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1.
J Cell Biochem ; 121(2): 1101-1113, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31478222

RESUMO

OBJECTIVE: This study aims to offer insights about the biological influence of TAZ, which is a transcriptional coactivator containing a PDZ-binding motif, upon the apoptosis, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (h-PDLSCs). METHODS: We used the green fluorescence protein lentivirus infection system to knockdown or overexpress TAZ in h-PDLSCs. 5-ethynyl-2'-deoxyuridine (EdU) staining detected the proliferative activity, and h-PDLSC apoptosis was analyzed by Annexin V-APC staining. TAZ knockdown or overexpression was performed to determine the osteogenic differentiation function of TAZ during the osteogenic induction of h-PDLSCs. The molecular mechanism of TAZ in the promotion of h-PDLSC osteogenesis was also explored. The chemical inhibitor of SMAD2/3 SIS3 HCL was used to identify the effects in vitro osteogenic differentiation and bone formation in h-PDLSCs overexpressing TAZ. RESULTS: TAZ overexpression resulted in enhanced cell rapid multiplication, which increased the expression of messenger RNA in stemness-related genes. By comparison, TAZ knockdown reduced proliferative activity and increased the apoptosis of h-PDLSCs. After the 7-day osteogenic induction period, alkaline phosphatase activity in the TAZ-overexpression group was significantly increased, and mineralized nodules increased significantly after osteogenic induction for 21 days. Similarly, osteoblast differentiation of h-PDLSCs was impaired after TAZ knockdown. However, the osteogenic potential of the group exposed to the p-SMAD3 inhibitor was restored to its original level. CONCLUSION: Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3.

2.
Sci Total Environ ; 705: 135979, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31841912

RESUMO

Climate change and eutrophication are both critical environmental issues currently. Climate change induces more critical microplastic pollution and sediment resuspension in eutrophic lakes, and conversely the presence of microplastics and resuspension events would intensify these two environmental effects. Via evaluating the impacts of microplastics and sediment resuspension on climate change and eutrophication, it is favorable to provide recommendations for ecological protection and policy formulation in regard to the nutrient input as well as the production and utilization of plastic. In this review, we explore how climate change and eutrophication interact with microplastic pollution and sediment resuspension in shallow lakes, highlighting that both of the latter two play a significant role in the former two. Furthermore, future prospects are put forward on the further and deeper research on the global warming and eutrophication in shallow lakes with microplastic pollution.

3.
Sci Rep ; 9(1): 18102, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792332

RESUMO

Acute liver failure is divided into hyperacute, acute and subacute liver failure. Ascites is a common complication of subacute liver failure. Although animal models of acute liver failure have been established, the study of the pathogenesis of subacute liver failure with ascites complication is hampered by the lack of experimental animal model. The present study aimed at providing a mouse model of subacute liver failure with ascites complication. Kunming mice were intraperitoneally injected with (-)-epigallocatechin-3-gallate (EGCG), a redox-active polyphenol from green tea, for 32 consecutive days with step-wise increased dosage. The EGCG treatment resulted in liver failure as evidenced by extensive hepatocyte necrosis observed histologically along with significant elevation of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin levels as well as significant reduction of serum albumin. Liver fibrosis was not observed by Masson staining and fibrosis-associated proteins were not increased. The mortality was less than 12% and the survival mice developed noticeable ascites. Hepatic thioredoxin and glutathione systems were activated by the EGCG. These adaptive responses might render most mice tolerable to the EGCG treatment. The EGCG treatment significantly up-regulated renal urea transporter A1 and promoted its trafficking to apical membrane. These alterations, known to increase water reabsorption, may be responsible, at least in part, for the formation of the ascites. Overall, the mice treated with gradually elevated doses of EGCG exhibits some of the features observed in patients with subacute liver failure, especially ascites. This mouse model is a useful tool for investigating the pathogenesis of subacute liver failure with ascites complication.

4.
Nat Commun ; 10(1): 5605, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811130

RESUMO

Solitary, persistent wave packets called solitons hold potential to transfer information and energy across a wide range of spatial and temporal scales in physical, chemical, and biological systems. Mechanical solitons characteristically emerge either as a single wave packet or uncorrelated propagating topological entities through space and/or time, but these are notoriously difficult to control. Here, we report a theoretical framework for programming static periodic topological solitons into a metamaterial, and demonstrate its implementation in real metamaterials computationally and experimentally. The solitons are excited by deformation localizations under quasi-static compression, and arise from buckling-induced kink-antikink bands that provide domain separation barriers. The soliton number and wavelength demonstrate a previously unreported size-dependence, due to intrinsic length scales. We identify that these unanticipated solitons stem from displacive phase transitions with periodic topological excitations captured by the well-known [Formula: see text] theory. Results reveal pathways for robust regularizations of stochastic responses of metamaterials.

5.
ACS Appl Mater Interfaces ; 11(46): 43093-43106, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31701752

RESUMO

The interphase layer that forms on either the anode or the cathode is considered to be one of the critical components of a high performing battery. This solid-electrolyte interphase (SEI) layer determines the stability of the electrode in the presence of a given electrolyte as well as the internal resistance of a battery, and hence the overpotential of a cell. In the case of lithium ion batteries where carbonate based electrolytes are used, additives including hexafluorophosphate (PF6), bis-trifluoromethylsulfonimide (TFSI), (fluorosulfonyl)(trifluoromethanesulfonyl)imide (FTFSI), and fluorosulfonimde (FSI) are used to obtain favorable SEI layers. Ionic liquids and salts based on anions containing nitrile groups, including dicyanamide (DCA), offer a less expensive alternative to a fluorinated anion and have also been shown to support stable electrochemistry in lithium and sodium systems. However, longer term cycling leads to the eventual passivation of the electrode, presumed to be due to the instability of the DCA anion. We herein consider the use of a fluorinated anion to control the interfacial electrochemistry and provide a more stable SEI in DCA ILs. We investigate the addition of NaDCA, NaFSI, NaTFSI, and NaFTFSI to the methylpropylpyrrolidinium dicyanamide ([C3mpyr]DCA) ionic liquid. NaFSI was found to generate a more stable SEI layer, as evidenced by extended symmetric cell cycling, while the TFSI and FTFSI salts both lead to thicker, highly passivating surfaces. We use molecular dynamics, infrared spectroscopy and X-ray photoelectron spectroscopy to interrogate and discuss the influence of the anion on the bulk electrolyte, the interfacial electrolyte structure, and the formation of the SEI layer, in order to rationalize the contrasting electrochemical observations.

6.
ACS Appl Mater Interfaces ; 11(49): 46044-46053, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718126

RESUMO

In this article, the inkjet printing technique is demonstrated for the stacking of reduced graphene oxide (RGO) and molybdenum trioxide (MoO3) nanosheets for flexible all-solid-state micro-supercapacitors. The ammonium molybdate tetrahydrate/graphene oxide ((NH4)6Mo7O24·4H2O/GO) aqueous inks are facilely printed on polymide (PI) film and transformed to RGO/MoO3 hybrids via thermal treatments at air atmosphere. The compound inks are water-based, inkjet-printable, and nontoxic for inkjet printing to form two-dimensional crystal materials. The physical properties of aqueous inks are optimized within a printable range characterized by the Ohnesorge number of 1 < Z < 14. The inkjet-printed symmetric micro-supercapacitors (MSCs) with poly(vinyl alcohol) (PVA)-H2SO4 gel electrolyte possess a wide voltage window of 0-0.8 V, excellent flexibility, a high volumetric specific capacitance of 22.5 F cm-3 at 0.044 A cm-3, as well as good cyclic stability due to the synergistic effect of RGO and MoO3. Furthermore, the inkjet-printed composite MSCs delivered a maximum energy density of 2 mWh cm-3 and a power density of 0.018 W cm-3, and the capacity retention rate of inkjet-printed MSCs is still retained 82% even after 10 000 charge-discharge cycles, indicating good electrochemical properties. Above all, the as-designed inkjet printing technique shows potential for flexible and wearable energy storage electronics.

7.
ACS Appl Mater Interfaces ; 11(49): 45596-45605, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31714055

RESUMO

The sluggish kinetics and large overpotential of the oxygen reduction reaction (ORR) severely limit the widespread production and application of metal-air batteries. Herein, a conductive three-dimensional (3D) porous spiral-like polyhedron structure composed of nitrogen-doped carbon nanosheets (L/D-SPNC) was utilized as catalysts with combination of 3D hierarchical porous properties and distinguishing intrinsic properties of two-dimensional (2D) nanosheets for ORR. The chiral template, l/d-tartaric acid, induces the self-assembly of the supramolecule and the formation of an orderly array of carbon with spiral-like surface feature on a molecular scale. The resulting L/D-SPNC exhibits a small wall thickness (2.5 nm), large specific surface area (2034.2 m2/g), and high conductivity (155.76 S/m), which indicates that the properties of 2D nanosheets building blocks are kept in 3D mode. As catalysts for ORR, the optimized L-SPNC-950-1 exhibits a more positive onset potential of 1.03 V compared with those of Pt/C (1.00 V) and a half-wave potential of 0.87 V is also comparable to those of Pt/C (0.87 V). Al-air battery discharge data demonstrate that the spiral-like structure facilitates the diffusion of the electrolyte and oxygen on a three-phase interface, causing weak polarization. Density functional theory (DFT) calculations prove that the twisted surface aggravates the differential charge distribution between C-C/C-N bonds.

8.
Toxins (Basel) ; 11(11)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739564

RESUMO

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 µg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/ß, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway.

9.
J Cancer ; 10(22): 5597-5607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632504

RESUMO

Barrett's esophagus (BE) is an acquired condition in which normal squamous epithelium is replaced with metaplastic columnar epithelium as a consequence of gastroesophageal reflux disease. BE is known as a precursor of esophageal adenocarcinoma. Currently, the molecular mechanism underlying epithelial metaplasia in BE patients remains unknown. Therefore, we investigated the role of Krüppel-like factor 5 (KLF5) signaling in the initiation of BE-associated metaplasia. Sprague-Dawley (SD) rats were used to create a surgical model of bile reflux injury. Immunohistochemistry was performed to analyze human and mouse esophageal specimens. Human esophageal squamous epithelial (HET-1A) cells were treated with bile acid and used in transfection experiments. Quantitative real-time PCR and western blot analysis were performed to detect the expression of KLF5, CDX2, MUC2 and villin. Epithelial tissue from both the rat BE model and human BE patients strongly expressed KLF5, CDX2, MUC2, and villin. Bile acid treatment also increased the expression of KLF5, CDX2, MUC2 and villin in esophageal epithelial cells in a time-dependent manner. Moreover, siRNA-mediated knockdown of KLF5 blocked the expression of CDX2, MUC2 and villin, but transfection of a KLF5 expression vector into esophageal epithelial cells promoted their transdifferentiation into columnar-like cells, as demonstrated by increased expression of the intestinal markers CDX2, MUC2 and villin. Thus, in addition to its function as a transcription factor, KLF5 may be linked to an increased risk of BE development.

10.
Nanoscale ; 11(39): 18071-18080, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506662

RESUMO

The construction of three-dimensional (3D) photonic micro/nanostructures is regarded as one of the most promising approaches to develop highly efficient photoelectrodes for solar water splitting. Here, we report the design and fabrication of an indium tin oxide glass with 3D micro concave-pit arrays (MCPAs) as an effective photonic substrate for dramatically enhanced photoelectrochemical (PEC) water splitting. Compared with the planar counterpart, more than three-fold photocurrent density can be obtained for the 3D photoelectrodes with In2S3 nanosheet arrays grown on the inner surfaces of the MCPAs, mainly ascribable to their largely improved light trapping ability and increased surface area for charge separation and extraction. The PEC performance is further elevated by constructing an effective In2S3/ZnO heterojunction to accelerate the photocarrier separation. As a result, the 3D MCPA-based photoanodes demonstrate a maximum incident photon to current efficiency of 11.7% at 380 nm, which is about four times higher than that of the planar counterpart. The significant advancement demonstrated here provides a facile and low-cost route for the large-scale fabrication of 3D photonic electrodes aiming to achieve highly efficient PEC water splitting.

11.
Medicine (Baltimore) ; 98(36): e17022, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490387

RESUMO

Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16-5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47-7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50-8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09-26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Nucleosídeos/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Humanos , Masculino , Estudos Retrospectivos , Soroconversão , Adulto Jovem
12.
ChemSusChem ; 12(17): 4054-4063, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31301269

RESUMO

A series of electrospun binder-free carbon nanofiber (CNF) mats have been studied as air cathodes for Na-oxygen batteries using a pyrrolidinium-based electrolyte and compared with the commercial air cathode Toray 090. A tenfold increase in the discharge capacity is attained when using CNFs in comparison with Toray 090, affording a discharge capacity of 1.53 mAh cm-2 at a high discharge rate of 0.63 mA cm-2 . The good specific discharge and charge capacities of these CNFs are determined by the void space and the highly accessible surface of the carbon fiber. Furthermore, a threefold increase has been attained in terms of specific capacity by controlling the flooding of the air cathode and hence the location of the three-phase boundary within the CNF mat. The enhancement in performance has been correlated to the morphology, composition, distribution, and location of the discharge products. Sodium superoxide and peroxide were identified as the discharge products and, more importantly, the common side reaction discharge products, which are known to be detrimental to battery performance (including sodium fluoride, sodium hydroxide, and formate), were not observed, exemplifying the stability of the pyrrolidinium-based electrolyte and these binder-free CNF air cathodes.

13.
Vet World ; 12(4): 558-564, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190711

RESUMO

Background and Aim: Brucellosis is one of the most widespread zoonotic diseases globally. Studies indicated the existence of Brucella infection in goats in some province of China. Thus this study aimed to estimate the prevalence of brucellosis in goats of Anhui Province, China. Materials and Methods: Serum and milk samples obtained from goats in different regions of Anhui province were studied through rose Bengal plate test (RBPT), serum agglutination test (SAT), milk ring test (MRT), and polymerase chain reaction (PCR). Results: The investigation frequency of brucellosis using RBPT, SAT, MRT, and PCR methods was 3.9% (n=7), 4.45% (n=8), 11.67% (n=7), and 86.67% (n=156), respectively. The prevalence recorded for brucellosis in sex-wise animals as in females 5.55%, 6.67%, 11.67%, and 78.8% through above methods, while in males, it was 2.23% and 2.23% by RBPT and SAT. However, in age-wise animals, the results 6.36%, 7.27%, 11.67%, and 74.5% were perceived positive by RBPT, SAT, MRT, and PCR in adult females, respectively, but young males and females (up to 9 months) were considered free from brucellosis. Conclusion: These results show that prevalence of brucellosis was relatively higher in females than male's goats and SAT was relatively specific and accurate as compared to RBPT and MRT, but for diagnosis of brucellosis, molecular method (PCR) is recommended.

14.
Sci Signal ; 12(582)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113851

RESUMO

Gasdermin-D (GSDMD) is cleaved by caspase-1, caspase-4, and caspase-11 in response to canonical and noncanonical inflammasome activation. Upon cleavage, GSDMD oligomerizes and forms plasma membrane pores, resulting in interleukin-1ß (IL-1ß) secretion, pyroptotic cell death, and inflammatory pathologies, including periodic fever syndromes and septic shock-a plague on modern medicine. Here, we showed that IRF2, a member of the interferon regulatory factor (IRF) family of transcription factors, was essential for the transcriptional activation of GSDMD. A forward genetic screen with N-ethyl-N-nitrosourea (ENU)-mutagenized mice linked IRF2 to inflammasome signaling. GSDMD expression was substantially attenuated in IRF2-deficient macrophages, endothelial cells, and multiple tissues, which corresponded with reduced IL-1ß secretion and inhibited pyroptosis. Mechanistically, IRF2 bound to a previously uncharacterized but unique site within the GSDMD promoter to directly drive GSDMD transcription for the execution of pyroptosis. Disruption of this single IRF2-binding site abolished signaling by both the canonical and noncanonical inflammasomes. Together, our data illuminate a key transcriptional mechanism for expression of the gene encoding GSDMD, a critical mediator of inflammatory pathologies.

15.
J Asian Nat Prod Res ; : 1-7, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30924356

RESUMO

Two new compounds 7-hydroxy-4'-methoxy-3'-(7''-hydroxy-3'',7''-dimethyl-octa-2'',5''-dienyl)-isoflavone (1) and 7-hydroxy-4'-methoxy-3'-(6''-hydroxy-3'',7''-dimethyl-octa-2'',7''-dienyl)-isoflavone (2), together with five known compounds (3-7), were isolated from EtOAc-soluble extract of the seeds of Psoralea corylifolia. Their structures were elucidated on the basis of detailed spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against diacylglycerol acyltransferase (DGAT). And compounds 1-7 displayed significant inhibitory activity on DGAT1 with IC50 values ranging from 51.2 ± 1.1 to 116.4 ± 1.3 µM.

16.
Biosci Trends ; 13(1): 23-31, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30814402

RESUMO

Cholestasis is a pathological process in which bile drainage is poor for a variety of reasons. Many studies have shown that cholestatic liver injury is a neutrophil-mediated inflammatory response, and oxidative stress induced by neutrophils is the main mechanism of liver cell death. The literature summarizes the bile acid signaling pathway, the neutrophil chemotaxis recruitment process during cholestasis, and the oxidative stress damage produced by neutrophil activation, summarizes the latest research progress. Sphingosine-1-phosphate receptor (S1PR) is a potential therapeutic target for cholestasis that reduces neutrophil aggregation without inhibiting systemic immune status. Early growth response factor 1 (Egr-1) may play a central role in the inflammation induced by cholestasis, and it is also a potential therapeutic target to inhibit the inflammation induced by cholestasis. Strengthening the antioxidant system of hepatocytes to cope with oxidative stress of neutrophils is a feasible treatment for cholestatic liver injury.


Assuntos
Colestase Intra-Hepática/imunologia , Animais , Ácidos e Sais Biliares/metabolismo , Bilirrubina/metabolismo , Colestase Intra-Hepática/metabolismo , Humanos , Imunidade Inata , Terapia de Alvo Molecular , Neutrófilos/fisiologia , Transdução de Sinais
17.
Exp Ther Med ; 17(4): 2473-2484, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30906435

RESUMO

The association between hepatitis B virus (HBV) quasispecies (QS) and the efficacy of nucleos(t)ide analog therapy is currently not well defined, particularly in the case of lamivudine (LAM)/adefovir (ADV) combination rescue therapy for patients with chronic HBV infection (CHB) presenting with LAM resistance. In the present study, 16 CHB patients with the rtM204I/V mutation in the tyrosine-methionine-aspartate-aspartate motif of the C domain of the polymerase gene who switched to LAM/ADV treatment due to LAM resistance were assessed. HBV DNA was isolated from these patients and the reverse transcriptase (RT) region was sequenced. The QS heterogeneity and distribution was analyzed, the mutation sites were recorded and the phylogenetic trees were constructed. The results indicated that QS heterogeneity and distribution in the RT and S regions were not significantly different between responders (RS) and non-RS (NRS) at baseline (P>0.05), except for the higher frequency of a dominant strain in the RT region at the nucleotide level in the RS group (P=0.039). In addition, in NRS, no significant difference in QS heterogeneity or distribution in these regions was identified at six months vs. the baseline. Furthermore, although in the non-responder group the frequency of the LAM resistance-associated mutations (rtM204V/I) decreased at 6 months compared with the baseline, it did not disappear in any of the patients after six months of treatment. Analysis of individual patients did not indicate any consistent selection of specific HBV mutants during LAM/ADV rescue therapy. In conclusion, the baseline HBV QS within the RT and S regions may not be a valid predictor of the response to LAM/ADV rescue treatment in CHB patients with LAM resistance.

18.
BMC Cancer ; 19(1): 181, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819119

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. METHODS: To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets. RESULTS: After adjusting for age and gender, the "AA" genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05-3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03-4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13-5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04-4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01-4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs. CONCLUSIONS: This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-1alfa/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Estudos de Casos e Controles , China/epidemiologia , Mapeamento Cromossômico , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Padrões de Herança , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Razão de Chances
19.
Biol Blood Marrow Transplant ; 25(6): 1092-1098, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30769193

RESUMO

CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but this has not been explored in detail in any previous study. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT), are quantitative indicators of baseline tumor burden. Using FDG PET-CT, we calculated baseline and post-CAR-T cell therapy MTV and TLG in 19 patients with NHL. The median MTV was 72 cm3 (range, .02 to 1137.7 cm3), and the median TLG was 555.9 (range, .011 to 8990.3). After a median follow-up of 5 months (range, 1 to 12 months), the best overall response rate was 79.0%. The baseline MTV and TLG did not differ significantly between patients with response and those without response (P = .62 and .95, respectively). On Cox regression analysis, baseline MTV and TLG were not significantly associated with overall survival (P = .67 and .45, respectively). Patients with mild and moderate CRS (grade 0 to 2) had significantly lower MTV and TLG than those with severe CRS (grade 3 to 4) (P = .008 for MTV comparison, P = .011 for TLG comparison). Using FDG PET-CT, we also demonstrated that CAR-T cell therapy in patients with NHL was associated with pseudoprogression and local immune activation. Our data indicate that patients with higher baseline disease burden have more severe CRS, and that CAR-T cell therapy is associated with lymphoma pseudoprogression and local immune activation.

20.
Biomed Chromatogr ; 33(5): e4511, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30773664

RESUMO

The purpose of this study was to develop and validate an LC-MS/MS method for simultaneous determination of idelalisib and GS-563117 in dog plasma. The analytes were extracted using ethyl acetate and then separated on a Waters Acquity UPLC BEH C18 column (50 × 2.1 mm, i. d., 1.7 µm) using 0.1% formic acid in water and acetonitrile as mobile phase at a flow rate of 0.3 mL/min in gradient elution mode. The analytes were quantified using selected reaction monitoring with precursor-to-product transitions at m/z 416.2 → 176.1, m/z 432.2 → 192.1 and m/z 421.2 → 176.1 for idelalisib, GS-563117 and [2 H5 ]-idelalisib (internal standard). The assay showed good linearity (r > 0.9992) over the tested concentration range of 0.1-600 ng/mL for idelalisib and 0.1-300 ng/mL for GS-563117. The intra- and inter-day RSD values for idelalisib and GS-563117 were <8.84 and 12.41%, respectively. The intra- and inter-day RE values were within the range of -7.21-8.52%, and -6.44-14.23%, respectively. The extraction recovery was found to be >84.59% and no matrix effects were observed. The validated LC-MS/MS method has been successfully applied for the simultaneous determination of idelalisib and GS-563117 in a pharmacokinetic study in dogs. Our results suggested that idelalisib was rapidly metabolized into its metabolite GS-563117 in dog and the in vivo exposure of GS-563117 was 17.59% of that of idelalisib.


Assuntos
Cromatografia Líquida/métodos , Purinas/sangue , Purinas/metabolismo , Quinazolinonas/sangue , Quinazolinonas/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Cães , Estabilidade de Medicamentos , Limite de Detecção , Modelos Lineares , Masculino , Purinas/química , Purinas/farmacocinética , Quinazolinonas/química , Quinazolinonas/farmacocinética , Reprodutibilidade dos Testes
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