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Objective: Air pollution is a leading public health issue. This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai. Methods: The study monitored 27 asthma outpatients for a year, collecting data on weather, patient self-management [daily asthma diary, peak expiratory flow (PEF) monitoring, medication usage], spirometry and serum markers. To explore the potential mechanisms of any effects, asthmatic mice induced by ovalbumin (OVA) were exposed to PM 2.5. Results: Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma. Acute exposure showed a correlation between PEF and levels of ozone (O 3) and nitrogen dioxide (NO 2). Chronic exposure indicated that interleukin-5 (IL-5) and interleukin-13 (IL-13) levels correlated with PM 2.5 and PM 10 concentrations. In asthmatic mouse models, exposure to PM 2.5 increased cytokine levels and worsened lung function. Additionally, PM 2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways. Conclusion: Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation. Specifically, PM 2.5 significantly contributes to these adverse effects. Further research is needed to elucidate the mechanisms by which PM 2.5 impacts asthma.
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Contaminantes Atmosféricos , Asma , Pulmón , Asma/inducido químicamente , China , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/toxicidad , Animales , Humanos , Femenino , Masculino , Adulto , Ratones , Persona de Mediana Edad , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Ratones Endogámicos BALB C , Inflamación/inducido químicamente , Material Particulado/toxicidad , Material Particulado/efectos adversos , Citocinas/sangre , Citocinas/metabolismo , OvalbúminaRESUMEN
Acute liver failure is an uncommon and dramatic clinical syndrome with a high risk of mortality. Previous treatments existed some limitations of poor bioavailability and targeting the efficiency of drugs. In this study, a novel glycyrrhizin mediated liver-targeted alginate nanogels, which can deliver the antioxidant quercetin to the liver for the treatment of acute liver injury. In vitro radical scavenging results showed that the antioxidant activity of quercetin was increased 81-fold. The tissue distribution results indicated that glycyrrhizin-mediated nanogels showed stronger fluorescence intensity in the liver, which improved liver targeting and therapeutic efficacy. Quercetin-glycyrrhizin nanogels were more effective at restoring liver injury as indicated on serum markers, including alanine transaminase, aspartate aminotransferase, and total bilirubin. The histopathology result showed that quercetin-glycyrrhizin nanogels reversed liver damage. Oxidative parameters of malondialdehyde and glutathione s-transferase were decreased, which provided supporting evidence of antioxidation. Moreover, quercetin-glycyrrhizin nanogels were more effective in down-regulating the inflammation-related gene expression of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase and monocyte chemotactic protein-1. In conclusion, the novel glycyrrhizin mediated liver-targeted alginate nanogels might be a promising treatment for acute liver failure.
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Alginatos/química , Ácido Glicirrínico/metabolismo , Quercetina/administración & dosificación , Alanina Transaminasa/sangre , Alginatos/farmacología , Animales , Antioxidantes/farmacología , Aspartato Aminotransferasas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , China , Ácido Glicirrínico/química , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Fallo Hepático Agudo/metabolismo , Masculino , Ratones , Nanogeles/administración & dosificación , Nanogeles/química , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Quercetina/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objective: To explore impact of Candida on the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) outcome. Methods: A retrospective, multi-center, case-control study was performed. Patients hospitalized for AECOPD in 25 centers during Jan 2011-Dec 2016 were enrolled. Data were collected, including demographic information, conditions during the stable phase of COPD, clinical characteristics of AECOPD, and follow-up information within 1 year after discharge. Univariate analysis and binary logistic regression were applied, and p < 0.05 was regarded as significant. Results: Totally 1,103 patients were analyzed, with 644 lower respiratory airway (LTR) Candida positive cases and 459 Candida negative controls. Long-term prognosis was significantly different between Candida positive and negative group, including the recurrent AECOPD within 180 days (75.5 vs. 6.6%, p < 0.001) and mortality within 1 year (6.9 vs. 0.4%, p < 0.001). Univariate logistic analysis showed that LTR Candida isolation was related to higher recurrence rate of AECOPD within 180 days and mortality within 1 year. Binary logistic regression analysis demonstrated that LTR Candida isolation was independently associated with recurrence of AECOPD within 180 days. Conclusions: LTR Candida isolation was associated with worse long-term prognosis of AECOPD and independently related to higher risks of recurrent AECOPD within 180 days.
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Candida , Enfermedad Pulmonar Obstructiva Crónica , Estudios de Casos y Controles , Humanos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND The suitability of mechanical thrombectomy (MT) for patients with acute mild ischemic stroke (AMIS) caused by large vessel occlusion (LVO) is controversial. This study evaluated MT in patients with AMIS and LVO. MATERIAL AND METHODS Forty-seven patients diagnosed as AMIS with LVO received MT or intravenous thrombolysis (IVT). Primary outcomes were National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale scores. Secondary outcomes were incidence of systemic complications and symptomatic intracranial hemorrhage. RESULTS There were no significant differences between IVT and MT groups for gender, age, risk factors of cerebrovascular disease, past history, NIHSS score at admission, blood pressure, and LVO sites. For all patients, the NIHSS scores at discharge were lower than those at admission. Patients with excellent outcomes were 66.6% (16/24) in the IVT group and 60.8% (14/23) in the MT group; favorable outcome rates were 75% (18/24) in the IVT group and 69.6% (16/23) in the MT group, with no significant differences between groups. Twelve patients (52.2%) in the MT group and 5 (20.8%) in the IVT group had systemic complications. Symptomatic intracranial hemorrhage was not detected in the IVT group, but manifested in 2 (8.7%) patients in the MT group. During 90-day follow-up, 1 patient died in each of the IVT and MT groups, with 4.2% and 4.4% mortality rates, respectively. CONCLUSIONS The efficacy of MT and IVT was comparable in AMIS patients with LVO. While MT had a higher incidence of systemic complications, its short- and long-term effects were equivalent to IVT.
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Accidente Cerebrovascular Isquémico/terapia , Trombolisis Mecánica/métodos , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Trombectomía/métodos , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: SNF-related Kinase 1 (SnRK1) is a key component of the cell signaling network. SnRK1 is known to respond to a wide variety of stresses, but its exact role in salt stress response and tolerance is still largely unknown. RESULTS: In this study, we reported that overexpression of the gene encoding the α subunit of Prunus persica SnRK1 (PpSnRK1α) in tomato could improve salt stress tolerance. The increase in salt stress tolerance in PpSnRK1α-overexpressing plants was found to correlate with increased PpSnRK1α expression level and SnRK1 kinase activity. And PpSnRK1α overexpression lines exhibited a lower level of leaf damage as well as increased proline content and reduced malondialdehyde (MDA) compared with wild-type (WT) lines under salt stress. Furthermore, PpSnRK1α enhanced reactive oxygen species (ROS) metabolism by increasing the expression level of antioxidase genes and antioxidant enzyme activities. We further sequenced the transcriptomes of the WT and three PpSnRK1α overexpression lines using RNA-seq and identified about 1000 PpSnRK1α-regulated genes, including many antioxidant enzymes, and these genes were clearly enriched in the MAPK signaling pathway (plant), plant-pathogen interactions and plant hormone signaling transduction and can respond to stimuli, metabolic processes, and biological regulation. Furthermore, we identified the transcriptional levels of several salt stress-responsive genes, SlPP2C37, SlPYL4, SlPYL8, SlNAC022, SlNAC042, and SlSnRK2 family were altered significantly by PpSnRK1α, signifying that SnRK1α may be involved in the ABA signaling pathway to improve tomato salt tolerance. Overall, these findings provided new evidence for the underlying mechanism of SnRK1α conferment in plant salt tolerance phenotypes. CONCLUSIONS: Our findings demonstrated that plant salt stress resistance can be affected by the regulation of the SnRK1α. Further molecular and genetic approaches will accelerate our knowledge of PpSnRK1α functions, and inform the genetic improvement of salt tolerance in tomato through genetic engineering and other related strategies.
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Regulación de la Expresión Génica de las Plantas/fisiología , Proteínas de Plantas/genética , Proteínas Serina-Treonina Quinasas/genética , Prunus persica/fisiología , Tolerancia a la Sal/genética , Solanum lycopersicum/fisiología , Ácido Abscísico/metabolismo , Solanum lycopersicum/genética , Oxígeno/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Prunus persica/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Colitis-associated colorectal cancer (CAC) is a common malignancy that develops in chronically inflamed mucosa and is usually accompanied by metastases at other sites. Puerarin, a natural isoflavone isolated from the root of the Pueraria lobata (Willd.) Ohwi, has potential anti-colon cancer activity. However, the poor solubility and low bioavailability of puerarin has restricted its application in the pharmaceutical industry. In the present study, pH-responsive alginate microspheres loaded with puerarin were prepared by emulsification/internal gelation for targeted treatment of colitis-associated colorectal cancer. Herein, puerarin, as an active drug, could participate in the construction of alginate microspheres with hydrogen bonding. The microspheres exhibited pH-responsive release behavior with little release of puerarin in simulated gastric fluid and high amounts (approximately 55%) of release in simulated colonic fluid. A fluorescence tracer indicated microspheres had high retention time of more than 20â¯h in the colon. Meanwhile, puerarin-loaded alginate microspheres not only significantly decreased the inflammatory response by downregulating the levels of pro-tumorigenic cytokines, but they reduced tumorigenesis and metastasis by inhibiting epithelial-mesenchymal transitions in AOM/DSS-induced colitis-associated colorectal cancer in mice. The overall results suggested that puerarin-loaded alginate microspheres could effectively inhibit development of colonic tumors, which could be developed as a promising therapeutic strategy for colitis-associated colorectal cancer.
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Carcinogénesis/efectos de los fármacos , Colitis/complicaciones , Colon/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/etiología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/etiología , Isoflavonas/farmacología , Alginatos/química , Animales , Líquidos Corporales/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Inflamación/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Isoflavonas/química , Masculino , Ratones , Ratones Endogámicos BALB C , MicroesferasRESUMEN
The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both medicinal and nutritional importance. Our previous study has found that the 80% ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in mouse behavioral despair depression models. However, its mechanisms are still unclear. The present study aimed to observe the antidepressant-like mechanisms of RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF). CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure. Sucrose preference test was carried out to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. Results demonstrated that CUMS induced depression-like behavior, whereas RGEE and FH administration inhibited this symptom. Furthermore, CUMS caused excessively elevated levels of serum corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE administration also further elevated monoamine neurotransmitters and BDNF levels, up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may partially be associated with restoring HPA axis dysfunctions, enhancing monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.
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Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Corticosterona/sangre , Trastorno Depresivo/tratamiento farmacológico , Modelos Animales de Enfermedad , Etanol/farmacología , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Ratas Sprague-Dawley , RehmanniaRESUMEN
Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increasing the risk of fracture. Icariin (ICA) as a phytoestrogen shows osteogenic effects, and the mechanical stimulation has been demonstrated the improving effect on osteoporosis. The objective of this study was to investigate the effect of ICA in combination with constrained dynamic loading (CDL) stimulation on osteoporosis in ovariectomized (OVX) mice. The serum hormone levels, bone turnover markers, trabecular architecture, ulnar biomechanical properties, and the expression of osteoblast-related gene (alkaline phosphatase, ALP; osteocalcin, OCN; bone morphogenetic protein-2, BMP-2; Collagen I (α1), COL1; osteoprotegerin, OPG) and osteoclast-related genes (receptor activators of NF-κB ligand, RANKL; tartrate-resistant acid phosphatase, TRAP) were analyzed. The results showed that ICA + CDL treatment could increase the osteocalcin (20.85%), estradiol levels (20.61%) and decrease the TRAP activity (26.27%) significantly than CDL treatment. The combined treatment attenuated bone loss and biomechanical decrease more than single use of CDL treatment. ICA + CDL treatment significantly up-regulated the level of osteoblast-related gene expression and down-regulated the osteoclast-related genes expression; moreover, the combined treatment increased the ratio of OPG/RANKL significantly compared to ICA (72.83%) or CDL (65.63%) treatment alone. The present study demonstrates that icariin in combination with constrained dynamic loading treatment may have a therapeutic advantage over constrained dynamic loading treatment alone for the treatment of osteoporosis, which would provide new evidence for the clinical treatment of osteoporosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1415-1424, 2018.
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Flavonoides/uso terapéutico , Osteoporosis/terapia , Estrés Mecánico , Animales , Fenómenos Biomecánicos , Remodelación Ósea , Colágeno Tipo I/genética , Estradiol/sangre , Femenino , Ratones , Ratones Endogámicos ICR , Osteoporosis/sangre , Osteoprotegerina/análisis , Ovariectomía , Ligando RANK/análisisRESUMEN
AIM: To investigate the correlation between lumican (LUM) gene and high myopia in a Southern Chinese population. METHODS: The study comprised of 95 high myopia patients with a spherical equivalent ≤-6.5 diopters (D). The control group recruited 95 individuals with a spherical equivalent ranging from -0.5 D to +0.5 D. Direct sequencing was used to detect the single nucleotide polymorphisms (SNPs) of LUM gene in coding region. Genotype distributions were tested for Hardy-Weinberg disequilibrium. Genotypic and allelic frequencies were analyzed through Chi-square test or Fisher's exact test. RESULTS: We identified 3 SNPs of the LUM gene: LUM c.32 (rs577456426), LUM c.507 (rs17853500) and LUM c.849 (rs181915277). Among the three SNPs, the genotype and allele frequencies of rs17853500 showed a significant difference between patients and control subjects (P<0.05). However, there were no significant differences in rs181915277 and rs577456426 between the two groups (P>0.05). CONCLUSION: LUM c.507 polymorphism may be a risk factor for the pathogenesis of high myopia in the Southern Chinese population.
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BACKGROUND: To explore the incidence and risk factors, including type of seizures for post-traumatic epilepsy (PTE) after severe traumatic brain injury (TBI). SUBJECTS AND METHODS: This was a retrospective follow-up study of patients discharged from Liaocheng People's Hospital between March 2011 and June 2015 with a diagnosis of post-traumatic seizures. Risk factors for PTE were evaluated in 68 inpatients by using Kaplan-Meier curves and the Cox model. RESULTS: Complete clinical information was available for 68 patients. A total of 54 cases (79.4%) were diagnosed as presenting with PTE, occurring from 10 days to 179 months after severe TBI. Nineteen out of 54 cases (35.2%) had been defined as PTE within the first 6 months after the trauma, 17 cases (31.5%) within 7-12 months, 8 cases (14.8%) within 13-24 months, 2 cases (3.7%) within 25-36 months, and 8 cases (14.8%) within 37-179 months after the TBI. The Kaplan-Meier curves demonstrated that simple partial seizures, surgical treatment, and onset of seizures occurring within 6 months after injury were associated with PTE. CONCLUSIONS: The Cox model indicated that, for patients aged >34 years at the time of injury, the PTE risk was 2.55 times greater than for those aged ≤34 years. In addition, simple partial seizures, surgical treatment and onset of seizures occurring within 6 months after injury were significant risk factors for the development of PTE.
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PURPOSE: Conventional inhaled corticosteroids or ß2-adrenergic receptor agonists do not work well in some asthmatic populations while empirical antifungal therapy has obvious impact on those patients. The study was designed to investigate whether short-term exposure to Aspergillus fumigatus (A. fumigatus) could decrease glucocorticoid receptor (GCR) and ß2-adrenergic receptor (ADRB2) expression in lung tissue of asthmatic rats. MATERIALS AND METHODS: A rat model of chronic asthma was first established by ovalbumin sensitization and challenge. Rats with chronic asthma were then exposed to short-term application of A. fumigatus spores. Airway hyper-responsiveness, eosinophil ratio in bronchoalveolar lavage (BAL) fluid and total IgE in serum were counted in these experimental animals. GCR and ADRB2 expression in the lung were detected and analyzed. Furthermore, the levels of toll-like receptors (TLRs) 2, 3 and 4 in lung tissue were measured. RESULTS: Short-term exposure to A. fumigatus could down-regulate the expression of GCR, aggravate airway hyper-responsiveness and increase the level of TLR2 in rats with asthma. There were no obvious changes in the levels of ADRB2 expression, recruited eosinophils, total IgE, TLR3 and TLR4 after application of A. fumigatus in asthmatic rats. CONCLUSIONS: These findings indicate that A. fumigatus exposure may be involved in glucocorticoids unresponsiveness by down-regulating the expression of GCR in asthmatics. The possibility of A. fumigatus colonization or infection should not be ignored in patients of steroid-resistant asthma.
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Aspergillus fumigatus/patogenicidad , Asma/microbiología , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Glucocorticoides/metabolismo , Animales , Asma/metabolismo , Glucocorticoides/farmacología , Ratas , Hipersensibilidad Respiratoria , Receptor Toll-Like 2RESUMEN
In recent years, oral colon specific drug delivery system has been paid more attention in the treatment of inflammatory bowel disease (IBD). As the special pH condition in gastrointestinal tract, the challenge for treatment of IBD was that the colon drug delivery system should endure the low pH in stomach and release drugs quickly in high pH in colon. Icariin with the poor solubility and low bioavailability limited the treatment of many diseases in clinic. In this study, the protective mechanism of alginate-chitosan microspheres loaded with icariin were investigated with trinitrobenzene sulfonic acid (TNBS)/ethanol induced colonic mucosal injury in rats. The results of drug release showed that the icariin loaded into microspheres released only 10% in simulated gastric fluid and a high amount of 65.6% released in simulated colonic fluid. The fluorescence tracer indicated high retention of targeted microspheres more than 12h in colon. The microspheres loaded with icariin could not only reduce the colonic injury by decreasing the colon mucosa damage index in rats, but also reduce the inflammatory response by reducing the production and gene expression of inflammatory mediators and cytokines in colonic mucosa. All the results indicate that targeted microspheres loaded with icariin could exert the colon-protective effects through reducing the inflammatory response, which would be developed as a potential drug controlled release system for treatment of ulcerative colitis.
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Alginatos/química , Quitosano/química , Colon/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Animales , Disponibilidad Biológica , Colitis Ulcerosa/tratamiento farmacológico , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Flavonoides/metabolismo , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Inflamación/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Masculino , Microesferas , Ratas , Ratas Sprague-Dawley , Solubilidad , Ácido Trinitrobencenosulfónico/químicaRESUMEN
AIM: To construct adenovirus vectors of lumican gene by gateway recombinant cloning technology to further understand the role of lumican gene in myopia. METHODS: Gateway recombinant cloning technology was used to construct adenovirus vectors. The wild-type (wt) and mutant (mut) forms of the lumican gene were synthesized and amplified by polymerase chain reaction (PCR). The lumican cDNA fragments were purified and ligated into the adenovirus shuttle vector pDown-multiple cloning site (MCS)-/internal ribozyme entry site (IRES)/enhanced green fluorescent protein (EGFP). Then the desired DNA fragments were integrated into the destination vector pAV.Des1d yielding the final expression constructs pAV.Ex1d-cytomegalovirus (CMV)>wt-lumican/IRES/EGFP and pAV.Ex1d-CMV>mut-lumican/IRES /EGFP, respectively. RESULTS: The adenovirus plasmids pAV.Ex1d-CMV>wt-lumican/IRES/EGFP and pAV.Ex1d-CMV>mut-lumican/IRES/EGFP were successfully constructed by gateway recombinant cloning technology. Positive clones identified by PCR and sequencing were selected and packaged into recombinant adenovirus in HEK293 cells. CONCLUSION: We construct adenovirus vectors containing the lumican gene by gateway recombinant cloning technology, which provides a basis for investigating the role of lumican gene in the pathogenesis of high myopia.
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In liver tissue engineering, scaffolds with porous structure desgined to supply nutrient and oxygen exchange for three-dimensional (3-D) cells culture, and maintain liver functions. Meanwhile, genipin, as a natural crosslinker, is widely used to crosslink biomaterials in tissue engineering, with lower cytotoxicity and better biocompatibility. In present study, chitosan/gelatin 3-D scaffolds crosslinked by genipin, glutaraldehyde or 1-(3-dimethylaminopropyl)-3-ethyl-carbodimide hydrochloride (EDC) were prepared and characterized by Fourier-transform infrared (FT-IR) and scanning electron microscopy (SEM). The biocompatibility of chitosan/gelatin scaffolds corsslinked with different crosslinkers was investigated by cell viability, morphology and liver specific functions. The result showed that the 1% and 2% genipin crosslinked chitosan/gelatin scaffolds possess ideal porosity. The genipin crosslinked 3-D scaffolds possessed the best biocompatibility than that of the others, and maintained liver specific functions when HepG2 cells seeded on scaffolds. The cellular morphology of HepG2 cells seeded on scaffolds showed that cells could penetrate into the scaffolds and proliferate significantly. Therefore, genipin crosslinked chitosan/gelatin scaffolds could be a promising biomaterial used in liver tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1863-1870, 2016.
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Quitosano/química , Reactivos de Enlaces Cruzados/química , Gelatina/química , Iridoides/química , Hígado/fisiología , Andamios del Tejido/química , Animales , Bovinos , Movimiento Celular , Proliferación Celular , Forma de la Célula , Células Hep G2 , Humanos , Imagenología Tridimensional , Espectroscopía Infrarroja por Transformada de Fourier , Ingeniería de Tejidos/métodosRESUMEN
Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in "Danxi's experiential therapy" for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1ß in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these microspheres could be developed as a potential controlled release drug for treatment of gastric ulcer.
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Alginatos/química , Alcaloides/farmacología , Antiulcerosos/farmacología , Quitosano/farmacología , Coptis/química , Portadores de Fármacos , Medicamentos Herbarios Chinos/farmacología , Etanol , Evodia/química , Mucosa Gástrica/efectos de los fármacos , Úlcera Gástrica/prevención & control , Adhesividad , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antiulcerosos/química , Antiulcerosos/aislamiento & purificación , Química Farmacéutica , Quitosano/análogos & derivados , Citoprotección , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Mediadores de Inflamación/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Ratones Endogámicos ICR , Microesferas , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fitoterapia , Plantas Medicinales , Ratas Sprague-Dawley , Solubilidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain.
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Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ciclooxigenasa 2/metabolismo , Depresión/tratamiento farmacológico , Glucósidos Iridoides/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Ciclooxigenasa 2/genética , Depresión/etiología , Depresión/metabolismo , Dinoprostona/genética , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Preferencias Alimentarias , Regulación de la Expresión Génica/efectos de los fármacos , Hidrocortisona/sangre , Masculino , Ratas , Ratas Sprague-Dawley , Receptor trkB/genética , Receptor trkB/metabolismo , Estrés Psicológico/complicaciones , Sacarosa/administración & dosificaciónRESUMEN
AIM: To observe effects of trabeculectomy with amniotic membrane transplantation (AMT) in controlling postoperative intraocular pressure (IOP) in patients with medically uncontrolled glaucoma. METHODS: This study included adult patients with requiring bilateral glaucoma surgery. Each patient underwent trabeculectomy (Non-AMT group) in one eye and with AMT (AMT group) in the other eye according to randomized principle. Success was defined as intraocular pressure (IOP)<21mmHg without any anti-glaucoma medications at 24 months follow-up. The two groups were compared in terms of IOP, complications and success rate. RESULTS: Thirty-four eyes of 17 patients were investigated in this study. There was no statistically signifcant difference in pre-operative IOP between the two groups. The mean IOP was lower in AMT group compared with Non-AMT group on follow up months 12, 18, and 24.Postoperative complications were more frequent in Non-AMT group (35.3%, 6/17) compared with AMT group (5.9%, 1/17). The success rate of surgery was 88.2% (15/17) in Non-AMT group and 100% (17/17) in AMT group. CONCLUSION: Trabeculectomy with AMT is an effective procedure to reduce IOP and complications, thereby improving surgical success rates.
RESUMEN
OBJECTIVE: To investigate the influential factors for the prognosis in patients with paraquat poisoning. METHODS: Retrospective analysis was performed on 40 patients with acute paraquat poisoning to evaluate serum urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels and organ injuries. RESULTS: Among the patients, 21 had lung injury, 26 had kidney injury, 13 had multiple organ dysfunction syndrome, and 12 died. The factors associated with lung injury were kidney injury and serum urea nitrogen and creatinine levels within 24 hours after paraquat poisoning. CONCLUSION: The renal function in early stage of paraquat poisoning is related to lung injury and thus can be used asa predictor for the incidence of lung injury.
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Lesión Pulmonar/diagnóstico , Paraquat/envenenamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/diagnóstico , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
The p-sulfonatocalix[n]arenes are supposed to show potential application in the clinical treatment of viologen poisoning. In the present study, p-sulfonatocalix[4]arene (C4AS), the most common derivative of p-sulfonatocalix[n]arenes, is used to study the antidotic mechanism for paraquat (PQ) by pharmacokinetics in vivo. A high-performance liquid chromatography (HPLC) method was established to determine the concentration of PQ in rat plasma. The results showed that the peak plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-t)) were significantly lower after C4AS intervention than in the PQ intoxication group. It was considered that C4AS has great effective detoxication to PQ poisoning, and the results of in vitro intestinal absorption studies showed that C4AS can inhibit the absorption of PQ via oral administration by forming a stable inclusion constant.
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Herbicidas/farmacocinética , Inactivación Metabólica , Paraquat/farmacocinética , Animales , Área Bajo la Curva , Calixarenos , Cromatografía Líquida de Alta Presión , Herbicidas/toxicidad , Absorción Intestinal , Masculino , Paraquat/toxicidad , Fenoles , Ratas , Reproducibilidad de los ResultadosRESUMEN
The hydrolytic kinetics and degradation mechanism of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glycoside (THSG) extracted from Radix Polygoni Multiflori (a commonly used official Chinese herbal Heshouwu), were investigated using reversed-phase high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). The influences of pH (1.5-9.9), temperature (25-60°C) and irradiation on the hydrolysis of THSG were studied in aqueous solutions. The results showed that the degradation of THSG was pH-, temperature- and irradiation-dependent and all followed first-order kinetics. The effect of temperature on the rate of THSG degradation was characterized using the Arrhenius equation. Maximum stability of THSG was found at pH 1.5 (t(0.5)=47.57 d). THSG was unstable in alkaline and irradiation conditions. The active energy (E(a)) of THSG degradation in aqueous solution at pH 6.8 (most frequently adopted extract solvent) under lucifugal and irradiation conditions was 47.7kJmol(-1) and 25.3kJmol(-1), respectively. Three hydrolytic products of THSG were identified by LC-MS. Cis-trans isomerism took place under irradiation, and hydrolysis took place in acid-base conditions. Moreover, further oxidation on aglycon occurred after hydrolytic cleavage of phenolic glycoside in acidic conditions. The possible hydrolytic pathways of THSG are proposed.