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1.
Biomed Pharmacother ; 131: 110524, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152900

RESUMO

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine, commonly used to treat a variety of diseases. However, the hepatotoxicity associated with PM hampers its clinical application and development. In this study, we refined the zebrafish hepatotoxicity model with regard to the following endpoints: liver size, liver gray value, and the area of yolk sac. The levels of alanine aminotransferase, aspartate transaminase, albumin, and microRNAs-122 were evaluated to verify the model. Subsequently, this model was used to screen different extracts, components, and constituents of PM, including 70 % EtOH extracts of PM, four fractions from macroporous resin (components A, B, C, and D), and 19 compounds from component D. We found that emodin, chrysophanol, emodin-8-O-ß-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in PM, whereas polyphenols showed lower hepatotoxicity. To the best of our knowledge, this study is the first to identify that dianthrones may account for the hepatotoxicity of PM. We believe that these findings will be helpful in regulating the hepatotoxicity of PM.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33231418

RESUMO

Planar heterojunction (PHJ) organic photodetectors are potentially more stable than traditional bulk heterojunction counterparts because of the absence of uncontrolled phase separation in the donor and acceptor binary blend system. This work reports a new class of PHJ organic photodetectors based on the medium-band gap fullerene C60 and low-band gap fused-ring non-fullerene acceptor ID-MeIC bilayer structure, which allows a wide range of spectral response tuning across the UV-visible-near-infrared (UV-vis-NIR) region by tailoring individual layer thickness. The C60 layer not only increases the external quantum efficiency at 745 nm by 57% but also reduces dark currents by two orders of magnitude. More importantly, the p-type poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)-benzi] is found to be the key compound to conduct the layer-by-layer fabrication as combined with n-type ID-MeIC for higher charge extraction efficiency. In light of the above information, PHJ organic photodetectors exhibited a specific detectivity of 6.5 × 1010 Jones to detect NIR light at 745 nm under -0.1 V. The linear dynamic range was estimated to be 80 dB. This work has demonstrated a feasible approach to develop a PHJ architecture with tunable spectral response in the UV-vis-NIR range toward long-term stable organic photodetectors for potential applications in flexible and wearable biomedical sensors.

3.
Phytochemistry ; 181: 112544, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33130375

RESUMO

Phytochemical investigation of the roots of Streblus asper Lour. resulted in the isolation of six previously undescribed cardiac glycosides, designated 2'-de-O-methylstrebloside (1), cannogenol-3α-O-ß-D-gluopyranosyl-(1 â†’ 4)-6-deoxy -2,3-dimethoxyl-ß-D-fucopyranoside (2), periplogenin-3-O-α-L-rhamnopyranosyl -(1 â†’ 4)-6-deoxy-ß-D-allopyranoside (3), 5-de-O-hydroxylstrebloside (4), 5ßH-16ß-hydroxylkamaloside (5), and 17S, 21R-21-hydroxylstrebloside (6), and three known analogues (7-9). The structures were elucidated using NMR spectroscopic techniques, mass spectrometry, and comparison of the spectroscopic data with previously reported data. Compound 6 is a novel C-21 hydroxyl cardiac glycoside, its absolute configuration was established from the analysis of computational ECD calculations and NMR spectroscopic data. The effects of the cardiac glycosides on apoptosis and cytotoxicity were examined in human A549 lung cancer cells. All the compounds showed remarkable inhibitory activities, with IC50 values in the range of 0.01-6.08 µM. Furthermore, compound 3 was able to significantly inhibit A549 cell growth proliferation via the induction of apoptosis, due to the activation of caspases-3, -8 and -9 in A549 cells, as revealed by Western blot analysis.

4.
Biomed Res Int ; 2020: 2616930, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083460

RESUMO

Blocking glioma cell invasion has been challenging due to cancer cells that can swiftly switch their migration mode, and agents that can block more than one migration mode are sought after. We found that small molecule 2-(1H-indole-3-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous aryl hydrocarbon receptor (AHR) agonist, can block more than one mode of glioma cell migration, based on cultured cell behavior captured by videos. Data from wound-healing assays and mouse xenograft glioma models corroborated ITE's migration-inhibiting effects while knocking down AHR by siRNA abolished these effects. To identify genes that mediated ITE-AHR's effect, we first collected gene expression changes upon ITE treatment by RNA-seq, then compared them against literature reported migration-related genes in glioma and that were potentially regulated by AHR. MYH9, a component of nonmuscle myosin IIA (NMIIA), was confirmed to be reduced by ITE treatment. When MYH9 was overexpressed in the glioma cells, a good correlation was observed between the expression level and the cell migration ability, determined by wound-healing assay. Correspondingly, overexpression of MYH9 abrogated ITE's migration-inhibiting effects, indicating that ITE-AHR inhibited cell migration via inhibiting MYH9 expression. MYH9 is essential for cell migration in 3D confined space and not a discovered target of AHR; the fact that ITE affects MYH9 via AHR opens a new research and development avenue.

5.
J Exp Psychol Gen ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119358

RESUMO

In English, unfair treatment and social injustice are often described as "bitter" experiences, whereas "eating bitterness" refers to endurance in the face of hardship in Chinese. This suggests that bitter taste may ground experiences of adversity in both cultures, but in culture-specific forms. We tested this possibility by assessing Canadian and Chinese participants' responses to fairness and achievement scenarios after incidental exposure to bitter or neutral tastes. Tasting something bitter increased self-reported motivation and intention to invest effort for Chinese participants, but not Anglo-Canadian participants (Studies 1, 4, 5). Tasting something bitter decreased perceived fairness for Anglo-Canadian participants (Studies 1-3) but not Chinese participants living in China (Study 2). The fairness judgments of Chinese participants living in Canada shed light on adaptation to the host culture: Bitter taste decreased these participants' fairness judgments after living in Canada for 4 years or more (Study 4), provided they were tested in English (Studies 3-4), but exerted no influence when they were tested in Chinese (Study 4). The observed cultural differences are compatible with a relatively higher emphasis on self-improvement in China versus self-enhancement in Canada. Supporting this conjecture, the fairness judgments of Chinese students in Canada followed the Anglo-Canadian pattern when primed with a self-enhancement motive and the effort judgments of Anglo-Canadian students followed the Chinese pattern when primed with a self-improvement motive (Study 5). This suggest that a universal aversive experience (bitter taste) grounds thought about adversity in ways compatible with cultural orientations and reflected in culture-specific metaphors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

7.
Eur J Pharmacol ; 888: 173586, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32971086

RESUMO

Exposure to fenpropathrin (Fen), one of the most widely used pyrethroid pesticides, has been reported to increase the incidence of Parkinson's disease (PD). However, the molecular mechanisms underlying Fen-induced Parkinsonism remain unknown. Here we investigated the role of the lysosomal protease asparagine endopeptidase (AEP) in Fen-induced neurodegeneration and tested the protective effect of an AEP inhibitor Compound #11 (CP11). Fen induced AEP activation, α-synuclein aggregation, and dopaminergic neuronal degeneration both in vitro and in vivo. CP11 alleviated Fen-induced cell injury in cultured SH-SY5Y cells and A53T α-synuclein transgenic mice. CP11 protected SH-SY5Y cells against Fen-induced toxicity and decreased α-synuclein aggregation in HEK293 cells stably transfected with α-synuclein. In Fen-treated mice, CP11 attenuated the degeneration of dopaminergic neurons and reduced neuroinflammation. Our findings demonstrate that neurodegeneration in Fen-treated models might be attributed to the activation of AEP. AEP might be a novel therapeutic target in PD induced by Fen and other environmental factors.

8.
Sleep Med ; 75: 428-433, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32980664

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is adversely affecting sleep quality and mental health, especially in individuals with chronic disease such as Parkinson's disease (PD). METHODS: We conducted a quantitative study, which included 119 Chinese PD patients who had been treated in an outpatient neurology clinic in Wuhan and 169 age- and sex-matched healthy controls. The questionnaire survey focused on the impact of the COVID-19 pandemic on sleep, mental status, symptoms, and daily life and medical treatment of PD patients. RESULTS: Compared to healthy controls, PD patients had significantly higher scores in both the Pittsburgh Sleep Quality Index (PSQI) (8.13 vs 5.36, p < 0.001) and the Hospital Anxiety and Depression Scale (HADS) -Depression (4.89 vs 3.82, p = 0.022), as well as a higher prevalence of sleep disturbances with PSQI > 5 points (68.9% vs 44.4%, p < 0.001). Sleep disturbance was identified in 68.9% of PD patients. A logistic regression analysis showed that sleep disturbance of PD patients was independently associated with exacerbation of PD symptoms (OR = 3.616, 95%CI= (1.479, 8.844), p = 0.005) and anxiety (OR = 1.379, 95%CI= (1.157, 1.642), p < 0.001). Compared to male PD patients, female ones had higher PSQI scores (9.28 ± 4.41 vs 7.03 ± 4.01, p = 0.009) and anxiety (32.8% vs 0.1%, p = 0.002) and depression prevalence (34.5% vs 11.5%, p = 0.003). CONCLUSION: The findings of the present study emphasize the importance of mental and sleep health interventions in PD patients during the COVID-19 pandemic. Additional attention should be paid to the difficulty encountered by PD patients in seeking medical treatment.

9.
Health Qual Life Outcomes ; 18(1): 269, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758237

RESUMO

BACKGROUND: The original version of Victorian Institute of Sport Assessment-Patella Questionnaire (VISA-P) is developed in English, and aimed to assess the severity of patellar tendinopathy symptoms. Before used in China, it should be translated to Chinese version. OBJECTIVES: Our aim is to make a translation/cross-culturally adaption for the VISA-P into simplified Chinese version (VISA-PC). And primarily validate the VISA-PC in Chinese speaking population. METHODS: The translation process of VISA-P questionnaire into simplified Chinese version (VISP-PC) followed the International recognized guideline. Cross-cultural adaptation was carried out with a clinical measurement study. A total of 128 projects which consisted 33 healthy students, 39 patients with patellar tendinopathy and 56 military students (receive military training as at-risk population) were included into this study. Internal consistency was evaluated with Cronbach's alpha, and test-retest reliability was assessed with intraclass correlation coefficients (ICCs). Construct validity and floor and ceiling effects were also tested. RESULTS: The scores were 95.84 ± 5.97 of healthy group, 91.87 ± 9.03 of at-risk group, 62.49 ± 11.39 of pathological group. There is no ceiling and floor effect of VISA-PC. The Cronbach's alpha (0.895) and ICC (0.986) values showed good internal consistency and reliability. There were high correlations between VISA-PC and Kujala patellofemoral score (r = 0.721). VISA-PC score also had good correlation with the relevant SF-36 items. CONCLUSION: The VISA-PC was well translated into simplified Chinese version (VISA-PC), which is reliable and valid for Chinese-speaking patients with patellar tendinopathy. LEVEL OF EVIDENCE: II.


Assuntos
Ligamento Patelar/fisiopatologia , Inquéritos e Questionários/normas , Tendinopatia/fisiopatologia , Adaptação Fisiológica , Adulto , Traumatismos em Atletas/fisiopatologia , Estudos de Casos e Controles , China , Comparação Transcultural , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Tendinopatia/diagnóstico , Adulto Jovem
10.
BJU Int ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32772468

RESUMO

OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32600941

RESUMO

BACKGROUND: The efficacy of partial nephrectomy (PN) in setting of pT3a pathologic-upstaged renal cell carcinoma (RCC) is controversial. We compared oncologic and functional outcomes of radical nephrectomy (RN) and PN in patients with upstaged pT3a RCC. PATIENTS AND METHODS: This was a multicenter retrospective analysis of patients with cT1-2N0M0 RCC upstaged to pT3a postoperatively. The primary outcome was recurrence-free survival, with secondary outcomes of overall survival and de novo estimated glomular filtration rate (eGFR) < 60. Multivariable analysis was performed to identify predictive factors for oncologic outcomes. Kaplan-Meier analyses (KMA) were obtained to elucidate survival outcomes. RESULTS: A total of 929 patients had pT3a upstaging (686 [72.6%] RN; 243 [25.7%] PN; mean follow-up, 48 months). Tumor size was similar (RN 7.7 cm vs. PN 7.3 cm; P = .083). PN had decreased ΔeGFR (6.1 vs. RN 19.4 mL/min/1.73m2; P < .001) and de novo eGFR < 60 (9.5% vs. 21%; P = .008). Multivariable analysis for recurrence showed increasing RENAL score (hazard ratio [HR], 3.8; P < .001), clinical T stage (HR, 1.8; P < .001), positive margin (HR, 1.57; P = .009), and high grade (HR, 1.21; P = .01) to be independent predictors, whereas surgery was not (P = .076). KMA revealed 5-year recurrence-free survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 79%, 74%, 70%, and 51%, respectively (P < .001). KMA revealed 5-year overall survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 64%, 65.2%, 56.4%, and 55.2%, respectively (P = .059). CONCLUSIONS: In pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit. Surgical decision-making in patients at risk for T3a upstaging should be individualized and driven by tumor as well as functional risks.

12.
World J Urol ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32556559

RESUMO

PURPOSE: To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. METHODS: Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73m2). Cox regression Multivariable analysis (MVA) was carried out for predictors of de novo CKD. Linear regression was carried out for factors associated with increasing deltaGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year CKD-free survival. RESULTS: 295 patients were analyzed (224 PN/71 AS, median follow-up 37.4 months). No differences were noted for clinical tumor size (AS 2.6 vs. PN 2.9 cm, p = 0.108), and baseline eGFR (AS 79.6 vs. PN 77, p = 0.9670). Median change in tumor diameter for AS was 0.42 cm. Compared to PN, AS had deltaGFR (-15.3 vs. -6.4 mL/min/1.73m2, p < 0.001) and de novo CKD (28.2% vs. 12.1%, p = 0.002). AS patients who developed CKD had higher RENAL score (p = 0.005) and lower baseline eGFR (73 vs. 91.2 mL/min/1.73m2, p < 0.001) than AS patients who did not. MVA demonstrated increasing age (OR = 1.03, p = 0.025), tumor size (HR = 1.26, p = 0.032) and AS (HR = 4.91, p < 0.001) to be predictive for de novo CKD. Linear regression demonstrated AS was associated with larger decrease in deltaGFR (B = -0.219, p < 0.001). KMA revealed 5-year CKD survival was higher in PN (87%) vs. AS (62%, p < 0.001). CONCLUSION: AS was associated with greater functional decline than PN in oncocytoma. PN may be considered to optimalize renal functional preservation in select circumstances. Further investigation into mechanisms of functional decline in oncocytoma is requisite.

13.
Bioorg Chem ; 100: 103889, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32388432

RESUMO

The chemical constituents of the roots, seeds, and bark of Azadirachta indica var. siamensis were investigated, leading to the isolation of six tricyclic diterpenoids and five limonoids, including two new compounds (2, 5). The structures were elucidated based on NMR spectroscopic techniques, mass spectrometry and single-crystal X-ray diffraction as well as comparison with the literature. Moreover, the cytotoxicity activities of the isolates were evaluated. The results indicated that the compounds 1-3, 5-9 exhibited cytotoxicities against one or more cancer cell lines tested, with IC50 values in the range of 1.7-88.1 µM. The mechanism of action studies indicated that the most active compound, compound 5, could induce the apoptosis of AZ521 cells. Furthermore, the Western blot analysis showed that compound 5 could reduce the expression levels of procaspases-3, -8, -9 and promote the expression of Bid and AIF.

14.
ACS Nano ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32432458

RESUMO

Among various energy storage devices, aqueous zinc-ion batteries (ZIBs) have captured great attention due to their high safety and low cost. One of the most promising cathodes of aqueous ZIBs is layered vanadium-based compounds. However, they often suffer from the capacity decaying during cycling. Herein, we prepared KV3O8·0.75H2O (KVO) and further incorporated it into a single-walled carbon nanotube (SWCNT) network, achieving freestanding KVO/SWCNT composite films. The KVO/SWCNT cathodes exhibit a Zn2+/H+ insertion/extraction mechanism, resulting in fast kinetics of ion transfer. In addition, the KVO/SWCNT composite films possess a segregated network structure, which offers the fast kinetics of electron transfer and guarantees an intimate contact between KVO and SWCNTs during cycling. As a result, the resultant batteries deliver a high capacity of 379 mAh g-1, excellent rate capability, and an ultralong cycle life up to 10,000 cycles with a high capacity retention of 91%. In addition, owing to the high conductivity and flexibility of KVO/SWCNT films, flexible soft-packaged ZIBs based on KVO/SWCNT film cathodes were assembled and displayed stable electrochemical performance at different bending states.

15.
J Psychiatry Neurosci ; 45(6): 379-386, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32293839

RESUMO

Background: Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism. Methods: We included 2236 Han Chinese adults in this study, including 736 patients with GAD and 1500 healthy participants. We genotyped the 5-HTTLPR and rs25531 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism method. We used the Neuroticism scale of the Maudsley Personality Inventory (MPI) short version (MPI-Neuroticism) to measure participants' tendency toward neuroticism. Results: Using endophenotype-based path analyses, we found significant indirect effects of the tri-allelic genotype on risk of GAD, mediated by MPI-Neuroticism in both men and women. Compared to women carrying the S'S' genotype, women carrying the L' allele had higher levels of MPI-Neuroticism, which in turn were associated with higher risk of GAD. Men, however, showed the opposite pattern. Using traditional case-control comparisons, we observed that the effect of tri-allelic genotype on GAD was significant, but only in women. Limitations: Participants were restricted to Han Chinese, and we used only 1 questionnaire to assess neuroticism. Conclusion: These findings are the first to show that the triallelic 5-HTTLPR polymorphism is associated with elevated risk of GAD, and that this effect is mediated via increased trait neuroticism, a sex-dependent risk pathway.

16.
Small ; : e1907153, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32285595

RESUMO

Lithium-sulfur (Li-S) batteries as a promising energy storage candidate have attracted attention due to their high energy density (2600 Wh kg-1 ). However, the serious shuttle effect caused by the dissolution of the lithium polysulfides (LiPS) in electrolyte significantly degrades their cycling life and rate performance. Herein, the "binary active sites" concept in a Li-S battery system via the design of a cobalt vanadium oxide (CVO) modified multifunctional separator is designed. In the case of CVO, active vanadium sites simultaneously anchor the LiPS through the chemical affinity and active cobalt sites can dominate a rapid kinetic conversion. Such a synergistic effect contributes to improving the utilization of sulfur in the electrochemical process for the enhanced electrochemical performance. As a result, the Li-S battery with the CVO modified separator possesses a high reversible capacity of 1585.5 mAh g-1 at 0.1 C and superior cycling stability with 0.012% capacity decay cycle-1 after 3000 cycles. More impressively, the assembled soft-packaged Li-S devices can exhibit the excellent stability under bending states. This binary active sites strategy provides a route to design the functional materials for modifying separators of Li-S batteries to improve the performance.

17.
J Affect Disord ; 270: 124-130, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32339102

RESUMO

BACKGROUND: Norepinephrine transporter (NET), which regulates synaptic norepinephrine for noradrenergic signaling, is involved in the pathogenesis of anxiety, while expression of the NET gene differs at different ages. Here, we examine whether genetic variants in the NET gene are associated, in an age-specific manner, with increased risk of generalized anxiety disorder (GAD), one of the most disabling anxiety disorders. METHODS: Three common single-nucleotide polymorphisms (SNPs) in the promoter (rs168924: A/G; rs2242446: T/C) and 5'-untranslated region (5'-UTR) (rs2397771: G/C) of the NET gene were genotyped in 2,317 Han-Chinese participants (791 GAD patients and 1,526 controls; age: 20-65). Potential confounding factors, such as gender, stress levels and psychiatric comorbidities, were included as covariates. RESULTS: An interaction between age and NET genotypes and haplotypes was found for the risk of GAD. In the younger participants, rs168924 minor allele G homozygotes had the lowest incidence of GAD; however, older subjects displayed an inverse pattern, with homozygous G/G carriers presenting the highest prevalence of GAD. Additionally, younger individuals carrying 2 copies of the GGT haplotype composed of rs2397771-rs168924-rs2242446 had the lowest rate of GAD. However, those with 2 copies of the same haplotype exhibited the highest risk of GAD in the older groups. LIMITATIONS: Only 3 common SNPs in the promoter and 5'-UTR of the NET gene were analyzed. CONCLUSIONS: Our findings are the first to demonstrate that potentially functional SNPs in the NET promoter and 5'-UTR are associated with an increased risk of GAD, and that such associations are determined in an age-specific way.

18.
Asian J Androl ; 22(6): 602-607, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32031084

RESUMO

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

19.
J Abnorm Psychol ; 129(3): 237-247, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32077707

RESUMO

The valine66methionine (Val66Met) polymorphism (rs6265) of the brain-derived neurotrophic factor (BDNF) gene has been shown to influence autonomic arousal pathways, which in turn predict elevated syndromal anxiety in healthy humans. We examined whether the BDNF variant is associated with an increased risk of generalized anxiety disorder (GAD), one of the most prevalent anxiety disorders, through altering parasympathetic stress/relaxation reactivity. A total of 2,250 Han Chinese adults (750 GAD patients and 1,500 healthy controls) were included in the genotyping. High-frequency heart rate variability, an index of vagal (parasympathetic) activity, was measured during the supine-standing-supine test (5 min in each position); vagal withdrawal and vagal activation were calculated as baseline supine minus standing and recovery supine minus standing, respectively. Analysis of healthy participants indicated that Val/Val homozygotes displayed significantly blunted vagal withdrawal and vagal activation compared with Met allele carriers. After analyzing the entire sample, these effects remained significant. Furthermore, both attenuated vagal response patterns were found to be significantly associated with a higher incidence of GAD. Lastly, the path analysis identified a significant indirect effect of BDNF on the risk of GAD via diminishing vagal response to either orthostatic stress or supine relaxation. Even when further testing the subsample comprising only comorbidity- and medication-free GAD patients and healthy controls to minimize the confounding bias, the results still remained. Our findings demonstrate that individuals carrying the BDNF Val/Val genotype, compared to Met-carriers, may be at higher risk of GAD due to blunted vagal reactivity in response to both stress and relaxation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Transtornos de Ansiedade/genética , Ansiedade/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Genótipo , Sistema Nervoso Parassimpático/fisiopatologia , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Ansiedade/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Nível de Alerta/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Vago/fisiopatologia
20.
Rheumatology (Oxford) ; 59(10): 2872-2880, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32087013

RESUMO

OBJECTIVES: Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS: To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS: CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION: CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.

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