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1.
Ergonomics ; 66(12): 2074-2090, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36825638

RESUMEN

Digital image processing has been widely used for researches in the fashion industry. This study presented a method to classify women's waist-hip-leg position based on body images. 135 healthy female students were selected as the experimental subjects, and then photo and 3D body measuring methods were used to obtain 40 shape parameters. Through factor analysis, five factors were extracted for the waist-hip position and eight factors for the leg position. The waist-hip and leg were separately classified into four categories after clustering analysis with optimised factors. The distribution of waist-hip-leg shape was analysed by combining the waist-hip and leg classification results. The results showed that 12.31% of the subjects had prominent abdomens, flat buttocks, and round and thin legs. The landmarks and parameters were automatically extracted for waist-hip-leg shape identification. The image-based shape analysis approach (ISA) was finally verified with an accuracy rate of over 90% with 30 new subjects.Practitioner summary: This study will propose an image-based shape analysis approach (ISA) to realise the quick automatic shape identification of the waist-hip-leg position based on body images. In addition, the method can be applied to pants' pattern alteration for different body types by analysing the relationship between the waist-hip-leg shape and pants.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Pierna , Humanos , Femenino , Índice de Masa Corporal , Abdomen , Estudiantes
2.
Pharmacol Res ; 139: 431-439, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30503840

RESUMEN

Inflammatory reaction and cell apoptosis are two important processes in intestinal ischemia/reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating inflammation and apoptosis is critical important. In this paper, the results indicated that dioscin significantly increased cell viability, and inhibited inflammation and apoptosis caused by hypoxia-reoxygenation (H/R) injury in IEC-6 cells. in vivo II/R injury, dioscin markedly suppressed inflamma- tion and apoptosis, improved pathological changes, and depressed chiu' score in rats. Mechanistic studies indicated that dioscin notably up-regulated the expression level of MAPK13 through decreasing miR-351-5p level, and thereby decreased the expression levels of p-PKD1, NF-κB, Apaf-1, cleaved Caspase-3 and cleaved Caspase-9. Furthermore, miR-351-5p mimic and inhibitor experiments in IEC-6 cells further proved that dioscin up-regulated MAPK13 expression by decreasing miR-351-5p level to inhibit inflammation and apoptosis. Therefore, dioscin showed protective effect against II/R injury via adjusting miR-351-5/MAPK13-mediated inflammation and apoptosis. Dioscin should be considered as one potent candidate and miR-351-5/ MAPK13 should be one effective drug target for the treatment of II/R injury.


Asunto(s)
Antiinflamatorios/uso terapéutico , Diosgenina/análogos & derivados , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Diosgenina/farmacología , Diosgenina/uso terapéutico , Mucosa Intestinal/metabolismo , Masculino , MicroARNs/metabolismo , Proteína Quinasa 13 Activada por Mitógenos/metabolismo , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo
3.
Biomacromolecules ; 19(4): 1223-1233, 2018 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-29481061

RESUMEN

Interfacial dynamics, assembly processes, and changes in nanostructures and mechanical properties of Bombyx mori silk fibroin (SF) proteins under varying degrees of nanoconfinement without and with lateral shear are investigated. When only compressive confinement forces were applied, SF proteins adsorbed on the surfaces experienced conformational changes following the Alexander-de Gennes theory of polymer brushes. By contrast, when SF proteins were exposed to a simultaneous nanoconfinement and shear, remarkable changes in interaction forces were observed, displaying the second order phase transitions, which are attributed to the formation of SF micelles and globular superstructural aggregates via hierarchical assembly processes. The resultant nanostructured SF aggregates show several folds greater elastic moduli than those of SF films prepared by drop-casting and compression-only and even degummed SF fibers. Such a striking improvement in mechanical strength is ascribed to a directional organization of ß-sheet nanocrystals, effectively driven by nanoconfinement and shear stress-induced stiffing and ordering mechanisms.


Asunto(s)
Fibroínas/química , Nanoestructuras/química , Polímeros/química , Animales , Bombyx/química , Elasticidad , Agregado de Proteínas
4.
Pharmacol Res ; 137: 56-63, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30240824

RESUMEN

Oxidative stress plays important roles in intestinal ischemia-reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating oxidative stress is necessary. In this study, the effects and possible mechanisms of dioscin against hypoxia-reoxygenation (H/R) injury in IEC-6 cells and II/R injury in mice were investigated. The results showed that dioscin markedly increased cell viability, and reduced ROS level caused by H/R injury in IEC-6 cells. in vivo, dioscin significantly reduced the levels of MDA, MPO and chiu' score, increased SOD level, and improved pathological changes caused by II/R injury in mice. Mechanism investigation showed that dioscin markedly up-regulated the expression levels of Sirt6 by decreasing miR-351-5p levels, decreased the expression levels of p-FoxO3α via activating AMPK, and increased the expression levels of MnSOD and CAT. In addition, miR-351-5p mimic in IEC-6 cells and agomir in mice increased ROS levels and aggravated II/R injury. MiR-351-5p inhibitor in IEC-6 cells and antagomir in mice alleviated these actions by adjusting Sirt6 signal pathway. MiR-351-5p interference experiment further confirmed that dioscin increased Sirt6 expression level by down- regulating miR-351-5p level to inhibit oxidative stress and reduce II/R injury. Furthermore, we also demonstrated that dioscin inhibited the expression level of miR-351-5p via reducing TRBP expression level during the generation of miR-351-5p mature body. Dioscin showed protective effect against II/R injury via adjusting miR- 351-5/Sirt6 signal to reduce oxidative stress, which should be considered as one potent candidate to treat II/R injury. In addition, miR-351-5/Sirt6 could be one effective drug target against II/R injury.


Asunto(s)
Diosgenina/análogos & derivados , MicroARNs/genética , Sustancias Protectoras/farmacología , Daño por Reperfusión/genética , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diosgenina/farmacología , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Superóxido Dismutasa/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-36900867

RESUMEN

Female breasts are regarded as a factor reflecting women's morphological beauty. An appropriate bra can fulfill aesthetic needs, thus boosting self-esteem. This study proposed a method to analyze young women's breast-bra morphological variations between two identical bras with different bra cup thicknesses. The 3D surface scan data of 129 female students who were braless and wore a thin bra (13 mm) and a thick bra (23 mm) were analyzed. Integral sections of the breasts and bra were cut at a fixed thickness of 10 mm, and slice maps were derived. Morphological parameters were extracted in braless and the two bra conditions. The variations in breast-bra shape caused by different thicknesses of bra cups were evaluated by quantifying breast ptosis, gathering, and breast slice area. The results showed that the thin bra lifted the breasts by 2.16 cm, whereas the thick bra decreased breast separation, gathering the breasts and moving them 2.15 cm laterally towards the center of the chest wall. Moreover, prediction models constructed using the critical morphological parameters were used to characterize breast-bra shape after wearing the provided bras. The findings lay the groundwork for quantifying the breast-bra shape variation caused by different bra cup thicknesses, allowing young females to choose optimally fitting bras to achieve their desired breast aesthetics.


Asunto(s)
Vestuario , Pared Torácica , Femenino , Humanos , Mama , Autoimagen
8.
Waste Manag ; 171: 281-291, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37690403

RESUMEN

Single-use plastics (SUPs) have been the focus of plastic pollution control, and limiting their use while shifting to other alternatives have been widely promoted in various countries. This study tries to verify the life cycle environmental performances of single-use plastic bag and its alternatives under different scenarios in real world. China is chosen as case study, where provincial variability is prominent in waste disposal, and strictest plastics ban has issued lately in this worldwide biggest market. The study found that HDPE plastic bags have relatively lowest environmental footprints regarding to Acidification Potential, Global Warming Potential, Chemical Oxygen Demand, Eutrophication Potential, Fossil Fuel Depletion Potential and Water Use. Sticking to current waste treatment, large-scale promotion of degradable products will increase environmental impacts by 1.4-22.6 times nationwide. Xinjiang has highest impact of using plastic bag at household level, due to its long-distance transport and high landfill ratio. Henan and Hebei will trigger the most significant changes in Global Warming Potential of 4.6 and 4.4 times if single-use plastic bags are all replaced with other alternatives. Uncertainty and sensitivity test further prove the robustness of results, and extends geographical implications of the findings. These suggest that introduction of new alternatives requires systematic deployment with full life cycle thinking, and SUPs pollution control should be a holistic transformation. Reducing bag weight while ensuring carrying capacity, purchasing local products to shorten transportation distances and shifting towards cleaner energy sources are synergetic ways to reduce the environmental impact of single-use plastic products.

9.
J Am Chem Soc ; 134(51): 20722-7, 2012 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-23240683

RESUMEN

Several biological processes involve glycans, yet understanding their ligand specificities is impeded by their inherent diversity and difficult acquisition. Generating broad synthetic sugar libraries for bioevaluations is a powerful tool in unraveling glycan structural information. In the case of the widely distributed heparan sulfate (HS), however, the 48 theoretical possibilities for its repeating disaccharide call for synthetic approaches that should minimize the effort in an undoubtedly huge undertaking. Here we employed a divergent strategy to afford all 48 HS-based disaccharides from just two orthogonally protected disaccharide precursors. Different combinations and sequence of transformation steps were applied with many downstream intermediates leading up to multiple target products. With the full disaccharide library in hand, affinity screening with fibroblast growth factor-1 (FGF-1) revealed that four of the synthetic sugars bind to FGF-1. The molecular details of the interaction were further clarified through X-ray analysis of the sugar-protein cocrystals. The capability of comprehensive sugar libraries in providing key insights in glycan-ligand interaction is, thus, highlighted.


Asunto(s)
Disacáridos/química , Disacáridos/farmacología , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Heparitina Sulfato/química , Heparitina Sulfato/farmacología , Sitios de Unión , Factor 1 de Crecimiento de Fibroblastos/química , Humanos , Modelos Moleculares , Unión Proteica
10.
J Am Chem Soc ; 134(21): 8988-95, 2012 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-22587381

RESUMEN

Numerous biomolecules possess α-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted ß-isomer. We report herein a versatile approach in affording full α-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.


Asunto(s)
Disacáridos/química , Disacáridos/síntesis química , Glucosamina/metabolismo , Heparina/análogos & derivados , Heparina/síntesis química , Lectinas/metabolismo , Mycobacterium tuberculosis , Disacáridos/metabolismo , Glucosamina/química , Glicosilación , Heparina/metabolismo , Lectinas/química , Fragmentos de Péptidos/metabolismo , Estereoisomerismo , Especificidad por Sustrato
11.
Nanomaterials (Basel) ; 11(4)2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33921395

RESUMEN

Natural convection heat transfer in a porous annulus filled with a Cu nanofluid has been investigated numerically. The Darcy-Brinkman and the energy transport equations are employed to describe the nanofluid motion and the heat transfer in the porous medium. Numerical results including the isotherms, streamlines, and heat transfer rate are obtained under the following parameters: Brownian motion, Rayleigh number (103-105), Darcy number (10-4-10-2), nanoparticle volume fraction (0.01-0.09), nanoparticle diameter (10-90 nm), porosity (0.1-0.9), and radius ratio (1.1-10). Results show that Brownian motion should be considered. The nanoparticle volume fraction has a positive effect on the heat transfer rate, especially with high Rayleigh number and Darcy number, while the nanoparticle diameter has an inverse influence. The heat transfer rate is enhanced with the increase of porosity. The radius ratio has a significant influence on the isotherms, streamlines, and heat transfer rate, and the rate is greatly enhanced with the increase of radius ratio.

12.
IEEE Trans Image Process ; 30: 4667-4677, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33900915

RESUMEN

Due to the continuous booming of surveillance and Web videos, video moment localization, as an important branch of video content analysis, has attracted wide attention from both industry and academia in recent years. It is, however, a non-trivial task due to the following challenges: temporal context modeling, intelligent moment candidate generation, as well as the necessary efficiency and scalability in practice. To address these impediments, we present a deep end-to-end cross-modal hashing network. To be specific, we first design a video encoder relying on a bidirectional temporal convolutional network to simultaneously generate moment candidates and learn their representations. Considering that the video encoder characterizes temporal contextual structures at multiple scales of time windows, we can thus obtain enhanced moment representations. As a counterpart, we design an independent query encoder towards user intention understanding. Thereafter, a cross-model hashing module is developed to project these two heterogeneous representations into a shared isomorphic Hamming space for compact hash code learning. After that, we can effectively estimate the relevance score of each "moment-query" pair via the Hamming distance. Besides effectiveness, our model is far more efficient and scalable since the hash codes of videos can be learned offline. Experimental results on real-world datasets have justified the superiority of our model over several state-of-the-art competitors.

13.
Interdiscip Sci ; 13(4): 717-730, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34259999

RESUMEN

With the proliferation of IoMT (Internet of Medical Things), billions of connected medical devices are constantly producing oceans of time series sensor data, dubbed as time series for short. Considering these time series reflect various functional states of the human body, how to effectively detect the corresponding abnormalities is of great significance for smart healthcare. Accordingly, we develop a horizontal visibility graph-based temporal classification model for disease diagnosis. We conduct extensive comparison experiments on the benchmark datasets to justify the superiority of our method in term of accuracy and efficiency. Besides, we have released the codes and parameters to facilitate the community research. We propose an identifiable temporal feature selection via horizontal visibility graph for time series classification (TSC) based disease diagnosis. We conduct comparison experiments on the benchmark datasets to justify the superiority of our method in term of accuracy and efficiency. As a side contribution, we have released the codes and parameters to facilitate the community research ( https://github.com/sdujicun/SSVG ).

14.
IEEE Trans Image Process ; 30: 5933-5943, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34166192

RESUMEN

Video moment localization, as an important branch of video content analysis, has attracted extensive attention in recent years. However, it is still in its infancy due to the following challenges: cross-modal semantic alignment and localization efficiency. To address these impediments, we present a cross-modal semantic alignment network. To be specific, we first design a video encoder to generate moment candidates, learn their representations, as well as model their semantic relevance. Meanwhile, we design a query encoder for diverse query intention understanding. Thereafter, we introduce a multi-granularity interaction module to deeply explore the semantic correlation between multi-modalities. Thereby, we can effectively complete target moment localization via sufficient cross-modal semantic understanding. Moreover, we introduce a semantic pruning strategy to reduce cross-modal retrieval overhead, improving localization efficiency. Experimental results on two benchmark datasets have justified the superiority of our model over several state-of-the-art competitors.

15.
Mater Sci Eng C Mater Biol Appl ; 100: 514-522, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30948088

RESUMEN

Acute wounds are worldwide problems affecting millions of people and causing heavy economic burden to national healthcare systems. Herein, we describe novel wound dressing materials relying on core/shell electrospun mats incorporated with flurbiprofen and vancomycin for achieving programmable release of anti-inflammatory and anti-bacterial agents. The shell matrix of nanofibers consisted of polyethylene oxide while the core matrix was made from a blend of silk and collagen. Several optimal mat architectures were engineered with distinct configurations, of which release profiles displayed an exponential trend, which indicates a first-order process following Fickian diffusion behavior. The flurbiprofen release lasted from 2 to 6 days, which was much faster compared to the one of vancomycin prolonged up to about 20 days. Mechanical data indicated tensile modulus, tensile strength, elongation before break of core/shell electrospun mats became enhanced or comparable to those for human skin after methanol vapor treatment. Desirable release kinetics and mechanical characteristics achieved by novel core/shell electrospun mats were attributable to induced enrichment of ß-sheet phase in silk via methanol vapor treatment as well as water annealing process with time and judicious selections for matrix materials and mat configurations. The design principles considered in this study successfully addressed a range of inflammation and infection requirements in wound healing, potentially guiding construction of other biomedical coatings and devices.


Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios/farmacología , Rastreo Diferencial de Calorimetría , Preparaciones de Acción Retardada , Flurbiprofeno/farmacología , Cinética , Metanol/química , Nanofibras/química , Estrés Mecánico , Vancomicina/farmacología
16.
ACS Appl Mater Interfaces ; 10(45): 39091-39099, 2018 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-30350936

RESUMEN

Conjugated-polymer field-effect transistors are attractive for flexible electronics. However, relatively high chemical doping (oxidation) concentration of p-type polymer semiconductors is usually not compatible with good transistor performance, due to poor switching-off capability and short-channel performance. Here, we propose a combined simulation and experimental investigation on charge transport in a semiconductor-insulator alternating bulk junction composed of repeating semiconductor and insulator regions, which shows better transistor performance at higher doping levels, as compared with traditional planar transistors. Moreover, the doped semiconductor transport layers in the junction should be less than 2 nm thick to ensure sufficient pinch-off capability. Using some semiconductors including poly(3-hexylthiophene), we utilize a fast solvent evaporation approach to obtain semiconductor-insulator alternating bulk junctions with ultrathin (thickness < 2 nm) semiconductor crystallites and with vertical gradients of both morphology and electronic properties. Doping with a concentration of up to 1019 cm-3 simultaneously induces the improvement of field-effect mobility, on/off ratio, and subthreshold swing, which leads to long-term (>1 year) stability, without lowering the short-channel performance. Moreover, these heterojunctions are optically transparent, nearly colorless, and flexible, thus could be exploited for wide electronic and photonic applications.

17.
Br J Pharmacol ; 175(17): 3594-3609, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29952043

RESUMEN

BACKGROUND AND PURPOSE: Intestinal ischaemia-reperfusion (II/R) injury is a serious clinical problem. Here we have investigated novel mechanisms and new drug targets in II/R injury by searching for microRNAs regulating such injury. EXPERIMENTAL APPROACH: We used hypoxia/reoxygenation (H/R) of IEC-6 cell cultures and models of II/R models in rats and mice. Microarray assays were used to identify target miRNAs from rat intestinal. Real-time PCR, Western blot and dual luciferase reporter assays, and agomir and antagomir in vitro and in vivo were used to assess the effects of the target miRNA on II/R injury. KEY RESULTS: The miR-351-5p was differentially expressed in our models and it targeted MAPK13 and sirtuin-6. This miRNA reduced levels of sirtuin-6 and AMP-activated protein kinase phosphorylation, and activated forkhead box O3 (FoxO3α) phosphorylation to cause oxidative stress. Also, miR-351-5p markedly reduced MAPK13 level, activated polycystic kidney disease 1/NF-κB signal and increased NF-κB (p65). Moreover, miR-351-5p up-regulated levels of Bcl2-associated X, cytochrome c, apoptotic peptidase activating factor 1, cleaved-caspase 3 and cleaved-caspase 9 by reducing sirtuin-6 levels to promote apoptosis. In addition, miR-351-5p mimic in IEC-6 cells and agomir in mice aggravated these effects, and miR-351-5p inhibitor and antagomir in mice alleviated these actions. CONCLUSIONS AND IMPLICATIONS: Our data showed that miR-351-5p aggravated II/R injury by promoting intestinal mucosal oxidative stress, inflammation and apoptosis by targeting MAPK13 and sirtuin-6.These data provide new insights into the mechanisms regulating II/R injury, and of miR-351-5p could be considered as a novel therapeutic target for such injury.


Asunto(s)
Intestinos/irrigación sanguínea , MicroARNs/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Daño por Reperfusión/prevención & control , Sirtuinas/metabolismo , Animales , Apoptosis , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Ratas Wistar , Daño por Reperfusión/enzimología , Daño por Reperfusión/metabolismo , Transducción de Señal
18.
Chem Biol Interact ; 258: 234-44, 2016 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-27649624

RESUMEN

BACKGROUND: We previously reported the promising effects of dioscin against cerebral and renal ischemia-reperfusion (I/R) injury. However, its role against gastric I/R injury has not yet been reported. Thus, the aim of the present work was to investigate the protective effect and possible mechanisms of dioscin against gastric I/R. MATERIALS AND METHODS: The hypoxia-reoxygenation (H/R) model in GES-1 cells and the celiac artery occlusion model in rats were carried out in the study. RESULTS: Dioscin markedly attenuated H/R insult in GES-1 cells and gastric I/R injury in rats. Mechanistic studies demonstrated that dioscin-induced gastric protection was accompanied by inhibiting the levels of PKCα, PKCß2 and phosphorylation via decreasing Raf-1 level. Blockade of PKC/ERK1/2 signaling pathway by dioscin decreased MEK1/2 level, ERK1/2 phosphorylation and the nuclear translocation, NF-κB and AP-1 transcriptional activities, pro-inflammatory cytokine responses, and up-regulated PPAR-γ level. Moreover, the results of small interfering RNA (siRNA) and overexpression of PKCα and PKCß2 confirmed that dioscin attenuated gastric I/R injury through inhibiting PKC/ERK1/2 signaling by down-regulating PKCα and PKCß2. CONCLUSION: These data confirmed the protective effect of dioscin against gastric I/R injury, which should be developed as a therapeutic agent for the treatment of acute gastric mucosal lesions in the future.


Asunto(s)
Diosgenina/análogos & derivados , Regulación hacia Abajo/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteína Quinasa C beta/metabolismo , Proteína Quinasa C-alfa/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Diosgenina/química , Diosgenina/farmacología , Diosgenina/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Humanos , Isoenzimas/metabolismo , Masculino , Modelos Biológicos , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Ratas Sprague-Dawley , Daño por Reperfusión/patología , Estómago/irrigación sanguínea , Estómago/patología
19.
ACS Chem Biol ; 9(8): 1712-7, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-24959968

RESUMEN

Heparan sulfate (HS) is a linear sulfated polysaccharide that mediates protein activities at the cell-extracellular interface. Its interactions with proteins depend on the complex patterns of sulfonations and sugar residues. Previously, we synthesized all 48 potential disaccharides found in HS and used them for affinity screening and X-ray structural analysis with fibroblast growth factor-1 (FGF1). Herein, we evaluated the affinities of the same sugars against FGF2 and determined the crystal structures of FGF2 in complex with three disaccharides carrying N-sulfonated glucosamine and 2-O-sulfonated iduronic acid as basic backbones. The crystal structures show that water molecules mediate different interactions between the 3-O-sulfonate group and Lys125. Moreover, the 6-O-sulfonate group forms intermolecular interactions with another FGF2 unit apart from the main binding site. These findings suggest that the water-mediated interactions and the intermolecular interactions influence the binding affinity of different disaccharides with FGF2, correlating with their respective dissociation constants in solution.


Asunto(s)
Disacáridos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Heparitina Sulfato/metabolismo , Cristalografía por Rayos X , Disacáridos/química , Heparitina Sulfato/química , Modelos Moleculares
20.
Curr Opin Chem Biol ; 17(6): 1023-9, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24182748

RESUMEN

Heparin and heparan sulfate bind a host of basic proteins that take advantage of the sugar's dense structural information. The significance of these interactions in various aspects of development, physiology, and disease stimulated keen interest in evaluating structure-activity relationships. The well-defined heparin and heparan sulfate oligosaccharides needed for these studies can be mainly accessed by chemical synthesis and, more recently by chemoenzymatic means. The various synthetic strategies available to chemical synthesis have recently enabled the acquisition of several regular and irregular sequences, including a number of dodecasaccharides, through improved coupling methods and judicial protecting group manipulations. Controlled chain elongation and critical application of modification enzymes allowed the generation of well-defined constructs via chemoenzymatic synthesis. Investigations of various protein interactions with the synthetic constructs delivered valuable information that could aid future drug development endeavors.


Asunto(s)
Heparina/química , Heparina/metabolismo , Heparitina Sulfato/química , Heparitina Sulfato/metabolismo , Oligosacáridos/química , Oligosacáridos/metabolismo , Proteínas/metabolismo , Animales , Descubrimiento de Drogas , Heparina/síntesis química , Heparina/farmacología , Heparitina Sulfato/síntesis química , Heparitina Sulfato/farmacología , Humanos , Modelos Moleculares , Oligosacáridos/síntesis química , Oligosacáridos/farmacología
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