intransive dice $D^{(1)}, \ldots, D^{(\ell)}$ are dice such that $D^{(1)}$ has advantage with respect to $D^{(2)}$, dice $D^{(2)}$ has advantage with respect to $D^{(3)}$ and so on, up to $D^{(\ell)}$, which has advantage over $D^{(1)}$. In this twofold work, we present: first, (deterministic) results on existence of general intransitive dice. Second and mainly, a central limit theorem for the vector of normalized victories of a die against the next one in the list when the faces of a die are i.i.d.\ random variables and all dice are independent, but different dice may have distinct distributions associated to, as well as they may have distinct number of faces. From this central limit theorem we derive a criteria to assure that the asymptotic probability of observing intransitive dice is null, which applies for many cases, including all continuous distributions and many discrete ones.Comment: 37 pages, 3 figure

Long-Lasting Effects of Undernutrition

Undernutrition is one of the most important public health problems, affecting more than 900 million individuals around the World. It is responsible for the highest mortality rate in children and has long-lasting physiologic effects, including an increased susceptibility to fat accumulation mostly in the central region of the body, lower fat oxidation, lower resting and postprandial energy expenditure, insulin resistance in adulthood, hypertension, dyslipidaemia and a reduced capacity for manual work, among other impairments. Marked changes in the function of the autonomic nervous system have been described in undernourished experimental animals. Some of these effects seem to be epigenetic, passing on to the next generation. Undernutrition in children has been linked to poor mental development and school achievement as well as behavioural abnormalities. However, there is still a debate in the literature regarding whether some of these effects are permanent or reversible. Stunted children who had experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted. Children treated before 6 years of age in day-hospitals and who recovered in weight and height have normal body compositions, bone mineral densities and insulin production and sensitivity

Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice

Ghrelin stimulates both GH secretion and food intake. The orexigenic action of ghrelin is mainly mediated by neurons that coexpress agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). GH also stimulates food intake and, importantly, ARHAgRP/NPY neurons express GH receptor (GHR). Thus, ghrelin-induced GH secretion may contribute to the orexigenic effect of ghrelin. Here, we investigated the response to ghrelin in male mice carrying GHR ablation specifically in neurons (brain GHR knockout [KO] mice) or exclusively in ARHAgRP/NPY neurons (AgRP GHR KO mice). Although brain GHR KO mice showed normal ghrelin-induced increase in plasma GH levels, these mutants lacked the expected orexigenic response to ghrelin. Additionally, brain GHR KO mice displayed reduced hypothalamic levels of Npy and Ghsr mRNA and did not elicit ghrelin-induced c-Fos expression in the ARH. Furthermore, brain GHR KO mice exhibited a prominent reduction in AgRP fiber density in the ARH and paraventricular nucleus of the hypothalamus (PVH). In contrast, AgRP GHR KO mice showed no changes in the hypothalamic Npy and Ghsr mRNAs and conserved ghrelin-induced food intake and c-Fos expression in the ARH. AgRP GHR KO mice displayed a reduced AgRP fiber density (∼16%) in the PVH, but this reduction was less than that observed in brain GHR KO mice (∼61%). Our findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARHAgRP/NPY neurons.Fil: Wasinski, Frederick. Universidade de Sao Paulo; BrasilFil: Barrile, Franco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Pedroso, João A. B.. Universidade de Sao Paulo; BrasilFil: Quaresma, Paula G. F.. Universidade de Sao Paulo; BrasilFil: Dos Santos, Willian O.. Universidade de Sao Paulo; BrasilFil: List, Edward O.. Ohio University; Estados UnidosFil: Kopchick, John J.. Ohio University; Estados UnidosFil: Perelló, Mario. Multidisciplinary Institute Of Cell Biology; ArgentinaFil: Donato, Jose. Universidade de Sao Paulo; Brasi

Photocatalytic activity of TiO2/graphene and TiO2/graphene oxide nanocomposites

Semiconductor-based heterogeneous photocatalysis has been one of the most promising processes for the treatment of contaminated water. Among the available catalysts, titanium dioxide (TiO2) presents the best photocatalytic properties, being chemically and biologically inert, stable, non-toxic, cheap and easy to produce. However, its energy bang gap lies in the ultraviolet (UV) range, which is responsible for a reduced spectral activation, since UV radiation corresponds to only 5% of the solar spectrum [1]. For this reason, one of the main purposes of the scientific community has been to improve the photocatalytic performance of TiO2, namely through an adequate doping of this material, or through the creation of nanocomposites, to enable photocatalysis occurrence by the incidence of visible light. One alternative concerns the application of nanocomposites of TiO2 with graphene and graphene oxide to photocatalytic processes [2]. In this work, nanocomposites of TiO2 with different weight concentrations of graphene and graphene oxide (namely 0.5%, 1%, 1.5% and 3%) were synthetized by a one-step hydrothermal method and characterized in terms of morphology, crystalline structure, vibrational modes and optical band gap. The photocatalytic activity of these nanocomposites was then evaluated through the degradation of methylene blue and ciprofloxacin solutions under UV and visible radiation. The results indicated that the studied nanocomposites presented higher degradation rates of the methylene blue than the pure TiO2, which increased with the content of graphene/graphene oxide. However, these composites proved to be less suitable to degrade the ciprofloxacin solution than the pure TiO2 nanoparticles.Portuguese Foundation for Science and Technology (FCT) - UID/FIS/04650/2013, PTDC/CTM-ENE/5387/2014 and SFRH/BD/98616/2013; Basque Government Industry Department under the ELKARTEK Program.info:eu-repo/semantics/publishedVersio

Sulfonyldibenzoate coordination polymers as bioactive dopants for polysaccharide films with antibacterial and antibiofilm properties

This work describes the preparation, characterization, and antimicrobial properties of bioactive silver(I) and copper(II) coordination polymers (bioCPs) and derived biopolymer materials. Two bioCPs, [Ag2(6-sdba)]n (1) and [Cu(4-sdba)H2O]n·1.5nH2O (2), were assembled from metal salt precursors and 4,4-sulfonyldibenzoic acid (H2sdba). Both compounds were used as dopants for preparing hybrid biopolymer films based on agarose (AGR) or potato starch (PS) as model polysaccharide biopolymers with varying rates of degradability and silver/copper release. BioCPs and derived biopolymer films (1@[AGR]n, 2@[AGR]n, 1@[PS]n, and 2@[PS]n) with a low loading of dopant (15 wt%) show promising antibacterial activity against Gram-positive (S. aureus and S. epidermidis) and Gram-negative (E. coli and P. aeruginosa) bacteria. Silver-doped biopolymer films also totally impair the formation of bacterial biofilms, with undetectable biofilm cells in several cases (7.5log or 99.99999% inhibition). By reporting new bioCPs and biopolymer films obtained from renewable polysaccharides, this multidisciplinary work extends the application of coordination compounds as components of hybrid functional materials with antimicrobial properties and prospective biomedical relevance.This study was supported by the Foundation for Science and Technology (FCT) (projects PTDC/QUI-QIN/3898/2020, PTDC/QUI-QIN/29697/2017, UIDP/00100/2020, UIDB/00100/2020, LA/P/0056/2020, and REM2013; contracts under DL No. 57/2016, CEECIND/02725/2018, CEECIND/00283/2018 and CEECIND/00194/2020) as well as ISEL (IPL/2022/3DBioProd_ISEL, and IPL/2021/Naf4Med3D_ISEL). We thank Dr. Ivo M. F. Bragança for studying the mechanical properties.info:eu-repo/semantics/publishedVersio

Self-assembled RGD dehydropeptide hydrogels for drug delivery applications

Peptide-based self-assembled hydrogels have triggered remarkable research interest in recent years owing to their biocompatibility and biomimetic properties and responsiveness, which warrant many technological and biomedical applications. Dehydrodipeptides N-capped with naproxen emerged from our research as effective hydrogelators endowed with resistance to proteolysis. Dehydrodipeptide-based hydrogels are promising nanocarriers for drug delivery applications. In this work, we demonstrate that dehydrodipetide Npx-L-Ala-Z-ΔPhe-OH can be deployed as a minimalist hydrogelator module for synthesizing a gelating construct Npx-L-Ala-Z-ΔPhe-G-R-G-D-G-OH bearing a GRGDG adhesion motif. The self-assembly of the peptide construct and the drug delivery properties of the hydrogel were studied in this work. The peptide construct showed no toxicity towards a fibroblast cell line expressing the αvβ3 integrin. Docking studies suggest that the hydrogelator block does not interfere with the recognition of the RGD motif by the integrin receptor. The self-assembly seems to be directed by intermolecular naphthalene π–π stacking interactions, with the peptide backbone assuming a random coil conformation both in solution and in the gel phase. TEM and STEM imaging revealed that the hydrogel is made of entangled bundles of long thin fibres (width circa 23 nm). The hydrogel exhibits viscoelastic properties, thermo-reversibility and recovery after mechanical fluidization. FRET studies showed that curcumin incorporated into the hydrogel interacts non-covalently with the hydrogel fibrils. Delivery of curcumin from the hydrogel into Nile red loaded model membranes (SUVs) was demonstrated by FRET. Naproxen N-capped dehydrodipeptides are efficacious minimalist hydrogelator modules for obtaining hydrogels functionalized with peptide ligands for cell receptors. These hydrogels are potential nanocarriers for drug delivery

Association of serum lipid components and obesity with genetic ancestry in an admixed population of elderly women

The prevalence of metabolic disorders varies among ethnic populations and these disorders represent a critical health care issue for elderly women. This study investigated the correlation between genetic ancestry and body composition, metabolic traits and clinical status in a sample of elderly women. Clinical, nutritional and anthropometric data were collected from 176 volunteers. Genetic ancestry was estimated using 23 ancestry-informative markers. Pearsons correlation test was used to examine the relationship between continuous variables and an independent samples t-test was used to compare the means of continuous traits within categorical variables. Overall ancestry was a combination of European (57.49%), Native American (25.78%) and African (16.73%). Significant correlations were found for European ancestry with body mass index (r = 0.165; p = 0.037) and obesity (mean difference (MD) = 5.3%; p = 0.042). African ancestry showed a significant correlation with LDL (r = 0.159, p = 0.035), VLDL (r = -0.185; p = 0.014), hypertriglyceridemia (MD = 6.4%; p = 0.003) and hyperlipidemia (MD = 4.8%; p = 0.026). Amerindian ancestry showed a significant correlation with triglyceride levels (r = 0.150; p = 0.047) and hypertriglyceridemia (MD = 4.5%; p = 0.039). These findings suggest that genetic admixture may influence the etiology of lipid metabolism-related diseases and obesity in elderly women

Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line

Glioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of Hedychium coronarium, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer.This research was funded by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/06636–7 and 2016/06137–6), financiadora de Estudos e Projetos FINEP (MCTI/FINEP/MS/SCTIE/DECIT–01/2013–FPXII–BIOPLAT)