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1.
Thorac Cancer ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571407

RESUMO

BACKGROUND: Taxane-based chemotherapy is widely used in lung cancer. ABCB1 have a role in the prediction of treatment response and toxicity of chemotherapy in solid tumors. In this retrospective study, we investigated ABCB1 polymorphism on response and toxicity in taxane-based chemotherapy in lung cancer patients. METHODS: A total of 122 lung cancer patients who received taxane-based chemotherapy were included in this study. Fluorescence in situ hybridization (FISH) was used for ABCB1 polymorphism detection. Turbidimetric inhibition immunoassay was used for pharmacokinetic analysis. Statistical analysis was performed using SPSS 20.0. RESULTS: The frequency of the ABCB1 2677 site TT/TG/GG genotype was 32.8%, 43.4% and 23.8%, respectively and the frequency of the 3435 sites the TT/TC/CC genotype was 13.9%, 44.3% and 41.8%, respectively. The occurrence of neurotoxicity was higher in patients who had ABCB1 3435 site mutation (TT 88.2%, TC 22.2%, CC 21.6% P = 0.004). There was no significant difference between ABCB1 genotypes with regard to other chemotherapy-induced toxicity. For non-small cell lung cancer (NSCLC) patients, those harboring ABCB1 2677 and 3435 site wild-type patients had longer median progression-free survival (PFS) in the paclitaxel subgroup (3435 site: TT 3.87 vs. TC 9.50 vs. CC 14.13 months; P < 0.001; 2677 site: TT 4.37 vs. TG 9.73 vs. GG 12.1 months; P = 0.013). The area under the concentration-time curve (AUC) of 20 patients treated with docetaxel increased for ABCB1 mutation subgroups. CONCLUSION: ABCB1 mutation is associated with higher neurotoxicity of taxane-based chemotherapy. It also predicts shorter PFS for NSCLC in paclitaxel-based treatment.

2.
Biomed Pharmacother ; 120: 109478, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568987

RESUMO

Resistance to chemotherapeutic agents is a major cause of treatment failure in patients with oral cancer. Proton pump inhibitors (PPIs), essentially H+-K+-ATPase inhibitors which are currently used in the treatment of acid related diseases, have demonstrated promising antitumor and chemo-sensitizing efficacy. The main purpose of the present study was to investigate whether pantoprazole (PPZ, one of PPIs) could increase the sensitivity of chemoresistant oral epidermoid carcinoma cells (KB/V) to vincristine (VCR) and elucidate the underlying action mechanism. Results showed that combination treatment of PPZ and VCR synergistically inhibited the proliferation of KB/V cells in vitro and in vivo. Furthermore, administration of PPZ and VCR not only induce apoptosis and G2/M phase arrest in KB/V cells but also suppress the migration and invasion of KB/V cells. The mechanism underlying synergistic anti-tumor effect of PPZ and VCR was related to the inhibition of the function and expression of P-glycoprotein (P-gp) and the down-regulation of EGFR/MAPK and PI3K/Akt/mTOR signaling pathways in KB/V cells. Additionally, we observed that PPZ treatment induced an increase in lysosomal pH and inhibited the activity of lysosomal enzyme acid phosphatase in KB/V cells, which could functionally reduce the sequestration of VCR in lysosomes and sensitized KB/V cells to VCR. In conclusion, our study demonstrated that PPZ could be included in new combined therapy of human oral cancer (especially on VCR-resistant therapy) together with VCR.

3.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2914-2925, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602833

RESUMO

To systematically review the efficacy and safety of Huoxiang Zhengqi Pills combined with Western medicine in the treatment of acute gastroenteritis. Four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,EMbase) were systematically and comprehensively searched from the database establishment to April 2019 to collect the randomized controlled trials( RCTs) about the treatment of acute gastroenteritis with Huoxiang Zhengqi Pills combined with Western medicine. Two investigators independently performed literature screening,data extraction and bias risk assessment. Rev Man 5. 3 software was used for data analysis. A total of 316 articles were retrieved and finally 44 studies were included in this study,involving 4153 patients. The overall quality of the included studies was generally low. Meta-analysis results showed that in the total clinical effective rate,Huoxiang Zhengqi Pills combined with conventional treatment or norfloxacin tablets was superior to conventional treatment or norfloxacin tablets alone. In terms of the time for improving clinical symptoms,Huoxiang Zhengqi Pills combined with conventional treatment or norfloxacin tablets could better relieve fever than conventional treatment or norfloxacin tablets alone. In terms of incidence of adverse reactions,there was no statistical difference between Huoxiang Zhengqi Pills combined with conventional treatment and conventional treatment alone. Other outcome measures were affected by various factors( such as inclusion of only 1 study or excessive heterogeneity among studies) and could not be concluded. Due to the limitations of the quality and quantity of included studies,this conclusion still needs to be verified by more high quality researches.

4.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3129-3134, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602863

RESUMO

The best time of tumor intervention is before the formation of tumor. However,due to the limited number of tumor cells,it is difficult to quantify tumor cells and immunity by the current methods available( such as CTC,ct DNA). This affects the tumor prevention in this period,and the in-depth detection,intervention and evaluation of traditional Chinese medicine( TCM)( tumor) prevention. Due to the limitations of the current detection,the evaluation system turns to detect tumor neoantigen-specific CTL( naCTL) that are directly relating to tumor cells and proliferate to high order of magnitudes after activation,and immune repertoire( TCR/BCR/HLA) effective diversity,introduces immune checkpoints,uses information of " disease" in Western medicine and " syndrome" in TCM( prevention),and sets up a multi-dimensional statistical immunity model using a variety of data analysis and related algorithms. This model can amplify the ultra-early information of tumor,indirectly evaluate the quantity and status of tumor cells,and provide quantitative measurement and new evaluation methods for the normalization of immunity and TCM( tumor) prevention. This model is not only one of important evaluation methods for resisting tumor immunity and treating TCM( tumor) prevention,but also will reveal the scientific connotation of TCM syndrome from the perspective of immunology.

5.
Food Chem ; 306: 125560, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31590002

RESUMO

To control the oxidation in chicken fat by immobilized lipoxygenase (LOX), Maillard reaction products (MRPs) with chicken flavor were prepared and analyzed for flavor mechanism. >50% activity of immobilized LOX was retained after repeated use for five times or five weeks. The oxidized chicken fats were prepared by thermal, free LOX, and immobilized LOX treatments. After addition of chicken fats, Maillard reaction produced more aliphatic aldehydes and alcohols (126.0-839.5 ng/g and 493.5-2332.4 ng/g, respectively) which resulted in noticeable enhanced reaction, but the content of sulfur compounds such as thiols and thiophenes decreased significantly (870.8-1233.9 ng/g and 1125.0-2880.3 ng/g, respectively), and the structure of sulfur compounds could easily form alkyl side chains. However, there was no significant difference in sensory and flavors between oxidized chicken after treatments, which may be related to oxidized degree. The mechanism was proposed or aromatic effects of oxidized chicken fat on flaxseed derived MRPs.

6.
Thorac Cancer ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574576

RESUMO

BACKGROUND: Thymic carcinomas (TCs) are rare aggressive tumors with no standard first-line treatment. This study was conducted to determine the optimal chemotherapy regimen for advanced TC. METHODS: This retrospective study included 67 patients treated for stage IV TC in 2006-2015. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS) with different chemotherapy regimens. Multivariate Cox regression analysis was used to identify factors associated with PFS, including metastatic status, radiotherapy post-chemotherapy, primary lesion resection before chemotherapy, and chemotherapy regimen. RESULTS: A total of 36 patients received a paclitaxel-platinum regimen, 31 received a gemcitabine-platinum regimen, 14 underwent primary lesion resection, and 33 underwent radiotherapy. ORR was 31% (11/36) and 29% (9/31) in the paclitaxel-platinum and gemcitabine-platinum groups, respectively (P = 0.890). Median PFS, one-year PFS rate, and two-year PFS rate were 7.0 months, 26%, and 6% with paclitaxel-platinum treatment and 12 months, 48%, and 24% with gemcitabine-platinum treatment (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 18.0 months, 57%, and 33% with surgical resection and 7.3 months, 31%, and 7% without resection (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 13.0 months, 52%, and 20% with radiotherapy and 4.3 months, 22%, and 7% without radiotherapy (log-rank P = 0.001). In multivariate analysis, metastatic status (hazard ratio [HR], 0.33, P = 0.004), surgical resection (HR, 0.32; P = 0.004), and radiotherapy (HR, 0.32; P < 0.001) were associated with superior PFS. CONCLUSIONS: Both gemcitabine-platinum and paclitaxel-platinum regimens were efficacious for advanced TC. Primary lesion resection and radiotherapy may also benefit selected patients.

7.
Nat Commun ; 10(1): 4530, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594940

RESUMO

A phase transition is often accompanied by the appearance of an order parameter and symmetry breaking. Certain magnetic materials exhibit exotic hidden-order phases, in which the order parameters are not directly accessible to conventional magnetic measurements. Thus, experimental identification and theoretical understanding of a hidden order are difficult. Here we combine neutron scattering and thermodynamic probes to study the newly discovered rare-earth triangular-lattice magnet TmMgGaO4. Clear magnetic Bragg peaks at K points are observed in the elastic neutron diffraction measurements. More interesting, however, is the observation of sharp and highly dispersive spin excitations that cannot be explained by a magnetic dipolar order, but instead is the direct consequence of the underlying multipolar order that is "hidden" in the neutron diffraction experiments. We demonstrate that the observed unusual spin correlations and thermodynamics can be accurately described by a transverse field Ising model on the triangular lattice with an intertwined dipolar and ferro-multipolar order.

8.
Diabetes Ther ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595458

RESUMO

INTRODUCTION: Diabetic foot ulcers develop with deviations in the distribution of plantar pressure. It is difficult to interpret any alteration in plantar pressure under different conditions of type 2 diabetes mellitus (T2DM). The aim of this study was to gain a better insight into the variations in plantar pressure with increased duration of diabetes. METHODS: Plantar pressure was examined in 1196 participants with or without T2DM. Subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) were assigned to control groups, and those with T2DM were divided into five groups according to diabetes duration (< 2 years, 2-5 years, 5-10 years, 10-15 years, and > 15 years). The clinical characteristics, plantar peak pressure, and pressure-time integral (PTI) were compared among the seven study groups, and factors associated with peak pressure and the PTI were analyzed. RESULTS: At the hallux, peak pressure exhibited an upward trend in patients with T2DM within 5 years of diabetes duration, followed by a distinct downward slope with further progression of the disease (trend analysis, p < 0.05). An uneven distribution of peak pressure was found at other locations, but this unevenness was ultimately lower than that in the two control groups (p < 0.05). No obvious trend was noted for PTI among patients with different diabetes duration; however, those with diabetes for > 10 years manifested a significantly sharper increase in the PTI at the metatarsus (11.63 Ns/cm2, p < 0.05) and heel (14.12 Ns/cm2, p < 0.05) than at the hallux (8.76 Ns/cm2). A fluctuation in the PTI was also detected at the hallux and midfoot of diabetes patients, which was broadly flat when compared with that of the two control groups. The stepwise multiple regression analysis revealed that the variation in plantar pressure was independently associated with age, body mass index, and vibration perception threshold (VPT) (p < 0.05). CONCLUSIONS: There would appear to be an association between longer diabetes duration and decreased peak pressure for the hallux, suggesting that individuals with diabetes for > 10 years will have an increased PTI for the metatarsus and heel. The reduced pressure on the hallux is believed to be transferred to the metatarsus. Age, BMI, and VPT are distinct risk factors of abnormal plantar pressure.

9.
J Mater Chem B ; 7(39): 6035-6047, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545329

RESUMO

Silicon nitride (SN) with good osteoconductivity has been introduced as an implantable biomaterial for joint replacement and interbody fusion devices. In this study, SN was coated on a polyetheretherketone (PEEK) surface by inductively coupled plasma-enhanced chemical vapor deposition (ICPECVD). The results showed that a dense coating (thickness of about 500 nm) of amorphous SN was closely combined with a PEEK substrate (PKSN) with a binding strength of 6.88 N. In addition, the coating surface showed hierarchical nanostructures containing many spherical bulges (sizes about 150 nm), which were composed of many small humps (sizes about 10 nm). Moreover, the roughness, hydrophilicity, surface energy, surface charge and adsorption of bovine serum albumin (BSA) of PKSN were obviously higher than those of PEEK. After immersion into simulated body fluid (SBF), the Si ions were gradually released from PKSN into SBF and a weak alkaline environment was created. Antibacterial experiments showed that PKSN exhibited a greater antibacterial activity than that of PEEK. Moreover, compared with PEEK, PKSN significantly promoted adhesion, proliferation, differentiation and expression of osteogenic related genes of the rat bone marrow stromal cells (rBMSCs). In conclusion, the SN coating of PKSN with hierarchical nanostructures exhibited excellent antibacterial activity and cytocompatibility, which would make it a great candidate for orthopedic applications.

10.
Nanotechnology ; 30(49): 495201, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31476738

RESUMO

By means of density functional theory calculations, we successfully predict two stable 2D triangular borophenes, namely B3H and B6O. Our results indicate that B3H is a Dirac material and its cone point is located at the K point of the Brillouin zone (BZ). B6O is identified as having a node-line ring and Dirac cones together. Its node-line ring formed by the intersection of the extended energy band from the two Dirac cones located on K point. This modified 2D borophene has great thermal and dynamic stability due to the electron transfer from the triangular boron lattice to the O atoms. The electronic structure of B6O nanofilm demonstrates novel properties such as two Dirac cones, more than 1.3 eV linear dispersion bands at some points of the BZ, as well as excellent transport properties for the extremely high mobility brought by the combination of the node-line semimetal and Dirac cones. Our study may motivate potential applications of 2D materials in nanoelectronics.

11.
J Phys Chem Lett ; : 6055-6060, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31553182

RESUMO

Applications of metallic glass thin films (MGTFs) in the optical area have seldom been reported. We successfully design and fabricate a broadband and durable absorber with MGTFs. It is found that the absorber, with a total thickness of only ∼230 nm smaller than the light wavelength, exhibits excellent performance, that is, an average absorption of >90% from the visible to the near-infrared range (500-1300 nm). This is of significance for the optical application of MGTFs with the potential for large-scale fabrication using superplastic deformation in the supercooled liquid region of MGTFs.

12.
JCI Insight ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31557131

RESUMO

Transcriptomic profiling classifies pancreatic ductal adenocarcinoma (PDAC) into several molecular subtypes with distinctive histological and clinical characteristics. However, little is known about the molecular mechanisms that define each subtype and their correlation with clinical outcome. Mutant KRAS is the most prominent driver in PDAC, present in over 90% of tumors, but the dependence of tumors on oncogenic KRAS signaling varies between subtypes. In particular, squamous subtype are relatively independent of oncogenic KRAS signaling and typically display much more aggressive clinical behavior versus progenitor subtype. Here, we identified that YAP1 activation is enriched in the squamous subtype and associated with poor prognosis. Activation of YAP1 in progenitor subtype cancer cells profoundly enhanced malignant phenotypes and transformed progenitor subtype cells into squamous subtype. Conversely, depletion of YAP1 specifically suppressed tumorigenicity of squamous subtype PDAC cells. Mechanistically, we uncovered a significant positive correlation between WNT5A expression and the YAP1 activity in human PDAC, and demonstrated that WNT5A overexpression led to YAP1 activation and recapitulated YAP1-dependent but Kras-independent phenotype of tumor progression and maintenance. Thus, our study identifies YAP1 oncogene as a major driver of squamous subtype PDAC and uncovers the role of WNT5A in driving PDAC malignancy through activation of the YAP pathway.

13.
Genes Dev ; 33(19-20): 1361-1366, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31488580

RESUMO

The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential druggable target for this intractable disease.

14.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 311-314, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31544415

RESUMO

OBJECTIVE: To understand the epidemiological features and changing patterns of intestinal parasitic diseases in Jiangxi Province from 1989 to 2014, so as to provide scientific evidence for formulating the preventive and control strategy for intestinal parasitic diseases. METHODS: The data regarding the status of intestinal parasitic diseases in Jiangxi Province were captured from the 1989 national survey on the distribution of human parasites in China and the 2014 national survey on major human parasitic diseases in China, and the status of human intestinal parasite infections was compared between the two surveys in Jiangxi Province. RESULTS: The prevalence rate of human intestinal parasite infections was 79.59% and 9.64% in Jiangxi Province in 1989 and 2014, with a decline rate of 87.89% during the 25-year period (χ2 = 30 870.5, P < 0.01). There were 24 and 20 species of human intestinal parasites detected in Jiangxi Province in 1989 and 2014, respectively, with totally 26 species detected during the two surveys. In Jiangxi Province, the 3 most highly prevalent human intestinal parasites included Ascaris lumbricoides (71.06%), hookworm (17.61%) and Enterobius vermicularis (17.59%) in 1989, and E. vermicularis (13.73%), hookworm (4.66%), whipworm (0.95%) in 2014. A higher rate of human intestinal parasite infections was found in females than in males in both surveys in Jiangxi Province (P < 0.01), and the prevalence of human intestinal parasite infections reduced by 82.50% to 95.31% in different age groups in Jiangsu Province during the 25-year period. CONCLUSIONS: The prevalence of human intestinal parasite infections shows a remarkable decline tendency in Jiangxi Province, and soil-transmitted nematodes remain the main species of human intestinal parasites in Jiangxi Province.


Assuntos
Enteropatias Parasitárias , Ancylostomatoidea , Animais , Ascaris lumbricoides , China/epidemiologia , Enterobius , Feminino , Humanos , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/parasitologia , Masculino , Prevalência , Inquéritos e Questionários
15.
Br J Cancer ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31523058

RESUMO

BACKGROUND: Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. METHODS: Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate. RESULTS: Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand-foot syndrome, increased L-gamma-glutamyltransferase. CONCLUSIONS: Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted. TRIAL REGISTRATION: NCT02945852.

16.
Sensors (Basel) ; 19(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540538

RESUMO

Aiming at the problem of multiple-source direction of arrival (DOA) tracking in impulse noise, this paper models the impulse noise by using the symmetric α stable (SαS) distribution, and proposes a DOA tracking algorithm based on the Unscented Transform Multi-target Multi-Bernoulli (UT-MeMBer) filter framework. In order to overcome the problem of particle decay in particle filtering, UT is adopted to select a group of sigma points with different weights to make them close to the posterior probability density of the state. Since the α stable distribution does not have finite covariance, the Fractional Lower Order Moment (FLOM) matrix of the received array data is employed to replace the covariance matrix to formulate a MUSIC spatial spectra in the MeMBer filter. Further exponential weighting is used to enhance the weight of particles at high likelihood area and obtain a better resampling. Compared with the PASTD algorithm and the MeMBer DOA filter algorithm, the simulation results show that the proposed algorithm can more effectively solve the issue that the DOA and number of target are time-varying. In addition, we present the Sequential Monte Carlo (SMC) implementation of the UT-MeMBer algorithm.

17.
Oncol Rep ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31545502

RESUMO

As an important regulator of neddylation, neural precursor cell expressed developmentally downregulated 8 (Nedd8)­conjugating enzyme E2M (UBE2M) mediates cullin neddylation. Upregulation of the neddylation pathway is associated with tumor progression in intrahepatic cholangiocarcinoma (ICC). The present study was designed to assess the effects of Nedd8­conjugating enzyme UBE2M knockdown on intrahepatic cholangiocarcinoma cells, and to determine the potential underlying mechanisms. UBE2M and associated protein expression levels were determined via immunohistochemistry and western blotting. ICC cells were transfected with short hairpin RNA to knockdown UBE2M expression. Cell Counting Kit­8 and colony formation assays, and xenograft experiments were used to examine cell viability and colony survival in vitro, and tumor formation in vivo. Survival was evaluated using Kaplan­Meier analysis and log­rank tests. Patients with ICC presenting high expression of UBE2M exhibited worse accumulative recurrence and overall survival compared with patients with low expression. Knockdown of UBE2M expression led to a decrease in the viability and clonogenic survival of QBC939 and HUCCT1 cells, and suppressed tumor formation in vivo. UBE2M silencing caused accumulation of cullin­RING ligase substrates (chromatin­licensing and DNA replication factor 1 and origin recognition complex subunit 1), inducing DNA damage responses and apoptosis. The present findings suggested that UBE2M serves an important role in ICC progression and may present as a novel target for the treatment of ICC.

18.
Chin J Nat Med ; 17(8): 591-599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472896

RESUMO

Whitmania pigra has been used as a traditional Chinese medicine (TCM) for promoting blood circulation, alleviating blood coagulation, activating meridians and relieving stasis for several hundred years. However, the therapeutic components of this species, especially proteins and peptides were poorly exploited. Until now only a few of them were obtained by using chromatographic isolation and purification. In recent decade, transcriptome techniques were rapidly developed, and have been used to fully reveal the functional components of many animal venoms. In the present study, the cDNA of the salivary gland of Whitmania pigra was sequenced by illumina and the transcriptome was assembled by using Trinity. The proteome were analysed by LC-MS/MS. Based on the data of the transcriptome and the proteome, a potential antiplatelet protein named pigrin was found. Pigrin was cloned and expressed using P. pastoris GS115. The antiplatelet andantithrombotic bioactivities of pigrin were tested by using aggregometer and the rat arterio-venous shunt thrombosis model, respectively. Thebleeding time of pigrin was measured by a mice tail cutting method. The docking of pigrin and protease-activated receptor 1 (PAR1) or collagen were conducted using the ZDOCK Server. Pigrin was able to selectively inhibit platelet aggregation stimulated by PAR1 agonist and collagen. Pigrin attenuated thrombotic formation in vivo in rat, while did not prolong bleeding time at its effective dosage. There are significant differences in the key residues participating in binding of Pigrin-Collagen complex from Pigrin-PAR1 complex. In conclusion,a novel PAR1 inhibitor pigrin was found from the leech Whitmania pigra. This study helped to elucidate the mechanism of the leech for the treatment of cardiovascular disorder.

19.
Biol Reprod ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31504210

RESUMO

The underlying mechanism of the Chemokine-C Receptor 7 (CCR7) that leads to aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA) remains unknown. CCR7 is considered crucial for migration and invasion and has been associated with the risk of miscarriage. However, the functional role of CCR7 in RSA is not fully understood. Our study found that CCR7 mRNA and protein abundance were significantly decreased in the villous from RSA patients compared with healthy controls. Knockdown of CCR7 caused a significant reduction of migration and invasion in JAR and JEG-3 cells. Meanwhile, CCR7 functioned as a positive upstream factor of the AKT pathway contributing to the expression of GATA2, promoting trophoblast migration, and invasion via MMP2. Notably, a decreased abundance of CCR7 was positively correlated with the phosphorylation of AKT and with an abundance of GATA2 and MMP2 in human villous specimens of RSA compared with the control group. CCL19, a ligand of CCR7, could promote trophoblast migration and invasion by activating the deregulation of the CCR7-mediated pathway in RSA. We are convinced that CCR7 and its downstream factors may be possible mechanisms for the pathogenesis of RSA.

20.
Molecules ; 24(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505837

RESUMO

Cistanche tubulosa is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-ß1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC50 values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 µg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.

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