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1.
Theranostics ; 10(2): 741-756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903148

RESUMO

Bone defects affect millions of people worldwide each year, leading to severe disabilities. Biomimetic scaffolds mediated tissue regeneration represents a promising alternative for bone repair. However, the major problem associated with most currently clinical available artificial bone substitutes (scaffolds) is that they mainly possess filling function but lack of osteo-induction abilities. Therefore, development of biomaterials with osteo-induction property for effective bone regeneration is highly desired. Methods: We report the design and fabrication of a photo-crosslinked sericin methacryloyl (SerMA)/ graphene oxide (GO) hydrogel (SMH/GO) as a biomimetic scaffold for the functional repair of the bone. The mechanical strength, degradation and biocompatibility behavior of SMH/GO hydrogel were measured in vitro. The effect of SMH/GO hydrogel on BMSCs proliferation, migration, osteogenesis differentiation was assessed. After that, SMH/GO-2 was used as an artificial bone substitute for bone regeneration after calvarial defects and effect on bone repair was evaluated by histological, X-Ray and microCT analysis. Furthermore, the potential mechanism of SMH/GO hydrogel regulating BMSCs migration and differentiation was investigated by RNA sequencing. Results: This scaffold has good biocompatibility, cell adhesive property, proliferation- and migration-promoting effects, and osteogenic induction property. After being implanted in a rat calvarial defect model, this SMH/GO scaffold effectively promotes new bone regeneration and achieves structural and functional repair within 12 weeks by inducing autologous bone marrow-derived mesenchymal stem cells (BMSCs) differentiation. By utilizing cell-biological assays and RNA sequencing, we reveal its possible regeneration mechanisms: the SMH/GO hydrogel regulates BMSCs migration and osteo-differentiation via activating MAPK, TNF, and chemokine signaling for bone regeneration. Conclusion: Aiming to meet clinical demands and overcome current limitations of existing artificial bones, we have developed a new type of sericin/ graphene oxide composite scaffold and provided histological, functional, and molecular evidence demonstrating that it is capable of effectively repairing defective bones by inducing autologous BMSCs directional migration and osteogenic differentiation.

2.
Nanoscale ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894795

RESUMO

Exosomes are membrane nanovesicles carrying molecular information that may reflect the biological and genetic characteristics of their parent cells. Numerous studies have demonstrated the potential of exosomes as noninvasive cancer biomarkers. Hence, specific detection of cancer cell-derived exosomes is of significant importance. Here, we developed a fluorescence assay for the determination of gastric cancer exosomes based on branched rolling circle amplification (BRCA) and an aptamer to target specific exosomes. The designed padlock probe was cyclized after incubation with an aptamer binding with the target exosome. BRCA was triggered by adding a second primer and the resulting long tandem double-stranded DNA product was detected using SYBR Green I as the fluorescent dye. This method demonstrated a high specificity for target exosomes with a detection limit of 4.27 × 104 exosomes per mL. Moreover, plasma from gastric cancer patients was tested to verify the clinical applicability of this assay. Our results demonstrated that this aptamer-based biosensor may show potential for the early diagnosis of gastric cancer.

3.
Artif Cells Nanomed Biotechnol ; 48(1): 298-304, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852295

RESUMO

This study aimed to investigate the effect of Fyn gene silencing on the apoptosis of oligodendrocytes (OLs) in epileptic model in vitro and the involved mechanism. Primary oligodendrocyte pro-genitor cells (OPCs) were separated from rats and differentiated to OLs. Immunofluorescent labeling showed positive expression of A2B5 in OPCs and Olig2 in OLs, suggesting the successful separation of OPCs and OLs. Three Fyn siRNAs (si-Fyn) and Fyn siRNA negative control (NC) were transfected into OLs. Western blot showed that among three si-Fyn groups, si-Fyn3 caused the lowest Fyn expression, so si-Fyn3 was chosen for following experiment. Cells were divided into four groups: Control, Model, NC and si-Fyn. In the Model group, cells were cultured in Mg-free extracellular fluid for 3 h. The morphology of control cells was normal. However, the migration of neurons, the aggregation of cell bodies and the "grid-like" changes of neural networks were observed in the model cells. OLs apoptosis in various groups was assessed by flow cytometry. Expression of Fyn, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in OLs of various groups was evaluated by western blot. Compared with the Control group, the apoptotic rates, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the Model and NC groups increased significantly (p < .05). However, the apoptotic rate, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the si-Fyn group were remarkably smaller than those in the Model group (p < .05). In conclusion, Fyn gene silencing reduced the apoptosis of OLs through inhibiting the phosphorylation of ERK1/2 in epileptic model.

4.
Huan Jing Ke Xue ; 41(1): 242-252, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854925

RESUMO

Heavy metals are typical pollutants in the environment and microplastics are relatively newly recognized environmental pollutants, with their coexistence potentially compounding pollution and ecological risks. In this study, we investigate the contents and morphological characteristics of microplastics and heavy metals (Cu, Cd, Pb, Zn, and Cr) in the estuarine sediments of Poyang Lake and the Yangtze River as a means of exploring the relationship between them. The results showed that the abundance of microplastics ranged from 356 n·kg-1 to 1452 n·kg-1, with an average abundance of 982.33 n·kg-1 in the dry sediments. Microplastics were identified as being of three main types:fragments, fibers, and films, whereby fragments were the most dominant type found and accounted for 48.23% of the total microplastics in the sediments. The main color of microplastics in the sediments was chromatic, and the particle size of most microplastics was<1 mm. The major polymer components were polyethylene (PE), low density polyethylene (LDPE), and polyethylene (PP). Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) results indicated that the surfaces of microplastics were rough, porous, cracked, and torn, and that the five heavy metals were found on the surfaces of different microplastics. These heavy metals accumulated to different degrees in the estuarine sediments, and redundancy analysis indicated that environmental factors[including the total organic carbon (TOC), pH, electrical conductivity (EC), and sediment particle size] and the occurrence of microplastics all had significant (P<0.05) effects on the distribution of heavy metal concentrations in sediments. Variation partitioning analysis (VPA) showed that the contribution rates of environmental factors and microplastics to the bioavailability of heavy metals were 37.70% and 0.70% respectively, but the combined effect was 49.60%. We conclude that microplastics in sediments may act as carriers of heavy metals and activate their bioavailability, hence posing a potential threat to the ecological security of estuaries and wetlands.

5.
Pancreas ; 49(1): 46-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31856079

RESUMO

OBJECTIVES: This work aimed to study the early predictive value of extrapancreatic inflammation on magnetic resonance imaging (EPIM) for acute pancreatitis (AP) severity. METHODS: The EPIM score, magnetic resonance severity index, Acute Physiology and Chronic Health Evaluation (APACHE II) score, bedside index of severity in AP, and high-sensitivity C-reactive protein levels were evaluated for 337 AP patients. The extrapancreatic inflammation on computed tomography (EPIC) was also assessed for 86 patients undergoing computed tomography. The predictive values of these scores for severe AP and organ failure were evaluated using receiver operating characteristic curve analyses. RESULTS: Of the 337 AP patients, 55 (16.3%) had organ failure and 17 (5.0%) had severe AP. The EPIM showed a strong correlation with the EPIC (r = 0.794, P < 0.001) and had a higher correlation with the APACHE II and hospital stay compared with the EPIC. The accuracy of the EPIM in predicting severe AP and organ failure (areas under the curve, 0.844 and 0.817) was consistent with that of the APACHE II and bedside index of severity in AP, and higher than that of the magnetic resonance severity index. CONCLUSION: The EPIM is more helpful in assessing AP severity than the EPIC and can indicate the occurrence of severe AP and organ failure early.

6.
J Am Chem Soc ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825602

RESUMO

Although the gelation process and lower critical solution tempera-ture (LCST) behavior are well acknowledged in polymer systems, low-molecular-weight gelators (LMWGs) rarely display LCST behavior during supramolecular gelation. Herein, we report an LMWG system with LCST-type thermo-responsiveness and an LCST-triggered supramolecular gelation process. Temperature plays a crucial role in this system, not only affecting the LCST phase separation, but also triggering the gelation process. The backbones (three-dimensional structures) of the resulting hydrogel are the hierarchical assemblies of the LMWG undergoing the LCST phase separation. Hence, the gelation of the LMWG is only realized when the gelation temperature is above the critical transition tem-perature (Tcloud) of the LCST behavior, which is different to many supramolecular or polymeric hydrogel systems.

7.
Biosci Rep ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808518

RESUMO

Previous studies have shown that lipid metabolism in granulosa cells (GCs) plays a vital role during mammalian ovarian follicular development. However, little research has been done on lipid metabolism in avian follicular GCs. The goal of this study was to investigate the dynamic characteristics of lipid metabolism in GCs from geese pre-hierarchical (6-10 mm) and hierarchical (F4-F2 and F1) follicles during a six-day period of in vitro culture. Oil red O staining showed that with the increasing incubation time, the amount of lipids accumulated in three cohorts of GCs increased gradually, reached the maxima after 96 h of culture, and then decreased. Moreover, the lipid content varied among these three cohorts, with the highest in F1 GCs. The qPCR results showed genes related to lipid synthesis and oxidation were highest expressed in pre-hierarchical GCs, while those related to lipid transport and deposition were highest expressed in hierarchical GCs. These results suggested that the amount of intracellular lipids in GCs increases with both the follicular diameter and culture time, which is accompanied by significant changes in expression of genes related to lipid metabolism. Therefore, it is postulated that the lipid accumulation capacity of geese GCs depends on the stage of follicle development and is finely regulated by the differential expression of genes related to lipid metabolism.

8.
Echocardiography ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31872923

RESUMO

PURPOSE: We set out to undertake a preliminary assessment of the left ventricular hemodynamic status with right ventricular double-chamber pacing by energy loss (EL), wall shear stress (WSS), and circulation intensity (CIR) of vector flow mapping (VFM). We also planned to evaluate the value of VFM technology by measuring cardiac function after pacemaker implantation. METHOD: Data from 58 patients living with right ventricular double-chamber (right ventricular septal) pacemakers as well as 58 healthy volunteers matched in age and gender were collected. The EL, numbers of vortex cycles (n), area (A), CIR, and WSS of the left ventricle with different phases of the same cardiac cycle were obtained. RESULTS: The EL of the left ventricle was significantly higher in the pacemaker group than the control group at partial section of atrial contraction (AC), isovolumetric contraction (IVC), and rapid ejection (RE) (P < 0.05). The WSS of the left ventricle was significantly lower in the pacemaker group than the control group at part of the section in the rapid filling (RF), the AC, IVC, and RE phase (P < 0.05). DISCUSSION: EL in the left ventricular was significantly increased, while related WSS was significantly decreased in patients with right ventricular double-chamber pacing. Our exploration of the state of the flow field in the left ventricular cavity revealed that the implantation of the right ventricular double-chamber pacemaker led to an abnormal left ventricular hemodynamic state, reducing the left ventricular systolic efficiency.

9.
Opt Express ; 27(23): 33359-33368, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31878406

RESUMO

Miniaturizing optical devices with desired functionality is a key prerequisite for nanoscale photonic circuits. Based on Fano resonance, an on-chip high-sensitivity sensor, composed of two waveguides coupling with a symmetry breaking ring resonator, is theoretically and numerically investigated. The established theoretical model agrees well with the finite-difference time-domain simulations, which reveals the physics of Fano resonance. Differing with the coupled cavities, the Fano resonance originates from the interference between symmetry-mode and asymmetry-mode in a single symmetry-broken cavity. The spectral responses and sensing performances of the plasmonic structure rely on the degree of asymmetry of cavity. In particular, the plasmonic sensor can detect the refractive index changes as small as 10-5, and the figure of merit (FOM) of symmetry-breaking cavity structure is 17 times larger than that of symmetrical cavity system. Additionally, the sensitivity to temperature of ethanol analyte achieves 0.701 nm/○C. Compared with the coupled cavities, the on-chip high-sensitivity sensor using a single cavity is more compact, which paves the way toward highly integrated photonic devices.

10.
Front Genet ; 10: 988, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708963

RESUMO

Follicle development is characterized by the recruitment, growth, selection, and dominance of follicles, and follicle selection determines the lifetime reproductive performance. However, in birds, the molecular mechanisms underlying follicle selection still remain elusive. This study analyzed genome-wide changes in the mRNA and miRNA expression profiles in both the granulosa and theca layers of geese ovarian follicles before selection (4-6- and 8-10-mm follicles) and after selection (F5). The sequencing results showed that a higher number of both differentially expressed (DE) mRNAs and DE miRNAs were identified between 8-10-mm and F5 follicles compared with those between the 4-6- and 8-10-mm follicles, especially in the granulosa layer. Moreover, a Short Time-series Expression Miner analysis identified a large number of DE mRNAs and DE miRNAs that are associated with follicle selection. The functional enrichment analysis showed that DE genes in the granulosa layer during follicle selection were mainly enriched in five pathways related to junctional adhesion and two pathways associated with lipid metabolism. Additionally, an interaction network was constructed to visualize interactions among protein-coding genes, which identified 53 junctional adhesion- and 15 lipid regulation-related protein-coding genes. Then, a co-expression network between mRNAs and miRNAs in relation to junctional adhesion was also visualized and mainly included acy-miR-2954, acy-miR-218, acy-miR-2970, acy-miR-100, acy-miR-1329, acy-miR-199, acy-miR-425, acy-miR-181, and acy-miR-147. Furthermore, miRNA-mRNA interaction pairs related to lipid regulation were constructed including acy-miR-107, acy-miR-138, acy-miR-130, acy-miR-128, and acy-miR-101 during follicular selection. In summary, these data highlight the key roles of junctional adhesion and lipid metabolism during follicular selection and contribute to a better understanding of the mechanisms underlying follicle selection in birds.

12.
Cancer Manag Res ; 11: 9025-9035, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695494

RESUMO

Background and aim: Preoperative systemic inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have been developed to predict patient outcome in several types of carcinomas. The aim of this study was to investigate the potential prognostic value of NLR, dNLR, PLR, and LMR, and establish a prognostic nomogram in postoperative GBC patients who underwent radical cholecystectomy. Methods: 169 GBC patients were retrospectively enrolled in the present study. ROC curve analysis was used to determine the optimal cut-off values of systemic inflammatory biomarkers. The prognostic value of those biomarkers was investigated according to the Kaplan-Meier method and Cox regression model. A relevant prognostic nomogram was established. Results: Results showed that NLR, dNLR, PLR, and LMR were significantly associated with overall survival (OS); whereas, NLR and LMR were retained as independent indicators. Based on these independent predictors including tumor differentiation, T stage, N stage, CEA, NLR, and LMR, a nomogram was generated with an accuracy of 0.801. Conclusion: Based on our findings, the predictive nomogram could accurately predict individualized survival probability of postoperative GBC patients, and might support clinicians in treatment optimization and clinical decision-making.

13.
Acad Radiol ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31767534

RESUMO

RATIONALE AND OBJECTIVES: To study the MRI characteristics of early extrapancreatic necrosis and compare them with those of peripancreatic fluid collections in acute pancreatitis (AP). MATERIALS AND METHODS: This retrospective study enrolled 70 AP patients who had extrapancreatic collections visible on MRI within 1 week of onset. Extrapancreatic collections were divided into extrapancreatic necrosis and peripancreatic fluid collections based on follow-up MRI, CT, or pathology. The number and area of extrapancreatic collections, extrapancreatic inflammation on MRI (EPIM) score, MR severity index score and clinical characteristics were evaluated and compared between the two groups. RESULTS: Of the seventy AP patients, 32 (45.7%) had extrapancreatic necrosis, and 38 (54.3%) had peripancreatic fluid collections. The number and area of extrapancreatic collections, MR severity index score, EPIM score, and prevalence of associated hemorrhage were significantly higher in extrapancreatic necrosis patients than in those with peripancreatic fluid collections (p < 0.001). Among the single indicators, the accuracy of the area of extrapancreatic collections (AUC = 0.871) was comparable to that of the EPIM score for predicting extrapancreatic necrosis and was significantly higher than that of the other two indicators. The combination of all indicators showed the highest predictive accuracy (AUC = 0.949), and combinations of two or more indicators demonstrated significantly higher predictive accuracy for extrapancreatic necrosis than any single indicator (p < 0.05) except for the area of extrapancreatic collections (p > 0.05). CONCLUSION: The MRI characteristics have the potential to differentiate early extrapancreatic necrosis from peripancreatic fluid collections and help indicate extrapancreatic necrosis.

14.
J Biomed Nanotechnol ; 15(12): 2393-2400, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748019

RESUMO

Hepatitis B virus (HBV) is closely related to occurrence and development of viral hepatitis. A mutation of 1896nt locus in its pre-C region can promote replication of HBV DNA and improve stability of pre-genome RNA structure, and can even help HBV evade immune clearance. In this study, magnetic beads-probe (MBs@probe) method, combined with single base extension (SBE) technology, was developed for in-situ mutation detection of HBV pre-C region 1896nt locus. Before successfully completing the genotyping of 165 HBV samples, the crucial reaction conditions were first optimized, such as SBE temperature, MBs size and amount, and probe concentration on the surface of MBs. Experimental results showed that these conditions had significant effects on MBs@probe in-situ mutation detection. Comprehensive considerations, such as 58 °C of SBE temperature, high fluorescence intensity and signal-to-noise ratios (SNRs) were obtained when MBs@probe complex was made by 100 µg of 300 nm-MBs and 3.0 µM of probes in the system. Finally, 1896nt locus mutation in pre-C region of 165 HBV samples was successfully genotyped, among which 71 HBV samples were wild types and the remaining 94 samples were mutant types. Meanwhile, 14 randomly chosen samples were taken to further analyze fluorescence intensity and SNRs respectively, and sequencing results for the first two samples were consistent with results from the MBs@probe in-situ mutation detection method. Compared with two-color fluorescence hybridization (TCFH) genotyping technology, this method generally improves the SNRs to more than 10 (which is more than 2-fold), has higher reliability and is more suitable to detect SNPs for known sites.


Assuntos
Vírus da Hepatite B , Herpesvirus Cercopitecino 1 , Polimorfismo de Nucleotídeo Único , DNA Viral , Genótipo , Hepatite B , Humanos , Mutação , Reprodutibilidade dos Testes
15.
Crit Rev Eukaryot Gene Expr ; 29(2): 105-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679265

RESUMO

OBJECTIVE: In this study, the molecular mechanism by which EPO regulates the angiogenesis after cerebral ischemia through AMPK-KLF2 signaling pathway was investigated. METHODS: Sixty healthy, male, C57BL/6 mice were randomly divided into three groups of 20 mice: a sham group, the middle cerebral artery occlusion (MCAO) group, and a MCAO+EPO treatment group. The MCAO model was established using a modified ZeaLonga method. Mice in the EPO treatment group were injected with EPO immediately after reperfusion (5000 IU/kg), and EPO was injected the following day. The number of mouse deaths and neurologic function scores were recorded during the experiment. On day 7 after cerebral ischemia, brain tissue proteins were extracted. The following proteins expressions were detected by western blot assay: EPO, vascular endothelial growth factor (VEGE), vascular endothelial growth factor receptor (KDR), adenosine activated protein kinase (AMPK), and alpha HIF-1α alpha (HIF-1α), KLF2 and nitric oxide synthase (eNOS). RESULTS: Compared with the MCAO group, the survival rate of mice in the EPO group was significantly improved and neurological function was significantly improved (P < 0.01). Western blot results showed that the content of EPO in brain tissue in MCAO group significantly increased compared with sham group. The content of EPO in the brain tissue of mice in the MCAO+EPO treatment group was significantly higher than in that of the MCAO group, which indicates that EPO increased the content of EPO in mouse brain tissue. Compared with the sham group, the protein expression of vascular endothelial growth factor (VEGE) and its receptor (KDR) in brain tissue of the MCAO group significantly decreased. However, the protein expression of VEGE and its receptor KDR in brain tissue of rats treated with MCAO+EPO was significantly higher than in that of the MCAO group. Thus, in this study, EPO was associated with vascular endothelial differentiation after cerebral ischemia in mice. The results of AMPK and KLF2 showed that the expression levels of AMPK and KLF2 in brain tissues of MCAO group mice significantly decreased compared with the sham group. However, the expression levels of AMPK and KLF2 in brain tissues of mice treated with MCAO+EPO were significantly higher than those in the MCAO group. Thus, EPO can activate AMPK and upregulate the expression of the transcription factor KLF2. The protein expression of HIF-1α in the brain tissue of mice in the MCAO group significantly increased compared with the sham group. However, the expression of HIF-1α in mice brain tissues in the MCAO+EPO treatment group was significantly lower than in that of the MCAO group, indicating that EPO was involved in regulating HIF-1α expression. The eNOS results showed that, compared with Sham group, the protein expression of eNOS in brain tissue of MCAO group mice significantly decreased. In the MCAO+EPO treatment group, the protein expression of eNOS was significantly higher in the brain tissue of the mice than in that of the MCAO group, indicating that EPO was involved in the synthesis of NO and promoted the angiogenesis. CONCLUSION: EPO promotes VEGE and its receptor (KDR) expression and participates in the regulation of HIF-1α and eNOS protein expression through the activation of AMPK-KLF2 signaling pathways to promote new vascular development after cerebral ischemia.

16.
Cancer Med ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724334

RESUMO

BACKGROUND: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. METHODS: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. RESULTS: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. CONCLUSION: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).

18.
Animals (Basel) ; 9(10)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623192

RESUMO

Anti-Müllerian hormone (AMH) is recognized as a reliable marker of ovarian reserve. However, the regulatory mechanism of goose AMH gene remains poorly understood. In the present study, both the full-length coding sequence (CDS) and promoter sequence of goose AMH have been cloned. Its CDS consisted of 2013 nucleotides encoding 670 amino acids and the amino acid sequence contained two structural domain: AMH-N and transforming growth factor beta (TGF-ß) domain. The obtained promoter sequence spanned from the -2386 bp to its transcription start site (ATG). Core promoter regions and regulatory elements were identified as well as transcription factors were predicted in its promoter sequence. The luciferase activity was the highest spanning from the -331 to -1 bp by constructing deletion promoter reporter vectors. In CHO cells, the luciferase activity significantly increased by co-expression of AMH and GATA binding protein 4 (GATA-4), while that significantly decreased by mutating the binding sites of GATA-4 located in the -778 and -1477 bp. Results from quantitative real-time polymerase chain reaction (qPCR) indicated that levels of AMH mRNA in geese granulosa layers decreased gradually with the increasing follicular diameter. Taken together, it could be concluded that the transcriptional activity of AMH was activated by GATA-4 to inhibit the development of small follicles in goose.

19.
Environ Res ; 179(Pt A): 108778, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629946

RESUMO

BACKGROUND: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. OBJECTIVE: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. METHOD: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. RESULTS: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10). CONCLUSIONS: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

20.
Environ Sci Technol ; 53(20): 12026-12034, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525872

RESUMO

The effects of disinfection byproducts (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n = 1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC versus GG (Pint = 0.07) and associations with decreased birth length, ponderal index, and gestational age were observed only among subjects with GSTZ1 rs7975 GA/AA versus GG (Pint = 0.07, 0.02, and 0.02, respectively). Our results suggested that prenatal DBP exposure was negatively associated with birth weight and ponderal index, and maternal genetic polymorphisms in CYP2E1 and GSTZ1 might modify these associations.


Assuntos
Citocromo P-450 CYP2E1 , Efeitos Tardios da Exposição Pré-Natal , Biomarcadores , Peso ao Nascer , Desinfecção , Feminino , Glutationa Transferase , Humanos , Exposição Materna , Polimorfismo Genético , Gravidez , Trialometanos
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