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1.
Anal Chim Acta ; 1094: 122-129, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761038

RESUMO

Hypochlorite (HClO) is involved in various physiological and pathological processes as well as regulation of lysosomal functions. Thus, it is appreciated to develop efficient molecule tools for precisely detecting HClO in lysosomes. Although several lysosomal-targetable fluorogenic probes for HClO have been developed to date, they still suffered from the discounted sensing performance under lysosomal acidic condition. Herein, on the basis of the "AND" logic gate strategy, a novel dual-activatable fluorogenic probe CS has been rationally designed by simultaneously incorporating HClO recognition site and pH-sensitive group with lysosomal-targetable characteristic into a coumarin fluorophore. Different from the single-activated ones previously reported, CS exhibited good sensitivity, high specificity and fast response towards HClO under the acidic conditions but was out of operation in the neutral or alkaline environment. Importantly, it had been successfully applied for spatial-resolution imaging of exogenous or endogenous HClO in lysosomes.

2.
Food Chem ; 302: 125331, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404867

RESUMO

Adulteration of the high-value silver pomfret (Pampus argenteus) is a serious problem worldwide, necessitating accurate identification and quantification of the species. In this study, optimisation of the digital droplet PCR (ddPCR) assay for the identification and quantification of the silver pomfret was carried out. The primer and probe concentrations, melting temperature, and PCR cycle number were optimised by combining single-factor experiments with an orthogonal experimental design. The absolute limits of detection and quantification of the ddPCR were 2copies/µl and 21 copies/µl, respectively. Its sensitivity was 0.1% for meat mixtures and 0.5% for DNA mixtures. The ddPCR was 156 times more sensitive than the real-time PCR, although both methods had similar specificities. However, the overall time needed to complete the ddPCR method was twice that of the real-time PCR. Notwithstanding, the ddPCR methodology established in this study can be a valuable tool for addressing species adulteration issues.


Assuntos
Produtos Pesqueiros/análise , Análise de Alimentos/métodos , Perciformes/genética , Reação em Cadeia da Polimerase/métodos , Animais , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
Virus Res ; 275: 197793, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31676367

RESUMO

Zika virus (ZIKV) is an emergent flavivirus associated with severe neurological disorders. ZIKV NS3 protein is a viral protease that cleaves the ZIKV polyprotein precursor into individual viral proteins. In this study, we found that ZIKV NS3 by itself exhibited mitochondrial localization, which was quite different from its endoplasmic reticulum (ER) localization in ZIKV-infected cells. We screened viral proteins and identified NS2B as the bona fide recruiter of NS3 to the ER. The NS2B C-terminal tail interacted with NS3 protease domain to retain NS3 on the ER. ß-Sheet motifs that formed between NS2B and the NS3 protease domain played important roles in their interaction, while mutation in the ß-strand of NS2B attenuated NS2B-NS3 interaction and impaired the ability of NS3 protease to cleave the polyprotein precursor into multiple viral proteins. Consequently, NS2B mutations led to severe inhibition of ZIKV replication and production due to insufficient NS3 protease activity. In summary, our study reveals the critical role of NS2B in NS3 recruitment and protease function and provides mechanistic insight into ZIKV replication.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(10): 1252-1257, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31771724

RESUMO

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS: It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1099-1104, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753092

RESUMO

OBJECTIVE: To investigate the current status of neglect in children aged 3-6 years in the rural areas of Urumqi, China and risk factors for neglect. METHODS: Stratified random cluster sampling was performed to select 1 326 children, aged 3-6 years, from 6 kindergartens in the rural areas of Urumqi. A self-designed questionnaire and "Chinese Neglect Evaluation Questionnaire for Rural Children Aged 3-6 Years" were used for investigation. RESULTS: Of the 1 326 children, the neglect rate was 51.89% (688 cases), and the degree of neglect was 49±6. There were significant differences in the neglect rate and the degree of neglect between the children in different age groups (P<0.01). The single-parent families and the remarried families had significantly higher child neglect rate and degree of neglect than the families of three generations under one roof and the core families (P<0.01). The children in left-behind status had a significantly higher degree of neglect (P<0.01). The multivariate logistic regression analysis showed that younger children, mothers with low education level, employment status of the mother as a migrant worker, single-parent and remarried families, low-income families, and left-behind status were risk factors for child neglect (P<0.05). CONCLUSIONS: The neglect of children aged 3-6 years in the rural areas of Urumqi is serious, and more attention should be paid to younger children, children whose mothers with low education level, left-behind children, and children from single-parent families, remarried families and low-income families.


Assuntos
Maus-Tratos Infantis , Criança , Pré-Escolar , China , Feminino , Humanos , Mães , Fatores de Risco , População Rural , Inquéritos e Questionários
6.
Artigo em Inglês | MEDLINE | ID: mdl-31738503

RESUMO

We report a thiol-ene click strategy for the preparation of a novel phenylboronic acid-functionalized covalent organic framework (COF) for selective removal of catechol in aqueous solution. Vinyl-functionalized 2,5-diallyloxyterephthalaldehyde (Da-V) was prepared as a building ligand. Da-V was then condensed with 1,3,5-tris(4-aminophenyl)benzene (Tab) to give a vinyl-functionalized COF DhaTab-V. Subsequently, 4-mercaptophenylboronic acid (4-MPBA) was covalently linked on DhaTab-V via thiol-ene click reaction to give phenylboronic acid-functionalized COF DhaTab-PBA. The adsorption isotherms, energetics and kinetics, and reusability of DhaTab-PBA for the adsorption and removal of catechol from aqueous solution were investigated in detail. This phenylboronic acid-functionalized COF is promising as a new sorbent for selective removal of catechol from aqueous solution with high adsorption capacity and good reusability.

7.
Bioorg Med Chem Lett ; : 126791, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31740251

RESUMO

Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our in-house library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56 µM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed. Molecular docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22 µM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31744716

RESUMO

BACKGROUND AND AIMS: Recent studies have recognized triglyceride-glucose index (TyG) as a practical surrogate of insulin resistance. Previous studies have demonstrated that insulin resistance contributes to ischemic stroke via multiple mechanisms. Our study aimed to investigate the association between TyG and prevalent ischemic stroke, exploring the value of TyG to optimize the risk stratification of ischemic stroke. METHODS AND RESULTS: This cross-sectional study included 10,900 subjects (mean age: 59.95 years, 59.8% females) from rural areas of northeast China between September 2017 to May 2018. TyG was calculated as ln[fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. The prevalence of ischemic stroke was 5.49%. After adjusting for all covariates, each SD increment of TyG caused 22.8% additional risk for ischemic stroke. When dividing TyG into quartiles, the top quartile had a 1.776 times risk for ischemic stroke against the bottom category. Furthermore, smoothing curve fitting demonstrated this association was linear in the whole range of TyG. Finally, AUC revealed an improvement when introducing TyG into clinical risk factors (0.746 vs 0.751, p = 0.029). Consistently, category-free net reclassification index (0.195, 95% CI: 0.112-0.277, P < 0.001) and integrated discrimination index (0.003, 95% CI: 0.001-0.004, P < 0.001) confirmed the improvement by TyG to stratify ischemic stroke risk. CONCLUSION: The prevent ischemic stroke correlated proportionally with the increment of TyG, implicating the linearity of TyG as an indicator of ischemic stroke. Our findings suggest the potential value of TyG to optimize the risk stratification of ischemic stroke in a general population.

9.
Dig Liver Dis ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31744773

RESUMO

BACKGROUND: High body mass index (BMI) and alcohol use are well-defined risk factors for liver cancer. AIMS: We aim to describe the contribution of high BMI and alcohol use to liver-cancer-related death at the global and national levels. METHODS: The data of liver cancer-related mortality attributable to all known risk factors, high BMI, and alcohol use were collected from the Global Burden of Disease database. The estimated average percentage change was used to quantify the liver cancer age-standardized mortality rate (ASMR) trends. RESULTS: Globally, approximately 819,435 liver cancer-related deaths occurred in 2017, among which 415,867, 98,552, and 129,287 deaths could be ascribed to all 9 known risk factors, high BMI, and alcohol use, respectively. The overall ASMR increased from 4.42 per 100,000 to 5.17 per 100,000 in the study period. The liver cancer ASMR attributable to high BMI consistently increased at the global level and in most countries. The alcohol use-related liver cancer mortality decreased by 0.17% per year during the study period. However, a significant increase was found after 2008. CONCLUSION: The increase in high BMI-related liver cancer mortality suggests scarce attention to overweight and highlights its priority in future prevention schedules for liver cancer. Effective prevention measures are still needed to mitigate the adverse impact of alcohol consumption.

10.
Sci Adv ; 5(10): eaax7142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31681849

RESUMO

Zika virus (ZIKV) infection during pregnancy increases the risk of postnatal microcephaly. Neurovascular function provides a homeostatic environment for proper brain development. The major facilitator superfamily domain-containing protein 2 (Mfsd2a) is selectively expressed in human brain microvascular endothelial cells (hBMECs) and is the major transporter mediating the brain uptake of docosahexaenoic acid (DHA). We have discovered a pivotal role for Mfsd2a in the pathogenesis of ZIKV. ZIKV disrupted Mfsd2a both in cultured primary hBMECs and in the neonatal mouse brain. ZIKV envelope (E) protein specifically interacted with Mfsd2a and promoted Mfsd2a polyubiquitination for proteasome-dependent degradation. Infection with ZIKV or ectopic expression of ZIKV E impaired Mfsd2a-mediated DHA uptake. Lipidomic analysis revealed obvious differences in DHA-containing lipids after ZIKV infection. Supplementation with DHA rescued ZIKV-caused growth restriction and microcephaly. Our findings suggest endothelial Mfsd2a as an important pathogenic mediator and supplementation with DHA as a potential therapeutic option for ZIKV infection.

11.
Aesthetic Plast Surg ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701201

RESUMO

INTRODUCTION: The size and shape of the chin strongly influence facial profile and harmony. The current correction of chin deficiency mostly relies on genioplasty surgery involving osteotomy. To avoid osteotomy, one possible alternative is to enhance bone growth at the mental protuberance area with cell sheet transplantation. This study was undertaken to evaluate the efficacy of this approach in a pig model. MATERIALS AND METHODS: Five 4-month-old pigs were included for mandibular bone marrow aspiration and MSC isolation. Triple-layer MSC sheets were then fabricated and utilized using culture-expanded MSCs. Four weeks after bone marrow aspiration, subperiosteal pockets were created on the labial symphyseal surface, followed by transplantation of autogenous MSC sheets to one randomly chosen side with the other side (control) receiving no transplantation. Six weeks after the surgery, the pigs were euthanized and the specimens from both sides were collected for computed tomography (CT) and histological and immunohistochemical analysis. Measurements between the experimental and control sides were compared using paired t tests. RESULTS: MSC sheet fabrication and transplantation were reliably conducted. The labial cortical bone thickness increased significantly with MSC sheet transplantation by an average of 2 mm (p = 0.0001). The average measurements of mineral apposition rate and cell proliferation at the cell sheet side tended to be higher than the control side although the differences did not reach statistical significance (p = 0.1-0.2). Tissue mineral density measurements from CT images and bone volume fraction (BV/TV) measurements from histologic images were identical between the two sides (p > 0.5). CONCLUSION: These data provide a proof of concept that autologous MSC sheets may be transplanted to the subperiosteal region of the mandibular symphysis to stimulate local surface bone growth. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

12.
J Agric Food Chem ; 67(46): 12761-12769, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31675233

RESUMO

There is convincing evidence that consuming whole grains (WGs) may decrease the risk of colorectal cancer (CRC). Wheat bran (WB) is a rich source of dietary fiber and phytochemicals with health-promoting properties. However, the active components especially the interaction between different components in WG wheat have not been fully explored. Here, we investigated whether one of the major WB phytochemicals, alkylresorcinol (AR) C21, and the major active intestinal microbial metabolite of fiber, butyrate, could synergistically suppress human colon cancer cells. Our results demonstrated for the first time that the combination of C21 and butyrate synergistically inhibited the growth of human colon cancer cells and induced apoptosis. Further mechanistic studies demonstrated that the cotreatment of C21 and butyrate induced significant up-regulations in cleaved Poly(ADP-ribose) polymerase (PARP), cleaved caspase 3, p53 upregulated modulator of apoptosis (PUMA), cytochrome C, lipid-conjugated membrane-bound form of microtubule-associated protein 1A/1B-light chain 3 (LC3-II), and C/EBP homologous protein (CHOP) expressions, indicating the synergistic anticancer effects of C21 and butyrate were associated with induction of apoptosis, autophagy, and ER stress pathways. Notably, the C21 concentrations in the large intestinal tract of mice treated with human relevant doses of C21, were from 0.86 to 1.78 µmol/g, suggesting the C21 doses used in vitro may be achievable after daily WG wheat intake. These results provide novel insights into the dietary prevention of CRC regarding the potential interaction of bioactive WG wheat phytochemicals and the microbial metabolites of fiber.

13.
Plant Biotechnol J ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705705

RESUMO

Boron (B) deficiency is one of the major causes of growth inhibition and yield reduction in Brassica napus (B. napus). However, the molecular mechanisms of low B adaptation in B. napus are largely unknown. Here, fifty-one BnaWRKY transcription factors were identified as responsive to B deficiency in B. napus, in which BnaAn.WRKY26, BnaA9.WRKY47, BnaA1.WKRY53 and BnaCn.WRKY57 were tested in yeast one-hybrid assays and showed strong binding activity with conserved sequences containing a W box in the promoters of the B transport-related genes BnaNIP5;1s and BnaBOR1s. Green fluorescent protein fused to the target protein demonstrated the nuclear localization of BnaA9.WRKY47. CRISPR/Cas9-mediated knockout lines of BnaA9.WRKY47 in B. napus had increased sensitivity to low B and lower contents of B than wild-type plants. In contrast, overexpression of BnaA9.WRKY47 enhanced the adaptation to low B with higher B contents in tissues than in wild-type plants. Consistent with the phenotypic response and B accumulation in these transgenic lines, the transcription activity of BnaA3.NIP5;1, a B efficiency candidate gene, was decreased in the knockout lines but was significantly increased in the overexpressing lines under low B conditions. Electrophoretic mobility shift assays, transient expression experiments in tobacco and in situ hybridizations showed that BnaA9.WRKY47 directly activated BnaA3.NIP5;1 expression through binding to the specific cis-element. Taken together, our findings support BnaWRKYs as new participants in response to low B, and BnaA9.WRKY47 contributes to the adaptation of B. napus to B deficiency through up-regulating BnaA3.NIP5;1 expression to facilitate efficient B uptake.

14.
Int J Biol Macromol ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726152

RESUMO

Bulk homogeneous polyelectrolyte complex hydrogels (PCH) are difficult to prepare due to the flocculation effect between polyelectrolytes with opposite charges. Herein, novel chitosan/sodium polyacrylate (PAAS) polyelectrolyte complex hydrogels (CPG) were fabricated successfully by cross-linking chitosan and PAAS with epichlorohydrin (ECH) through inhibiting protonation effect of chitosan in alkali/urea aqueous solution. The swelling behaviors of CPG were studied systematically in different solutions. The equilibrium swelling ratio of chitosan hydrogel in water increased dramatically from 46.3 to 404.8 g/g by the introduction of PAAS. CPG exhibited different swelling ratios towards different pH solutions, physiological solutions and salt solutions with different concentrations, showing obvious smart responsive properties. Moreover, CPG hydrogels exhibited relatively high compressive strength, good biocompatibility and in vitro biodegradability. Therefore, this work provided a novel PCH and shed light on the fabrication of other PCH, showing potential applications in the fields of agriculture, foods, tissue engineering and drug delivery.

15.
Cancer Med ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31769229

RESUMO

LncRNAs have been shown to play essential roles in bladder cancer (BC) progress. Our microarrays of clinical samples firstly screened that lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) was poorly expressed in BC tissues. However, its biological function in BC remains not well understood. Here we examined the clinical correlations with MBNL1-AS1 in BC patients. Then, 5673 and T24 cell lines were employed to investigate the role of MBNL1-AS1 in the proliferation and apoptosis of BC cells in vitro and in vivo. Furthermore, miR-135a-5p (miR-135a)/PHLPP2/FOXO1 axis was focused to explore its regulatory mechanism in BC. The results showed that MBNL1-AS1 was significantly downregulated in bladder tumor tissues, and associated with BC progression. In vitro, MBNL1-AS1 knockdown increased the number of viable cells and bromodeoxyuridine-positive cells, accelerated cell cycle, and dysregulated proliferative regulators (Ki67, p21, p27, and Cyclin D1) in BC cells. The apoptotic cells and the cleavages of caspase-3/9 were reduced in MBNL1-AS1-silenced BC cells. Overexpression of MBNL1-AS1 had opposite effects on BC cell proliferation and apoptosis. Moreover miR-135a was demonstrated to interact with MBNL1-AS1, and inhibiting miR-135a reversed the effects of shMBNL1-AS1 on BC cells. The downstream effectors (PHLPP2 and FOXO1) were positively regulated by MBNL1-AS1, but negatively regulated by miR-135a. Similar results were also observed in xenograft tumors. In conclusion, this study firstly suggests that MBNL1-AS1 acts as a tumor suppressor of BC by targeting miR-135a/PHLPP2/FOXO1 axis, providing a novel insight for BC diagnosis and treatment.

16.
Exp Cell Res ; : 111741, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31759968

RESUMO

Survivin is a newly identified tumour-associated antigen and has been demonstrated to be an excellent target for immunotherapy in several cancers, but its role in hepatocellular carcinoma treatment is still unknown. In this study, survivin-derived peptide-specific cytotoxic T lymphocytes (CTLs) from peripheral blood mononuclear cells of healthy donors were induced by multiple stimulations with HLA-A2- restricted survivin peptide-pulsed T2 cells. The induced CTLs exhibited specific lysis of T2 cells pulsed with the peptide and HLA-A2+ hepatocellular carcinoma cells expressing survivin, while HLA-A2+ hepatocellular carcinoma cell lines that did not express survivin were not recognized by the CTLs. These results suggest that the survivin peptide epitope could be a potential target of specific immunotherapy for HLA-A2+ patients with hepatocellular carcinoma.

17.
Aging (Albany NY) ; 11(21): 9626-9642, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727865

RESUMO

Bone marrow stromal cells from patients with myelodysplastic syndrome (MDS) display a senescence phenotype, but the underlying mechanism has not been elucidated. Pro-inflammatory signaling within the malignant clone and the bone marrow microenvironment has been identified as a key pathogenetic driver of MDS. Our study revealed that S100A9 is highly-expressed in lower-risk MDS. Moreover, normal primary mesenchymal stromal cells (MSCs) and the human stromal cell line HS-27a co-cultured with lower-risk MDS bone marrow mononuclear cells acquired a senescence phenotype. Exogenous supplemented S100A9 also induced cellular senescence in MSCs and HS-27a cells. Importantly, Toll-like receptor 4 (TLR4) inhibition or knockdown attenuated the cellular senescence induced by S100A9. Furthermore, we showed that S100A9 induces NLRP3 inflammasome formation, and IL-1ß secretion; findings in samples from MDS patients further confirmed these thoughts. Moreover, ROS and IL-1ß inhibition suppressed the cellular senescence induced by S100A9, whereas NLRP3 overexpression and exogenous IL-1ß supplementation induces cellular senescence. Our study demonstrated that S100A9 promotes cellular senescence of bone marrow stromal cells via TLR4, NLRP3 inflammasome formation, and IL-1ß secretion for its effects. Our findings deepen the understanding of the molecular mechanisms involved in MDS reprogramming of MSCs and indicated the essential role of S100A9 in tumor-environment interactions in bone marrow.

18.
Psychiatry Res ; : 112690, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31757642

RESUMO

OBJECTIVE: We aimed to study the association among venlafaxine antidepressive outcome, NR3C2 gene polymorphisms and the change of two neuroendocrine hormones during treatment. METHODS: 195 Chinese Han major depressive disorder (MDD) patients were recruited and received a 6-week venlafaxine treatment in this study. Adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) levels were measured at the beginning and at the end of treatment. Six single-nucleotide polymorphisms (SNPs) (NR3C2: rs1512325, rs1512342, rs2070951; NR3C1: rs6191, rs6196, rs10482614) were selected for high-throughput SNP genotyping. Allele and genotype frequencies of them were compared between remission and non-remission groups. RESULTS: We found that genotype frequency of the rs1512325 located in the NR3C2 gene was significantly different between remission and non-remission groups respectively (p < 0.05). Meanwhile, the frequency of the rs1512325 C-allele was significantly lower (p < 0.05) in remission group. The TSH concentration significantly increased after venlafaxine treatment in remission group (p < 0.05). CONCLUSION: The rs1512325 in NR3C2 gene and TSH concentration may be related to venlafaxine treatment outcome in Chinese Han MDD patients.

19.
Plant Cell Environ ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31759338

RESUMO

Considerable genetic variation in agronomic nitrogen (N) use efficiency (NUE) has been reported among genotypes of Brassica napus. However, the physiological and molecular mechanisms underpinning these differences remain poorly understood. In this study, physiological and genetic factors impacting NUE were identified in field trials and hydroponic experiments using two B. napus genotypes with contrasting NUE. The results showed that the N-efficient genotype (D4-15) had greater N uptake and utilization efficiencies, more root tips, larger root surface and root volume, and higher N assimilation and photosynthesis capacity than the N-inefficient genotype (D2-1). Genomic analysis revealed that D4-15 had a greater genome diversity related to NUE than D2-1. By combining genomic and transcriptomic analysis, genes involved in photosynthesis and C/N metabolism were implicated in conferring NUE. Co-expression network analysis of genes that differed between the two genotypes suggested gene clusters impacting NUE. A nitrate transporter gene BnaA06g04560D (NRT2.1) and two vacuole nitrate transporter CLC genes (BnaA02g11800D and BnaA02g28670D) were up-regulated by N starvation in D4-15 but not in D2-1. The study revealed that high N uptake and utilization efficiencies, maintained photosynthesis and coordinated C/N metabolism confer high NUE in B. napus, and identified candidate genes that could facilitate breeding for enhanced NUE in B. napus.

20.
BMC Public Health ; 19(1): 1453, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690294

RESUMO

BACKGROUND: Health care workers have a high risk of occupational exposure. However, the risk of occupational exposure for pediatric health care workers has not been acknowledged in previous studies. The purpose of this study was to investigate the occupational exposure rate of pediatric health care workers in Chinese public hospitals, to explore risk factors for occupational exposure, and to put forward corresponding countermeasures to reduce occupational exposure of pediatric health care workers and protect their physical and mental health. METHODS: A cross-sectional study was conducted with pediatric health care workers in 43 hospitals in 15 provinces in eastern, central, and western China between July and October 2018. With this sample, we computed the descriptive statistics of the demographic characteristics, calculated the frequency of various types of occupational exposure, and tested risk factors for occupational exposure using a chi-squared test and binary logistic regression analysis. RESULTS: Most respondents were nursing staff (61.1%) and workers with a low-ranking professional title (50.5%). The most common style of occupational exposure in our sample was a hazard in the work environment (62.6%). Notably, physicians were less likely to experience occupational exposure than nurses (OR = 0.320, 95% CI = 0.241, 0.426). Meanwhile, pediatric health care workers who interpreted the doctor-patient relationship as harmonious (OR = 0.304, 95% CI = 0.152, 0.607) were less likely to suffer occupational exposure. CONCLUSION: Pediatric health care workers in Chinese public hospitals have a high occupational exposure risk and the risk factors are complex and diverse. The state, society, hospitals should acknowledge this issue and develop strategies to protect the physical and mental health of pediatric health care workers.

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