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1.
Prep Biochem Biotechnol ; : 1-6, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33600297

RESUMEN

Chrysomycin A is one of the valuable drug leads used to treat infectious diseases such as tuberculosis and methicillin-resistant Staphylococcus aureus. In order to increase its yield, this work firstly focuses on optimization of fermentation conditions and medium compositions of a wild-type chrysomycin A-producing strain Streptomyces sp. 891 from marine sediment. By single-factor experiment, effects of fermentation conditions (fermentation time, seed age, initial pH, inoculum amount, liquid loading, shaking speed) and medium composition (carbon sources, nitrogen sources, inorganic salts) on the yield of chrysomycin A were carefully evaluated and analyzed followed by optimization at shake-flask level. The results indicated its optimal fermentation conditions for producing chrysomycin A were as follows: fermentation time 168 h, seed age 48 h, initial pH 6.5, inoculum amount 5.0%, liquid loading 30 mL in 250-mL Erlenmeyer flask and shaking speed 220 rpm. By orthogonal test, the optimal fermentation medium constitutes 40 g/L glucose, 20 g/L corn starch, 25 g/L hot-pressed soybean flour, 3 g/L CaCO3. Verification tests suggested the yield of chrysomycin A under optimized conditions reaches up to 3648 ± 119 mg/L, which is increased by almost 5 times. These findings definitely pave the way for scale-up preparation of chrysomycin A and application in the pharmaceutical industry.

2.
Food Chem ; 341(Pt 1): 128148, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-33038776

RESUMEN

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.

3.
Mar Drugs ; 18(9)2020 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-32867177

RESUMEN

A low fasting blood glucose level is a common symptom in diabetes patients and can be induced by high-fat diet (HFD) feeding at an early stage, which may play important roles in the development of diabetes, but has received little attention. In this study, five polysaccharides were prepared from Sargassumfusiforme and their effects on HFD-induced fasting hypoglycemia and gut microbiota dysbiosis were investigated. The results indicated that C57BL/6J male mice fed an HFD for 4 weeks developed severe hypoglycemia and four Sargassumfusiforme polysaccharides (SFPs), consisting of Sf-2, Sf-3, Sf-3-1, and Sf-A, significantly prevented early fasting hypoglycemia without inducing hyperglycemia. Sf-1 and Sf-A could also significantly prevent HFD-induced weight gain. Sf-2, Sf-3, Sf-3-1, and Sf-A mainly attenuated the HFD-induced decrease in Bacteroidetes, and all five SFPs had a considerable influence on the relative abundance of Oscillospira, Mucispirillum, and Clostridiales. Correlation analysis revealed that the fasting blood glucose level was associated with the relative abundance of Mucispinllum and Oscillospira. Receiver operating characteristic analysis indicated that Mucispinllum and Oscillospira exhibited good discriminatory power (AUC = 0.745-0.833) in the prediction of fasting hypoglycemia. Our findings highlight the novel application of SFPs (especially Sf-A) in glucose homeostasis and the potential roles of Mucispinllum and Oscillospira in the biological activity of SFPs.

4.
J Enzyme Inhib Med Chem ; 35(1): 1736-1742, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32928007

RESUMEN

Gut microbial ß-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety (1-13) were evaluated for inhibitory activity against Escherichia coli ß-glucuronidase (EcGUS). All of them showed more potent inhibition than a commonly used positive control, d-saccharic acid 1,4-lactone, with the IC50 values ranging from 1.2 µM to 23.1 µM. Inhibition kinetics studies indicated that compound 1-3 were competitive type inhibitors for EcGUS. Molecular docking studies were performed and predicted the potential molecular determinants for their potent inhibitory effects towards EcGUS. Structure-inhibitory activity relationship study revealed that chloro substitution on the phenyl moiety was essential for EcGUS inhibition, which would help researchers to design and develop more effective thiazolidin-2-cyanamide type inhibitors against EcGUS.

5.
J Cell Mol Med ; 24(18): 10604-10614, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32735065

RESUMEN

Inflammatory cell infiltration contributes to the pathogenesis of acute respiratory distress syndrome (ARDS). Protectin DX (PDX), an endogenous lipid mediator, shows anti-inflammatory and proresolution bioactions. In vivo, the mice were intraperitoneally injected with PDX (0.1 µg/mouse) after intratracheal (1 mg/kg) or intraperitoneal (10 mg/kg) LPS administration. Flow cytometry was used to measure inflammatory cell numbers. Clodronate liposomes were used to deplete resident macrophages. RT-PCR, and ELISA was used to measure MIP-2, MCP-1, TNF-α and MMP9 levels. In vitro, sorted neutrophils, resident and recruited macrophages (1 × 106 ) were cultured with 1 µg/mL LPS and/or 100 nmol/L PDX to assess the chemokine receptor expression. PDX attenuated LPS-induced lung injury via inhibiting recruited macrophage and neutrophil recruitment through repressing resident macrophage MCP-1, MIP-2 expression and release, respectively. Finally, PDX inhibition of neutrophil infiltration and transmembrane was associated with TNF-α/MIP-2/MMP9 signalling pathway. These data suggest that PDX attenuates LPS-stimulated lung injury via reduction of the inflammatory cell recruitment mediated via resident macrophages.

6.
J Cell Mol Med ; 24(17): 9646-9657, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32757380

RESUMEN

Acute respiratory distress syndrome (ARDS) is a fatal disease characterized by excessive infiltration of inflammatory cells. MCTR1 is an endogenously pro-resolution lipid mediator. We tested the hypothesis that MCTR1 accelerates inflammation resolution through resident M2 alveolar macrophage polarization. The mice received MCTR1 via intraperitoneal administration 3 days after LPS stimulation, and then, the bronchoalveolar lavage (BAL) fluid was collected 24 hours later to measure the neutrophil numbers. Flow cytometry was used to sort the resident and recruited macrophages. Post-treatment with MCTR1 offered dramatic benefits in the resolution phase of LPS-induced lung injury, including decreased neutrophil numbers, reduced BAL fluid protein and albumin concentrations and reduced histological injury. In addition, the expression of the M2 markers Arg1, FIZZ1, Remlα, CD206 and Dectin-1 was increased on resident macrophages in the LPS + MCTR1 group. Resident macrophage depletion abrogated the therapeutic effects of MCTR1, and reinjection of the sorted resident macrophages into the lung decreased neutrophil numbers. Finally, treatment with MCTR1 increased STAT6 phosphorylation. The STAT6 inhibitor AS1517499 abolished the beneficial effects of MCTR1. In conclusion, MCTR1 promotes resident M2 alveolar macrophage polarization via the STAT6 pathway to accelerate resolution of LPS-induced lung injury.

7.
Eur Spine J ; 29(4): 786-793, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32112152

RESUMEN

PURPOSE: No study so far has paid attention to strabismus-related spinal imbalance. This study aimed to determine the epidemiology of thoracic scoliosis in children and adolescents with strabismus and investigate the association of two diseases. METHODS AND DESIGN: A cross-sectional study. Study group consists of 1935 consecutive candidates for strabismus surgery (4-18 years); Control group consists of the age- and sex-matched patients with respiratory diseases. All subjects underwent a screening program based on chest plain radiographs using the Cobb method. Their demographic information, clinical variables and results of Cobb angle were recorded and analyzed. RESULTS: A significantly higher prevalence of thoracic scoliosis (289/1935, 14.94% versus 58/1935, 3.00%) was found in study group compared with control group. Among strabismic patients, the coronal thoracic scoliosis curve mainly distributed in right and in main thoracic (198/289) and in the curves 10°-19° (224/289); Age range 7-9 years (103/1935), female (179/1935) and concomitant exotropia patients (159/851) were more likely to have thoracic scoliosis. According to the logistic regression, thoracic scoliosis had no significant association with age, BMI, duration of illness and onset age (p > 0.05). However, gender, BCVA, type of strabismus and degree of strabismus showed a significant relationship with the prevalence of thoracic scoliosis (p < 0.05). CONCLUSIONS: With a pooled prevalence of 14.94%, strabismus patients showed a great higher risk of developing thoracic scoliosis. Screening for scoliosis in strabismus patients can be helpful to discover a high prevalence of potential coronal scoliosis. More attention should be paid to ophthalmological problems in patients with scoliosis. These slides can be retrieved under Electronic Supplementary Material.

8.
Chin J Nat Med ; 17(10): 778-784, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31703758

RESUMEN

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC50 39.6 ± 1.9 µmol·L-1) and HepG2 cells(IC50 41.5 ± 1.1 µmol·L-1), respectively. Compound 9 (23S, 24S)-24-[(O-ß-D-fucopyranosyl)oxy]-3ß, 23-dihydroxy-spirosta-5, 25(27)-diene-1ß-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[ß-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC50 33.6 ± 2.1 µmol·L-1).


Asunto(s)
Citotoxinas/química , Medicamentos Herbarios Chinos/química , Helleborus/química , Esteroides/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citotoxinas/aislamiento & purificación , Citotoxinas/toxicidad , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/toxicidad , Humanos , Estructura Molecular , Raíces de Plantas/química , Esteroides/aislamiento & purificación , Esteroides/farmacología
9.
Int Immunopharmacol ; 76: 105877, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31522017

RESUMEN

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are life-threatening critical syndromes characterized by the infiltration of a large number of inflammatory cells that lead to an excessive inflammatory response. Resolvin D1 (RvD1), an endogenous lipid mediator, is believed to have anti-inflammatory and proresolving effects. In the present study, we examined the impact of RvD1 on the pulmonary inflammatory response, neutrophil influx, and lung damage in a murine model of lipopolysaccharide (LPS)-induced ALI. Treatment with RvD1 protected mice against LPS-induced ALI, and compared to untreated mice, RvD1-treated mice exhibited significantly ameliorated lung pathological changes, decreased tumor necrosis factor-α (TNF-α) concentrations and attenuated neutrophil infiltration. In addition, treatment with RvD1 attenuated LPS-induced neutrophil infiltration via the downregulation of CXCL2 expression on resident alveolar macrophages. Finally, BOC-2, which inhibits the RvD1 receptor lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2), reversed the protective effects of RvD1. These data demonstrate that RvD1 ameliorates LPS-induced ALI via the suppression of neutrophil infiltration by an ALX/FPR2-dependent reduction in CXCL2 expression on resident alveolar macrophages.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Quimiocina CXCL2/antagonistas & inhibidores , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Macrófagos Alveolares/efectos de los fármacos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Animales , Quimiocina CXCL2/genética , Quimiocina CXCL2/inmunología , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Macrófagos Alveolares/inmunología , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos
10.
Chin J Nat Med ; 17(8): 624-630, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31472900

RESUMEN

Five new polyhydroxylated furostanol saponins were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as tupistrosides J-N (1-5), together with four known furostanol saponins (6-9), on the basis of physico-chemical properties and spectral analysis. Among them, compounds 3 and 5 showed cytotoxicity against human cancer cell lines SW620 with IC50 values of 72.5 ± 2.4 and 77.3 ± 2.5 µmol·L-1, respectively. Compound 4 showed cytotoxicity against human cancer cell line HepG2 with IC50 value of 88.6 ± 2.1 µmol·L-1.


Asunto(s)
Antineoplásicos/química , Liliaceae/química , Saponinas/química , Esteroles/química , Células A549 , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Extractos Vegetales/química , Rizoma/química , Saponinas/farmacología , Esteroles/farmacología
11.
Nanoscale ; 11(14): 6876-6885, 2019 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-30912790

RESUMEN

Structural defects can greatly inhibit electron transfer in two-dimensional (2D) layered polymeric carbon nitride (CN) unit, seriously lowering its utilization ratio of photogenerated charges during photocatalysis. Herein, we propose a new strategy based on intra-melon hydrogen bonding interactions in 2D CN frameworks to improve the crystallinity of CN. This concept was validated by removing some amino groups and connecting melon using codoped B and F atoms via a simple one-step sodium fluoroborate-assisted thermal treatment. The enhancement in crystallinity effectively promoted exciton dissociation and charge transfer in the CN nanosheets. Furthermore, the B/F dopants also improved the separation of photogenerated carriers by promoting charge capture. The highly efficient visible-light photocatalytic activity of the crystalline B/F-codoped CN nanosheets was demonstrated by degrading methyl orange, Rhodamine B, colorless phenol and tetracycline hydrochloride as models, where their degradation rate constant was more than 10, 5, 32 and 3 times higher than that of pure CN, respectively. Moreover, the B/F-codoped CN exhibited an excellent photoelectrocatalytic performance for the oxygen evolution reaction (OER), outperforming the precious-metal IrO2 catalyst. The simple and effective strategy proposed herein provides a direct route to engineer high crystallinity in 2D materials for tunable charge carrier separation and migration for electronic and optoelectronic applications.

12.
J Sci Food Agric ; 99(3): 1405-1412, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30120787

RESUMEN

BACKGROUND: Macamides, the main active components contained in maca, have attracted increasing attention due to their various bioactivities. In this study, crude macamide extract (CME) and purified macamide extract (PME) were prepared by enzyme-assisted extraction and macroporous resin separation, and the anti-fatigue effects of CME and PME were evaluated in a forced swimming model. RESULTS: The composition analysis results revealed that both CME and PME mainly contain eight kinds of macamide. Based on the results of a weight-loaded forced swimming test, compared with a control group, CME and and PME groups could prolong exhaustive swimming time, increase levels of liver glycogen (LG) and muscle glycogen (MG), accelerate fatty acid oxidation in serum to provide energy, eliminate the accumulation of blood lactic acid (BLA) and blood urea nitrogen (BUN), and decrease the serum biomarkers for muscle damage, such as lactate dehydrogenase (LDH) and creatine kinase (CK). Histological analysis also indicated that CME and PME attenuated damage to skeletal muscle and the myocardium in mice during exercise. CONCLUSION: Two macamide extracts have a beneficial effect on relieving physical fatigue by attenuating the damage of skeletal muscle and myocardium during exercise, and a better effect was observed in the PME group. © 2018 Society of Chemical Industry.


Asunto(s)
Amidas/administración & dosificación , Fatiga/tratamiento farmacológico , Lepidium/química , Fatiga Muscular/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Amidas/química , Amidas/aislamiento & purificación , Animales , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Creatina Quinasa/metabolismo , Fatiga/metabolismo , Fatiga/fisiopatología , Glucógeno/metabolismo , Humanos , L-Lactato Deshidrogenasa/metabolismo , Masculino , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/enzimología , Músculo Esquelético/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Natación
13.
Org Lett ; 20(22): 7341-7344, 2018 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-30394758

RESUMEN

Purpurolide A (1), an unprecedent sesquiterpene lactone with a rarely encountered 5/5/5 spirocyclic skeleton, along with two new 6/4/5/5 tetracyclic sesquiterpene lactones (2 and 3), were isolated from the cultures of the endophytic fungus Penicillium purpurogenum IMM003. The structures and absolute configurations of 1-3 were established by spectroscopic analysis, single-crystal X-ray diffraction, and calculations of the 13C NMR and ECD data. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase.


Asunto(s)
Inhibidores Enzimáticos/aislamiento & purificación , Lactonas/aislamiento & purificación , Penicillium/metabolismo , Sesquiterpenos/aislamiento & purificación , Compuestos de Espiro/aislamiento & purificación , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Lactonas/química , Lactonas/farmacología , Lipasa/antagonistas & inhibidores , Estructura Molecular , Penicillium/aislamiento & purificación , Hojas de la Planta/microbiología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Estereoisomerismo , Thymelaeaceae/microbiología
14.
J Geriatr Cardiol ; 15(10): 618-627, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30416510

RESUMEN

Background: Growth-differentiation factor-15 (GDF-15) is a promising prognostic biomarker in patients with chronic heart failure (CHF). Comparatively little is known about the value of repeated measurement of GDF-15 with CHF in Chinese Han population. This study sought to identify the clinical value of repeated measurement of GDF-15 in Chinese Han patients with post-myocardial infarction CHF. Methods: In total, 232 consecutive Chinese Han patients with post-myocardial infarction CHF were enrolled prospectively from January 2014 to June 2016.The plasma concentration of GDF-15 was determined on admission and over 12 months. Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE) included all-cause death, myocardial infarction and first heart failure (HF) re-hospitalization. Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored. Results: The median baseline GDF-15 level was 2025 ng/L. Baseline GDF-15 was moderately associated with baseline N-terminal pro-B type natriuretic peptide (NT-proBNP) (coefficient 0.561, P < 0.001). During a median follow-up of 20 months, there were 53 deaths and 100MACE. GDF-15 remained an independent predictor of all-cause death (adjusted hazard ratio 1.826 per 1 Ln U, 95% CI: 1.037-8.360; P = 0.037) and MACE (adjusted hazard ratio 2.243 per 1 Ln U, 95% CI: 1.181-1.775; P < 0.001) adjusted for established risk factors. Repeated measurement of GDF-15 was performed in 173 survivals over 12months. Increase of GDF-15 over 12 months was associated with dilatation of left ventricle and acted as an independent predictor of subsequent all-cause death (adjusted HR = 3.164, 95% CI: 1.245-0.041; P = 0.015). In the joint model, GDF-15 was also shown to be a risk factor for all-cause death (HR = 2.749, 95% CI: 1.667-3.831; P < 0.001) and MACE (HR = 2.434, 95% CI: 1.425-3.443; P < 0.001). Conclusions: Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CHF post-myocardial infarction. GDF-15 may influence the post-myocardial infarction CHF through the path physiological pathway of myocardial remodeling.

15.
Yi Chuan ; 40(7): 525-533, 2018 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-30021716

RESUMEN

Long non-coding RNAs (lncRNAs) are designated as the transcripts longer than 200 nucleotides without protein-coding capacity. As a category of important gene regulatory factors, lncRNAs regulate the expression of target genes at epigenetic, transcription and post-transcriptional levels by various mechanisms, such as chromatin remodeling, DNA modification, transcription inhibition and RNA-RNA interactions, etc. In recent years, studies have shown that many lncRNAs can be induced by viruses or interferon (IFN) and to regulate the expression of related antiviral genes in IFN-mediated antiviral innate immune responses. In this review, we focus on the regulation of lncRNAs in IFN-mediated antiviral innate immune responses, especially in the transcription of IFN-stimulated genes (ISGs). In addition, we summarize the regulatory network of lncRNAs, IFN and ISGs. This review will provide a valuable reference for the researchers working in this field.


Asunto(s)
Inmunidad Innata/genética , Interferones/inmunología , ARN Largo no Codificante/genética , Virosis/inmunología , Humanos , Virosis/genética
16.
Eur J Med Chem ; 145: 717-725, 2018 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-29353723

RESUMEN

Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C (2 and 3), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha, together with a known octaketide, paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds 1-3 were tested for their antimicrobial activities. Only compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus with MIC values of 32 and 64 µg/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were evaluated. The results demonstrated that bysspectin A (1) was a novel and highly selective inhibitor against hCE2 with the IC50 value of 2.01 µM. Docking simulation also demonstrated that active compound 1 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2.


Asunto(s)
Antibacterianos/farmacología , Byssochlamys/química , Carboxilesterasa/antagonistas & inhibidores , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Policétidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Biocatálisis , Carboxilesterasa/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Dimerización , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Policétidos/química , Policétidos/aislamiento & purificación , Relación Estructura-Actividad
17.
Zhen Ci Yan Jiu ; 42(1): 20-4, 2017 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-29071993

RESUMEN

OBJECTIVE: To observe the influence of electroacupuncture (EA) stimulation with different electrical current intensities and therapeutic intervals on learning-memory ability and expression of ß-amyloid peptide Aß 1-40 and arginine vasopressin (AVP) genes in the hippocampal CA 1 region in vascular dementia (VD) rats, so as to provide evidence for treatment of VD. METHODS: A total of 48 male SD rats were randomly divided into sham, model, 0.5 mA-5 d-EA, 1.5 mA-5 d-EA, 0.5 mA-1 d-EA and 1.5 mA-1 d-EA groups (n=8 in each group). The VD model was established using modified 4-vessels occlusion method. EA (alternative 2 Hz/15 Hz, 0.5 mA, 1.5 mA) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) for 30 min, once a day (1 d) or once every 5 d for 10 times. The learning-memory ability was detected using Morris water maze tests (place navigation task and spatial probe trials), and the expression of Aß 1-40 and AVP genes in hippocampal CA 1 region was determined using real time-PCR. RESULTS: In comparison with the sham group, the average escape latency of place navigation task, and the duration for crossing the target-platform for the 1st time (spatial navigation task) were significantly increased (P<0.05), and the times to cross the target-platform within 2 min (spatial probe trials) were significantly decreased in the model group (P<0.05), suggesting a reduction of learning-memory ability. The expression level of Aß 1-40 mRNA was remarkably increased (P<0.05), and that of AVP mRNA notably decreased in the model group (P<0.05). Following EA intervention, the increased escape latency and the duration of crossing the target-platform for the 1st time and the increased Aß 1-40 mRNA expression, and the decreased target-platform crossing times within 2 min as well the down-regulated AVP mRNA expression level were reversed in the 4 EA groups compared with the model group (P<0.05). The therapeutic effects of higher stimulating intensity (1.5 mA-1 d-EA and 1.5 mA-5 d-EA) were markedly superior to those of lower intensity (0.5 mA-1 d-EA and 0.5 mA-5 d-EA), and the effects of higher frequency of EA intervention (0.5 mA-5 d-EA and 1.5 mA-5 d-EA) were obviously superior to those of lower frequency of EA (0.5 mA-1 d-EA and 1.5 mA-1 d-EA) in suppressing the increased 3 indexes and the decreased 2 indexes mentioned above (P<0.05). CONCLUSIONS: EA can improve the learning-memory ability of VD rats, which Feb be related to its effects in inhibiting the expression of Aß 1-40 mRNA and up-regulating the expression of AVP mRNA in hippocampal CA 1 region; and the therapeutic effects of higher stimulating intensity and higher intervention frequency are obviously better than those of lower stimulating intensity and lower therapeutic frequency.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Arginina Vasopresina/metabolismo , Región CA1 Hipocampal/metabolismo , Electroacupuntura , Fragmentos de Péptidos/metabolismo , Puntos de Acupuntura , Animales , Arginina Vasopresina/genética , Demencia Vascular/genética , Demencia Vascular/metabolismo , Demencia Vascular/psicología , Demencia Vascular/terapia , Modelos Animales de Enfermedad , Humanos , Aprendizaje , Masculino , Memoria , Ratas , Ratas Sprague-Dawley
19.
Lab Invest ; 97(5): 543-554, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28218740

RESUMEN

Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Ácidos Docosahexaenoicos/farmacología , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Canales Epiteliales de Sodio/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Lipoxina/metabolismo , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Lipopolisacáridos , Pulmón/química , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ubiquitina-Proteína Ligasas Nedd4 , Alveolos Pulmonares/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
20.
J Geriatr Cardiol ; 13(9): 768-775, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27899941

RESUMEN

BACKGROUND: Epicardial adipose tissue (EAT) is significantly associated with the formation and composition of coronary atherosclerotic plaque, cardiac events and the clinical prognosis of coronary heart disease. But, whether increased EAT deposition may affect the incidence of in-stent restenosis (ISR) is currently unclear. This study used coronary computed tomography angiography (CCTA) as a mean to investigate whether increased EAT volume was associated with ISR. METHODS: A total of 364 patients who underwent 64-slice CCTA examination for the evaluation of suspected coronary artery disease, and subsequently underwent percutaneous coronary intervention (PCI) for the first time, and then accepted coronary angiography (CA) follow-up for ISR examination in one year, were retrospectively included in this study. EAT volume was measured by CCTA examination. CA follow-up was obtained between 9 and 15 months. ISR was defined as ≥ 50% luminal diameter narrowing of the stent segment or peri-stent segment. EAT volume was compared between patients with and without ISR and additional well-known predictors of ISR were compared. RESULTS: EAT volume was significantly increased in patients with ISR compared with those without ISR (154.5 ± 74.6 mL vs. 131.0 ± 52.2 mL, P < 0.001). The relation between ISR and EAT volume remained significant after adjustment for conventional cardiovascular risk factors and angiographic parameters. CONCLUSIONS: EAT volume was related with ISR and may provide additional information for future ISR.

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