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1.
Pharm Nanotechnol ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167435

RESUMO

BACKGROUND: Indomethacin (IND) is a class of non-steroidal anti-inflammatory drugs that is used to treat various kinds of ocular inflammation, and has been reported that could prevent posterior capsule opacification (PCO) by inhibiting the mitosis and collagen synthesis of human lens epithelial cells (LECs). In addition, the specific absorption spectrum of indomethacin has the effect of absorbing short-wavelength blue-violet light. OBJECTIVE: We intend to prepare a hydrogel loaded with indomethacin as potential intraocular lens (IOLs) material that can prevent endophthalmitis, PCO and filter harmful blue light. METHOD: Indomethacin prodrug (HEMA-IND) (HI) were prepared by esterification of indomethacin and 2-hydroxyethyl methacrylate (HEMA), and poly (HEMA-co-MAA-co-MMA-co-HI) (HAMI) hydrogels were prepared by free radical polymerization of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), methacrylic acid (MAA) and HI. And their physical and chemical properties, drug release behavior and cytotoxicity were determined. RESULTS: HAMI hydrogels can filter harmful short-wavelength blue light and showed other necessary properties like visible light transparency, glass transition temperatures, mechanical strength, and biocompatibility for making intraocular lenses. In addition, MAA increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and faster drug release from the hydrogels. CONCLUSION: In summary, HAMI hydrogels show great potential as IOL biomaterials that can maintain the sustained release of indomethacin and filter harmful blue light after cataract surgery.

2.
J Zhejiang Univ Sci B ; 21(2): 178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115915

RESUMO

Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2019 20(7):605-612. https://doi.org/10.1631/jzus.B1900051. The original version of this article unfortunately contained a mistake. In p.605, the number of the Zhejiang Provincial Natural Science Foundation of China (No. Y17H160118) in Funding is incorrect. The correct number should be LY17H160026, which is the approval number of the project, whereas Y17H160118 is the application number of the project.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32202402

RESUMO

Ocular dryness and contact lens(CL)-related microbial keratitis (MK) are two major risks of wearing CLs. The development of multifunctional surface coating for CLs with excellent hydrating and antimicrobial properties is a practical strategy to improve the comfort of CL wearers and to prevent corneal infection. Here, we develop zwitterionic and antimicrobial metal-phenolic networks (MPNs) based on the coordination of copper ions (CuII) and the poly(carboxylbetaine-co-dopamine methacrylamide) copolymer (PCBDA), which can be easily one-step prepared onto CLs due to the near-universal adherent properties of catechol groups. The zwitterionic and antifouling carboxybetaine (CB) groups of the CuII-PCBDA coating can significantly increase the wettability of CLs and reduce their protein adsorptions, resulting in a lens surface that is more water retentive and with lower protein binding to prevent tear film evaporation and eye dryness. In addition, since the immobilized copper ions in the MPNs impart them with ion-mediated antimicrobial activity, the CuII-PCBDA coating exhibits a strong and broad-spectrum antimicrobial activity against MK related pathogenic microbes, including bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and fungi, such as Candida albicans. Compared with a pristine CL, the CuII-PCBDA-coated CL effectively inhibited biofilm formation even after daily exposure to the above microbial environment for 14 days. Notably, the CuII-PCBDA coating developed in this study is not only biocompatible with 100% cell viability following direct contact with human corneal epithelial cells (HCECs) for 48 h but also maintains the optical clarity of the native CLs. Thus, the CuII-PCBDA coating has a great application potential for the development of a multifunctional surface coating for CLs for increased CL comfort and prevention of MK.

4.
Int J Artif Organs ; : 391398820908877, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191150

RESUMO

OBJECTIVE: This study aims to evaluate the clinical efficacy and visual function prognosis of macular hole retinal detachment treatment for high myopia by inverting the internal limiting membrane to overlay the macular hole with the assistance of perfluorocarbon liquids. METHODS: A total of 55 high myopia patients, who received macular hole retinal detachment treatment from 2013 to 2016, were included in this study. Among these patients, 38 patients were assigned to the first group and 17 patients (perfluorocarbon liquids) were assigned to the second group. The second group was further divided into two subgroups, according to the overlaying layer number of the internal limiting membrane valve: A group (multiple layers) and B group (single layer). RESULTS: The success rate of the internal limiting membrane inversion and overlaying on the macular hole was 23.68% and 100% in the first and second group, respectively. The differences in macular hole closing rate and postoperative best-corrected visual acuity between these two groups were statistically significant (p < 0.05). Furthermore, the differences in macular morphology recovery between the A and B groups were also statistically significant (p = 0.004 < 0.05). CONCLUSION: Perfluorocarbon liquids play a positive role in the operation process of the internal limiting membrane.

5.
Adv Clin Exp Med ; 29(1): 135-145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011832

RESUMO

BACKGROUND: Anesthetics, such as isoflurane, sevoflurane, ketamine, and desflurane, are commonly used in clinics. Specifically, isoflurane is one of the most commonly used inhalational anesthetics, which can be used in surgery patients of all ages, including children. OBJECTIVES: The aim of the study was to investigate the mechanisms of vitexin against isoflurane-induced neurotoxicity. MATERIAL AND METHODS: Reference memory testing was performed for 5 days (4 trials, 2 per day) before anesthesia. Reversal testing was performed on the 3rd day after anesthesia. The cell viability and apoptosis of PC-12 cells were detected using MTT and TUNEL assays, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum tumor necrosis factor α (TNF­α), interleukin 6 (IL­6), glutathione (GSH), and superoxide dismutase (SOD) concentrations. The concentration of reactive oxygen species (ROS) was detected using ROS measurement. Expression of miR-409 was determined using quantitative reverse-transcription polymerase chain reaction (qPT-PCR). Protein expression levels were detected using western blotting. RESULTS: Rats treated with isoflurane showed significant increases in the escape latency periods (ELP) and the apoptosis of hippocampus neuron cells; this effect was reversed by 3 mg/kg or 10 mg/kg of vitexin (p < 0.05). Further testing showed that isoflurane could significantly decrease the cell viability and increase the apoptosis of PC-12, the expression of inflammatory cytokines (TNF­α and IL­6) and ROS (p < 0.05). However, these results were reversed by 10/100 µM of vitexin. In addition, vitexin could significantly increase the expression of miR-409 (p < 0.05). Further studies showed that overexpression of miR-409 could significantly promote the effect of vitexin on isoflurane-induced neurotoxicity (p < 0.05). Finally, overexpression miR-409 could significantly increase the expression of p-AMPK/t-AMPK and p-GSK3ß/t-GSK3ß. CONCLUSIONS: Vitexin has protective effects against isoflurane-induced neurotoxicity by targeting miR-409 and the AMPK/GSK3ß pathway.


Assuntos
Anestésicos Inalatórios , Apigenina/farmacologia , Isoflurano/farmacologia , MicroRNAs/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP , Animais , Apoptose/efeitos dos fármacos , Criança , Ensaio de Imunoadsorção Enzimática , Glutationa/sangue , Glicogênio Sintase Quinase 3 beta , Humanos , Interleucina-6/sangue , MicroRNAs/genética , Ratos , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
6.
Small ; 16(10): e1906538, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022444

RESUMO

Codelivery of diagnostic probes and therapeutic molecules often suffers from intrinsic complexity and premature leakage from or degradation of the nanocarrier. Inspired by the "Y" shape of indocyanine green (ICG), the dye is integrated in an amphiphilic lipopeptide (RNF). The hydrophilic segment is composed of arginine-rich dendritic peptides, while cyanine dyes are modified with two long carbon chains and employed as the hydrophobic moiety. They are linked through a disulfide linkage to improve the responsivity in the tumor microenvironment. After formulation with other lipopeptides at an optimized ratio, the theranostic system (RNS-2) forms lipid-based nanoparticles with slight positive zeta potential enabling efficient condensation of DNA. The RNS-2 displays glutathione responded gene release, activatable fluorescence recovery, and up to sevenfold higher in vitro transfection than Lipofectamine 2000. Compared with a Cy3 and Cy5 labeled fluorescence resonance energy transfer indicator for gene release, the "turn-on" indocyanine green analogs exhibit longer emission wavelength and better positive correlation with the dynamic processes of gene delivery. More importantly, the RNS-2 system enables efficient near infrared imaging guided gene transfer in tumor-bearing mice and thus provides more precise and accurate information on location of the cargo gene and synthesized carriers.

8.
Development ; 147(4)2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31988189

RESUMO

Cellular proliferation is a basic process during organ development, tissue homeostasis and disease progression. Likewise, after injury typically multiple cell lineages respond to various cues and proliferate to initiate repair and/or remodeling of the injured tissue. Unravelling the specific role of proliferation of one cell type and its lineage in the context of the whole organism during tissue regeneration and/or disease progression would provide valuable information on these processes. Here, we report a new genetic system that allows cell proliferation to be inhibited in a tissue-specific manner. We generated Cre- or Dre-inducible p21-GFP (ip21-GFP) transgenic mice that enable experimentally induced permanent cell cycle arrest of specific cell lineages of interest, while genetically marking these cells. This system allows for the inhibition of pathogenic cell proliferation. We found that cardiac fibroblast proliferation inhibition significantly reduced scar formation, and promoted neovascularization and cardiomyocyte survival. Additionally, we found that inhibition of one type of cell proliferation (namely, hepatocytes) induces the lineage conversion of another type cells (i.e. ductal cells) during tissue regeneration. These results validate the use of ip21-GFP mice as a new genetic tool for cell lineage-specific inhibition of cell proliferation in vivo.

9.
Acta Biomater ; 103: 281-292, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866569

RESUMO

Iron oxide nanoparticles (IONPs) have been widely used as contrast agents for magnetic resonance imaging (MRI) and other biomedical applications in both clinical and preclinical cases. In the present study, we show that two clinically used IONPs, ferumoxytol and ferucarbotran, have an intrinsic inhibitory effect on receptor activator NF-κB ligand (RANKL)-induced osteoclastogenesis of bone marrow-derived monocytes/macrophages (BMMs). IONPs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts and functional actin ring structures. More importantly, the inhibitory effect was also verified in vivo by its capacity to rescue the bone loss of ovariectomized (OVX) mice after intravenous injection with IONPs. Mechanistically, we found that IONPs trigger the upregulation of p62 which result in recruitment of CYLD and enhanced deubiquitination of TRAF6, a master controller of RANKL signaling. The downstream activation of NF-κB and MAPK signals was accordingly attenuated, ultimately leading to reduced expression of osteoclatogenesis-related genes. Taken together, clinically used IONPs can inhibit osteoclastogenesis through regulating TRAF6-p62-CYLD signaling complex, and they may be considered as alternative options for treatment of osteoporosis. STATEMENT OF SIGNIFICANCE: Nanoparticles have been developed as drug delivery systems for treatment of osteoporosis, mostly an age-related health problem with risk of fractures. In this work, we show that two clinically used iron oxide nanoparticles (IONPs) ferumoxytol and ferucarbotran themselves can significantly reduce the osteoporosis of ovariectomized (OVX) mice through inhibiting Osteoclastogenesis. We found that IONPs trigger the upregulation of p62 which result in recruitment of CYLD and enhanced deubiquitination of TRAF6, a master controller of RANKL signaling. The downstream activation of NF-κB and MAPK signals was accordingly attenuated, leading to reduced expression of osteoclatogenesis-related genes. Taken together, clinically used IONPs inhibit osteoclastogenesis through regulating TRAF6-p62-CYLD signaling complex, and they may be considered as alternative options for treatment of osteoporosis.

10.
Cell Stem Cell ; 26(1): 81-96.e4, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31883835

RESUMO

Rapid regeneration of smooth muscle after vascular injury is essential for maintaining arterial function. The existence and putative roles of resident vascular stem cells (VSCs) in artery repair are controversial, and vessel regeneration is thought to be mediated by proliferative expansion of pre-existing smooth muscle cells (SMCs). Here, we performed cell fate mapping and single-cell RNA sequencing to identify Sca1+ VSCs in the adventitial layer of artery walls. After severe injury, Sca1+ VSCs migrate into the medial layer and generate de novo SMCs, which subsequently expand more efficiently compared with pre-existing smooth muscle. Genetic lineage tracing using dual recombinases distinguished a Sca1+PDGFRa+ VSC subpopulation that generates SMCs, and genetic ablation of Sca1+ VSCs or specific knockout of Yap1 in Sca1+ VSCs significantly impaired artery repair. These findings provide genetic evidence of a bona fide Sca1+ VSC population that produces SMCs and delineates their critical role in vessel repair.

11.
Surg Today ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858238

RESUMO

PURPOSE: We implemented the individualized treatment (IT) regimen for children with inguinal hernia and the Lichtenstein hernioplasty using an acellular tissue matrix patch (LHAP) for those with high risks. This retrospective study compares the complications of conventional laparoscopic high hernia sac ligation (LHSL) with those of the IT regimen for the management of pediatric inguinal hernia and investigates whether the recurrence rate of inguinal hernias in children treated by IT is lower than that of those treated by LHSL. METHODS: The subjects of this retrospective study were 3006 children who underwent LHSL or IT for inguinal hernia between February, 2008 and February, 2016 at the Beijing Chao-Yang Hospital (Beijing, China). They comprised 1516 (50.4%) children who underwent LHSL between February, 2008 and December, 2012, and 1490 (49.6%) who underwent IT between January, 2013 and June, 2016. We analyzed the patients' data, including clinical characteristics and postoperative complications. The mean follow-up was 85.31 months for the LHSL group and 43.34 months for the IT group (P < 0.01). Given the difference in the follow-up periods, the log-rank test was used to analyze the recurrence rate. RESULTS: The mean age, weight, and height of these children at the time of surgery were 6 years old, 24.17 kg, and 114.48 cm in the LHSL group and 6 years old, 24.57 kg, and 115.18 cm in the IT group, respectively (P = 0.647, P = 0.393, P = 0.505). The mean age, body weight, and height for adolescents at the time of surgery were 14.7 years old, 57.19 kg, and 168.37 cm in the LHSL group and 14.9 years old, 57.96 kg and 169.21 cm in the IT group, respectively (P = 0.099, P = 0.061, P = 0.059). The male/female ratio was 5.1:1 (1268/248) in the LHSL group and 4.9:1 (1241/249) in the IT group (P = 0.795). The side ratio of inguinal hernia (right/left/bilateral) was about 10:7:8 (602/430/484) in the LHSL group and 3.8:2.8:3.4 (567/422/501) in the IT group (P = 0.551). The comorbidities of the male patients included hydrocele (206), cryptorchidism (15), umbilical hernia (12), congenital heart disease (16), and other congenital diseases (25). The comorbidities in the female patients included round ligament cysts (11). There was no significant difference between the groups in postoperative complications including hydrocele (P = 0.687), hematoma (P = 0.061), surgical site infection (P = 0.742), testicular atrophy (not found), and umbilical trocar hernia (P = 0.585). There were two cases of recurrence in the IT group and eight in the LHSL group (P = 0.07). The frequency of postoperative recurrence of adolescent inguinal hernia was 3.16% (7/221) in the LHSL group, 0 (0/223) in the IT group (P = 0.008), and 0 (0/128) in the LHSL subgroup in the IT group (P = 0.045). CONCLUSION: The favorable outcomes of IT, which had a lower recurrence rate than LHSL for adolescent inguinal hernia, demonstrate that this is a reasonable treatment regimen for pediatric inguinal hernia.

12.
Hepatobiliary Surg Nutr ; 8(5): 502-505, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31673539
13.
ACS Nano ; 13(11): 13015-13026, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31689086

RESUMO

Overcoming the reticuloendothelial system (RES) has long been a vital challenge to nanoparticles as drug carriers. Modification of nanoparticles with polyethylene glycol helps them avoid clearance by macrophages but also suppresses their internalization by target cells. To overcome this paradox, we developed an RES-specific blocking system utilizing a "don't-eat-us" strategy. First, a CD47-derived, enzyme-resistant peptide ligand was designed and placed on liposomes (d-self-peptide-labeled liposome, DSL). After mainline administration, DSL was quickly adsorbed onto hepatic phagocyte membranes (including those of Kupffer cells and liver sinusoidal endothelial cells), forming a long-lasting mask that enclosed the cell membranes and thus reducing interactions between phagocytes and subsequently injected nanoparticles. Compared with blank conventional liposomes (CL), DSL blocked the RES at a much lower dose, and the effect was sustained for a much longer time, highly prolonging the elimination half-life of the subsequently injected nanoparticles. This "don't-eat-us" strategy by DSL was further verified on the brain-targeted delivery against a cryptococcal meningitis model, providing dramatically enhanced brain accumulation of the targeted delivery system and superior therapeutic outcome of model drug Amphotericin B compared with CL. Our study demonstrates a strategy that blocks the RES by masking phagocyte surfaces to prolong nanoparticle circulation time without excess modification and illustrates its utility in enhancing nanoparticle delivery.

14.
Medicine (Baltimore) ; 98(41): e17387, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593088

RESUMO

BACKGROUND: Double-lumen bronchial tubes (DLBT) and bronchial blockers (BB) are commonly used in the anesthesia for clinical thoracic surgery. But there are few systematic clinical comparisons between them. In this study, the effects of BB and DLBT on one-lung ventilation (OLV) are studied. METHODS: The 200 patients with thoracic tuberculosis undergoing thoracic surgery, were randomly assigned to group A (DLBT) and group B (BB). Intubation time, hemodynamic changes (mean arterial pressure [MAP], heart rate [HR]), and arterial blood gas indicators (arterial partial pressure of carbon dioxide [PaCO2], arterial partial pressure of oxygen [PaO2], airway plateau pressure [Pplat], and airway peak pressure [Ppeak]) at 4 time points were recorded. Complications such as hoarseness, pulmonary infection, pharyngalgia, and surgical success rate were also evaluated postoperatively. RESULTS: Intubation times were shorter in group B. Both MAP and HR in group A were significantly higher 1 minute after intubation than before, but also higher than those in group B. PaO2 levels were lower in both groups during (OLV) than immediately after anesthesia and after two-lung ventilation (TLV), with PaO2 being lower after 60 minutes of OLV than after 20 minutes of OLV. Furthermore, at both points during OLV, PaO2 was lower in group A than in group B. No significant differences in PaCO2 were found between the 2 groups. Ppeak and Pplat were increased in both groups during OLV, with both being higher in group A than in group B. The incidence of postoperative hoarseness, pulmonary infection, and pharyngalgia were lower in group B. There was no significant difference in the success rate of operation between the 2 groups. CONCLUSIONS: Compare with using DLBT, implementation of BB in general anesthesia has less impact on hemodynamics, PaO2 and airway pressures, and achieves lower incidence of postoperative complication.


Assuntos
Anestesia Geral/métodos , Broncoconstritores/administração & dosagem , Ventilação Monopulmonar/métodos , Procedimentos Cirúrgicos Torácicos/métodos , Tuberculose Pulmonar/cirurgia , Idoso , Feminino , Hemodinâmica , Humanos , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Pressão Parcial
15.
J Int Med Res ; 47(11): 5453-5464, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31640440
17.
Cell Rep ; 28(4): 966-978.e4, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340157

RESUMO

Platelet-derived growth factor receptor (PDGFR) signaling is involved in proliferation and survival in a wide array of cell types. The role of PDGFR signaling in heart regeneration is still unknown. We find that PDGFR-ß signaling decreases in myocardium with age and that conditional activation PDGFR-ß in cardiomyocytes promotes heart regeneration. Employing RNA sequencing, we show that the enhancer of zeste homolog 2 (Ezh2) can be upregulated by PDGFR-ß signaling in primary cardiomyocytes. Conditional knockout of Ezh2 blocks cardiomyocyte proliferation and H3K27me3 modification during neonatal heart regeneration with Ink4a/Arf upregulation, even in mice with myocyte-specific conditional activation of PDGFR-ß. We also show that PDGFR-ß controls EZH2 expression via the phosphatidylinositol 3-kinase (PI3K)/p-Akt pathway in cardiomyocytes. Gene therapy with adeno-associated virus serotype 9 (AAV9) encoding activated PDGFR-ß enhances adult heart regeneration and systolic function. Our data demonstrate that the PDGFR-ß/EZH2 pathway is critical for promoting cardiomyocyte proliferation and heart regeneration, providing a potential target for cardiac repair.

18.
J Gene Med ; 21(7): e3111, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31359562
19.
Medicine (Baltimore) ; 98(30): e16632, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348314

RESUMO

BACKGROUND: This study aims to systematically explore the efficacy and safety of mometasone furoate (MTF) for patients with nasal polyps (NP). METHODS: We will search MEDLINE, Cochrane Library, PubMed, Springer, Web of Science, Ovid, Wangfang and Chinese Biomedical Literature Database from their inception to April 30, 2019 without language restrictions. All randomized controlled trials (RCTs) of MTF for the treatment of NP will be considered for inclusion. RevMan 5.3 software will be used for data synthesis, subgroup analysis, sensitivity analysis, as well as the meta-analysis. RESULTS: Primary outcomes include change in symptom scores (as measured by any symptom scores), and polyp size (as assessed by any Polyp size scores or tools). Secondary outcomes consist of polyp recurrence, change in nasal air flow, quality of life outcomes (as measured by any quality of life scales, such as Short Form Health Survey is a 36-item), and adverse events. CONCLUSION: This study will provide evidence for judging whether MTF is an effective and safe treatment for NP or not. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019134037.


Assuntos
Anti-Inflamatórios/uso terapêutico , Furoato de Mometasona/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Administração Intranasal , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Projetos de Pesquisa
20.
J Genet ; 98(2)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31204705

RESUMO

Hypoplastic right heart syndrome(HRHS) is characterized by hypoplastic right ventricle (RV); Numerous transcriptional cascades in the second heart field (SHF) regulate RVdevelopment. The relationship of SHF gene variants with human HRHS remains unknown. The whole lengths of 17 SHF genes were sequenced in 16 HRHS, and the selected single-nucleotide variants (SNVs) were then genotyped in HRHS, other congenital heart disease (CHD) and healthy control. Luciferase assay was performed to verify the effect of FOXC2: rs34221221A>GandTBX20: rs59854940C>Gat the transcription level. There were 151 (12.86%) novel SNVs after sequence analysis, of which three were in exons (one was synonymous SNV and two were nonsynonymous SNVs), two in promoter, and most SNVs (89.95%) were in intronic regions. Genotype analyses revealed that the minor alleles of FOXC2: rs34221221 A>G and TBX20: rs59854940 C>G could increase HRHS risk (P<0.05), but not in other CHD or healthy control. Luciferase assay showed that the minor G allele in rs34221221 significantly increased FOXC2 transcription while in rs59854940 it decreased TBX20 transcription significantly. Novel variants of SHF gene associated with HRHS were identified. Minor alleles in two variants from FOXC2 and TBX20 could increase the risk of HRHS.


Assuntos
Alelos , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Biomarcadores , Ecocardiografia , Eletrocardiografia , Elementos Facilitadores Genéticos , Fatores de Transcrição Forkhead/metabolismo , Estudos de Associação Genética/métodos , Testes Genéticos , Genótipo , Cardiopatias Congênitas/epidemiologia , Humanos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Proteínas com Domínio T/genética , Transcrição Genética
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