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The present study aims to analyze the interaction between Rhodotorula toruloides and magnetic nanoparticles and evaluate their effect on carotenoid production. The manganese ferrite nanoparticles were synthesized without chitosan (MnFe2O4) and chitosan coating (MnFe2O4-CS) by the co-precipitation method assisted by hydrothermal treatment. XRD (X-ray diffraction), Magnetometry, Dynamic Light Scattering (DLS) and FTIR (Fourier-Transform Infrared Spectroscopy), are used to characterize the magnetic nanoparticles. The crystallite size of MnFe2O4 was 16 nm for MnFe2O4 and 20 nm for MnFe2O4-CS. The magnetic saturation of MnFe2O4-CS was lower (39.6 ± 0.6 emu/g) than the same MnFe2O4 nanoparticles (42.7 ± 0.3 emu/g), which was attributed to the chitosan fraction presence. The MnFe2O4-CS FTIR spectra revealed the presence of the characteristic chitosan bands. DLS demonstrated that the average hydrodynamic diameters were 344 nm for MnFe2O4 and 167 nm for MnFe2O4-CS. A kinetic study of cell immobilization performed with their precipitation with a magnet demonstrated that interaction between magnetic nanoparticles and R. toruloides was characterized by an equilibrium time of 2 h. The adsorption isotherm models (Langmuir and Freundlich) were fitted to the experimental values. The trypan blue assay was used for cell viability assessment. The carotenoid production increased to 256.2 ± 6.1 µg/g dry mass at 2.0 mg/mL MnFe2O4-CS. The use of MnFe2O4-CS to stimulate carotenoid yeast production and the magnetic separation of biomass are promising nanobiotechnological alternatives. Magnetic cell immobilization is a perspective technique for obtaining cell metabolites.
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A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically "mutated" CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When co-administered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a "designer" cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., "inflammo-attraction").
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Quimiocina CXCL12/genética , Neuronas/metabolismo , Unión Proteica/genética , Receptores CXCR4/genética , Astrocitos/metabolismo , Astrocitos/patología , Movimiento Celular/genética , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Humanos , Células Madre Pluripotentes Inducidas , Inflamación/genética , Ligandos , Mutagénesis/genética , Células-Madre Neurales/metabolismo , Células-Madre Neurales/trasplante , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/terapia , Neuronas/patologíaRESUMEN
In the present study, Trichoderma reesei cellulase was covalently immobilized on chitosan-coated magnetic nanoparticles using glutaraldehyde as a coupling agent. The average diameter of magnetic nanoparticles before and after enzyme immobilization was about 8 and 10 nm, respectively. The immobilized enzyme retained about 37 % of its initial activity, and also showed better thermal and storage stability than free enzyme. Immobilized cellulase retained about 80 % of its activity after 15 cycles of carboxymethylcellulose hydrolysis and was easily separated with the application of an external magnetic field. However, in this reaction, K m was increased eight times. The immobilized enzyme was able to hydrolyze lignocellulosic material from Agave atrovirens leaves with yield close to the amount detected with free enzyme and it was re-used in vegetal material conversion up to four cycles with 50 % of activity decrease. This provides an opportunity to reduce the enzyme consumption during lignocellulosic material saccharification for bioethanol production.
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Agave/química , Biomasa , Celulasas/química , Quitosano/química , Proteínas Fúngicas/química , Lignina/química , Nanopartículas de Magnetita/química , Trichoderma/enzimología , Enzimas Inmovilizadas/química , HidrólisisRESUMEN
In the present study, the interactions between chitosan-coated magnetic nanoparticles (C-MNP) and Trichoderma sp. spores as well as Kluyveromyces marxianus cells were studied. By Plackett-Burman design, it was demonstrated that factors which directly influenced on yeast cell immobilization and magnetic separation were inoculum and C-MNP quantity, stirring speed, interaction time, and volume of medium, while in the case of fungal spores, the temperature also was disclosed as an influencing factor. Langmuir and Freundlich models were applied for the mathematical analysis of adsorption isotherms at 30°C. For Trichoderma sp. spore adsorption isotherm, the highest correlation coefficient was observed for lineal function of Langmuir model with a maximum adsorption capacity at 5.00E + 09 spores (C-MNP g-1). Adsorption isotherm of K. marxianus cells was better adjusted to Freundlich model with a constant (Kf) estimated as 2.05E + 08 cells (C-MNP g-1). Both systems may have a novel application in fermentation processes assisted with magnetic separation of biomass.
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Quitosano/química , Kluyveromyces/citología , Nanopartículas de Magnetita/química , Esporas Fúngicas/aislamiento & purificación , Trichoderma/citología , Adsorción , Separación CelularRESUMEN
Intracranial transplantation of neural stem cells (NSCs) delayed disease onset, preserved motor function, reduced pathology and prolonged survival in a mouse model of Sandhoff disease, a lethal gangliosidosis. Although donor-derived neurons were electrophysiologically active within chimeric regions, the small degree of neuronal replacement alone could not account for the improvement. NSCs also increased brain beta-hexosaminidase levels, reduced ganglioside storage and diminished activated microgliosis. Additionally, when oral glycosphingolipid biosynthesis inhibitors (beta-hexosaminidase substrate inhibitors) were combined with NSC transplantation, substantial synergy resulted. Efficacy extended to human NSCs, both to those isolated directly from the central nervous system (CNS) and to those derived secondarily from embryonic stem cells. Appreciating that NSCs exhibit a broad repertoire of potentially therapeutic actions, of which neuronal replacement is but one, may help in formulating rational multimodal strategies for the treatment of neurodegenerative diseases.
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Encéfalo/citología , Células Madre Embrionarias/citología , Neuronas/citología , Enfermedad de Sandhoff/terapia , Trasplante de Células Madre , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/farmacología , Animales , Humanos , Inmunohistoquímica , Ratones , Ratones Noqueados , Microglía/metabolismo , Técnicas de Placa-Clamp , Enfermedad de Sandhoff/tratamiento farmacológico , beta-N-Acetilhexosaminidasas/antagonistas & inhibidores , beta-N-Acetilhexosaminidasas/genética , beta-N-Acetilhexosaminidasas/metabolismoRESUMEN
Ethical considerations regarding our treatment of animals have gained strength, leading to legislation and a societal focus across various disciplines. This is a subject of study within curricula related to agri-food sciences. The aim was to determine the perceptions of agronomy university students concerning animal welfare in livestock production systems. A survey was conducted to encompass various aspects, from participants' sociodemographic attributes to their attitudes and behaviors regarding animal welfare and the consumption of animal products. Statistical analysis, performed using R software, delved into the associations between participants' characteristics and their perspectives on the ethical, bioethical, and legal dimensions of animal welfare. Associations between demographic factors and ethical viewpoints among students were identified. Gender differences emerged in animal treatment perceptions, while rural and urban environments impacted perspectives on various animals. Bioethical considerations revealed distinctive disparities based on gender and education in concerns regarding animal welfare, value perceptions, evaluations of animal behaviors, and opinions on animal research. It is crucial to distinguish between animal welfare and the ethical considerations arising from coexisting with sentient beings capable of experiencing suffering. Ethical theories provide a lens through which we perceive our obligations toward animals. The responsibility to ensure animal welfare is firmly rooted in recognizing that animals, like humans, experience pain and physical suffering. Consequently, actions causing unjustified suffering or mistreatment, particularly for entertainment purposes, are considered morally unacceptable.
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The present study aims to obtain manganese ferrite nanoparticles functionalized with chitosan (C-MNP) or ethylenediamine (E-MNP) by coprecipitation and polyol one-step methods, characterize their interaction with S. griseus demonstrating cell immobilization, and evaluate the antimicrobial activity of the free cell extracts obtained from immobilized S. griseus fermentation in the presence of different concentrations of MNP. The adsorption isotherms were analyzed mathematically using Langmuir and Freundlich models. The highest coefficient of determination (R2) for the S. griseus cell adsorption isotherm with C-MNP was observed with a linear function of the Langmuir model. The adsorption isotherm of S. griseus cells with E-MNP was better fitted to the Freundlich model. Cell immobilization by adsorption on magnetic nanoparticles was demonstrated in both cases. Different concentrations of C-MNP and E-MNP were used in fermentations to prepare cell-free extracts with antifungal activity. The best results were obtained with E-MNP, with a 91.5% inhibition of radial fungal growth. Magnetic nanoparticles offer potential applications in different fields and easy biomass separation.
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Approximately 3,500 mammalian genes are predicted to be secreted or single-pass transmembrane proteins. The function of the majority of these genes is still unknown, and a number of the encoded proteins might find use as new therapeutic agents themselves or as targets for small molecule or antibody drug development. To analyze the physiological activities of the extracellular proteome, we developed a large-scale, high-throughput protein expression, purification, and screening platform. For this study, the complete human extracellular proteome was analyzed and prioritized based on genome-wide disease association studies to select 529 initial target genes. These genes were cloned into three expression vectors as native sequences and as N-terminal and C-terminal Fc fusions to create an initial collection of 806 purified secreted proteins. To determine its utility, this library was screened in an OCT4-based cellular assay to identify regulators of human embryonic stem-cell self-renewal. We found that the pigment epithelium-derived factor can promote long-term pluripotent growth of human embryonic stem cells without bFGF or TGFbeta/Activin/Nodal ligand supplementation. Our results further indicate that activation of the pigment epithelium-derived factor receptor-Erk1/2 signaling pathway by the pigment epithelium-derived factor is sufficient to maintain the self-renewal of pluripotent human embryonic stem cells. These experiments illustrate the potential for discovering novel biological functions by directly screening protein diversity in cell-based phenotypic or reporter assays.
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Células Madre Embrionarias/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Células Madre Pluripotentes/metabolismo , Proteoma/metabolismo , Células Madre Embrionarias/citología , Células Madre Embrionarias/efectos de los fármacos , Estudio de Asociación del Genoma Completo , Ensayos Analíticos de Alto Rendimiento , Humanos , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/efectos de los fármacos , Proteoma/genética , Receptores de Neuropéptido/genética , Receptores de Neuropéptido/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND Endometriosis is a unique entity described in ample literature as the decidualization of endometrial tissues under the influence of gynecological hormones outside the uterine cavity. The post-surgical presence of ectopic endometrial tissue on the skin is known as abdominal wall endometriosis, cutaneous endometriosis, or scar endometriosis. Iatrogenic implantation of detached endometrial tissues at the incision site is the most widely accepted theory for this rare monad. The unspecific scar endometriosis presentation makes it challenging to diagnose. Moreover, it can easily be confused with hematoma, hernia, lipoma, abscess, scar granuloma, and tumor. Here, we report and discuss a rare case of scar endometriosis with various available treatment modalities. CASE REPORT We delineate a case of a 39-year-old woman with abdominal wall cutaneous endometriosis. An "inverted T" incision opened the abdominal and uterine cavity as it was a problematic preterm breech in labor. After an uneventful postoperative and postpartum period, she presented with a painful, discolored nodular mass of approximately 3 cm in diameter at the left border of the cesarian scar, developed over 1.5 years, often accompanied by drainage of brownish discharge. Ultrasonography with color Doppler showed a hypoechoic lesion with internal vascularity, corroborated our preliminary diagnosis of scar endometriosis, which was further confirmed by surgical excision and histopathology. CONCLUSIONS A proper surgical resection is the standard treatment line for scar endometriosis. However, patients need regular follow-up to look for recurrences, even after treatment. Further studies are recommended to establish factors associated with cutaneous endometriosis recurrence.
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Pared Abdominal , Endometriosis , Pared Abdominal/patología , Pared Abdominal/cirugía , Adulto , Cesárea , Cicatriz , Endometriosis/diagnóstico , Endometriosis/cirugía , Femenino , Humanos , Recién Nacido , Recurrencia Local de Neoplasia/patología , EmbarazoRESUMEN
In this work, polyphenols from Moringa oleifera (Mor) leaves were extracted by microwave-assisted extraction (MAE) and encapsulated by spray-drying (SD). Particularly, we explored the influence of tragacanth gum (TG), locust bean gum (LBG), and carboxymethyl-cellulose (CMC) as wall-materials on the physicochemical behavior of encapsulated Mor. Single or combined wall-material treatments (100:00 and 50:50 ratios, and total solid content 1%) were tested. The results showed the wall-material had a significant effect on the process yield (55.7-68.3%), encapsulation efficiency (24.28-35.74%), color (yellow or pale-yellow), total phenolic content (25.17-27.49 mg GAE g-1 of particles), total flavonoid content (23.20-26.87 mg QE g-1 of particles), antioxidant activity (DPPH⢠= 5.96-6.95 mg GAE g-1; ABTSâ¢+ = 5.61-6.18 mg TE g-1 of particles), and particle size distribution (D50 = 112-1946 nm) of the encapsulated Mor. On the other hand, SEM analysis showed smooth and spherical particles, while TGA and DSC analyses confirmed the encapsulation of bioactive compounds based on the changes in thermal peaks. Finally, XRD analysis showed that the particles have an amorphous behavior. The encapsulated Mor produced with individual TG or CMC demonstrated better properties than those obtained from mixed gums. Thus, TG or CMC might be feasible wall materials for manufacturing encapsulated Mor that conserve the phenolic content and antioxidant activity.
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Saltamontes , Moringa oleifera , Tragacanto , Animales , Carboximetilcelulosa de Sodio , Microondas , PolifenolesRESUMEN
The present review describes the basic properties of colloidal and vesicular vehicles that can be used for immobilization of enzymes. The thermodynamic aspects of the immobilization of enzymes (laminarinase and chitinase) in liposomes are discussed. These systems protect enzymes against environmental stress and allow for a controlled and targeted release. The diversity of colloidal and vesicular carriers allows the use of enzymes for different purposes, such as mycolytic enzymes used to control phytopathogenic fungi.
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In Mexico, mistletoes have several applications in traditional medicine due to the great variety of compounds with biological activities that have not been characterized to date. The goals of the present study are to analyze the composition of minerals and phytochemical compounds in Mexican mistletoes Phoradendron bollanum and Viscum album subs. austriacum qualitatively and quantitatively, identify the compounds using HPLC-MS, and assess the antimicrobial potential in phytopathogenic microorganism control. Mineral content was evaluated with X-ray fluorescence. Three types of extracts were prepared: ethanol, water, and aqueous 150 mM sodium chloride solution. Characterization was carried out using qualitative tests for phytochemical compound groups, analytical methods for proteins, reducing sugars, total phenol, flavonoids quantification, and HPLC-MS for compound identification. The antimicrobial activity of mistletoe's liquid extracts was evaluated by microplate assay. K and Ca minerals were observed in both mistletoes. A qualitative test demonstrated alkaloids, carbohydrates, saponins, flavonoids, tannins, and quinones. Ethanolic extract showed flavonoids, 3845 ± 69 and 3067 ± 17.2 mg QE/g for Phoradendron bollanum and Viscum album subs. austriacum, respectively, while aqueous extracts showed a total phenol content of 65 ± 6.9 and 90 ± 1.19 mg GAE/g Phoradendron bollanum and Viscum album subs. austriacum, respectively. HPLC-MS identified largely hydroxycinnamic acids and methoxycinnamic acids. Clavibacter michiganenses was successfully inhibited by aqueous extract of both mistletoes.
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Citrus wax is a waste generated during the purification process of the citrus essential oil. A lot of citrus wax wastes are globally produced, despite this, its composition and properties are not well known. Here we present comprehensive results proving the chemical composition and the physical properties of citrus wax. Additionally, our study provides the basis for obtaining value-added products from citrus wax wastes. The qualitative/quantitative analysis revealed the presence of different compounds, which range from flavonoids, saponins, carbohydrates, unsaturated compounds, phenolic hydroxyls, and long-chain fatty acid esters. Given that citrus wax is a source of many bioactive compounds, they were preferably extracted with ethanol. The ethanolic extracts demonstrated the presence in citrus wax of different bioactives, such as 5-5'-dehydrodiferulic acid, 3,7-dimethylquercetin, 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone, tangeretin, and limonene. After the extraction of bioactives from citrus wax, a washed waxy material with high content of long-chain fatty acid esters was obtained. It was shown that this washed wax can be used for the production of biodiesel. The transesterification reactions in acid media was the preferred process because higher content of fatty acid methyl esters (such as hexadecanoic acid methyl ester and 9,12-octadecadienoic acid (Z,Z)-, methyl ester) were obtained. Currently, citrus wax does not have any industrial application, here we shown that under the concept of waste biorefinery, the citrus wax wastes are useful sources for producing value-added products such as bioactive compounds and biodiesel.
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Citrus , Biocombustibles , Esterificación , Ésteres , Ácidos GrasosRESUMEN
We have previously shown that human parthenogenetic stem cells (hpSC) can be chemically directed to differentiate into a homogeneous population of multipotent neural stem cells (hpNSC) that are scalable, cryopreservable, express all the appropriate neural markers, and can be further differentiated into functional dopaminergic neurons. Differentiation of hpSC into hpNSC provides a platform to study the molecular basis of human neural differentiation, to develop cell culture models of neural disease, and to provide neural stem cells for the treatment of neurodegenerative diseases. Additionally, the hpNSC that are generated could serve as a platform for drug discovery and the determination of pharmaceutical-induced neural toxicity. Here, we describe in detail the stepwise protocol that was developed in our laboratory that facilitates the highly efficient and reproducible differentiation of hpSC into hpNSC.
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Diferenciación Celular , Células-Madre Neurales/citología , Células Madre Pluripotentes/citología , Técnicas de Cultivo de Célula , Humanos , Inmunohistoquímica , Inmunofenotipificación , Microscopía , Células-Madre Neurales/metabolismo , Neuronas/citología , Células Madre Pluripotentes/metabolismo , Trasplante de Células MadreRESUMEN
International Stem Cell Corporation human parthenogenetic neural stem cells (ISC-hpNSC) have potential therapeutic value for patients suffering from traumatic brain injury (TBI). Here, we demonstrate the behavioral and histological effects of transplanting ISC-hpNSC intracerebrally in an animal model of TBI. Methods: Sprague-Dawley rats underwent a moderate controlled cortical impact TBI surgery. Transplantation occurred at 72 h post-TBI with functional readouts of behavioral and histological deficits conducted during the subsequent 3-month period after TBI. We characterized locomotor, neurological, and cognitive performance at baseline (before TBI), then on days 0, 1, 7, 14, 30, 60, and 90 (locomotor and neurological), and on days 28-30, 58-60, and 88-90 (cognitive) after TBI. Following completion of behavioral testing at 3 months post-TBI, animals were euthanized by transcardial perfusion and brains harvested to histologically characterize the extent of brain damage. Neuronal survival was revealed by Nissl staining, and stem cell engraftment and host tissue repair mechanisms such as the anti-inflammatory response in peri-TBI lesion areas were examined by immunohistochemical analyses. Results: We observed that TBI groups given high and moderate doses of ISC-hpNSC had an improved swing bias on an elevated body swing test for motor function, increased scores on forelimb akinesia and paw grasp neurological tests, and committed significantly fewer errors on a radial arm water maze test for cognition. Furthermore, histological analyses indicated that high and moderate doses of stem cells increased the expression of phenotypic markers related to the neural lineage and myelination and decreased reactive gliosis and inflammation in the brain, increased neuronal survival in the peri-impact area of the cortex, and decreased inflammation in the spleen at 90 days post-TBI. Conclusion: These results provide evidence that high and moderate doses of ISC-hpNSC ameliorate TBI-associated histological alterations and motor, neurological, and cognitive deficits.
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Lesiones Traumáticas del Encéfalo/terapia , Regeneración Cerebral , Células-Madre Neurales/fisiología , Trasplante de Células Madre/métodos , Animales , Cognición , Modelos Animales de Enfermedad , Humanos , Locomoción , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
The immobilization of microorganisms has been reported as an alternative to improve the efficiency of processes such as fermentation, anaerobic digestion, bioadsorption, and many others. Since the kinetics of bioprocesses are governed by the adsorbent/adsorbate interaction, it is important to know the mechanisms of interaction between biological materials and supports. This could help to define optimal operating conditions. In this research, the fungus that produces the cellulases, was selected, and the characterization of the interaction between fungal spores and cobalt ferrite magnetic nanoparticles, was performed. In order to select a fungal strain produces cellulase enzymes, a qualitative Congo Red test was carried out with a culture medium rich in carboxymethylcellulose. From five strains, Aspergillus niger was selected. Chitosan coated cobalt ferrite magnetic nanoparticles (CoMNP-C) were synthesized by single-step co-precipitation. The nano-size of CoMNP-C was demonstrated by XRD. The presence of a high content of amino groups (0.144 mM g-1) was observed, that could have an important role in the interaction between nanoparticles and spores. Adsorption kinetic studies were carried out. The pseudo-equilibrium time was estimated as 90 min. Spores adsorption isotherm was obtained with 3.45 mg of synthesized material at 30 °C. It was found that the adsorption of spores may be described by both models (Langmuir and Freundlich), suggesting a homogeneous surface of the nanoparticles and a multilayer adsorption phenomenon. These results can have transcendence in multiple applications based on the studied process.
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Aspergillus niger/química , Quitosano/química , Cobalto/química , Compuestos Férricos/química , Nanopartículas/química , Esporas Fúngicas/química , Adsorción , Aspergillus niger/metabolismo , Celulasa/metabolismoRESUMEN
Phytopathogenic bacteria affect a wide variety of crops, causing significant economic losses. Natural biocides are the alternative to chemical methods of phytopathogens control. The goal of the present study is the evaluation of the biocidal activity of the following: 1) the extract of orange wax (EOW); 2) zinc ferrite nanoparticles (ZF-NPs); 3) the EOW adsorbed on the ZF-NPs; and 4) the EOW/ZF-NPs washed with 40% ethanol. For the biocidal activity, three phytopathogenic bacteria were used, namely, Xanthomonas axonopodis pv. Vesicatoria (Xav) Erwinia amylovora (Ew), and Pseudomonas syringae pv. Phaseolicola (Psph). For the ZF-NPs, an inhibitory effect higher than 50% ( ) was observed for Xav respect to the antibiotic used as positive control. On the other hand, the ZF-NPs did not show inhibitory effects on both Ew and Psph. In addition, the EOW in dimethyl sulfoxide (DMSO) at 100% caused growth inhibition on Xav, bacteriostatic activity on Ew, and had not biological activity on Psph. To the best of our knowledge, the control of Xav by zinc ferrites and orange wax, and the bacteriostatic effect produced by orange wax extract on Ew have not been reported elsewhere. Orange wax and zinc ferrite nanoparticles show potential in control of phytopathogenic bacteria. However, the bactericidal effect depends on the bacterium, the concentration of treatments, and the method of preparation.
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Antibacterianos/administración & dosificación , Citrus sinensis , Compuestos Férricos/administración & dosificación , Nanopartículas/administración & dosificación , Extractos Vegetales/administración & dosificación , Zinc/administración & dosificación , Erwinia amylovora/efectos de los fármacos , Erwinia amylovora/crecimiento & desarrollo , Pseudomonas syringae/efectos de los fármacos , Pseudomonas syringae/crecimiento & desarrollo , Xanthomonas axonopodis/efectos de los fármacos , Xanthomonas axonopodis/crecimiento & desarrolloRESUMEN
In this commentary we discuss International Stem Cell Corporation's (ISCO's) approach to developing a pluripotent stem cell based treatment for Parkinson's disease (PD). In 2016, ISCO received approval to conduct the world's first clinical study of a pluripotent stem cell based therapy for PD. The Australian regulatory agency Therapeutic Goods Administration (TGA) and the Melbourne Health's Human Research Ethics Committee (HREC) independently reviewed ISCO's extensive preclinical data and granted approval for the evaluation of a novel human parthenogenetic derived neural stem cell (NSC) line, ISC-hpNSC, in a PD phase 1 clinical trial ( ClinicalTrials.gov NCT02452723). This is a single-center, open label, dose escalating 12-month study with a 5-year follow-up evaluating a number of objective and patient-reported safety and efficacy measures. A total of 6 years of safety and efficacy data will be collected from each patient. Twelve participants are recruited in this study with four participants per single dose cohort of 30, 50, and 70 million ISC-hpNSC. The grafts are placed bilaterally in the caudate nucleus, putamen, and substantia nigra by magnetic resonance imaging-guided stereotactic surgery. Participants are 30-70 years old with idiopathic PD ≤13 years duration and unified PD rating scale motor score (Part III) in the "OFF" state ≤49. This trial is fully funded by ISCO with no economic involvement from the patients. It is worth noting that ISCO underwent an exhaustive review process and successfully answered the very comprehensive, detailed, and specific questions posed by the TGA and HREC. The regulatory/ethic review process is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines or novel therapies.
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Células-Madre Neurales/trasplante , Enfermedad de Parkinson/terapia , Trasplante de Células Madre , Células Madre/citología , Australia , Diferenciación Celular/genética , Ensayos Clínicos como Asunto , Humanos , Imagen por Resonancia Magnética , Enfermedad de Parkinson/patología , Células Madre PluripotentesRESUMEN
Repair or regeneration of hyaline cartilage in knees, shoulders, intervertebral discs, and other assorted joints is a major therapeutic target. To date, therapeutic strategies utilizing chondrocytes or mesenchymal stem cells are limited by expandability or the generation of mechanically inferior cartilage. Our objective is to generate robust cartilage-specific matrix from human mesenchymal stem cells suitable for further therapeutic development. Human mesenchymal stem cells, in an alginate 3D format, were supplied with individual sugars and chains which comprise the glycan component of proteoglycans in articular cartilage (galactose, hyaluronic acid, glucuronic acid, and xylose) during chondrogenesis. After an initial evaluation for proteoglycan deposition utilizing Alcian blue, the tissue was further evaluated for viability, structural elements, and hypertrophic status. With the further addition of serum, a substantial increase was observed in viability, the amount of proteoglycan deposition, glycosaminoglycan production, and an enhancement of Hyaluronic Acid, Collagen II and Aggrecan deposition. Suppression of hypertrophic markers (COL1A1, COL10A1, MMP13, and RUNX2) was also observed. When mesenchymal stem cells were supplied with the raw building materials of proteoglycans and a limited amount of serum during chondrogenesis, it resulted in the generation of viable hyaline-like cartilage with deposition of structural components which exceeded previously reported in vitro-based cartilage.
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Carbohidratos/farmacología , Diferenciación Celular , Condrogénesis/efectos de los fármacos , Matriz Extracelular/metabolismo , Células Madre Mesenquimatosas/citología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/crecimiento & desarrollo , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno Tipo II/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Ácido Hialurónico/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Proteoglicanos/metabolismo , SueroRESUMEN
Mammalian gonadotropin-releasing hormone (GnRH) was initially isolated from hypothalamus and its receptor from anterior pituitary, although extrapituitary GnRH receptors have been reported. The aim of the present study was to investigate whether GnRH receptor and its mRNA are expressed in cerebral cortical neurons of rat embryos and adult rats using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The immunohistochemistry and RT-PCR analysis showed expression of GnRH receptor and presence of its mRNA, in both cerebral cortical neurons of rat embryos and cerebral cortical tissues of adult rats. Additional experiments showed a decrease in the receptor mRNA expression when cultured neurons of rat embryos were treated with GnRH. It is possible that the presence of GnRH receptors in cortical neurons of rat may be involved in other physiological roles such as neurohormone or neuromodulator.