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1.
Artigo em Inglês | MEDLINE | ID: mdl-31478171

RESUMO

This paper offers a perspective for the link between air quality and stock returns in China through quantile Granger causality test. Compared to previous studies, the study makes the following innovations. Given the Chinese government plays an important role in economic development, its industrial policies are regarded as a new indispensable supplement of analysis framework apart from investor mood. Next, due to different reflections from cross-industries for different AQ levels, the industry heterogeneity is further considered. Also, nine industries are chosen as a sample, including environmental protection, wind power equipment, steel, photovoltaic equipment, thermal power, tourism, coal, medical service, and medical equipment. Besides, the quantile Granger causality test is robust to misspecification errors when detecting the potential dependence structure between the variables of air quality and stock returns. The empirical results show that the causal link exists in all industries, except medical service. Meanwhile, this impact presents asymmetrical features that when air quality is unhealthy, it has an influence on stock returns of the remaining eight industries. It can be explained by increasing cortisol level, more stringent environmental protection, and industrial policies. These conclusions have essential implications for market participants due to the fact that air quality generates various influences on the stock market. That is why a sustainable environmental design, strict regulatory framework, and special monitoring activities should be highly regarded in China.

2.
Toxicol Appl Pharmacol ; 380: 114696, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31381904

RESUMO

TGFß signaling plays an important role in orchestrating a favorable microenvironment for tumor cell growth and promoting epithelial-mesenchymal transition. As a conventional nonsteroidal anti-inflammation drugs, tolfenamic acid (TA) has been previously reported to exhibit anti-cancer activity. Herein, we investigated the effect of TA on TGFß-mediated pro-metastatic activity and the underlying mechanisms in hepatocellular carcinoma (HCC). As a result, TA suppresses TGFß-induced migration and glycolysis in HCC cells, which is accompanied with reduced Smad phosphorylation and subsequent nuclear transcription activity. Mechanistically, TA promotes lipid raft-caveolar internalization pathway of TGFß receptor, therefore leading to its rapid turnover. Consistently, TA inhibits constitutively active TGFß type I receptor induced Smad phosphorylation and EMT markers, whereas ectopic expression of TGFß type II receptor could partially rescue TGFß-mediated Smad2 phosphorylation and downstream genes expression in the presence of TA. Furthermore, TA inhibited HCC cells invasion in nude mice, associated with the alteration of characteristics related with EMT and glycolysis of cancer cells. Our study suggests TA could activate lipid raft pathway and modulate TGFß mediated metastasis, implicating the potential application of TA as a modulator of tumor microenvironment in HCC.

3.
Virus Genes ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375995

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes one of the most economically important swine diseases worldwide. Tripartite motif-containing 22 (TRIM22), a TRIM family protein, has been identified as a crucial restriction factor that inhibits a group of human viruses. Currently, the role of cellular TRIM22 in PRRSV infection remains unclear. In the present study, we analyzed the effect of TRIM22 on PRRSV replication in vitro and explored the underlying mechanism. Ectopic expression of TRIM22 impaired the viral replication, while TRIM22-RNAi favored the replication of PRRSV in MARC-145 cells. Additionally, we observed that TRIM22 deletion SPRY domain or Nuclear localization signal (NLS) losses the ability to inhibit PRRSV replication. Finally, Co-IP analysis identified that TRIM22 interacts with PRRSV nucleocapsid (N) protein through the SPRY domain, while the NLS2 motif of N protein is involved in interaction with TRIM22. Although the concentration of PRRSV N protein was not altered in the presence of TRIM22, the abundance of N proteins from simian hemorrhagic fever virus (SHFV), equine arteritis virus (EAV), and murine lactate dehydrogenase-elevating virus (LDV) diminished considerably with increasing TRIM22 expression. Together, our findings uncover a previously unrecognized role for TRIM22 and extend the antiviral effects of TRIM22 to arteriviruses.

4.
J BUON ; 24(3): 1100-1105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424667

RESUMO

PURPOSE: To investigate the anticancer effects of Trifolirhizin in SNU-5 human gastric cancer cells along with evaluation of its effects on autophagy, apoptosis, cell cycle phase distribution and m-TOR/PI3K signalling pathway. METHODS: The antiproliferative effect on gastric cancer cells was assessed by MTT assay. Autophagy was detected by electron microscopy and western blot. Apoptotic cell death was revealed by acridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) staining using flow cytometry. Cell cycle analysis was carried out by flow cytometry. Protein expression was determined by immunoblotting. Xenografted mice models were used to evaluate in vivo the anticancer effects of Trifolirhizin. RESULTS: Trifolirhizin could significantly inhibit the proliferation of the gastric cancer cells. The anticancer activity of Trifolirhizin against the gastric cancer cells was found to be due to induction of autophagy and mitochondrial-mediated apoptosis. It was further observed that both apoptosis and autophagy-related protein expressions sere significantly altered. Further, it was found that Trifolirhizin could inhibit the m-TOR/PI3K/AKT signalling pathway. In vivo evaluation in xenografted mice indicated that Trifolirhizin inhibited significantly both tumor weight and tumor volume. CONCLUSIONS: In conclusion, it can be safely stated that Trifolirhizin has the potential to be developed as a potent anticancer agent against gastric carcinoma provided further in depth evaluation of this compound is performed.

5.
Stem Cells ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31414513

RESUMO

The targeted delivery of therapeutic agents to secondary lymphoid organs (SLOs), where are the niches for immune initiation, provides an unprecedented opportunity for immune intolerance induction. The allo-immune rejection post vascularized composite allotransplantation (VCA) is mediated by T lymphocytes. Human adipose derived stem cells (hASCs) possess the superiority of convenient availability and potent immunoregulatory property, but its therapeutic results in the VCA is unambiguous thus far. Chemokine receptor 7 (CCR7) can specifically guide immune cells migrating into SLOs. There, genes of CCR7-GFP or GFP alone were introduced into hASCs by lentivirus. hASCs/CCR7 maintained the multi-differentiation and immunoregulatory abilities but gained the migration capacity elicited by SCL (CCR7 ligand) in vitro. Noteworthily, intravenously infused hASCs/CCR7 targetly relocated in the T cell aggression area in SLOs. In a rat VCA model, hASCs/GFP transfusion had rare effect on the allo-grafted vascularized composite. However, hASCs/CCR7 infusion potently prolonged the grafts' survival time. The ameliorated pathologic exhibition and the regulated inflammatory cytokines in the peripheral blood were also observed. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs may underlie the down-regulated rejection response. Moreover, the proteomics examination of splenic T lymphocytes also confirmed that hASCs/CCR7 decreased the proteins related to cytokinesis, lymphocyte proliferation, differentiation and apoptotic process. In conclusion, our present study demonstrated that targeted migration of hASCs/CCR7 to SLOs highly intensify their in vivo immunomodulatory effect in VCA model for the first time. We believe this SLOs targeting strategy may improve the clinical theraputic efficacy of hASC for allogeneic and autogeneic immune disease. SIGNIFICANCE STATEMENT: Targeted migration after infusion determined their immunoregulatory efficiency of hASCs in vivo. Secondary lymphoid organs (SLOs) are sites for immue initiation and ideal sites for immune tolerance induction. CCR7 can guide hASCs migrating to the T cell aggression area in SLOs. In a rat VCA model, hASCs/CCR7 infusion potently prolonged grafts' survival time. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs and proteomic profile of splenic T lymphocyte explained the down-regulated rejection response. The specific targeting of therapeutic agents particles or drugs to SLOs provides new insight for future clinical applications in the allo-immune and auto-immune diseases. © AlphaMed Press 2019.

6.
J Chin Med Assoc ; 82(7): 562-567, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31274788

RESUMO

BACKGROUND: Several ARID5B single nucleotide polymorphisms (SNPs) were confirmed to be significantly associated with the susceptibility of childhood acute lymphoblastic leukemia (ALL) based on Caucasian populations in previous studies. Similar investigations in Asian populations were less. The aim of this study is to explore the relationship between ARID5B SNPs rs7089424, rs10994982, and the risk of ALL in Chinese pediatric population. METHODS: A total of 190 pediatric ALL patients and 270 controls were enrolled in this study. PCR amplification combined with mass spectrometry were used to evaluate the genotypes of ARID5B rs7089424 and rs10994982. χ test was used in allele frequencies and genotype distributions of the SNPs for analyzing statistical differences between patients and controls. RESULTS: There were significant differences in the risk allele frequencies of ARID5B rs7089424 and rs10994982 between B-lineage ALL (B-ALL) patients and controls (rs7089424, G allele: p = 0.001; rs10994982, A allele: p = 0.000). The genotype distributions of ARID5B rs7089424 and rs10994982 were also statistically different in B-ALL patients compared with controls (rs7089424, p = 0.004; rs10994982, p = 0.001). Further analyzing the relevance of ARID5B rs7089424 and rs10994982 genotypes to clinical risk classification of ALL showed GG genotype of rs7089424 and AA genotype of rs10994982 were strikingly correlated with the medium-risk and low-risk groups of B-ALL. Finally, GG and GT genotypes of rs7089424 and AA genotype of rs10994982 seemed to be responsible for the hyperdiploid subtype susceptibility of childhood B-ALL. CONCLUSION: ARID5B rs7089424 and rs10994982 might serve as genetic susceptibility markers for B-ALL in Chinese pediatric population. Moreover, the two ARID5B SNPs are associated with the risk of B-hyperdiploid ALL, which had a better therapeutic response than other ALL subtypes.

7.
J Virol ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341055

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is one of the most important infectious diseases affecting the global pig industry. Previous studies from our and other groups showed that cholesterol 25-hydroxylase (CH25H), a multi-transmembrane endoplasmic reticulum-associated enzyme, catalyzes the production of 25-hydroxycholesterol (25HC) and inhibits PRRS virus (PRRSV) replication. However, PRRSV infection also actively decreases porcine CH25H (pCH25H) expression through unidentified mechanism(s). In this study, we found that the ubiquitin-proteasome pathway plays a major role in pCH25H degradation during PRRSV infection, and that the PRRSV-encoded envelope (E) protein interacts with pCH25H. PRRSV E protein degraded pCH25H via ubiquitination, and the ubiquitination site was at pCH25H Lys28. Interestingly, PRRSV E protein appeared to specifically degrade pCH25H but not human CH25H, likely because of a Lys28Arg substitution in the human orthologue. As expected, ubiquitin-mediated degradation by E protein attenuated the antiviral effect of pCH25H by downregulating 25HC production. In addition, we found that knockdown of pCH25H decreased E protein-induced inflammatory cytokine expression and that pCH25H overexpression had the opposite effect. These findings suggested that regulation of pCH25H expression was associated with E protein-induced inflammatory responses. Taken together, our results and those of previous studies of the anti-PRRSV effects of CH25H highlight the complex interplay between PRRSV and pCH25H.IMPORTANCECholesterol 25-hydroxylase (CH25H) has received significant attention due to its broad antiviral activity, which it mediates by catalyzing the production of 25-hydroxycholesterol (25HC). Most studies have focused on the antiviral mechanisms of CH25H; however, whether viruses also actively regulate CH25H expression has not yet been reported. Previous studies demonstrated that porcine CH25H (pCH25H) inhibits PRRSV replication not only via production of 25HC, but also by ubiquitination and degradation of viral nonstructural protein 1α. In this study, we expanded on previous work and found that PRRSV actively degrades pCH25H through the ubiquitin-proteasome pathway. PRRSV envelope protein, a viral structural protein, is involved in this process. This study reveals a novel interaction mechanism between virus and host during PRRSV infection.

8.
Life Sci ; 232: 116618, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265854

RESUMO

AIMS: Mitochondrial dysfunction has been regarded as one of the hallmarks of cerebral ischemia-reperfusion injury. In previous studies, we have provided evidence that the extracellular signaling pathway (ERK) 1/2 inhibitor PD98059 improved the neurological deficits by modulating antioxidant and anti-apoptotic activities in rats subjected to cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Since oxidative stress can activate mitochondria-dependent apoptosis and autophagy, we further explored the effects of PD98059 on mitochondria involved with apoptosis and autophagy in rat CA model. MATERIALS AND METHODS: We disposed PD98059 in CA/CPR rats, tested the mitochondrial-mediated apoptosis pathway in brain tissues at 24 h post-resuscitation by mitochondrial permeability transition pores (MPTP), cytochrome c (CytC), BCL-2, BAX, caspase-3, as well as autophagy by LC3, Beclin-1, and p62. Furthermore, we explored the relationship of dynamin-related protein 1 (Drp1) with apoptosis and autophagy. KEY FINDINGS: Our study showed that PD98059 decreased the openings of MPTP, CytC release, caspase3 activation, apoptotic indices, LC3-II, Beclin-1and increased P62. PD98059 also inhibited mitochondria-dependent apoptosis and the activity of autophagy in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. The generation of phosphorylated Drp1-616 was down-regulated accompanied by a decrease of TUNEL-positive cells and LC3 in dual immunostaining after PD98059 inhibited activation of ERK signaling pathway in a dose-dependent manner in rat cerebral cortices at 24 h post-resuscitation. SIGNIFICANCE: PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy at 24 h post-resuscitation in rats subjected to CA/CPR, which is linked with the downregulation of Drp1 expression.

9.
Mult Scler Relat Disord ; 35: 1-4, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31276911

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) refers to a range of autoimmune inflammatory demyelinating diseases affecting the optic nerves, spinal cord, and periependymal regions of the brain. Classical NMOSD is characterized by the presentation of autoantibodies against the water channel aquaporin-4 (AQP4). However, a subset of patients fulfilling the clinical criteria for NMOSD is negative for AQP4-IgG but positive for autoantibodies against myelin oligodendrocyte glycoprotein (MOG); these patients are associated with different clinical manifestations and pathogenesis. METHODS: Patients who received a first diagnosis of NMOSD were reviewed retrospectively between April 2015 and December 2018. Patients were classified according to the presence of AQP4-IgG and MOG-IgG in serum and/or cerebrospinal fluid. Clinical characteristics, magnetic resonance imaging findings, disease severity, and serum C3 and C4 levels at the first episode were compared between the groups. RESULTS: The NMOSD patients with AQP4-IgG and MOG-IgG demonstrated specific, differential clinical features. The AQP4-IgG group featured more women, the presentation of transverse myelitis attacks and simultaneous occurrence of optic neuritis and transverse myelitis were more common, and intrathecal synthesis was more evident. The MOG-IgG group featured younger patients, more acute disseminated encephalomyelitis (ADEM) or ADEM-like attacks, more frequent cerebrospinal fluid pleocytosis, and a better overall outcome. C3 levels were significantly lower in AQP4-IgG-positive patients and higher in MOG-IgG-positive patients relative to healthy controls. C4 levels were significantly lower in the AQP4-IgG-positive NMOSD group when compared to both MOG-IgG-positive patients and controls. C3 and C4 were then combined in a receiver operating characteristic model. The area under the curve of the model was calculated to differentiate the AQP4-IgG-positive group from the MOG-IgG-positive group was 0.787, which was considered moderately predictive. CONCLUSION: The combination of C3 and C4 could assist in the differential diagnosis of AQP4-IgG-positive NMOSD from MOG-IgG-positive NMOSD.

10.
Infect Genet Evol ; 75: 103955, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284044

RESUMO

OBJECTIVE: To investigate the genetic polymorphisms of mitochondrial large ribosomal subunit (mtLSU)-rRNA, dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), cytochrome b (CYB), and superoxide dismutase (SOD) genes and its correlation with clinical outcomes of Pneumocystis jirovecii pneumonia in acquired immune deficiency(AIDS) patients. METHODS: Eighty AIDS patients with P. jirovecii pneumonia that were admitted to our hospital from 2016 to 2018 were included in this study. Their demographic information and clinical data were collected, as well as corresponding saliva specimens for PCR and sequencing of mtLSU-rRNA, DHFR, DHPS, CYB, and SOD genes to analyze genetic polymorphisms, different polymorphic combinations, and clinical outcomes. RESULTS: Of the 80 saliva specimens, mtLSU-rRNA was successfully amplified and sequenced in 30 cases; CYB was successfully amplified and sequenced in 26 cases; and SOD, DHFR, and DHPS were successfully amplified and sequenced in 18 cases. These results indicate that The mtLSU-rRNA, CYB, and SOD genes were highly polymorphic. mt85T and CYB1 were the variants dominantly detected at the mtLSU-rRNA and CYB loci, respectively. The SOD1 and SOD2 variants (each in 50% of the cases) were detected at the SOD locus. Among the 18 cases that were successfully amplified and sequenced for DHFR and DHPS, three DHFR nonsense mutations and no DHPS mutation were observed. The mt85C, CYB1, SOD1, and DHFR312T genes harbored common polymorphisms (n = 4; 22.22%) and the mt85T, CYB1, SOD1, DHFR312T genes were associated with poor clinical outcomes. CONCLUSION: The types of genetic polymorphisms and polymorphic combinations of mtLSU-rRNA, DHFR, DHPS, CYB, and SOD in P. jirovecii were related to the clinical outcomes of patients with P. jirovecii pneumonia in Zhejiang Province, China.

11.
Endocr Connect ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31336363

RESUMO

OBJECTIVE: The aim of this study was to evaluate thyroid function in Cushing's syndrome (CS), and the dynamic changes of thyroid hormones and antithyroid antibodies in Cushing's disease (CD) pre- and postoperatively. DESIGN AND METHODS: This is a retrospective study enrolling 118 patients with CS [102 CD, 10 adrenal CS and 6 ectopic adrenocorticotropic syndrome (EAS)]. Thyroid functions [thyroid-stimulation hormone (TSH), T3, free T3 (FT3), T4, and free T4 (FT4)] were measured in all CS at the time of diagnosis and in all CD 3 months after transsphenoidal pituitary tumor resection. Postoperative hormone monitoring within 3 months was conducted in 9 CD patients completing remission. 28 remitted CD patients experienced hormone and antithyroid antibody evaluation preoperatively and on the 3rd, 6th, and 12th month after surgery. RESULTS: TSH, T3, and FT3 were below the reference range in 31%, 69% and 44% of the 118 CS patients. Remitted CD patients (81/102) had significantly higher TSH (P=0.000), T3 (P=0.000), and FT3 (P=0.000) than those in the non-remission group (21/102). After remission of CD, TSH, T3, and FT3 showed a significant increase, with a few cases above the reference range. By 12 months, most CD patients' thyroid functions returned to normal. Thyroid hormones (including TSH, T3, and FT3) were negatively associated with serum cortisol levels both before and after surgery. No significant changes of antithyroid autoantibodies were observed. CONCLUSIONS: TSH, T3, and FT3 are suppressed in endogenous hypercortisolemia. After remission of CD, TSH, T3, and FT3 increased significantly, even above the reference range, but returned to normal one year after surgery in most cases. Antithyroid antibodies didn't change significantly after remission of CD.

12.
Pediatr Neonatol ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31324476

RESUMO

BACKGROUND: Human cytomegalovirus (HCMV) is a common pathogen that causes many diseases in young children. HCMV glycoprotein H (gH) genotypes may be associated with the type and severity of some diseases. In this study, systematic surveillance was conducted on the prevalence of HCMV infections and HCMV gH genotypes in children. METHODS: Urine samples were collected from children admitted to the inpatient wards and outpatient departments between January 2015 and December 2016 in the Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China), and these were tested by real-time PCR for HCMV DNA detection and HCMV gH genotyping. RESULTS: During the study period, a total of 32,542 urine samples were collected and analyzed using real-time PCR to confirm HCMV infection, and 5286 (16.2%) cases were positive for HCMV DNA. From our results, children aged less than one year were the most susceptible population to HCMV. Based on the data obtained from gH probes combined with real-time PCR assay, 964 HCMV-positive samples were genotyped for gH. Among them, 584 (60.6%) were positive for gH1 subtype, 307 (31.8%) for gH2 subtype, and 73 (7.6%) for both gH1 and gH2 subtypes. The gH2 rate of 42.9% indicated HCMV infection was the highest subtype in the group aged ≤28 days while gH1 rate of 77% was the highest in the group aged >3 years. The highest gH2 rate (36.4%) and lowest gH1 rate (50.0%) were detected in children with HCMV viremia, whereas the highest gH1 rates (65.0%) and lowest gH2 rates (28.8%) were found in children with HCMV hepatitis. CONCLUSION: The findings of our study show that children less than 1-year-old are the major population among HCMV-infected children. gH1 is the predominant genotype of HCMV in China, which occurs more frequently than gH2 genotype in the case of HCMV hepatitis. However, the opposite tendency is observed in HCMV viremia, where the gH2 genotype is predominant.

13.
J Biomed Nanotechnol ; 15(3): 555-570, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165700

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal diseases worldwide. Ginkgo Biloba Leaves polyprenol (GBP) is considered potential efficacy in the treatment of HCC. This study involved oil-in-water type nanoemulsion (NE) loading GBP and Fullerene C60 (C60F) were prepared by dissolving GBP and C60F in NE using inversed phase emulsification (EIP) with ultrasonic-assisted emulsification (UAE) method. Folic acid (FA) coupled Chitosan (CS) and Graphene oxide (GO) nanocomposites (NCs): FA-CS-GO-NCs were fabricated by ionic cross-linking of positively charged FA-CS-GO solution conjugates and negative charged NE with TPP. We combined these materials for preparing NCs loading GBP and C60F (GBP-C60F-FA-CS-GO-NCs) based GBP-C60F-NE. GBP-C60F-FA-CS-GO-NCs in the NE were the mean size was 44.9 nm, PdI was 0.267 and the mean zeta potential was 47.8 mV. And they had good drug loading efficiency, encapsulation efficiency, drug release property and storage stability. In this cytotoxic study, it demonstrated the GBP-C60F-FA-CS-GO-NCs were greater inhibition capacity on MHCC97H cells compared with GBP-NE, C60F-NE, GBP-C60F-NE, GBP-FA-CS-GO-NCs and C60F-FA-CS-GO-NCs. In this genotoxic study, GBP-C60F-FA-CS-GO-NCs at low C60F concentration showed low genotoxicity on MHCC97H and L02 cells. By comparison, GBP-C60F-FA-CS-GO-NCs had higher cytotoxicity on MHCC97H than L02 cells. By the cell apoptosis analysis, the results revealed that GBP-C60F-NE and GBP-C60F-FA-CS-GO-NCs could obviously induce MHCC97H cell apoptosis, especially high concentration GBP-C60F-FA-CS-GO-NCs had the strongest apoptosis inducing ability. The treatment against MHCC97H cells with moderate C60F concentrations of GBP-C60F-FA-CS-GO-NCs effectively inhibited the overexpressions of Akt1 and Akt2, and significantly increased the expression of PTEN. Our results suggest that PTEN, Akt1 and Akt2 might play an important role in the aspect of GBP-C60F-FA-CS-GO-NCs inhibiting against HCC cells. It provides further evidence to speculation that up-regulated PTEN expression and down-regulated Akt1 and Akt2 expression might be one of the important mechanisms for GBP-C60F-FA-CS-GO-NCs inhibiting HCC cells. All these results suggest that GBP-C60F-FA-CS-GO-NCs effectively inhibited the HCC malignant development and has potentially important value in the HCC treatment.


Assuntos
Carcinoma Hepatocelular , Quitosana , Fulerenos , Grafite , Neoplasias Hepáticas , Nanocompostos , Ácido Fólico , Humanos , Óxidos
14.
J Cell Biochem ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31211445

RESUMO

BACKGROUND: Cell division cycle associated protein-3 (CDCA3) has been reported frequently upregulated in various cancers. It has been progressively realized that changed DNA methylations occur in diverse carcinomas. However, the concrete involvement of CDCA3 and DNA methylation in gastric cancer (GC) still needs to be further elucidated. METHODS: In this study, quantitative reverse-transcription polymerase chain reaction (PCR) was utilized to determine the relative expressions of CDCA3 in GC and normal tissue samples. The methylation condition of CDCA3 was determined by bisulfite-sequencing PCR (BSP) and methylation-specific PCR (MSP). A chromatin immunoprecipitation (ChIP) assay and luciferase activity assay was used for the interaction between transcription factors and promoters and binding site determination, respectively. The effects of knockdown or overexpression of specificity protein 1 (SP1) or CDCA3 on GC cells in vitro were further assessed via wound healing assay, colony formation assay, and matrigel invasion assay. RESULTS: In comparison to paired normal tissues, CDCA3 expressions were significantly increased in the GC tissues. The CDCA3 expression was regulated by DNA methylation, with the CpG island hypomethylation responsible for CDCA3 upregulation of GC. ChIP assays verified that the activity of SP1 binding to the CDCA3 promoter was dramatically increased. When the CDCA3 expression was downregulated in MKN45 cells by knockdown SP1, the proliferation ability, healing ability, and invasive ability were significantly suppressed. CONCLUSION: The process by which SP1 bound to the nearest promoter region was expedited in GC cells, by which DNA was hypomethylated and CDCA3 expression was promoted. The effect on cell proliferation and invasion by CDCA3 was under the regulation of SP1 and also affected by hypomethylation of DNA.

15.
Appl Opt ; 58(14): 3926-3931, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31158211

RESUMO

By analyzing Newton's rings, often encountered in interferometry, using fractional Fourier transform (FRFT), we can estimate the physical parameters, such as the curvature radius of the spherical surface and the rings' center. However, parameter estimation from large images using FRFT consumes considerable time. We introduce an improved method that resamples the image before applying FRFT. Because Newton's rings are sparse in the FRFT domain, this method reduces the computational time without decreasing the accuracy. Experimental results show that compared to traditional FRFT-based algorithms, this method can estimate parameters in about 1.3 s when processing 1920×1080 pixel images.

16.
Am J Epidemiol ; 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31165875

RESUMO

We propose a general class of two-phase, epidemiological study designs for quantitative, longitudinal data that are useful when phase one longitudinal outcome and covariate data are available, but the exposure (e.g., biomarker) can only be collected on a subset of subjects during phase two. To conduct a design in the class, one first summarizes the longitudinal outcomes by fitting a simple linear regression of the response on a time-varying covariate for each subject. Sampling strata are defined by splitting the estimated regression intercept or slope distributions into distinct (low, medium, and high) regions. Stratified sampling is then conducted from strata defined by the intercepts, slopes, or from a mixture. In general, samples selected with extreme intercept values will yield low variances for time-fixed exposure associations with the outcome and samples enriched with extreme slope values will yield low variances for time-varying exposure associations with the outcome (including interactions with time-varying exposures). We describe ascertainment corrected maximum likelihood and multiple imputation estimation procedures that permit valid and efficient inferences. We embed all methodological developments within the framework of conducting a sub-study that seeks to examine genetic associations with lung function in continuously smoking participants in the Lung Health Study.

17.
Genomics Proteomics Bioinformatics ; 17(2): 183-189, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31233833

RESUMO

Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 µM) was significantly higher than that of the controls (9.73 µM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.

18.
Nature ; 570(7762): 514-518, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31217584

RESUMO

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions13-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.

19.
Neurosci Lett ; 707: 134313, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31167116

RESUMO

BACKGROUND: To explore the related factors of impulse control disorders (ICDs) in patients with Parkinson's disease (PD). METHODS: We conducted a comprehensive search to identify studies on impulse control disorders in patients with Parkinson's disease. The related factors were compared to discriminate between PD patients with ICDs (PD-ICDs+)and PD patients without ICDs(PD-ICDs-)by a meta-analysis. RESULTS: 96 full-texts were assessed, and 15 were included (PD-ICDs+: 999; PD-ICDs-: 3507). The results showed that PD-ICDs + were significantly associated with younger age (SMD =-0.39, 95% CI: -0.50 - -0.28, P < 0.01), male sex(OR = 1.64, 95% CI: 1.34-2.02, P < 0.01), smoking habit(OR = 2.28, 95% CI: 1.16-4.47,P = 0.02), dopamine receptor agonist use(DA use) (OR = 3.41, 95% CI: 1.86-6.26,P < 0.01), dopamine receptor agonist equivalent daily dose(DA LEDD) (SMD = 0.42, 95% CI: 0.14 - 0.70,P = 0.003), levodopa equivalent daily dose(total LEDD) (SMD = 0.32, 95% CI: 0.14 - 0.49,P < 0.01), and amantadine use(OR = 2.26, 95% CI: 1.67-3.06,P < 0.01). While levodopa dose (SMD = 0.05, 95% CI: -0.09 -0.19,P = 0.48), Hoehn and Yahr stage(H & Y stage) (SMD =-0.05, 95% CI: -0.14 - 0.04,P = 0.27), MDS-UPDRS Part III score(UPDRS III score) (SMD =-0.05, 95% CI: -0.13 - 0.03,P = 0.24), PD duration (SMD =-0.23, 95% CI: 0.10 - 0.37,P < 0.01)and Mini-Mental Status Examination score (MMSE score) (SMD = 0.10, 95% CI: -0.11 - 0.31,P = 0.33)were not related with PD-ICDs+. CONCLUSION: Our study confirmed the previous results that younger age, male gender, smoking habit, longer PD duration, DA use, DA LEDD, total LEDD were high risk factors of PD-ICDs+.

20.
Neuron ; 103(2): 203-216.e8, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31174959

RESUMO

The hippocampus formation, although prominently implicated in schizophrenia pathogenesis, has been overlooked in large-scale genomics efforts in the schizophrenic brain. We performed RNA-seq in hippocampi and dorsolateral prefrontal cortices (DLPFCs) from 551 individuals (286 with schizophrenia). We identified substantial regional differences in gene expression and found widespread developmental differences that were independent of cellular composition. We identified 48 and 245 differentially expressed genes (DEGs) associated with schizophrenia within the hippocampus and DLPFC, with little overlap between the brain regions. 124 of 163 (76.6%) of schizophrenia GWAS risk loci contained eQTLs in any region. Transcriptome-wide association studies in each region identified many novel schizophrenia risk features that were brain region-specific. Last, we identified potential molecular correlates of in vivo evidence of altered prefrontal-hippocampal functional coherence in schizophrenia. These results underscore the complexity and regional heterogeneity of the transcriptional correlates of schizophrenia and offer new insights into potentially causative biology.

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