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1.
J Med Chem ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675229

RESUMO

Metastasis is the cause of 90% of mortality in cancer patients. For metastatic colorectal cancer (mCRC), the standard of care drug therapies only palliate the symptoms but are ineffective, evidenced by a low survival rate of ~11%. T-cell factor (TCF) transcription is a major driving force in CRC and we have characterized it to be a master regulator of epithelial-mesenchymal transition (EMT). EMT transforms relatively benign epithelial tumor cells into quasi-mesenchymal or mesenchymal cells that possess cancer stem cell properties, promoting multidrug resistance and metastasis. We have identified topoisomerase IIα (TOP2A) as a DNA-binding factor required for TCF-transcription. Herein, we describe the design, synthesis, biological evaluation, and in vitro and in vivo pharmacokinetic analysis of TOP2A ATP-competitive inhibitors that prevent TCF-transcription and modulate or reverse EMT in mCRC. Unlike TOP2A poisons, ATP-competitive inhibitors do not damage DNA, potentially limiting adverse effects. This work demonstrates a new therapeutic strategy targeting TOP2A for the treatment of mCRC and potentially other types of cancer.

2.
Food Chem ; 309: 125745, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31678670

RESUMO

Simultaneous determination of multiclass illegal dyes possessing different chemical properties is difficult. By using LC-MS/MS via negative/positive ion switching mode, an efficient and fast multi-residual method for simultaneous determination of multiclass 52 illegal dyes with different acidic-basic properties in foodstuffs was developed and validated during one single run, including 23 fat-soluble neutral azo dyes, 8 acidic sulfonated azo dyes, 12 triphenylmethane basic dyes, three basic indole dyes, three xanthene dyes, one quinoline dye, and two anthraquinones dyes. The illegal dyes were extracted with methanol-acetonitrile and further purified with d-SPE procedure to reduce interference. Sample dilution with 100-fold was used for the elimination of matrix effects of the quantitation of LC-MS/MS analysis. Validation data showed the good recoveries in the range of 71.2-111.2%, with relative standard deviations less than 20%, suggesting the developed method is suitable for the identification and quantitation of multiclass illegal dyes at trace levels in foods.

3.
Nutr Diabetes ; 9(1): 32, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685792

RESUMO

OBJECTIVE: The aim of this case-control study was to assess the efficacy of dapagliflozin combined with metformin for type-2 diabetes mellitus (T2DM) with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 36 patients with newly-diagnosed T2DM and OSAHS were randomized divided into two groups. Eighteen OSAHS patients with T2DM, who were treated with dapagliflozin and metformin, were assigned as the dapagliflozin group. These patients were given dapagliflozin and metformin for 24 weeks between February 2017 and February 2018. Another 18 OSAHS patients with T2DM, who were treated with glimepiride and metformin for 24 weeks, were assigned as the control group. Fasting plasma glucose (FPG) level, postprandial blood glucose (PPG), hemoglobin A1C (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), minimum oxygen saturation (LSpO2), and Epworth Somnolence Scale (ESS) score were measured before and at 24 weeks after the initiation of treatment. RESULTS: In the dapagliflozin group, triglyceride (TG), systolic pressure (SBP) and diastolic pressure (DBP) significantly decreased following treatment, while high-density lipoprotein cholesterol (HDL-C) significantly increased (P < 0.05). Furthermore, a reduction in AHI, an increase in LSpO2 and a decrease in ESS score were observed in the dapagliflozin group (P < 0.05), but not in the control group. Moreover, blood glucose, HbA1c, HOMA-IR, and BMI significantly decreased in these two groups, and the decrease was more significant in the dapagliflozin group. CONCLUSION: These present results indicate that dapagliflozin can significantly reduce glucose, BMI, blood pressure and AHI, and improve hypoxemia during sleep and excessive daytime sleepiness, which thereby has potential as an effective treatment approach for OSAHS.

4.
Ital J Pediatr ; 45(1): 108, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439016

RESUMO

INTRODUCTION: Pentoxifylline may be an important approach to treat neonatal sepsis. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of pentoxifylline treatment for neonatal sepsis. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of pentoxifylline treatment on neonatal sepsis are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis is performed using the random-effect model. RESULTS: Seven RCTs involving 439 patients are included in the meta-analysis. Compared with control intervention for neonatal sepsis, pentoxifylline treatment is associated with reduced hospital stay (Std. MD = -0.61; 95% CI = -0.93 to - 0.29; P = 0.0002) and metabolic acidosis (RR = 0.38; 95% CI = 0.22 to 0.66; P = 0.0006), but has no remarkable impact on mortality (RR = 0.59; 95% CI = 0.30 to 1.16; P = 0.13), serum TNF-α (Std. MD = -0.38; 95% CI = -1.29 to 0.52; P = 0.41), serum CRP (Std. MD = -0.25; 95% CI = -0.92 to 0.42; P = 0.47), plasma IL-6 (Std. MD = -0.13; 95% CI = -0.41 to 0.15; P = 0.37), disseminated intravascular coagulopathy (RR = 0.55; 95% CI = 0.25 to 1.21; P = 0.14), and oliguria/anuria (RR = 0.77; 95% CI = 0.28 to 2.16; P = 0.62). In addition, pentoxifylline treatment can significantly reduce mortality (RR = 0.50; 95% CI = 0.29 to 0.88; P = 0.02) after excluding the study conducted by Akdag during the sensivity analysis. CONCLUSIONS: Pentoxifylline treatment may be associated with reduced mortality and hospital stay in neonatal sepsis.

5.
BMC Ophthalmol ; 19(1): 194, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455273

RESUMO

BACKGROUND: To investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with diabetic macular edema (DME) treated monthly with ranibizumab. METHODS: We retrospectively analyzed the medical records of all patients who received intravitreal ranibizumab (IVR) treatment for DME at the First Affiliated Hospital of Nanchang University between December 2015 and December 2017. Clinicopathological parameters, including NLR, were evaluated to identify predictors of better outcomes of IVR monotherapy. RESULTS: Ninety-one treatment-naïve eyes treated with IVR for DME were retrospectively analyzed in this study. Baseline best-corrected visual acuity (BCVA), neutrophils, NLR, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were negatively correlated with the changes in BCVA at 24 weeks compared with the baseline, while baseline central retinal thickness and lymphocytes were positively correlated with the changes in BCVA at 24 weeks compared with the baseline. Multiple linear regression analysis revealed that NLR was independently associated with the mean change of BCVA between baseline and week 24. In addition, patients with NLR < 2.27 showed a better improvement in letter score than those with NLR > 2.27. CONCLUSION: Pretreatment NLR is independently associated with the BCVA in DME patients treated with IVR, and higher pretreatment NLR may contribute to inferior BCVA outcomes.

6.
J Neuroinflammation ; 16(1): 164, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395092

RESUMO

BACKGROUND: Astrocytes respond to central nervous system (CNS) injury and disease by transforming to a reactive astrogliosis cell state that can contribute to either CNS dysfunction or repair. Neuroinflammation is a powerful driver of a harmful A1 astrogliosis phenotype associated with in vitro neurotoxicity and histopathology in human neurodegenerative diseases. Here we report a protocol for the rapid development of a human cell culture model of neuroinflammatory astrogliosis using induced pluripotent stem cells (iPSCs). METHODS: Using RNA sequencing and in vitro cell assays, we measured transcriptional and cellular effects of chronic exposure of human iPSC-derived astrocytes to the cytokines TNFα (tumor necrosis factor alpha) or IL-1ß (interleukin-1 beta). RESULTS: We show TNFα and IL-1ß induce pro-inflammatory gene signatures but by widely different magnitudes. TNFα treatment results in 606 differential expressed genes, the suppression of glutamate-uptake, and increased phagocytic activity in astrocyte cultures. In contrast, IL-1ß effects are attenuated to 33 differential expressed genes and no significant effects on glutamate-uptake or increased phagocytic activity. CONCLUSION: Our approach demonstrates a rapid tool for modeling neuroinflammatory human astrocytic responses in nervous system trauma and disease. In particular, we reveal a model for robust TNFα-induced human astrogliosis suitable for the study of neurotoxic A1 astrocytes.

7.
Phys Rev Lett ; 122(25): 256601, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31347904

RESUMO

We report the discovery of giant and anisotropic magnetoresistance due to the orbital rearrangement in a non magnetic correlated metal. In particular, we measured the magnetoresistance under fields up to 31.4 T in the cubic Pr-based heavy fermion superconductor PrV_{2}Al_{20} with a non magnetic Γ_{3} doublet ground state, exhibiting antiferroquadrupole ordering below 0.7 K. For the [100] direction, we find that the high-field phase appears between 12 and 25 T, accompanied by a large jump at 12 T in the magnetoresistance (ΔMR∼100%) and in the anisotropic magnetoresistivity ratio by ∼20%. These observations indicate that the strong hybridization between the conduction electrons and anisotropic quadrupole moments leads to the Fermi surface reconstruction upon crossing the field-induced antiferroquadrupole (orbital) rearrangement.

8.
Exp Appl Acarol ; 78(2): 273-293, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31168751

RESUMO

Tetranychus urticae (Acari: Tetranychidae) is an extremely serious cassava (Manihot esculenta) pest. Building a genomic resource to investigate the molecular mechanisms of cassava responses to T. urticae is vital for characterizing cassava resistance to mites. Based on the tolerance of cassava varieties to mite infestation (focusing on mite development rate, fecundity and physiology), cassava variety SC8 was selected to analyze transcriptomic and proteomic changes after 5 days of T. urticae feeding. Transcriptomic analysis revealed 698 and 2140 genes with significant expression changes under low and high mite infestation, respectively. More defense-related genes were found in the enrichment pathways at high mite density than at low density. In addition, iTRAQ-labeled proteomic analysis revealed 191 proteins with significant expression changes under low mite infestation. Differentially expressed genes and proteins were mainly found in the following defense-related pathways: flavonoid biosynthesis, phenylpropanoid biosynthesis, and glutathione metabolism under low-density mite feeding and plant hormone signal transduction and plant-pathogen interaction pathways under high-density mite feeding. The plant hormone signal transduction network, involving ethylene, jasmonic acid, and salicylic acid transduction pathways, was explored in relation to the M. esculenta response to T. urticae. Correlation analysis of the transcriptome and proteome generated a Pearson correlation coefficients of R = 0.2953 (P < 0.01), which might have been due to post-transcriptional or post-translational regulation resulting in many genes being inconsistently expressed at both the transcript and protein levels. In summary, the M. esculenta transcriptome and proteome changed in response to T. urticae, providing insight into the general activation of plant defense pathways in response to mite infestation.


Assuntos
Cadeia Alimentar , Manihot/fisiologia , Proteínas de Plantas/análise , Proteoma , Tetranychidae/fisiologia , Transcriptoma , Animais , Antibiose , Manihot/genética , Transdução de Sinais
9.
Chemosphere ; 232: 403-414, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31158635

RESUMO

The Three Gorges Reservoir (TGR) of China, the largest hydropower project over the world, has attracted much attention to the water impoundment and water-level manipulation. In this study, we evaluated potential effects of water impoundment and seasonal water-level manipulation on the bioaccumulation, trophic transfer and health risk of HMs (Cu, Fe, Zn, Hg, Cd and Pb) in food web components (seston, aquatic invertebrate and fish) in TGR. Our results show that, after the impoundment for eight years (2003-2010), all of the six metal concentrations in aquatic biota fell within the criteria of safety quality guidelines. The concentrations of Cu, Fe, Zn and Hg in fish and aquatic invertebrates were higher than those before impoundment, whereas Cd and Pb were lower than those before impoundment. Nonetheless, Hg, Cd and Pb in aquatic consumers underwent an increasing trend during the entire impoundment, implying potential reservoir effect in the future. Only the concentrations of Hg, Cd and Pb in aquatic consumers exhibited a declining trend towards the dam, showing consistent with the background level at the three reaches. Seasonal variations in HM concentrations of fish and aquatic invertebrates were ascribed to the water-level manipulation associated with reservoir management. Our findings show that Hg or Cd biomagnified through aquatic food web during different hydrological periods, whereas Pb, Cu, Fe and Zn exhibited weak biomagnification power. Overall, Hg, Cd and Pb showed a higher risk than that of Cu, Fe and Zn.


Assuntos
Organismos Aquáticos/metabolismo , Monitoramento Ambiental/métodos , Metais Pesados/análise , Poluentes Químicos da Água/análise , Abastecimento de Água/métodos , Animais , China , Peixes/metabolismo , Cadeia Alimentar , Invertebrados/química
10.
J Obstet Gynaecol ; : 1-7, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215279

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) during pregnancy is rare and seldom reported in literature. Here we report a case of pregnancy-associated HLH. A patient was admitted at 26 weeks and 2 days pregnancy complaining of cough and fever was admitted. She was found having bi-cytopenia, elevated ferritin and hypertriglyceridaemia. HLH was not confirmed because of the negative results from the first bone marrow biopsy. As the situation worsened, a timely termination of pregnancy was carried out. The second bone marrow biopsy did reveal hemophagocytosis and then pregnant-related HLH was confirmed. Prompt treatment of dexamethasone and etoposide have the puerpernat in a better situation. From this case, we learned HLH can be likely ignored and not be diagnosed promptly in a pregnant patient. In order to confirm this disease, a bone marrow biopsy should be performed promptly or repeatly for suspicious HLH. The time of termination and treatment is both essential for the foetus and the puerperant. Given the high morbidity and mortality of this disease in recent years, an expert consensus or clinical guideline should be developed.

11.
Am J Reprod Immunol ; 82(2): e13150, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131948

RESUMO

PROBLEM: Cortisol, which is regenerated from biologically inactive cortisone by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) in human fetal membranes, may play an important role in human parturition. Recently, we have demonstrated that human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute-phase protein of inflammation, and SAA1 may be engaged in multiple actions associated with human parturition. It remains to be determined whether SAA1 can interact with cortisol in the regulation of 11ß-HSD1 in the fetal membranes. METHOD OF STUDY: In the current study, we examined the regulation of 11ß-HSD1 expression by SAA1, and the interaction between SAA1 and cortisol in the regulation of 11ß-HSD1 expression in primary human amnion fibroblasts and amnion tissue. RESULTS: Either SAA1 or cortisol induced 11ß-HSD1 expression in a concentration-dependent manner. Combination of SAA1 and cortisol synergistically enhanced 11ß-HSD1 expression. Mechanism studies revealed that SAA1 and cortisol induced the phosphorylation of the transcription factor STAT3 in a sequential order with the induction by SAA1 preceding the induction by cortisol. Furthermore, the induction of 11ß-HSD1 expression by either SAA1 or cortisol or combination of SAA1 and cortisol was blocked by STAT3 inhibition with its antagonist S3I-201 or siRNA-mediated knockdown. CONCLUSION: This study has demonstrated that SAA1 and cortisol can reinforce each other in the induction of 11ß-HSD1 expression through sequential phosphorylation of STAT3. The synergistic enhancement of 11ß-HSD1 expression by SAA1 and cortisol may lead to excessive cortisol accumulation in the fetal membranes at parturition.

12.
Radiat Oncol ; 14(1): 82, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109371

RESUMO

BACKGROUND: The clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer. METHODS: We retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival. RESULTS: A total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6-114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort. CONCLUSION: In this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted.

13.
Medicine (Baltimore) ; 98(15): e15013, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985648

RESUMO

RATIONALE: Sitosterolemia is a rare autosomal recessive disorder of dyslipidemia due to mutations of genes ABCG5 and ABCG8, leading to highly elevated plasma levels of plant sterols and expanded body pools of cholesterol. PATIENT CONCERNS: We present a 9-year-old and a 7-year-old Chinese boy with hypercholesterolemia and xanthomas of sitosterolemia due to ABCG5 gene mutations. We also make a literature review of another 30 sitosterolemic children cases that have been reported with virulence ABCG5 gene mutations. DIAGNOSIS: We took peripheral blood samples from 2 patients and their parents to conduct genetic analysis by next-generation sequencing (NGS) technologies. INTERVENTIONS: The 2 patients received dietary modifications without pharmaceuticals treatment. OUTCOMES: A c.1166G>A (Arg389His) homozygosis mutation in exon 9 was observed in case 1, whereas a c.751C>T (Gln251*) homozygosis mutation in exon 6 was found in case 2. Literature review found another 30 pediatric cases with sitosterolemia due to ABCG5 gene mutation. The lipid profile was normalized and xanthomas got smaller with combined therapy of a combined low-cholesterol and low-phytosterols diet. LESSONS: These suggested that in patients (especially Asian patients) with multiple xanthomas, severe hypercholesterolemia, or elevated low-density lipoprotein-cholesterol, sitosterolemia should be considered in the differential diagnosis. Early diagnosis is important, and restriction of both cholesterol and phytosterols diet should suggested for these patients.


Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Hipercolesterolemia/genética , Enteropatias/genética , Erros Inatos do Metabolismo Lipídico/genética , Lipoproteínas/genética , Fitosteróis/efeitos adversos , Criança , Diagnóstico Diferencial , Humanos , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/patologia , Hipercolesterolemia/fisiopatologia , Enteropatias/dietoterapia , Enteropatias/patologia , Enteropatias/fisiopatologia , Erros Inatos do Metabolismo Lipídico/dietoterapia , Erros Inatos do Metabolismo Lipídico/patologia , Erros Inatos do Metabolismo Lipídico/fisiopatologia , Masculino , Fenótipo , Fitosteróis/genética
14.
Acta Radiol ; : 284185119845089, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023069

RESUMO

BACKGROUND: Retinal vein occlusion (RVO) is among the commonest retinal vascular conditions that can cause severe visual loss. However, the relationship between RVO and altered spontaneous brain activity is still unknown. PURPOSE: To apply regional homogeneity (ReHo) for the evaluation of abnormal brain activity in patients with RVO and explore the relationship between anomalous cerebral activity and behavioral manifestations. MATERIAL AND METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed in 26 patients with RVO (12 men, 14 women) and 24 healthy controls (12 men, 12 women) matched by age, sex, and education. ReHo was used to evaluate the local characteristics of spontaneous brain activity. The receiver operating characteristic (ROC) curve was applied to classify RVO and healthy control characteristics. Pearson correlation analysis was used to assess the relationship between the ReHo value of specific brain regions and clinical manifestations in RVO patients. RESULTS: ReHo values of the right posterior lobe of the cerebellum, fusiform gyrus, and right inferior temporal gyrus of patients with RVO were remarkably higher than those of controls (P < 0.05). ReHo values of the right cuneus in patients with RVO were significantly lower than those of controls (P < 0.05). ROC curve analysis of each brain region revealed a perfect accuracy of the areas under the curve (AUC). There was a negative correlation between the ReHo values of some regions and clinical manifestations. CONCLUSION: RVO may cause dysfunction in many brain regions, which may help reveal the neural mechanisms underlying RVO.

15.
Biosci Rep ; 39(5)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-30914454

RESUMO

Background and objective: Deregulation of the expression of amyloid precursor protein (APP) can lead to the development of Alzheimer's disease (AD). Recent studies have shown that many single nucleotide polymorphisms (SNPs) in the 3' untranslated region (UTR) of APP are associated with the development of AD. Since microRNAs (miRNAs) are involved in the regulation of APP expression, we believe that the APP 3'UTR polymorphism may affect the regulation of APP expression in miRNAs. Results: The levels of miR-101-3p, miR-153-3p, miR-144-3p, miR-381-3p, and miR-383-5p in plasma of patients with AD were significantly lower than those in the control group. The APP-534G/A site A allele was a protective factor for AD risk (adjusted odds ratio (OR) = 0.700, 95% confidence interval (95% CI): 0.573-0.840, P<0.001). The APP-369C/G site variation was not associated with AD risk. The APP-118C/A site A allele was a protective factor for AD (adjusted OR = 0.762, 95% CI: 0.639-0.897, P=0.001). The APP-534G/A site mutation affects the regulation of APP protein expression by miR-101-3p, miR-144-3p, miR-153-3p, and miR-381-3p, and the mutation of the APP-118C/A site affects miR-101-3p, miR-144-3p, miR-153-3p, and miR-383-5p regulation of APP expression. Conclusion: APP 3'UTR polymorphisms can affect the regulation of APP expression by miRNAs and thus affect the occurrence of AD.

16.
Chem Asian J ; 14(9): 1582-1589, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-30817068

RESUMO

Metal-organic gels showing potential application in catalysis have received much concern. In this work, we designed and synthesized two metal-organic gels based on coordination between FeIII and pyridine ligands at room temperature. The gels were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to reveal their assembly structures and morphologies, and it was found the metal-organic gel derived from di-topic ligand was composed of three-dimensional network of nanofibers, while the gel derived from tri-topic ligand was constituted of sponge-like structure with amorphous phase. Rheological analysis showed the gel consisting of nanofiber networks displayed self-healing property. The gels were used as catalysts for selective ethylene dimerization, and the optimum catalysis results of the gel with nanofibers reached the maximal catalytic activity of 1.48×105  g/(mol Fe⋅h) with C4 yield more than 90 %, whereas the sponge-like gel only gave 38 % C4 products at the same condition. The higher dimerization selectivity of the former FeIII gel was attributed to its regular assembly structure and lower steric hindrance of the surface metal sites. Due to its catalytic activity, high selectivity and preparation simplicity, the FeIII gel might be potentially applicable for the preparation of C4 α-olefins.

17.
J Mol Med (Berl) ; 97(5): 619-631, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30834948

RESUMO

IL-26 is a potentially important player in host defense and may be a pathogenic factor in the chronic inflammatory disorders of humans. However, the involvement of IL-26 in tuberculous pleural effusion (TPE) has not been investigated. The concentration of IL-26 was determined in pleural fluids and sera from patients with pleural effusions. Flow cytometry was performed to identify the cell origin of IL-26. The effects of tuberculosis-specific antigen (ESAT-6/CFP-10) on IL-26 expression of CD4+ T cell were explored. The impacts of IL-26 on modulating CD4+ T cell polarization were also investigated. The concentrations of IL-26 were much higher in tuberculous, malignant, and infectious PE than those in the corresponding serum. The expression of IL-26 on CD4+ T cells was much higher in tuberculous PE than those in the corresponding serum, and pleural Th1 and Th17 cells might be the major cell sources of IL-26. The addition of ESAT-6/CFP-10 to CD4+ T cells led to increasing the number of IL-26-producing CD4+ T cells and IL-26 expression on Th1 and Th17 cells. IL-26 could induce the differentiation and generation of IL-22 by memory and naive CD4+ T cells. IL-26 also upregulated the mRNA encoding CC-chemokine ligand 20 (CCL20) and CCL22 by mononuclear cells isolated from TPE. This study implies that pleural Th1 and Th17 cells are the major cell sources of IL-26, which could induce the differentiation and generation of Th22 cells by CD4+ T cells, suggesting the involvement of IL-26 in the pathogenesis of human TPE. KEY MESSAGES: IL-26 is overexpressed in TPE patients and presents a higher concentration in pleural effusion than the corresponding peripheral blood. Pleural Th1 and Th17 cells might be the major cell sources of IL-26 in TPE patients. IL-26 promotes IL-22 secretion and Th22 generation by CD4+ T cells isolated from TPE patients. IL-26 may play an active role in the pathogenesis of tuberculous pleurisy.

18.
FASEB J ; 33(7): 8148-8160, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30917001

RESUMO

Human amnion fibroblasts produce abundant prostaglandin E2 (PGE2), which plays a crucial role in parturition by stimulating not only myometrial contraction and cervical ripening but also the expression of the rate-limiting enzyme in PGE2 synthesis-namely, cyclooxygenase-2 (COX-2). This feed-forward induction of COX-2 expression by PGE2 is mediated via its receptors coupled with the cAMP and PKA pathway and subsequent phosphorylation of the transcription factors cAMP-response element binding protein (CREB) and signal transducer and activator of transcription 3 (STAT3). Although prostaglandin E receptor (EP)-2 and EP4 for PGE2 are coupled with activation of the cAMP and PKA pathway, the exact roles of these 2 receptors in the regulation of COX-2 expression in amnion fibroblasts remain to be determined. Here, we clarify this issue by employing human amnion tissue and fibroblasts with the long-term objective of specific targeting of prostaglandin synthesis in prevention of preterm birth. We find that an EP2 agonist caused long-lasting increases in CREB phosphorylation and COX-2 expression, whereas an EP4 agonist induced only transient increases in CREB phosphorylation and COX-2 expression in amnion fibroblasts. Moreover, only EP2 stimulation increased STAT3 phosphorylation, whereas only EP4 stimulation increased PI3K activity. EP4 antagonist or inhibition of PI3K enhanced the induction of CREB and STAT3 phosphorylation and COX-2 expression by PGE2 or EP2 stimulation, which was attenuated by EP4 overexpression. Of interest, PGE2 and cortisol, both well-demonstrated stimulants of COX-2 expression in amnion fibroblasts, increased EP2 but decreased EP4 receptor expression. Furthermore, increased EP2 but decreased EP4 abundance were observed in amnion tissue at parturition. We conclude that EP2 and EP4 receptors play different roles in the regulation of COX-2 expression in human amnion fibroblasts. EP2 is the dominant PGE2 receptor mediating the induction of COX-2 at parturition, which can be attenuated by simultaneous activation of PI3K coupled to the EP4 receptor.-Lu, J.-W., Wang, W.-S., Zhou, Q., Gan, X.-W., Myatt, L., Sun, K. Activation of prostaglandin EP4 receptor attenuates the induction of cyclooxygenase-2 expression by EP2 receptor activation in human amnion fibroblasts: implications for parturition.

19.
Mol Cancer Res ; 17(5): 1036-1048, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30733375

RESUMO

Cancer cell lines are critical models to study tumor progression and response to therapy. In 2008, we showed that approximately 50% of thyroid cancer cell lines were redundant or not of thyroid cancer origin. We therefore generated new authenticated thyroid cancer cell lines and patient-derived xenograft (PDX) models using in vitro and feeder cell approaches, and characterized these models in vitro and in vivo. We developed four thyroid cancer cell lines, two derived from 2 different patients with papillary thyroid cancer (PTC) pleural effusions, CUTC5, and CUTC48; one derived from a patient with anaplastic thyroid cancer (ATC), CUTC60; and one derived from a patient with follicular thyroid cancer (FTC), CUTC61. One PDX model (CUTC60-PDX) was also developed. Short tandem repeat (STR) genotyping showed that each cell line and PDX is unique and match the original patient tissue. The CUTC5 and CUTC60 cells harbor the BRAF (V600E) mutation, the CUTC48 cell line expresses the RET/PTC1 rearrangement, and the CUTC61 cells have the HRAS (Q61R) mutation. Moderate to high levels of PAX8 and variable levels of NKX2-1 were detected in each cell line and PDX. The CUTC5 and CUTC60 cell lines form tumors in orthotopic and flank xenograft mouse models. IMPLICATIONS: We have developed the second RET/PTC1-expressing PTC-derived cell line in existence, which is a major advance in studying RET signaling. We have further linked all cell lines to the originating patients, providing a set of novel, authenticated thyroid cancer cell lines and PDX models to study advanced thyroid cancer.

20.
Biomed Res Int ; 2019: 7698038, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30729130

RESUMO

Little is known about the clinical value of the Hadlock and INTERGROWTH-21st EFW standards for predicting adverse perinatal outcomes (APOs) in the third trimester. The purpose of this study was to study the association between low estimated fetal weight percentile (EFWc) in the third trimester and the risk of APOs and compare predictions of APOs between Hadlock and INTERGROWTH-21st EFW standards. A prospective cohort of 690 singleton pregnancies with ultrasonography performed in the third trimester between March 2015 and March 2016 in China was conducted. EFW and the corresponding EFWc were measured using the Hadlock and INTERGROWTH-21st standards, respectively. Cox proportional hazard models were used to assess the relationship between low EFWc (i.e., <5 percentile, P5) and the risk of APOs. Compared with fetuses with ≥P5 of the EFWc, fetuses with

Assuntos
Peso ao Nascer/fisiologia , Peso Fetal/fisiologia , Terceiro Trimestre da Gravidez/fisiologia , Ultrassonografia Pré-Natal , China , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/fisiopatologia , Feto/diagnóstico por imagem , Feto/fisiopatologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Gravidez
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