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1.
Curr Biol ; 33(3): 533-542.e5, 2023 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-36657449

RESUMEN

The root nodule symbiosis with its global impact on nitrogen fertilization of soils is characterized by an intracellular colonization of legume roots by rhizobia. Although the symbionts are initially taken up by morphologically adapted root hairs, rhizobia persistently progress within a membrane-confined infection thread through several root cortical and later nodular cell layers. Throughout this transcellular passaging, rhizobia have to repeatedly pass host plasma membranes and cell walls. Here, we investigated this essential process and describe the concerted action of one of the symbiosis-specific pectin methyl esterases (SyPME1) and the nodulation pectate lyase (NPL) at the infection thread and transcellular passage sites. Their coordinated function mediates spatially confined pectin alterations in the cell-cell interface that result in the establishment of an apoplastic compartment where bacteria are temporarily released into and taken up from the subjacent cell. This process allows successful intracellular progression of infection threads through the entire root cortical tissue.


Asunto(s)
Medicago truncatula , Medicago truncatula/metabolismo , Simbiosis , Pared Celular/metabolismo , Pectinas/metabolismo , Raíces de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Nodulación de la Raíz de la Planta
2.
New Phytol ; 238(1): 25-32, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36565041

RESUMEN

Plant cells are surrounded by a structured cell wall, which not only defines cell shape but also provides a structural barrier for protection against pathogen infection. However, the presence of this barrier does not impede the establishment of mutualistic symbioses between plants and several microbes (e.g. ectomycorrhizal fungi, arbuscular mycorrhizal fungi, and rhizobia). To establish such beneficial associations, symbiotic microbes need to colonize the plant tissues via intercellular and/or intracellular infection, a process that requires cell wall modifications. Although cell wall composition and changes during this process have interested researchers for years, the functional characterization of the molecular players involved is still limited. In this viewpoint, based on several new studies, I discuss how the PME-PL/PG pathway mediates cell wall pectin modifications at the symbiotic interface and highlight further research directions which can broaden our understanding of how beneficial root symbioses are established.


Asunto(s)
Micorrizas , Rhizobium , Pectinas/metabolismo , Simbiosis , Plantas/microbiología , Raíces de Plantas/metabolismo
3.
Phytomedicine ; 106: 154399, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36057143

RESUMEN

BACKGROUND: 6-acetylacteoside (6-AA) is a phenylethanoid glycoside isolated from Cistanche deserticola which had been previously proven to possess anti-osteoporotic activity previously. Currently, it is still unknown whether 6-AA plays a crucial role on the anti-osteoporotic effects of C. deserticola. PURPOSE: To elucidate the therapeutic effect and mechanism of 6-AA on osteoporosis by employing an ovariectomized mouse model in vivo and RAW264.7 cells in vitro. METHODS: Sixty female ICR mice were randomly assigned into six groups: sham-operated control group (SHAM, vehicle), ovariectomized model group (OVX, vehicle), positive group (EV, 1 mg/kg/day of estradiol valerate), low dosage (10 mg/kg/day of 6-AA), medium dosage (20 mg/kg/day of 6-AA) and high dosage (40 mg/kg/day of 6-AA) treatment groups. All substances were administered daily by intragastric gavage. After 12 weeks of intervention, trabecular bone microarchitecture was estimated and bone biomechanics were determined. Bone formation and resorption factors were determined by using the corresponding Elisa kits. The related proteins and metabolites were estimated by using western-blot and metabolomics techniques. RESULTS: OVX mice demonstrated significant atrophy of the uterine and vagina, declined biomechanical parameters such as flexural strength and maximum load, deteriorated trabecular bone microarchitecture such as decreased BMD, BMC, TMC, TMD, BVF, Tb. N, and Tb. Th and increased Tb. Sp, as well as increased bone resorption factors such as TRAP, cathepsin K, and DPD, all after 12 weeks of ovariectomy operation. Following administration of 6-AA to OVX mice, parameters related to the bone microarchitecture, bone resorption activities as well as biomechanical properties were all significantly improved. Meanwhile, the levels of NF-κB, NFATc1, RANK, RANKL and TRAF6 were significantly downregulated, while OPG, PI3K and AKT were upregulated after 6-AA intervention. This indicates that, 6-AA could prevent bone resorption by regulating the RANKL/RANK/OPG mediated NF-κB and PI3K/AKT pathways. Furthermore, 26 different metabolites corresponding to 25 metabolic pathways were identified, and 5 of which were related to the formation of osteoporosis. Interestingly, 23 abnormal metabolites were recovered after 6-AA treatment. CONCLUSION: Our results revealed the significant anti-osteoporotic effects of 6-AA on ovariectomized mice which were probably exerted via suppression of osteoclast formation and bone resorption.


Asunto(s)
Resorción Ósea , Osteoporosis , Animales , Femenino , Ratones , Densidad Ósea , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Catepsina K/metabolismo , Estradiol/farmacología , Glicósidos/farmacología , Glicósidos/uso terapéutico , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoporosis/metabolismo , Ovariectomía/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando RANK/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-35942381

RESUMEN

Chronic kidney disease, including renal failure (RF), is a global public health problem. The clinical diagnosis mainly depends on the change of estimated glomerular filtration rate, which usually lags behind disease progression and likely has limited clinical utility for the early detection of this health problem. Now, we employed Q-Exactive HFX Orbitrap LC-MS/MS based metabolomics to reveal the metabolic profile and potential biomarkers for RF screening. 27 RF patients and 27 healthy controls were included as the testing groups, and comparative analysis of results using different techniques, such as multivariate pattern recognition and univariate statistical analysis, was applied to screen and elucidate the differential metabolites. The dot plots and receiver operating characteristics curves of identified different metabolites were established to discover the potential biomarkers of RF. The results exhibited a clear separation between the two groups, and a total of 216 different metabolites corresponding to 13 metabolic pathways were discovered to be associated with RF; and 44 metabolites showed high levels of sensitivity and specificity under curve values of close to 1, thus might be used as serum biomarkers for RF. In summary, for the first time, our untargeted metabolomics study revealed the distinct metabolic profile of RF, and 44 metabolites with high sensitivity and specificity were discovered, 3 of which have been reported and were consistent with our observations. The other metabolites were first reported by us. Our findings might provide a feasible diagnostic tool for identifying populations at risk for RF through detection of serum metabolites.

5.
Int J Mol Sci ; 23(14)2022 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-35887036

RESUMEN

Mulberry (Morus alba L.) is a flowering tree traditionally used in Chinese herbal medicine. Mulberry leaf flavonoids (MLFs) have been reported to exert important anti-inflammatory and antioxidant properties. The purpose of this study was to select the MLF with the best anti-inflammatory and antioxidative activities from MLFs eluted by different ethanol concentrations (30%, 50%, and 75%) and explore its pharmacological properties. Three types of MLFs inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells. All MLFs boosted the antioxidative capacity by decreasing the reactive oxygen species (ROS) production and the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and improving the metal ion chelating activity and reducing power. The results revealed that the MLFs eluted by 30% ethanol exhibited the best anti-inflammatory and antioxidative activities. A nontargeted metabolomic analysis was used to analyze 24 types of differential flavonoids between the MLFs. Quercetin, kaempferol, and their derivatives in 30%MLF were more abundant than the other two MLFs. Furthermore, we evaluated the pharmacological activities of 30%MLF in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. The 30%MLF could alleviate the clinical symptoms, reduce the secretion of inflammatory cytokines, and inhibit the activation of the inflammatory pathway in DSS-induced colitis mice. This study will provide valuable information for the development of MLFs eluted by 30% ethanol as a functional food.


Asunto(s)
Morus , Animales , Antiinflamatorios/análisis , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/análisis , Antioxidantes/farmacología , Citocinas/metabolismo , Sulfato de Dextran , Etanol/química , Flavonoides/análisis , Flavonoides/farmacología , Ratones , Morus/química , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Hojas de la Planta/metabolismo
6.
Oxid Med Cell Longev ; 2022: 7319563, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35578728

RESUMEN

As a traditional Chinese medicine formula, Mi-Jian-Chang-Pu decoction (MJCPD) has been successfully used in patients with language dysfunction and hemiplegia after ischemic stroke (IS). Given the excellent protective effects of MJCPD against nerve damage caused by IS in clinical settings, the present investigation mainly focused on its underlying mechanism on ischemia-reperfusion (IR) injury. Firstly, by applying the MCAO-induced cerebral IR injury rats, the efficacy of MJCPD on IS was estimated using the neurological deficit score, TTC, HE, and IHC staining, and neurochemical measurements. Secondly, an UHPLC-QTOF-MS/MS-based nontargeted metabolomics was developed to elucidate the characteristic metabolites. MJCPD groups showed significant improvements in the neurological score, infarction volume, and histomorphology, and the changes of GSH, GSSG, GSH-PX, GSSG/GSH, LDH, L-LA, IL-6, TNF-α, and VEGF-c were also reversed to normal levels after the intervention compared to the MCAO model group. Metabolomics profiling identified 21 different metabolites in the model group vs. the sham group, 10 of which were significantly recovered after treatment of MJCPD, and those 10 metabolites were all related to the oxidative stress process including glucose, fatty acid, amino acid, glutamine, and phospholipid metabolisms. Therefore, MJCPD might protect against IS by inhibiting oxidative stress during IR.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Animales , Isquemia Encefálica/tratamiento farmacológico , Disulfuro de Glutatión , Humanos , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Espectrometría de Masas en Tándem
7.
J Ethnopharmacol ; 285: 114882, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34848358

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: To explore the effective components, potential targets and neuroprotective related mechanisms of Mijianchangpu decoction (MJCPD), a well-known TCM used by the Chinese Hui minorities to treat stroke, on the prevention and treatment of ischemic stroke (IS) by using experimental models combined with network pharmacology. MATERIALS AND METHODS: The neuroprotective efficacy of MJCPD was estimated by applying the middle cerebral artery occlusion (MCAO) induced cerebral ischemia rats, and the neurological deficits score, TTC and HE staining as well as behavioral evaluation tests were employed to evaluate the beneficial effects. Meanwhile, the bioactive components of MJCPD responsible for the neuroprotective effects were identified by detecting the constituents in the brain of the MCAO rats with UHPLC-QTOF-MS/MS techniques, and these compounds were then underwent for network pharmacology analysis. Firstly, the targets of the bioactive compounds of MJCPD were predicted using Pharmmapper database, and simultaneously, the targets of IS disease were obtained from disease databases including DisGenet, OMIM, and GeneCards. Secondly, the protein-protein interaction (PPI) network between the targets and diseases were established to give the possible therapeutic targets for IS. Thirdly, the go function and KEGG pathway enrichment analysis were carried out and the compound-target-pathway network was constructed by Cytoscape software. Finally, the effective compounds, core targets and possible pathways were obtained by analyzing the connectivity of the network. More importantly, the core targets were verified by western blot experiments to validate the reliability of this study. RESULTS: MJCPD exhibited significant neuroprotective effect on IS, and 16 bioactive components of MJCPD were identified in the brain of the MCAO rats. 59 and 1982 targets related with IS disease were explored from Pharmapper and disease databases, respectively, and 32 intersecting targets were obtained as hypothetical therapeutic targets. Based on the results of the compound-target-pathway and PPI network with the degree was greater than the median, 8 effective compounds (suberic acid, epishyobunone, crocetin monomethyl ester, sfaranal, (Z)-6-octadccenoic acid, nerolidol and gurjunene) and 5 hub targets (SRC, MAPK8, MAPK14, EGFR and MAPK1) as well as 12 pathways were predicted. Western blot results showed that EGFR, p38, ERK and SRC proteins were expressed significantly different after MJCPD treatment as compared with the model group. CONCLUSION: The present study employed network pharmacology, pharmacodynamics and molecular biology techniques to predict and validate the core potential targets and signaling pathways as well as the bioactive components of MJCPD responsible for the treatment of IS. All of which are very helpful to clarify the neuroprotective mechanism of MJCPD, and obviously, the active compounds and targets in this study can also provide clues for the treatment of IS.


Asunto(s)
Isquemia Encefálica , Medicamentos Herbarios Chinos , Farmacología en Red , Fitoterapia , Accidente Cerebrovascular , Animales , Masculino , Isquemia Encefálica/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Infarto de la Arteria Cerebral Media , Nimodipina , Ratas Sprague-Dawley , Organismos Libres de Patógenos Específicos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/patología
8.
Mol Ther ; 30(2): 644-661, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-34547462

RESUMEN

Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Adenoviridae/genética , Humanos , Muerte Celular Inmunogénica , Neoplasias/terapia , Virus Oncolíticos/fisiología , Microambiente Tumoral
9.
Molecules ; 26(20)2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34684830

RESUMEN

Gynostemma pentaphyllum (Thunb.) Makino (GP), also named Jiaogulan in Chinese, was known to people for its function in both health care and disease treatment. Initially and traditionally, GP was a kind of tea consumed by people for its pleasant taste and weight loss efficacy. With the passing of the centuries, GP became well known as more than just a tea. Until now, numbers of bioactive compounds, including saponins (also named gypenosides, GPS), polysaccharides (GPP), flavonoids, and phytosterols were isolated and identified in GP, which implied the great medicinal worth of this unusual tea. Both in vivo and in vitro tests, ranging from different cell lines to animals, indicated that GP possessed various biological activities including anti-cancer, anti-atherogenic, anti-dementia, and anti-Parkinson's diseases, and it also had lipid-regulating effects as well as neuroprotection, hepatoprotective, and hypoglycemic properties. With the further development and utilization of GP, the research on the chemical constituents and pharmacological properties of GP were deepening day by day and had made great progress. In this review, the recent research progress in the bioactive compounds, especially gypenosides, and the pharmacological activities of GP were summarized, which will be quite useful for practical applications of GP in the treatment of human diseases.


Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Gynostemma/química , Plantas Medicinales/química , Animales , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Técnicas In Vitro , Estructura Molecular , Fitosteroles/aislamiento & purificación , Fitosteroles/farmacología , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Saponinas/aislamiento & purificación , Saponinas/farmacología , Relación Estructura-Actividad
10.
Artículo en Inglés | MEDLINE | ID: mdl-34471418

RESUMEN

Kava (Piper methysticum Forst) is a popular and favorable edible medicinal herb which was traditionally used to prepare a nonfermented beverage with relaxant beneficial for both social and recreational purposes. Numerous studies conducted on kava have confirmed the presence of kavalactones and flavokawains, two major groups of bioactive ingredients, in this miraculous natural plant. Expectedly, both kavalactone and flavokawain components exhibited potent antianxiety and anticancer activities, and their structure-activity relationships were also revealed. However, dozens of clinical data revealed the hepatotoxicity effect which is indirectly or directly associated with kava consumption, and most of the evidence currently seems to point the compounds of flavokawains in kava were responsible. Therefore, our aim is to conduct a systematic review of kavalactones and flavokawains in kava including their biological activities, structure-activity relationships, and toxicities, and as a result of our systematic investigations, suggestions on kava and its compounds are supplied for future research.

11.
Food Funct ; 12(16): 7546-7556, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34227645

RESUMEN

The preventive and therapeutic effects of dark tea fermented by Eurotium cristatum (DTE) in glucose metabolism have been demonstrated. However, few studies have investigated comprehensive changes in the chemical composition and activity in DTE before and after fermentation. In this study, the metabolic profiling of raw samples and fermented samples was determined by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). Furthermore, a systematic analytical strategy combining global metabolomics and the spectrum-effect relationship based on α-glucosidase inhibition was employed for screening discriminant metabolites. As a result, 15 discriminant metabolites were identified in DTE samples. Among them, 10 metabolites (4 fatty acids, 1 dyphylline derivative, 3 lysophosphatidylcholines, and 2 triterpenes) increased in relative contents and the contents of the other 5 polyphenol metabolites decreased after fermentation. These metabolites were critical constituents possibly associated with DTE's hypoglycemic activity, which also might be suitable as quality evaluation indicators. This study provided a worthy insight into the exploration of representative active constituents or quality indicators of DTE.


Asunto(s)
Aspergillus/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Hipoglucemiantes/metabolismo , Espectrometría de Masas en Tándem/métodos , Té/metabolismo , Aspergillus/química , Reactores Biológicos , Fermentación , Hipoglucemiantes/química , Metabolómica , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Té/química
12.
J Sep Sci ; 44(14): 2705-2716, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33951745

RESUMEN

Kava, the rhizomes and roots of Piper methysticum Forst, is a popular edible medicinal herb traditionally used to prepare beverages for anxiety reduction. Since the German kava ban has been lifted by the court, the quality evaluation is particularly important for its application, especially the flavokawains which were believed to be responsible for hepatotoxicity. Now, by employing two different standard references and four different methods to calculate the relative correction factors, eight different quantitative analyses of multicomponents by single-marker methods have been developed for the simultaneous determination of eight major kavalactones and flavokawains in kava. The low standard method difference on quantitative measurement of the compounds among the external standard method and ours confirmed the reliability of the mentioned methods. A radar plot clearly illustrated that the contents of dihydrokavain and kavain were higher, whereas flavokawains A and B were lower in different kava samples. Only one of eight samples did not detect flavokawains that may be related to hepatotoxicity. In summary, by using different agents as an internal standard reference, the developed methods were believed as a powerful analytical tool not only for the qualitative and quantitative of kava constituents but also for the other multicomponents when authentic standard substances were unavailable.


Asunto(s)
Chalcona/análogos & derivados , Kava/química , Pironas , Chalcona/análisis , Chalcona/química , Cromatografía Líquida de Alta Presión/métodos , Suplementos Dietéticos , Lactonas/análisis , Lactonas/química , Fitoterapia , Extractos Vegetales/análisis , Extractos Vegetales/química , Raíces de Plantas/química , Plantas Medicinales , Pironas/análisis , Pironas/química
13.
J Food Sci ; 85(9): 2933-2942, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32794200

RESUMEN

Fuzhuan Brick-Tea is a postfermented product with the hypoglycemic effect, which is prepared from the leaves of Camellia sinensis var. sinensis. However, the material basis associated with the hypoglycemic effect was not clear. The present research was designed to explore the hypoglycemic effect of extract/fractions from Fuzhuan Brick-Tea in streptozotocin-induced type II diabetic mice. Then an ultra-high pressure liquid chromatography along with quadrupole time of flight mass spectrometry was used to analyze the phytochemicals in Fuzhuan Brick-Tea fractions. As a result, the hypoglycemic and hypolipidemic effects were evidently observed from the serum biochemical indexes and liver pathological examination in type II diabetic mice. In addition, there were total of 20 major components including eight lysophosphatidylcholines (Lyso-PCs), five fatty acids, and seven novel theophylline derivatives tentatively identified in the active fraction from water extract. Therefore, these components were assumed to contribute partly to the hypoglycemic effect of Fuzhuan Brick-Tea. These findings also give the evidence that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. PRACTICAL APPLICATION: This study suggests that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. It can be taken as a beneficial diet additive or nutraceutical.


Asunto(s)
Camellia sinensis/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Extractos Vegetales/administración & dosificación , Animales , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Experimental/metabolismo , Ácidos Grasos/metabolismo , Fermentación , Humanos , Hipoglucemiantes/química , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Ratones , Extractos Vegetales/química , Hojas de la Planta/química , Estreptozocina , Espectrometría de Masas en Tándem/métodos , Té/química
14.
Turk J Med Sci ; 50(5): 1444-1453, 2020 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-32252500

RESUMEN

Background/aim: Drynaria fortunei (Gusuibu; GSB) is a popular traditional Chinese medicine used for bone repair. An increasing number of studies have reported that GSB induces osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). These results provide insight into the application of GSB for bone tissue engineering techniques used to repair large bone defects. However, few studies have described the molecular mechanisms of GSB. Materials and methods: In the present study, the effects of GSB and naringin, a marker compound, on the binding of BMP-2 to BMPR and BMP-2-derived signal transduction were investigated using surface plasmon resonance (SPR) and coculturing with BMPR- expressed cell line, C2C12, respectively. Furthermore, naringin was also used to prepare naringin contained scaffolds for bone tissue engineering. The physical and chemical properties of these scaffolds were analysed using scanning electron microscopy (SEM) and highperformance liquid chromatography (HPLC). These scaffolds were cocultured with rabbit BMSCs in vitro and implanted into rabbit calvarial defects for bone repair assessment. Results: The results showed that GSB and naringin affect the binding of BMP and BMPR in SPR experiments. GSB is a subtle BMP modulator that simultaneously inhibits the binding of BMP-2 to BMPR-1A and enhances its binding to BMPR-1B. In contrast, naringin inhibited BMP-2 binding to BMPR-1A. In vitro studies involving the phosphorylation of signals downstream of BMPR and Smad showed that GSB and naringin affected stem cell differentiation by inhibiting BMPR-1A signalling. When using GSB for bone tissue engineering, naringin exhibited a higher capacity for slow and gradual release from the scaffold, which promotes bone formation via osteoinduction. Moreover, control and naringin scaffolds were implanted into rabbit calvarial defects for 4 weeks, and naringin enhanced bone regeneration in vivo significantly. Conclusions: GSB and its marker compound (naringin) could inhibit the binding of BMP-2 and BMPR-1A to control cell differentiation by blocked BMPR-1A signalling and enhanced BMPR-1B signalling. GSB and naringin could be good natural BMP regulators for bone tissue engineering.


Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Flavanonas/farmacología , Polypodiaceae/química , Ingeniería de Tejidos/métodos , Animales , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Huesos/efectos de los fármacos , Huesos/metabolismo , Células Cultivadas , Masculino , Osteogénesis/efectos de los fármacos , Conejos , Transducción de Señal/efectos de los fármacos
15.
Exp Biol Med (Maywood) ; 242(1): 92-101, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27510582

RESUMEN

Ocular complications associated with diabetes mellitus are progressive and becoming one of the most important causes of morbidity worldwide. The purpose of the study is to evaluate the protective effect of Polygonatum sibiricum polysaccharide, an important component of Polygonatum sibiricum, on ocular complications in streptozotocin-induced diabetes mellitus rats. Sprague Dawley rats were made diabetic with streptozotocin(60 mg/kg, i.v.) and then the rats were treated with Polygonatum sibiricum polysaccharide 200, 400 and 800 mg/kg.d by gavage for 12 weeks. Biochemical analysis indicated that Polygonatum sibiricum polysaccharide lowered the levels of fasting blood glucose and glycated hemoglobin in blood and elevated the levels of insulin and C-peptide in plasma of diabetes mellitus rats in a dose-dependent manner. Physical measurements revealed that Polygonatum sibiricum polysaccharide improved clinical symptoms of polydipsia, polyphagia, polyuria and weight loss in diabetes mellitus rats. The content of malondialdehyde and activity of superoxide dismutase in plasma were determined, and the data showed Polygonatum sibiricum polysaccharide suppressed oxidative stress reaction. Lens opacification was observed using slit lamp illumination, and the data showed Polygonatum sibiricum polysaccharide delayed cataract progression in a dose-dependent manner. Electroretinogram showed Polygonatum sibiricum polysaccharide treatment reversed the decrease of electroretinogram b and OPs2 waves' amplitudes. Flash-visual evoked potential test indicated that the peak time of P2 wave was prolonged, and the amplitude of N2-P2 was lowered in diabetes mellitus group, and Polygonatum sibiricum polysaccharide suppressed these changes. Fundus fluorescein angiography showed Polygonatum sibiricum polysaccharide alleviated the retinal vasculopathy in a dose-dependent manner. In conclusion, these results suggest that the administration of Polygonatum sibiricum polysaccharide slows the progression of diabetic retinopathy and cataract through alleviating hyperglycemia and reducing oxidative stress in streptozotocin-induced diabetes mellitus rats.


Asunto(s)
Catarata/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Hipoglucemiantes/farmacología , Polygonatum/química , Polisacáridos/farmacología , Animales , Catarata/etiología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/tratamiento farmacológico , Electrorretinografía , Potenciales Evocados Visuales/efectos de los fármacos , Glucosa/metabolismo , Hemoglobina Glucada/metabolismo , Masculino , Plantas Medicinales/química , Polidipsia/tratamiento farmacológico , Polidipsia/etiología , Poliuria/tratamiento farmacológico , Ratas Sprague-Dawley , Estreptozocina
16.
Int J Nanomedicine ; 11: 4583-4594, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27695319

RESUMEN

Osteoporosis is a result of imbalance between bone formation by osteoblasts and resorption by osteoclasts (OCs). In the present study, we investigated the potential of limiting the aggravation of osteoporosis by reducing the activity of OCs through thermolysis. The proposed method is to synthesize bisphosphonate (Bis)-conjugated iron (II, III) oxide (Fe3O4) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe3O4 were first synthesized by chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe3O4 particles were then conjugated with Bis to form Bis/Dex/Fe3O4. Transmission electron microscopy revealed that the average diameter of the Bis/Dex/Fe3O4 particles was ~20 nm. All three kinds of nanoparticles were found to have cubic inverse spinel structure of Fe3O4 by the X-ray diffraction analysis. Fourier transform infrared spectroscopy confirmed that the Dex/Fe3O4 and Bis/Dex/Fe3O4 nanoparticles possessed their respective Dex and Bis functional groups, while a superconducting quantum interference device magnetometer measured the magnetic moment to be 24.5 emu. In addition, the Bis/Dex/Fe3O4 nanoparticles were fully dispersed in double-distilled water. Osteoblasts and OCs were individually cultured with the nanoparticles, and an MTT assay revealed that they were non-cytotoxic. An RF system (42 kHz and 450 A) was used to raise the temperature of the nanoparticles for 20 minutes, and the thermal effect was found to be sufficient to destroy OCs. Furthermore, in vivo studies verified that nanoparticles were indeed magnetic resonance imaging contrast agents and that they accumulated after being injected into the body of rats. In conclusion, we developed a water-dispersible magnetic nanoparticle that had RF-induced thermogenic properties, and the results indicated that the Bis/Dex/Fe3O4 nanoparticle had the potential for controlling osteoporosis.


Asunto(s)
Alendronato/farmacología , Nanopartículas de Magnetita/química , Osteoporosis/tratamiento farmacológico , Alendronato/química , Animales , Células Cultivadas , Precipitación Química , Medios de Contraste/química , Dextranos/química , Óxido Ferrosoférrico/química , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/administración & dosificación , Masculino , Ratones , Microscopía Electrónica de Transmisión , Osteoclastos/efectos de los fármacos , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Difracción de Rayos X
17.
Mol Med Rep ; 13(2): 1257-62, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26647727

RESUMEN

Neurodegenerative diseases are frequently associated with the loss of synapses and neurons. Senegenin, extracted from the Chinese herb Polygala tenuifolia Willd, was previously found to promote neurite outgrowth and neuronal survival in primary cultured rat cortical neurons. The aim of the present study was to investigate the underlying mechanisms of senegenin-induced neurotrophic effects on rat cortical neurons. Primary cortical rat neurons were treated with various pharmacological antagonists and with or without senegenin, and subjected to MTT and western blot analysis to explore the effects of senegenin on cell survival as well as the activation of signaling pathways. Neurite outgrowth and neuronal survival induced by senegenin were significantly inhibited by A2A receptor antagonist ZM241385 and specific phosphoinositide-3 kinase (PI3K) inhibitor LY294002, but not by tropomyosin receptor kinase A receptor inhibitor K252a, mitogen-activated protein kinase kinase inhibitor PD98059 or protein kinase C inhibitor GÖ6976. Furthermore, senegenin enhanced the phosphorylation of Akt, which was blocked by LY294002. The present study revealed that the PI3K/Akt signaling pathway may be involved in the neurotrophic effects of senegenin.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/biosíntesis , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Animales , Supervivencia Celular/efectos de los fármacos , Cromonas/administración & dosificación , Medicamentos Herbarios Chinos/química , Humanos , Morfolinas/administración & dosificación , Neuritas/efectos de los fármacos , Neuritas/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Neuronas/patología , Fosfatidilinositol 3-Quinasas/genética , Polygala/química , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Transducción de Señal/efectos de los fármacos , Triazinas/administración & dosificación , Triazoles/administración & dosificación
18.
Sci Rep ; 5: 16427, 2015 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-26553557

RESUMEN

Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.


Asunto(s)
Adyuvantes Inmunológicos , Vacunas contra el Cáncer/inmunología , Células Dendríticas/inmunología , Neoplasias/inmunología , Ácido Úrico , Traslado Adoptivo , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Citocinas/metabolismo , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Femenino , Inmunización , Inmunoglobulinas/administración & dosificación , Interferón gamma , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Activación de Linfocitos/inmunología , Ratones , Neoplasias/metabolismo , Neoplasias/mortalidad , Neoplasias/terapia , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Ácido Úrico/administración & dosificación , Ácido Úrico/inmunología , Ácido Úrico/metabolismo
19.
Schizophr Res ; 129(2-3): 97-103, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21458957

RESUMEN

OBJECTIVE: To estimate the incidence and relative risk of developing cancer as well as the mortality rate after cancer diagnosis for patients with schizophrenia compared with the general population. METHODS: Our population for this study was identified before the end of 1999. The study included 59,257 patients with schizophrenia and 178,156 age- and gender-matched individuals without schizophrenia as controls, who were selected from the 23,981,020 subjects in the National Health Insurance Research Database (NHIRD), which consists of 96% of the entire Taiwanese population. From the 2000 to 2008 NHIRD, we calculated the cancer incidence and survival time after cancer diagnosis in each of the two groups. Based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), the cancers were divided into nine groups. RESULTS: During the nine-year follow-up period, 1145 (1.93%) of the patients with schizophrenia and 5294 (2.97%) of the control group developed cancer. The patients with schizophrenia had a significantly lower cancer incidence than those in the control group in both the male (OR=0.50, 95% CI, 0.46-0.55) and female (OR=0.81, 95% CI, 0.74-0.88) populations. Patients with schizophrenia were less likely to develop cancer than individuals in the control group for every cancer type except breast and cervical/uterine cancer. After adjustment using the Cox regression model, patients with schizophrenia had an overall decreased cancer risk (adjusted hazard ratio 0.71, 95% CI, 0.66-0.76) compared to the control population. For all cancer patients, the mortality adjusted hazard ratio for patients with schizophrenia versus the control group was 1.36 (95% CI, 1.24-1.50) after adjusting for other variables. CONCLUSIONS: Although the likelihood of developing cancer among patients with schizophrenia (0.64) was less than that of the non-schizophrenia group, the mortality rate among patients with schizophrenia was higher than that of the control group.


Asunto(s)
Neoplasias/epidemiología , Esquizofrenia/epidemiología , Femenino , Humanos , Incidencia , Clasificación Internacional de Enfermedades/estadística & datos numéricos , Estudios Longitudinales , Masculino , Programas Nacionales de Salud/estadística & datos numéricos , Neoplasias/clasificación , Neoplasias/economía , Neoplasias/mortalidad , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Factores de Riesgo , Esquizofrenia/economía , Taiwán/epidemiología
20.
Chin J Integr Med ; 16(4): 348-52, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20697947

RESUMEN

OBJECTIVE: To observe the efficacy of retention enema with Huchang Jiedu Decoction (, HJD) in treating chronic severe hepatitis B (CSHB). METHODS: Sixty patients of CSHB were equally randomized into the treated group and the control group. Both groups were treated with conventional integrative medicine, but to patients in the treated group, retention enema with HJD was given in addition, once every day for 3 weeks. The dominant symptoms, physical signs, and related biochemical indices, as well as the incidence of complications in patients before and after treatment, were observed. RESULTS: Good therapeutic effects were shown in the treated group, with a total effective rate better than that in the control group (83.3% versus 60.0%, P<0.05), superior in terms of lowering alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), globulin (Glb), and endotoxin (ET) levels and increasing prothrombin activity (PTA), total cholesterol (TC), and calcium (Ca) levels, as well as eliminating ascites and preventing hepatic encephalopathy (P<0.05); especially in treating middle/early stage patients with Chinese medicine syndrome differentiated as water-toxin accumulation pattern. CONCLUSION: Retention enema with HJD is surely effective in treating CSHB, and its primary mechanism may be related to the mitigation of enterogenous endotoxemia.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Enema , Hepatitis B Crónica/tratamiento farmacológico , Adulto , Anciano , Ascitis/metabolismo , Medicamentos Herbarios Chinos/efectos adversos , Endotoxinas/sangre , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Resultado del Tratamiento
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