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1.
Hematol Oncol ; 42(3): e3281, 2024 May.
Article in English | MEDLINE | ID: mdl-38775115

ABSTRACT

The FLT3-ITD mutation represents the most frequent genetic alteration in newly diagnosed acute myeloid leukemia (AML) patient and is associated with poor prognosis. Mutation result in the retention of a constitutively active form of this receptor in the endoplasmic reticulum (ER) and the subsequent modification of its downstream effectors. Here, we assessed the impact of such retention on ER homeostasis and found that mutant cells present lower levels of ER stress due to the overexpression of ERO1α, one of the main proteins of the protein folding machinery at the ER. Overexpression of ERO1α resulted essential for ITD mutant cells survival and chemoresistance and also played a crucial role in shaping the type of glucose metabolism in AML cells, being the mitochondrial pathway the predominant one in those with a higher ER stress (non-mutated cells) and the glycolytic pathway the predominant one in those with lower ER stress (mutated cells). Our data indicate that FLT3 mutational status dictates the route for glucose metabolism in an ERO1α depending on manner and this provides a survival advantage to tumors carrying these ITD mutations.


Subject(s)
Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Leukemia, Myeloid, Acute , fms-Like Tyrosine Kinase 3 , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/metabolism , Endoplasmic Reticulum/metabolism , Mutation , Cell Line, Tumor , Membrane Glycoproteins , Oxidoreductases
2.
Int J Mol Sci ; 24(20)2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37894844

ABSTRACT

Huntington's disease (HD) is an inherited neurodegenerative disorder considered a rare disease with a prevalence of 5.7 per 100,000 people. It is caused by an autosomal dominant mutation consisting of expansions of trinucleotide repeats that translate into poly-glutamine enlarged mutant huntingtin proteins (mHTT), which are particularly deleterious in brain tissues. Since there is no cure for this progressive fatal disease, searches for new therapeutic approaches are much needed. The small molecule pytren-4QMn (4QMn), a highly water-soluble mimic of the enzyme superoxide dismutase, has shown in vivo beneficial anti-inflammatory activity in mice and was able to remove mHTT deposits in a C. elegans model of HD. In this study, we assessed 4QMn therapeutic potential in zQ175 neo-deleted knock-in mice, a model of HD that closely mimics the heterozygosity, genetic injury, and progressive nature of the human disease. We provide evidence that 4QMn has good acute and chronic tolerability, and can cross the blood-brain barrier, and in male, but not female, zQ175 mice moderately ameliorate HD-altered gene expression, mHtt aggregation, and HD disease phenotype. Our data highlight the importance of considering sex-specific differences when testing new therapies using animal models and postulate 4QMn as a potential novel type of small water-soluble metal complex that could be worth further investigating for its therapeutic potential in HD, as well as in other polyglutamine diseases.


Subject(s)
Huntington Disease , Female , Mice , Humans , Male , Animals , Mice, Transgenic , Huntington Disease/drug therapy , Huntington Disease/genetics , Huntington Disease/metabolism , Caenorhabditis elegans , Disease Models, Animal , Water , Huntingtin Protein/genetics
3.
Int J Food Sci Nutr ; 74(6): 707-718, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37604816

ABSTRACT

The objective was to analyse the associations between anthropometric characteristics and diet in male rugby players according to the playing position. A cross-sectional study was developed. The forwards had higher body weight (107 kg) and fat mass (FM; 12%) than the backs (87.8 kg and 8.47%, respectively) (p < 0.05). The quality of diet needs to improve (KIDMED value of 5.87 and 6.36 for forwards and backs, respectively). Nutritional imbalances, such as deficits in carbohydrates, fibre, calcium, magnesium and vitamin D, and excess of fats, saturated fatty acid, cholesterol and sugars were found. Carbohydrates and proteins intake were significant associated (p < 0.05) with a minor FM. Forwards with a KIDMED index of less than 8 had a significantly higher FM than those who maintained an optimal diet (p < 0.05). The diet of rugby players should be more in line with dietary recommendations and take into account the player position to optimise sports performance.


Subject(s)
Calcium, Dietary , Rugby , Male , Humans , Cross-Sectional Studies , Anthropometry , Vitamin D
4.
Chemistry ; 29(40): e202301078, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37103792

ABSTRACT

Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted C-H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for non-cancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.


Subject(s)
Antineoplastic Agents , Platinum , Humans , Platinum/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Ligands , Bromides , HEK293 Cells , Guanosine , Cell Line, Tumor , Drug Screening Assays, Antitumor
5.
Front Psychol ; 13: 909928, 2022.
Article in English | MEDLINE | ID: mdl-36571012

ABSTRACT

Introduction: The spillover effect is the psychological overflow due to daily stress in one context and the transfer of its consequences to another close environment. The aim is to explore the spillover effect in conflicts within the family, on the one hand, and school with peers on the other hand, as an inferred measure of daily stress according to the literature. Method: The study consisted of a sample of 208 6-year-old students and their families. A methodology based on daily report records was used, by means of two ad hoc checklists with simultaneous measurements, for 2 consecutive weeks and 3 academic years, for both family and school contexts. A repeated measures design, together with a nonparametric statistical data analysis with Friedman's test and contrast measures, was used. Results: Daily stress shows significant differences in the family setting throughout the week (χ 2 = 32.44; p = 0.000) and at different times of the day (χ 2 = 29.65; p = 0.000). In the school setting, differences were found across the different days of the week (χ 2 = 36.96; p = 0.000). Spillover effect has been discovered between conflicts at home in the evening and conflicts at school. At the same time, conflicts at school are related to conflicts at home from Wednesday onward. Discussion: The results suggest further research on daily stress through the interrelation of the different contexts, as well as the impact that moments of conflict may have on the psychological and emotional development of the child.

6.
Int J Environ Res ; 16(5): 94, 2022.
Article in English | MEDLINE | ID: mdl-36187465

ABSTRACT

The COVID-19 health crisis has wreaked devastation on the world economy, especially on the tourism sector. The camping sector has been little studied despite its high economic impact and participation rate. Moreover, the observable effects of phenomena such as the COVID-19 pandemic have received little research attention. Consequently, the objective of this paper is therefore to analyse the effects of the pandemic on camping tourism by characterising the factors that determine it. The study is carried out by providing a geographical perspective of the sector by tourist areas, whereby two types of tourist destinations are considered: campsites located in coastal areas, and campsites located in natural areas. This is the main contribution of the work, as the proposed geographical analysis studies smaller territorial units than those usually used in tourism research. For the study, Multivariate Analysis techniques are applied, specifically Factor Analysis and Cluster Analysis. The results show that there is a balance between supply and demand in the sector, with a significant economic impact, especially on employment and the performance of the sector. The impact of the COVID-19 pandemic has led to nature tourism gaining greater popularity, and shows an evolution in travellers' preferences for tourist destinations in favour of campsites located in natural areas over those located in coastal destinations. The geographical location of the tourist destination, therefore, plays a key role in the characterisation of Spanish campsites. This has practical implications for both camping companies and institutions, as the fact that some areas are more attractive than others is a decisive factor in deciding on the location of new campsites.

7.
Int J Mol Sci ; 23(16)2022 Aug 11.
Article in English | MEDLINE | ID: mdl-36012207

ABSTRACT

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD.


Subject(s)
Huntington Disease , Quinolines , Animals , Disease Models, Animal , Humans , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntington Disease/drug therapy , Huntington Disease/metabolism , Manganese , Models, Theoretical , Proteasome Endopeptidase Complex/metabolism , Proteostasis , Quinolines/therapeutic use
8.
Cell Oncol (Dordr) ; 45(3): 415-428, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35499815

ABSTRACT

PURPOSE: Chondrosarcoma and osteosarcoma are the most frequently occurring bone cancers. Although surgery and chemotherapy are currently clinically applied, improved treatment options are urgently needed. Melatonin is known to inhibit cell proliferation in both tumor types. Although the underlying mechanisms are not clear yet, calcium homeostasis has been reported to be a key factor in cancer biology. Here, we set out to investigate whether regulation of calcium by this indolamine may be involved in its antitumor effect. METHODS: Cell viability was measured using a MTT assay and flow cytometry was used to measure levels of cytosolic calcium, intracellular oxidants, mitochondrial membrane potential and cell cycle progression. Mitochondrial calcium was analyzed by fluorimetry. Cell migration was determined using a scratch wound-healing assay. Western blot analysis was used to assess the expression of proteins related to cell cycle progression, epithelial to mesenchymal transition (EMT), Ac-CoA synthesis and intracellular signaling pathways. RESULTS: We found that melatonin decreases cytosolic and mitochondrial Ca2+ levels, intracellular oxidant levels, mitochondrial function and the expression of the E1 subunit of the pyruvate dehydrogenase complex. These changes were found to be accompanied by decreases in cell proliferation, cell migration and EMT marker expression. The addition of CaCl2 prevented the changes mentioned above, while co-treatment with the calcium chelator BAPTA enhanced the effects. CONCLUSIONS: Our data indicate that regulation of calcium homeostasis is a key factor in the inhibition of cell proliferation and migration by melatonin. This effect should be taken into consideration in combined therapies with traditional or new antitumor compounds, since it may circumvent therapy resistance.


Subject(s)
Bone Neoplasms , Melatonin , Osteosarcoma , Soft Tissue Neoplasms , Bone Neoplasms/pathology , Calcium/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Humans , Melatonin/pharmacology , Melatonin/therapeutic use , Osteosarcoma/pathology
9.
Chem Commun (Camb) ; 58(32): 5021-5024, 2022 Apr 19.
Article in English | MEDLINE | ID: mdl-35373809

ABSTRACT

A novel amino-nanozyme, based on boehmite nanoparticles (BNPs) functionalised with a tetra-azapyridinophane (L1), has been designed to undermine some of the key issues underlying Huntington disease. L1 forms Cu2+ complexes with a striking SOD activity, while when grafted to the BNPs displays mitoROS scavenging properties and ability to disaggregate mutant huntingtin deposits in cells.


Subject(s)
Antioxidants , Huntington Disease , Aluminum Hydroxide , Aluminum Oxide , Antioxidants/pharmacology , Humans , Inclusion Bodies
10.
Int J Mol Sci ; 22(19)2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34638956

ABSTRACT

NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis. However, how NANOG regulates tumor progression is still not known. We previously showed in medaka fish that Nanog regulates primordial germ cell migration through Cxcr4b, a chemokine receptor known for its ability to promote migration and metastasis in human cancers. Therefore, we investigated the role of human NANOG in CXCR4-mediated cancer cell migration. Of note, we found that NANOG regulatory elements in the CXCR4 promoter are functionally conserved in medaka fish and humans, suggesting an evolutionary conserved regulatory axis. Moreover, CXCR4 expression requires NANOG in human glioblastoma cells. In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.


Subject(s)
Brain Neoplasms/metabolism , Cell Movement/genetics , Chemokine CXCL12/metabolism , Glioblastoma/metabolism , Nanog Homeobox Protein/metabolism , Receptors, CXCR4/metabolism , Signal Transduction/genetics , Animals , Brain Neoplasms/pathology , Cell Line, Tumor , Gene Knockdown Techniques , Glioblastoma/pathology , HEK293 Cells , Humans , Nanog Homeobox Protein/genetics , Oryzias/embryology , Promoter Regions, Genetic , Transfection
11.
J Cell Physiol ; 236(1): 27-40, 2021 01.
Article in English | MEDLINE | ID: mdl-32725819

ABSTRACT

Several oncogenic pathways plus local microenvironmental conditions, such as hypoxia, converge on the regulation of cancer cells metabolism. The major metabolic alteration consists of a shift from oxidative phosphorylation as the major glucose consumer to aerobic glycolysis, although most of cancer cells utilize both pathways to a greater or lesser extent. Aerobic glycolysis, together with the directly related metabolic pathways such as the tricarboxylic acid cycle, the pentose phosphate pathway, or gluconeogenesis are currently considered as therapeutic targets in cancer research. Melatonin has been reported to present numerous antitumor effects, which result in a reduced cell growth. This is achieved with both low and high concentrations with no relevant side effects. Indeed, high concentrations of this indolamine reduce proliferation of cancer types resistant to low concentrations and induce cell death in some types of tumors. Previous work suggest that regulation of glucose metabolism and other related pathways play an important role in the antitumoral effects of high concentration of melatonin. In the present review, we analyze recent work on the regulation by such concentrations of this indolamine on aerobic glycolysis, gluconeogenesis, the tricarboxylic acid cycle and the pentose phosphate pathways of cancer cells.


Subject(s)
Glucose/metabolism , Melatonin/administration & dosage , Neoplasms/metabolism , Animals , Carcinogenesis/drug effects , Carcinogenesis/metabolism , Cell Proliferation/drug effects , Gluconeogenesis/drug effects , Glycolysis/drug effects , Humans
12.
Int J Mol Sci ; 21(16)2020 Aug 11.
Article in English | MEDLINE | ID: mdl-32796742

ABSTRACT

Continuous overexposure to sunlight increases its harmful effects on the skin. For this reason, there is a growing need to characterize economic models more representative of the negative effects and counteracting responses that irradiation causes on human skin. These models will serve for the screening of protective compounds against damage caused by ultraviolet (UV) and high energy visible light (HEV). Therefore, two common in vitro models employed for sunlight irradiation studies, namely human keratinocyte HaCat culture and reconstructed human epidermis (RHE), were compared with the medaka fish embryo model, traditionally used in other scientific disciplines. Using suberythemal doses of UVA and HEV to determine the level of Reactive Oxygen Species (ROS) generation and thymine dimers formed by UVB, we show that medaka embryo responds with a lower damage level, more comparable to human skin, than the other two models, probably due to the protective mechanisms that work in a complete organism. In the same way, the protective effects of antioxidant compounds have the greatest effect on medaka embryos. Taken together, these findings suggest that medaka embryos would be a good alternative in vitro model for sunlight effect studies, and for the screening of molecules with counteracting capacity against the damage caused by UV and HEV.


Subject(s)
DNA Damage , Drug Evaluation, Preclinical , Embryo, Nonmammalian/radiation effects , Models, Biological , Oryzias/embryology , Ultraviolet Rays , Animals , Antioxidants/pharmacology , Epidermis/radiation effects , HaCaT Cells , Humans , Reactive Oxygen Species/metabolism
13.
Oncol Rep ; 44(1): 293-302, 2020 07.
Article in English | MEDLINE | ID: mdl-32319665

ABSTRACT

The FMS­like tyrosine kinase 3 internal tandem duplication (FLT3­ITD) mutation represents the most frequent genetic alteration in acute myeloid leukemia (AML) and is associated with poor prognosis. The mutation promotes cancer cell survival and proliferation, and shifts their glucose metabolism towards aerobic glycolysis, a frequent alteration in cancer. In the present study, the impact of melatonin on the viability of AML cell lines with (MV­4­11 and MOLM­13) or without the FLT3­ITD mutation (OCI­AML3 and U­937) was evaluated. Melatonin induces cell death in AML cells carrying the FLT3­ITD mutation, but only inhibits the proliferation of AML cells without this mutation. Consistently, melatonin decreases tumor growth and increases animal survival in a xenograft model of FLT3­ITD AML. Toxicity is related to a decrease in glucose uptake, lactate dehydrogenase activity, lactate production and hypoxia­inducible factor­1α activation. Melatonin also regulates the expression of glucose metabolism­related genes, impairing the balance between anaplerosis and cataplerosis, through the upregulation of the expression of phosphoenolpyruvate carboxykinase 2 (PCK2). Collectively, the present findings highlight the regulation of glucose metabolism, currently considered a possible therapeutic target in cancer, as a key event in melatonin­induced cytotoxicity, suggesting its potential as a therapeutic tool for the treatment of patients with AML, particularly those carrying the FLT3­ITD mutation that results in low basal expression levels of PCK2.


Subject(s)
Glucose/metabolism , Leukemia, Myeloid, Acute/drug therapy , Melatonin/administration & dosage , Mutation , fms-Like Tyrosine Kinase 3/genetics , Animals , Cell Line, Tumor , Cell Survival/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , L-Lactate Dehydrogenase/metabolism , Lactic Acid/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Melatonin/pharmacology , Mice , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Xenograft Model Antitumor Assays
14.
Chem Mater ; 31(17): 7080-7084, 2019 Sep 10.
Article in English | MEDLINE | ID: mdl-32063677

ABSTRACT

Local drug delivery directly to the source of a given pathology using retrodialysis is a promising approach to treating otherwise untreatable diseases. As the primary material component in retrodialysis, the semipermeable membrane represents a critical point for innovation. This work presents a new ionic hydrogel based on polyethylene glycol and acrylate with dopamine counterions. The ionic hydrogel membrane is shown to be a promising material for controlled diffusive delivery of dopamine. The ionic nature of the membrane accelerates uptake of cationic species compared to a nonionic membrane of otherwise similar composition. It is demonstrated that the increased uptake of cations can be exploited to confer an accelerated transport of cationic species between reservoirs as is desired in retrodialysis applications. This effect is shown to enable nearly 10-fold increases in drug delivery rates from low concentration solutions. The processability of the membrane is found to allow for integration with microfabricated devices which will in turn accelerate adaptation into both existing and emerging device modalities. It is anticipated that a similar materials design approach may be broadly applied to a variety of cationic and anionic compounds for drug delivery applications ranging from neurological disorders to cancer.

15.
ACS Omega ; 3(7): 7424-7431, 2018 Jul 31.
Article in English | MEDLINE | ID: mdl-30087913

ABSTRACT

Conducting polymer scaffolds can promote cell growth by electrical stimulation, which is advantageous for some specific type of cells such as neurons, muscle, or cardiac cells. As an additional feature, the measure of their impedance has been demonstrated as a tool to monitor cell growth within the scaffold. In this work, we present innovative conducting polymer porous scaffolds based on poly(3,4-ethylenedioxythiophene) (PEDOT):xanthan gum instead of the well-known PEDOT:polystyrene sulfonate scaffolds. These novel scaffolds combine the conductivity of PEDOT and the mechanical support and biocompatibility provided by a polysaccharide, xanthan gum. For this purpose, first, the oxidative chemical polymerization of 3,4-ethylenedioxythiophene was carried out in the presence of polysaccharides leading to stable PEDOT:xanthan gum aqueous dispersions. Then, by a simple freeze-drying process, porous scaffolds were prepared from these dispersions. Our results indicated that the porosity of the scaffolds and mechanical properties are tuned by the solid content and formulation of the initial PEDOT:polysaccharide dispersion. Scaffolds showed interconnected pore structure with tunable sizes ranging between 10 and 150 µm and Young's moduli between 10 and 45 kPa. These scaffolds successfully support three-dimensional cell cultures of MDCK II eGFP and MDCK II LifeAct epithelial cells, achieving good cell attachment with very high degree of pore coverage. Interestingly, by measuring the impedance of the synthesized PEDOT scaffolds, the growth of the cells could be monitored.

16.
Mol Cancer Ther ; 17(3): 614-624, 2018 03.
Article in English | MEDLINE | ID: mdl-29339551

ABSTRACT

Internal tandem duplication (ITD) or tyrosine kinase domain mutations of FLT3 is the most frequent genetic alteration in acute myelogenous leukemia (AML) and are associated with poor disease outcome. Despite considerable efforts to develop single-target FLT3 drugs, so far, the most promising clinical response has been achieved using the multikinase inhibitor midostaurin. Here, we explore the activity of the indolocarbazole EC-70124, from the same chemical space as midostaurin, in preclinical models of AML, focusing on those bearing FLT3-ITD mutations. EC-70124 potently inhibits wild-type and mutant FLT3, and also other important kinases such as PIM kinases. EC-70124 inhibits proliferation of AML cell lines, inducing cell-cycle arrest and apoptosis. EC-70124 is orally bioavailable and displays higher metabolic stability and lower human protein plasma binding compared with midostaurin. Both in vitro and in vivo pharmacodynamic analyses demonstrate inhibition of FLT3-STAT5, Akt-mTOR-S6, and PIM-BAD pathways. Oral administration of EC-70124 in FLT3-ITD xenograft models demonstrates high efficacy, reaching complete tumor regression. Ex vivo, EC-70124 impaired cell viability in leukemic blasts, especially from FLT3-ITD patients. Our results demonstrate the ability of EC-70124 to reduce proliferation and induce cell death in AML cell lines, patient-derived leukemic blast and xenograft animal models, reaching best results in FLT3 mutants that carry other molecular pathways' alterations. Thus, its unique inhibition profile warrants EC-70124 as a promising agent for AML treatment based on its ability to interfere the complex oncogenic events activated in AML at several levels. Mol Cancer Ther; 17(3); 614-24. ©2018 AACR.


Subject(s)
Carbazoles/pharmacology , Indoles/pharmacology , Leukemia, Myeloid/drug therapy , Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors , Xenograft Model Antitumor Assays , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Acute Disease , Animals , Biological Availability , Caco-2 Cells , Carbazoles/pharmacokinetics , Carbazoles/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Female , Gene Expression Regulation, Leukemic/drug effects , HL-60 Cells , Humans , Indoles/pharmacokinetics , Indoles/therapeutic use , Leukemia, Myeloid/genetics , Leukemia, Myeloid/metabolism , Mice, SCID , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-pim-1/genetics , Proto-Oncogene Proteins c-pim-1/metabolism , THP-1 Cells , fms-Like Tyrosine Kinase 3/metabolism
17.
ACS Biomater Sci Eng ; 4(6): 2100-2105, 2018 Jun 11.
Article in English | MEDLINE | ID: mdl-33435033

ABSTRACT

Alginate hydrogels are biocompatible, biodegradable, low-cost, and widely used as bioinks, cell encapsulates, three-dimensional culture matrices, drug delivery systems, and scaffolds for tissue engineering. Nevertheless, their limited stiffness hinders their use for certain biomedical applications. Many research groups have tried to address this problem by reinforcing alginate hydrogels with graphene, carbon nanotubes, or silver nanoparticles. However, these materials present nanotoxicity issues, limiting their use for biomedical applications. Other studies show that electrospinning or wet spinning can be used to fabricate biocompatible, micro- and nanofibers to reinforce hydrogels. As a relatively simple and cheap alternative, in this study we used bioengineered bacteria to fabricate amyloid curli fibers to enhance the stiffness of alginate hydrogels. We have fabricated for the first time bioengineered amyloid curli fibers-hydrogel composites and characterized them by a combination of (i) atomic force microscopy (AFM) to measure the Young's modulus of the bioengineered amyloid curli fibers and study their topography, (ii) nanoindentation to measure the Young's modulus of the amyloid curli fibers-alginate nanocomposite hydrogels, and (iii) Fourier-transform infrared spectroscopy (FTIR) to analyze their composition. The fabricated nanocomposites resulted in a highly improved Young's modulus (up to 4-fold) and showed very similar physical and chemical properties, opening the window for their use in applications where the properties alginate hydrogels are convenient but do not match the stiffness needed.

18.
Polymers (Basel) ; 10(9)2018 Sep 05.
Article in English | MEDLINE | ID: mdl-30960914

ABSTRACT

In recent years, gels based on ionic liquids incorporated into polymer matrices, namely iongels, have emerged as long-term contact media for cutaneous electrophysiology. Iongels possess high ionic conductivity and negligible vapor pressure and can be designed on demand. In spite of the extensive efforts devoted to the preparation of biodegradable ionic liquids, the investigations related to the preparation of iongels based on biodegradable polymers remain scarce. In this work, biodegradable polycarbonate-based iongels are prepared by ring-opening polymerization of N-substituted eight ring membered cyclic carbonate monomers in the presence of imidazolium lactate ionic liquid. Our iongels are able to take up 10⁻30 wt % of ionic liquid and become softer materials by increasing the amount of free ionic liquid. Rheological measurements showed that the cross-over point between the storage modulus G' and loss modulus G″ occurs at lower angular frequencies when the loading of free ionic liquid increases. These gels are able to take up to 30 wt % of the ionic liquid and the ionic conductivity of these gels increased up to 5 × 10-4 S·cm-1 at 25 °C as the amount of free ionic liquid increased. Additionally, we assess the biodegradation studies of the iongels by immersing them in water. The iongels decrease the impedance with the human skin to levels that are similar to commercial Ag/AgCl electrodes, allowing an accurate physiologic signals recording. The low toxicity and biodegradability of polycarbonate-based iongels make these materials highly attractive for cutaneous electrophysiology applications.

19.
Rejuvenation Res ; 21(4): 323-332, 2018 Aug.
Article in English | MEDLINE | ID: mdl-28982278

ABSTRACT

Oxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of the cocoa extract increased fish life span. Our study demonstrates that the polyphenol-enriched cocoa extract decreases OS and extends life span in medaka fish, validating the use of medaka embryos as an economical platform to screen the antioxidant capacity of food compounds.


Subject(s)
Cacao/chemistry , Longevity/physiology , Oryzias/physiology , Oxidative Stress/drug effects , Polyphenols/pharmacology , Animals , Dietary Supplements , Embryo, Nonmammalian/drug effects , Flavonoids/pharmacology , Gene Expression Regulation, Developmental/drug effects , Hydrogen Peroxide/toxicity , Longevity/drug effects , Oryzias/embryology , Oryzias/genetics , Plant Extracts/pharmacology , Superoxide Dismutase/metabolism , Vitamin K 3/toxicity
20.
Saúde Soc ; 26(3): 798-810, Jul.-Set. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-903876

ABSTRACT

Resumen El sector de Residuos Sólidos Urbanos tiene amplia trayectoria en la implementación de planes de prevención en riesgos laborales. Analizamos dos aspectos: cuáles son los factores de riesgos laborales a los que se encuentran expuestos los empleados y que pueden afectar fundamentalmente a su salud dentro del sector analizado; y diferencias en la prevención de riesgos laborales por las empresas del sector que presentaron enfermedades profesionales en función del género de los trabajadores. El procedimiento metodológico consistió en el análisis descriptivo transversal en ocho provincias de Andalucía (España). Como herramienta de estudio se ha utilizado el cuestionario de 75 preguntas para la elaboración del informe sobre "condiciones de trabajo y gestión preventiva en las empresas de gestión de residuos sólidos urbanos en Andalucía" realizado por el Instituto Andaluz de Prevención de Riesgos Laborales. Como técnica estadística se ha usado el análisis de correspondencias múltiple y el test Chi-Cuadrado de independencia. En los resultados se han encontrado dos percepciones bien diferenciadas sobre los riesgos laborales en las organizaciones que vienen fijadas por la jerarquía en la organización. Se puede establecer relación directa entre los puestos de mando de la empresa y la preocupación por los riesgos laborales. A mayor distancia a puestos de dirección mayor es la preocupación de los empleados respecto a los riesgos laborales a los que están expuestos. En cuanto a los riesgos psicosociales se identifica que las mujeres se ven más afectadas que los hombres.


Abstract The Urban Solid Waste sector has a great trajectory in the implementation of preventive plans in workplace risks. We analyzed two aspects: which are the factors of workplace risks to what the employees are exposed and can essentially affect their health inside of the analyzed sector; and the differences in preventive management performed in companies that had informed their workers about occupational diseases, and analyzed these differences according to workers' gender. The method used was cross-sectional analysis in eight provinces of Andalusia (Spain). As research tool, a 75-question questionnaire was used to prepare the report on "Working conditions and safety management in enterprises specialized in management of urban solid wastes in Andalusia" by the Andalusian Institute of Occupational Health and Safety. As statistical technique, it has been used multiple correspondence analysis and the Chi-Squared test of independence. In the results there are two different perceptions of workplace risks in organizations that are fixed by the hierarchy in the company. It is possible to establish a direct relationship between the Team Management of the company and the concerning about workplace risks. The greater the distance between leadership's positions, the greater concern of employees exposed to the workplace risks. Regarding psychosocial risks, we concluded that women are more affected than men.


Subject(s)
Humans , Male , Female , Risk Management , Occupational Risks , Solid Waste , Solid Waste Collection , Occupational Health , Working Conditions , Urban Area , Occupational Diseases
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