RESUMEN
Herein we report a strategy concerning Rh(III)-catalyzed direct ortho-C-H bond carbonylation to construct benzoxazinones from anilines and their derivatives with high atom economy. Interestingly, the corresponding amides were generated in situ from anilines when excess Ac2O was added and directed the following C-H bond carbonylation to form benzoxazinones. Extensive functional group tolerance can be achieved when the alkyl amide directing groups were installed. Moreover, this method allows convenient derivatization of some drugs with aryl amine groups to show its potential application.
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Compuestos de Anilina , Benzoxazinas , Estructura Molecular , Compuestos de Anilina/química , Catálisis , Amidas/químicaRESUMEN
We report the preparation of multivalent amide-sialoside-decorated human serum albumin (HSA) and bovine serum albumin (BSA) as mimics of natural mucin and bioshields against influenza virus infection. Free sialic acid with an amine on C-2 was covalently attached to the protein scaffolds using di-(N-succinimidyl) adipate. Dynamic light scattering (DLS) showed that the synthetic neomucins were able to act as bioshields and aggregate the influenza virion particles. The dissociation constants (KD) of the interactions between the prepared glycoconjugates and three different viral strains were measured by isothermal titration calorimetry (ITC) indicating the multivalent presentation of sialyl ligands on the HSA and BSA backbones can dramatically enhance the adsorbent capability compared to the corresponding monomeric sialoside. Hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) assays showed that the glycoconjugates acted as moderate HA and NA inhibitors, thus impeding viral infection. Moreover, the different binding affinities of the glycoproteins to HA and NA proteins from different influenza viruses demonstrated the importance of HA/NA balance in viral replication and evolution. These findings provide a foundation for the development of antiviral drugs and viral adsorbent materials based on mimicking the structure of mucin.
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Antivirales/farmacología , Glicerol/farmacología , Gripe Humana/prevención & control , Mucinas/metabolismo , Orthomyxoviridae/efectos de los fármacos , Estearatos/farmacología , Amidas/química , Amidas/farmacología , Animales , Antivirales/química , Bovinos , Combinación de Medicamentos , Glicerol/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Estructura Molecular , Mucinas/química , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/metabolismo , Albúmina Sérica Bovina/metabolismo , Albúmina Sérica Humana/metabolismo , Ácidos Siálicos/química , Ácidos Siálicos/farmacología , Estearatos/químicaRESUMEN
BACKGROUND: Extreme lumbar spinal stenosis was thought to be a relative contraindication for lateral lumbar interbody fusion (LLIF) and was excluded in most studies. This is a retrospective study to analyze the radiographic and clinical outcome of LLIF for extreme lumbar spinal stenosis of Schizas grade D. METHODS: For radiographic analysis, we included 181 segments from 110 patients who underwent LLIF between June 2017 and December 2018. Lumbar spinal stenosis was graded according to Schizas' classification. Anterior and posterior disc heights, disc angle, foramen height, spinal canal diameter and central canal area were measured on CT and MRI. For clinical analysis, 18 patients with at least one segment of grade D were included. Visual analogue scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate clinical outcome. Continuous variables were compared using Student's t-test, with P-values < 0.05 considered to indicate statistically significant differences. RESULTS: Among the 181 segments included for radiological evaluation, there were 23 grade A segments, 37 grade B segments, 103 grade C segments and 18 grade D segments. Postoperatively, the average change of midsagittal canal diameter of grade D was significantly greater than that of grade A, and not significantly different compared to grades B and C. As to the average change of disc height, bilateral foraminal height, disc angle and central canal area (CCA), grade D was not significantly different from the others. The average postoperative CCA of grade D was significantly smaller than the average preoperative CCA of grade C. Eighteen patients with grade D stenosis were followed up for an average of 19.61 ± 6.32 months. Clinical evaluation revealed an average improvement in the ODI and VAS scores for back and leg pain by 20.77%, 3.67 and 4.15 points, respectively. Sixteen of 18 segments with grade D underwent posterior decompression. CONCLUSION: The radiographic decompression effect of LLIF for Schizas grade D segments was comparable with that of other grades. Posterior decompression was necessary for LLIF to achieve a satisfactory clinical outcome for extreme lumbar spinal stenosis of Schizas grade D.
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Descompresión Quirúrgica/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Fusión Vertebral/métodos , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Anciano , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
In order to make a further optimization of process design via increasing the stability of design space, we brought in the model of Support Vector Regression (SVR). In this work, the extraction of podophyllotoxin was researched as a case study based on Quality by Design (QbD). We compared the fitting effect of SVR and the most used quadratic polynomial model (QPM) in QbD, and an analysis was made between the two design spaces obtained by SVR and QPM. As a result, the SVR stayed ahead of QPM in prediction accuracy, the stability of model and the generalization ability. The introduction of SVR into QbD made the extraction process of podophyllotoxin well designed and easier to control. The better fitting effect of SVR improved the application effect of QbD and the universal applicability of SVR, especially for non-linear, complicated and weak-regularity problems, widened the application field of QbD.
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Podofilotoxina/química , Algoritmos , Diseño de Fármacos , Modelos EstadísticosRESUMEN
Pinellia ternata (PT) is a widely used traditional Chinese medicine. The raw material has a throat-irritating toxicity that is associated with the PT lectin (PTL). PTL is a monocot lectin isolated from the tubers of PT, which exhibits mouse peritoneal acute inflammatory effects in vivo. The present study aimed to investigate the pro-inflammatory effect of PTL on macrophages. PTL (50 µg/ml)stimulated macrophages enhanced the chemotactic activity of neutrophils. PTL (50, 100, 200 and 400 µg/ml) significantly elevated the production of cytokines [tumor necrosis factorα (TNF-α) , interleukin (IL)1ß and IL6]. PTL (25, 50 and 100 µg/ml) induced intracellular reactive oxygen species (ROS) overproduction. PTL also caused transfer of p65 from the macrophage cytoplasm to the nucleus and activated the nuclear factorκB (NFκB) signaling pathway. Scanning electron microscope images revealed severe cell swelling and membrane integrity defection of macrophages following PTL (100 µg/ml) stimulation, which was also associated with inflammation. PTL had proinflammatory activity, involving induced neutrophil migration, cytokine release, ROS overproduction and the activation of the NF-κB signaling pathway, which was associated with the activation of macrophages.
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Citocinas/biosíntesis , Macrófagos Peritoneales/metabolismo , Pinellia/química , Lectinas de Plantas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Animales , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Macrófagos Peritoneales/patología , Masculino , Ratones , Ratones Endogámicos ICR , Lectinas de Plantas/químicaRESUMEN
To explore the antagonistic effect of gingerols against the inflammation induced by lectin from Pinellia ternata. In this study, ELISA method was used to determine the effect of different extracts from gingerols on the release of inflammatory factor TNF-α from macrophages induced by lectin from P. ternata. The fluorescence probe was used to determine the effect of gingerols on the changes in ROS of macrophages induced by lectin from P. ternata. The western-blot method was applied to study the effect of gingerols on the increase in expression of cell receptor interacting protein RIP3 in macrophages induced by lectin from P. ternata. The scanning electron microscope (SEM) was used to study the effect of gingerols on morphological changes in macrophages induced by lectin from P. ternata. According to the results, gingerols can significantly inhibit the release of inflammatory factor from macrophages induced by lectin from P. ternata, ROS overproduction and increase in RIP3 expression. SEM results showed that gingerols can inhibit the cytomorphosis and necrocytosis induced by lectin from P. ternata. Fresh ginger's detoxication may be related to gingerols' effects in inhibiing release of inflammatory factor, ROS overproduction and increase in RIP3 expression caused by macrophages induced by lectin from P. ternata, which are mainly inflammatory development.
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Catecoles/farmacología , Alcoholes Grasos/farmacología , Lectinas/toxicidad , Macrófagos/efectos de los fármacos , Pinellia/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Factor de Necrosis Tumoral alfa/metabolismo , Zingiber officinale/química , Animales , Células Cultivadas , Antagonismo de Drogas , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Pinellia/química , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OBJECTIVE: To extract and separate toxic components from Phytolaccae Radix, and to comare the changes in toxicity of Phytolaccae Radix before and after being processed with vinegar. METHOD: The mucous membrane irritation response, mouse peritoneal inflammation model and in vitro macrophages release NO model were applied to compared the changes in inflammatory toxicity of toxic components from Phytolaccae Radix before and after being processed with vinegar. RESULT: Toxic components of Phytolacca Radix had significant inflammatory toxicity, which could cause conjunctival edema in rabbits, and increase of PGE2 and macrophages release NO content in peritoneal exudate in mice. After being processed with vinegar, they showed reduced irritation, which resulted in decrease of PGE2 and macrophages release NO content in peritoneal exudate in mice. CONCLUSION: After being processed with vinegar, the toxicity of toxic components from Phytolacca Radix decreased obviously.
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Química Farmacéutica/métodos , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/toxicidad , Phytolacca/química , Ácido Acético/química , Animales , Ojo/efectos de los fármacos , Ojo/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , ConejosRESUMEN
Serratia marcescens strain JPP1 was isolated from peanut hulls in Huai'an city, Jiangsu Province, China. Its potential to inhibit the mycelial growth of Aspergillus parasiticus and the subsequent aflatoxin production was evaluated. The strain JPP1 could produce chitinase to degrade fungal cell walls, which was the main mechanism of strain JPP1 for biocontrol. Scanning electron microscopy of fungi treated with the crude chitinase revealed abnormal morphological changes. While the strain was grown in the peanut hulls-based medium, the chitinase activity reached 7.39 units. RT-PCR analysis showed that the crude chitinase repressed the transcription of genes involved in the aflatoxin gene cluster, such as aflR, aflC (pksL1), and aflO (dmtA) genes. By visual agar plate assay and tip culture method, the strain JPP1 exhibited remarkable inhibitory effect on mycelia growth (antifungal ratio >95%) and subsequent aflatoxin production (antiaflatoxigenic ratio >98%). An in vitro assay with seed coating agent of bacterial suspension showed that strain JPP1 effectively reduced fungal growth and subsequent aflatoxin production on peanut seeds, and its antagonistic effect was superior to the common agricultural fungicide of carbendazim. These characteristics suggest that S. marcescens JPP1 strain could potentially be utilized for the biological control of phytopathogenic fungi and aflatoxin in Chinese peanut main producing areas.
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Aflatoxinas/metabolismo , Aspergillus/fisiología , Quitina/metabolismo , Serratia marcescens/fisiología , Antifúngicos/farmacología , Aspergillus/efectos de los fármacos , Aspergillus/genética , Secuencia de Bases , Quitinasas/metabolismo , Regulación Fúngica de la Expresión Génica , Genes Fúngicos/genética , Micelio/efectos de los fármacos , Micelio/crecimiento & desarrollo , Micelio/ultraestructura , Control Biológico de Vectores , Filogenia , ARN Ribosómico 16S/genética , Serratia marcescens/efectos de los fármacos , Serratia marcescens/genética , Serratia marcescens/ultraestructuraRESUMEN
OBJECTIVE: To study the toxic mechanism of toxic raphides from Pinellia ternata. METHOD: Mouse peritoneal macrophage in vitro culture model was adopted to study dose-dependent and time-dependent curves of toxic raphides, with TNF-alpha, IL-1beta and IL-6 in supernatant as indexes. Scanning electron microscopy was used to observe the changes in surface morphology of raphides-treated macrophages. Macrophages-neutrophils co-cultured the transport model to study the effect of toxic raphides' stimulation of macrophages on neutrophils migration. RESULT: Toxic raphides' stimulation of macrophages could cause the increase in the levels of TNF-alpha, IL-1beta and IL-6 released, and showed dose dependence and time dependence. Scanning electron microscopy showed that toxic raphides were swallowed by macrophages, with notable cell membrane creases, increase in the number of pseudopods and decrease in integrity of cell membranes, and could significantly induce migration of neutrophils. CONCLUSION: The inflammatory process induced by toxic raphides is mainly mediated by macrophages. The toxic mechanism of toxic raphides from P. ternata is that toxic raphides penetrate into tissues to activate resident macrophages, release phagocytic and inflammatory cytokines, and cause migration of neutrophils, which finally results in acute inflammatory response.
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Medicamentos Herbarios Chinos/toxicidad , Mediadores de Inflamación/toxicidad , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Pinellia/química , Animales , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVE: To explore the pro-inflammatory toxicity of Pinellia pedatiecta, as well as the alum processing method on its pro-inflammatory effect. METHOD: Raphide and agglutinin (PPA) proteins were isolated from fresh P. pedatiecta. The overall animal and cellular level models were applied to investigate the pro-inflammatory effect of raphide and PPA in P. pedatiecta, as well as the impact of the alum processing method on the pro-inflammatory effect, with inflammatory mediators as the index. RESULT: Intraperitoneal injection with P. pedatiecta raphide suspension could significantly increase the content of inflammatory mediators PGE2 and NO. After the alum processing method was adopted, fresh P. pedatiecta and raphide-induced PGE2 and NO release significantly reduced. The stimulation of mice macrophages with P. pedatiecta agglutinin protein could cause the content of dose-dependent inflammatory mediators TNF-alpha and IL-6. After the alum processing method was adopted, PGE2 content in P. pedatiecta agglutinin protein-induced mice peritoneal exudate notably decreased. CONCLUSION: The irritation and toxicity of P. pedatiecta were inflammatory responses in organisms. Its raphide and agglutinin proteins were toxic components, both could cause significant the release of inflammatory medium. The alum processing method could help significantly reduce the pro-inflammatory toxicity of P. pedatiecta.
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Composición de Medicamentos/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/toxicidad , Mediadores de Inflamación/química , Mediadores de Inflamación/toxicidad , Pinellia/química , Compuestos de Alumbre/química , Animales , Femenino , Interleucina-6/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones Endogámicos ICR , Pinellia/efectos adversos , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Repair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly (lactic-co-glycolic acid) (PLGA) to promote new bone formation within rabbit ulnar segmental bone defects. METHODS: Rabbit bone marrow-derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental bone defects, each 15 mm in length, were created in the rabbit ulna, from which periosteum was obtained. Bone defects were treated with either PLGA alone (group A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum-wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were detected by gross observation, radiological examination (X-ray and micro-CT) and histological analyses. RESULTS: Group D, comprising both periosteum and MSCs, showed better bone quality, higher X-ray scores and a greater amount of bone volume compared with the other three groups at each time point (P < 0.05). No significant differences in radiological scores and amount of bone volume were found between groups B and C (P > 0.05), both of which were significantly higher than group A (P < 0.05). CONCLUSIONS: Implanted MSCs combined with periosteum have a synergistic effect on segmental bone regeneration and that periosteum plays a critical role in the process. Fabrication of angiogenic and osteogenic cellular constructs or tissue-engineered periosteum will have broad applications in bone tissue engineering.
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Ácido Láctico/química , Células Madre Mesenquimatosas/citología , Periostio/citología , Ácido Poliglicólico/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Regeneración Ósea/fisiología , Células Cultivadas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , ConejosRESUMEN
OBJECTIVE: To analyze the potential association between the single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF) gene with the risk of endometriosis by meta-analysis. METHODS: Published case-control studies about the influence of VEGF polymorphisms on endometriosis were searched and screened in Medline, the Cochrane library, China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM), data base of Wanfang and Foreign Medical Journal Full-Text Service (FMJS). RevMan 5.0 software was used for meta-analysis. RESULTS: Finally, there were 9 literatures including 1610 endometrisis patients and 1643 controls cases, which were eligible for the criteria to investigating the VEGF SNP about -460C/T, +405C/G and +936C/T. The results of meta-analysis showed that there was no evidence for association between endometriosis and the VEGF -460C/T SNP in the genotype or allele frequencies distribution (P > 0.05). Significant differences were found between the frequencies distribution of VEGF +405CC genotype (P = 0.009, OR = 1.45, 95%CI: 1.10 - 1.91) and +405C allele (P = 0.020, OR = 1.19, 95%CI: 1.03 - 1.38), also between the +936CC genotype (P = 0.050, OR = 0.81, 95%CI: 0.66 - 1.00) and +936T allele (P = 0.040, OR = 1.20, 95%CI: 1.01 - 1.43). CONCLUSIONS: The VEGF +405C/G and +936C/T SNP may be associated with the risk of endometriosis. Women carrying the +405C or the +936T allele could significantly increase the risk of developing endometriosis.
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Endometriosis/genética , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular/genética , Alelos , Estudios de Casos y Controles , Endometriosis/patología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Humanos , Factores de RiesgoRESUMEN
OBJECTIVE: To assess the experimental and clinical data regarding the effects of electromagnetic fields (EMFs) on fracture non-union. DATA SOURCES: The English language literature regarding EMFs on fracture non-union were searched using MEDLINE, Web of Science and Embase, for the period January 2006 to June 2011. The search terms were electromagnetic fields and non-union/bone marrow stem cells (BMSCs)/bone. STUDY SELECTION: Articles were included in the review if they were related to the use of EMFs on BMSCs or bone tissue. Papers without full manuscripts available were excluded. RESULTS: The basic and clinical research in this field, while somewhat limited, supports the insightful application of EMFs to ameliorate disability due to fracture non-union. CONCLUSIONS: Further basic and clinical research to validate the use of EMFs in facilitating function and bone reparative processes in fracture non-union is required.
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Regeneración Ósea/fisiología , Campos Electromagnéticos , Animales , HumanosRESUMEN
The monocot lectin from the tubers of Arisaema erubescens (Wall.) Schott has been purified by consecutive hydrophobic chromatography and ion exchange chromatography methods. The molecular weight of this A. erubescens lectin (AEL) was determined to be about 12 kDa by high performance liquid chromatography (HPLC) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) methods. AEL could agglutinate rabbit erythrocytes. The haemagglutination activity of AEL was only inhibited by asialofetuin, while monosaccharide did not react. Rat paw edema and neutrophil migration models were used to investigate the pro-inflammatory activity of AEL. AEL (100 and 200 µg/paw) could induce significant rat paw edema. In addition, AEL (100, 200 and 300 µg/mL/cavity) could induce significant and dose-dependent neutrophil migration in the rat peritoneal cavities. Besides, AEL at doses ranging from 100 to 300 µg/mL/cavity could significantly increase the concentration of nitric oxide (NO), prostaglandin E(2 )(PGE(2)) and tumor necrosis factor alpha (TNF-α) in peritoneal fluid. As compared with control animals, 75% depletion in the number of resident cells following peritoneal lavage did not reduce the AEL-induced neutrophil migration. However, pre-treatment with 3% thioglycollate which increased the peritoneal macrophage population by 201%, enhanced the neutrophil migration induced by AEL (200 µg/mL/cavity) (p < 0.05). Reduction of peritoneal mast cell population by chronic treatment of rat peritoneal cavities with compound 48/80 (N-methyl-p-methoxyphenethylamine with formaldehyde) did not modify AEL-induced neutrophil migration. The results provided the basis for identifying the toxic components of A. erubescens and AEL could be a new useful tool for pro-inflammatory research.