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1.
Cell Death Dis ; 10(11): 831, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685803

RESUMO

Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

2.
Inorg Chem ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710468

RESUMO

The first open hollow Sn13-oxo cluster family has been successfully prepared and characterized. These Sn13 clusters contain a {Sn7} moiety that is similar to the basic structure unit of rutile SnO2. Interestingly, the Sn13 clusters show labile coordination sites on the edge, which could be functionalized by different ligands. With the different decorated types of functionalized ligands, the open hollow Sn13 clusters present different structural details and framework diameters. The presented results provide a new open hollow structural motif of tin-oxo clusters and also a good platform for their ligand functionalization.

3.
Medicine (Baltimore) ; 98(44): e17744, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689826

RESUMO

Congenital syphilis (CS) can cause serious impact on the fetus. However, congenital syphilis presenting as sepsis is a critical condition but hardly identified by the clinic for the first time. In this study, we aimed to identify the benefit of earlier and accurate diagnosis for the infants who suffer congenital syphilis presenting as sepsis.A retrospective study was performed with patients diagnosed of congenital syphilis presenting as sepsis who were the inpatients in the West China Second Hospital between 2011 and 2018. The control group was collected in the neonatal sepsis patients whose blood culture are positive.Fifty-eight patients were included in the study. In the congenital syphilis group, one patient died and 12 (41.3%) patients get worse to MODS (multiple organ dysfunction syndrome). Symptoms, signs, and lab examinations are found to be significantly different (P < .05) between two groups as below, including rash, palmoplantar desquamation, abdominal distension, splenomegaly, hepatomegaly, etc. And, at the aspect of Hb, PLT, WBC, CRP, ALT, AST, these differences occurred in the different groups. It is obvious that the prognosis of children with syphilis is worse. According to a comparison between the different outcomes in the CS, the worse outcome subgroup of patients is significantly younger and have more severely impaired liver function.Because of the high mortality of these infants, pediatricians should improve awareness of CS. Syphilis screening is recommended for pregnant women.


Assuntos
Sepse Neonatal/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Sepse/diagnóstico , Sífilis Congênita/diagnóstico , Sífilis/diagnóstico , Estudos de Casos e Controles , China , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/microbiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Sepse Neonatal/microbiologia , Sepse Neonatal/mortalidade , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/mortalidade , Estudos Retrospectivos , Sepse/microbiologia , Sepse/mortalidade , Sífilis/microbiologia , Sífilis/mortalidade , Sorodiagnóstico da Sífilis , Sífilis Congênita/mortalidade
4.
Environ Int ; 134: 105284, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31707300

RESUMO

BACKGROUND: Perfluorinated compounds (PFCs) were reported to result in the endocrine disruption by activating the estrogen receptor (ER) and inducing ER-mediated transcriptions. OBJECTIVE: The aim of the present work was to perform cross-species comparisons on the characteristics of eight PFCs binding to humans ERα and to rats ERα. METHODS: In the present work, in vivo tests, including serum estradiol level assay and immunohistochemical staining, fluorescence assay and molecular models were applied. RESULTS: Based on the in vivo experiments, the exposure of PFOA and PFOS to female rats was proved to increase the ERα expression in the terus, suggesting that PFCs may act as estrogenic compounds to activate ERα in vivo. The further fluorescence assay presented that these eight PFCs have stronger binding abilities to human ERα than to rat ERα. In addition, the differences in binding specificities between human ERα and rat ERα were identified in the process of molecular dynamics modeling with the term of helix position and the ability of coregulator recruitment. It can be found that more and stronger charge clamps could form between PFCs with human ERα than with rat ERα. Also, the eight PFCs presented lower binding energies in human ERα systems, which proved that eight PFCs presented much stronger binding abilities with human ERα. DISCUSSION: In all, it can be concluded that PFCs might be more sensitive to human ERα than to that of rats, which also suggested the greater susceptibility to adverse effects on humans. The present work was a beginning assessment of a cross-species comparison, providing important information on health impacts of PFCs in humans.

5.
Sci Rep ; 9(1): 15836, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676842

RESUMO

Aphid-parasitoid interactions have been widely used as a model system in research studies on the structure and functions of arthropod food web. Research on aphid-parasitoid food webs is hindered by their micromorphological characteristics and the high amount of labor associated with their development. Species-specific primers for cotton aphids and their parasitoids were designed and integrated into two multiplex PCRs and six singleplex PCRs, and all PCRs were optimized to achieve high specificity and sensitivity (100-10,000 DNA copies). One cotton aphid (Aphis gossypii) as well as three primary parasitoid and seven hyperparasitoid species or genera were detected using this molecular approach. This group comprises all the primary parasitoids and 97.2-99.6% of the hyperparasitoids reported in cotton fields in northern China. A tritrophic aphid-primary parasitoid-hyperparasitoid food web was then established. The described method constitutes an efficient tool for quantitatively describing the aphid-primary parasitoid-hyperparasitoid food webs and assessing the efficiency of the biological control of parasitoids in cotton fields in northern China.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31720813

RESUMO

PURPOSE: Tumor-associated macrophages (TAMs) exist as heterogeneous subsets and have dichotomous roles in cancer-immune evasion. This study aims to assess the clinical effects of Galectin-9+ tumor-associated macrophages (Gal-9+TAMs) in muscle-invasive bladder cancer (MIBC). EXPERIMENTAL DESIGN: We identified Gal-9+TAMs by immunohistochemistry (IHC) analysis of a tumor microarray (TMA) (n = 141) from the Zhongshan Hospital and by flow cytometric analysis of tumor specimens (n = 20) from the Shanghai Cancer Center. The survival benefit of platinum-based chemotherapy in this subpopulation was evaluated. The effect of the tumor-immune microenvironment with different percentages of Gal-9+TAMs was explored. RESULTS: The frequency of Gal-9+TAMs increased with tumor stage and grade. Gal-9+TAMs predicted poor overall survival (OS) and recurrence-free survival (RFS) and were better than Gal-9-TAMs and TAMs to discriminate prognostic groups. In univariate and multivariate Cox regression analyses, patients with high percentages of Gal-9+TAMs showed the prominent survival benefit after receiving adjuvant chemotherapy (ACT). High Gal-9+TAM infiltration correlated with increasing numbers of regulatory T cells (Tregs) and mast cells and decreasing numbers of CD8+T and dendritic cells (DCs). Dense infiltration of Gal-9+TAMs was related to reduced cytotoxic molecules, enhanced immune checkpoints or immunosuppressive cytokines expressed by immune cells, as well as active proliferation of tumor cells. Additionally, the subpopulation accumulated was strongly associated with PD-1+TIM-3+CD8+T cells. CONCLUSIONS: Gal-9+TAMs predicted OS and RFS and response to ACT in MIBC patients. High Gal-9+TAMs were associated with a pro-tumor immune contexture concomitant with T cell exhaustion.

7.
Carbohydr Polym ; 226: 115285, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582075

RESUMO

The gel behavior of low methoxyl pectin (LMP) de-esterified by high hydrostatic pressure-assisted enzymatic (HHP-pectin, 400 MPa/40 °C/12 min), atmospheric enzymatic (E-pectin, 40 °C/2 h), and alkaline method (A-pectin, pH = 12/25 °C/25 min) was comparatively investigated, with regard to gel strength, water-holding capacity (WHC), rheological properties, and microstructure of pectin gels. Results showed that the de-esterification method had a strong influence on gelling properties of LMPs. The gelation of all LMPs was significantly affected by pectin, Ca2+ concentration and pH of the solution, but enzymatically de-esterified LMPs formed gels with higher gel strength, WHC and better viscoelasticity than those from alkaline de-esterified method. HHP-pectin gels showed even higher gel strength at the same Ca2+ concentrations and better WHC at the same pH, as compared to those from E-pectin. Moreover, the de-esterification time for HHP-pectin was much shorter than that for E-pectin. These findings indicated that HHP could be a potential alternative for high efficient pectin de-esterification, preparing LMPs with better gelling property.

8.
Psychiatry Res ; 282: 112608, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31655405

RESUMO

OBJECTIVES: Abnormalities in insular functional connectivity have been implicated in many clinical features of schizophrenia. The aim of this study was to determine to what degree such abnormalities occur in individuals with clinical high risk for psychosis (CHR), and whether which is associated with symptom severity. METHODS: Resting-state fMRI data were collected from 47 healthy controls, 24 CHR individuals and 19 patients with first-episode schizophrenia. Using the posterior, dorsal and ventral insular subregions as separate seeds, we examined resting-state functional connectivity differences between different groups and the association between concurrent symptom severity and dysconnectivity. RESULTS: Compared with healthy controls, both CHR individuals and schizophrenia patients showed hypoconnectivity between posterior insula (PI) and somatosensory areas, and between dorsal anterior insula (dAI) and putamen. Schizophrenia patients also showed dAI and ventral anterior insula(vAI) hyperconnectivity with visual areas relative to controls and CHR individuals. Correlation analysis revealed that dAI functional connectivity with superior temporal gyrus was positively correlated with positive symptoms of CHR, and vAI connectivity with dorsolateral prefrontal cortex was negatively correlated with the severity of the symptoms of first-episode schizophrenia. CONCLUSIONS: Our findings suggest that insular functional dysconnectivity with the sensory cortex may be a system-level neural substrate preceding the onset of psychosis.

9.
Int J Cancer ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584197

RESUMO

Our previous researches have identified immunoevasive subtype muscle-invasive bladder cancer (MIBC) characterized with immune cells infiltration patterns. Our study explored the clinical significance, immunoregulatory role and therapeutic value of intratumoral IL22-producing cells in MIBC. Two hundred and fifty-nine formalin-fixed paraffin-embedded MIBC samples and 83 freshly resected MIBC tissues and 391 TCGA MIBC samples were retrospectively evaluated. Immunohistochemistry and flow cytometry were applied to identify immune cell infiltration and functional status. In vitro intervention studies were to test the therapeutic and predictive potential of IL22+ cells. Our data revealed patients with high IL22+ cells infiltration suffered poor overall survival and recurrence-free survival in both training and validation cohorts. Only pT2 patients of combined cohort with low IL22+ cells infiltration gained survival benefits from adjuvant chemotherapy (ACT) significantly. Besides, immune contexture featured with increased pro-tumor cells and immunosuppressive cytokines was identified in patients with high IL22+ cells density. The expression pattern of exhausted and effector markers in CD8+ T cells from high IL22+ cells subgroup indicated their dysfunctional status. Importantly, nivolumab showed tumor-killing efficacy in tumors with high IL22+ cells infiltration, and immunosuppressive contexture with CD8+ T cells exhaustion was abrogated in tumors treated with anti-IL22 antibody. In summary, IL22+ cells infiltration determined immunosuppressive contexture with CD8+ T cell dysfunction. Tumor-infiltrating IL22+ cells could be used as an independent marker to predict prognosis and ACT responses. IL22+ cells infiltration possessed the potential to be a favorable predictor for nivolumab application and IL22 blockade could be a novel therapeutic strategy in MIBC.

10.
Neurophysiol Clin ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31610944

RESUMO

OBJECTIVES: To investigate and compare split-hand phenomenon quantified by motor unit number index (MUNIX) between patients with cervical spondylotic amyotrophy (CSA) and those with amyotrophic lateral sclerosis (ALS). METHODS: MUNIX was performed on abductor pollicis brevis (APB), abductor digiti minimi (ADM) and first dorsal interosseous (FDI) in 46 CSA patients, 39 ALS patients and 41 healthy subjects. Split-hand measurements including split-hand index (SHI=ABP×FDI/ADM), ratio of APB to ADM (AA), ratio of FDI to ADM (FA) were measured by compound muscle action potential (CMAP) and MUNIX. RESULTS: There was a significant difference in both AA and SHI measured by two different methods between ALS and CSA patients (P<0.05). Receiver operating characteristic (ROC) curve and logistic regression analysis demonstrated good differential diagnostic accuracy for AA, SHI and their combination between ALS and CSA. A larger area under the curve (AUC) was observed in these measurements calculated by MUNIX than those measured by CMAP (AA: 0.885 vs. 0.700, SHI: 0.865 vs. 0.703, Combination: 0.925 vs. 0.750; P<0.05). Sub-group analysis of ROC curves revealed an AUC of 0.893 for AAMUNIX, 0.801 for SHIMUNIX and 0.896 for their combination in differentiating "clinically possible" ALS (Awaji-Shima criteria) from CSA (P<0.05). CONCLUSIONS: Both AA and SHI measured by two different methods are useful in distinguishing ALS from CSA, and those quantified by MUNIX may be a better differential diagnostic marker to provide an accurate and noninvasive additional test for distinguishing CSA from ALS, even in their early stages.

11.
J Biomed Mater Res A ; 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31606920

RESUMO

The titanium (Ti) implant is widely used in implant dentistry; yet peri-implantitis has always been one of the most common and serious complications. Here, we demonstrated that magnesium-doping would be an effective way of enhancing the integration between implant surfaces and gingival tissues, which is critical to peri-implant health. The magnesium (2.76-6.35 at %) was immobilized onto the titanium substrate by a magnesium plasma immersion ion implantation (Mg-PIII) technique. Mg-PIII treatments did not alter surface topographies of the original titanium substrate but improved its hydrophilicity. The in vitro study including cell viability, adhesion, proliferation, migration, and real-time polymerase chain reaction assays disclosed improved adhesion, proliferation, migration, and extracellular matrix remodeling abilities of human gingival fibroblasts (HGFs) on the magnesium-doped titanium. The results of western blot suggested that the Mg-modified titanium induced the phosphorylation of AKT through the activation of PI3K. Our results revealed that magnesium-doping would potentially enhance soft tissue sealings by promoting cellular functions of HGFs in a dose-dependent manner, boding well for its applications on surfaces of implant necks in early peri-implant soft tissue integrations.

12.
Asian J Surg ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31629636

RESUMO

OBJECTIVE: To explore the likelihood of resolution of diabetes postoperatively. Besides, we would like to determine the risk factors associated with development and prognosis of diabetes. METHODS: All patients in our hospital undergoing surgical removal of pheochromocytoma (PHEO) from 10 October 2010 to 21 July 2017 were retrospectively analyzed to determine those with preoperative diabetes. Preoperatively demographic data and information on diabetes were recorded. The median follow-up was 45.2 months. RESULTS: Finally, 67 (36.2%) patients were with diabetes among 185 patients undergoing surgery. Furthermore, 47 patients had complete follow-up. And 37 (78.7%) patients had improvement of diabetes after resection of PHEO. In details, 29 (61.7%) patients had complete resolution. Older patients were more likely to develop diabetes, and symptomatic patients with longer course of PHEO were also more susceptible to preoperative diabetes. Elevated body mass index (BMI) was a risk factor of persistent diabetes postoperatively after surgery. CONCLUSIONS: 36.2% of PHEO patients might be with preoperative diabetes mellitus. Older patients were more likely to present diabetes preoperatively. And the increasing length of PHEO course might be another risk factor on developing diabetes preoperatively. Resection of tumors improved diabetes in 78.7% of patients, with resolution in 61.7%. Patients with higher BMI might need treatment for diabetes postoperatively.

13.
Medicine (Baltimore) ; 98(41): e17425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593095

RESUMO

To evaluate whether the adult patients with acquired pure red cell aplasia (PRCA) could benefit more from cyclosporine A (CsA) combined with corticosteroids (CS) than CsA or CS alone.Seventy-three patients were evaluated in 2 institutions (6 patients lost to follow-up).The induction therapy included CsA (n = 21), CS (n = 21), or CsA combined with CS (n = 31), and remission was achieved in 16/21 (76.2%), 10/21 (47.6%), and 21/31 (71.0%) patients, respectively. Higher complete remission (CR) rate was achieved in CsA combined with CS group than in CS group (61.3% vs 19.0%, P = .003). Patients achieved CR faster in CsA combined with CS group than in CS group or CsA group (median time, 1 month vs 2 month vs 3 month, P = .010). By multivariate analysis, CsA combined with CS therapy and primary PRCA were the influence factors for CR rate. Twenty-seven patients relapsed due to discontinuation or tapering therapy, and 19 patients regained response by increasing the dose of original regimens or changing to other immunosuppressive therapy. Complete remission to induction therapy was a correlative factor for death (P = .035).CsA combined with CS produced faster and higher CR rate in treating adult patients with PRCA than did CsA or CS alone.


Assuntos
Corticosteroides/administração & dosagem , Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Quimioterapia de Indução/métodos , Aplasia Pura de Série Vermelha/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Environ Pollut ; 255(Pt 2): 113292, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31597112

RESUMO

The wide application of bisphenol A (BPA) leads to the emergence of BPA residuals in natural water environments. Dissolved organic matter (DOM) existed in water can bind with BPA, hence influencing the migration and transformation of BPA in aquatic environments. pH is a crucial factor governing the binding interactions between DOM and BPA. However, the mechanisms driven the binding process under different pH conditions are still unclear. In this study, the interactions between BPA and humic acids (HA), a primary component of DOM, are investigated over a wide pH range of 3-12 by integrating fluorescence quenching, dynamic light scattering and microcalorimetry. pH dependence of the binding interactions between HA and BPA are interpreted from a thermodynamic perspective. The results indicate that HA can spontaneously interact with BPA to form a stable HA-BPA complex. With the increasing pH, the binding interactions change from entropy driven to entropy-enthalpy co-driven. Hydrophobic force dominate the binding interactions under acidic condition. The synergy of hydrophobic force and hydrogen bond promotes the binding process under neutral condition. Under alkaline conditions, electrostatic repulsion participates the binding process in addition to hydrophobic force and hydrogen bond, weakening the binding strength. Therefore, neutral pH is favorable for HA to bind with BPA, consequently enhancing the dissolution of BPA in natural water bodies. The results are beneficial to better understand the pH dependent distribution of BPA in aquatic environments.

15.
Sensors (Basel) ; 19(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554328

RESUMO

The terrestrial water storage anomaly (TWSA) gap between the Gravity Recovery and Climate Experiment (GRACE) and its follow-on mission (GRACE-FO) is now a significant issue for scientific research in high-resolution time-variable gravity fields. This paper proposes the use of singular spectrum analysis (SSA) to predict the TWSA derived from GRACE. We designed a case study in six regions in China (North China Plain (NCP), Southwest China (SWC), Three-River Headwaters Region (TRHR), Tianshan Mountains Region (TSMR), Heihe River Basin (HRB), and Lishui and Wenzhou area (LSWZ)) using GRACE RL06 data from January 2003 to August 2016 for inversion, which were compared with Center for Space Research (CSR), Helmholtz-Centre Potsdam-German Research Centre for Geosciences (GFZ), Jet Propulsion Laboratory (JPL)'s Mascon (Mass Concentration) RL05, and JPL's Mascon RL06. We evaluated the accuracy of SSA prediction on different temporal scales based on the correlation coefficient (R), Nash-Sutcliffe efficiency (NSE), and root mean square error (RMSE), which were compared with that of an auto-regressive and moving average (ARMA) model. The TWSA from September 2016 to May 2019 were predicted using SSA, which was verified using Mascon RL06, the Global Land Data Assimilation System model, and GRACE-FO results. The results show that: (1) TWSA derived from GRACE agreed well with Mascon in most regions, with the highest consistency with Mascon RL06 and (2) prediction accuracy of GRACE in TRHR and SWC was higher. SSA reconstruction improved R, NSE, and RMSE compared with those of ARMA. The R values for predicting TWS in the six regions using the SSA method were 0.34-0.98, which was better than those for ARMA (0.26-0.97), and the RMSE values were 0.03-5.55 cm, which were better than the 2.29-5.11 cm RMSE for ARMA as a whole. (3) The SSA method produced better predictions for obvious periodic and trending characteristics in the TWSA in most regions, whereas the detailed signal could not be effectively predicted. (4) The predicted TWSA from September 2016 to May 2019 were basically consistent with Global Land Data Assimilation System (GLDAS) results, and the predicted TWSA during June 2018 to May 2019 agreed well with GRACE-FO results. The research method in this paper provides a reference for bridging the gap in the TWSA between GRACE and GRACE-FO.

16.
J Diabetes Res ; 2019: 5920676, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31559315

RESUMO

Diabetic wounds, as a kind of refractory wound, are very difficult to heal. Both endothelial progenitor cell (EPC) transplantation and platelet-rich plasma (PRP) can improve diabetic wound healing to some extent. However, PRP application cannot provide reparative cells, while EPC transplantation cannot replenish the required growth factors for wound healing. Thus, when applied alone, neither of these factors is sufficient for effective wound healing. Furthermore, the proliferation, differentiation, and fate of the transplanted EPCs are not well known. Therefore, in this study, we examined the efficacy of combined PRP application with EPC transplantation in diabetic wound healing. Our results indicated that PRP application improved EPC proliferation and migration. The Notch signaling pathway plays a key role in the regulation of the proliferation and differentiation of stem cells and angiogenesis in wound healing. The application of PRP upregulated the Notch pathway-related gene and protein expression in EPCs. Furthermore, experiments with shNotch1-transfected EPCs indicated that PRP enhanced the function of EPCs by upregulating the Notch1 signaling pathway. In vivo studies further indicated that the combination of PRP and EPC transplantation increased neovascularization, reduced wound size, and improved healing in rat wound models. Thus, PRP application can provide the necessary growth factors for wound healing, while EPC transplantation offers the required cells, indicating that the combination of both is a potent novel approach for treating diabetic wounds.

17.
Oncol Rep ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31524272

RESUMO

Glioblastoma multiforme (GBM) is the most commonly occurring brain cancer, and is characterized by its poor patient outcomes. The present study examined the mRNA expression levels of the transient receptor potential melastatin (TRPM) family in various types of cancer using the ONCOMINE database, along with their corresponding expression profiles in an array of cancer cell lines based on the Cancer Cell Line Encyclopedia (CCLE) datasets. Kaplan­Meier plotter survival analysis via the Chinese Glioma Genome Atlas (CGGA) database was also used to evaluate the prognostic value of transient receptor potential melastatin 8 (TRPM8). For the activity test on the TRPM8 channel, patch­clamp recordings and Ca2+ measurements by fluorescence imaging of Fluo­4am were performed. Short hairpin RNA (shRNA) targeting TRPM8 was designed, synthesized and then transfected into the U251 cells via Lipofectamine 2000. The expression of extracellular singnal­regulated kinase (ERK), cyclin D1 and Bcl­2 were detected by performing western blotting and immunofluorescence. The apoptosis, proliferation and invasion of glioma cells were detected by using flow cytometry, and CCK­8 and Transwell invasion assays. In the present study, TRPM8 was distinctively upregulated in GBM cell lines. TRPM8 is functional and has the characteristic of outward rectification, which was verified via electrophysiology and Ca2+ fluorescence imaging in U251 cells. The western blot and immunofluorescence results revealed that the expression of ERK, cyclin D1 and Bcl­2 were decreased in the shRNA interference group. The CCK­8 assay demonstrated that the proliferation ability of U251 cells in the U251/TRPM8 group was higher than that in the U251 group and U251/Con group (P<0.05). The result of the Transwell invasion assay indicated that the invasion of human glioblastoma U251 cells was positively correlated with the expression level of TRPM8. Collectively, the results of the present study indicated that Ca2+­permeable TRPM8 nonselective cation channels contribute to survival, proliferation, apoptosis, and local tumor invasion of glioblastoma. Therefore, TRPM8 is a promising biomarker for aggressiveness of GBM, and a potential target in future anti­glioblastoma therapies.

18.
Proc Natl Acad Sci U S A ; 116(40): 19815-19820, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31527234

RESUMO

Secondary formamides are widely encountered in biology and exist as mixtures of both cis and trans isomers. Here, we assess hydrophilicity differences between isomeric formamides through direct competition experiments. Formamides bearing long aliphatic chains were sequestered in a water-soluble molecular container having a hydrophobic cavity with an end open to the aqueous medium. NMR spectroscopic experiments reveal a modest preference (<1 kcal/mol) for aqueous solvation of the trans formamide terminals over the cis isomers. With diformamides, the supramolecular approach allows staging of intramolecular competition between short-lived species with subtle differences in hydrophobic properties.

19.
Sci Rep ; 9(1): 13869, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554874

RESUMO

We compared the therapeutic effects between botulinum toxin and surgery for acute acquired comitant esotropia (AACE) and analyze its clinical characteristics. The data of the 29 cases, who received treatment for AACE in the Ophthalmic Center of the First Affiliated Hospital of Zhengzhou University and Henan Provincial Ophthalmology Hospital between January 2016 and January 2017, were collected. The 29 cases with AACE were followed for 6 months or more, and received either botulinum toxin injection (group A with 13 cases) or squint correction (group B with 16 cases). The distant and near deviation angles were compared between the two groups before and after treatment. The success rate (total horizontal deviation of 10 prism diopters or less) and stereopsis were compared between the two groups at post-treatment 6 months. At the same time, the relations between distant and near deviation angles were analyzed among different myopia levels and different AACE types. Results indicated that he success rate was not significantly different at post-treatment 6 months (84.6% vs 81.3%, P = 1.00). The distant and near deviation angles were all significantly different one day and one month after treatment (all P < 0.05); but at post-treatment 6 months, they were not significantly different (all P > 0.05) between the two groups. There were no significant differences in the distant and near stereoacuity between the two groups at post-treatment 6 months (all P > 0.05). Among the 25 cases with myopia, the pre-treatment distant deviation angle was significantly higher than pre-treatment near deviation angle in the cases with myopia level >-2.5 D (P < 0.05), and the pre-treatment distant and near deviation angles were all significantly higher in the cases with type-IIAACE than in the cases with type-IIIAACE (all P < 0.05). This study suggests that Botulinum toxin is as effective as surgery in the treatment of AACE at post-treatment 6 months. For the cases with myopia level >-2.5 D, the pre-treatment distant deviation angle is significantly higher than pre-treatment near deviation angle; and both pre-treatment distant and near deviation angles are greater in the cases with type-IIAACE than in the cases with type-IIIAACE.

20.
Chem Commun (Camb) ; 55(74): 11123-11126, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31463500

RESUMO

A Pd-catalyzed decarboxylative cross-coupling of α,ß-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both ß-monosubstituted and ß-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,ß-unsaturated carboxylic acids.

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