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1.
J Pharm Biomed Anal ; 177: 112880, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31546137

RESUMO

Hepatitis E, which is caused by infection with hepatitis E virus (HEV), is a global health problem in both developed and developing countries. An efficacious hepatitis E vaccine was licensed (by China) in 2011 with a trade name of Hecolin®. The antigen contained in this vaccine is a truncated version of the sole capsid protein encoded by open reading frame 2, which is designated p239. In this study, the real-time and real-condition stability and accelerated stability of five lots of hepatitis E vaccine products at the end of the designated shelf life, were assessed by a well-established quality analysis platform. The protein integrity of p239 that was recovered from the vaccine lots was demonstrated using CE-SDS, LC-MS and MALDI-TOF MS. The particle characteristics of the recovered vaccine antigen were assessed by TEM and HPSEC. The immunogenicity of hepatitis E vaccines was assessed by a mouse potency assay, which is part of product release and stability testing. Several methods were employed to assess the antigenicity of vaccines with or without adjuvant dissolution. Specifically, the well-established methods of sandwich ELISA and surface plasma resonance (SPR)-based BIAcore were used with unique murine monoclonal antibodies. Most interesting, two 'dissolution-free' immunoassays were also used for in situ antigenicity assessment of the vaccines. In addition to the confirmation of vaccine stability at the end of expiry dating, i.e., after storage in recommended conditions (2-8 °C) for 36 months, the mouse potency assay and sandwich ELISA were used to assess the accelerated stability of prefilled syringes to demonstrate the feasibility of out-of-cold-chain storage. In summary, molecular and functional characterization confirmed the shelf life stability of the vaccine at the end of expiry dating and the feasibility of transporting the hepatitis E vaccine for a given period of time out of cold chains.

2.
Neurosci Lett ; 714: 134579, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669315

RESUMO

Nondystrophic myotonias are disorders of Na+ (Nav1.4 or SCN4A) and Cl- (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity. The molecular mechanism underlying their pathophysiology and phenotype heterogeneity remains unclear. As zebrafish models have been recently exploited for studies of the pathophysiology and phenotype heterogeneity of various human genetic diseases, a zebrafish model may be useful for delineating nondystrophic myotonias. Here, we generated transgenic zebrafish expressing a human mutant allele of SCN4A, referred to as Tg(mylpfa:N440K), and needle electromyography revealed increased number of myotonic discharges and positive sharp waves in the muscles of Tg(mylpfa:N440K) than in controls. In addition, forced exercise test at a water temperature of 24 °C showed a decrease in the distance moved, time spent in and number of visits to the zone with stronger swimming resistance. Finally, a forced exercise test at a water temperature of 18 °C exhibited a higher number of dive-bombing periods and drifting-down behavior than in controls. These findings indicate that Tg(mylpfa:N440K) is a good vertebrate model of exercise- and cold-induced human nondystrophic myotonias. This zebrafish model may contribute to provide insight into the pathophysiology of myotonia in sodium channelopathy and could be used to explore a new therapeutic avenue.

3.
Biomed Pharmacother ; 121: 109596, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731193

RESUMO

Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1ß, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1ß and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1ß and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.

4.
Clin Nucl Med ; 45(1): 57-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31693617

RESUMO

Primary hepatic angiosarcoma was diagnosed in a 59-year-old woman who presented an arthralgia of limbs and dry cough for 6 weeks. Physical examination revealed digital clubbing. A Tc-MDP bone scintigraphy showed diffusely increased uptake along the cortical margins of long bones, suggesting hypertrophic osteoarthropathy.

5.
Food Chem ; 304: 125397, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31479996

RESUMO

Branched polyethyleneimine functionalized reduced graphene oxide (BPEIGn) was prepared by a one-step reaction, catalyzed by NaOH, using branched polyethyleneimine (BPEI) and graphene oxide (GO) without reductant hydrazine hydrate or sodium borohydride. The branched polyethylenimine acted as both a grafting agent and a reducing agent of GO. An competitive electrochemical immunosensor based on the Au/sodium mercaptopropanesulfonate/BPEIGn/gold nanoparticles/melamine (Au/MPS/BPEIGn/AuNPs/Mel) modified electrode was constructed for the determination of melamine. The double amplification of BPEIGn and AuNPs increased the sensitivity of the sensor. The melamine was detected by differential pulse voltammetry (DPV) in buffer solution (pH 7.4) containing K3(Fe(CN)6]/K4[Fe(CN)6]. Under optimized conditions, the proposed melamine immunosensor showed a linear relationship in the concentration range of 1 × 10-6 to 1 µM, with a detection limit of 2.66 × 10-7 µM.


Assuntos
Técnicas Eletroquímicas/métodos , Eletrodos , Ouro/química , Grafite/química , Nanopartículas Metálicas/química , Triazinas/análise , Limite de Detecção , Polietilenoimina/química
6.
J Nanosci Nanotechnol ; 20(2): 949-956, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383091

RESUMO

To improve lithium storage performances of Si anode for lithium-ion batteries, Si nanoparticles encapsulated into porous N-doped carbon (Si@PNC) was devised and prepared by metal nitrate accelerated polymer blowing process. The Si@PNC composites have large specific surface area of 221.7 m² g-1 and possess a great deal of mesopores and micropores, which are attributed to the carbonization of PVP and etching metallic nanoparticles. As anode for lithium ion battery, the initial discharge capacity of Si@PNC composites is high to 1626 mA h g-1, and the specific capacity still retains 1030 mA h g-1 after 200 cycles at 200 mA g-1. Meanwhile, remarkably improved rate capability is achieved with an excellent reversible specific capacity of 375 mA h g-1 at 5.0 A g-1. The excellent lithium storage performances benefit from the unique porous core-shell structure of Si@PNC composites, which improve electroconductivity, reduce volume dilatation and accelerate lithium ion transmission.

7.
J Colloid Interface Sci ; 558: 85-94, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585225

RESUMO

Synergistic photocatalysis offers great potential for simultaneously treating organic and heavy metal pollutants. Although considerable progress has been made, this technology is seriously restricted by the poor photoactivity of heterogeneous catalysts, and the contribution from homogeneous intermoleculars has been overlooked. In this paper, the Ag/ZnO@CF with 3-D hierarchical porous structure was fabricated and used to synergistically remove phenol and Cr(VI) from water. Due to the enhanced mass transfer and cocatalysts-facilitated charge separation, 3-D photocatalysts exhibited significantly improved activity for heterogeneous photocatalysis. Furthermore, both experimental characterizations and DFT calculations evidenced the formation of phenol-chromate(VI) esters with ligand-to-metal charge transfer from benzene ring to central chromium ion under photoexcitation. Thereafter, the effects of heterogeneous and homogeneous photocatalysis on the treatment efficiency of multiplex pollutants were investigated. In an ideal scenario, 2.4 and 2.3 times higher phenol and Cr(VI) removal rate were achieved compared to single catalytic reactions. This work not only offers new material strategy for photocatalyst exploration, but also provides new insights into the multiphase homogeneous catalysis contributed by intermolecular interactions.

8.
Virology ; 539: 80-91, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31706163

RESUMO

To identify potential pathogens responsible for a disease outbreak of cultured peafowls in China in 2013, metagenomic sequencing was conducted. The genomes of two closely related parvoviruses, namely peafowl parvovirus 1 (PePV1) and PePV2, were identified with size of 4428 bp and 4348 bp, respectively. Phylogenetic analysis revealed that both viruses are novel parvoviruses, belonging to the proposed genus Chapparvovirus of Parvoviridae. The transcriptional profile of PePV1 was analyzed by transfecting a nearly complete PePV1 genome into HEK-293T cells. Results revealed that PePV1 employs one promoter and two polyadenylation sites to start and terminate its transcriptions, with one donor site and two acceptor sites for pre-mRNA splicing. PePV1 DNA and structural protein were detected in several tissues of a dead peafowl, which appeared to have suffered enteritis, pneumonia and viremia. These results provide novel information of chapparvoviruses, and call for attention to the potential pathogens.

9.
Sensors (Basel) ; 19(23)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31795476

RESUMO

In this paper, we prepared a high-performance zinc oxide (ZnO) humidity sensor in an alkaline environment using one-step hydrothermal method. Experiments showed that the pH value of the precursor solution affects the performance of ZnO humidity sensors. There are abundant hydroxyl group and oxygen vacancies on the surface of ZnO with a precursor pH value of 10. Abundant hydroxyl groups on the surface of ZnO can adsorb a large number of water molecules and rich oxygen vacancies can accelerate the decomposition of water molecules, thus increasing the number of conductive ions (H3O+) and further improving the performance of the sensor. So, such a ZnO humidity sensor exhibited high sensitivity (14,415), good linearity, small hysteresis (0.9%), fast response/recovery time (31/15 s) in the range from 11% to 95% relative humidity (RH). Moreover, the ZnO-2 humidity sensor has good repeatability and can be effectively used for a long time. This study provides a new idea for the development of low-cost, high-performance and reusable ZnO resistive humidity sensors.

10.
Med Phys ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799718

RESUMO

PURPOSE: In this paper, for the purpose of accurate and efficient mass detection, we propose a new deep learning framework, including two major stages: Suspicious region localization (SRL) and Multi-context Multi-task Learning (MCMTL). METHODS: In the first stage, SRL focuses on finding suspicious regions (regions of interest, ROIs) and extracting multi-size patches of these suspicious regions. A set of bounding boxes with different size is used to extract multi-size patches, which aim to capture diverse context information. In the second stage, MCMTL networks integrate features from multi-size patches of suspicious regions for classification and segmentation simultaneously, where the purpose of this stage is to keep the true positive suspicious regions and to reduce the false positive suspicious regions. RESULTS: According to the experimental results on two public datasets (i.e., CBIS-DDSM and INBreast), our method achieves the overall performance of 0.812 TPR@2.53 FPI and 0.919 TPR@0.12 FPI on test sets, respectively. CONCLUSIONS: Our proposed method suggests comparable performance to the state-of-the-art methods.

11.
World Neurosurg ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785439

RESUMO

INTRODUCTION: The suboccipital midline approach is common dealing with posterior fossa tumors but facing a high risk of postoperative complications, such as pseudomeningocele, cerebrospinal fluid (CSF) leak and meningitis. Neurosurgeons used various kinds of method to lower its rate. METHODS: A retrospective, single-center review of patients diagnosed with posterior fossa tumor underwent a suboccipital midline approach. Compare the rate of pseudomeningocele, CSF leak and meningitis between two groups (artificial dura-mater or cervical fascia autograft). We get the cervical fascia autograft from the superficial layer of deep cervical fascia just above the trapezius. RESULTS: Our retrospective review involved 123 patients matching the inclusion criteria between January 2009 and April 2019. The complication rate of pseudomeningocele, CSF leak and meningitis were 8.9%, 4.9% and 17.9% respectively. Presence of pseudomeningocele or CSF leak for group "artificial" were 11 of 75 (14.67%), for group "autograft" 3 of 48 (6.25%). The rate of meningitis for group "artificial" (24.0%, 18 of 75) was significantly higher(P=0.027) than the one for group "autograft" (8.33%, 4 of 48). Multivariate regression analysis suggested that the age was negatively correlated with postoperative pseudomeningocele or CSF leak (P=0.006), with meningitis (P<0.001). Using cervical fascia autograft decreased the rate of meningitis (P=0.021), while showed no statistically significant clinical impact on pseudomeningocele or CSF leak. CONCLUSIONS: Applying the cervical fascia autograft to reconstruct the dura during posterior fossa surgery is a simple and effective method to reduce the rate of meningitis as compared with artificial dura mater.

12.
Pediatr Res ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785592

RESUMO

BACKGROUND: Retinol-binding protein 4 (RBP-4) is an adipokine involved in regulating insulin sensitivity which would affect fetal growth. It is unclear whether RBP-4 is associated with fetal overgrowth, and unexplored which fetal growth factor(s) may mediate the association. METHODS: In the Shanghai Birth Cohort, we studied 125 pairs of larger-for-gestational-age (LGA, birth weight >90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25-75th percentiles) control infants matched by sex and gestational age. We measured cord blood concentrations of RBP-4, insulin, proinsulin, insulin-like growth factor-I (IGF-I), and IGF-II. RESULTS: Cord blood RBP-4 concentrations were elevated in LGA vs. OGA infants (21.9 ± 6.2 vs. 20.2 ± 5.1 µg/ml, P = 0.011), and positively correlated with birth weight z score (r = 0.19, P = 0.003), cord blood proinsulin (r = 0.21, P < 0.001), IGF-I (r = 0.24, P < 0.001), and IGF-II (r = 0.15, P = 0.016). Adjusting for maternal and neonatal characteristics, each SD increment in cord blood RBP-4 was associated with a 0.28 (0.12-0.45) increase in birth weight z score (P < 0.001). Mediation analyses showed that IGF-I could account for 31.7% of the variation in birth weight z score in association with RBP-4 (P = 0.01), while IGF-II was not an effect mediator. CONCLUSIONS: RBP-4 was positively associated with fetal overgrowth. IGF-I (but not IGF-II) may mediate this association.

13.
J Diabetes Complications ; : 107495, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31785994

RESUMO

BACKGROUND AND OBJECTIVE: Advanced glycation end products (AGEs) have been hypothesized as the etiologic factors of diabetic periodontitis. The discovery of incretins (including GLP-1 and GIP) provides a novel therapy for the treatment of diabetes. Recent reports have shown that glucagon-like peptide-1 (GLP-1) is an important modulator of bone growth and remodeling. The aim of this study was to clarify the mechanism of how GLP-1 weakens/inhibits the effect of AGEs in hPDLSCs (human periodontal ligament stem cells). MATERIALS AND METHODS: The hPDLSCs were cultured under simulated conditions of osteogenic culture, AGEs, AGEs + GLP-1, AGEs + GLP-1 + PMA and AGEs + GLP-1 + LY333531. The phenomenon and related mechanism of cell osteogenesis under different microenvironments were evaluated by Alizarin red staining, ALP staining and quantitative activity measurement, RT-qPCR, western blotting and immunofluorescence staining. RESULTS: RT-qPCR showed that AGEs negatively regulated the expression of osteogenic differentiation markers (ALP, BSP, OPN, and Runx2); in contrast, GLP-1 increased the expression of these markers. Furthermore, the expression of RAGE and pPKCß (PKC phosphorylation) in the AGE group was upregulated, while the expression of RAGE and pPKCß was decreased in the GLP-1 group compared with the AGE group. CONCLUSIONS: AGEs impaired the osteogenic potential of hPDLSCs via PKCß2. Our phenomenon showed that GLP-1 could reverse the function of AGEs on osteogenic potential. In addition, the mechanism of GLP-1 weakens/inhibits the effect of AGEs in hPDLSCs, possibly by inhibiting PKCß2 phosphorylation.

14.
Biochim Biophys Acta Gen Subj ; : 129496, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786107

RESUMO

BACKGROUND: Germline mutations in heat shock factor 4 (HSF4) cause congenital cataracts. Previously, we have shown that HSF4 is involved in regulating lysosomal pH in mouse lens epithelial cell in vitro. However, the underlying mechanism remains unclear. METHODS: HSF4-deficient mouse lens epithelial cell lines and zebrafish were used in this study. Immunoblotting and quantitative RT-PCR were used for expression analysis. The protein-protein interactions were tested with GST-pull downs. The lysosomes were fractioned by ultracentrifugation. RESULTS: HSF4 deficiency or knock down of αB-crystallin elevates lysosomal pH and increases the ubiquitination and degradation of ATP6V1A by the proteasome. αB-crystallin localizes partially in the lysosome and interacts solely with the ATP6V1A protein of the V1 complex of V-ATPase. Furthermore, αB-crystallin can co-precipitate with mTORC1 and ATP6V1A in GST pull down assays. Inhibition of mTORC1 by rapamycin or siRNA can lead to dissociation of αB-crystallin from the ATP6V1A and mTORC1complex, shortening the half-life of ATP6V1A and increasing the lysosomal pH. Mutation of ATP6V1A/S441A (the predicted mTOR phosphorylation site) reduces its association with αB-crystallin. In the zebrafish model, HSF4 deficiency reduces αB-crystallin expression and elevates the lysosomal pH in lens tissues. CONCLUSION: HSF4 regulates lysosomal acidification by controlling the association of αB-crystallin with ATP6V1A and mTOR and regulating ATP6V1A protein stabilization. GENERAL SIGNIFICANCE: This study uncovers a novel function of αB-crystallin, demonstrating that αB-crystallin can regulate lysosomal ATP6V1A protein stabilization by complexing to ATP6V1A and mTOR. This highlights a novel mechanism by which HSF4 regulates the proteolytic process of organelles during lens development.

15.
Eur J Med Chem ; : 111888, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31787359

RESUMO

Targeting L858R/T790M/C797S mutant EGFR is a major challenge in the new-generation EGFR tyrosine kinase inhibitors development for conquering drug resistant NSCLC. In this study, a series of novel 9-heterocyclyl substituted 9H-purine derivatives were designed as EGFRL858 R/T790 M/C797S tyrosine kinase inhibitors. Among these compounds, D4, D9, D11 and D12 showed significantly potent anti-proliferation and EGFRL858 R/T790 M/C797S inhibition activity. In particular, the most potent compound D9 showed anti-proliferation against HCC827 and H1975 cell lines with the IC50 values of 0.00088 and 0.20 µM, respectively. And D9 inhibited the EGFRL858R/T790M/C797S with an IC50 value of 18 nM. Furtherly, D9 could significantly suppress the EGFR phosphorylation, induce the apoptosis, arrest cell cycle at G0/G1, and inhibit colony formation in HCC827 cell line by a concentration-dependent manner. Molecular docking indicated that the introduction of a cyclopropylsulfonamide group in D9 led to the formation of additional two hydrogen bonds with mutant Ser797 which played key roles in generating efficient EGFRL858 R/T790 M/C797S inhibitory activity. These findings strongly indicated that 9-heterocyclyl substituted 9H-purine derivatives were promising L858R/T790M/C797S mutant EGFR-TKIs. The introduction of extra hydrogen bond interaction with mutant Ser797 is efficient method for the design of the fourth-generation EGFR-TKIs.

16.
J Pediatr Nurs ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31787470

RESUMO

PURPOSE: To explore Chinese parents' experiences and expectations of having preterm infants in a Chinese neonatal intensive care unit. DESIGN AND METHODS: A qualitative descriptive design with semi-structured interviews was used to describe the experiences and expectations of parents of preterm infants in a neonatal intensive care unit in the central region of China. Purposive sampling was adopted to recruit parents (n = 15) of preterm infants and data were collected by face-to-face interviews from January to May 2018. Themes were identified by thematic analysis. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULTS: Five themes emerged from the analysis: (1) mixed emotional experiences; (2) separation from the infants; (3) perceived incompetence in taking care of preterm infants; (4) obtained support through various sources; (5) desired more from healthcare professionals. CONCLUSIONS: Parents experienced additional emotional burdens due to separation from their infants as well as a lack of an effective approach to their associated needs. While NICU staff adopted several strategies to help parents cope with their infant hospitalization, these parents still expected to receive more support from healthcare providers to meet their needs. PRACTICE IMPLICATIONS: Healthcare providers should be more aware of parents' various needs in neonatal intensive care units and of their important role as constant caregivers. Hospital-based neonatal care should be specifically designed to supply positive support and necessary strategies for parents to strengthen their confidence in parenting infants.

17.
Front Immunol ; 10: 2577, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787974

RESUMO

Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine of IL12 cytokine family, however, the role of IL-35 in patients with AIH and its effect on myeloid-derived suppressor cells (MDSCs) has not yet been analyzed. The expression of IL-35 subunits (p35 and EBI3) in liver tissues was quantified by immunochemistry and its correlation with clinical parameters was explored in patients with AIH. The expression of MDSCs and IL-35 receptor (gp130 and IL-12Rß2) were analyzed using flow cytometry and confocal staining. Besides, we utilized in vitro culture to explore the role of IL-35 on MDSCs expansion and activation. We found that the elevated expression of both IL-35 subunits (EBI3 and p35) in liver tissue was positively associated with degrees of hepatic inflammatory and fibrosis in patients with AIH. Furthermore, the expression of EBI3 in liver was positively correlated with patient age, serum IgG levels and serum AST, and was negatively correlated with hemoglobin and albumin. Moreover, our results showed that ratio of MDSC in peripheral blood increased significantly in AIH patients as compared with healthy controls. Further study showed that CD33, a representative marker of MDSCs, co-localized well with gp130 and IL12Rß2, suggesting MDSCs as target cell for IL-35. Consistently, MDSCs from AIH displayed a substantial higher abundance of gp130 and IL12Rß2 and were expanded by IL-35 in vitro. IL-35-induced MDSCs showed a significant increase in Nitric oxide (NO) production but not reactive oxygen species (ROS). Conclusions: IL-35 might play an important role in AIH by regulating MDSCs and it could provide new insights into the therapy of AIH.

18.
Mol Med Rep ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31789415

RESUMO

Pancreatic cancer (PC) is the fourth leading cause of cancer­related mortality worldwide. Leptin is an adipokine that is significantly increased in obese patients and that functions in various biological processes of cancer, such as tumor growth and metastasis. However, its role in PC cell proliferation and glucose metabolism and the underlying mechanisms remain unclear. In the present study, in vitro leptin treatment significantly promoted cell proliferation and increased glucose uptake and lactate production of human PC and healthy pancreas cells in a dose­dependent manner, accompanied by increased expression of the glycolytic enzymes hexokinase II and glucose transporter 1. Furthermore, leptin receptor­specific short hairpin RNAs were used to silence leptin receptor expression in PC cells, which had the opposite effect to leptin stimulation and decreased AKT phosphorylation. In addition, the effects of leptin stimulation were significantly counteracted by the AKT inhibitor LY294002, whereas the effects of leptin silencing were counteracted by AKT activator insulin­like growth factor 1. The results of the present study suggested that leptin may contribute to cell proliferation and glucose metabolism of human PC cells, which may be through activation of the AKT pathway.

19.
BMJ Open ; 9(11): e032237, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31791965

RESUMO

OBJECTIVE: It remains unclear what roles placenta-originated angiogenic factors play in the pathogenesis of preeclampsia among hypertensive women. We compared maternal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) levels throughout pregnancy in women with normal blood pressure (BP), elevated BP and hypertension in early pregnancy and their risks of developing preeclampsia. DESIGN: A prospective cohort study. SETTING: KK Women's and Children's Hospital, Singapore. PARTICIPANTS: 923 women with singleton pregnancy <14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Systolic, diastolic, mean arterial blood pressure (MAP) were measured at 11-14 weeks. PRIMARY AND SECONDARY OUTCOMES: Maternal serum sFlt-1, PlGF and sFlt-1/PlGF ratio were tested at 11-14, 18-22, 28-32 and 34 weeks onwards of gestation. Preeclampsia was main pregnancy outcome. RESULTS: Women were divided based on their BP in early pregnancy: normal (n=750), elevated BP (n=98) and hypertension (n=75). Maternal sFlt-1 levels and sFlt-1/PlGF ratios were higher in hypertensive women throughout pregnancy, but maternal PlGF levels were not significantly lower. Rise in maternal systolic, diastolic BP and MAP at 11-14 weeks were significantly associated with higher sFlt-1/PlGF ratios during pregnancy. A 10 mm Hg increase in MAP was associated with a 5.6-fold increase in risk of preterm preeclampsia and a 3.3-fold increase in risk of term preeclampsia, respectively. CONCLUSION: Women with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia. In contrast, PlGF levels in these women remained normal.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1207-1212, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801718

RESUMO

OBJECTIVE: To compare the effects of cetrorelix and ganirelix in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles for preventing premature luteinizing hormone (LH) surges and on clinical outcomes of IVF-ET cycles. METHODS: We retrospectively analyzed 2572 GnRH-ant cycles of in vitro fertilization and embryo transfer from January, 2013 to December, 2016, including 1368 cycles with cetrorelix treatment and 1204 cycles with ganirelix treatment. The baseline characteristics of the patients and the clinical outcomes of the two groups were compared. RESULTS: Compared with those receiving ganirelix treatment, the patients with cetrorelix treatment had a significantly younger age (33.10 vs 33.89 years, P < 0.001) and a lower body mass index (21.57 vs 21.84 kg/m2, P=0.024). After adjustment for age and body mass index of the patients, no significant differences were found between the two groups in the levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), progesterone (P) levels either at the baseline or on the day of hCG triggering, or in the number of oocytes retrieved (P > 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% vs 3.2%) and similar spontaneous ovulation rate (0.6% vs 0.5%), clinical pregnancy rate (47.7% vs 45.9%) and live birth rate (37.5% vs 33.6%) following fresh embryo transfer (P > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% vs 0.1%, P=0.006). CONCLUSIONS: Cetrorelix and ganirelix can achieve comparable effects for preventing premature LH surges and can achieve similar clinical outcomes of GnRH-ant cycles, but ganirelix is associated with a significantly higher incidence of moderate to severe ovarian hyperstimulation syndrome.

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