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1.
ACS Appl Mater Interfaces ; 12(47): 53247-53256, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33185423

RESUMO

Conductive hydrogels have shown great potential in the field of flexible strain sensors. However, their application is greatly limited due to the low conductivity and poor mechanical properties at subzero temperatures. Herein, an ultrastretchable, tough, antifreezing, and conductive cellulose hydrogel was fabricated by grafting acrylonitrile and acrylamide copolymers onto the cellulose chains in the presence of zinc chloride using ceric ammonium nitrate as the initiator. The resulting hydrogel exhibited ultrastretchability (1730%), excellent tensile strength (160 kPa), high elasticity (90%), good toughness (1074.7 kJ/m3), and fatigue resistance property due to the existence of dipole-dipole and multiple hydrogen-bonding interactions on the hydrogel network. In addition, the introduced zinc chloride endowed the cellulose-based hydrogel with remarkable electric conductivity (1.54 S/m) and excellent antifreezing performance (-33 °C). Finally, the hydrogel showed high sensitivity and stability to monitor human activities. In summary, this work presented a facile strategy to construct conductive hydrogel with excellent antifreezing and mechanical properties simultaneously, which showed great potential for wearable strain sensors.

2.
J Biomater Appl ; : 885328220952594, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854570

RESUMO

In this work, gold embedded chitosan nanoparticles (Au@CS NPs) were fabricated by a one-pot method. The benzaldehyde-terminated poly[(2-methacryloyloxy) ethyl phosphorylcholine] (PMPC) was applied to modification of the gold doped chitosan nanoparticles. The obtained Au@CS-PMPC NPs had the diameter of 135 nm with a narrow distribution. The size of the Au@CS-PMPC NPs, as well as the size of the embedded gold NPs, might be well-controlled by adjusting the feeding ratio between chitosan and HAuCl4. Furthermore, the Au@CS-PMPC NPs showed increased colloidal stability, high drug loading content, pH-responsive drug release, excellent biocompatibility and bright fluorescence emission. The results demonstrated that Au@CS-PMPC NPs showed a great potential for tumor therapy via the combination advantages of pH-sensitive controlled drug release and cellular fluorescence imaging.

3.
Zhongguo Zhen Jiu ; 40(5): 465-71, 2020 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-32394651

RESUMO

OBJECTIVE: To compare the clinical effect differences among different acupoint selection methods for primary insomnia. METHODS: A total of 333 patients with primary insomnia were recruited from 3 study centers and randomly divided into a group A (111 cases, 7 cases dropped off), a group B (111 cases, 5 cases dropped off) and a group C (111 cases, 2 cases dropped off). The patients in the group A were treated with acupuncture at Shenmen (HT 7) and Baihui (GV 20), the patients in the group B were treated with acupuncture at Sanyinjiao (SP 6) and Baihui (GV 20), and the patients in the group C were treated with acupuncture at non-acupoint and Baihui (GV 20). All the treatment was given once a day, 30 min each time; 5 treatments were taken as a course and 5 courses of treatment were given. The Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS) scores were evaluated before and after treatment as well as 4 weeks after treatment. The encephalofluctuograph technology (ET) was observed before and after treatment. RESULTS: Compared before treatment, the PSQI scores after treatment and at follow-up were significantly decreased in three groups (P<0.01), and the decrease in the group A and the group B was greater than that in the group C (P<0.01). Compared before treatment, the AIS scores after treatment and at follow-up was significantly decreased in three groups (P<0.01), and the decrease in the group A was greater than that in the group C (P<0.05). The interclass and between-groups ET before and after treatment had no significant difference (P>0.05). CONCLUSION: The acupuncture at acupoints along the meridians could improve the sleep quality in patients with primary insomnia, and the therapeutic effect of acupoint along the meridians is better than that of non-acupoint.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Meridianos , Distúrbios do Início e da Manutenção do Sono/terapia , Humanos , Resultado do Tratamento
4.
Colloids Surf B Biointerfaces ; 176: 1-8, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590344

RESUMO

In this study, we modified the well-known photothermal polydopamine nanoparticles with the poly[(2-methacryloyloxy)ethyl phosphorylcholine-b-(2-dimethylamino)ethyl methacrylate] (PMPC-b-PDMAEMA) diblock copolymers, containing both biocompatible cell membrane phosphorylcholine zwitterions segments and pH-responsive dimethylaminoethyl units on the polymer chains, to achieve both the photothermal property and pH-responsive release behavior. The results showed that the obtained nanoparticles had a narrow size distribution with the diameter about 220 nm. Besides, the modified polydopamine nanoparticles showed enhanced colloidal stability, pH-sensitive drug release behavior, excellent biocompatibility and remarkable near-infrared photothermal property. Thus, it is highly anticipated that PMPC-b-PDMAEMA modified polydopamine nanoparticles can serve as a powerful drug delivery system for combined pH-sensitive drug release and near-infrared photothermal therapeutic.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Nanopartículas/química , Fototerapia , Polímeros/química , Antibióticos Antineoplásicos/química , Membrana Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
5.
Zhen Ci Yan Jiu ; 43(6): 360-4, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-30091541

RESUMO

OBJECTIVE: To observe the effect of manual acupuncture stimulation of paired "Baihui" (GV 20)+ "Shenmen" (HT 7), GV 20+ "Sanyinjiao" (SP 6), and GV 20+ non-acupoint on expression of melatonine (MT) and suprachiasmatic melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) mRNAs in insomnia rats, so as to explore their action difference and the underlying mechanism in improving insomnia. METHODS: Male SD rats were randomly divided into normal control (n=12), mo-del (n=8), GV 20+HT 7(n=12), GV 20+SP 6(n=11), and GV 20+ non-acupoint (n=10) groups. The insomnia model was established by intraperitoneal injection of Para-chlorophenylalanine suspension (50 mg/mL, 50 mg/100 g), once daily for 2 days. The abovementioned acupoints GV 20, bilateral HT 7, SP 6 and non-acupoints (the midpoint between the elbow-tip and armpit on the medial side of the upper-arm) were punctured with filiform needles and manipulated by rotating the needle for about 1 min which was repeated once again every 10 min during 30 minutes' needle-retaining. The treatment was conducted once daily for 7 days. The expression levels of MT immunoactivity in the conarium tissue, and MT1 and MT2 mRNAs of the suprachiasmatic nucleus (SCN) region were detected using immunohistochemistry and fluorescence quantitative real time-PCR, respectively. RESULTS: After modeling, the expression levels of pineal MT (an increase of gray value means a decrease of immunoactivity), SCN MT1 and MT2 mRNAs were notably down-regulated in the model group relevant to the normal control group (P<0.05, P<0.01). Following the treatment, the down-regulated expression levels of MT protein, and MT1 and MT2 mRNAs were obviously reversed in the GV 20 + HT 7, GV 20 + SP 6 groups relevant to the model group (P<0.05, P<0.01). The therapeutic effect of GV 20+ HT 7 was superior to that of GV 20+ non-acupoint in up-regulating the expression of MT1 mRNA (P<0.01), and markedly superior to that of GV 20+ SP 6 and GV 20+ non-acupoint in increasing the sleep duration and in up-regulating the expression of MT2 mRNA (P<0.01). No significant differences were found among the 3 treatment groups in up-regulating the expression of MT (P>0.05). CONCLUSION: Manual acupuncture stimulation of GV 20+ HT 7 and GV 20+ SP 6 can improve the sleep disorder in insomnia rats, which may be related to its effects in increasing the levels of pineal MT protein, and MT1 and MT2 mRNAs in hypothalamic SCN.


Assuntos
Melatonina , Distúrbios do Início e da Manutenção do Sono , Pontos de Acupuntura , Animais , Masculino , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Núcleo Supraquiasmático
6.
Zhen Ci Yan Jiu ; 43(3): 169-74, 2018 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-29560632

RESUMO

OBJECTIVE: To observe the effect of different strength of electroacupuncture (EA) stimulation on gastrointestinal motility and Ras homolog gene family member (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) signaling in diabetic gastroparesis (DGP) rats, so as to reveal the underlying mechanisms of EA for improving DGP. METHODS: Sixty SD rats were randomly and equally divided into blank control, DGP model, weak EA, medium EA, and strong EA groups (n=12 rats in each). The DGP model was established by intraperitoneal injection of streptozotocin (STZ, 55 mmol/kg, 2%) and high-sugar and high-fat fodder feeding for 8 weeks. EA (0.12, 0.24, 0.36 mA, 20 Hz/100 Hz) was applied to "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Liangmen" (ST 21) for 20 min, once daily for 15 successive days. Blood glucose levels were measured weekly with blood glucose meter and blood glucose test paper. Fecal phenol red excretion method was used to display gastric emptying and small intestinal propulsion function. The expression of RhoA protein in the gastric antral smooth muscle tissue was detected by immunohistochemistry and Western blot (WB), separately, and that of ROCK, myosin phosphatase target subunit 1 (MYPT 1) and phosphorylated (p)-MYPT 1 proteins in gastric antrum detected by WB. RESULTS: Compared with the blank control group, the gastric emptying rate and small intestine propulsion rate of the model group were significantly decreased (P<0.05), and the blood glucose level was remarkably increased (P<0.05). Moreover, the expression levels of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins in the gastric antrum were significantly down-regulated relevant to the control group (P<0.05). After administration of EA, the decreased gastric emptying rate and intestinal propulsion rate, and the down-regulated expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins were significantly increased in the strong, medium and weak EA stimulation groups (P<0.05). Comparison among the 3 EA groups showed that the strong stimulation was significantly superior to weak stimulation in up-regulating the expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins, and obviously superior to the medium stimulation in up-regulating RhoA and MYPT 1 protein levels (P<0.05), while the medium stimulation was significantly stronger than the weak stimulation in up-regulating the expression of ROCK, MYPT 1 and p-MYPT 1 proteins (P<0.05). There were no significant differences among the 3 EA groups in up-regulating the gastric emptying rate and small intestinal propulsion rate, and between the strong stimulation and medium stimulation in the expression levels of ROCK and p-MYPT 1 proteins (P>0.05). CONCLUSION: Electroacupuncture stimulation of ST 36-SP 6-ST 21 at 0.12, 0.24 and 0.36 mA can promote the gastrointestinal motility in DGP rats, which may be associated with its effects in enhancing RhoA/ROCK signaling in the gastric antral smooth muscle at different degrees.


Assuntos
Diabetes Mellitus , Eletroacupuntura , Gastroparesia , Pontos de Acupuntura , Animais , Motilidade Gastrointestinal , Músculo Liso , Antro Pilórico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína rhoA de Ligação ao GTP
7.
Zhen Ci Yan Jiu ; 42(5): 429-33, 2017 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-29105472

RESUMO

OBJECTIVE: To observe the effect of manual acupuncture stimulation (MAS) of "Baihui"(GV 20)-"Shenmen"(HT 7)or GV 20-"Sanyinjiao"(SP 6) on sleep and expression of circadian rhythm genes (Clock and Bmal 1) in the hypothalamus in insomnia rats, so as to select a better acupoint group for insomnia. METHODS: A total of 53 SD rats were randomly divided into normal control (n=12),insomnia model (n=8), GV 20-HT 7(n=12), GV 20-SP 6(n=11),and GV 20-non-acupoint (n=10) groups. The insomnia model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA,500 mg/kg,100 mg/mL) once daily for 2 days. The MAS (uniform reinforcing-reducing needling) was applied to GV 20-HT 7, GV 20-SP 6 or GV 20-non-acupoint for 30 min,once daily for 7 days. The sleep onset latency and sleep duration were gauged after intraperitoneal injection of pentobarbital sodium (35 mg/kg). The expression levels of Clock mRNA and Bmal 1 mRNA in the hypothalamic tissues containing ventrolateral preoptic area (VLPO) and suprachiasmatic nucleus (SCN) region were detected by fluorescence quantitative real-time PCR. RESULTS: Following administration of pentobarbital sodium,the sleep latency was significantly prolonged and the sleep duration was considerably shortened in rats of the model group(P<0.05). After the treatment, the increased sleep latencies in the GV 20-HT 7, GV 20-SP 6 and GV 20-non-acupoints were all significantly down-regulated (P<0.05), and the decreased sleep duration was significantly increased only in the GV 20-HT 7 group relevant to the model group (P<0.05), but not in the GV 20-SP 6 and GV 20-non-acupoint groups (P<0.05). There were no significant differences in the sleep latency among the 3 treatment groups (P<0.05). The sleep duration was obviously prolonged in the GV 20-HT 7 group than in the GV 20-SP 6 and GV 20-non-acupoint groups (P<0.05). After modeling, the expression levels of Clock mRNA and Bmal 1 mRNA in hypothalamic VLPO and SCN regions were significantly down-regulated relevant to the normal control group (P<0.01). Following the treatment, the expression levels of Clock mRNA in the VLPO and SCN regions of the GV 20-SP 6 and GV 20-HT 7 groups, and those of Bmal 1 mRNA in the VLPO and SCN regions of the 3 treatment groups were considerably increased relevant to the model group (P<0.05, P<0.01). The effects of GV 20-HT 7 were significantly superior to those of GV 20-SP 6 and GV 20-non-acupoint (and also the action of GV 20-SP 6 was evidently superior to that of GV 20-non-acupoint) in up-regulating the expression of Clock mRNA and Bmal 1 mRNA in both VLPO and SCN regions (P<0.05, P<0.01). CONCLUSIONS: Manual acupuncture stimulation of GV 20-HT 7 can improve the sleep latency and duration in insomnia rats,which may be associated with its effects in up-regulating the expression levels of circadian Clock mRNA and Bmal 1 mRNA in hypothalamic VLPO and SCN regions, and the efficacy of GV 20-HT 7 is obviously better than that of GV 20-SP 6 and GV 20-non-acupoint.


Assuntos
Relógios Circadianos , Distúrbios do Início e da Manutenção do Sono , Fatores de Transcrição ARNTL , Pontos de Acupuntura , Animais , Hipotálamo , Ratos , Ratos Sprague-Dawley , Distúrbios do Início e da Manutenção do Sono/terapia
8.
Proc Natl Acad Sci U S A ; 109(34): 13757-62, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22875704

RESUMO

The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH) has been identified by genome-wide association studies as being significantly associated with age-related macular degeneration (AMD). However, the precise mechanism by which this CFH variant impacts the risk of AMD remains largely unknown. Oxidative stress plays an important role in many aging diseases, including cardiovascular disease and AMD. A large amount of oxidized phospholipids (oxPLs) are generated in the eye because of sunlight exposure and high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages and strongly activate downstream inflammatory cascades. We hypothesize that CFH may impact the risk of AMD by modulating oxidative stress. Here we demonstrate that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170 genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In addition, plasma from non-AMD subjects with the protective genotype has a lower level of systemic oxidative stress measured by oxPLs per apolipoprotein B (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes involved in macrophage infiltration, inflammation, and neovascularization in the eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal injection of oxPLs induces choroidal neovascularization in mice. In addition, we show that the CFH risk allele confers higher complement activation and cell lysis activity. Together, these findings suggest that CFH influences AMD risk by modulating oxidative stress, inflammation, and abnormal angiogenesis.


Assuntos
Fator H do Complemento/genética , Degeneração Macular/genética , Fosfolipídeos/química , Idoso de 80 Anos ou mais , Angiografia/métodos , Animais , Genótipo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Drusas do Disco Óptico/metabolismo , Oxigênio/química
9.
J Biol Chem ; 287(2): 1520-6, 2012 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-22049084

RESUMO

Genome-wide association study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 has been reported to interact with members of the transforming growth factor-ß (TGF-ß) family and regulate their signaling pathways. Growth differentiation factor 6 (GDF6), a member of the TGF-ß family, is involved in ectoderm patterning and eye development. Mutations in GDF6 have been associated with abnormal eye development that may result in microphthalmia and anophthalmia. In this report, we identified a single nucleotide polymorphism (SNP) rs6982567 A/G near the GDF6 gene that is significantly associated with AMD (p value = 3.54 × 10(-8)). We demonstrated that the GDF6 AMD risk allele (rs6982567 A) is associated with decreased expression of the GDF6 and increased expression of HTRA1. Similarly, the HTRA1 AMD risk allele (rs10490924 T) is associated with decreased GDF6 and increased HTRA1 expression. We observed decreased vascular development in the retina and significant up-regulation of GDF6 gene in the RPE layer, retinal and brain tissues in HTRA1 knock-out (htra1(-/-)) mice as compared with the wild-type counterparts. Furthermore, we showed enhanced SMAD signaling in htra1(-/-) mice. Our data suggests a critical role of HTRA1 in the regulation of angiogenesis via TGF-ß signaling and identified GDF6 as a novel disease gene for AMD.


Assuntos
Fator 6 de Diferenciação de Crescimento/biossíntese , Degeneração Macular/metabolismo , Neovascularização Patológica/metabolismo , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/biossíntese , Idoso , Alelos , Animais , Estudos de Coortes , Feminino , Regulação da Expressão Gênica/genética , Fator 6 de Diferenciação de Crescimento/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Degeneração Macular/genética , Degeneração Macular/patologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Retina/metabolismo , Retina/patologia , Fatores de Risco , Serina Endopeptidases/genética , Transdução de Sinais/genética , Proteínas Smad/genética , Proteínas Smad/metabolismo
10.
Br J Ophthalmol ; 95(12): 1749-54, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21873315

RESUMO

BACKGROUND: Truncation mutations in the elongation of very long chain fatty acids-4 (AF277094, MIM #605512) (ELOVL4) gene cause Stargardt-like macular dystrophy type 3 (STGD3). Mice expressing truncated ELOVL4 develop rapid retinal degeneration, but are poor STGD3 models since mice lack a macula. Photoreceptor topography in the pig retina is more similar to that in humans as it includes the cone rich, macula-like area centralis. The authors generated transgenic pigs expressing human disease-causing ELOVL4 mutations to better model the pathobiology of this macular disease. METHODS: Pronuclear DNA microinjection and somatic cell nuclear transfer were used to produce transgenic pigs for two different ELOVL4 mutations: the 5 base pair deletion (5 bpdel) and the 270 stop mutation (Y270terEYFP). Retinal transgene expression, morphology and electrophysiology were examined. RESULTS: The authors obtained four lines of Y270terEYFP and one line of 5 bpdel transgenic animals. Direct fluorescence microscopy indicated that the Y270terEYFP protein is expressed in photoreceptors and mislocalised within the cell. Immunohistochemical examination of transgenic pigs showed photoreceptor loss and disorganised inner and outer segments. Electroretinography demonstrated diminished responses in both transgenic models. CONCLUSIONS: These transgenic pigs provide unique animal models for examining macular degeneration and STGD3 pathogenesis.


Assuntos
Eletrorretinografia , Proteínas do Olho/biossíntese , Degeneração Macular , Proteínas de Membrana/biossíntese , Retina/metabolismo , Retina/patologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Proteínas do Olho/genética , Deleção de Genes , Imuno-Histoquímica , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Degeneração Macular/fisiopatologia , Proteínas de Membrana/genética , Microscopia de Fluorescência , Mutação , Retina/fisiopatologia , Suínos
11.
J Biol Chem ; 286(12): 10210-5, 2011 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-21177847

RESUMO

The Wnt pathway plays important yet diverse roles in health and disease. Mutations in the Wnt receptor FZD4 gene have been confirmed to cause familial exudative vitreoretinopathy (FEVR). FEVR is characterized by incomplete vascularization of the peripheral retina, which can lead to vitreous bleeding, tractional retinal detachment, and blindness. We screened for mutations in the FZD4 gene in five families with FEVR and identified five mutations (C45Y, Y58C, W226X, C204R, and W496X), including three novel mutations (C45Y, Y58C, and W226X). In the retina, Norrin serves as a ligand and binds to FZD4 to activate the Wnt signaling pathway in normal angiogenesis and vascularization. The cysteine-rich domain (CRD) of FZD4 has been shown to play a critical role in Norrin-FZD4 binding. We investigated the effect of mutations in the FZD4 CRD in Norrin binding and signaling in vitro and in vivo. Wild-type and mutant FZD4 proteins were assayed for Norrin binding and Norrin-dependent activation of the canonical Wnt pathway by cell-surface and overlay binding assays and luciferase reporter assays. In HEK293 transfection studies, C45Y, Y58C, and C204R mutants did not bind to Norrin and failed to transduce FZD4-mediated Wnt/ß-catenin signaling. In vivo studies using Xenopus embryos showed that these FZD4 mutations disrupt Norrin/ß-catenin signaling as evidenced by decreased Siamois and Xnr3 expression. This study identified a new class of FZD4 gene mutations in human disease and demonstrates a critical role of the CRD in Norrin binding and activation of the ß-catenin pathway.


Assuntos
Proteínas do Olho/metabolismo , Receptores Frizzled/metabolismo , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , Proteínas do Olho/genética , Vitreorretinopatias Exsudativas Familiares , Feminino , Receptores Frizzled/genética , Regulação da Expressão Gênica/genética , Células HEK293 , Humanos , Ligantes , Masculino , Proteínas do Tecido Nervoso/genética , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Ligação Proteica/genética , Estrutura Terciária de Proteína , Receptores Acoplados a Proteínas-G/genética , Vitreorretinopatia Proliferativa/genética , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia , Proteínas Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
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