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1.
Artigo em Inglês | MEDLINE | ID: mdl-32246145

RESUMO

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the two main autoimmune thyroid diseases with both similarities and differences. Determining the genetic basis that distinguishes HT from GD is key for a better understanding of the differences between these two closely related diseases. OBJECTS&DESIGN: In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2,682 patients with HT, 4,980 patients with GD and 3,892 controls, The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS with the logistic regression analysis adjusted for sex and age. RESULTS: we identified 11 susceptibility loci for HT in the Chinese Han population, with four loci including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in MHC-IB region and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5×10-8. Five loci were reported to be associated with HT for the first time. We also identified six susceptibility loci with heterogeneity between GD and HT. Out of them, four loci were associated with GD, but not with HT including HLA-DPB1, CD40, TSHR and TG, and the association of HLA-B with GD was stronger than that with HT but the association of SLAMF6 was reversed. CONCLUSION: Our findings suggested that the pathogenesis of HT and GD was different.

2.
Pharm Biol ; 58(1): 200-207, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32114864

RESUMO

Context: Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits.Objective: This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice.Materials and methods: C57BL/6J mice were pre-treated with either GSP 25-100 mg/kg/d for seven days or GSP 100-400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed.Results: Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway.Discussion and conclusions: These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stress-related cognitive decline.

3.
Zhongguo Gu Shang ; 33(1): 4-10, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32115917

RESUMO

OBJECTIVE: To compare the clinical effect of proximal fibular osteotomy (PFO) and single condyle replacement (UKA) in the treatment of knee osteoarthritis of different severity. METHODS: From June 2015 to September 2017, 53 patients with knee osteoarthritis were analyzed retrospectively. According to the operation mode, they were divided into PFO group (26 cases) and UKA group (27 cases) . According to Kellygren-Lawrence imaging classification standard:PFO group, 5 cases of gradeⅡ, 11 cases of grade Ⅲ, 10 cases of grade Ⅳ; UKA group, 7 cases of gradeⅡ, 9 cases of grade Ⅲ, 11 cases of grade Ⅳ. The amount of intraoperative bleeding, operation time and postoperative hospital stay were compared between the two groups. The patients were followed up regularly in the outpatient clinic before operation, 3 months after operation and 1 year after operation. The WOMAC score and the angle of tibiofemoral angle at each time point in the same group were compared, and the OMAC score and the angle of tibiofemoral angle at each time between the two groups were compared. RESULTS: Fifty-three patients were followed up for 12 to 24 (16.6±4.8) months. Compared with UKA group, PFO group had less intraoperative bleeding, shorter operative time and shorter postoperative hospital stay (P<0.05) . The scores of pain, stiffness and body function in UKA group were better than those in PFO group (P<0.05) . After 3 months and 1 year, the WOMAC index in PFO group was significantly improved (P<0.05) ; after 3 months and 1 year, the WOMAC index in UKA group was significantly better than that in PFO group (P<0.05) ; after 3 months, the WOMAC index in PFO group was significantly better than that in UKA group (P<0.05) . The tibiofemoral angle of gradeⅡand Ⅲ patients in both groups decreased gradually (P<0.05) ; the tibiofemoral angle of grade Ⅳ patients in UKA group was smaller than that of grade Ⅳ patients in PFO group (P<0.05) . CONCLUSION: Compared with UKA, PFO has the advantages of small trauma, fast recovery and low cost. The curative effect of PFO is equal to or more than UKA in the patients with gradeⅡand Ⅲ knee osteoarthritis. It is an alternative surgical method for the treatment of knee osteoarthritis.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Joelho/cirurgia , Osteotomia , Estudos Retrospectivos , Resultado do Tratamento
4.
Sci Rep ; 10(1): 3888, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127590

RESUMO

Adult stem cells divide to renew the stem cell pool and replenish specialized cells that are lost due to death or usage. However, little is known about the mechanisms regulating how stem cells adjust to a demand for specialized cells. A failure of the stem cells to respond to this demand can have serious consequences, such as tissue loss, or prolonged recovery post injury. Here, we challenge the male germline stem cells (GSCs) of Drosophila melanogaster for the production of specialized cells, sperm cells, using mating experiments. We show that repeated mating reduced the sperm pool and increased the percentage of GSCs in M- and S-phase of the cell cycle. The increase in dividing GSCs depended on the activity of the highly conserved G-proteins. Germline expression of RNA-Interference (RNA-i) constructs against G-proteins, or a dominant negative G-protein eliminated the increase in GSC division frequency in mated males. Consistent with a role for the G-proteins in regulating GSC division frequency, RNA-i against seven out of 35 G-protein coupled receptors (GPCRs) within the germline cells also eliminated the capability of males to increase the numbers of dividing GSCs in response to mating.

5.
J Chromatogr A ; : 460850, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31983414

RESUMO

In-source fragmentation of ginsenosides in the positive ESI mode (pISF-G) frequently occurs, which results in little fragment information useful for the structural elucidation. We are aimed to unveil the genesic mechanism and explore its potential significance in quality control of Ginseng and the related compound formulae. By applying six high-resolution mass spectrometers from Agilent, Waters, and Thermo Fisher, we could primarily demonstrate the susceptibility of pISF-G. The ion clusters in the positive full-scan MS1 spectra were generated from the protonated sapogenins by successive elimination of H2O, and showed specificity for ginsenoside classification. Selective ion monitoring (SIM) of the sapogenin product ions could delineate group-target ginsenoside profiles from Ginseng. A high-selectivity characteristic chromatogram (CC) was elaborated for Ginseng, on the Vion™ IMS-QTOF mass spectrometer by IM (ion mobility) separation and quadrupole filtering of four sapogenin fragments (m/z 407.37/CCS 206.24 Å2; m/z 423.36/CCS 211.26 Å2; m/z 439.36/CCS 209.60 Å2; m/z 457.37/CCS 217.81 Å2). Chemometric analysis, based on the CC data of seven Ginseng drugs (P. ginseng, P. quinquefolius, P. notoginseng, Red ginseng, leaf of P. ginseng, P. japonicus, and P. japonicus var. major), disclosed 35 marker compounds. We could readily discriminate among P. ginseng, P. quinquefolius, and P. notoginseng, in 15 different compound formulae by identifying these marker compounds on both the Vion IMS-QTOF and QTrap 4500 mass spectrometers. Conclusively, SIM of the pISF-G sapogenin product ions renders a new concept of CC enabling the group-target profiling of ginsenosides and authentication of Ginseng and the related compound formulae.

6.
Langmuir ; 35(49): 16290-16296, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31721588

RESUMO

As an important subclass of MOFs, ZIF-8, built from 2-methylimidazole and Zn(NO3)2·6H2O, possesses excellent biocompatibility and high stability in aqueous solution. Recently, it has been found that ZIF-8 can efficiently adsorb DNA and quench the adsorbed fluorophores to a large extent. These properties make it possible to prepare DNA-based optical sensors using ZIF-8. Although practical analytical applications are being demonstrated, the basic understanding of the binding between ZIF-8 and DNA in solution has received relatively little attention. In this work, we report that the adsorption of 12-, 18-, 24-, and 36-mer single-stranded DNAs on ZIF-8 are affected by several factors. It is found from the outcomes that shorter DNAs are adsorbed more rapidly to the surface of ZIF-8. On the other hand, desorption of the probe DNA can be achieved using complementary strand DNA to restore the fluorescence value. Furthermore, the salt contributes to adsorption to some extent. These findings are important for further understanding of the interactions between DNA and ZIF-8 and for the optimization of DNA and MOF-based devices and sensors.

9.
Neurochem Res ; 44(11): 2527-2535, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515677

RESUMO

Mas-related G-protein-coupled receptor subtype C (MrgC) has been shown to play an important role in the development of bone cancer pain. Ubiquitination is reported to participate in pain. However, whether MrgC ubiquitination plays a role in bone cancer pain remains unclear. To answer this question, we designed and performed this study. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer pain. MrgC agonist bovine adrenal medulla 8-22 (BAM 8-22) or MrgC antagonist anti-MrgC antibody were injected intrathecally on day 14 after bone cancer pain was successfully induced. The pain behaviors, the MrgC ubiquitination levels and intracellular calcium concentration in spinal neurons were measured before and after injection, respectively. With comparison to normal and sham group, mice in tumor group exhibited serious bone cancer pain on day 14, and the level of MrgC ubiquitination and intracellular calcium concentration in spinal neurons was significantly higher. Intrathecal injection of BAM 8-22 significantly alleviated bone cancer pain, increased the MrgC ubiquitination level and decreased intracellular calcium concentration in spinal neurons; however, these effects were reversed by administration of anti-MrgC antibody. Our study reveals that MrgC ubiquitination participates in the production and maintenance of bone cancer pain in mice, possibly through the regulation of intracellular calcium concentration in mice spinal neurons.

10.
PLoS One ; 14(9): e0222471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513679

RESUMO

In all metazoan species, sperm is produced from germline stem cells. These self-renew and produce daughter cells that amplify and differentiate dependent on interactions with somatic support cells. In the male gonad of Drosophila melanogaster, the germline and somatic cyst cells co-differentiate as cysts, an arrangement in which the germline is completely enclosed by cytoplasmic extensions from the cyst cells. Notch is a developmentally relevant receptor in a pathway requiring immediate proximity with the signal sending cell. Here, we show that Notch is expressed in the cyst cells of wild-type testes. Notch becomes activated in the transition zone, an apical area of the testes in which the cyst cells express stage-specific transcription factors and the enclosed germline finalizes transit-amplifying divisions. Reducing the ligand Delta from the germline cells via RNA-Interference or reducing the receptor Notch from the cyst cells via CRISPR resulted in cell death concomitant with loss of germline cells from the transition zone. This shows that Notch signaling is essential for the survival of the germline stem cell lineage.

11.
J Phys Chem B ; 123(41): 8675-8685, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31553604

RESUMO

Calculation of the absolute free energy of binding (ΔGbind) for a complex in solution is challenging owing to the need for adequate configurational sampling and an accurate energetic description, typically with a force field (FF). In this study, Monte Carlo (MC) simulations with improved side-chain and backbone sampling are used to assess ΔGbind for the complex of a druglike inhibitor (MIF180) with the protein macrophage migration inhibitory factor (MIF) using free energy perturbation (FEP) calculations. For comparison, molecular dynamics (MD) simulations were employed as an alternative sampling method for the same system. With the OPLS-AA/M FF and CM5 atomic charges for the inhibitor, the ΔGbind results from the MC/FEP and MD/FEP simulations, -8.80 ± 0.74 and -8.46 ± 0.85 kcal/mol, agree well with each other and with the experimental value of -8.98 ± 0.28 kcal/mol. The convergence of the results and analysis of the trajectories indicate that sufficient sampling was achieved for both approaches. Repeating the MD/FEP calculations using current versions of the CHARMM and AMBER FFs led to a 6 kcal/mol range of computed ΔGbind. These results show that calculation of accurate ΔGbind for large ligands is both feasible and numerically equivalent, within error limits, using either methodology.

12.
Mol Cell Endocrinol ; 494: 110492, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31255731

RESUMO

Approximately 20% of Graves' disease (GD) patients may result eventually in hypothyroidism in their natural course. Uterus globulin-associated protein 1 (UGRP1) was associated with GD in our previous study. Here we investigated the role of UGRP1 in the development of autoimmune thyroid disease (AITD). The results showed that UGRP1 was expressed in the thyrocytes of most Hashimoto's thyroiditis (HT) patients and a proportion of GD patients (293 HT and 198 GD). The pathologic features of UGRP1-positive thyrocytes resembled "Hürthle cells", and were surrounded by infiltrated leukocytes. The positivity rate of TPOAb in UGRP1-positive GD patients was much higher than that in -negative GD patients. Moreover, UGRP1 was co-expressed with Fas and HLA-DR in the thyrocytes of AITD patients. We also found IL-1ß but not Th1 or Th2 cytokines was able to upregulate the expression of UGRP1. Our findings indicated that UGRP1 may be a novel marker in thyrocytes to predict GD patients who develop hypothyroidism.

13.
JAMA Dermatol ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31339524
14.
Clin Chim Acta ; 497: 147-152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31356790

RESUMO

BACKGROUND: Defects in the human thyroid stimulating hormone receptor (TSHR) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify mutations in Chinese patients with CH and analyze the relationships between TSHR phenotypes and clinical phenotypes. METHODS: 220 patients with primary CH were screened for TSHR mutations by performing next-generation sequencing. All the exons and exon-intron boundaries of TSHR were analyzed. The function of 8 mutants in TSHR were further investigated in vitro. RESULTS: Among 220 patients with CH, 15 distinct TSHR mutations were identified in 13 patients (5.91%, 13/220, including our previous reported 110 patients, carried with 10 mutations in 8 patients). We found five distinct mutations in the additional cohort of 110 CH patients and identified 7 mutations (including a novel mutation, p.S567R) were loss-of-function mutations. CONCLUSION: Our study indicated that the prevalence of TSHR mutations was 5.91% among studied Chinese patients with CH. One novel TSHR variant was found and four genetic alterations revealed important role of the Ile216, Ala275, Asn372, Ser567 residues in signaling.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hipotireoidismo Congênito/genética , Análise Mutacional de DNA , Mutação , Receptores da Tireotropina/genética , Adulto , China , DNA/genética , Feminino , Células HEK293 , Humanos , Masculino , Fenótipo
15.
Soc Sci Med ; 235: 112365, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31229359

RESUMO

The educational gradient in U.S. mortality has been rising among non-Hispanic whites. A common intuition sees the growing educational divide in marital status and increases in educational homogamy as potential explanations. To empirically assess this possibility, we analyze mortality from 1986 to 2015 using the National Health Interview Survey Linked Mortality Files (562,584 persons; 204,756 deaths). At the individual level, being unmarried and spouse's lower educational attainment are associated with higher mortality. Counterfactual analyses, however, reveal that the growing educational divide in marital status and increases in educational homogamy contribute little (8%-15%) to the widening educational gradient in mortality. Our simulation analyses further show that extreme educational divide in marital status could substantially drive up mortality inequality, whereas educational homogamy, even when pushed to the maximum level, would play a limited role in increasing mortality inequality. Combined, the results suggest that changes in the educational divide in marital status have the potential to affect mortality inequality, but the actual changes over the past decades were not strong enough to have a major impact; increases in education homogamy, in contrast, barely affect mortality inequality by education. Along with other research showing small effects of educational homogamy on income inequality, our research suggests that the consequences of changing marriage patterns for social inequalities in general and health inequalities in particular may be more limited than commonly assumed.

19.
Biomaterials ; 213: 119195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132643

RESUMO

Hypoxia is one of the critical features in solid tumors, and hypoxia-targeting contrast agents (CAs) could greatly enhance the magnetic resonance imaging (MRI) of tumors by increasing its specificity and providing more diagnosis information. In this article, an internally hydroxy dendrimer of high molecular weight was facilely synthesized by "epoxy-amine" and "thiol-ene" reactions with a ß-cyclodextrin (ß-CD) as the core, and a hypoxia-targeting dendritic contrast agent (DCA) was synthesized through conjugating Gd chelates onto the internal hydroxyl groups and grafting the hypoxia-targeting groups sulfonamides and zwitterionic groups onto the exterior groups of the dendrimer. The zwitterionic surface without disturbance from internally conjugated CAs could reduce unspecific cellular uptake by normal cells, while the hypoxia-targeting group mediate the cellular uptake by hypoxic tumor cells. The in vitro and in vivo study showed that the hypoxia-targeting DCA could be selectively uptake by hypoxic cancer cells and greatly enhance the MRI of orthotopic breast tumor in a mouse model.

20.
Sci Total Environ ; 683: 609-616, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31146065

RESUMO

Excess fluoride in water can be efficiently removed by lanthanum based material, however, different lanthanum species exhibited distinct fluoride removal capability. In this study, three typical lanthanum based nanoparticles denoted as L1, L2 and L3 in the form of La(OH)3, La2O3·nH2O and LaCO3OH respectively were synthesized and well characterized for fluoride removal. They differ in terms of morphology, surface charge, water content, specific surface area and crystallinity. L2 (La2O3·nH2O) exhibited the highest adsorption capacity (~28.9 mg/g) and selectivity towards fluoride, followed by L3 (LaCO3OH) (~25.1 mg/g) and L1 (La(OH)3) (~6.03 mg/g). Despite the relatively low capacity for L1, it could be efficiently regenerated by alkaline solution for repeated use. However, both L2 and L3 suffered significant from capacity loss after regeneration. X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) analysis and molecular configuration modelling suggested the distinct mechanism of fluoride adsorption onto the three materials. Fluoride was captured by L1 and L3 via electrostatic attraction and ligand exchange of different bond strength. However, a stronger LaF interaction via chemical adsorption by L2 was observed. This study provided new insights into the role of commonly used La species for fluoride removal.

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