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2.
Bioprocess Biosyst Eng ; 42(8): 1353-1365, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31062087

RESUMO

Candicidin is one of the frequent antibiotics for its high antifungal activity, but the productivity is still extremely low. Introduction of adpA into Streptomyces ZYJ-6 could improve candicidin productivity significantly and achieved 9338 µg/mL, which was the highest value ever reported in the literature. Combined analyses of transcriptional levels, metabolic flux and metabolomics indicate that para-aminobenzoic acid and the first step of shikimic acid metabolism were not the bottleneck for the candicidin production in the control. However, methylmalonyl-CoA played a central role in the candicidin production and the gene methB responsible for the biosynthesis of methylmalonyl-CoA might be the candidate gene target for further improving the production of candicidin.

3.
Pharmacology ; 104(1-2): 28-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31039578

RESUMO

BACKGROUND: Anthroquinones are considered remarkable anticancer agents. Chrysophanol is an important anthroquinone and it has shown to have the potential to inhibit the growth of the range of cancers. However, there are no studies regarding the anticancer effects of chrysophanol against the malignant meningioma of optic nerve. In this review, the potential of chrysophanol in the treatment of malignant -meningioma of optic nerve was explored by evaluating its anticancer activity against the malignant meningioma CH157-MN cells. MATERIALS AND METHODS: The 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay was used for cell viability determination. The 4',6-diamidino-2-phenylindole (DAPI), acridine orange and ethidium bromide (AO/EB) and annexin V/PI assays were used to determine the induction of apoptosis. The potential of reactive oxygen species and the mitochondrial membrane was estimated by flow cytometry. Western blot analysis was performed to determine the protein expression. RESULTS: The results showed that chrysophanol caused significant decline in the viability of the CH157-MN cells and exhibited an IC50 of 30 µmol/L. Anticancer effects were found to be due to the induction of apoptosis as evident form the DAPI and AO/EB staining. The annexin V/PI staining revealed that the apoptotic cells increased from 1.77% in control to 37.21% at 60 µmol/L concentration of chrysophanol. The Bcl-2/Bax expression ratio was decreased and the caspases-3 and 9 were activated upon chrysophanol treatment of the CH157-MN cells. Chrysophanol also triggered the formation of reactive oxygen species and reduction of the mitochondrial membrane potential in the CH157-MN cells and also blocked the Mitogen-activated protein kinase signaling pathway. CONCLUSION: The findings of the present study suggest that chrysophanol may prove beneficial in the treatment of malignant meningioma of optic nerve. Key Message: The study revealed the anticancer potential of chrysophanol against the malignant optic nerve meningioma.

4.
Genome Med ; 11(1): 30, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101064

RESUMO

BACKGROUND: Exome sequencing (ES) has been successfully applied in clinical detection of single nucleotide variants (SNVs) and small indels. However, identification of copy number variants (CNVs) using ES data remains challenging. The purpose of this study is to understand the contribution of CNVs and copy neutral runs of homozygosity (ROH) in molecular diagnosis of patients referred for ES. METHODS: In a cohort of 11,020 consecutive ES patients, an Illumina SNP array analysis interrogating mostly coding SNPs was performed as a quality control (QC) measurement and for CNV/ROH detection. Among these patients, clinical chromosomal microarray analysis (CMA) was performed at Baylor Genetics (BG) on 3229 patients, either before, concurrently, or after ES. We retrospectively analyzed the findings from CMA and the QC array. RESULTS: The QC array can detect ~ 70% of pathogenic/likely pathogenic CNVs (PCNVs) detectable by CMA. Out of the 11,020 ES cases, the QC array identified PCNVs in 327 patients and uniparental disomy (UPD) disorder-related ROH in 10 patients. The overall PCNV/UPD detection rate was 5.9% in the 3229 ES patients who also had CMA at BG; PCNV/UPD detection rate was higher in concurrent ES and CMA than in ES with prior CMA (7.2% vs 4.6%). The PCNVs/UPD contributed to the molecular diagnoses in 17.4% (189/1089) of molecularly diagnosed ES cases with CMA and were estimated to contribute in 10.6% of all molecularly diagnosed ES cases. Dual diagnoses with both PCNVs and SNVs were detected in 38 patients. PCNVs affecting single recessive disorder genes in a compound heterozygous state with SNVs were detected in 4 patients, and homozygous deletions (mostly exonic deletions) were detected in 17 patients. A higher PCNV detection rate was observed for patients with syndromic phenotypes and/or cardiovascular abnormalities. CONCLUSIONS: Our clinical genomics study demonstrates that detection of PCNV/UPD through the QC array or CMA increases ES diagnostic rate, provides more precise molecular diagnosis for dominant as well as recessive traits, and enables more complete genetic diagnoses in patients with dual or multiple molecular diagnoses. Concurrent ES and CMA using an array with exonic coverage for disease genes enables most effective detection of both CNVs and SNVs and therefore is recommended especially in time-sensitive clinical situations.

5.
Chem Commun (Camb) ; 55(38): 5408-5419, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31020957

RESUMO

1,2,3,5-Tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) is a typical donor-acceptor fluorophore, with carbazolyl as an electron donor and dicyanobenzene as an electron acceptor. It has emerged as a powerful organophotocatalyst since 2016. Excellent redox window, good chemical stability and broad applicability make 4CzIPN an attractive metal-free photocatalyst. In this review, the recent advances of the application of 4CzIPN as a photoredox catalyst in the past three years (2016-2018) for various organic reactions are summarized.

6.
J Org Chem ; 84(10): 6065-6071, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999750

RESUMO

A general and efficient protocol for the direct preparation of various S-thiocarbamates with readily available and inexpensive sulfonyl chlorides as an odorless sulfur source was developed. The employment of easily available reactants, excellent functional group tolerability, and mild reaction conditions make this process very practical.

7.
Hum Mutat ; 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30520571

RESUMO

Next-generation sequencing has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome and whole genome sequencing in 4 independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter and thinning of the corpus callosum, we identified 4 previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co-Immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin-488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by bi-allelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway. This article is protected by copyright. All rights reserved.

8.
Org Biomol Chem ; 16(46): 9064-9068, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30456395

RESUMO

A simple and practical method for the synthesis of alkenyl dithiocyanates and alkenyl diselenocyanates has been developed via stereoselective difunctionalization of alkynes with NaSCN or KSeCN at room temperature. Through this methodology, a series of alkenyl dithiocyanates and alkenyl diselenocyanates could be efficiently and conveniently obtained in moderate to good yields under mild and metal-free conditions by the simple use of oxone and PhI(OAc)2 as the oxidants.

9.
Ann Clin Transl Neurol ; 5(10): 1277-1285, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30349862

RESUMO

De novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID) cases and are amongst the most common causes of ID especially in females. Forty-seven patients (44 females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique DDX3X variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or ID, and one fetus with abnormal ultrasound findings. Rare or novel phenotypes observed include respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders.

10.
Genome Med ; 10(1): 74, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30266093

RESUMO

BACKGROUND: Exome sequencing is now being incorporated into clinical care for pediatric and adult populations, but its integration into prenatal diagnosis has been more limited. One reason for this is the paucity of information about the clinical utility of exome sequencing in the prenatal setting. METHODS: We retrospectively reviewed indications, results, time to results (turnaround time, TAT), and impact of exome results for 146 consecutive "fetal exomes" performed in a clinical diagnostic laboratory between March 2012 and November 2017. We define a fetal exome as one performed on a sample obtained from a fetus or a product of conception with at least one structural anomaly detected by prenatal imaging or autopsy. Statistical comparisons were performed using Fisher's exact test. RESULTS: Prenatal exome yielded an overall molecular diagnostic rate of 32% (n = 46/146). Of the 46 molecular diagnoses, 50% were autosomal dominant disorders (n = 23/46), 41% were autosomal recessive disorders (n = 19/46), and 9% were X-linked disorders (n = 4/46). The molecular diagnostic rate was highest for fetuses with anomalies affecting multiple organ systems and for fetuses with craniofacial anomalies. Out of 146 cases, a prenatal trio exome option designed for ongoing pregnancies was performed on 62 fetal specimens, resulting in a diagnostic yield of 35% with an average TAT of 14 days for initial reporting (excluding tissue culture time). The molecular diagnoses led to refined recurrence risk estimates, altered medical management, and informed reproductive planning for families. CONCLUSION: Exome sequencing is a useful diagnostic tool when fetal structural anomalies suggest a genetic etiology, but other standard prenatal genetic tests did not provide a diagnosis.

11.
Org Biomol Chem ; 16(37): 8403-8407, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30215086

RESUMO

A simple and practical molecular iodine-mediated method for the efficient construction of thiocarbamates from isocyanides, thiols and water under metal-free and mild conditions has been developed. A variety of thiocarbamates were easily synthesized through this methodology, which has the advantages of simple operation, eco-friendly conditions, good functional group tolerance, and readily accessible raw materials.

12.
J Org Chem ; 83(16): 9422-9429, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30025451

RESUMO

Fluoroalkylated quinoxlines with various groups were efficiently synthesized via a one-pot tandem Michael addition/azidation/cycloamination process. Under the mild and metal-free conditions, a bis-imine intermediate (4a) was detected and isolated for the first time. KI played a crucial role in this reaction. The mechanism was described.

13.
Org Biomol Chem ; 16(27): 5050-5054, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29956708

RESUMO

A simple palladium-catalyzed selective synthesis of structurally diverse 3,4-dihydroquinazolines from electron-rich arylamines, electron-poor arylamines and glyoxalates has been developed under mild conditions. This reaction is carried out in a tandem manner constituted by the condensation of arylamines and glyoxalates, the selective Diels-Alder cycloaddition and oxidation processes, in which 4-nitrothiophenol was used as the key ligand.

14.
Medicine (Baltimore) ; 97(21): e10845, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794780

RESUMO

RATIONALE: Diffuse large B-cell lymphoma (DLBCL) and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) belong to Non-Hodgkin's lymphoma (NHL). DLBCL rarely involves the orbit. MALT lymphomas, which account for 8.0% of NHLs, rarely involve parotid gland, trachea and bronchus. PATIENT CONCERNS: We present a rare case of a long-surviving patient (≥10 years) with sequential development of multifocal recurrent non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT) and diffuse large B-Cell lymphoma (DLBCL). In August 2007, a 41-year-old man developed MALT lymphoma in the parotid gland and local irradiation was administered. In July 2008, he exhibited systemic multifocal lymphadenopathy and was diagnosed with DLBCL. He received standard combination chemotherapy and autologous hematopoietic stem cell transplantation. He was well until February 2013 when he developed MALT lymphoma of the bronchus. Subsequently, he received standard combination chemotherapy. In November 2013, the patient had a relapse of the MALT lymphoma by tracheal biopsy and received local radiation. He was well until March 2015 when he developed a MALT lymphoma of the left thigh. He underwent surgery, local irradiation and rituximab monotherapy. In September 2015, surgical resection of the left orbital masses was performed, and the biopsy revealed the presence of DLBCL. One month later, lymphadenopathy was palpated in the neck, the lower left region of the umbilicus, and the left calf. Then he received chemotherapy with rituximab and lenalidomide. In March 2016, the patient underwent surgical resection for a right popliteal mass, and the resection biopsy revealed DLBCL. To date, the patient is still alive. DIAGNOSES: The patient was diagnosed as multifocal recurrent MALT and DLBCL. INTERVENTIONS: Repeated positron emission tomography-computed tomography (CT) and biopsy were performed. OUTCOMES: CT and biopsy revealed sequential development of multifocal recurrent NHLs of MALT lymphoma and DLBCL. The correlation between MALT and DLBCL may represent a Richter transformation. Standard treatments, such as combination chemotherapy, autologous hematopoietic stem cell transplantation, and irradiation, may be driving factors for phenotypic changes in neoplastic cells. LESSONS: Physicians should pay particular attention to the long-term development of other types of NHL after achieving complete remission of one type of NHL.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Glândula Parótida/patologia , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Fatores Imunológicos/uso terapêutico , Lenalidomida , Linfadenopatia/patologia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/radioterapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/radioterapia , Linfoma não Hodgkin/patologia , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Rituximab/uso terapêutico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Transplante Autólogo , Resultado do Tratamento
15.
Echo Res Pract ; 5(2): 71-77, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29643125

RESUMO

BACKGROUND: There are limited data on what is the minimum change that can be detected in cancer patients undergoing treatment with cardiotoxic drugs and are referred for monitoring left ventricular (LV) function. OBJECTIVE: To assess the variability in the measurement of LV volumes and ejection fraction (EF) in contrast echocardiography and to determine the minimum detectable difference (MDD) between two EF measurements that can be deemed significant. METHODS: A total of 150 patients were divided into three groups according to EF (EF <53, 53-60, and >60%). Each group consisted of 50 randomly selected cancer patients who underwent contrast echocardiography between July 2010 and May 2014. Repeated measurements of LV volumes and EF were performed offline by a sonographer and a cardiologist. Inter-observer variability was assessed by analysis of variance. Measurement error was estimated by standard error of measurement and MDD. RESULTS: The 95% confidence interval with a single measurement of EF was 2 percentage points in the groups of patients with EF <53% and EF >60%, and 2.5 percentage points for patients with EF 53-60%. The MDD for EF, end-diastolic volume and end-systolic volume that could be recognized with 95% confidence interval were 4 percentage points, 7 mL and 4 mL, respectively. CONCLUSION: Contrast echocardiography is a reliable tool for serial measurements of EF to monitor cardiotoxicity due to chemotherapy. In a high-volume echocardiography laboratory with experienced staff, the MDD for EF of 4 percentage points on a good-quality recording demonstrates the high reproducibility of the Simpson's method using contrast echocardiography.

16.
Org Biomol Chem ; 16(17): 3177-3180, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29645051

RESUMO

A convenient and efficient indium-catalyzed approach to synthesize alkenyl iodides has been developed through direct iodoalkylation of alkynes with alcohols and aqueous HI under mild conditions. This catalytic protocol offers an attractive approach for the synthesis of a diverse range of alkenyl iodides in good to excellent yields.

17.
Echocardiography ; 35(3): 322-328, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29272561

RESUMO

OBJECTIVE: To investigate the influence of length difference in left ventricular (LV) long axis between the apical four-chamber and two-chamber views on measurements of LV volumes and ejection fraction (EF). METHODS: Seven hundred consecutive cancer patients underwent contrast echocardiography from July 2010 to May 2014. All patients received the echocardiographic contrast agent Definity. Recordings of apical views were analyzed by a sonographer and then by a cardiologist. The end-diastolic and end-systolic LV volumes (EDV and ESV), and LV lengths as well as EF, were measured using the biplane Simpson's method. Inter-observer variability was assessed using relative mean error (RME) and Bland-Altman analysis. RESULTS: Six hundred ninety-two patients had contrast echocardiograms with complete endocardial definition. The LV length difference of the long axis measured by the cardiologist was ≤1 mm in 284 studies (41%), 2 mm in 146 studies (21%), 3 mm in 103 studies (15%), and ≥4 mm in 159 studies (23%). The limits of agreement (LOA) and RME increase with the increasing length difference. Compared to the groups with length difference <4 mm, the RME of the measurements of indexed EDV, indexed ESV, and EF was significantly greater in the group with length difference ≥4 mm (P < .05). CONCLUSION: These results highlight the need for reviewing the LV long axis length measurements in order to provide reproducible LV volumes and EF measurements and may be used as benchmarks for quality control. A length difference of ≤3 mm can be achieved in most of our patients and is associated with an excellent inter-observer agreement.


Assuntos
Antineoplásicos/efeitos adversos , Meios de Contraste , Ecocardiografia/métodos , Ventrículos do Coração/patologia , Aumento da Imagem/métodos , Disfunção Ventricular Esquerda/induzido quimicamente , Estudos de Coortes , Feminino , Fluorcarbonetos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tamanho do Órgão , Estudos Prospectivos , Reprodutibilidade dos Testes , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
18.
Sci Rep ; 7(1): 17533, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29235518

RESUMO

The study evaluated clinical efficacy of intensity modulated radiation therapy (IMRT) in treating patients with thyroid-associated ophthalmopathy (TAO) and defined predictive factors that associated with treatment response. A total of 178 TAO patients were treated with retro-orbital IMRT with radiation dose of 20 Gy in 10 fractions. The immediate and long-term treatment response and complications were evaluated. Besides, logistic-regression analysis was conducted to identify possible predictive factors. TAO symptom score significantly fell from the initiation to 6-month post-treatment (P < 0.001). 134 patients (73.2%) had mild to significant response to IMRT, and 172 patients (96.6%) achieved stabilization of TAO without future progression. Current smoker (OR 2.88, 95% CI 1.32-6.29; P = 0.008) and symptom duration longer than 18 months (OR 3.33, 95% CI 1.24-8.93; P = 0.017) were identified as independent predictive factors for non-response of TAO to retro-orbital IMRT. Immediate complications were slight and self-limited, and long-term complications mainly included chronic xerophthalmias in12 patients (6.74%) and cataract formation in 4 patients (2.25%). The study suggested that IMRT was a viable option for treating TAO patients, with a satisfactory symptom control ability and acceptable post-treatment complications.

19.
Radiat Oncol ; 12(1): 171, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29110673

RESUMO

BACKGROUND: Radiation for Graves' ophthalmopathy (GO) has traditionally utilized lateral opposing fields (LOF) or three-dimensional conformal radiotherapy (3DCRT) technique. The current study was conducted to report clinical outcomes and therapeutic effects of intensity modulated radiation therapy (IMRT) in treating GO patients. METHODS: One hundred sixteen patients with GO were treated with IMRT as initial local therapy between July 2010 and August 2013, with a median follow-up of 62 months (range 45-81 months). Radiotherapy dose was 20 Gy in 10 fractions within two to three weeks. The immediate and long-term response to IMRT was evaluated in GO severity score and in each category of symptoms. Acute and long-term complications were recorded to assess its safety. RESULTS: Symptom severity score significantly fell from the start of treatment to 4- or 6- month post-IMRT (P < 0.01). In total, 85 patients (73.3%) experienced improvement of GO symptoms in the first half-year, and only 4 of them (4.7%) suffered recurrence of the GO symptoms during the subsequent follow-ups. Orbital pain, tearing and extraocular muscle dysfunction had the best treatment reaction to IMRT, while proptosis and blurred vision were the most refractory symptoms. Acute complications were slight and self-limited, mainly including intermittent eye redness in 9 patients (7.8%), sideburns hair loss in 19 patients (16.4%), increased milphosis or madarosis in 23 patients (19.8%) and pseudo-progression of GO symptoms in 15 patients (12.9%). For long-term complications, chronic xerophthalmias occurred in 7 patients (6.03%), cataract developed in 2 patients (1.72%), and all were well-managed by medical interventions. Radiation retinopathy and secondary malignancy was not presented in the cohort. CONCLUSION: The study demonstrated that IMRT could serve as a viable option in treating GO patients, with a satisfactory symptom control ability, and relatively slight and acceptable post-radiotherapeutic complications.


Assuntos
Oftalmopatia de Graves/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(5): 727-731, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29130665

RESUMO

OBJECTIVE: To explore the effects of insulin-like growth factor1 (IGF1) receptor (IGF1R) on the synthesis of hyaluronic acid (HA) in orbital fibroblasts of thyroid associated ophthalmopathy (TAO) and its signal pathway. METHODS: Orbital fibroblasts were harvested from TAO ( n=19) and normal control ( n=5),then were primary cultured and treated with recombinant human IGF1 in different concentrations. Before the treatment of IGF1,the cells were pretreated respectively with 1H7,LY294002 or AKT inhibitor Ⅳ for 24 h. The production of HA was measured using a commercial ELISA kit,and the synthesis of PI3K,Akt and pAkt was measured by Western blot. RESULTS: Along with the increase of recombinant human IGF1 concentration,the synthesis of HA by TAO orbital fibroblasts were increased as well,the synthesis of HA peaked at the concentration of 10 nmol/L in IGF1 in TAO group ( P<0.01). Compared with the normal control,orbital fibroblasts from TAO had the synthesis of HA increased after the treatment of IGF1 ( P<0.01). The pretreatment of 1H7 or AKT inhibitor Ⅳ significantly decreased the HA concentration in culture media ( P<0.01),while the decrease of HA synthesis in the group pretreated with LY294002 was not statistically significant ( P=0.390). IGF1 treatment increased the level of pAkt expression,but it seems no effects on PI3K and Akt expression. 1H7 and LY294002 decreased the expression of PI3K and pAkt protein,but no obvious inhibitory effect on total Akt protein. Akt inhibitor Ⅳ decreased the expression of PI3K,Akt and pAkt. CONCLUSION: The synthesis of HA by orbital fibroblasts could be increased in TAO,which may partially via phosphoinositide 3kinase/Akt pathway.

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