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1.
Biomed Res Int ; 2020: 9063808, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047818

RESUMO

Abstract. Persistent urban-rural disparity in subjective health and quality of life is a growing concern for healthcare systems across the world. In general, urban population performs better on most health indicators compared with their rural counterparts. However, research evidence on the urban-rural disparity on perceived health, happiness, and quality of life among the young adult population is scarce in South American countries like Guyana. Therefore, in the present study we aimed to investigate whether subjective health, happiness, and quality of life differ according to place of residence among the young adult population in Guyana. Methods: Cross-sectional data on 2,434 men and women aging between 15 and 24 years were collected from the most recent Guyana Multiple Indicator Cluster Survey conducted in 2014. Outcome variables were perceived: satisfaction about health, life, and happiness, as well as life satisfaction before and after one year from the time of the survey. The urban-rural disparity in reporting satisfaction for these indicators was assessed by multivariate regression methods and by adjusting for relevant sociodemographic factors. Results: More than four-fifth of the respondents reported satisfaction with health (82.4%) and life (81.4%) and 77.9% reported being happy. A vast majority expressed improvement in life situation compared with a year ago (81.4%), and nearly all of the participants (95.4%) expect to have better life situation a year later. Multivariate analysis revealed an inverse association between rural residence and subjective health among men [OR = 0.518, 95%CI = 0.297, 0.901], and happiness [OR = 0.662, 95%CI = 0.381, 0.845] and life satisfaction [OR = 3.722, 95%CI = 1.502, 9.227] among women. Women having secondary [OR = 2.219, 95%CI = 1.209, 3.720] and higher [OR = 1.600, 95%CI = 1.041, 3.302] education also had higher odds of satisfaction with happiness. Conclusions: Our findings demonstrate the existence of significant urban-rural disparities in perceived health and quality of life among the young adult population in Guyana, especially among women. National health promotion projects should therefore take proper policy actions to address the underlying factors contributing to the urban-rural gaps in order to establish a more equitable healthcare system. Further researches are necessary to explore the underlying causes behind such disparities.

2.
BMC Med Genet ; 21(1): 29, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046680

RESUMO

BACKGROUND: The goal of this study was to review relevant case-control studies to determine the association of tumor necrosis factor-α (TNF-α) gene polymorphisms and coronary artery disease (CAD) susceptibility. METHODS: Using appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through April 2019 were considered for inclusion. Based on eligible studies, we performed a meta-analysis of association between 308G/A, 238G/A, 857C/T, 863C/A and 1031 T/C polymorphisms in TNF-α and risk of CAD. RESULTS: We found 25 studies that were consistent with this meta-analysis, including 7697 patients in the CAD group and 9655 control patients. TNF-α 308G/A locus A showed no significant association with CAD susceptibility by the five models in the analysis of the overall population, European, African, South Asian, and North Asian patients. TNF-α 863C/A locus A and 1031 T/C locus C exhibited no significant association with CAD susceptibility. TNF-α 238G/A locus A had no significant association with CAD susceptibility in the overall population. However, TNF-α 238G/A locus A showed significant association with higher CAD susceptibility in the subgroup of Europeans and north Asians. TNF-α 857C/T locus T had no significant association with CAD susceptibility in the analysis of the overall population and Europeans. In the north Asian population, TNF-α 857C/T locus T was associated with lower CAD susceptibility by the heterozygote model. CONCLUSION: TNF-α 308G/A, 857C/T, 863C/A, and 1031 T/C has no significant association with CAD susceptibility. TNF-α 238G/A locus A has significant association with CAD susceptibility in Europeans and north Asians, but has no significant association in the overall population. Studies with a larger sample size are required to confirm the association between TNF-α 238G/A and CAD susceptibility.

3.
Dig Liver Dis ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32008975

RESUMO

BACKGROUND: We sought to explore the association of red blood cell distribution width (RDW) with the severity and long-term prognosis of chronic hepatitis B (CHB)-related liver diseases. METHODS: 1482 treatment-naïve CHB patients without liver cirrhosis (LC), 485 CHB-related LC (CHB-LC) patients and 325 healthy controls (HCs) were enrolled. The median follow-up time for CHB-LC patients was 33.9 months. RESULTS: RDW was significantly higher in CHB-LC (15.0%) than CHB (12.7%) patients or HCs (12.5%). RDW was slightly higher in CHB patients than HCs (p < 0.001). Among CHB patients, the RDW of immune clearance and HBeAg negative hepatitis patients was significantly higher than immune-tolerant and low-replicative phase patients. RDW was positively correlated with Child-Turcotte-Pugh (r = 0.363; p < 0.001) and the model of end-stage liver disease scores (r = 0.218; p < 0.001). The areas under the receiver operating characteristic curve of RDW in predicting one-year, three-year, five-year and global mortality rates were 0.696, 0.668, 0.628 and 0.660, respectively. Through multivariable Cox regression analysis, RDW (p = 0.048) was identified as an independent predictor of liver-related mortality. Over a median follow-up of 33.9 months, CHB-LC patients with RDW ≥ 15.1% had significantly higher liver-related mortality than RDW < 15.1% patients (18.8% vs. 8.6%; p = 0.002). CONCLUSIONS: RDW is positively associated with the severity of CHB and can independently predict the long-term prognosis of CHB-LC patients.

4.
J Cell Physiol ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037547

RESUMO

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

5.
Medicine (Baltimore) ; 99(2): e18609, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914039

RESUMO

BACKGROUND: Cerebral palsy (CP) is a common disability in children featured with pathological gait and limb function limitation due to muscle weakness. Improving limb function and quality of life is currently considered to be highlighted. Physiotherapy is a chief component of rehabilitation for children with CP, correcting gait and improve walking capacity through muscle strength training. Standard rehabilitation programs for CP have not been determined. Core stability training (CST), which coordinates limb balance via trunk control, is widely used in sports competition. And it is gradually introduced into the rehabilitation of children with cerebral palsy with a positive impact on the patients' gait performance. By screening published literatures, this study aims to conduct a meta-analysis to systematically evaluate the effectiveness and safety of CST in gait of children with CP. METHODS: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on CST in the treatment of children with CP were searched from 6 databases. Moreover, the reference lists of conference papers and included literatures will be manually searched to avoid omissions. Literature screening and data extraction were performed independently by 2 researchers. RCTs carry out the risk of bias analysis evaluation from seven aspects through the Cochrane Collaboration's risk of bias tool. Fixed or random effect model will be performed to analyze the outcomes. When higher heterogeneity occurs (I > 50%), the sensitivity or subgroup analysis will also be conducted to find potential factors. And the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is used for assessing the quality of evidence. RESULTS: The study will evaluate the effect of CST on gait of children with CP from multiple outcomes, including walking speed, endurance, stride length, and safety. CONCLUSION: Based on evidence-based medicine, the conclusion of this study can demonstrate the effectiveness and safety of CST in gait correction for children with CP. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42019134094.


Assuntos
Paralisia Cerebral/reabilitação , Terapia por Exercício/métodos , Fenômenos Biomecânicos , Criança , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Metiltiouracila , Força Muscular , Projetos de Pesquisa
6.
Sci Adv ; 6(3): eaax5032, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31998834

RESUMO

While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8+ T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.

7.
J Viral Hepat ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31981279

RESUMO

Noninvasive tests (NITs) for liver fibrosis are highly needed for chronic hepatitis B (CHB) patients. We aimed to investigate whether plateletcrit (PCT) could be used as a NIT in predicting liver fibrosis for CHB patients. Five hundred and sixty-seven treatment-naïve CHB patients with available liver biopsies were included. Patients were randomly divided into a derivation cohort (n = 378) and a validation cohort (n = 189). The diagnostic accuracy of PCT was evaluated using receiver operating characteristic (ROC) curves. In the derivation cohort, PCT in CHB patients with S2-S4 (0.14%), S3-S4 (0.13%) and S4 (0.12%) was lower than patients with S0-S1 (0.17%, P < .001), S0-S2 (0.17%, P < .001) and S0-S3 (0.16%, P < .001), respectively. PCT was an independent predictor of significant fibrosis (≥S2), advanced fibrosis (≥S3) and cirrhosis (S4). The area under the ROC curve (AUROC) of PCT in predicting significant fibrosis, advanced fibrosis and cirrhosis was 0.645, 0.709 and 0.714, respectively. The AUROC of PCT was higher than the aspartate transaminase to platelet ratio index (APRI) in identifying advanced fibrosis and cirrhosis, while this was comparable with APRI in identifying significant fibrosis. The diagnostic value of PCT was comparable with fibrosis-4 score (FIB-4) in predicting significant fibrosis, advanced fibrosis and cirrhosis. In the validation cohort, PCT could also identify significant fibrosis, advanced fibrosis and cirrhosis with similar diagnostic accuracy as in the derivation cohort. PCT represents a simple and inexpensive indictor for liver fibrosis in CHB patients. PCT is just as good or better than other more complex tools for staging liver fibrosis in CHB patients.

8.
Eur J Surg Oncol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31948838

RESUMO

BACKGROUND: Adjuvant chemotherapy(AC) following the curative resection could improve the survival outcome of advanced gastric cancer(GC) patients. However, there is no specific timing interval from radical surgery to initiation of AC. Whether delayed initiation of AC could affect the survival outcome of these patients remains unclear. In this study, we performed a systematic review and meta-analysis to evaluate the relationship between delaying AC and the survival outcome of GC patients. METHODS: PubMed, Embase and Cochrane Library databases were systematically searched for eligible studies that evaluated the relationship between time to AC and survival outcome. Survival data for HR and 95% CI were extracted and converted to a regression coefficient(ß) corresponding to a continuous representation per 4-week delay of AC. Individual adjusted ß were combined using a fixed-effects or random-effects model. Heterogeneity was assessed by I2 statistic and publication bias was detected using standard error-based funnel plots. RESULTS: A total of 11 eligible studies involving 6,017 patients were included in this meta-analysis. Eight studies evaluated the impact of delaying AC on overall survival(OS) and five evaluated the impact of delaying AC on disease-free survival(DFS). The pooled results demonstrated that the initiation of AC per 4-week delay was associated with a significant decrease in OS(HR:1.05, 95% CI: 1.03-1.08, P < 0.001; I2 = 18.5%) and DFS (HR:1.06, 95% CI: 1.02-1.10, P = 0.001; I2 = 40.6%). CONCLUSION: The initiation of AC per 4-week delay was associated with worse survival outcomes in GC patients. If physical status and postoperative recovery were appropriated, GC patients should be recommended to receive adjuvant chemotherapy timely.

9.
Carbohydr Polym ; 232: 115810, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952604

RESUMO

In the present work, lotus root amylopectin (LRA)-chitosan (CS) composite hydrogel was developed as a delivery system for curcumin (CUR). Results exhibited that a stable LRA-CS-CUR hydrogel was formed using LRA and CS in the ratio of 3:2 (w/w) at pH 4.0. Under this condition, the particle size, polydispersity index and zeta potential of the LRA-CS-CUR was 410.3 nm, 0.211 and +26.47 mV, respectively. The analysis of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffractometer revealed that curcumin was successfully encapsulated in the LRA-CS hydrogel, giving a high encapsulation efficiency of 90.3 %. Moreover, this composite hydrogel could significantly improve the solubility and stability of curcumin. The release characteristics of encapsulated curcumin in simulated gastric fluid and simulated intestinal fluid were further investigated. Results exhibited that the LRA-CS hydrogel enabled curcumin to be stable in stomach and release in small intestine.

10.
Thyroid ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31964278

RESUMO

PURPOSE: To systemically investigate the prognostic value of pre-ablation stimulated thyroglobulin (s-Tg) in children and adolescents with differentiated thyroid cancer. METHODS: Clinical records from 118 children and adolescents were retrospectively reviewed. RESULTS: The median age was 16 years, and the majority were female (79.7%). All children and adolescents underwent total thyroidectomy and received radioactive iodine therapy. After a median follow-up of 5.3 years, 68 (57.6%) patients were disease free, while 50 patients (42.4%) had persistent/recurrent disease. In multivariate analysis, pre-ablation s-Tg and M1 were the independent predictive factors for persistent/recurrent disease. According to the receiver operating curve analysis, the best pre-ablation s-Tg cutoff to predict disease-free status was 17.8 ng/mL with a negative predictive value of 96.8%. Integration of pre-ablation s-Tg into ATA pediatric risk categories indicated that the presence of pre-ablation s-Tg ≤17.8 ng/mL was associated with a decreased chance of having persistent/recurrent disease in intermediate- and high-risk patients (22.6% to 2.6% in intermediate-risk patients, and 64.4% to 5.6% in high-risk patients). CONCLUSIONS: Our findings suggest that pre-ablation s-Tg has the capability of predicting the clinical outcomes in children and adolescents with thyroid cancer.

11.
Head Neck ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31976610

RESUMO

BACKGROUND: To evaluate the prognostic value of post-ablation whole-body scintigraphy (PAS) in children with thyroid cancer following 131 I therapy. METHODS: A retrospective analysis of children with thyroid cancer who underwent remnant ablation was performed. PAS results were correlated with clinical and histopathologic characteristics of the primary tumor and compared with the follow-up data. RESULTS: One hundred and sixty-eight children were eligible for the analysis. The median age was 17 years, and the majority were female (81.5%). In multivariate analysis, N1b classification and 131 I ablative dose were associated with PAS positivity. After a median follow-up of 49 months, 89 (71.8%) of 124 children with normal PAS achieved complete remission. Fifteen of 44 (34.1%) children with positive PAS had complete remission. Kaplan-Meier analysis showed that positive PAS was negatively associated with cumulative complete remission rates (P < .001). CONCLUSIONS: PAS could provide prognostic information in children with thyroid cancer undergoing 131 I therapy.

12.
Chemosphere ; 243: 125355, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31759214

RESUMO

Cyanobacteria produce a series of secondary metabolites, one of which is beta-N-methylamino-l-alanine (BMAA). BMAA is considered to be the cause of human neurodegeneration. Compared with other cyanotoxins, the role of BMAA in cyanobacteria remains unclear. To investigate this question, six strains of cyanobacteria were cultured and tested in this experiment with an optimized and validated BMAA determination method. The results show that four strains can produce BMAA. The effects of nutrient levels on the production of BMAA by Anabaena sp. FACHB-418 were studied by changing the initial concentrations of nitrate (NaNO3) and phosphate (K2HPO4) in mediums. Bound BMAA was detected in all samples and the concentrations were within 50-100 ng/g. Free BMAA was presence when the concentration of nitrogen was lower than 1.7 mg/L (121.43 µM). Free BMAA was released from the dead and ruptured cells during the cell decline period, so dissolved BMAA cannot be detectable in the adaptation and logarithmic periods, but could be abundant in the decline periods. Statistical analyses show that free BMAA concentrations were negatively correlated with nitrogen strongly (p = 2.334 × 10-10 and r = -0.842), but positively correlated with phosphorus weakly (p = 0.016 and r = 0.405). Moreover, the results of culture experiments indicated that exogenous BMAA could inhibit the growth of cyanobacteria that cannot produce BMAA, and the effect was enhanced as the concentration of exogenous BMAA increased. This phenomenon implies that the production of BMAA may be the stress response by some cyanobacteria to low nitrogen conditions to kill other cyanobacteria, i.e., their competitors.

13.
Sci Total Environ ; 703: 135513, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31761374

RESUMO

ß-N-Methylamino-l-alanine (BMAA), a new cyanobacterial toxin, is found in different aquatic ecosystems worldwide and is to threaten the human nervous system. Therefore, it is important for water plants to develop feasible methods to counter the effects of BMAA. In this study, the removal of BMAA by chlorine, as well as its intermediate products, at different pH values and the mechanism of pH on the removal BMAA were investigated. The results showed that the chlorination of BMAA is in accordance with the second-order kinetics model. The reaction rate of chlorinated BMAA increased with the increase in the concentration of chlorine. The pH of the solution significantly affected the reaction rate. The apparent kinetic constant (kapp) decreased from 6.00 × 103 M-1·min-1 to 35.5 M-1·min-1 when the pH increased from 4.5 to 9 in the chlorine concentration of 32.23 µM. It is probable that the species distribution and proportion of BMAA and chlorine at different pH values were the main causes of this phenomenon. Additionally, the chlorination reaction consisted of four elementary reactions and hydrogen ions were beneficial to the reaction. The temperature also affected the reaction rate and the activation energy of the reaction was 16.6 ± 1.99 kJ·M-1. A variety of degradation products were detected and the path of degradation was speculated. Chlorination, dechlorination, and decarboxylation were the main processes of oxidative degradation. Furthermore, the composition of the degradation products was the same at different pH values.

14.
Angew Chem Int Ed Engl ; 59(1): 154-160, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697030

RESUMO

Conversion of carbon monoxide to high value-added ethylene with high selectivity by traditional syngas conversion process is challenging because of the limitation of Anderson-Schulz-Flory distribution. Herein we report a direct electrocatalytic process for highly selective ethylene production from CO reduction with water over Cu catalysts at room temperature and ambient pressure. An unprecedented 52.7 % Faradaic efficiency of ethylene formation is achieved through optimization of cathode structure to facilitate CO diffusion at the surface of the electrode and Cu catalysts to enhance the C-C bond coupling. The highly selective ethylene production is almost without other carbon-based byproducts (e.g. C1 -C4 hydrocarbons and CO2 ) and avoids the drawbacks of the traditional Fischer-Tropsch process that always delivers undesired products. This study provides a new and promising strategy for highly selective production of ethylene from the abundant industrial CO.

15.
J Hazard Mater ; 385: 121518, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704121

RESUMO

Research interests have been recently thrust into the nonradical reactions in persulfate-based advanced oxidation processes (AOPs), whilst the underlying mechanism of the nonradical pathway remains ambiguous especially in metal-based AOPs systems. In this study, we investigated the reactivity of cuprous oxide (Cu2O) for activating peroxymonosulfate (PMS) to decompose diverse organic contaminants. Cu2O exhibited a strong catalytic dependence on the crystal morphology, and cubic Cu2O was more reactive than the octahedral and rhombic dodecahedral structures for catalytic degradation of bisphenol A with PMS. Chemical quenching tests, electron paramagnetic resonance (EPR), solvent exchange and selective oxidation experiment were corporately conducted to illustrate that Cu2O-catalyzed PMS did not produce free radicals or singlet oxygen. In contrast, a surface-confined metastable intermediate would be formed via outer-sphere interactions between PMS and Cu2O, which directly attacked the organic substrate. Such a reaction pathway is intrinsically distinct from the electron-shuttling regime in carbon (or noble metal)/persulfate systems via the conductive surface of the catalyst, and the outer-sphere interactions let the activated PMS demonstrate a higher oxidizing capacity toward organic contaminants. Therefore, this study dedicates to providing new insights into the copper-catalyzed AOPs and vital supplementary to the ongoing dialogue of the nonradical catalysis in persulfate-based oxidation.

16.
Eur J Clin Pharmacol ; 76(2): 277-284, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31745585

RESUMO

PURPOSE: Acute nephrotoxicity is a common adverse reaction of tacrolimus therapy; however, its risk factors in pediatric nephrotic syndrome (NS) remain to be evaluated. The objective of this study was to investigate the risk factors and characteristics of tacrolimus-induced acute nephrotoxicity in children with NS. METHODS: Past records of children with NS admitted to our hospital from 2014 to 2018 were reviewed. The incidence and characteristics of nephrotoxicity were analyzed. Multivariate logistic regression analysis was used to identify the risk factors of nephrotoxicity. A clinically applicable risk score was developed and validated. RESULTS: Tacrolimus-induced nephrotoxicity occurred in 25 of 129 patients, 13 patients were grade 1, and the renal function was recovered in 22 patients. Multivariate regression analysis showed that the maximum trough concentrations (C12h) of tacrolimus (OR, 1.48; 95% CI, 1.16 to 1.88; P < 0.001), huaiqihuang granules (OR, 0.095; 95% CI, 0.014 to 0.66; P = 0.017), and diarrhea (OR, 22.00; 95% CI, 1.58 to 306.92; P = 0.022) were independently associated with tacrolimus-induced nephrotoxicity. The maximum C12h were significantly higher in patients with nephrotoxicity (median 9.0 ng/ml) and the cut-off value for acute nephrotoxicity was 6.5 ng/ml. The area under the receiver operating characteristic curve was 0.821 for the proposed model based on the observations used to create the model and 0.817 obtained from k-fold cross-validation. CONCLUSIONS: High trough concentration of tacrolimus and diarrhea can potentiate the risk of tacrolimus-induced acute nephrotoxicity in children with NS, while huaiqihuang granules can protect this condition.

17.
Br J Pharmacol ; 177(2): 372-387, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31621893

RESUMO

BACKGROUND AND PURPOSE: This study investigates the antifibrotic activities and potential mechanisms of costunolide (COS), a natural sesquiterpene compound. EXPERIMENTAL APPROACH: Rats subjected to bile duct ligation and mice challenged with CCl4 were used to study the antifibrotic effects of COS in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 also served as an in vitro liver fibrosis models. The expression of fibrogenic genes and signaling proteins in the neurogenic locus notch homologue protein 3 (Notch3)-hairy/enhancer of split-1 (HES1) pathway was examined using western blot and/or real-time PCR. Notch3 degradation was analysed using immunofluorescence and coimmunoprecipitation. KEY RESULTS: In animals, COS administration attenuated hepatic histopathological injury and collagen accumulation and reduced the expression of fibrogenic genes. COS time- and dose-dependently suppressed the levels of fibrotic markers in LX-2 cells and mouse pHSCs. Mechanistic studies showed COS destabilized Notch3 and subsequently inhibited the Notch3-HES1 pathway, thus inhibiting HSC activation. Furthermore, COS blocked the WW domain-containing protein 2 (WWP2)/protein phosphatase 1G (PPM1G) interaction and enhanced the effect of WWP2 on Notch3 degradation. CONCLUSIONS AND IMPLICATIONS: COS exerted potent antifibrotic effects in vitro and in vivo by disrupting the WWP2/PPM1G complex, promoting Notch3 degradation and inhibiting the Notch3/HES1 pathway. This indicates that COS may be a potential therapeutic candidate for the treatment of liver fibrosis.

18.
Int J Neurosci ; 130(2): 144-152, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31554446

RESUMO

Purpose: Recent studies have shown that growth-associated protein-43 (GAP-43) may influence the mitotic-spindle orientation of Madin-Darby Canine Kidney (MDCK) cells through interacting with G proteins in vitro. However, whether GAP-43 interacts with the G proteins under the influence of mitotic spindle positioning related to the orientation of cell division during neurogenesis remains unclear. In order to explore the molecular mechanism in vivo, the GAP-43 transgenic mice were produced and the angles of cell division in the ventricular zone (VZ) during neurogenesis (embryonic period between 13.5 and 17.5 days) were measured in both transgenic mice and wild type mice by spindle angle analysis.Materials and methods: The interaction of GAP-43 and Gαi was detected by co-immunoprecipitation (co-IP), whereas the localization of GAP-43 was determined by immunofluorescence.Results: The results obtained using co-IP and immunofluorescence showed that GAP-43 is localized on the cell membrane and interacts with Gαi. This interaction dramatically induced a significant increase in the proportion of horizontally and intermediately dividing cells during the embryonic period of 13.5 days in the transgenic mouse brain, as observed by spindle angle analysis.Conclusions: It can be concluded that GAP-43 is involved in the orientation of cell division by interacting with Gαi, and that this may be an important mechanism for neurogenesis in the mammalian brain.

19.
J Infect Dis ; 221(3): 389-399, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31550363

RESUMO

BACKGROUND: Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort. METHODS: Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score. RESULTS: A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001). CONCLUSIONS: The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.

20.
J Gynecol Obstet Hum Reprod ; 49(1): 101642, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31563698

RESUMO

OBJECTIVE: To investigate the effects of ginsenoside Rg3 on human ectopic endometriotic stromal cells in vitro. MATERIALS AND METHODS: Ectopic endometrial tissue specimens were obtained from 6 female patients with ovarian endometriosis who underwent laparoscopic surgical procedures. Endometrial stromal cells derived from isolated ectopic endometriotic lesions were cultured, and the purity and homogeneity of cells were verified by Immunocytochemistry. The effect of Rg3 on cell proliferation was detected by Cell Counting Kit-8 (CCK8). After treatment with Rg3, the protein expression of NF-κB p65 subunit, VEGF, and caspases3 were measured by western blot analysis. Meanwhile, the mRNA expression of NF-κB p65 subunit was determined by Quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Rg3 inhibited the proliferation of ectopic endometriotic cells in a time- and dose-dependent manner. The treatment with Rg3 significantly diminished the level of NF-κB p65 subunit as well as TNF-α induced nuclear translocation of NF-κB p65 subunit in ectopic endometriotic cells. Moreover, Rg3 upregulated the expression of caspases3 but suppressed the expression of VEGF. CONCLUSION: Our results indicate that Ginsenoside Rg3 suppresses endometriosis by reducing the viability of human ectopic endometrial stromal cells involving the nuclear factor-kappaB signaling pathway in vitro.

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