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1.
Microb Pathog ; 174: 105894, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36496057

RESUMEN

PURPOSE OF RESEARCH: The aim of the current study was gut profiling of culturable Candida species and their possible pathogenic potential to asses role in obesity. METHODS: This case control study includes stool samples from 75 obese individuals and 50 controls. Isolation and identification of various Candida species was carried out by standard microbiological techniques. For pathogenic profiling, extracellular enzymatic assays, biofilm forming ability and resistance to azole were analyzed. RESULTS: Culturable gut profiling identified comparative higher abundance and diversity of Candida species among obese compared to controls. The most abundant specie among both groups was C.kefyr. A comparatively higher pathogenic potential as more hydrolases expression was detected in C.kefyr, C.albicans and Teunomyces krusei from obese group. Majority isolates from obese group were strong biofilm formers (47.1%) compared to control group (35.4%) suggesting it as strong risk factor for obesity. Fluconazole resistance was highest among C.kefyr (51%) followed by Teunomyces krusei and C.albicans. All the isolates from different species were voriconazole sensitive except C.kefyr displaying a 4.2% resistance in obese group only. A significant association of dominant colonizing species with meat, fruit/vegetable consumption and residence area was present (p < 0.05). CONCLUSION: The presence of hydrolytic enzymes in gut Candida species showed strong association with protein's degradation and enhanced pathogenicity. C.kefyr and Teunomyces krusei has emerged as potential pathogen showing increased colonization as result of protein rich and low carb diet. Thus presenting it as a bad choice for weight loss in obese individuals.


Asunto(s)
Antifúngicos , Candida , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Estudios de Casos y Controles , Fluconazol/farmacología , Candida albicans , Obesidad , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica
2.
Neurochem Res ; 47(4): 813-824, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34988899

RESUMEN

Neuroinflammation is characterized by reactive microglia and astrocytes (collectively called gliosis) in the central nervous system and is considered as one of the main pathological hallmarks in different neurodegenerative diseases such as Alzheimer's disease, age-related dementia, and multiple sclerosis. Upon activation, glia undergoes structural and morphological changes such as the microglial cells swell in size and astrocytes become bushy, which play both beneficial and detrimental roles. Hence, they are unable to perform the normal physiological role in brain immunity. Curcumin, a cytokine suppressive anti-inflammatory drug, has a high proven pre-clinical potency and efficacy to reverse chronic neuroinflammation by attenuating the activation and morphological changes that occur in the microglia and astrocytes. This review will highlight the recent findings on the tree structure changes of microglia and astrocytes in neuroinflammation and the effects of curcumin against the activation and morphology of glial cells.


Asunto(s)
Curcumina , Astrocitos , Curcumina/farmacología , Curcumina/uso terapéutico , Humanos , Inflamación/patología , Microglía , Neuroglía , Enfermedades Neuroinflamatorias
3.
Arch Toxicol ; 91(4): 1623-1634, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28204864

RESUMEN

Neuroinflammation is a pathophysiological process present in a number of neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, traumatic brain injury including chronic traumatic encephalopathy and other age-related CNS disorders. Although there is still much debate about the initial trigger for some of these neurodegenerative disorders, during the progression of disease, broad range anti-inflammatory drugs including cytokine suppressive anti-inflammatory drugs (CSAIDs) might be promising therapeutic options to limit neuroinflammation and improve the clinical outcome. One of the most promising CSAIDs is curcumin, which modulates the activity of several transcription factors (e.g., STAT, NF-κB, AP-1) and their pro-inflammatory molecular signaling pathways. However, normal curcumin preparations demonstrate low bioavailability in vivo. To increase bioavailability, preparations of high bioavailability curcumin have been introduced to achieve therapeutically relevant concentrations in target tissues. This literature review aims to summarize the pharmacokinetic and toxicity profile of different curcumin formulations.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Curcumina/administración & dosificación , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacocinética , Disponibilidad Biológica , Curcumina/efectos adversos , Curcumina/farmacocinética , Progresión de la Enfermedad , Humanos , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Enfermedades Neurodegenerativas/fisiopatología , Transducción de Señal/efectos de los fármacos
4.
Biomed Phys Eng Express ; 10(3)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38224615

RESUMEN

Guided tissue/bone regeneration (GTR/GBR) is a widely used technique in dentistry to facilitate the regeneration of damaged bone and tissue, which involves guiding materials that eventually degrade, allowing newly created tissue to take its place. This comprehensive review the evolution of biomaterials for guided bone regeneration that showcases a progressive shift from non-resorbable to highly biocompatible and bioactive materials, allowing for more effective and predictable bone regeneration. The evolution of biomaterials for guided bone regeneration GTR/GBR has marked a significant progression in regenerative dentistry and maxillofacial surgery. Biomaterials used in GBR have evolved over time to enhance biocompatibility, bioactivity, and efficacy in promoting bone growth and integration. This review also probes into several promising fabrication techniques like electrospinning and latest 3D printing fabrication techniques, which have shown potential in enhancing tissue and bone regeneration processes. Further, the challenges and future direction of GTR/GBR are explored and discussed.


Asunto(s)
Regeneración Tisular Dirigida , Membranas Artificiales , Regeneración Tisular Dirigida/métodos , Materiales Biocompatibles , Huesos , Regeneración Ósea
5.
Environ Pollut ; 349: 123902, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38580061

RESUMEN

The textile industry contributes substantially to water pollution. To investigate bioremediation of dye-containing wastewater, the decolorization and biotransformation of three textile azo dyes, Red HE8B, Reactive Green 27, and Acid Blue 29, were considered using an integrated remediation approach involving the microalga Chlamydomonas mexicana and activated sludge (ACS). At a 5 mg L-1 dye concentration, using C. mexicana and ACS alone, decolorization percentages of 39%-64% and 52%-54%, respectively, were obtained. In comparison, decolorization percentages of 75%-79% were obtained using a consortium of C. mexicana and ACS. The same trend was observed for the decolorization of dyes at higher concentrations, but the potential for decolorization was low. The toxic azo dyes adversely affect the growth of microalgae and at high concentration 50 mg L-1 the growth rate inhibited to 50-60% as compared to the control. The natural textile wastewater was also treated with the same pattern and got promising results of decolorization (90%). Moreover, the removal of BOD (82%), COD (72%), TN (64%), and TP (63%) was observed with the consortium. The HPLC and GC-MS confirm dye biotransformation, revealing the emergence of new peaks and the generation of multiple metabolites with more superficial structures, such as N-hydroxy-aniline, naphthalene-1-ol, and sodium hydroxy naphthalene. This analysis demonstrates the potential of the C. mexicana and ACS consortium for efficient, eco-friendly bioremediation of textile azo dyes.


Asunto(s)
Biodegradación Ambiental , Colorantes , Microalgas , Aguas del Alcantarillado , Industria Textil , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua , Colorantes/metabolismo , Colorantes/química , Aguas del Alcantarillado/química , Contaminantes Químicos del Agua/metabolismo , Microalgas/metabolismo , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Textiles , Compuestos Azo/metabolismo
6.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38931416

RESUMEN

The treatment adherence of narcotics-addicted individuals with reduced incidences of relapse can be enhanced by a sustained drug release formulation of antinarcotics. So far, different drug formulations have been reported with sustained drug release periods of 28 and 35 days. To further enhance this duration, different formulations of injectable hydrogels (IHs) have been developed by combining low molecular weight (LMW) and high molecular weight (HMW) chitosan (CS) with guar gum (GG) and crosslinking them by sodium bi phosphate dibasic. The structural, morphological, and physicochemical properties of LMW-CS IH, and HMW-CS IH were evaluated using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and rheological, swelling, and biodegradation analysis. The HMW-CS IH showed high crosslinking, increased thermal stability, high mechanical strength, elevated swelling, and low biodegradation. The antinarcotic drugs naltrexone (NTX) and disulfiram (DSF) were loaded separately into the HMW-CS IH and LMW-CS IH. The release of NTX and DSF was investigated in phosphate buffer saline (PBS) and ethanol (0.3%, 0.4%, and 0.5%) over a 56-day period using an UV spectrophotometer. The drug release data were tested in zero-order, first-order, and Korsemeyer-Peppas mathematical models. In PBS, all prepared formulations followed non-Fickian drug release, while in ethanol, only NTX HMW-CS IH followed non-Fickian release in all three different concentrations of ethanol.

7.
Int J Biol Macromol ; 232: 123476, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-36731696

RESUMEN

With the advancement in 3D bioprinting technology, cell culture methods can design 3D environments which are both, complex and physiologically relevant. The main component in 3D bioprinting, bioink, can be split into various categories depending on the criterion of categorization. Although the choice of bioink and bioprinting process will vary greatly depending on the application, general features such as material properties, biological interaction, gelation, and viscosity are always important to consider. The foundation of 3D bioprinting is the exact layer-by-layer implantation of biological elements, biochemicals, and living cells with the spatial control of the implantation of functional elements onto the biofabricated 3D structure. Three basic strategies underlie the 3D bioprinting process: autonomous self-assembly, micro tissue building blocks, and biomimicry or biomimetics. Tissue engineering can benefit from 3D bioprinting in many ways, but there are still numerous obstacles to overcome before functional tissues can be produced and used in clinical settings. A better comprehension of the physiological characteristics of bioink materials and a higher level of ability to reproduce the intricate biologically mimicked and physiologically relevant 3D structures would be a significant improvement for 3D bioprinting to overcome the limitations.


Asunto(s)
Bioimpresión , Andamios del Tejido , Andamios del Tejido/química , Impresión Tridimensional , Ingeniería de Tejidos , Tecnología
8.
Int J Biol Macromol ; 230: 123131, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36610570

RESUMEN

3-D Bioprinting is employed as a novel approach in biofabrication to promote skin regeneration following chronic-wounds and injury. A novel bioink composed of carbohydrazide crosslinked {polyethylene oxide-co- Chitosan-co- poly(methylmethacrylic-acid)} (PEO-CS-PMMA) laden with Nicotinamide and human dermal fibroblast was successfully synthesized via Free radical-copolymerization at 73 °C. The developed bioink was characterized in term of swelling, structural-confirmation by solid state 13C-Nuclear Magnetic Resonance (NMR), morphology, thermal, 3-D Bioprinting via extrusion, rheological and interaction with DNA respectively. The predominant rate of gelation was attributed to the electrostatic interactions between cationic CS and anionic PMMA pendant groups. The morphology of developed bioink presented a porous architecture satisfying the cell and growth-factor viability across the barrier. The thermal analysis revealed two-step degradation with 85 % weight loss in term of decomposition and molecular changes in the bioink moieties By applying low pressure in the range of 25-50 kPa, the optimum reproducibility and printability were determined at 37 °C in the viscosity range of 500-550 Pa. s. A higher survival rate of 92 % was observed for (PEO-CS-PMMA) in comparison to 67 % for pure chitosan built bioink. A binding constant of K ≈ 1.8 × 106 M-1 recognized a thermodynamically stable interaction of (PEO-CS-PMMA) with the Salmon-DNA. Further, the addition of PEO (5.0 %) was addressed with better self-healing and printability to produce skin-tissue constructs to replace the infected skin in human.


Asunto(s)
Bioimpresión , Quitosano , Humanos , Hidrogeles/química , Polimetil Metacrilato , Reproducibilidad de los Resultados , Impresión Tridimensional , Tecnología , Andamios del Tejido/química , Ingeniería de Tejidos
9.
Front Mol Neurosci ; 16: 1295991, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38095013

RESUMEN

Chemobrain is a condition that negatively affects cognition in cancer patients undergoing active chemotherapy, as well as following chemotherapy cessation. Chemobrain is also known as chemotherapy-induced cognitive impairment (CICI) and has emerged as a significant medical contingency. There is no therapy to ameliorate this condition, hence identification of novel therapeutic strategies to prevent CICI is of great interest to cancer survivors. Utilizing the platinum-based chemotherapy cisplatin in an investigative approach for CICI, we identified increased expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in the adult mouse hippocampus, and in human cortical neuron cultures derived from induced pluripotent stem cells (iPSCs). Notably, administration of NS398, a selective COX-2 inhibitor, prevented CICI in vivo without negatively affecting the antitumor efficacy of cisplatin or potentiating tumor growth. Given that dysfunctional mitochondrial bioenergetics plays a prominent role in CICI, we explored the effects of NS398 in cisplatin-induced defects in human cortical mitochondria. We found that cisplatin significantly reduces mitochondrial membrane potential (MMP), increases matrix swelling, causes loss of cristae membrane integrity, impairs ATP production, as well as decreases cell viability and dendrite outgrowth. Pretreatment with NS398 in human cortical neurons attenuated mitochondrial dysfunction caused by cisplatin, while improving cell survival and neurite morphogenesis. These results suggest that aberrant COX-2 inflammatory pathways may contribute in cisplatin-induced mitochondrial damage and cognitive impairments. Therefore, COX-2 signaling may represent a viable therapeutic approach to improve the quality of life for cancer survivors experiencing CICI.

10.
Polymers (Basel) ; 14(23)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36501482

RESUMEN

Aromatic polyamides are well-known as high-performance materials due to their outstanding properties making them useful in a wide range of applications. However, their limited solubility in common organic solvents restricts their processability and becomes a hurdle in their applicability. This study is focused on the synthesis of processable ferrocene-based terpolyamides and their polydimethylsiloxane (PDMS)-containing block copolymers, using low-temperature solution polycondensation methodology. All the synthesized materials were structurally characterized using FTIR and 1H NMR spectroscopic techniques. The ferrocene-based terpolymers and block copolymers were soluble in common organic solvents, while the organic analogs were found only soluble in sulfuric acid. WXRD analysis showed the amorphous nature of the materials, while the SEM analysis exposed the modified surface of the ferrocene-based block copolymers. The structure-property relationship of the materials was further elucidated by their water absorption and thermal behavior. These materials showed low to no water absorption along with their high limiting oxygen index (LOI) values depicting their good flame-retardant behavior. DFT studies also supported the role of various monomers in the polycondensation reaction where the electron pair donation from HOMO of diamine monomer to the LUMO of acyl chloride was predicted, along with the calculation of various other parameters of the representative terpolymers and block copolymers.

11.
Front Neurosci ; 15: 699329, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34393713

RESUMEN

Chronic neuroinflammation characterized by microglia reactivity is one of the main underlying processes in the initiation and progression of neurodegenerative diseases such as Alzheimer's disease. This project characterized spatial memory during healthy aging and prolonged neuroinflammation in the chronic neuroinflammatory model, glial fibrillary acidic protein-interleukin 6 (GFAP-IL6). We investigated whether chronic treatment with the natural flavonoid, apigenin, could reduce microglia activation in the hippocampus and improve spatial memory. GFAP-IL6 transgenic and wild-type-like mice were fed with apigenin-enriched or control chow from 4 months of age and tested for spatial memory function at 6 and 22 months using the Barnes maze. Brain tissue was collected at 22 months to assess microgliosis and morphology using immunohistochemistry, stereology, and 3D single cell reconstruction. GFAP-IL6 mice showed age-dependent loss of spatial memory recall compared with wild-type-like mice. Chronic apigenin treatment decreased the number of Iba-1+ microglia in the hippocampus of GFAP-IL6 mice and changed microglial morphology. Apigenin did not reverse spatial memory recall impairment in GFAP-IL6 mice at 22 months of age. GFAP-IL6 mice may represent a suitable model for age-related neurodegenerative disease. Chronic apigenin supplementation significantly reduced microglia activation, but this did not correspond with spatial memory improvement in the Barnes Maze.

12.
Front Neurosci ; 14: 170, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32226360

RESUMEN

Chronic glial activation is characterized by an increased number of activated microglia and astroglia; these secrete free radicals and cytotoxic cytokines, subsequently causing neuronal damage. This study investigated the hypothesis that a soy-lecithin based phytosomal curcumin formulation can decrease glial activation in the brains of GFAP-IL6 mice, a model of chronic glial activation, which exhibits gliosis in various regions of the brain. Three doses of Meriva curcumin (MC) (874, 436, and 218 PPM) were fed to 3-month-old GFAP-IL6 and wild-type (WT) mice for 4 weeks. As markers of glial activation, the total numbers of Iba-1+ and TSPO+ microglia and macrophages, and GFAP+ astrocytes, were determined in the cerebellum and hippocampus by immunohistochemistry and unbiased stereology. Furthermore, the morphology of the glial cells was assessed by confocal microscopy and Sholl analysis. Administration of phytosomal curcumin led to a dose-dependent reduction in neuroinflammatory markers. Phytosomal curcumin (874 PPM) decreased the number of microglia by 26.2% in the hippocampus and by 48% in the cerebellum of the GFAP-IL6 mice compared with the GFAP-IL6 mice on normal food. Additionally, GFAP+ astrocyte numbers in the hippocampus of the GFAP-IL6 mice were decreased by 42%. The GFAP-IL6 mice exhibited a different microglial morphology to the WT mice, showing an increased soma size and perimeter. This difference was significantly reduced by the 874 PPM phytosomal curcumin dose. Our findings demonstrate that phytosomal curcumin is able to attenuate the inflammatory pathology, and potentially reverse the detrimental effects of chronic glial activation.

13.
Sci Rep ; 10(1): 2365, 2020 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-32047191

RESUMEN

Chronic glial activation is characterized by increased numbers of activated glial cells, secreting free radicals and cytotoxic cytokines, subsequently causing neuronal damage. In order to investigate the anti-inflammatory activity of Longvida® Optimised Curcumin (LC), we fed 500 ppm of LC to 2-month-old wild type and GFAP-IL6 mice for 6 months. LC feeding led to a significant reduction in the number of Iba-1+ microglia by 26% in the hippocampus and by 48% in the cerebellum, GFAP+ astrocytes by 30%, and TSPO+ cells by 24% in the hippocampus and by 31% in the cerebellum of the GFAP-IL6 mice. The morphology of the cells was assessed and LC significantly decreased the dendritic length of microglia and the convex area, convex perimeter, dendritic length, nodes and number of processes of astrocytes in the hippocampus while decreasing the soma area and perimeter in the cerebellum, in LC-fed GFAP-IL6 mice. In addition, LC feeding increased pre- and postsynaptic protein levels and improved balance measured by Rotarod. Together, these data suggest that LC is able to attenuate the inflammatory pathology and ameliorate neurodegeneration and motor deficits in GFAP-IL6 mice. For patients with neuro-inflammatory disorders, LC might potentially reverse the detrimental effects of chronic glial activation.


Asunto(s)
Antiinflamatorios/farmacología , Astrocitos/efectos de los fármacos , Curcumina/farmacología , Microglía/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Animales , Antiinflamatorios/uso terapéutico , Astrocitos/metabolismo , Cerebelo/citología , Curcumina/análogos & derivados , Curcumina/uso terapéutico , Dendritas/efectos de los fármacos , Dendritas/metabolismo , Femenino , Proteína Ácida Fibrilar de la Glía/genética , Hipocampo/citología , Interleucina-6/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Movimiento , Enfermedades Neurodegenerativas/genética , Fármacos Neuroprotectores/uso terapéutico
14.
Int J Biol Macromol ; 147: 853-866, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31739066

RESUMEN

Gums; composed of polysaccharides, carbohydrates, proteins, and minerals, are high molecular weight hydrophilic compounds with several biological applications. This study describes the nutritional and toxic elements content, chemical composition, synthesis of silver nanoparticles (G-AgNPs), and pharmacological and catalytic properties of Prunus armeniaca (apricot), Prunus domestica (plums), Prunus persica (peaches), Acacia modesta (phulai), Acacia arabica (kikar), and Salmalia malabarica (silk cotton tree) gums. The elemental contents were analyzed by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and ICP-mass spectrometry (ICP-MS). NMR spectroscopy was used for the identification of class of compounds in the mixture, their functional groups were determined through FTIR techniques, and plasmon resonance and size of G-AgNPs through UV-Vis spectroscopic technique and transmission electron microscopy (TEM). From the results, nutritional elements were present at appreciable concentrations, whereas toxic elements showed content below the maximum permissible ranges. Using the elemental data, linear discriminant and principal component analyses classified the gums to 99.9% variability index. Furthermore, G-AgNPs exhibited significant antioxidant, antibacterial, and redox catalytic potential. Hence, the subject G-AgNPs could have promising nutritional, therapeutic and environmental remediation applications.


Asunto(s)
Antibacterianos , Antioxidantes , Nanopartículas del Metal/química , Gomas de Plantas/química , Plata/química , Antibacterianos/síntesis química , Antibacterianos/química , Antioxidantes/síntesis química , Antioxidantes/química , Catálisis
15.
Front Neurosci ; 13: 303, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31001075

RESUMEN

Chronic microglial activation is a prominent feature of many chronic neurodegenerative diseases, including Parkinson's and Alzheimer's disease. To investigate the effects of chronic microglial activation on cerebellar structure and motor function throughout the lifespan, the transgenic GFAP-IL6 mouse model was used. The aim of the study was to examine inflammatory markers and neuronal degeneration while simultaneously characterizing the motor performance of GFAP-IL6 mice at 3, 6, 14, and 24 months of age in comparison to WT (C57BL/6) mice. In respect to markers of neuroinflammation in the cerebellum, increased numbers of Iba1+ microglia were observed as early as at 3 months of age. In addition, TNF-α levels proved to be significantly higher in the GFAP-IL6 compared to WT mice at all time points. A difference in cerebellar volume between the GFAP-IL6 and WT mice was observed later in life, starting at 6 months and increasing to a loss of about 50% in aged (24 months old) GFAP-IL6 mice. Synaptic deficits were also assessed by using pre- (synaptophysin) and post-synaptic (PSD95) markers. While synaptophysin levels remained unchanged, PSD95 levels decreased in the aging GFAP-IL6 mice compared to their WT littermates from 14 months onward. To assess the effect of microglia activation and neurodegeneration on behavior, a variety of motor function tests, semi-quantitative cerebellar ataxia score, accelerod, beam walking, and open field tests were performed. An age-dependent difference between the genotypes was observed in many of the motor function tests. For example, reduced performance on the accelerod and higher ataxia scores were observed at 6 months of age, followed by the beam walking test showing differences at 14 months of age. In summary, this study constitutes a comprehensive, age-dependent examination of inflammatory, synaptic and neurodegenerative changes in the brains of GFAP-IL6 mice leading to a deterioration in motor performance. The results also indicate that early chronic microglia activation in the GFAP-IL6 mouse leads to observable cerebellar volume loss and motor deficits later in life.

16.
J Biomater Sci Polym Ed ; 29(4): 376-396, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29285989

RESUMEN

Addressing the functional biomaterials as next-generation therapeutics, chitosan and alginic acid were copolymerized in the form of chemically crosslinked interpenetrating networks (IPNs). The native hydrogel was functionalized via carbodiimide (EDC), catalyzed coupling of soft ligand (1,2-Ethylenediamine) and hard ligand (4-aminophenol) to replace -OH groups in alginic acid units for extended hydrogel- interfaces with the aqueous and sparingly soluble drug solutions. The chemical structure, Lower solution critical temperature (LCST ≈ 37.88 °C), particle size (Zh,app ≈ 150-200 nm), grain size (160-360 nm), surface roughness (85-250 nm), conductivity (37-74 mv) and zeta potential (16-32 mv) of native and functionalized hydrogel were investigated by using FT-IR, solid state-13C-NMR, TGA, DSC, FESEM, AFM and dynamic light scattering (DLS) measurements. The effective swelling, drug loading (47-78%) and drug release (53-86%) profiles were adjusted based on selective functionalization of hydrophobic IPNs due to electrostatic complexation and extended interactions of hydrophilic ligands with the aqueous and drug solutions. Drug release from the hydrogel matrices with diffusion coefficient n ≈ 0.7 was established by Non- Fickian diffusion mechanism. In vitro degradation trials of the hydrogel with a 20% loss of wet mass in simulated gastric fluid (SGF) and 38% loss of wet mass in simulated intestinal fluid (SIF), were investigated for 400 h through bulk erosion. Consequently, a slower rate of drug loading and release was observed for native hydrogel, due to stronger H-bonding, interlocking and entanglement within the IPNs, which was finely tuned and extended by the induced hydrophilic and functional ligands. In the light of induced hydrophilicity, such functional hydrogel could be highly attractive for extended release of sparingly soluble drugs.


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Hidrogeles/química , Ácido Algínico/química , Aminofenoles/química , Materiales Biocompatibles/química , Reactivos de Enlaces Cruzados/química , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Etilenodiaminas/química , Humanos , Hidrogeles/síntesis química , Interacciones Hidrofóbicas e Hidrofílicas , Imidas/química , Polimerizacion
18.
J Neuroimmune Pharmacol ; 11(1): 48-60, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26139594

RESUMEN

Recent studies have demonstrated a close interaction between neuroinflammatory responses, increased production of inflammatory mediators, and neurodegeneration. Pathological findings in neurological diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease have shown common signs of neuroinflammation and neurodegeneration. Lupeol, a natural pentacyclic triterpene, has revealed a number of pharmacological properties including an anti-inflammatory activity. This study aimed to evaluate the effect of lupeol against lipopolysaccharide (LPS)-induced neuroinflammation in the cortex and hippocampus of adult mice. Our results showed that systemic administration of LPS induced glial cell production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1ß, while co-treatment with lupeol significantly inhibited the LPS-induced activation of microglia and astrocytes, and decreased the LPS-induced generation of TNF-α, iNOS, and IL-1ß. The intracellular mechanism involved in the LPS-induced activation of inflammatory responses includes phosphorylation of P38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which was significantly inhibited by lupeol. We further elucidated that lupeol inhibited the LPS-induced activation of the mitochondrial apoptotic pathway and reversed the LPS-induced expression of apoptotic markers such as Bax, cytochrome C, caspase-9, and caspase-3. Taken together; our results suggest that lupeol inhibits LPS-induced microglial neuroinflammation via the P38-MAPK and JNK pathways and has therapeutic potential to treat various neuroinflammatory disorders.


Asunto(s)
Antiinflamatorios/farmacología , Encéfalo/efectos de los fármacos , Encefalitis/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Triterpenos Pentacíclicos/farmacología , Animales , Western Blotting , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Encefalitis/inducido químicamente , Técnica del Anticuerpo Fluorescente , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL
19.
Carbohydr Polym ; 136: 1182-93, 2016 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-26572461

RESUMEN

This study attempted to clarify the influence of a cross-linker, N,N-methylenebisacrylamide (MBA), and N-isopropylacrylamide (NIPAM) on the non-isothermal kinetic degradation, solid state and lifetime of hydrogels using the Flynn-Wall-Ozawa (F-W-O), Kissinger, and Coats-Redfern (C-Red) methods. The series of dual-responsive Cs-PNIPAM-MBA microgels were synthesized by soapless-emulsion free radical copolymerization in an aqueous medium at 70 °C. The thermal properties were investigated using thermogravimetric analysis (TG) and differential scanning calorimetry (DSC) under nitrogen atmosphere. The apparent activation energy using the chosen Flynn-Wall-Ozawa and Kissinger methods showed that they fitted each other. Meanwhile, the type of solid state mechanism was determined using the Coats-Redfern method proposed for F1 (pure Cs) and F2 (Cs-PNIPAM-MBA hydrogel series) types, which comprise random nucleation with one nucleus reacting on individual particles, and random nucleation with two nuclei reacting on individual particles, respectively. On average, a higher Ea was attributed to the greater cross-linking density of the Cs hydrogel.

20.
Int J Biol Macromol ; 83: 376-84, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26597568

RESUMEN

A new approach to design multifunctional chitosan based nanohydrogel with enhanced glucose sensitivity, stability, drug loading and release profile are reported. Two approaches were followed for functionalization of chitosan based nanohydrogel with 3-APBA via EDC and 3-APTES. The effective functionalization, structure and morphology of Chitosan based IPN respectively were confirmed by FTIR, SEM and AFM. At physiological conditions, the glucose-induced volume phase transition and release profile of the model drug Alizarin Red with 1,2-diol structure (comparative to insulin as a drug as well as a dye for bio separation) were studied at various glucose concentrations, pH and ionic strengths. The results suggested a new concept for diabetes treatment and diols sensitivity in view of their potential hi-tech applications in self-regulated on-off response to the treatment (drug delivery and bio separation concurrently).


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Glucosa/química , Hidrogeles/química , Nanoestructuras/química , Antraquinonas/química , Diseño de Fármacos , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Concentración Osmolar , Propilaminas , Silanos/química , Propiedades de Superficie
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