Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 112
Filtrar
1.
Nat Commun ; 14(1): 8288, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38092773

RESUMEN

Metabotropic glutamate receptors (mGluRs) are dimeric class C G-protein-coupled receptors that operate in glia and neurons. Glutamate affinity and efficacy vary greatly between the eight mGluRs. The molecular basis of this diversity is not understood. We used single-molecule fluorescence energy transfer to monitor the structural rearrangements of activation in the mGluR ligand binding domain (LBD). In saturating glutamate, group II homodimers fully occupy the activated LBD conformation (full efficacy) but homodimers of group III mGluRs do not. Strikingly, the reduced efficacy of Group III homodimers does not arise from differences in the glutamate binding pocket but, instead, from interactions within the extracellular dimerization interface that impede active state occupancy. By contrast, the functionally boosted mGluR II/III heterodimers lack these interface 'brakes' to activation and heterodimer asymmetry in the flexibility of a disulfide loop connecting LBDs greatly favors occupancy of the activated conformation. Our results suggest that dimerization interface interactions generate substantial functional diversity by differentially stabilizing the activated conformation. This diversity may optimize mGluR responsiveness for the distinct spatio-temporal profiles of synaptic versus extrasynaptic glutamate.


Asunto(s)
Receptores de Glutamato Metabotrópico , Receptores de Glutamato Metabotrópico/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Dimerización , Ácido Glutámico/metabolismo , Transferencia Resonante de Energía de Fluorescencia
2.
Artículo en Inglés | MEDLINE | ID: mdl-36520459

RESUMEN

Drug behavior in the bodies of fish is largely influenced by the water temperature. Antimicrobial drugs are needed for the control of bacterial outbreaks in farmed fish including Asian seabass (Lates calcarifer). However, little is known about the temperature effect on appropriate drug uses in this species. The purpose of this study was to investigate the differences in pharmacokinetics (PK), optimal dosages, tissue depletion, and withdrawal time (WDT) of florfenicol (FF) in Asian seabass reared at 25 and 30 °C. In the PK study, the fish were administered with a single oral dose of 10 mg/kg FF. The optimal dosing regimen was determined by the pharmacokinetic-pharmacodynamic (PK-PD) approach. In the tissue depletion and WDT study, FF was administered at the optimal dosages once daily for 5 days and the WDT was determined by linear regression analysis based on the sum of FF and its metabolite florfenicol amine (FFA) in the muscle/skin. When the temperature was increased from 25 to 30 °C, the elimination half-life of FF was significantly decreased from 11.0 to 7.2 h. While the other PK parameters were not changed significantly, the calculated optimal dosages for the target minimum inhibitory concentration (MIC) of 2 µg/mL were 10.9 and 22.0 mg/kg/day, respectively for 25 and 30 °C. The sum of FF + FFA is a preferable marker residue for WDT determination because differential FF metabolism was observed at different temperatures. The depletion half-life of the muscle/skin was shortened from 41.1 to 32.4 h by the 5 °C temperature increase. Despite different absolute amounts of FF given between the two temperature levels, the WDTs were very similar at 6-7 days. Thus, it appears that a single temperature-independent WDT can potentially be assigned when the drug was applied at the optimal dosage.


Asunto(s)
Perciformes , Tianfenicol , Animales , Antibacterianos/análisis , Temperatura , Perciformes/metabolismo
3.
Front Plant Sci ; 13: 909765, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812958

RESUMEN

Our previous study showed that colored net shading treatments had comparable effects on the reduction of bitter and astringent compounds such as flavonol glycosides in tea leaves, compared with black net shading treatment, whereas the effects on the biomass and phytohormones are still unclear. In this study, we investigated the phytohormone and transcriptome profiles of tea leaves under different shading treatments, using black, blue, and red nets with the same shade percentages. The bud density, fresh weight of 100 buds, and yield under blue net shading treatments were greatly elevated by 2.00-fold, 1.24-fold, and 2.48-fold, compared with black net shading treatment, while their effects on flavonoid composition were comparable with black net shading treatment. The transcriptome profiles of different shade net-treated samples were well resolved and discriminated from control. The KEGG result indicated that the pathways of phenylpropanoid biosynthesis, MAPK signaling pathways, and plant hormone signal transduction were differentially regulated by different shading treatments. The co-expression analysis showed that the contents of salicylic acid and melatonin were closely correlated with certain light signal perception and signaling genes (p < 0.05), and UVR8, PHYE, CRY1, PHYB, PHOT2, and HY5 had more close interactions with phytohormone biosynthetic genes (p < 0.05). Our results suggest that different shading treatments can mediate the growth of tea plants, which could be attributed to the regulatory effect on phytohormones levels, providing an instruction for the production of summer/autumn tea and matcha.

4.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-928904

RESUMEN

Mercury sphygmomanometer based on traditional auscultation method is widely used in primary medical institutions in China, but a large amount of blood pressure data can not be directly recorded and applied in scientific research analysis, meanwhile auscultation data is the clinical standard to verify the accuracy of non-invasive electronic sphygmomanometer. Focusing on this, we designed a miniature non-invasive blood pressure measurement and verification system, which can assist doctors to record blood pressure data automatically during the process of auscultation. Through the data playback function,the software of this system can evaluate and verify the blood pressure algorithm of oscillographic method, and then continuously modify the algorithm to improve the measurement accuracy. This study introduces the hardware selection and software design process in detail. The test results show that the system meets the requirements of relevant standards and has a good application prospect.


Asunto(s)
Auscultación , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea , Oscilometría , Esfigmomanometros
5.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-928898

RESUMEN

To solve the problem of real-time detection and removal of EEG signal noise in anesthesia depth monitoring, we proposed an adaptive EEG signal noise detection and removal method. This method uses discrete wavelet transform to extract the low-frequency energy and high-frequency energy of a segment of EEG signals, and sets two sets of thresholds for the low-frequency band and high-frequency band of the EEG signal. These two sets of thresholds can be updated adaptively according to the energy situation of the most recent EEG signal. Finally, we judge the level of signal interference according to the range of low-frequency energy and high-frequency energy, and perform corresponding denoising processing. The results show that the method can more accurately detect and remove the noise interference in the EEG signal, and improve the stability of the calculated characteristic parameters.


Asunto(s)
Algoritmos , Electroencefalografía , Procesamiento de Señales Asistido por Computador , Relación Señal-Ruido , Análisis de Ondículas
6.
J Am Chem Soc ; 143(24): 8951-8956, 2021 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-34115935

RESUMEN

G protein-coupled receptors (GPCRs) are the most common targets of drug discovery. However, the similarity between related GPCRs combined with the complex spatiotemporal dynamics of receptor activation in vivo has hindered drug development. Photopharmacology offers the possibility of using light to control the location and timing of drug action by incorporating a photoisomerizable azobenzene into a GPCR ligand, enabling rapid and reversible switching between an inactive and active configuration. Recent advances in this area include (i) photoagonists and photoantagonists that directly control receptor activity but are nonselective because they bind conserved sites, and (ii) photoallosteric modulators that bind selectively to nonconserved sites but indirectly control receptor activity by modulating the response to endogenous ligand. In this study, we designed a photoswitchable allosteric agonist that targets a nonconserved allosteric site for selectivity and activates the receptor on its own to provide direct control. This work culminated in the development of aBINA, a photoswitchable allosteric agonist that selectively activates the Gi/o-coupled metabotropic glutamate receptor 2 (mGluR2). aBINA is the first example of a new class of precision drugs for GPCRs and other clinically important signaling proteins.


Asunto(s)
Derivados del Benceno/farmacología , Receptores Acoplados a Proteínas G/agonistas , Regulación Alostérica/efectos de los fármacos , Derivados del Benceno/síntesis química , Derivados del Benceno/química , Humanos , Ligandos , Procesos Fotoquímicos
7.
Environ Sci Pollut Res Int ; 28(45): 64103-64112, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33982262

RESUMEN

It is very important to control agricultural water pollution and promote agricultural water saving, for high-quality development of Yangtze River Economic Belt (YREB). The efficiency of agricultural green water utilization (EAGWU) needs financial and technical support from the new-type urbanization, which also change agricultural production mode and resource utilization level. This paper introduces non-point source water pollution into the output, adopts the super efficiency-slack model (SE-SBM) to measure the EAGWU, and uses difference generalized method of moments (DIF-GMM) to examine how new-type urbanization affects EAGWU from its four core characteristics. The results of EAGWU show that the overall efficiency value has been increasing rapidly in the research period, while the eastern provinces performed better and the central provinces performed worse. On the other hand, the overall difference in EAGWU first diverged and then shrunk, while economically developed provinces has been converging all the time. The results of driving factor estimation show that population urbanization has a significantly positive effect on EAGWU, with the rural labor force transfer and agricultural land circulation. Economic urbanization and urban-rural integration have negative effects, with the widening gap of absolute income and the compressed space of agricultural development. The EAGWU lag phase has a positive effect, because of the ratchet or cumulative effect, while equilibrium-urbanization has an insignificant effect. The conclusions will provide preferable recommendations for decision-making of green and water-saving development in agriculture.


Asunto(s)
Ríos , Urbanización , Agricultura , China , Desarrollo Económico , Eficiencia , Agua
8.
Talanta ; 225: 121965, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33592719

RESUMEN

As an important sulfur compound, thiourea (TU) has caused great concern because of its wide application as well as its serious toxicity and hazard to the environment. Thus, it is necessary to develop a sensitive and selective method for TU analysis. In this work, gold nanorods (AuNRs) acted as an optical probe to realize the sensitive and colorimetric detection of TU. In HCl medium, Fe3+ at low concentration was difficult to oxide Au0 to form Au+ because of the high redox potential or the positive Gibbs free energy change. However, this process was possible when TU was present since the association constant between Au+ and TU is great enough to bind with TU to form a stable complex to further promote the etching of AuNRs, resulting in the lower aspect ratio of AuNRs with the blue shift and intensity decrease in extinction spectra, accompanied by the divisive colors of AuNRs solution or colorful dark-field light scattering imaging of single AuNR. The blue-shift of AuNRs longitudinal plasmon resonance absorption (LPRA) band was proportional to the concentration of TU in the range of 1-250 nM and the limit of detection (3σ/k) was as low as 0.4 nM. In addition, the colorimetric method was proven with high selectivity in the presence of potential interfering compounds, which was successfully applied to the detection of TU in fruit juice samples. This proposed colorimetric method provides a simple, sensitive yet selective measurement tool for TU sensing, which may offer new opportunities in the development of colorimetric sensors for food safety in the future.


Asunto(s)
Oro , Nanotubos , Colorimetría , Jugos de Frutas y Vegetales , Tiourea
9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-882210

RESUMEN

Objective:To investigate the association of alcohol drinking and the incident risk of type 2 diabetes in men and to provide evidences for early prevention of diabetes. Methods:Rural adult males without diabetes in Deqing County, Zhejiang Province were enrolled. A dynamic prospective cohort study was conducted. Data were collected through questionnaires, physical examination, experimental measurements and a electronic follow-up database. Cox multivariate regression was performed to assess the association of alcohol drinking and the incident risk of type 2 diabetes in men. Results:During the follow-up period (7.15±2.90 years), 354 men developed diabetes, and the incidence rate was 4.15/1 000 person-years. After adjusting for confounding factors, the incident risk of type 2 diabetes among the men with high alcohol drinking frequency (≥7 times/week) and low single alcohol intake (0.1-19.9 g/occasion) was lower than that among non-alcohol drinkers, and the value of HR (95%CI) was 0.72 (0.56-0.94) and 0.54 (0.30-0.99), respectively. Consumption of ≥40.0 g alcohol per occasion 3-6 times a week increased the incidence of type 2 diabetes, and consumption of <40.0 g alcohol per occasion over 7 times a week decreased the incidence of type 2 diabetes, with the value of HR (95%CI) of 1.53 (1.02-2.30) and 0.52 (0.28-0.99) respectively. Conclusion:Different alcohol drinking patterns affect the incident risk of type 2 diabetes among rural adult males in Deqing County. Further study on alcohol drinking and diabetes may have ethical and practical significance for the prevention and control of diabetes in rural China.

10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-881491

RESUMEN

Objective:To make a retrospective analysis on malaria epidemic history and control efforts in Deqing County from 1951 to 2015, and so as to provide a scientific basis for further consolidating the achievements after malaria elimination. Methods:Data on the epidemic, monitoring, prevention and control of malaria in Deqing from 1951 to 2015 were collected and analyzed by the method of descriptive research. Results:Totally 123 000 cases of malaria were reported in Deqing County from 1951 to 2015, and the annual average incidence was 529.61/100 000. There were 49 deaths with the mortality rate of 39.84/100 000. The epidemic peaked in 1960-1964 and reached its highest in 1963 with 21 942 cases and an incidence of 7825.25/100 000. After decades of the comprehensive prevention and control, eliminating malaria was accomplished in Deqing County in 2015. Conclusion:The prevention and control strategies/measures of malaria in different stages in Deqing County are effective. However, monitoring, health education and management for the migrant population, especial the returning workers from high-risk areas of malaria, should be further strengthened.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-942365

RESUMEN

Objective To evaluate the molluscicidal effect of 50% wettable powder of niclosamide ethanolamine salt (WPNES) against Oncomelania hupensis on the soil surface and inside the soil layer by immersion method in winter. Methods O. hupensis snails were placed on the soil surface and 2, 5 cm and 10 cm under the soil layer outdoors in winter, and then immersed in 50% WPNES at concentrations of 1 mg/L and 2 mg/L for 1, 3 d and 7 d, while dechlorinated water served as controls. Snail mortality was observed following immersion with 50% WPNES on the soil surface and inside the soil layer. Results Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 3-day corrected snail mortality rates were 98.0% and 76.0% on the soil surface, and the 7-day corrected snail mortality rate was both 100.0%. Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 7-day corrected snail mortality rates were 95.5% and 85.6% 2 cm below the soil layer, 66.0% and 6.4% 5 cm below the soil layer. However, the 7-day snail mortality rate swere comparable between the 50% WPNES treatment group (at 2 mg/L and 1 mg/L) and controls 10 cm below the soil layer (both P > 0.05). Conclusion Immersion of 50% WPNES at a concentration of 2 mg/L for 7 days presents a high molluscicidal efficacy against O. hupensis on the soil surface and 5 cm within the soil layers in winter.

12.
Chinese Journal of Rheumatology ; (12): 721-726,C11-1,C11-2, 2021.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-910217

RESUMEN

Objective:To investigate the effect of iguratimod (IGU) on transforming growth factor-β 1 (TGF-β 1)-induced primary human lung fibroblasts (pHLFs) activation and collagen secretion. Methods:Mice pulmonary fibrosis (PF) models were established in vivo and were divided into three groups: the control group (CTR group), the Bleomycin (BLM) group and the BLM+IGU group, hematoxylin-eosin (HE) staining was used to observe lung morphology, and Masson staining was used to observe the degree of collagen accumulation in lung. Fibronectin and smooth muscle 22 (SM22) were detected by immunofluorescence, and the content of hydroxyproline in lung tissue was detected by chloramine-T method. In vitro, pHLFs were used to assess the effect of IGU on TGF-β 1 stimulation in four groups: CTR group, IGU group, TGF-β 1 group and TGF-β 1+IGU group, the apoptosis of cells was detected by flow cytometry, and the mRNA expression of collagen type Ⅰ (COL-Ⅰ) and collagen type Ⅲ (COL-Ⅲ) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of α-smooth muscle actin (α-SMA), fibronectin, p-Smad2, p-Smad3 and transcription coactivator p300 were detected by Western blot and immunofluorescence. One-way ANOVA was used for all data, and LSD- t test or Kruskal-Wallis test was used for pair comparison. Results:The content of hydroxyproline in CTR group, the BLM group and the BLM+IGU group was (0.552±0.075) μg/mg, (1.293±0.081) μg/mg and (0.833±0.053) μg/mg ( F=169.672, P<0.01) respectively. IGU reduced the content of hydroxyproline in the lung tissue of mice, reduced the accumulation of collagen in the lung, and thus reduced the degree of BLM-induced pulmonary fibrosis, and improved the pathological changes in the lung of mice. In cell experiments, IGU had no significant effect on apoptosis ( F=0.83, P=0.54). The relative expression levels of COL-Ⅰ mRNA in the CTR group, TGF-β 1 group and TGF-β 1+IGU group were (100.4±1.2), (299.0± 13.0) and (202.5±7.0) respectively ( F=468.7, P<0.01). The relative expression levels of COL-Ⅲ mRNA in the CTR group, TGF-β 1 group and TGF-β 1+IGU group were (99.8±1.9), (350.6±8.0) and (220.3±9.9) respectively ( F=468.7, P<0.01). The relative expression levels of α-SMA protein were (0.193±0.038) in CTR group, (0.530±0.061) in TGF-β 1 group, and (0.410±0.065) in TGF-β 1+IGU group ( F=35.620, P<0.01); The relative expression levels of fibronectin in CTR group, TGF-β 1 group, and TGF-β 1+IGU group were (0.200±0.020), (0.700±0.020) and (0.410±0.066) respectively ( F=123.326, P<0.01). The relative expression levels of p-Smad3 protein in CTR group, TGF-β 1 group, and TGF-β 1+IGU group were (0.120±0.020), (0.573±0.586) and (0.327±0.252) respectively( F=92.987, P<0.01); The relative expression levels of p300 in CTR group, TGF-β 1 group and TGF-β 1+IGU group were (0.180±0.055), (0.923±0.025) and (0.650±0.050) respectively ( F=207.676, P<0.01). IGU significantly decreased the mRNA expression levels of COL-Ⅰ and COL-Ⅲ induced by TGF-β 1, inhibited the protein expression levels of α-SMA, fibronectin, p300, and phosphorylation of Smad2/3. Conclusion:Our results revealed the beneficial effect of IGU on the inhibition of TGF-β 1-mediated pHLFs activation and collagen secretion via the Smad3/p300 pathway, thus suggest that it might act as an effective anti-fibrotic agent in preventing the progression of PF.

13.
Healthcare (Basel) ; 8(4)2020 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-32987625

RESUMEN

Access to public health services is a cause that benefits the people and concerns the vital interests of the people. Everyone has access to basic health care services. The continuous improvement in people's health is an important indicator of the improvement in people's quality of life. This paper selects data from the European Union (EU) on aspects of public health expenditure, medical care resources, and government emergency coordination capacity from the period 2008 to 2017. Principal component analysis and factor analysis are used to measure their public health service capacity scores and conduct a comparative analysis. On this basis, the TOBIT model is adopted to explore the driving factors that lead to the spatial differentiation of public health service capabilities, and to combine it with the data of the COVID-19 epidemic as of 8 August 2020 from the official announcements of the World Health Organization and governments for further thinking. The results indicate that the public health service capacity of countries in the EU is showing a gradual increase. The capacity in Western Europe is, in turn, higher than that of Northern Europe, Southern Europe and Eastern Europe. In addition, the overall capacity in Western Europe is relatively high, but it is not balanced and stable, while Northern Europe has remained stable and balanced at a high level. Population density, degree of opening up, education level, economic development level, technological innovation level, and degree of aging have a positive effect on public health service capabilities. The level of urbanization has a negative effect on it. However, in countries with strong public health service capabilities, the epidemic of COVID-19 is more severe. The emergence of this paradox may be related to the detection capabilities of countries, the high probability of spreading thCOVID-19 epidemic, the inefficient implementation of government policy, the integrated system of the EU and the adverse selection of youth. This paper aims to improve the ability of the EU to respond to public health emergencies, improve the utilization of medical and health resources, and better protect people's health from the perspective of public health service capacity.

14.
Journal of Experimental Hematology ; (6): 2066-2070, 2020.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-880016

RESUMEN

OBJECTIVE@#To study the Polymorphism of the human platelet antigen(HPA) gene 1-17 and human leukocyte antigen(HLA) gene-A and B locus in Shandong Han population.@*METHODS@#A total of 962 samples from routine voluntary platelet donors were genotyped for HPA1-17 system and HLA-A site, B by PCR-SSP and PCR-SSOP respectively.Gene frequencies were calculated by counting. HPA1-17 and HLA genotype combinations were analyzed by Arelequin 3.5.@*RESULTS@#The gene frequencies of HPA-la, -1b, HPA-2a, -2b, HPA-3a, -3b, HPA-4a, -4b, HPA-5a, -5b, HPA-6a, -6b, HPA-15a, -15b were 0.9918, 0.0082, 0.9419, 0.0592, 0.5841, 0.4174, 0.9969, 0.0031, 0.9892, 0.0108, 0.9835, 0.0175,0.5488 and 0.4512, respectively. The most common HPA genotype combination was HPA-(1, 2, 4, 5, 6, 7-14, 16, 17) aa-3ab-15ab (0.2048). Moreover, HLA-A*2(0.3094) and HLA-B*13(0.1513) showed the highest frequency in their respective locus. The most common HLA genotype combination was HLA-A*2-B*13(0.1397) .@*CONCLUSION@#Distributions of HPA and HLA show high polymorphism in Shandong Han population. The ethnic and territorial difference of HPA distribution is also confirmed. It is imperative to establish local genetic database of volunteer platelet donors.


Asunto(s)
Humanos , Alelos , Antígenos de Plaqueta Humana/genética , Frecuencia de los Genes , Genotipo , Polimorfismo Genético
15.
Journal of Medical Postgraduates ; (12): 258-263, 2020.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-818415

RESUMEN

ObjectiveMicroRNAs (miRNA) play an important role in the development and regression of osteoporosis. This study aims to screen for miRNAs and genes closely related to osteoporosis, and to complete the construction of a miRNA-mRNA regulatory network of osteoporosis.MethodsThe gene chip expression profile of osteoporosis was obtained through the GEO database, and the differentially expressed genes (DEGs) and miRNAs were analyzed and screened via GEO2R. We used volcanic maps to display differential genes and miRNAs, and completed the GO and KEGG pathway analysis through the David online database. The String online database is used to complete PPI protein network analysis. The TargetScan, miRTarBase and miRDB were used to predict the targeted genes. Finally, the PPI and miRNA-mRNA regulatory networks were visualized by Cytoscape software.ResultsWe obtained 15 differential miRNAs and 174 differentially expressed genes through screening. The GO enrichment analysis mainly focused on drug response, angiogenesis, ion transport, regulation of small GTPase mediated signal ransduction, adaptive immune response, etc. NF-κB signaling pathway and HIF-1 signal were obtained through KEGG enrichment analysis. We obtained 10 hub genes through the cytohubba plug-in. We also obtained 3065 targeted genes by processing of seven miRNAs, and then intersected them with 174 DEGs to obtain 44 intersection genes. Finally, we successfully constructed a regulation map of miRNA-mRNA network. The miR-194-5p is significantly up-regulated in osteoporosis.ConclusionThe miR-194-5p might play an important role in osteoporosis by regulating its target gene CDH2, which provides candidate targets for the diagnosis and treatment of osteoporosis.

16.
Nat Commun ; 10(1): 5572, 2019 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-31804469

RESUMEN

Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors that operate at synapses. Macroscopic and single molecule FRET to monitor structural rearrangements in the ligand binding domain (LBD) of the mGluR7/7 homodimer revealed it to have an apparent affinity ~4000-fold lower than other mGluRs and a maximal activation of only ~10%, seemingly too low for activation at synapses. However, mGluR7 heterodimerizes, and we find it to associate with mGluR2 in the hippocampus. Strikingly, the mGluR2/7 heterodimer has high affinity and efficacy. mGluR2/7 shows cooperativity in which an unliganded subunit greatly enhances activation by agonist bound to its heteromeric partner, and a unique conformational pathway to activation, in which mGluR2/7 partially activates in the Apo state, even when its LBDs are held open by antagonist. High sensitivity and an unusually broad dynamic range should enable mGluR2/7 to respond to both glutamate transients from nearby release and spillover from distant synapses.


Asunto(s)
Conformación Proteica , Multimerización de Proteína , Receptores de Glutamato Metabotrópico/química , Animales , Ácido Glutámico/metabolismo , Células HEK293 , Humanos , Ratones , Microscopía Fluorescente , Técnicas de Placa-Clamp , Ratas Sprague-Dawley , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Sinapsis/genética , Sinapsis/metabolismo , Sinapsis/fisiología
17.
J Am Chem Soc ; 141(29): 11522-11530, 2019 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-31291105

RESUMEN

G protein-coupled receptors (GPCRs) are membrane proteins that play important roles in biology. However, our understanding of their function in complex living systems is limited because we lack tools that can target individual receptors with sufficient precision. State-of-the-art approaches, including DREADDs, optoXRs, and PORTL gated-receptors, control GPCR signaling with molecular, cell type, and temporal specificity. Nonetheless, these tools are based on engineered non-native proteins that may (i) express at nonphysiological levels, (ii) localize and turnover incorrectly, and/or (iii) fail to interact with endogenous partners. Alternatively, membrane-anchored ligands (t-toxins, DARTs) target endogenous receptors with molecular and cell type specificity but cannot be turned on and off. In this study, we used a combination of chemistry, biology, and light to control endogenous metabotropic glutamate receptor 2 (mGluR2), a Family C GPCR, in primary cortical neurons. mGluR2 was rapidly, reversibly, and selectively activated with photoswitchable glutamate tethered to a genetically targeted-plasma membrane anchor (membrane anchored Photoswitchable Orthogonal Remotely Tethered Ligand; maPORTL). Photoactivation was tuned by adjusting the length of the PORTL as well as the expression level and geometry of the membrane anchor. Our findings provide a template for controlling endogenous GPCRs with cell type specificity and high spatiotemporal precision.


Asunto(s)
Biología Molecular/métodos , Receptores de Glutamato Metabotrópico/genética , Aminoácidos/farmacología , Animales , Compuestos Azo/química , Membrana Celular/metabolismo , Ácido Glutámico/química , Células HEK293 , Humanos , Ligandos , Luz , Neuronas/metabolismo , Procesos Fotoquímicos , Ingeniería de Proteínas/métodos , Ratas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Receptores de Glutamato Metabotrópico/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Xantenos/farmacología
18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-779390

RESUMEN

Objective This study aimed to describe the prevalence of both type 2 diabetes (T2D) and hypertension, and to explore possible risk factors. Methods A Cross-sectional study was conducted in eight towns cluster-sampled randomly from Deqing County, Zhejiang Province. Totally. 29 306 subjects aged≥18 years old were recruited into this survey. Information on general information, life styles, health status and family history of chronic diseases was collected. Physical examinations including height, weight, blood pressure, etc. were done. Fasting plasma glucose was also tested. Results The prevalence of only T2DM, only hypertension and both of them was 3.34%, 28.72%, and 2.01%, respectively. Such prevalence of both reached a peak at the age of 70-79 years old.Family history of diabetes mellitus(OR=4.94, 95% CI:3.24-7.54, P<0.001) and having a spouse(OR=2.17, 95% CI: 1.18-4.00, P=0.013) were possible risk factors of diabetes mellitus, body mass index(BMI)<24 kg/m2(OR=0.48, 95% CI: 0.39-0.59, P<0.001) was the possible protective factor of diabetes mellitus, BMI<24 kg/m2(OR=0.60, 95% CI: 0.56-0.64, P<0.001), completing compulsory education(OR=0.54, 95% CI:0.49-0.59, P<0.001) and exercise(OR=0.77, 95% CI: 0.69-0.86, P<0.001) were protective factors of hypertension, drinking(OR=1.18 , 95% CI: 1.08-1.29, P<0.001) was the possible risk factor of hypertension. BMI<24 kg/m2(OR= 0.26, 95% CI: 0.21-0.31, P<0.001), completing compulsory education(OR=0.50, 95% CI: 0.35-0.72, P<0.001) and drinking tea(OR=0.80, 95% CI:0.64-0.99, P=0.045) were protective factors of these two diseases. Farmers(OR=1.35, 95% CI: 1.04-1.76, P=0.024), family history of diabetes(OR=4.21, 95% CI: 2.71-6.57, P<0.001) and family history of hypertension(OR=1.86, 95% CI: 1.31-2.64, P=0.001) were risk factors for the co occurrence of two diseases. Conclusions The prevalence of diabetes among adults in Deqing County was relatively lower than other places. The prevalence of hypertension was close to the level of other regions. Age, overweight, alcohol consumption, family history of diabetes and hypertension were the risk factors of diabetes and hypertension. Diabetes mellitus was a high-risk group of hypertension. Further means should be taken to strengthen the self-management and treatment of this group. Further intervention action should be taken to promote health and quality of life.

19.
Cytotechnology ; 70(2): 855-864, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29460197

RESUMEN

Early diagnosis and changes associated with atherosclerosis are crucial in clinical medicine. However, atherosclerosis is a multifactorial disease. Asiaticoside (AA), a triterpenoid derived from Centella asiatica, has anti-inflammatory activity. Endothelium-derived nitric oxide is important in modulating vascular tone in a distinct vessel size-dependent manner; it plays a dominant role in conduit arteries and endothelium-dependent hyperpolarisation in resistance vessels. This study evaluated the effects of AA administration on human umbilical endothelial cells with oxidised low-density lipoprotein-induced inflammation. We measured the levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Our results indicated that 10-30 µM AA modulated endothelial hyper permeability, adenosine triphosphate levels, ICAM-1 expression, VCAM-1 expression, E-selectin levels, and PECAM-1 expression to 90% (p < 0.005), 80% (p < 0.05), 105% (p < 0.01), 65% (p < 0.005), 70% (p < 0.05), and 105% (p < 0.01), respectively. Taken together, our data suggest that AA inhibits the augmentation of endothelial permeability, thus preventing the early events of atherosclerosis.

20.
J Formos Med Assoc ; 117(1): 6-13, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28877853

RESUMEN

Preeclampsia may affect between 2-8% of all pregnancies. It seriously affects maternal health after pregnancy. This meta-analysis was performed to define the efficacy of vitamins supplementation on the risk of preeclampsia. Potential articles were systematically searched on the databases of Pubmed, Embase and Web of Science up to May 2016. Relative risk (RR) and 95% confidence intervals (95%CIs) were used to analyze the relationship of vitamins supplementation with risk of preeclampsia. Cochran Q test was used to test inter-study heterogeneity. Begg's funnel plot was adopted to assess the potential publication bias. 28 eligible studies were selected. Pooled results indicated that vitamins supplementation could reduce the risk of preeclampsia (RR = 0.74, 95%CI = 0.64-0.86). The studies with non-randomized controlled trial (RCT) analysis also suggested the significant relationship of vitamins supplementation with risk of preeclampsia (RR = 0.60, 95%CI = 0.42-0.85). However, negative results were observed in studies with RCT analysis. Subgroup analysis by vitamin type was performed among the studies with RCT analysis. The results indicated that vitamin D supplementation could significantly reduce the risk of preeclampsia (RR = 0.41, 95%CI = 0.22-0.78). Similar results were observed in the studies with multivitamins supplementation (RR = 0.69, 95%CI = 0.51-0.93). Vitamins supplementation could reduce the onset of preeclampsia.


Asunto(s)
Suplementos Dietéticos , Preeclampsia/epidemiología , Preeclampsia/prevención & control , Vitaminas/uso terapéutico , Femenino , Humanos , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...