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1.
Methods ; 213: 26-32, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36924866

RESUMO

Amblyopia is an abnormal visual processing-induced developmental disorder of the central nervous system that affects static and dynamic vision, as well as binocular visual function. Currently, changes in static vision in one eye are the gold standard for amblyopia diagnosis. However, there have been few comprehensive analyses of changes in dynamic vision, especially eye movement, among children with amblyopia. Here, we proposed an optimization scheme involving a video eye tracker combined with an "artificial eye" for comprehensive examination of eye movement in children with amblyopia; we sought to improve the diagnostic criteria for amblyopia and provide theoretical support for practical treatment. The resulting eye movement data were used to construct a deep learning approach for diagnostic and predictive applications. Through efforts to manage the uncooperativeness of children with strabismus who could not complete the eye movement assessment, this study quantitatively and objectively assessed the clinical implications of eye movement characteristics in children with amblyopia. Our results indicated that an amblyopic eye is always in a state of adjustment, and thus is not "lazy." Additionally, we found that the eye movement parameters of amblyopic eyes and eyes with normal vision are significantly different. Finally, we identified eye movement parameters that can be used to supplement and optimize the diagnostic criteria for amblyopia, providing a diagnostic basis for evaluation of binocular visual function.


Assuntos
Ambliopia , Estrabismo , Criança , Humanos , Ambliopia/diagnóstico , Ambliopia/terapia , Movimentos Oculares , Estrabismo/diagnóstico , Visão Binocular/fisiologia , Sistema Nervoso Central
2.
BMC Ophthalmol ; 24(1): 278, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982388

RESUMO

OBJECTIVE: To investigate the characteristics of eye movement in children with anisometropic amblyopia, and to compare those characteristics with eye movement in a control group. METHODS: 31 children in the anisometropic amblyopia group (31 amblyopic eyes in group A, 31 contralateral eyes in group B) and 24 children in the control group (48 eyes in group C). Group A was subdivided into groups Aa (severe amblyopia) and Ab (mild-moderate amblyopia). The overall age range was 6-12 years (mean, 7.83 ± 1.79 years). All children underwent ophthalmic examinations; eye movement parameters including saccade latency and amplitude were evaluated using an Eyelink1000 eye tracker. Data Viewer and MATLAB software were used for data analysis. RESULTS: Mean and maximum saccade latencies, as well as mean and maximum saccade amplitudes, were significantly greater in group A than in groups B and C before and after treatment (P < 0.05). Mean and maximum saccade latencies were significantly different among groups Aa, Ab, and C (P < 0.05). Pupil trajectories in two detection modes suggested that binocular fixation was better than monocular fixation. CONCLUSIONS: Eye movement parameters significantly differed between contralateral normal eyes and control eyes. Clinical evaluation of children with anisometropic amblyopia should not focus only on static visual acuity, but also on the assessment of eye movement.


Assuntos
Ambliopia , Visão Binocular , Acuidade Visual , Humanos , Ambliopia/fisiopatologia , Criança , Masculino , Feminino , Acuidade Visual/fisiologia , Visão Binocular/fisiologia , Movimentos Sacádicos/fisiologia , Movimentos Oculares/fisiologia , Anisometropia/fisiopatologia , Anisometropia/complicações , Fixação Ocular/fisiologia
3.
Mar Drugs ; 22(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39195477

RESUMO

The inhibition of dipeptidyl peptidase-IV (DPP-IV) is a promising approach for regulating the blood glucose levels in patients with type 2 diabetes (T2D). Oysters, rich in functional peptides, contain peptides capable of inhibiting DPP-IV activity. This study aims to identify the hypoglycemic peptides from oysters and investigate their potential anti-T2D targets and mechanisms. This research utilized virtual screening for the peptide selection, followed by in vitro DPP-IV activity assays to validate the chosen peptide. Network pharmacology was employed to identify the potential targets, GO terms, and KEGG pathways. Molecular docking and molecular dynamics simulations were used to provide virtual confirmation. The virtual screening identified LRGFGNPPT as the most promising peptide among the screened oyster peptides. The in vitro studies confirmed its inhibitory effect on DPP-IV activity. Network pharmacology revealed that LRGFGNPPT exerts an anti-T2D effect through multiple targets and signaling pathways. The key hub targets are AKT1, ACE, and REN. Additionally, the molecular docking results showed that LRGFGNPPT exhibited a strong binding affinity with targets like AKT1, ACE, and REN, which was further confirmed by the molecular dynamics simulations showcasing a stable peptide-target interaction. This study highlights the potential of LRGFGNPPT as a natural anti-T2D peptide, providing valuable insights for potential future pharmaceutical or dietary interventions in T2D management.


Assuntos
Diabetes Mellitus Tipo 2 , Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV , Simulação de Acoplamento Molecular , Peptídeos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Animais , Dipeptidil Peptidase 4/metabolismo , Dipeptidil Peptidase 4/química , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/isolamento & purificação , Humanos , Simulação de Dinâmica Molecular , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Ostreidae/química , Farmacologia em Rede , Descoberta de Drogas
4.
Mar Drugs ; 22(8)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39195475

RESUMO

Pearl and nacre powders have been valuable traditional Chinese medicines with whitening properties for thousands of years. We utilized a high-temperature and high-pressure method along with compound enzyme digestion to prepare the enzymatic hydrolysates of nacre powder of Pinctada martensii (NP-PMH). The peptides were identified using LC-MS/MS and screened through molecular docking and molecular dynamics simulations. The interactions between peptides and tyrosinase were elucidated through enzyme kinetics, circular dichroism spectropolarimetry, and isothermal titration calorimetry. Additionally, their inhibitory effects on B16F10 cells were explored. The results showed that a tyrosinase-inhibitory peptide (Ala-His-Tyr-Tyr-Asp, AHYYD) was identified, which inhibited tyrosinase with an IC50 value of 2.012 ± 0.088 mM. The results of the in vitro interactions showed that AHYYD exhibited a mixed-type inhibition of tyrosinase and also led to a more compact enzyme structure. The binding reactions of AHYYD with tyrosinase were spontaneous, leading to the formation of a new set of binding sites on the tyrosinase. The B16F10 cell-whitening assay revealed that AHYYD could reduce the melanin content of the cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that AHYYD could be widely used as a tyrosinase inhibitor in whitening foods and pharmaceuticals.


Assuntos
Inibidores Enzimáticos , Melaninas , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Peptídeos , Pinctada , Animais , Monofenol Mono-Oxigenase/antagonistas & inibidores , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/isolamento & purificação , Camundongos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Melaninas/antagonistas & inibidores , Linhagem Celular Tumoral , Melanoma Experimental/tratamento farmacológico , Simulação de Dinâmica Molecular , Simulação por Computador , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação
5.
Mar Drugs ; 22(9)2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39330301

RESUMO

For thousands of years, pearl and nacre powders have been important traditional Chinese medicines known for their skin whitening effects. To prepare the enzymatic hydrolysates of Hyriopsis cumingii nacre powder (NP-HCH), complex enzymatic hydrolysis by pineapple protease and of neutral protease was carried out after the powder was pre-treated with a high-temperature and high-pressure method. The peptides were identified using LC-MS/MS and picked out through molecular docking and molecular dynamics simulations. Subsequently, the tyrosinase inhibitory and antioxidant properties of novel tyrosinase inhibitory peptides were investigated in vitro. In addition, the enzymatic activity of tyrosinase in B16F10 cells as well as melanin content and antioxidant enzyme levels were also examined. The results showed that a tyosinase inhibitory peptide (Tyr-Pro-Asn-Pro-Tyr, YPNPY) with an efficient IC50 value of 0.545 ± 0.028 mM was identified. The in vitro interaction results showed that YPNPY is a reversible competitive inhibitor of tyrosinase, suggesting that it binds to the free enzyme. The B16F10 cell whitening test revealed that YPNPY can reduce the melanin content of B16F10 cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that YPNPY could be widely used as a tyrosinase inhibitor in whitening foods and drugs.


Assuntos
Antioxidantes , Melaninas , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Peptídeos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Animais , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/isolamento & purificação , Camundongos , Antioxidantes/farmacologia , Antioxidantes/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Linhagem Celular Tumoral , Melanoma Experimental/tratamento farmacológico , Simulação por Computador , Espectrometria de Massas em Tandem , Preparações Clareadoras de Pele/farmacologia , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/isolamento & purificação , Simulação de Dinâmica Molecular
6.
Molecules ; 29(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38398650

RESUMO

Oysters contain significant amounts of the zinc element, which may also be found in their proteins. In this study, a novel zinc-binding protein was purified from the mantle of the oyster Magallana hongkongensis using two kinds of gel filtration chromatograms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that its molecular weight was approximately 36 kDa. The protein identified by the Q-Exactive mass spectrometer shared the highest sequence identity with carbonic anhydrase derived from Crassostrea gigas concerning amino acid sequence similarity. Based on homologous cloning and RACE PCR, the full-length cDNA of carbonic anhydrase from Magallana hongkongensis (designated as MhCA) was cloned and sequenced. The cDNA of MhCA encodes a 315-amino-acid protein with 89.74% homology to carbonic anhydrase derived from Crassostrea gigas. Molecular docking revealed that the two zinc ions primarily form coordination bonds with histidine residues in the MhCA protein. These results strongly suggest that MhCA is a novel zinc-binding protein in Magallana hongkongensis.


Assuntos
Anidrases Carbônicas , Proteínas de Transporte , Crassostrea , Animais , DNA Complementar/genética , Simulação de Acoplamento Molecular , Clonagem Molecular , Crassostrea/metabolismo , Anidrases Carbônicas/metabolismo , Zinco
7.
Crit Rev Food Sci Nutr ; : 1-20, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966171

RESUMO

Taste peptides are oligopeptides that enhance both aroma and taste of food, and they are classified into five categories based on their taste characteristics: salty, sour, umami, sweet, bitter, and kokumi peptide. Recently, taste peptides have attracted the attention of several fields of research in food science and commercial applications. However, research on taste receptors of taste peptides and their taste transduction mechanisms are not clearly understood and we present a comprehensive review about these topics here. This review covers the aspects of taste peptides perceived by their receptors in taste cells, the proposed transduction pathway, as well as structural features of taste peptides. Apart from traditional methods, molecular docking, peptidomic analysis, cell and animal models and taste bud biosensors can be used to explore the taste mechanism of taste peptides. Furthermore, synergistic effect, Maillard reaction, structural modifications and changing external environment are employed to improve the taste of taste peptides. Consequently, we discussed the current challenges and future trends in taste peptide research. Based on the summarized developments, taste peptides derived from food proteins potentially appear to be important taste substances. Their applications meet the principles of "safe, nutritious and sustainable" in food development.

8.
Mol Vis ; 28: 352-358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338666

RESUMO

Purpose: To investigate the molecular pathogenesis of a large group of Han Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and to evaluate the correlation between the phenotype and genotype for these patients. Methods: Seventy-six affected individuals, including 45 patients from 17 pedigrees and 31 sporadic patients, were recruited with their family members. All participants underwent complete clinical examinations and were classified as having type I or II based on whether they had premature ovarian failure. The patients' genomic DNA was extracted. A genetic test was performed with direct sequencing of the coding regions of the forkhead transcriptional factor 2 (FOXL2) gene. Variations were analyzed using online databases and programs. Genotype-phenotype correction was investigated. Results: Seventy-six affected and 75 unaffected individuals underwent clinical evaluations and genetic testing. Only one family was diagnosed with type I; the others could not be classified because of a lack of female patients or a definite history of premature ovarian failure. Twenty-seven variations were identified, including 12 novel and 15 previously reported variations. Six variations were detected repeatedly in different nonconsanguineous pedigrees. Four indel variations, located in the alanine/proline-rich region of the FOXL2 gene, presented with a relatively higher frequency. Two rare double variations were detected in two sporadic patients. FOXL2 gene variations were not detected in five sporadic patients. The phenotype varied among different families and patients, although they carried the same variations. Conclusions: We identified 12 novel variations in the FOXL2 gene that would expand the spectrum of the FOXL2 variation database. In addition, we found that the alanine/proline-rich region is a variation hotspot in the FOXL2 gene. The genotype-phenotype correlation is not easy to establish due to clinical and genetic heterogeneity.


Assuntos
Blefarofimose , Insuficiência Ovariana Primária , Humanos , Feminino , Blefarofimose/genética , Blefarofimose/diagnóstico , Linhagem , Insuficiência Ovariana Primária/genética , Mutação/genética , Proteína Forkhead Box L2/genética , Fatores de Transcrição Forkhead/genética , Alanina/genética , China , Prolina/genética
9.
Mar Drugs ; 20(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36547896

RESUMO

This study aimed to purify and identify antiphotoaging peptides from oyster (Crassostrea hongkongensis) protein enzymatic hydrolysates (OPEH) and to investigate the possible mechanism underlying its antiphotoaging effect. Multiple methods (Ultrafiltration, G25 Chromatography, RP-HPLC, and LC/MS/MS) had been used for this purpose, and eventually, two peptides, including WNLNP and RKNEVLGK, were identified. Particularly, WNLNP exerted remarkable antiphotoaging effect on the UVB-irradiated HaCaT photoaged cell model in a dose-dependent manner. WNLNP exerted its protective effect mainly through inhibiting ROS production, decreasing MMP-1 expression, but increasing extracellular pro-collagen I content. Furthermore, WNLNP downregulated p38, JNK, ERK, and p65 phosphorylation in the MAPK/NF-κB signaling pathway and attenuated bax over-expressions but reversed bcl-2 reduction in UVB- irradiated HaCaT cells. The molecular docking analysis showed that WNLNP forms five and seven hydrogen bonds with NF-κB (p65) and MMP-1, respectively. This study suggested that a pentapeptide WNLNP isolated from OPEH had great potential to prevent and regulate skin photoaging.


Assuntos
Crassostrea , Oligopeptídeos , Envelhecimento da Pele , Animais , Humanos , Crassostrea/química , Células HaCaT , Metaloproteinase 1 da Matriz/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Espectrometria de Massas em Tandem , Raios Ultravioleta/efeitos adversos , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Oligopeptídeos/farmacologia
10.
Int J Mol Sci ; 22(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34884714

RESUMO

As an important component that constitutes all the cells and tissues of the human body, protein is involved in most of the biological processes. Inspired by natural protein systems, considerable efforts covering many discipline fields were made to design artificial protein assemblies and put them into application in recent decades. The rapid development of structural DNA nanotechnology offers significant means for protein assemblies and promotes their application. Owing to the programmability, addressability and accurate recognition ability of DNA, many protein assemblies with unprecedented structures and improved functions have been successfully fabricated, consequently creating many brand-new researching fields. In this review, we briefly introduced the DNA-based protein assemblies, and highlighted the limitations in application process and corresponding strategies in four aspects, including biological catalysis, protein detection, biomedicine treatment and other applications.


Assuntos
DNA/química , Nanotecnologia , Proteínas/síntese química , Catálise , Sistemas de Liberação de Medicamentos , Proteínas/análise
11.
Molecules ; 26(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806637

RESUMO

Marine collagen peptides have high potential in promoting skin wound healing. This study aimed to investigate wound healing activity of collagen peptides derived from Sipunculus nudus (SNCP). The effects of SNCP on promoting healing were studied through a whole cortex wound model in mice. Results showed that SNCP consisted of peptides with a molecular weight less than 5 kDa accounted for 81.95%, rich in Gly and Arg. SNCP possessed outstanding capacity to induce human umbilical vein endothelial cells (HUVEC), human immortalized keratinocytes (HaCaT) and human skin fibroblasts (HSF) cells proliferation and migration in vitro. In vivo, SNCP could markedly improve the healing rate and shorten the scab removal time, possessing a scar-free healing effect. Compared with the negative control group, the expression level of tumor necrosis factor-α, interleukin-1ß and transforming growth factor-ß1 (TGF-ß1) in the SNCP group was significantly down-regulated at 7 days post-wounding (p < 0.01). Moreover, the mRNA level of mothers against decapentaplegic homolog 7 (Smad7) in SNCP group was up-regulated (p < 0.01); in contrast, type II TGF-ß receptors, collagen I and α-smooth muscle actin were significantly down-regulated at 28 days (p < 0.01). These results indicate that SNCP possessed excellent activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to reducing inflammation, improving collagen deposition and recombination and blockade of the TGF-ß/Smads signal pathway. Therefore, SNCP may have promising clinical applications in skin wound repair and scar inhibition.


Assuntos
Cicatriz/tratamento farmacológico , Colágeno/farmacologia , Queratinócitos/efeitos dos fármacos , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/farmacologia , Poliquetos/química , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Cicatriz/metabolismo , Colágeno/química , Humanos , Queratinócitos/metabolismo , Masculino , Camundongos , Fragmentos de Peptídeos/química , Transdução de Sinais , Pele/metabolismo
12.
Mar Drugs ; 18(6)2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32486363

RESUMO

Chronic exposure to ultraviolet B (UVB) irradiation is a major cause for skin photoaging. UVB induces damage to skin mainly by oxidative stress, inflammation, and collagen degradation. This paper investigated the photo-protective effects of peptides from oyster (Crassostrea hongkongensis) protein hydrolysates (OPs) by topical application on the skin of UVB-irradiated mice. Results from mass spectrometry showed that OPs consisted of peptides with a molecular weight range of 302.17-2936.43 Da. In vivo study demonstrated that topical application of OPs on the skin significantly alleviated moisture loss, epidermal hyperplasia, as well as degradation of collagen and elastin fibers caused by chronic UVB irradiation. In this study, OPs treatment promoted antioxidant enzymes (SOD and GPH-Px) activities, while decreased malondialdehyde (MDA) level in the skin. In addition, OPs treatment significantly decreased inflammatory cytokines (IL-1ß, IL-6, TNF-α) content, and inhibited inflammation related (iNOS, COX-2) protein expression in the skin. Via inhibiting metalloproteinase 1(MMP1) expression, OPs treatment markedly decreased the degradation of collagen and elastin fibers as well as recovered the altered arrangement of extracellular matrix network in the dermis of skin. Our study demonstrated for the first time that OPs protected against UVB induced skin photodamage by virtue of its antioxidative and anti-inflammatory properties, as well as regulating the abnormal expression of MMP-1. The possible molecular mechanism underlying OPs anti-photoaging is possibly related to downregulating of the MAPK/NF-κB signaling pathway, while promoting TGF-ß production in the skin.


Assuntos
Anti-Inflamatórios/farmacologia , Crassostrea/química , Hidrolisados de Proteína/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Raios Ultravioleta , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos
13.
Arch Gynecol Obstet ; 302(3): 579-584, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32617665

RESUMO

PURPOSE: To compare the effectiveness of the Cook vaginal cervical ripening balloon (CCRB) with prostaglandin E2 (PGE2) insert for induction of labor in late pregnancy in primipara. METHODS: We evaluated the effectiveness and safety of induction of labor using the improved Bishop score after CCRB or PGE2 administration, total stage of labor, hours until delivery (hours from placement of CCRB or PGE2 insert to parturition and delivery), delivery rate within 24 h, spontaneous delivery rate, successful induction rate, overstimulation syndrome, urgent delivery rate, pain scores, cesarean section rate, and outcomes related to delivery and perinatal morbidity, such as puerperal infection rate, total cost, satisfaction survey, and so on. RESULTS: The improved Bishop Score and delivery rate within 24 h in the CCRB group were significantly higher than in the PGE2 group. The total stage of labor and hours until delivery in the CCRB group were significantly shorter than that in the PGE2 group. Rate of overstimulation syndrome and pain scores in the CCRB group were significantly lower than in the PGE2 group. Compared with the PGE2 group, the mean duration of hospitalization in the CCRB group was shorter and the total cost was less. No difference in satisfaction between the PGE2 and CCRB groups was observed. CONCLUSIONS: Compared with PGE2, CCRB reduced the total stage of labor, hours until delivery, pain scores, mean length of hospitalization, and total cost. CCRB increased the rate of delivery within 24 h with similar safety and maternal satisfaction compared with PGE2.


Assuntos
Maturidade Cervical , Colo do Útero/efeitos dos fármacos , Dinoprostona/administração & dosagem , Trabalho de Parto Induzido/métodos , Ocitócicos/administração & dosagem , Administração Intravaginal , Adulto , Cesárea/estatística & dados numéricos , China , Dinoprostona/uso terapêutico , Feminino , Humanos , Ocitócicos/uso terapêutico , Gravidez , Resultado do Tratamento , Vagina
14.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(3): 460-468, 2020 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-32597088

RESUMO

In order to explore the effect of Sipunculus nudus extract (SNE) on skin wound healing in mice and its mechanism, hemostasis effect of SNE was measured, the mouse skin wound model was established by full-thickness excision. The morphological changes of the wound were observed after the treatment with SNE and the healing rate was measured. The changes of wound histology were observed by hematoxylin eosin (HE) staining, Masson staining and transmission electron microscope (TEM). The expression of cell factors and related proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that the SNE possessed hemostatic function. SNE could obviously improve the healing rate of wound in mouse and shorten time of scab removal compared with the none-treatment (NT) group ( P < 0.05).The pathological histology analysis results showed complete epidermal regeneration, with remarkable capillary and collagen fiber observed in the SNE group. The expression level of tumor necrosis factor-α (TNF -α), interleukin-1ß (IL-1ß) and transforming growth factor-ß1 (TGF-ß1) in SNE group was significantly lower than that of the NT group on 7 d ( P < 0.05). Moreover, compared with the NT group, the gene expressions level of Smad7 was significantly increased and the level of type II TGF-ß receptors (TGF-ßRII), collagen I (COL1A1) and α-smooth muscle actin (α-SMA) were significantly reduced in the SNE group on 28 d ( P < 0.05), but the difference was not statistically significant compared to Yunnanbaiyao group (PC group) ( P > 0.05). These results indicated that SNE possessed obvious activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to hemostatic function, regulation of inflammatory factors, collagen deposition, collagen fiber remodeling and intervening TGF-ß/Smads signal pathway. Therefore, SNE may have promising clinical applications in skin wound repair and scar inhibition.


Assuntos
Pele , Cicatrização , Aceleração , Animais , Anelídeos , Colágeno , Camundongos , Fator de Crescimento Transformador beta1
15.
J Physiol ; 593(17): 4067-79, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26108677

RESUMO

Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin's microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Adiponectina/fisiologia , Dieta Hiperlipídica , Resistência à Insulina , Insulina/fisiologia , Óxido Nítrico/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/sangue , Animais , Aorta/metabolismo , Insulina/sangue , Masculino , Microvasos/fisiologia , Músculo Esquelético/metabolismo , Ratos Sprague-Dawley
16.
Clin Sci (Lond) ; 129(12): 1025-36, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26265791

RESUMO

Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications.


Assuntos
Dieta Hiperlipídica , Inflamação/etiologia , Resistência à Insulina , Microcirculação , Microvasos/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Obesidade/etiologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores/sangue , Glicemia/metabolismo , Modelos Animais de Doenças , Inflamação/sangue , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Insulina/sangue , Masculino , Microcirculação/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/sangue , Obesidade/fisiopatologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Salicilato de Sódio/farmacologia , Fatores de Tempo
17.
Circ Res ; 112(9): 1263-71, 2013 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-23459195

RESUMO

RATIONALE: Adiponectin enhances insulin action and induces nitric oxide-dependent vasodilatation. Insulin delivery to muscle microcirculation and transendothelial transport are 2 discrete steps that limit insulin's action. We have shown that expansion of muscle microvascular surface area increases muscle insulin delivery and action. OBJECTIVE: To examine whether adiponectin modulates muscle microvascular recruitment thus insulin delivery and action in vivo. METHODS AND RESULTS: Overnight fasted adult male rats were studied. We determined the effects of adiponectin on muscle microvascular recruitment, using contrast-enhanced ultrasound, on insulin-mediated microvascular recruitment and whole-body glucose disposal, using contrast-enhanced ultrasound and insulin clamp, and on muscle insulin clearance and uptake with (125)I-insulin. Globular adiponectin potently increased muscle microvascular blood volume without altering microvascular blood flow velocity, leading to a significantly increased microvascular blood flow. This was paralleled by a ≈30% to 40% increase in muscle insulin uptake and clearance, and ≈30% increase in insulin-stimulated whole-body glucose disposal. Inhibition of endothelial nitric oxide synthase abolished globular adiponectin-mediated muscle microvascular recruitment and insulin uptake. In cultured endothelial cells, globular adiponectin dose-dependently increased endothelial nitric oxide synthase phosphorylation but had no effect on endothelial cell internalization of insulin. CONCLUSIONS: Globular adiponectin increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action.


Assuntos
Adiponectina/administração & dosagem , Glicemia/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Microcirculação/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Adiponectina/química , Animais , Glicemia/metabolismo , Bovinos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Inibidores Enzimáticos/farmacologia , Jejum/sangue , Técnica Clamp de Glucose , Membro Posterior , Hipoglicemiantes/metabolismo , Infusões Intravenosas , Injeções Intraperitoneais , Insulina/metabolismo , Masculino , Microvasos/diagnóstico por imagem , Músculo Esquelético/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de Tempo , Ultrassonografia
18.
Zhonghua Yan Ke Za Zhi ; 51(11): 844-9, 2015 Nov.
Artigo em Zh | MEDLINE | ID: mdl-26850587

RESUMO

OBJECTIVE: To evaluate the efficacy of surgery in the treatment of congenital nystagmus with convergence damping. METHODS: Retrospective and comparative case series. Eight patients diagnosed as congenital nystagmus with convergence damping at Beijing Children's Hospital between September 2010 and September 2012 were enrolled in this study. The ages were 9.5 (12, 6) years old, and follow-up was 9 (24, 6) months. All patients received prism induced convergence and the same surgery of bimedial rectus recession and bilateral rectus tenotomy. The best corrected visual acuity, the range of fusion and the nystagmus waveforms were analyzed before and after surgery. RESULTS: The range of fusion was -3.75±1.83° to +19.38±3.16° before surgery and -3.88±1.55° to +19.00±3.02° after surgery; there was no significant difference (t=0.24, P=0.82). The binocular visual acuity increased from 0.21±0.15 without convergence to 0.28±0.18 using convergence; there was significant difference (t=-4.43, P=0.00). The visual acuity was 0.32±0.20 after surgery, significantly different from that before surgery without convergence (t=-5.29, P=0.00), but not significantly different from that before surgery using convergence (t=-2.12, P=0.07). Patients had significant improvements in the frequency (t=3.28, 3.02, P<0.05) and intensity of the nystagmus waveforms when using convergence and postoperatively (t=3.27, 3.48; P<0.05), but there was no significant improvement in the amplitude of the waveforms (t=1.31, 1.57, 0.31, P>0.05). CONCLUSIONS: Surgery for congenital nystagmus with convergence damping can provide expectations for ocular motor and visual results. The range of fusion should be wide enough, and the effect of convergence on the frequency is greater than that on the amplitude.


Assuntos
Nistagmo Congênito/cirurgia , Músculos Oculomotores/cirurgia , Pequim , Criança , Seguimentos , Humanos , Nistagmo Congênito/fisiopatologia , Nistagmo Fisiológico , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo , Acuidade Visual
19.
J Biol Chem ; 288(13): 9313-20, 2013 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-23404499

RESUMO

In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or ß-arrestin 2 (siRNA)). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.


Assuntos
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Hepatócitos/citologia , Insulina/metabolismo , Leucina/metabolismo , Animais , Diabetes Mellitus/metabolismo , Inativação Gênica , Gluconeogênese , Glucose/metabolismo , Humanos , Camundongos , Modelos Biológicos , Obesidade/metabolismo , Fosforilação , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
20.
Pharm Biol ; 52(6): 723-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24428850

RESUMO

CONTEXT: Oysters [Crassostrea plicatula Gmelin (Ostreidae)] are widely used for food in coastal areas. It is reported to have several qualities such as improving sexual and immune function. They has been approved by Chinese Ministry of Health as a functional food. OBJECTIVE: The effects of five types of oyster components (oyster meat, oyster glycogen, oyster protein, cooked liquid components, and water-insoluble components) on the swimming endurance of mice were investigated. MATERIALS AND METHODS: First, the amino acid composition and sugar content of the five oyster components were analyzed by a physicochemical test. In the in vivo test, the control group was administered distilled water, and the five intervention groups were treated with various samples for 15 consecutive days [0.8 mg protein/(g BW·d) or 0.2 mg glycogen/(g BW·d)]. The swimming time was recorded through the exhaustive swimming test. The levels of serum lactic acid, blood urea nitrogen (BUN), liver glycogen, and gastrocnemius muscle glycogen were determined. RESULTS: Oyster protein had a minimum F-value (the mole ratio of branched-chain amino acids to aromatic amino acids) (2.68), contained 1.85 mmol/mL taurine and no sugar. The components (except for oyster protein) significantly improved endurance capacity of mice and increased the liver and muscle glycogen contents (p<0.05), and reduced the lactic acid and BUN levels (p<0.05). Oyster protein had little effect. DISCUSSION AND CONCLUSION: The effects of oyster components on the swimming endurance of mice may be attributed to the high ratio of the branched-chain amino acid composition, bioactivity of taurine, and glycogen.


Assuntos
Crassostrea , Glicogênio/farmacologia , Condicionamento Físico Animal/fisiologia , Resistência Física/fisiologia , Frutos do Mar , Natação/fisiologia , Animais , Glicogênio/isolamento & purificação , Glicogênio/metabolismo , Ácido Láctico/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/métodos , Resistência Física/efeitos dos fármacos
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