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1.
J Asian Nat Prod Res ; : 1-10, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565352

RESUMO

Polycyclic polyprenylated acylphloroglucinols (PPAPs) were mainly obtained from the plants of Hypericum genus of Guttiferae family, and possessed intriguing chemical structures and appealing biological activities. Two new PPAPs derivatives, hyperacmosin C (1) and hyperacmosin D (2) were isolated from H. acmosepalum. Their structures were established by NMR, HREIMS, and experimental electronic circular dichroism spectra. Besides, compound 1 showed significant hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage and compound 2 could moderately increase the relative glucose consumption.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33568277

RESUMO

Treatment of an impacted incisor with a dilacerated root is challenging for clinicians because of the position of the impacted incisor, the abnormality of the root, unfavorable prognosis, and, especially, the long treatment duration. We report on 2 young patients who had inversely impacted maxillary central incisors with developing labially dilacerated roots. Both patients were treated by a novel surgical approach, in situ rotation, by which the crowns of the inversely impacted incisors were carefully rotated to a relatively normal position, whereas the apical location remained relatively unchanged. About 2 weeks after surgery, spontaneous eruption of the treated incisors was observed. Three months later, the postoperative central incisors were further aligned into the maxillary arch with a fixed orthodontic appliance. Follow-up visits 2 or 3 years after surgery indicated that the positions of the dilacerated incisors maintained stability with good gingival esthetics, and the pulpal vitality was favorable. The roots grew further in a relatively normal direction of the incisor's longitudinal axis, which was t time was greatly reduced and resulted in a favorable prognosis compared with conventional treatment.

3.
J Nat Prod ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606538

RESUMO

Nine new glucosyloxybenzyl 2-hydroxy-2-isobutylsuccinates, pleionosides M-U (1-9), and 12 known compounds (10-21) were isolated from the pseudobulbs of Pleione yunnanensis. Their structures and absolute configurations were established through a combination of HRESIMS and NMR data and supported by physical and chemical methods. Compounds 5, 6, 10, and 15 showed significant in vitro hepatoprotective activity against d-galactosamine (d-GalN)-induced toxicity in HL-7702 cells with increasing cell viability by 27%, 22%, 19%, and 31% compared to the model group (cf. bicyclol, 14%) at 10 µM, respectively. Compounds 4, 9, and 11 exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with increasing cell viability by 9%, 16%, and 12% compared to the model group (cf. bicyclol, 9%) at 10 µM, respectively.

5.
Plant Cell ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33604650

RESUMO

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus.

6.
Nat Genet ; 53(1): 86-99, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33414553

RESUMO

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.


Assuntos
Variações do Número de Cópias de DNA/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Metástase Neoplásica , Polimorfismo de Nucleotídeo Único/genética , Sequenciamento Completo do Exoma
7.
J Am Soc Nephrol ; 32(2): 307-322, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33443052

RESUMO

BACKGROUND: FSGS caused by mutations in INF2 is characterized by a podocytopathy with mistrafficked nephrin, an essential component of the slit diaphragm. Because INF2 is a formin-type actin nucleator, research has focused on its actin-regulating function, providing an important but incomplete insight into how these mutations lead to podocytopathy. A yeast two-hybridization screen identified the interaction between INF2 and the dynein transport complex, suggesting a newly recognized role of INF2 in regulating dynein-mediated vesicular trafficking in podocytes. METHODS: Live cell and quantitative imaging, fluorescent and surface biotinylation-based trafficking assays in cultured podocytes, and a new puromycin aminoglycoside nephropathy model of INF2 transgenic mice were used to demonstrate altered dynein-mediated trafficking of nephrin in INF2 associated podocytopathy. RESULTS: Pathogenic INF2 mutations disrupt an interaction of INF2 with dynein light chain 1, a key dynein component. The best-studied mutation, R218Q, diverts dynein-mediated postendocytic sorting of nephrin from recycling endosomes to lysosomes for degradation. Antagonizing dynein-mediated transport can rescue this effect. Augmented dynein-mediated trafficking and degradation of nephrin underlies puromycin aminoglycoside-induced podocytopathy and FSGS in vivo. CONCLUSIONS: INF2 mutations enhance dynein-mediated trafficking of nephrin to proteolytic pathways, diminishing its recycling required for maintaining slit diaphragm integrity. The recognition that dysregulated dynein-mediated transport of nephrin in R218Q knockin podocytes opens an avenue for developing targeted therapy for INF2-mediated FSGS.

8.
Medicine (Baltimore) ; 100(2): e24032, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466149

RESUMO

RATIONALE: Long QT syndrome (LQTS) is an inheritable disease characterized by prolonged QT interval on the electrocardiogram. The pathogenesis of LQTS is related to mutations in LQTS-susceptible genes encoding cardiac ion channel proteins or subunits. PATIENT CONCERNS: Here, we reported a 37-year-old female Uygur patient with palpitation and loss of consciousness. DIAGNOSES: At the time of admission, a 12-lead electrocardiogram showed a QTc interval of 514 ms. Genetic analysis revealed KCNQ1 G219E and TRPM4 T160M mutations. INTERVENTIONS: Although beta-blockers remain the mainstay in treating LQTS, the patient underwent implantation of an automatic cardioverter defibrillator due to life-threatening arrhythmias. OUTCOMES: To explore the effect of the calcium ion antagonist verapamil on ion channels, we generated human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) from the peripheral blood mononuclear cells of the patient. The changes of action potential duration in response to verapamil were observed. LESSONS: Our results showed that patient-derived hiPSC-CMs could recapitulate the electrophysiological features of LQTS and display pharmaceutical responses to verapamil.


Assuntos
Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/genética , Canais de Cátion TRPM/genética , Adulto , Bloqueadores dos Canais de Cálcio/farmacologia , Desfibriladores Implantáveis , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Síndrome do QT Longo/cirurgia , Verapamil/farmacologia
9.
J Asian Nat Prod Res ; : 1-11, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33506714

RESUMO

Six new triterpenes, uncarinic acids KP (1-6), along with 24 known analogues, were isolated as minor constituents of an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). By comprehensive spectroscopic data analysis, their structures were elucidated as derivatives of olean-12-en-28-oic acid and urs-12-en-28-oic acid with different oxidized forms at C-3, C-6, and/or C-23, respectively. Cell-based preliminary bioassay showed that the (E)-/(Z)-coumaroyloxy and (E)-/(Z)-feruloyloxy units at C-27 of olean-12-en-28-oic acid and urs-12-en-28-oic acid played roles in their bioactivities.

10.
Pediatr Nephrol ; 36(1): 163-169, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32844290

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication of critically ill adult patients with COVID-19. However, currently, no studies investigate kidney impairment in children with COVID-19. We investigated incidence and treatment of AKI in pediatric patients with COVID-19 in Wuhan Children's Hospital during the early stages of the COVID-19 pandemic and discuss possible mechanisms of AKI related to SARS-CoV-2 infection. METHODS: By extracting data from electronic medical records, we conducted a retrospective observational study of kidney involvement in confirmed pediatric COVID-19 cases in Wuhan Children's Hospital during the coronavirus outbreak, from January 24 to March 20, 2020. Clinical presentations, clinical courses, laboratory findings, and medical interventions are described below. RESULTS: Among 238 confirmed COVID-19 cases, only three were critically ill and needed intensive care unit (ICU) admission. All three developed AKI, but AKI was not detected in any non-critically ill patients outside the ICU. Two of the three patients with AKI had prodromal gastrointestinal symptoms. Significantly elevated interleukin-6 (IL-6) levels and complement activation were observed in these patients with AKI. The three patients with AKI were treated with plasma exchange (PE) and continuous kidney replacement therapy (CKRT), resulting in one complete recovery, one partial recovery, and one mortality due to critical illness. CONCLUSIONS: Critically ill children with COVID-19 may develop AKI, especially following prodromal gastrointestinal symptoms. An inflammatory storm and complement-mediated injury may underlie AKI development in children with COVID-19. Our study supports implantation of PE and CKRT in management of critically ill patients with AKI.


Assuntos
Lesão Renal Aguda/etiologia , /complicações , Lesão Renal Aguda/diagnóstico por imagem , Lesão Renal Aguda/terapia , Criança , Estado Terminal/terapia , Síndrome da Liberação de Citocina/etiologia , Evolução Fatal , Feminino , Humanos , Lactente , Masculino , Pandemias , Troca Plasmática , Estudos Retrospectivos , Resultado do Tratamento
11.
Int J Neurosci ; 131(1): 95-101, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32083968

RESUMO

Objective: Recent studies have found that selenium (Se) levels were associated with the risk of Parkinson's disease (PD), but the results were contradictory. Therefore, this meta-analysis was conducted to investigate the correlation between Se levels and PD.Methods: PubMed, Embase and Web of Science were searched published up to 28 October 2019. The differences between groups were analyzed by forest plots and results were pooled and assessed using a random-effect model. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to assess the association between Se levels and the risk of PD. Subgroup analysis, meta-regression, and sensitivity analysis were also conducted. Publication bias was estimated using Begg's regression asymmetry test.Results: Finally, 12 articles involving 601 PD patients and 749 controls were included in this meta-analysis. The meta-analysis revealed a significantly higher cerebrospinal fluid (CSF) Se level in PD patients than those in controls (SMD = 1.22; 95%CI [0.05, 2.39]; p = 0.000). No publication bias was found.Conclusion: The meta-analysis indicated that CSF Se levels in PD patients were significantly higher than those in controls.

12.
Xenobiotica ; 51(3): 345-354, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33332226

RESUMO

Abstracts Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with Cmax and AUC0-∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The Cmax and AUC0-∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.

14.
Chin Med J (Engl) ; 133(23): 2803-2807, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33273328

RESUMO

BACKGROUND: Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART). METHODS: From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group. RESULTS: From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/µL) in the NK + ART group and (144 to 176 cells/µL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (ß = 54.59, P = 0.006) and CD8 level (ß = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course. CONCLUSIONS: This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).

15.
Artigo em Inglês | MEDLINE | ID: mdl-33259112

RESUMO

Stroke is a neurological disease with poor prognosis. Strong inflammatory and immune response exist after stroke, resulting in severe sequelae with high mortality. Microglia, the main immune cell in cerebrum, possess therapeutic potential for stroke as its specific anti-inflammatory phenotype can reduce inflammation and promote neuron regeneration. However, the on-demand anti-inflammatory polarization of microglia at stroke site is uncontrollable for therapeutic application. Here, we develop a platelet hybrid microglia platform which can specifically polarize to anti-inflammatory phenotype by ultrasound irradiation for targeted cerebrum repair after stroke. The engineered microglia have strong adherence to the injured cerebral vessels with platelet membrane fusion and can realize on-demand anti-inflammatory polarization with the ultrasound responsive IL-4 liposome decoration. Intravenously injected microglia platform showed anticipated anti-inflammatory polarization at stroke site with insonation control and accelerated the M2-type polarization of endogenous microglia for long-tern stroke recovery. Satisfied prognoses were achieved with reduced apoptosis, promoted neurogenesis and functional recovery, indicating the implications of microglia platform for stroke therapy.

16.
Ying Yong Sheng Tai Xue Bao ; 31(11): 3777-3785, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33300728

RESUMO

With landsat-series multi-temporal image data, percentage of vegetation cover (PVC) was estimated by pixel dichotomy. The linear regression analysis and center of gravity migration methods were used to explore the characteristics of the spatiotemporal changes of vegetation cover in Shenzhen from 2000 to 2018. The CA-Markov model was combined to predict future land cover in Shenzhen. The results showed that the PVC in Shenzhen demonstrated obvious regional differentiation characteristics from 2000 to 2018. The eastern region occupied larger proportion than the wes-tern part, while the southern region was larger than the north part. This feature exhibited good consistency with regional topographic effect. The spatial migration characteristic of the center of gravity of PVC was from northwest to southeast, and then from southeast to northwest, with a migration rate of 551.2 m·a-1. This process was closely related to urbanization in Shenzhen. The PVC in Shen-zhen tended to be generally improved from 2000-2018, with a improvement rate of 0.005·a-1. The percentage of significantly improved and degraded PVC area was 30.8% and 12.8%, respectively. The CA-Markov method was used to predict the land cover/use pattern of Shenzhen in 2024 under two scenarios, theoretical scenario and natural scenario. There was no significant difference in proportion of the area of the land cover/use patterns obtained by the two kinds of prediction method, with the difference threshold being 0-1.2%. Compared with the data before 2018, the proportion of arbor forests and arable land converted into construction land in Shenzhen would be significantly reduced in 2024, whereas the contradiction between supply and demand would be still tense.

17.
Ann Palliat Med ; 9(6): 4137-4145, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33302674

RESUMO

BACKGROUND: Airway humidification methods are commonly used in clinical practice, but no clear consensus exists on which particular method is best suited for specific clinical conditions. METHODS: In this retrospective study, we carried out a quantitative evaluation of three methods commonly used for patients with severe traumatic brain injury (STBI). We recruited 150 patients who received airway humidification after tracheotomy. Subjects were divided into three groups according to the humidification method they received which included oxygen atomizer (OA) group, heat and moisture exchangers (HMEs) group, and heated humidifiers (HHs) group. Variables including phlegm viscosity, humidification effects, phlegm formation rates, daily sputum inhalation times, airway spasm, secondary lung infections, daily nursing load, and evaluation of nurse job satisfaction levels were documented. RESULTS: Results indicated that the OA tended to cause either insufficient or excessive humidification, whereas phlegm scab formation was significantly reduced in HHs. HMEs and HHs displayed equal humidification effects, and a similar daily sputum induction and consequent nursing load. Airway spasm was a frequent occurrence in OA. The severity, but not the infection ratio, of secondary infection decreased significantly in HHs by the 30th day. The OA significantly reduced nursing load, but demonstrated the worst humidification effects. CONCLUSIONS: Overall results suggested that the HHs is more suitable for airway nursing of STBI patients who are bedridden for extended periods.

18.
Sensors (Basel) ; 20(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348807

RESUMO

Forest growing stem volume (GSV) reflects the richness of forest resources as well as the quality of forest ecosystems. Remote sensing technology enables robust and efficient GSV estimation as it greatly reduces the survey time and cost while facilitating periodic monitoring. Given its red edge bands and a short revisit time period, Sentinel-2 images were selected for the GSV estimation in Wangyedian forest farm, Inner Mongolia, China. The variable combination was shown to significantly affect the accuracy of the estimation model. After extracting spectral variables, texture features, and topographic factors, a stepwise random forest (SRF) method was proposed to select variable combinations and establish random forest regressions (RFR) for GSV estimation. The linear stepwise regression (LSR), Boruta, Variable Selection Using Random Forests (VSURF), and random forest (RF) methods were then used as references for comparison with the proposed SRF for selection of predictors and GSV estimation. Combined with the observed GSV data and the Sentinel-2 images, the distributions of GSV were generated by the RFR models with the variable combinations determined by the LSR, RF, Boruta, VSURF, and SRF. The results show that the texture features of Sentinel-2's red edge bands can significantly improve the accuracy of GSV estimation. The SRF method can effectively select the optimal variable combination, and the SRF-based model results in the highest estimation accuracy with the decreases of relative root mean square error by 16.4%, 14.4%, 16.3%, and 10.6% compared with those from the LSR-, RF-, Boruta-, and VSURF-based models, respectively. The GSV distribution generated by the SRF-based model matched that of the field observations well. The results of this study are expected to provide a reference for GSV estimation of coniferous plantations.

19.
J Pediatr Surg ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33189302

RESUMO

INTRODUCTION: Neuroblastoma (NB) is the most common solid tumor in children. Studies showed that long-chain noncoding RNA (lncRNA) HCP5 played an important role in tumorigenesis, but its role in NB remained unclear. This study aims to determine the role of HCP5 in NB and its possible molecular mechanism. METHODS: We analyzed the expression levels of miRNA-186-5p and HCP5 in neuroblastoma and neuroblastoma cell lines SHSY-5Y, Kelly, NBL-S and SK-N-AS, and explored their roles. RESULTS: We found that the HCP5 expression was up-regulated in NB tissues and cells. The higher the HCP5 expression in NB cells, the stronger the ability of clone formation. Down regulation of the HCP5 expression inhibited the proliferation of NB cells and the growth of subcutaneous transplanted tumor in nude mice. HCP5 could competitively bind miR-186-5p, while miR-186-5p could target the 3'-UTR of MAP3K2. The expression level of miR-186-5p was down regulated while the expression level of MAP3K2 was up-regulated in NB tissues. The expression level of HCP5 and miR-186-5p, the expression level of miR-186-5p and MAP3K2 were negatively correlated. The decreased proliferation of NB cells induced by down-regulation of HCP5 expression can be counteracted by miR-186-5p inhibitor or MAP3K2, and vice versa. CONCLUSION: This study showed that lncRNA HCP5, as ceRNA, regulated MAP3K2 to promote NB progression through competitive binding of miR-186-5p. We revealed a new signaling pathway that mediates NB, which provided a new target for the diagnosis and treatment of NB.

20.
Cancer Sci ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164305

RESUMO

High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism through which HMGA2 is transcriptionally regulated in hepatocellular carcinoma (HCC) cells remains largely unclear. Here, we demonstrated that the expression HMGA2 was upregulated in HCC, and the elevated HMGA2 could promote tumor metastasis. Incubation HCC cells with Epidermal Growth Factor (EGF) could promote the expression of HMGA2 mRNA and protein. Mechanistic studies suggested that EGF can phosphorylate p300 at Ser1834 residue through PI3K/Akt signaling pathway in HCC cells. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, while a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in a chemically induced HCC model in rats and human HCC specimens.

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