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1.
Heliyon ; 10(9): e29975, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38726171

ABSTRACT

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined. Objective: To reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS. Methods: The concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments. Results: In this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3+ T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue. Conclusion: The potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.

2.
Appl Opt ; 62(36): 9577-9582, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38108783

ABSTRACT

The thermal process of a (001) silicon wafer subjected to a continuous-wave (CW) laser and 100-10000 Hz pulsed laser irradiation is investigated experimentally and numerically. The temperature evolution of the spot center is measured using an infrared radiation pyrometer. The waveforms of the temperature evolution curves provide valuable information about melting, solidification, vaporization, and fracture. To gain a better understanding of the thermal process, a three-dimensional finite element model is established, and numerical simulations are conducted to analyze the temperature, stress, and dislocation field. The results show that the 10 kHz laser exhibits the highest heating efficiency before vaporization, but the lowest ablation efficiency after vaporization due to the shielding effect of vapor. The diffusion time of vapor is found to be more than 50 µs. Fracture occurs during 1 kHz laser irradiation. The motion of liquid may play a significant role, but it cannot be evidenced by a simulation due to complex dependence of material parameters on dislocation. This issue should be addressed as a priority in future studies.

3.
Adv Sci (Weinh) ; 10(20): e2300752, 2023 07.
Article in English | MEDLINE | ID: mdl-37162224

ABSTRACT

Promoting the activity of biological enzymes under in vitro environment is a promising technique for bioelectrocatalytic reactions, such as the conversion of carbon dioxide (CO2 ) into valuable chemicals, which is a promising strategy to address the environmental issue of CO2 in the atmosphere; however, this technique remains challenging. Herein, a nanocage structure for enzyme confinement is synthesized to enable the in situ encapsulation of formate dehydrogenase (FDH) in a porous metal-organic framework, which acts as a coenzyme and boosts the hybrid synergistic catalysis using enzymes. This study reveals that the synthesized FDH@ZIF-8 nanocage-structured hybrid (CSH) catalyst exhibits an improved catalytic ability of the enzymes and increases the hydrophobicity of the electrode and its affinity to CO2 . Thus, CSH can trap CO2 and control its microenvironments. The CSH catalyst boosts the conversion rate of CO2 to formic acid (HCOOH) to 28 times higher than that when using pure FDH. The in situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) spectra indicates that OCHO* is the key intermediate. Density functional theory (DFT) calculations show that CSH has extremely low overpotential and is particularly effective for producing formate. This protection architecture for enzymes considerably promotes their biological application under in vitro environments.


Subject(s)
Carbon Dioxide , Formates , Carbon Dioxide/chemistry , Catalysis , Formates/chemistry , Formate Dehydrogenases/chemistry
4.
Genomics Proteomics Bioinformatics ; 21(1): 127-149, 2023 02.
Article in English | MEDLINE | ID: mdl-36587654

ABSTRACT

Jasminum sambac (jasmine flower), a world-renowned plant appreciated for its exceptional flower fragrance, is of cultural and economic importance. However, the genetic basis of its fragrance is largely unknown. Here, we present the first de novogenome assembly of J. sambac with 550.12 Mb (scaffold N50 = 40.10 Mb) assembled into 13 pseudochromosomes. Terpene synthase (TPS) genes associated with flower fragrance are considerably amplified in the form of gene clusters through tandem duplications in the genome. Gene clusters within the salicylic acid/benzoic acid/theobromine (SABATH) and benzylalcohol O-acetyltransferase/anthocyanin O-hydroxycinnamoyltransferases/anthranilate N-hydroxycinnamoyl/benzoyltransferase/deacetylvindoline 4-O-acetyltransferase (BAHD) superfamilies were identified to be related to the biosynthesis of phenylpropanoid/benzenoid compounds. Several key genes involved in jasmonate biosynthesis were duplicated, causing an increase in copy numbers. In addition, multi-omics analyses identified various aromatic compounds and many genes involved in fragrance biosynthesis pathways. Furthermore, the roles of JsTPS3 in ß-ocimene biosynthesis, as well as JsAOC1 and JsAOS in jasmonic acid biosynthesis, were functionally validated. The genome assembled in this study for J. sambac offers a basic genetic resource for studying floral scent and jasmonate biosynthesis, and provides a foundation for functional genomic research and variety improvements in Jasminum.


Subject(s)
Jasminum , Jasminum/genetics , Jasminum/metabolism , Odorants , Cyclopentanes/metabolism , Flowers/genetics , Flowers/metabolism
5.
Chem Asian J ; 18(6): e202201305, 2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36696069

ABSTRACT

Developing a fast and highly active oxygen evolution reaction (OER) catalyst to change energy kinetics technology is essential for making clean energy. Herein, we prepare three-dimensional (3D) hollow Mo-doped amorphous FeOOH (Mo-FeOOH) based on the precatalyst MoS2 /FeC2 O4 via in situ reconstruction strategy. Mo-FeOOH exhibits promising OER performance. Specifically, it has an overpotential of 285 mV and a durability of 15 h at 10 mA cm-2 . Characterizations indicate that Mo was included inside the FeOOH lattice, and it not only modifies the electronic energy levels of FeOOH but also effectively raises the inherent activity of FeOOH for OER. Additionally, in situ Raman analysis indicates that FeC2 O4 gradually transforms into the FeOOH active site throughout the OER process. This study provides ideas for designing in situ reconstruction strategies to prepare heteroatom doping catalysts for high electrochemical activity.

6.
Talanta ; 251: 123789, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-35988345

ABSTRACT

Herein, lysozyme-encapsulated gold nanoclusters (AuNCs@Lzm, AuL) were favorably obtained by a simple and economical synthesis. The resulting AuL exhibits low toxicity, exceptional stability and intense red fluorescence at 650 nm, which can enter living cells and is mainly located in lysosomes. The AuL selectively and sensitively drove to detect folic acid (FA) with a detection limit as low as 0.19 nM based on the combination of the static quenching and the internal filtering effect. Interestingly, the fascinating results discovered that the AuL with ignorable toxicity was adsorbed from the intestine into the liver, and essentially was cleared from the body in 6 days without significant bioaccumulation in zebrafish. Furthermore, the hyaluronic acid (HA) coating AuLH exhibits remarkably targeted tumors towards MCF-7>HeLa > HepG2¼NIH/3T3≈DC, which attributed to the number of receptors expressed by the cells. All these advantages highlight that the AuL is a versatile nanoplatform for sensing, in vivo fluorescence imaging and tumor targeting.


Subject(s)
Gold , Metal Nanoparticles , Animals , Folic Acid , Hyaluronic Acid , Muramidase , Zebrafish
7.
Mater Horiz ; 9(7): 1962-1968, 2022 07 04.
Article in English | MEDLINE | ID: mdl-35583079

ABSTRACT

Directly targeting bacterial cells is the present paradigm for designing antimicrobial biomaterial surfaces and minimizing device-associated infections (DAIs); however, such pathways may create problems in tissue integration because materials that are toxic to bacteria can also be harmful to mammalian cells. Herein, we report an unexpected antimicrobial effect of calcium-doped titanium, which itself has no apparent killing effect on the growth of pathogenic bacteria (Pseudomonas aeruginosa, Pa, ATCC 27853) while presenting strong inhibition efficiency on bacterial colonization after fibrinogen adsorption onto the material. Fine X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy analyses reported calcium-dependent shifts of the binding energy in nitrogen and oxygen involved groups and wavenumbers in the amide I and II bands of the adsorbent fibrinogen, demonstrating that locally delivered calcium can react with the carboxy-terminal regions of the Aα chains and influence their interaction with the N-termini of the Bß chains in fibrinogen. These reactions facilitate the exposure of the antimicrobial motifs of the protein, indicating the reason for the surprising antimicrobial efficacy of calcium-doped titanium. Since protein adsorption is an immediate intrinsic step during the implantation surgery, this finding may shift the present paradigm on the design of implantable antibacterial biomaterial surfaces.


Subject(s)
Hemostatics , Titanium , Adsorption , Animals , Biocompatible Materials/chemistry , Calcium, Dietary , Fibrinogen/chemistry , Mammals/metabolism , Spectroscopy, Fourier Transform Infrared , Titanium/pharmacology
8.
Sensors (Basel) ; 21(19)2021 Sep 30.
Article in English | MEDLINE | ID: mdl-34640890

ABSTRACT

In recent years, machine learning for trading has been widely studied. The direction and size of position should be determined in trading decisions based on market conditions. However, there is no research so far that considers variable position sizes in models developed for trading purposes. In this paper, we propose a deep reinforcement learning model named LSTM-DDPG to make trading decisions with variable positions. Specifically, we consider the trading process as a Partially Observable Markov Decision Process, in which the long short-term memory (LSTM) network is used to extract market state features and the deep deterministic policy gradient (DDPG) framework is used to make trading decisions concerning the direction and variable size of position. We test the LSTM-DDPG model on IF300 (index futures of China stock market) data and the results show that LSTM-DDPG with variable positions performs better in terms of return and risk than models with fixed or few-level positions. In addition, the investment potential of the model can be better tapped by the reward function of the differential Sharpe ratio than that of profit reward function.


Subject(s)
Investments , Memory, Long-Term , Forecasting , Machine Learning , Policy
9.
Water Res ; 206: 117740, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34688096

ABSTRACT

A sequential cathode-anode cascade mode bioelectrochemical system (BES) was designed and developed to achieve the "self-degradation" of 2-chlorophenol (2-CP). With the cooperation of cathode and anode, the electrons supplied for the cathode 2-CP dechlorination come from its own dechlorinated product in the anode, phenol. Separate degradation experiments of cathode 2-CP and anode phenol were firstly conducted. The optimum concentration ratio of anode acetate to phenolic compound (3.66/1.56) and the phenolic compound degradation ability of BES were investigated. With the formation of the bioanode able to degrade phenol, the sequential cathode-anode cascade mode BES was further developed, where 2-CP could achieve sequential dechlorination and ring-cleavage degradation. When applied voltage was 0.6 V and cathode influent pH was 7, 1.56 mM 2-CP reached 80.15% cathode dechlorination efficiency and 58.91% total cathode-anode phenolic compounds degradation efficiency. The bioanodes played a decisive role in BES. Different operating conditions would affect the overall performance of BES by changing the electrochemical activity and microbial community structure of the bioanodes. This study demonstrated the feasibility of the sequential cathode-anode cascade mode BES to degrade 2-CP wastewater and provided perspectives for the cooperation of cathode and anode, aiming to explore more potential of BES in wastewater treatment field.


Subject(s)
Bioelectric Energy Sources , Chlorophenols , Water Purification , Electrodes , Wastewater
10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(3): 425-433, 2021 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-34180187

ABSTRACT

Motor imaging therapy is of great significance to the rehabilitation of patients with stroke or motor dysfunction, but there are few studies on lower limb motor imagination. When electrical stimulation is applied to the posterior tibial nerve of the ankle, the steady-state somatosensory evoked potentials (SSSEP) can be induced at the electrical stimulation frequency. In order to better realize the classification of lower extremity motor imagination, improve the classification effect, and enrich the instruction set of lower extremity motor imagination, this paper designs two experimental paradigms: Motor imaging (MI) paradigm and Hybrid paradigm. The Hybrid paradigm contains electrical stimulation assistance. Ten healthy college students were recruited to complete the unilateral movement imagination task of left and right foot in two paradigms. Through time-frequency analysis and classification accuracy analysis, it is found that compared with MI paradigm, Hybrid paradigm could get obvious SSSEP and ERD features. The average classification accuracy of subjects in the Hybrid paradigm was 78.61%, which was obviously higher than the MI paradigm. It proves that electrical stimulation has a positive role in promoting the classification training of lower limb motor imagination.


Subject(s)
Brain-Computer Interfaces , Electric Stimulation , Electroencephalography , Humans , Imagination , Lower Extremity , Movement
11.
Microsc Res Tech ; 84(2): 368-375, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32946130

ABSTRACT

Cetoniinae is one of the showiest scarab groups, exhibiting bright-metallic body colors, and usually attract great attention from entomologists and amateur collectors. Larvae of Cetoniinae show dramatically diversity on morphology and living habits. Although being considered one of the best-studied groups of Scarabaeidae, larvae have been described for less than 5% species to the known Cetoniinae. In this study, the final instar larva of Lasiotrichius succinctus hananoi was described using scanning electron microscopy. The larvae are peculiar for bearing a haptomeral process dividing 10 spines into two groups: six on the left side, four on the right side, different from the previous descriptions on L. succinctus (Pallas, 1781). The morphological differences under SEM imply the further requirement of taxonomic revision in Lasiotrichius. Both advantage and disadvantage of SEM utilizing in larval descriptions were briefly discussed.


Subject(s)
Coleoptera/anatomy & histology , Coleoptera/ultrastructure , Microscopy, Electron, Scanning , Animals , Larva/anatomy & histology , Larva/ultrastructure
12.
Tree Physiol ; 41(4): 571-588, 2021 04 08.
Article in English | MEDLINE | ID: mdl-32159802

ABSTRACT

Seed dormancy is crucial for plant survival and prevents seed germination out of season. However, little is known about the regulatory mechanism of morphophysiological seed dormancy. Ginkgo biloba L. is one of the most ancient gymnosperms, and the completion of seed germination in this species requires cold and moist stratification. Here, we observed that at the mature seed stage, the embryo was not fully developed in G. biloba seeds. During dormancy stages, the length and weight of the embryo significantly increased, and nutrients accumulated in cotyledons. We further found that abscisic acid (ABA), gibberellic acid (GA), cytokinin and ethylene were integrated in the seed dormancy induction, maintenance and release processes, and GA biosynthesis and signaling transduction specifically act on dormancy release. Combining mRNA and miRNA analyses, we demonstrated that miRNA156 is involved in the regulation of morphophysiological dormancy. Our analyses revealed that G. biloba seed dormancy belongs to the ancestral morphophysiological dormancy type, which is not only regulated by the balance of ABA/GA, but also by other hormones associated with embryo morphological development, as well as genes related to embryo differentiation and development. These findings helped with elucidating the comprehensive regulatory network of morphophysiological dormancy in tree seeds.


Subject(s)
MicroRNAs , Plant Dormancy , Abscisic Acid , Gene Expression Regulation, Plant , Germination , Ginkgo biloba/genetics , MicroRNAs/genetics , Plant Dormancy/genetics , Plant Growth Regulators , Seeds/genetics , Transcriptome
13.
Microsc Res Tech ; 84(5): 921-928, 2021 May.
Article in English | MEDLINE | ID: mdl-33231351

ABSTRACT

Melolonthinae are the largest subfamily of Scarabaeidae, considered as serious pests for their larvae attacking plant roots and tubers. The edaphic larvae are difficult to be identified because the study on larval taxonomy is far from satisfactory. In this study, multivoltine white grubs Melolontha incana (Motschulsky, 1853) were investigated using light and scanning electron microscopy, in order to provide more morphological characters for the pest identification. The white grubs are atypical for the epipharynx bearing 14 heli arranged in two rows; the mandible is furnished with a patch of minute granules; the maxilla is equipped with 18 acute stridulatory teeth arranged in line; each femur and tibiotarsus is furnished ventrally with a cluster of fossorial setae. The morphological comparisons with the other melolonthine species were provided. The adaptative relationship between the morphological feature and the multivoltine life history were briefly discussed.


Subject(s)
Coleoptera , Animals , Larva
14.
Appl Opt ; 59(23): 6803-6808, 2020 Aug 10.
Article in English | MEDLINE | ID: mdl-32788770

ABSTRACT

COMSOL Multiphysics was employed to establish a dislocation model based on the Alexander and Haasen (AH) model, the heat conduction equation, and Hooke's law for calculating the dislocation distribution of germanium (Ge) under laser irradiation. The numerical simulation results were obtained. A continuous 1080 nm laser was utilized to ablate the monocrystalline Ge wafers to validate the model. The experimental results show that no surface damage appears until the irradiances go up to 234W/cm2 for 100 ms laser ablation. This is consistent with the numerical findings. The initiation times of surface damage by the experiments at 234W/cm2 and above agree well with the numerical results, which means that the model can efficiently predict the dislocation field.

15.
Plant Signal Behav ; 14(12): 1674606, 2019.
Article in English | MEDLINE | ID: mdl-31595821

ABSTRACT

Long non-coding RNAs (lncRNAs) are important regulatory factors for plant growth and development. Despite this, little is known about the regulatory interactions of lncRNAs with mRNA during embryo development. Here, we used a bioinformatics genome-wide approach to identify lncRNAs involved in embryo development of Ginkgo biloba, based on RNA sequencing datasets from G. biloba embryos during early, middle, late developmental stages. In total, 2326 lncRNAs were identified in the G. biloba embryos, of which 1307 and 1019 could be classified as long intergenic non-coding RNAs and antisense lncRNAs, respectively. Among them, a total of 657 differentially expressed lncRNAs were identified in the different developmental stages of the G. biloba embryos. Based on the functional annotation of potential target genes of lncRNAs, 50, 33, and 76 lncRNAs were predicted to target genes involved in plant hormone signal transduction, plant hormone biosynthesis, and circadian rhythm regulation, respectively. A lncRNA (17)-miRNA (25)-PCgene (52) network was constructed for the G. biloba embryo. Three lncRNAs (lnc000823, lnc002072, lnc000866) were predicted as target mimics of miR159, which targeted two transcription factors with variety of functions, Gb_11536 (MYB33) and Gb_23921 (MYB101). The data generated in this study provide a better understanding of the roles of lncRNAs in embryo development of G. biloba and plants in general.


Subject(s)
Ginkgo biloba/embryology , Ginkgo biloba/genetics , RNA, Long Noncoding/genetics , Seeds/genetics , Circadian Rhythm/genetics , Down-Regulation/genetics , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , Gene Regulatory Networks , Plant Growth Regulators/biosynthesis , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/genetics , Up-Regulation/genetics
16.
Micron ; 120: 10-16, 2019 05.
Article in English | MEDLINE | ID: mdl-30742968

ABSTRACT

Lucanidae have long received great attention for their adults. However, differentiating between the larvae of stag beetles is difficult and remains unsatisfactorily resolved due to the microscopic features separating groups. In the current study, the larvae of Prismognathus dauricus Motschulsky, 1860 were investigated using light and scanning electron microscopy. The larvae of P. dauricus are atypical for the following characters: i) the epipharynx possesses anteriorly eleven protophoba arranged in a semi-round line; ii) the par stridens consists of 31 ± 0.7 (N = 10) subconical teeth arranged in a slightly curved, longitudinal row; iii) the plectrum is composed of 60 ± 1.4 (N = 10) carinae; iv) the claws of thoracic legs are apically blunt and bear four setae. Moreover, the size arrangement of the larval spiracles also provides valuable taxonomic information. Our SEM study reveals larval ultramorphological characters useful for identification of this species for the first time.

17.
Appl Opt ; 56(17): 4900-4904, 2017 Jun 10.
Article in English | MEDLINE | ID: mdl-29047632

ABSTRACT

Slip phenomenon on a (001) silicon surface under 1064 nm laser ablation was studied by experiments and simulations. The surface morphologies of the silicon wafers after laser irradiation were observed using an optical microscope. The slip patterns showed that slip that occurred before melting was responsible for a low-quality ablation surface. The slip damage was predicted by a three-dimensional finite element model based on heat transfer and thermoelasticity theory. The judging criterion of slip was explained in detail. The numerical results gave a better understanding of slip phenomenon in experiments. It is shown that low laser irradiances cause slip and high laser irradiances are helpful in preventing slip. The threshold irradiance is ∼1 MW/cm2. Lasers with higher irradiance are essential to obtain a slip-free ablation on a (001) silicon surface.

18.
Appl Opt ; 56(17): 5060-5067, 2017 Jun 10.
Article in English | MEDLINE | ID: mdl-29047654

ABSTRACT

The surface damage morphologies of single-crystal silicon induced by a combined pulse laser (CPL) and a single millisecond laser are investigated, respectively. The CPL includes a millisecond (ms) laser superposed by a nanosecond (ns) laser. Inspected by an optical microscope, it was found that the surface damage was more serious when the sample was irradiated by the CPL than by a single ms laser with the same incident laser energy. Besides surface cleavage, obvious ablation and fold areas were discovered by CPL irradiation. A two-dimensional spatial axisymmetric model was established to assess the difference between single ms laser and CPL irradiation and explain the generation mechanism of the different surface damage. This was attributed to the preheating effect by the ms laser and the surface damage caused by the ns laser.

19.
Int J Colorectal Dis ; 27(4): 437-45, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22076613

ABSTRACT

PURPOSE: Increased expression of tissue factor (TF) is associated with tumor invasion and metastasis in human colorectal cancer. We have previously observed that TF/FVIIa upregulates matrix metalloproteinase-7 (MMP-7) expression at the transcriptional level in colon cancer cells. MMP-7 overexpression is believed to play an important role in tumor invasion and metastasis. The aim of this study is to elucidate the molecular mechanisms by which TF/FVIIa induced MMP-7 expression and cell invasion in vitro. METHODS: Reverse transcription polymerase chain reaction, Western blot, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to determine the potential mechanism and signaling pathways by which TF/FVIIa induced MMP-7 expression and cell invasion in LoVo cells. Small interfering RNA (siRNA) and cell invasion assay was used to examine whether blocking c-Fos expression could abolish FVIIa-mediated upregulation of MMP-7 and cell invasion in vitro. RESULTS: The results showed that FVIIa induced the upregulation of MMP-7 both at the mRNA and protein levels in a time- and dose-dependent manner and increased the invasive behavior of LoVo cells. FVIIa enhanced the promoter activity of MMP-7, and the activator protein-1 (AP-1) binding site was responsible for the activation. Site mutation of the AP-1 binding site in the promoter almost completely abolished FVIIa-mediated response. Furthermore, ChIP assay confirmed that FVIIa promoted the direct binding of c-Fos with the MMP-7 promoter in vivo. FVIIa also induced the expression and nuclear accumulation of the AP-1 subunit c-Fos. siRNA-mediated knockdown of c-Fos eliminated FVIIa-stimulated MMP-7 expression and cell migration in vitro. In addition, selective mitogen-activated protein kinase (MAPK) kinase (MEK1/2) inhibitor (PD98059) and p38 MAPK inhibitor SB203580 suppressed MMP-7 upregulation induced by FVIIa. CONCLUSIONS: Our data suggest that a novel TF/FVIIa/MAPK/c-Fos/MMP-7 axis plays an important role in modulating the invasion of colon cancer cells and blockage of this pathway holds promise to treat colon cancer metastasis.


Subject(s)
Colonic Neoplasms/enzymology , Extracellular Signal-Regulated MAP Kinases/metabolism , Factor VIIa/metabolism , Matrix Metalloproteinase 7/genetics , Proto-Oncogene Proteins c-fos/metabolism , Thromboplastin/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Binding Sites , Cell Line, Tumor , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Enzyme Activation , Gene Expression Regulation, Neoplastic , Humans , MAP Kinase Signaling System , Matrix Metalloproteinase 7/metabolism , Neoplasm Invasiveness , Promoter Regions, Genetic/genetics , Protein Binding , Proto-Oncogene Proteins c-jun/metabolism , Time Factors , Transcription Factor AP-1/metabolism , Up-Regulation/genetics
20.
Chin Med J (Engl) ; 123(24): 3559-65, 2010 Dec.
Article in English | MEDLINE | ID: mdl-22166631

ABSTRACT

BACKGROUND: Blood coagulation factor VII (FVII) is physiologically synthesized in the liver and released into the blood. Binding of FVII to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FVII extrahepatically. However, little is known about FVII and CRC. We therefore hypothesized that CRC cells may synthese FVII, leading to tumor invasion and metastasis. METHODS: We detected the expression of FVII protein in 55 CRC specimens by immunohistochemical staining. The FVII mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FVIIa complex Western blotting assay. RESULTS: Extrahepatic synthesis of FVII was detected in the cytoplasm of 32 (58.2%) CRC specimens by immunohistochemistry, but not in normal mucosa. Liver metastasis (P = 0.003) and TNM staging (P = 0.005) were significantly correlated with FVII antigen expression. The positive ratios in stages I, II, III and IV were 33.3%, 40.0%, 52.4% and 87.5%, respectively. The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33 ± 2.88 vs. 1.47 ± 0.51, P = 0.03). Ectopic FVIIa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FVIIa complex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9 (4.7-fold) in a time-dependent and dose-dependent manner. CONCLUSIONS: Extrahepatic synthesis of FVII by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream effectors of TF/FVIIa signaling, facilitate the development of metastasis in colon cancer.


Subject(s)
Colorectal Neoplasms/pathology , Factor VII/biosynthesis , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Movement , Colorectal Neoplasms/metabolism , Factor VII/analysis , Factor VII/genetics , Female , Humans , Immunohistochemistry , Liver Neoplasms/secondary , Male , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 9/analysis , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , RNA, Messenger/analysis , Thromboplastin/physiology
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