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1.
Pathol Res Pract ; 215(11): 152677, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31591052

RESUMO

Sanguinarine (SAG), a benzophenanthridine alkaloid extracted from Sanguinaria canadensis, exerts antioxidant, anti-inflammatory and antiproliferative activities in a variety of malignancies. However, the underlying mechanisms by which SAG affects the tumorigenesis of gastric cancer (GC) are unclear. The common targets of SAG and GC were identified by network pharmacology, and the association of thymocyte selection-associated high mobility group box (TOX) with the clinicopathological characteristics and prognosis of patients with GC was analyzed by using datasets from The Cancer Genome Atlas (TCGA). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays, colony formation assays, flow cytometry analysis, and a xenograft tumor model were conducted to assess the effects of SAG on the growth of GC cells, and Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to determine the effects of SAG on the TOX/DNA-PKcs/KU70/80 signaling pathway. We identified 9 collective targets of SAG and GC, of which TOX expression levels were dramatically downregulated in GC tissues compared with adjacent normal tissues, and a low expression of TOX served as an independent prognostic factor of poor survival in patients with GC. SAG suppressed cell viability, colony formation and in vivo tumorigenesis and induced cell apoptosis and cell cycle arrest. Furthermore, SAG increased the expression levels of TOX but decreased those of DNA-PKcs and KU70/80 in GC cells. Our findings indicate that SAG inhibits the tumorigenesis of GC cells by regulating TOX/DNA-PKcs/KU70/80 signaling and may provide therapeutic strategies for the treatment of GC.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 680-684, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31315768

RESUMO

OBJECTIVE: To preliminarily investigate the relationship between stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) gene mutations and clinical phenotypes in children with congenital hypothyroidism (CH). METHODS: A total of 70 children with CH diagnosed by neonatal screening were enrolled. Their peripheral blood samples were collected to extract genomic DNA. GNAS and THRA genes were screened for mutations using next-generation sequencing. Bioinformatics software was used to analyze the pathogenicity of gene mutations. RESULTS: Of the 70 children with CH, nine missense mutations (three known mutations and six novel mutations) in the GNAS gene were detected in three patients (4%), and one gene polymorphism, c.508A>G(p.I170V), in the THRA gene was detected in four patients. The analysis results of bioinformatics software and ACMG/AMP guidelines showed that the two GNAS gene mutations [c.301C>T(p.R101C) and c.334G>A(p.E112K)] were more likely to be pathogenic. Three children with GNAS gene mutations showed different degrees of hypothyroidism. CONCLUSIONS: GNAS gene mutations are related to the development of CH, and children with CH have different clinical manifestations. THRA gene mutations may not be associated with CH.


Assuntos
Cromograninas/genética , Hipotireoidismo Congênito , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Receptores alfa dos Hormônios Tireóideos/genética , Genes erbA , Humanos , Recém-Nascido , Mutação , Fenótipo
3.
Am J Hum Genet ; 105(1): 166-176, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31178126

RESUMO

Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.

4.
Zhongguo Zhong Yao Za Zhi ; 44(7): 1314-1320, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090286

RESUMO

Salvia miltiorrhiza is one of the commonly used bulk medicinal materials, which has significant effect on cardiovascular disease, and are heavy demanded in Asia, Europe, North America, Russia and Africa. Consequently, increasing the yield and quality of S. miltiorrhiza has become a major concern worldwide. With the current wild resources of S. miltiorrhiza gradually decreasing, cultivated products occupy most of the markets. However, the cultivation area is widely distributed and the cultivation techniques is different, which lead to the quality and yield of S. miltiorrhiza in consistent. This paper combined visiting survey with document analysis to carry out the cultivation situation of S. miltiorrhiza in main cultivation areas of Shandong, Henan, Sichuan, Shanxi and Hebei provinces. There exist big differences of the ecological environment, mode of cultivation, fertilization, pest control, harvesting processing among the producing areas. We should carry on the ecological suitability zoning analysis and suitable cultivation of each area study to form a pattern of high quality and high yield for the sustainable development of S. miltiorrhiza cultivation.


Assuntos
Agricultura/métodos , Salvia miltiorrhiza/crescimento & desenvolvimento , Europa (Continente) , Plantas Medicinais/crescimento & desenvolvimento
5.
Mol Cancer ; 18(1): 103, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142332

RESUMO

N6-methyladenosine (m6A) is identified as the most common, abundant and conserved internal transcriptional modification, especially within eukaryotic messenger RNAs (mRNAs). M6A modification is installed by the m6A methyltransferases (METTL3/14, WTAP, RBM15/15B and KIAA1429, termed as "writers"), reverted by the demethylases (FTO and ALKBH5, termed as "erasers") and recognized by m6A binding proteins (YTHDF1/2/3, IGF2BP1 and HNRNPA2B1, termed as "readers"). Acumulating evidence shows that, m6A RNA methylation has an outsize effect on RNA production/metabolism and participates in the pathogenesis of multiple diseases including cancers. Until now, the molecular mechanisms underlying m6A RNA methylation in various tumors have not been comprehensively clarified. In this review, we mainly summarize the recent advances in biological function of m6A modifications in human cancer and discuss the potential therapeutic strategies.

6.
Curr Med Sci ; 39(1): 159-165, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868507

RESUMO

Molecularly imprinted polymers (MIPs) exhibit high selectivity resulting from imprinted cavities and superior performance from functional materials, which have attracted much attention in many fields. However, the combination of MIPs film and functional materials is a great challenge. In this study, hemin/graphene hybrid nanosheets (H-GNs) were used to initiate the imprinted polymerization by catalyzing the generation of free radicals. Thus, MIPs using sulfamethoxazole as the template was directly prepared on the surface of H-GNs without any film modification. Most importantly, the template could be absorbed on the H-GNs to enhance the number of imprinted sites per unit surface area, which could improve the selectivity of MIPs film. Thus, the composites could exhibit high adsorption capacity (29.4 mg/g), imprinting factor (4.2) and excellent conductivity, which were modified on the surface of electrode for rapid, selective and sensitive detection of sulfamethoxazole in food and serum samples. The linear range was changed from 5 µg/kg to 1 mg/g and the limit of detection was 1.2 µg/kg. This sensor was free from interference caused by analogues of sulfamethoxazole, which provides a novel insight for the preparation of MIPs-based sensor and its application in food safety monitoring and human exposure study.


Assuntos
Impressão Molecular/métodos , Polímeros/síntese química , Sulfametoxazol/análise , Adsorção , Técnicas Eletroquímicas , Grafite/química , Hemina/química , Humanos , Limite de Detecção , Nanoestruturas/química , Polímeros/química
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 239-245, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738477

RESUMO

OBJECTIVE: To investigate the change of microbial diversity and its relation with gastrointestinal (GI) graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Fecal samples were collected at the time point of 2 weeks before transplantation (pre-transplant group), 1 month after transplantation (post-tranplant group) and onset of GI GVHD in 65 hematonosis patients, which were also collected in 26 donors and 10 healthy subjects (control group). 16S rRNA was extracted from fecal microbiotas whose V4 variable region was amplified. The amplification products were sequenced in Illumina HiSeq 2500 platform, and the sequencing results were analyzed and compared. RESULTS: The microbial diversity was 5.70(3.74, 10.60)in pre-transplant group, 7.30(4.89, 11.41)in control group, and the differences between them were not statistically significant. The microbial diversity was 3.88(2.39, 6.49)in post-transplant group, lower than that in control group and pre-transplant group. After transplantation, the microbial diversity was 4.24(2.47, 7.16)in the patients without GI GVHD, while the microbial diverosity was 2.90 (1.48, 5.64) in patients subsequently suffered from GI GVHD, but the differences between them were not statistically significant. The microbial diversity was 2.13(1.76, 3.75)onset of GI GVHD, which was lower than that without GI GVHD. CONCLUSION: Intestinal microbial diversity decreases after allo-HSCT, and is associated with with Gl GVHD.


Assuntos
Trato Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , RNA Ribossômico 16S
8.
Oxid Med Cell Longev ; 2019: 9817576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30805086

RESUMO

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of Glycyrrhiza glabra L., could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Melanoma/metabolismo , Melanoma/patologia , Mitocôndrias/patologia , Proteínas Mitocondriais/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo
9.
J Mol Model ; 25(3): 63, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30756186

RESUMO

The crystal and electronic structures of four polymorphs of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) from 0 to 30 GPa were investigated by using density functional theory. The obtained structural parameters based on the GGA-PBE+TS calculations are in agreement with experimental results at ambient pressure. As the pressure increases, the volumes of the four types of HMX decrease monotonically and the band gaps gradually decrease without any significant discontinuity. Moreover, the peaks of the density of states become lower and the bandwidths become broader, which indicate that the hybridizations become strong under pressure. From the results, we suggest that the impact sensitivity for HMX becomes more and more sensitive with increasing pressure.

10.
J Clin Ultrasound ; 2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30318593

RESUMO

OBJECTIVES: To discuss Doppler ultrasonographic and clinical features of middle aortic syndrome (MAS). MATERIALS AND METHODS: Doppler ultrasonographic images and clinical dates of 11 patients with MAS confirmed by angiography were retrospectively analyzed from January 2004 to September 2016. RESULTS: The median age of 11 patients was 10 years (1-39 years). Ten patients presented with hypertension, only 2 cases presented with symptomatic intermittent claudication, and 1 case presented with abdominal pain. The ultrasonographic features of 11 patients with MAS included: (a) Gray-scale image showed significant segmental narrowing of the aorta in 9 cases. (b) Color Doppler demonstrated aliasing in the suspicious narrowed vessels of all cases. (c) On Spectral Doppler image, peak systolic velocity in the location of aorta coarctation was significantly elevated (range, 2.3~4.8 m/s). When infrarenal aorta was involved, a tardus-parvus waveform was only seen in the distal aorta. When suprarenal or inter-renal aorta was involved, a tardus-parvus pattern was seen in the distal aorta as well as renal artery. CONCLUSIONS: Significant segmental narrowing and a tardus-parvus waveform are the important ultrasonographic features in patients with MAS, the latter may be more reliable. Doppler ultrasound can be used as a simple screening method, especially for children and adolescents suspected of having a vascular cause of refractory hypertension.

12.
Int J Immunopathol Pharmacol ; 32: 2058738418790318, 2018 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30045644

RESUMO

Targeting of the programmed cell-death 1 ligand 1 (PD-L1) signal pathway is a promising treatment strategy in several cancers. The purpose of this study was to evaluate the clinical significance of PD-L1 in patients with colon adenocarcinoma (COAD). A total of 240 patients who were diagnosed with COAD from The Cancer Genome Atlas (TCGA) RNA-sequencing data and another cohort for pair-matched COAD samples (n = 40) in tissue microarray (TMA) were enrolled in this study. The correlation of PD-L1 or miR-191-5p expression with clinicopathological features and prognosis in patients with COAD was further analyzed using TCGA data and TMA. The Cox proportional hazard regression model was used to evaluate the association of PD-L1 or miR-191-5p expression with overall survival (OS) and tumor recurrence in patients with COAD. The microRNAs (miRNAs) that target PD-L1 gene were identified by bioinformatics and Spearman correlation analysis. We found that PD-L1 expression was increased in COAD tissues and was correlated with poor survival and tumor recurrence in patients with COAD. The increased expression of PD-L1 was attributed to the dysregulation of miR-191-5p expression rather than its genetic or epigenetic alterations. Moreover, the expression of miR-191-5p presented the negative correlation with PD-L1 expression and acted as an independent prognostic factor of OS in patients with COAD. Therefore, PD-L1 may predict poor prognosis and is negatively associated with miR-191-5p expression in patients with COAD.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30025875

RESUMO

Selective ß-cell loss is a characteristic of type 2 diabetes mellitus (T2DM). Inhibition of glucose-stimulated ß-cell proliferation is one of the in vivo results of the lipotoxicity of saturated fatty acids (SFAs). However, the mechanism by which lipotoxicity inhibits ß-cell proliferation is still unclear. In this study, we found palmitate, a saturated fatty acid, inhibited the ß-cell proliferation induced by high glucose through the induction of Wnt5a expression in vitro and in vivo. We also found that Wnt5a was both sufficient and necessary for inhibition of ß-cell proliferation. Additionally, Egr-1, but not NF-κB, FOXO1, Smad2, Smad3, SP1 or SP3 mediated the expression of Wnt5a. Deletion and site-directed mutagenesis of the WNT5A promoter revealed that activation of WNT5A gene transcription depends primarily on a putative Egr-binding sequence between nucleotides -52 to -44, upstream of the transcription start site. Furthermore, Egr-1 bound directly to this sequence in response to palmitate treatment, both in vitro and in vivo. Moreover, after mice islets were treated with Egr inhibitors, the expression of Wnt5a decreased significantly and the glucose-induced ß-cell proliferation inhibited by palmitate was resumed. These findings establish Wnt5a as an Egr-1 target gene in ß-cells, uncovering a novel Egr-1/Wnt5a pathway by which saturated free fatty acids block glucose-induced ß-cell proliferation. Our study lends support for the potential of Egr-1 inhibitors or Wnt5a antibodies as therapeutics for the treatment of T2DM.

14.
Biomolecules ; 8(2)2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921807

RESUMO

Pinocembrin is a natural flavonoid compound which is capable of antioxidant, antibacterial, anti-inflammatory, and antineoplastic activities. The present study aimed to enhance the solubility and antioxidant activities of pinocembrin by complex formation with lecithin. The physicochemical characteristics of pinocembrin⁻lecithin complex were analyzed by ultraviolet (UV), fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and solubility assay, and the antioxidant activities of pinocembrin⁻lecithin complex were evaluated via radical scavenging capacities for 2,2′-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl, and superoxide-anion. The results indicated that pinocembrin complex with lecithin could significantly improve the solubility of pinocembrin in water and n-octane, the pinocembrin⁻lecithin complex displayed no characteristic endothermic peak and the appearance of amorphous state, compared to the pinocembrin, and no new covalent bond was produced in the pinocembrin and lecithin compound. It was demonstrated that the antioxidant activities of pinocembrin were obviously enhanced by the complex with lecithin, and the scavenging capacities for hydroxyl radical, DPPH, superoxide-anion radical, and ABTS radical of pinocembrin⁻lecithin complex were 82.44 ± 2.21%, 40.07 ± 1.32%, 59.15 ± 0.86%, and 24.73 ± 1.04% at 1.0 mg/mL, respectively. It suggested that the pinocembrin⁻lecithin complex had a great potential application prospect in the healthcare industry and in clinical practice.

15.
Zhongguo Zhong Yao Za Zhi ; 43(9): 1749-1753, 2018 May.
Artigo em Chinês | MEDLINE | ID: mdl-29902880

RESUMO

Seven aromatic glycosides (1-7), including four phenylethanol glycosides, one phenylmethanol glycoside, one phenylpropane glycoside and one benzoside, were isolated from the methanolic extract of Uighur Medicine Elaeagnus angustifolia flowers. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HR-MS). Compound 1 is a new compound, named as angustifol A. Six known compounds were identified as 2-phenylethyl-O-ß-D-glucopyranoside(2), salidroside (3), vanillic acid 4-O-ß-D-glucopyranoside(4), vanilloloside (5), (Z)-isoconiferin (6), 2-phenylethyl-6-O-α-L-arabinofuranosyl-ß-D-glucopyranoside (7). Compounds 2-7 were isolated from the genus Elaeagnus for the first time. In vitro anti-inflammatory assays revealed that none of these compounds showed good COX inhibitory activities.

16.
Int Urol Nephrol ; 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29752626

RESUMO

BACKGROUND: As a tricyclic glycopeptide antibiotic used to treat acute infections, Vancomycin (VAN) is often administered with piperacillin/tazobactam (PT) to treat various infections in clinical practice. However, whether the combination of these two drugs, compared to VAN alone, can cause an increased risk of acute kidney injury (AKI) remains controversial. OBJECTIVES: This study aims to identify the correlation between the development of AKI and the combined use of VAN and PT. METHODS: We conducted a meta-analysis of eight observational cohort studies (a total of 10727 participants received VAN and PT versus VAN and other ß-lactams). PubMed, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI) Database, Wan Fang Digital Periodicals Database (WFDP), and China Science Citation Database (CSCD) were searched through April 2017 using "vancomycin" and "piperacillin" and "tazobactam" as well as "acute kidney injury" or "acute renal failure" or "AKI" or "ARF" or "nephrotoxicity." Two reviewers extracted the data and assessed the risk of bias. RESULTS: A correlation was found between the development of AKI and concurrent use of VAN and PT compared with concomitant VAN and ß-lactams (OR 1.57; 95% CI, 1.13-2.01; I2 = 76.4%, p < 0.001). Similar findings were obtained in an analysis of studies comparing concurrent VAN and PT use with concurrent VAN and ß-lactam (cefepime) use (OR 1.50; 95% CI, 1.07-1.93; I2 = 80.5%, p < 0.001). Exclusion of fair-quality and low-quality articles did not change the results (OR 1.49; 95% CI, 1.06-1.92; I2 = 84.1%, p < 0.001). CONCLUSIONS: Regarding ß-lactam therapy in clinical practice, an elevated risk of AKI due to the combined use of VAN and PT should be considered.

18.
J Sci Food Agric ; 98(14): 5242-5247, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29645274

RESUMO

BACKGROUND: Marinating meat with alcohol, such as wine and beer, is a common culinary practice in cultures worldwide. In this study we use a model marination solution comprising 0.2  mol L-1 glucose-0.2  mol L-1 glycine buffered to pH 4.3 containing either 0 or 50% ethanol and mimicked the cooking process by heating for 12 h. Antioxidative and antimutagenic characteristics of Maillard reaction products (MRPs) were investigated. Reducing power, antioxidant activity (ferrous ion chelating ability), and free radical neutralization ability generated from 1,1-diphenyl-2-pichrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) were determined. Ames testing was performed. RESULTS: Results indicate that MRPs from aqueous and alcoholic solution exhibit four antioxidative assays in a dose-dependent manner from 0.16 to 10.00 mg mL-1 . However, MRPs from the alcoholic model were superior. In Ames testing, MRPs from both models are neither toxic nor mutagenic at the test concentrations of 0.63-10.00 mg/plate. However, MRPs from the alcoholic model exhibited a higher inhibitory effect on the direct-acting mutagen 4-nitroquinoline-N-oxide compared with the aqueous model. This result is consistent with the observation that MRPs with higher antioxidative capacity exhibit superior antimutagenic activity, suggesting that there are more different products in the alcoholic model. CONCLUSION: Our results add to the current knowledge about the antioxidative and antimutagenic properties of MRPs arising when food is cooked in the presence of ethanol. © 2018 Society of Chemical Industry.


Assuntos
Bebidas Alcoólicas/análise , Antimutagênicos/química , Antioxidantes/química , Glucose/química , Produtos Finais de Glicação Avançada/química , Glicina/química , Reação de Maillard
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(3): 243-250, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29530127

RESUMO

Congenital hypothyroidism (CH), which results from insufficient thyroid hormone biosynthesis, is one of the most common neonatal endocrine disorders. Thyroid dysgenesis and thyroid dyshormonogenesis are the two causes of CH and either one will lead to deficiencies of enzymes during thyroid hormone biosynthesis and insufficient thyroid hormone biosynthesis. Recently, researchers have performed extensive studies on genetics of CH. This paper reviews genes reported to be associated with CH in China.


Assuntos
Hipotireoidismo Congênito/genética , Humanos , Iodeto Peroxidase/genética , Proteínas de Membrana/genética , Fator de Transcrição PAX8/genética , Receptores da Tireotropina/genética , Tireoglobulina/genética , Fatores de Transcrição/genética
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