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1.
Int J Biol Macromol ; 256(Pt 1): 128307, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992941

RESUMO

Films with simultaneously excellent mechanical and anti-fog properties are of great importance for food packaging. A novel strategy is described here to prepare long-lasting anti-fog film with antibacterial and antioxidant capabilities via a simple, green approach. The CMC (carboxymethyl chitosan) gel was integrated with CNF/TA (cellulose nanofibers/tannic acid) composite solution based on layer-by-layer assembly to form a membrane with a bilayer structure. The anti-fog performance of the bilayer film could be adjusted by regulating the CNF/TA layer thickness. On the whole, the developed anti-fog film had high mechanical strength and excellent UV shielding properties, as well as good antibacterial and antioxidant properties, and could be non-fogging for a long time under water vapor (40 °C). The effect of double layer anti-fog film (3%CmFT-3) on the fresh-keeping effect of white Hypsizygus marmoreus was compared at room temperature (28 °C) with commercially available anti-fog PVC film. The results showed that the bilayer anti-fog film could effectively prevent the generation of fog, delay the Browning, inhibit mildew, improve the overall acceptability, and effectively extend the shelf life of white Hypsizygus marmoreus. This biomass-based anti-fog film offers great potential for the development of multifunctional green food packaging.


Assuntos
Agaricales , Quitosana , Nanofibras , Polifenóis , Quitosana/farmacologia , Quitosana/química , Celulose/farmacologia , Celulose/química , Nanofibras/química , Antioxidantes/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Embalagem de Alimentos
2.
Curr Med Sci ; 43(1): 22-34, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36680685

RESUMO

OBJECTIVE: This study aimed to describe, optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides (CPs) with tetanus toxoid (TT) as bivalent conjugates. METHODS: Different molecular weights (MWs) of polysaccharides, activating agents and capsular polysaccharide/protein (CP/Pro) ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk. Using the described method and optimized parameters, a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models. RESULTS: The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC, while higher MWs were superior for Pn4-TT-Pn14, Pn6A-TT-Pn6B, Pn7F-TT-Pn23F and Pn8-TT-Pn11A. For activating polysaccharides, 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) was superior to cyanogen bromide (CNBr), but for Pn1, Pn3 and MenC, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) was the most suitable option. For Pn6A-TT-Pn6B and Pn8-TT-Pn11A, rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses, while for Pn4-TT-Pn14, higher CP/Pro ratio was better. Instead of interfering with the respective immunological activity, our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts. CONCLUSION: The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines, laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.


Assuntos
Neisseria meningitidis , Camundongos , Animais , Coelhos , Vacinas Conjugadas , Vacinas Combinadas , Streptococcus pneumoniae , Polissacarídeos Bacterianos , Toxoide Tetânico , Modelos Animais
3.
Bioprocess Biosyst Eng ; 45(10): 1673-1682, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35964262

RESUMO

Polymalic acid (PMA) is a water-soluble polyester produced by Aureobasidium pullulans. In this study, the physiological response of A. pullulans after the addition of vegetable oils was investigated. Soybean oil (SBO) is pivotal for shortening fermentation time and achieving high PMA titer. With the addition of 1% (w/v) SBO, the titer and productivity of PMA was, respectively, increased by 34.2% and 80%. SBO acted as a chemical stimulatory agent rather than a carbon source, the enhancement on PMA production was attributed to the component of fatty acid. SBO induced the dimorphism (yeast-like cells and mycelia) of A. pullulans, in vitro enzyme activities indicated that the TCA oxidative branch for malic acid synthesis might be strengthened, which could generate more ATP for PMA synthesis, and the assay of intracellular energy supply validated this deduction. This study provided a new sight for recognizing the regulatory behavior of SBO in A. pullulans.


Assuntos
Ascomicetos , Óleo de Soja , Trifosfato de Adenosina , Aureobasidium , Carbono/farmacologia , Ácidos Graxos , Fermentação , Malatos/farmacologia , Poliésteres , Polímeros , Óleo de Soja/farmacologia , Água
4.
Chem Biol Interact ; 363: 110008, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35667395

RESUMO

Doxorubicin (DOX) is an effective antitumor drug; however, but its clinical application is seriously limited by the cardiotoxicity induced by its use. Recent studies have found that ferroptosis is an important mechanism underlying DOX-induced cardiotoxicity. However, existing studies are based on DOX-induced acute or subacute cardiotoxicity model. Therefore, we established a murine model of DOX-induced chronic cardiotoxicity using the clinically relevant cumulative dose, to evaluate the potential molecular mechanism underlying ferroptosis of cardiomycocytes. Male C57 mice were received intraperitoneal injections of DOX at a dose of 3 mg/kg body weight, once a week for 12 weeks. We dynamically analysed echocardiographic findings, serum myocardial enzyme levels, haematological indexes and cardiac histopathological changes. The results showed that, after receiving a cumulative DOX dose of 15 mg/kg, the mice developed anaemia and the function and structure of the heart changed significantly with an increase in the cumulative DOX dose. Importantly, with a cumulative DOX dose of 36 mg/kg, iron overload occurred in the heart tissue. Moreover, RNA-sequencing analysis and experimental verification revealed that ferropotosis is the underlying mechanism of DOX-induced chronic cardiotoxicity. Our results showed that DOX inhibits Slc7a11 in system-Xc, resulting in the reduction of GSH synthesis to prevent GPX4 from scavenging lipid peroxides. In addition, DOX induced the occurrence of ferroptosis via down-regulating Nrf2 expression to inhibit HO-1 and GPx4 levels. Our study provides a new perspective for evaluating the pathophysiology of DOX-induced chronic cardiotoxicity in the future, and developing new potential therapeutic strategies for the prevention and treatment of DOX-induced cardiotoxicity.


Assuntos
Cardiotoxicidade , Ferroptose , Animais , Cardiotoxicidade/metabolismo , Modelos Animais de Doenças , Doxorrubicina/farmacologia , Coração , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo
5.
J Ethnopharmacol ; 287: 114943, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-34954266

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Di'ao Xinxuekang capsule (DXXK) extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product widely used in the treatment of cardiovascular disease, such as myocardial ischemia and arrhythmia. The active ingredients of DXXK were also traditionally utilized for treating cardiovascular disease in the former Soviet Union after the 1960s. As a specific type of cardiovascular disease, doxorubicin (DOX)-induced cardiotoxicity is characterized by arrhythmia, myocardial ischemia, and heart failure. AIM OF THE STUDY: This study aimed to investigate the potential protective effect of DXXK against chronic cardiotoxicity induced by DOX. MATERIALS AND METHODS: A mouse model of chronic cardiotoxicity induced by DOX and an in vitro model of DOX-induced myocardial damage were created to assess the protective effect of DXXK. Cardiac functional parameters, serum levels of CK-MB and LDH and cardiac histopathological indicators were determined in the mouse model. Moreover, cell viability was measured by the MTT method, and the effect of DXXK on the anticancer activity of DOX was also investigated by utilizing 4T1, HepG2, and H460 cell lines. Furthermore, the levels of markers of oxidative stress indexes (SOD, GSH, MDA) and inflammation (TNF-α, IL-1α) were measured using biochemical and Elisa kits, respectively. The level of ROS in H9c2 cardiomyocyte was determined by flow cytometry. The protein expression levels of HIF-1α and NF-κB p65 were measured by western blotting. Finally, molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. RESULTS: DXXK alleviated DOX-induced chronic cardiotoxicity as shown by the reversal of changes in levels of myocardial enzymes and left ventricular function and structure. DXXK exhibits antioxidant and anti-inflammatory activities. We also observed that DXXK might increase the protein expression level of HIF-1α and decrease the protein expression level of NF-κB p65. Further results of in vitro experiments showed that DXXK could protect cardiomyocyte against DOX-induced production of ROS, but DXXK had no effect on the anticancer activity of DOX. The results of molecular docking showed that dioscin and pseudoprotodioscin were the top two compounds of DXXK, which had high affinity with HIF-1α and NF-κB p65. CONCLUSIONS: Our results indicated that DXXK could protect against cardiotoxicity induced by DOX and alleviate oxidative stress and inflammation in vivo and in vitro via the regulation of HIF-1α and down NF-κB p65.


Assuntos
Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antibióticos Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Cardiotoxicidade/etiologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Células Hep G2 , Humanos , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos
6.
J Ethnopharmacol ; 274: 114018, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33716083

RESUMO

BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Dioscin and diosgenin derived from plants of the genus Dioscoreaceae such as D. nipponica and D. panthaica Prain et Burk. Were utilized as the main active ingredients of traditional herbal medicinal products for coronary heart disease in the former Soviet Union and China since 1960s. A growing number of research showed that dioscin and diosgenin have a wide range of pharmacological activities in heart diseases. AIM OF THE STUDY: To summarize the evidence of the effectiveness of dioscin and diosgenin in cardiac diseases, and to provide a basis and reference for future research into their clinical applications and drug development in the field of cardiac disease. METHODS: Literatures in this review were searched in PubMed, ScienceDirect, Google Scholar, China National Knowledge Infrastructure (CNKI) and Web of Science. All eligible studies are analyzed and summarized in this review. RESULTS: The pharmacological activities and therapeutic potentials of dioscin and diosgenin in cardiac diseases are similar, can effectively improve hypertrophic cardiomyopathy, arrhythmia, myocardial I/R injury and cardiotoxicity caused by doxorubicin. But the bioavailability of dioscin and diosgenin may be too low as a result of poor absorption and slow metabolism, which hinders their development and utilization. CONCLUSION: Dioscin and diosgenin need further in-depth experimental research, clinical transformation and structural modification or research of new preparations before they can be expected to be developed into new therapeutic drugs in the field of cardiac disease.


Assuntos
Cardiotônicos/farmacologia , Diosgenina/análogos & derivados , Diosgenina/farmacologia , Cardiopatias/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Cardiotônicos/efeitos adversos , Cardiotônicos/química , Cardiotônicos/uso terapêutico , Diosgenina/efeitos adversos , Diosgenina/química , Diosgenina/uso terapêutico , Coração/efeitos dos fármacos , Humanos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico
7.
Front Pharmacol ; 11: 918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32625099

RESUMO

Intestinal mucositis is a common toxicity of many anti-neoplastic therapies that negatively influences health, the quality of life, economic outcomes, and even the success of cancer treatment. Unfortunately, there is presently no optimal medicine that is able to effectively manage this condition. l-glutamine is one of the most frequently used agent in practice among the limited treatment choices due to its safety and inexpensiveness despite there being a lack of evidence. Previous studies indicated that l-glutamine may alleviate mucositis and mucosal atrophy but failed to improve patients' macroscopic conditions, such as the occurrence of diarrhea. A compound glutamine capsule (G-SJZ), composed of l-glutamine and the traditional Chinese herbal formula Si-Jun-Zi-Tang, has been used in China for 23 years to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy. However, the exact effect of G-SJZ on intestinal mucositis is unclear, and moreover, whether l-glutamine combined with Si-Jun-Zi-Tang is more effective than l-glutamine alone have not been studied. In the current study, we explored the effects of G-SJZ and l-glutamine in a mouse model of intestinal mucositis induced by 5-fluorouracil (5-Fu). The results revealed that pretreatment with G-SJZ ameliorated the physical manifestations of weight loss and the severity of diarrhea following continuous 5-Fu injections in mice. Likewise, the histopathological damage and the destruction of villus and crypt structures in the intestinal mucosa as well as the increase in circulating intestinal injury markers caused by 5-Fu were reversed with G-SJZ pretreatment. Furthermore, the protective effect of G-SJZ was accompanied by modulations in the immunohistochemical expression of tight junction proteins. Interestingly, although treatment with a dose of l-glutamine alone that was equivalent to the dose in G-SJZ also showed a protective effect, it did not appear to be as strong as treatment with G-SJZ. Si-Jun-Zi-Tang in G-SJZ may compensate for the deficiencies of l-glutamine in this model which seems not to be related to the regulation of tight junction proteins. Our study is the first to suggest that the combined use of l-glutamine and Si-Jun-Zi-Tang might be more effective than l-glutamine alone despite exact mechanism still needs further study. Because of the limited number of therapeutic agents, G-SJZ is likely to be a preferable choice for intestinal mucositis.

8.
RSC Adv ; 10(36): 21509-21516, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35518741

RESUMO

CO2 capture, utilization, and storage are promising strategies to solving the problems of superfluous CO2 or energy shortage. Here, mechanochemical reduction of CO2 by a MgH2/CaH2 mixture was first performed, by which we achieve selective methanation of CO2 and acquire an effective CaO-based CO2 sorbent, simultaneously. The selectivity of methanation is near 100% and the yield of CH4 reaches 30%. Four MgO and carbon-doped CaO-based CO2 sorbents (MgO/CaO/C, MgO/2CaO/C, MgO/4CaO/C, and MgO/8CaO/C) were formed as solid products in these reactions. Among them, the MgO/4CaO/C sorbent shows high initial adsorption amount of 59.3 wt% and low average activity loss of 1.6% after 30 cycles. This work provides a novel, well-scalable, and sustainable approach to prepare an efficient inert additive-including CaO-based CO2 sorbent and selectively convert CO2 to CH4 at the same time.

9.
PLoS One ; 14(9): e0221551, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31490966

RESUMO

With the development and universal application of satellite technology, an important way to expand the function of satellites is setting up inter-satellite networks to make them work together. Traditional satellite networking methods generally adopt a fixed time slot allocation method, which is not suitable for small satellite groups with low latency and high throughput requirements. In order to solve this problem, it has been proposed to apply the traditional Wifi protocol in satellite networking. As there are differences between satellite networks and terrestrial networks, it's necessary to improve the traditional 802.11 protocol. The Media Access Control (MAC) protocol in 802.11 is improved in this paper, which mainly includes the adaptive algorithm of maximum contention window size and the growth algorithm of Contention Window (CW) size. The maximum contention window is adjusted according to the conflict state of the current network, which makes the network accommodate more satellite nodes. The CW growth algorithm improves the traditional Binary Exponential Back-off (BEB) algorithm, where the CW is designed according to the priority of the data frame or the network load. In this way, high-priority satellite accusation information will have higher reliability or tolerate greater network load.


Assuntos
Redes de Comunicação de Computadores , Astronave , Tecnologia sem Fio , Algoritmos
10.
Biomed Pharmacother ; 111: 1315-1325, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841445

RESUMO

Diabetic retinopathy (DR) seriously endangers human beings' health, uncovering the underlying mechanism might help to cure DR. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose (50mM) promotes reactive oxygen species (ROS) generation and cell apoptosis, inhibits cell mitophagy as well as proliferative abilities, while low-glucose (15mM) induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose (50mM) on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose (50mM) induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose (50mM) inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose (50mM) or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucose's inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating ROS mediated inactivation of ROS/PINK1/Parkin signal pathway.


Assuntos
Apoptose/efeitos dos fármacos , Glucose/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais/fisiologia , Ubiquitina-Proteína Ligases/metabolismo
11.
Sensors (Basel) ; 17(1)2017 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-28117697

RESUMO

Breath acetone serves as a biomarker for diabetes. This article reports 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]), a type of room temperature ionic liquid (RTIL), as a selective sensing material for acetone. The RTIL sensing layer was coated on a quartz crystal microbalance (QCM) for detection. The sensing mechanism is based on a decrease in viscosity and density of the [bmim][BF4] film due to the solubilization of acetone leading to a positive frequency shift in the QCM. Acetone was detected with a linear range from 7.05 to 750 ppmv. Sensitivity and limit of detection were found to be 3.49 Hz/ppmv and 5.0 ppmv, respectively. The [bmim][BF4]-modified QCM sensor demonstrated anti-interference ability to commonly found volatile organic compounds in breath, e.g., isoprene, 1,2-pentadiene, d-limonene, and dl-limonene. This technology is useful for applications in non-invasive early diabetic diagnosis.


Assuntos
Técnicas de Microbalança de Cristal de Quartzo , Acetona , Cicloexenos , Imidazóis , Limoneno , Quartzo , Terpenos
12.
Cell Signal ; 29: 62-68, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27751914

RESUMO

Neuralized Homology Repeats (NHRs) were first identified in Neuralized, an E3-ubiquitin ligase that plays a key role in the Notch signalling pathway. Since their original discovery, NHR domains have been shown to regulate protein-protein interactions in a broad range of developmental processes and in a wide variety of species from flies to humans. The NHR family of proteins can be categorized into three groups: (1) those that contain a RING finger, (2) those that contain a SOCS box and, (3) those that only have NHR domains. Here we review the structure and function of NHR domains in various cellular and developmental processes.


Assuntos
Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Humanos , Domínios Proteicos
13.
Springerplus ; 2(Suppl 1): S7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24701390

RESUMO

The information of slope and vegetation coverage of the monitoring region were extracted, based on DEM (Digital Evaluation Model) and Spot5 Satellite data images, and fishnet grid was generated using GIS (Geographic Information System) and RS (Remote Sensing) technique. Applying the information of slop and vegetation coverage layers into the corresponding space grid by using the function of zonal statistics and analysis, it can realize overlay analysis based on Standards for Classification and Gradation of Soil Erosion (SL190-2007), and obtains the map of soil erosion intensity of the monitoring region. Finally, according to Specifications for Assessment of Forest Ecosystem Services (LY/T1721-2008) and monitoring data of typical plot, the soil and water conservation value from cropland to forest was evaluated quantitatively in 2009. The results showed that the area, on and below the moderate level, was 93600 ha, taking up 50.03% of total conversion of farmland to forest area (185100 ha), which indicates a 14.64 million (t/a) of soil conversion, and a 1520 million Yuan for erosion control. The results of the study showed that the soil and water conservation was very effective.

14.
Mol Cell Biol ; 32(24): 4933-45, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23045391

RESUMO

The Notch pathway plays an integral role in development by regulating cell fate in a wide variety of multicellular organisms. A critical step in the activation of Notch signaling is the endocytosis of the Notch ligands Delta and Serrate. Ligand endocytosis is regulated by one of two E3 ubiquitin ligases, Neuralized (Neur) or Mind bomb. Neur is comprised of a C-terminal RING domain, which is required for Delta ubiquitination, and two Neur homology repeat (NHR) domains. We have previously shown that the NHR1 domain is required for Delta trafficking. Here we show that the NHR1 domain also affects the binding and internalization of Serrate. Furthermore, we show that the NHR2 domain is required for Neur function and that a point mutation in the NHR2 domain (Gly430) abolishes Neur ubiquitination activity and affects ligand internalization. Finally, we provide evidence that Neur can form oligomers in both cultured cells and fly tissues, which regulate Neur activity and, by extension, ligand internalization.


Assuntos
Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo , Substituição de Aminoácidos , Animais , Animais Geneticamente Modificados , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular , Sequência Conservada , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Endocitose , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Ligantes , Modelos Biológicos , Mutação Puntual , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Proteínas Serrate-Jagged , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
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