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1.
J Diabetes ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605564

RESUMO

BACKGROUND: Male obesity is suggested to impact negatively on male fertility and semen quality in numerous studies. However, previous literatures regarding health effects of metabolic syndrome (MetS) on semen quality is rare and inconsistent. The aim of this study is to investigate the relationship between MetS and sperm parameters in a Taiwanese reproductive-age male population. METHODS: 8395 males who attended in a private medical screening program in Taiwan from 2010 to 2016 were included in this cross-sectional study. Semen analysis was assessed in accordance with the WHO guidelines such as sperm concentration, total motility, progressive motility and morphology. MetS was defined by the modified NCEP ATP III criteria with the Asian cut-off for waist circumference. The associations between MetS and semen analysis were examined by multivariable linear regressions. RESULTS: After fully adjusting for pertinent covariables, MetS was significantly associated with reduced percentage of sperm normal morphology. Blood pressure (BP), waist circumference (WC) and serum glucose had significantly negative association with sperm normal morphology. Individuals with increased number of MetS components had more closely association with reduced sperm progressive motility and percentage of normal morphology. CONCLUSION: MetS and its components exhibited deleterious effects on semen quality among reproductive-age males. Further studies are warranted to explore these pathophysiologic relationship and underlying mechanisms. This article is protected by copyright. All rights reserved.

2.
FEMS Microbiol Lett ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31598721

RESUMO

This study mainly investigated the effects of environmental factors on the germination/dormancy, sporulation, and resistance of Duddingtonia flagrans chlamydospores. Results showed that the germination temperature of chlamydospores were >10°C and ≤35°C. After the chlamydospores were treatmented at -20°C, -40°C, and -80°C for 12-24 h, they still have the ability to germinate. The chlamydospores germinated at pH 3-13 but did not germinate at pH 1-2 and pH 14. The chlamydospores could tolerate ultraviolet ray for 720 min, but visible light irradiation for 24 h significantly reduced their germination rate. The chlamydospores did not germinate under anaerobic conditions. After the chlamydospores were cultured on water agar (WA) containing 5%, 10%, and 20% NaCl, their germination rate was significantly inhibited. Once NaCl was removed, the chlamydospores almost completely recovered their germination ability. Among the nine kinds of additives used in the study, 0.3% arginine significantly promoted spore germination (P < 0.05) but 1% trehalose and 1% glycerine significantly inhibited spore germination during incubation from 24 h to 48 h (P < 0.05). This work indicated that the D. flagrans chlamydospores are highly resistant to environmental variations, which could be used for biocontrol of animal parasites.

3.
Se Pu ; 37(9): 1019-1025, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642308

RESUMO

An analytical method for the determination of 34 pesticide residues in plant-derived foods was established using an automated QuEChERS sample preparation system combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The sample extraction and dispersive solid-phase extraction in the manual QuEChERS method were combined using the vortex vibration and centrifugation functions of the automated QuEChERS sample preparation system. The operating parameters and pretreatment steps were optimized, and the analytes were detected in the multiple reaction monitoring (MRM) mode. The quantification analysis was performed by the matrix-matched external standard method. The automated and the manual QuEChERS methods were compared from the methodological verification standpoint. The calibration curves showed good linearity in a certain range, and the correlation coefficients (R2) were greater than 0.99. The limits of detection and limits of quantification were 0.76-3.60 µg/kg and 2.28-10.80 µg/kg, respectively. Moreover, the recoveries ranged from 53.0% to 125.2%, and the relative standard deviations (RSDs) were less than 1.59% (n=5). The results obtained by the manual QuEChERS method were not significantly different from those obtained by the automated QuEChERS method. This method can effectively reduce the labor intensity and probability of error in the determination of pesticide residues.


Assuntos
Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Verduras/química , Cromatografia Líquida de Alta Pressão , Extração em Fase Sólida , Espectrometria de Massas em Tandem
4.
Sensors (Basel) ; 19(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623199

RESUMO

Multisensor systems can overcome the limitation of measurement range of single-sensor systems, but often require complex calibration and data fusion. In this study, a three-dimensional (3D) measurement method of four-view stereo vision based on Gaussian process (GP) regression is proposed. Two sets of point cloud data of the measured object are obtained by gray-code phase-shifting technique. On the basis of the characteristics of the measured object, specific composite kernel functions are designed to obtain the initial GP model. In view of the difference of noise in each group of point cloud data, the weight idea is introduced to optimize the GP model, which is the data fusion based on Bayesian inference method for point cloud data. The proposed method does not require strict hardware constraints. Simulations for the curve and the high-order surface and experiments of complex 3D objects have been designed to compare the reconstructing accuracy of the proposed method and the traditional methods. The results show that the proposed method is superior to the traditional methods in measurement accuracy and reconstruction effect.

5.
Nutrients ; 11(10)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581608

RESUMO

BACKGROUND: The impact of serum phosphorus concentration on metabolic syndrome were limited. Therefore, this study aimed to explore the association between the serum phosphorus and incident metabolic syndrome in the elderly in Taiwan. METHODS: We included 1491 participants who had health check-ups in the Tri-Service General Hospital for the period 2007 to 2015 and divided them based on age to assess the incidence of metabolic syndrome. We performed the COX regression model to explore the impact of serum phosphorus for metabolic syndrome, diabetes mellitus, and hypertension by an age-specific group. RESULTS: Our result showed that higher serum phosphorus concentration was noted in the elderly in the baseline characteristics. In the group older than 60 years, serum phosphorus concentration was correlated with the incidence of metabolic syndrome (hazard ratios (HR) = 1.39, 95% CI 1.11-1.74) and diabetes mellitus (HR = 1.49, 95% CI 1.15-1.92) after adjustment. We further found the relationship between serum phosphorus and incidence of the components of metabolic syndrome, including higher waist circumference, high-density lipoprotein (HDL), serum triglyceride, and fast glucose. CONCLUSIONS: Our study might provide an epidemiological evidence that serum phosphorus was related with the incidence of metabolic syndrome in the elderly in Taiwan.

6.
Biol Chem ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665103

RESUMO

Pseudorabies virus (PRV) UL2 (pUL2) is a multifunctional protein, which is homologous with herpes simplex virus 1 early protein UL2 (hUL2) and crucial for the viral propagation. Yet, how pUL2 executes its roles in the viral life cycle remain inadequately understood. In order to uncover its effect on the procedure of PRV infection, investigation was performed to examine the subcellular distribution of pUL2 and establish its trafficking mechanism. In the present study, enhanced yellow fluorescent protein or Myc tag fused pUL2 was transiently overexpressed in transfected cells and exhibited an absolutely nuclear accumulation without the existence of other PRV proteins. Additionally, the nuclear trafficking of pUL2 was proved to rely on Ran-, transportin-1, importin ß1, importin α1, α3 and α5. Accordingly, these data will benefit the knowledge of pUL2-mediated biological effects in PRV infection cycle.

7.
Front Immunol ; 10: 2151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572371

RESUMO

Current combined antiretroviral therapy (cART) mainly targets 3 of the 15 HIV proteins leaving many potential viral vulnerabilities unexploited. To purge the HIV-1 latent reservoir, various strategies including "shock and kill" have been developed. A key question is how to restore impaired immune surveillance. HIV-1 protein Nef has long been known to mediate the downregulation of cell-surface MHC-I and assist HIV-1 to evade the immune system. Through high throughput screening of Food and Drug Administration (FDA) approved drugs, we identified lovastatin, a statin drug, to significantly antagonize Nef to downregulate MHC-I, CD4, and SERINC5, and inhibit the intrinsic infectivity of virions. In addition, lovastatin boosted autologous CTLs to eradicate the infected cells and effectively inhibit the subsequent viral rebound in CD4+ T-lymphocytes isolated from HIV-1-infected individuals receiving suppressive cART. Furthermore, we found that lovastatin inhibits Nef-induced MHC-I downregulation by directly binding with Nef and disrupting the Nef-AP-1 complex. These results demonstrate that lovastatin is a promising agent for counteracting Nef-mediated downregulation of MHC-I, CD4, and SERINC5. Lovastatin could potentially be used in the clinic to enhance anti-HIV-1 immune surveillance.

8.
Nat Commun ; 10(1): 4807, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641126

RESUMO

The upgrading of CO2/CO feedstocks to higher-value chemicals via energy-efficient electrochemical processes enables carbon utilization and renewable energy storage. Substantial progress has been made to improve performance at the cathodic side; whereas less progress has been made on improving anodic electro-oxidation reactions to generate value. Here we report the efficient electroproduction of value-added multi-carbon dimethyl carbonate (DMC) from CO and methanol via oxidative carbonylation. We find that, compared to pure palladium controls, boron-doped palladium (Pd-B) tunes the binding strength of intermediates along this reaction pathway and favors DMC formation. We implement this doping strategy and report the selective electrosynthesis of DMC experimentally. We achieve a DMC Faradaic efficiency of 83 ± 5%, fully a 3x increase in performance compared to the corresponding pure Pd electrocatalyst.

9.
Cancer Med ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489986

RESUMO

BACKGROUND: The aim of this study was to investigate the potential prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma (PDAC) patients after pancreaticoduodenectomy. METHODS: Kaplan-Meier survival analysis method with log-rank test and Cox proportional hazards regression analysis were performed to figure out the association between Kinesin-4 family genes expression and PDAC patients overall survival time. Joint-effect survival analysis and stratified survival analysis were carried out to assess the prognosis prediction value of prognosis-related gene. Nomogram was constructed for the individualized prognosis prediction. In addition, we had used the gene set enrichment analysis and genome-wide co-expression analysis to further explore the potential mechanism. RESULTS: KIF21A expression level was significantly associated with PDAC patient clinical prognosis outcome and patient with a high expression of KIF21A would have a shorter overall survival time. The prognosis prediction significance of KIF21A was well validated by the joint-effect survival analysis, stratified survival analysis, and nomogram. Meanwhile, the gene set enrichment analysis and genome-wide co-expression analysis revealed that KIF21A might involve in DNA damage and repair, transcription and translation process, post-translation protein modification, cell cycle, carcinogensis genes and pathways. CONCLUSIONS: Our current research demonstrated that KIF21A could serve as a potential prognostic biomarker for patient with early-stage PDAC after pancreaticoduodenectomy.

10.
Org Lett ; 21(18): 7351-7355, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31478674

RESUMO

The currently synthetic methods of peptide heterodimer involve tedious synthesis and purification steps. An acid-labile traceless linker was prepared, which is highly compatible with the Fmoc strategy and could be used to prepare peptide heterodimer on resin. The linker could be cleaved concomitantly with peptide cleavage, and two model heterodimers were synthesized. The proposed synthesis procedure is simple, straightforward, and provides great convenience for preparing disulfide-linked peptide heterodimers.

11.
Int J Oncol ; 55(4): 805-822, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485610

RESUMO

Hepatocellular carcinoma (HCC) is one the most common malignancies and has poor prognosis in patients. The aim of the present study is to explore the clinical significance of the main genes involved in the Janus kinase (JAK)­signal transducer and activator of transcription (STAT) pathway in HCC. GSE14520, a training cohort containing 212 hepatitis B virus­infected HCC patients from the Gene Expression Omnibus database, and data from The Cancer Genome Atlas as a validation cohort containing 370 HCC patients, were used to analyze the diagnostic and prognostic significance for HCC. Joint­effect analyses were performed to determine diagnostic and prognostic significance. Nomograms and risk score models were constructed to predict HCC prognosis using the two cohorts. Additionally, molecular mechanism analysis was performed for the two cohorts. Prognosis­associated genes in the two cohorts were further validated for differential expression using reverse transcription­quantitative polymerase chain reaction of 21 pairs of hepatitis B virus­infected HCC samples. JAK2, TYK2, STAT3, STAT4 and STAT5B had diagnostic significance in the two cohorts (all area under curves >0.5; P≤0.05). In addition, JAK2, STAT5A, STAT6 exhibited prognostic significance in both cohorts (all adjusted P≤0.05). Furthermore, joint­effect analysis had advantages over using one gene alone. Molecular mechanism analyses confirmed that STAT6 was enriched in pathways and terms associated with the cell cycle, cell division and lipid metabolism. Nomograms and risk score models had advantages for HCC prognosis prediction. When validated in 21 pairs of HCC and non­tumor tissue, STAT6 was differentially expressed, whereas JAK2 was not differentially expressed. In conclusion, JAK2, STAT5A and STAT6 may be potential prognostic biomarkers for HCC. JAK2, TYK2, STAT3, STAT4 and STAT5B may be potential diagnostic biomarkers for HCC. STAT6 has a role in HCC that may be mediated via effects on the cell cycle, cell division and lipid metabolism.

12.
ACS Nano ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31536322

RESUMO

The rational design and fabrication of promising electrodes with prominent energy storage property and conversion performance is crucial for supercapacitors and electrocatalysis. Herein, potato chip-like cobalt nickel-layered double hydroxide@polypyrrole-cotton pad (CoNi-LDH@PCPs) composite was synthesized by in situ polymerization, which was coupled with facile solution reaction and ion-exchange etching process. An interesting potato chip-like structure can effectively expedite the kinetics of the electrode reactions, while the three-dimensional PCPs texture affords efficient pathways for charge transport, and the voids between adjacent fibers are thoroughly accessible for electrolytes and bubble evolution. When evaluated as a positive electrode for wearable supercapattery, the hierarchical CoNi-LDH@PCPs electrode displayed high specific capacity and excellent flexibility. As an oxygen evolution reaction catalyst, this PCP-based electrode also reveals the lowest overpotential of 350 mV at 10 mA cm-2 and a Tafel slope of ∼58 mV dec-1. In addition, density functional theory calculations suggest that the synthesis strategy for controllable tuning of hollow CoNi-LDH arrays reported here represents a critical step toward high-performance electrodes for energy storage and electrochemical catalysis.

13.
Sensors (Basel) ; 19(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514439

RESUMO

Portable box volume measurement has always been a popular issue in the intelligent logistic industry. This work presents a portable system for box volume measurement that is based on line-structured light vision and deep learning. This system consists of a novel 2 × 2 laser line grid projector, a sensor, and software modules, with which only two laser-modulated images of boxes are required for volume measurement. For laser-modulated images, a novel end-to-end deep learning model is proposed by using an improved holistically nested edge detection network to extract edges. Furthermore, an automatic one-step calibration method for the line-structured light projector is designed for fast calibration. The experimental results show that the measuring range of our proposed system is 100-1800 mm, with errors less than ±5.0 mm. Theoretical analysis indicates that within the measuring range of the system, the measurement uncertainty of the measuring device is ±0.52 mm to ±4.0 mm, which is consistent with the experimental results. The device size is 140 mm × 35 mm × 35 mm and the weight is 110 g, thus the system is suitable for portable automatic box volume measurement.

14.
J Invest Surg ; : 1-9, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488005

RESUMO

Background and Objective: The preferred treatment for Cholangiocarcinoma (CCA) patients is surgery. Approximately, 35% of patients can undergo surgical resection in clinic. Biomarkers for CCA need to be identified for diagnosis, treatment, or prognosis prediction of this disease. Y-box binding protein-1 (YBOX-1) is highly correlated with tumor progression and poor overall survival in many malignancies. The prognostic value of YBOX-1 overexpression in CCA remains unclear. We examined the expression of YBOX-1 in resected tissue in CCA patients and studied the effect of YBOX-1 in CCA migration and invasion in vitro and in vivo. Methods: Expression of YBOX-1 in the tissue of 91 CCA patients was investigated by immunohistochemistry. The effects of YBOX-1 on migration, invasion, and proliferation in CCA cell lines were assessed by short hairpin RNA lentivirus or overexpression plasmid transfection. Results: A total of 55 (60.4%) of CCA cancerous tissues showed strongly positive YBOX-1 cytoplasmic staining. The strongly positive expression of YBOX-1 was close to early recurrence and poor overall survival by Kaplan-Meier analyses. Knockdown of YBOX-1 reduced migration and invasion in CCA cells and proliferation of tumor in xenotransplantation nude mice. Overexpression of YBOX-1 promoted migration and invasion in CCA cells and proliferation of tumor in xenotransplantation nude mice. Conclusion: YBOX-1 is correlated with early recurrence and poor overall survival in CCA. YBOX-1 may be a factor of predicting poor prognosis and overall survival.

15.
Chemosphere ; 235: 1050-1058, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561294

RESUMO

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 µM until 4 days post-fertilization. Our data showed that exposure to 10 µM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.


Assuntos
Autofagia/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo/prevenção & controle , Chumbo/toxicidade , Peixe-Zebra/embriologia , Animais , Expressão Gênica , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
16.
Int J Oncol ; 55(4): 860-878, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432149

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor­related mortalities worldwide. Long noncoding RNAs have been reported to be associated with tumor initiation, progression and prognosis. The present study aimed to explore the association between long noncoding RNA LINC00668 and its co­expression correlated protein­coding genes (PCGs) in HCC. Data of 370 HCC patients from The Cancer Genome Atlas database were used for analysis. LINC00668 and its top 10 PCGs were selected to determine their diagnostic and prognostic value. Molecular mechanisms were explored to identify metabolic processes that LINC00668 and its PCGs are involved in. Prognosis­related clinical factors and PCGs were used to construct a nomogram for predicting prognosis in HCC. A Connectivity Map was constructed to identify candidate target drugs for HCC. The top 10 PCGs identified were: Pyrimidineregic receptor P2Y4 (P2RY4), signal peptidase complex subunit 2 (SPCS2), family with sequence similarity 86 member C1 (FAM86C1), tudor domain containing 5 (TDRD5), ferritin light chain (FTL), stratifin (SFN), nucleolar complex associated 2 homolog (NOC2L), peroxiredoxin 1 (PRDX1), cancer/testis antigen 2 CTAG2 and leucine zipper and CTNNBIP1 domain containing (LZIC). FAM86C1, CTAG2 and SFN had significant diagnostic value for HCC (total area under the curve ≥0.7, P≤0.05); LINC00668, FAM86C1, TDRD5, FTL and SFN were of significant prognostic value for HCC (all P≤0.05). Investigation into the molecular mechanism indicated that LINC00668 affects cell division, cell cycle, mitotic nuclear division, and drug metabolism cytochrome P450 (all P≤0.05). The Connectivity Map identified seven candidate target drugs for the treatment of HCC, which were: Indolylheptylamine, mimosine, disopyramide, lidocaine, NU­1025, bumetanide, and DQNLAOWBTJPFKL­PKZXCIMASA­N (all P≤0.05). Our findings indicated that LINC00668 may function as an oncogene and its overexpression indicates poor prognosis of HCC. FAM86C1, CTAG2 and SFN are of diagnostic significance, while FAM86C1, TDRD5, FTL and SFN are of prognostic significance for HCC.

17.
Mol Genet Genomics ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31410611

RESUMO

P2RX7 (purinergic receptor P2X 7) is an important membrane ion channel and involved in multiple physiological processes. One non-synonymous SNP on P2RX7, rs3751143, had been proven to reduce ion channel function and further associated with multiple diseases. However, it was still unclear whether there were other cis-regulatory elements for P2RX7, which might further contribute to related diseases. Allele-specific expression (ASE) is a robust and sensitive approach to identify the potential functional region in human genome. In the current study, we measured ASE on rs3751143 in lung tissues and observed a consistent excess of A allele over C (P = 0.001), which indicated that SNP(s) in linkage disequilibrium (LD) could regulate P2RX7 expression. By analyzing the 1000 genomes project data for Chinese, one SNP locating ~ 5 kb away and downstream of P2RX7, rs11615992, was disclosed to be in strong LD with rs3751143. The dual-luciferase assay confirmed that rs11615992 could alter target gene expression in lung cell line. Through chromosome conformation capture, it was verified that the region surrounding rs11615992 could interact with P2RX7 promoter and effect as an enhancer. By chromatin immunoprecipitation, the related transcription factor POU2F1 (POU class 2 homeobox 1) was recognized to bind the region spanning rs11615992. Our work identified a novel long-distance cis-regulatory SNP for P2RX7, which might contribute to multiple diseases.

18.
Oncol Rep ; 42(5): 1856-1868, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31432181

RESUMO

The present study aimed to determine the clinical significance and potential molecular mechanisms of C­C motif chemokine receptor (CCR) genes in patients with early­stage pancreatic ductal adenocarcinoma (PDAC). The transcriptomic, survival and clinical data of 112 patients with early­stage PDAC who underwent pancreaticoduodenectomy were obtained from The Cancer Genome Atlas. The prognostic values of the CCR genes involved in early­stage PDAC were evaluated using Kaplan­Meier analysis and the multivariate Cox proportional risk regression model, and the potential molecular mechanisms were determined using bioinformatics tools. The identified CCRs closely interacted with each other at both the gene and protein levels. High expression levels of CCR5 [adjusted P=0.012; adjusted hazard ration (HR)=0.478, 95% confidence interval (CI)=0.269­0.852], CCR6 (adjusted P=0.026; adjusted HR=0.527, 95% CI=0.299­0.927) and CCR9 (adjusted P=0.001; adjusted HR=0.374, 95% CI=0.209­0.670) were significantly associated with longer overall survival times in patients with early­stage PDAC. The contribution of CCR5, CCR6 and CCR9 to the outcome of early­stage PDAC was also demonstrated. Combined survival analysis of CCR5, CCR6 and CCR9 suggested that patients with high expression levels of these CCRs exhibited the most favorable outcomes. A prognostic signature was constructed in terms of the expression level of CC5, CCR6 and CCR9, and time­dependent receiver operating characteristic curves indicated that this signature was able to effectively predict the outcome of patients with early­stage PDAC. The potential molecular mechanisms of CCR5, CC6 and CCR9 in PDAC include its intersection of the P53, nuclear factor (NF)­κB, generic transcription, mitogen­activated protein kinase and STAT signaling pathways. Collectively, this highlights that CCR5, CCR6 and CCR9 are potential prognostic biomarkers for early­stage PDAC.

19.
Int J Oncol ; 55(3): 657-670, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322171

RESUMO

Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer after hepatocellular carcinoma. Antiangiogenic therapy has been administered to patients with CCA, but the benefits of this therapy remain unsatisfactory. Improved understanding of the molecular mechanisms underlying angiogenesis in CCA is required. In the present study, the expression of GATA­binding protein 6 (GATA6), lysyl oxidase­like 2 (LOXL2) and vascular endothelial growth factor A (VEGFA), in addition to the microvessel density (MVD), were evaluated by performing immunohistochemical staining of human CCA microarrays. The expression of GATA6/LOXL2 was associated with poor overall survival (P=0.01) and disease­free survival (P=0.02), and was positively associated with VEGFA expression (P=0.02) and MVD (P=0.04). In vitro, western blotting, reverse transcription­quantitative PCR analysis and ELISAs revealed that altered GATA6 and LOXL2 expression regulated the expression levels of secreted VEGFA. Co­immunoprecipitation demonstrated a physical interaction between GATA6 and LOXL2 in CCA cell lines, and the scavenger receptor cysteine­rich domain of LOXL2 interacted with GATA6, which regulated VEGFA mRNA expression and protein secretion, and promoted tube formation. In vivo analyses further revealed that GATA6/LOXL2 promoted VEGFA expression, angiogenesis and tumor growth. The GATA6/LOXL2 complex represents a novel candidate prognostic marker for stratifying patients with CCA. Drugs targeting this complex may possess great therapeutic value in the treatment of CCA.

20.
Am J Physiol Lung Cell Mol Physiol ; 317(4): L456-L463, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322430

RESUMO

SCGB1A1 (secretoglobin family 1A member 1) is an important protein for multiple pulmonary diseases, especially asthma, chronic obstructive pulmonary disease, and lung cancer. One single-nucleotide polymorphism (SNP) at 5'-untranslated region of SCGB1A1, rs3741240, has been suggested to be associated with reduced protein expression and further asthma susceptibility. However, it was still unclear whether there were other cis-regulatory elements for SCGB1A1 that might further contribute to pulmonary diseases. Allele-specific expression (ASE) is a novel approach to identify the functional region in human genome. In the present study, we measured ASE on rs3741240 in lung tissues and observed a consistent excess of G allele over A (P < 10-6), which indicated that this SNP or the one(s) in linkage disequilibrium (LD) could regulate SCGB1A1 expression. By analyzing 1000 Genomes Project data for Chinese, one SNP locating ~10.2 kb away and downstream of SCGB1A1, rs2509956, was identified to be in strong LD with rs3741240. Reporter gene assay confirmed that both SNPs could regulate gene expression in the lung cell. By chromosome conformation capture, it was verified that the region surrounding rs2509956 could interact with SCGB1A1 promoter region and act as an enhancer. Through chromatin immunoprecipitation and overexpression assay, the related transcription factor RELA (RELA proto-oncogene, NF-kB subunit) was recognized to bind the region spanning rs2509956. Our work identified a novel long-distance cis-regulatory SNP for SCGB1A1, which might contribute to multiple pulmonary diseases.

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