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1.
Chemosphere ; 239: 124712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31499310

RESUMO

Selenium can regulate arsenic toxicity by strengthening antioxidant potential, but the antagonism between selenite or selenate nutrient and the translocation of arsenic species from paddy soil to different rice organs are poorly understood. In this study, a pot experiment was designed to investigate the effect of selenite or selenate on arsenite or arsenate toxicity to two indica rice cultivars (namely Ming Hui 63 and Lu You Ming Zhan), and the uptake and transportation of arsenic species from paddy soil to different rice organs. The results showed that selenite or selenate could significantly decrease the arsenate concentration in pore water of soils, and thus inhibited arsenate uptake by rice roots. However, the existence of selenite or selenate didn't decrease arsenate concentration in rhizosphere pore water of two indica rice cultivars. There existed good antagonistic effect between selenite or selenate and the uptake of arsenite and arsenate in rice plant in the case of low arsenic paddy soil. However, this antagonism depended on rice cultivars, arsenic species and arsenic level in soil. There existed both synergistic and inhibiting effects between the addition of selenite or selenate and the uptake of trimethylarsinoxide and dimethylarsinic acid by two indica rice cultivars, but the mechanism was unclear. Both selenite and selenate are all effective to decrease the translocation of inorganic arsenic from the roots to their above-ground rice organs in arsenite/arsenate-spiked paddy soil, but selenate had stronger inhibiting effect on their transfer factors than selenite.

2.
Eur J Pharmacol ; : 172788, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31712058

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies worldwide. Inhibition of the lipogenic enzymes involved in hepatic de novo lipogenesis can both effectively restrain proliferation of HCC cells in vitro and reduce the risk of hepatocarcinogenesis in vivo. Although a natural coumarin derivative osthole shows efficacy in suppressing cell proliferation and inducing apoptosis in cultured hepatoma cells and HCC xenograft tumors, the molecular mechanism by which osthole delays hepatocellular malignant transformation during lipogenesis-driven hepatocarcinogenesis remains unknown. Here, we evaluate the efficacy of osthole in a rapid HCC mouse model featuring excessive levels of hepatic steatosis established via hydrodynamic transfection of activated forms of AKT and c-Met proto-oncogenes. Moreover, human hepatoma cell lines were employed for in vitro assessment. Hematoxylin and eosin staining, immunoblotting and immunohistochemistry were applied for mechanistic investigations. The results revealed that if osthole was administered in the early stage of AKT/c-Met-driven HCC, it led to disease stabilization. Moreover, osthole alleviated hepatic steatosis in the AKT/c-Met mice. Further evidence at the molecular level suggested that osthole reduced the expression of phosphor-extracellular signal-regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA) and Ki67 in livers of the AKT/c-Met mice. Mechanically, osthole efficiently repressed the phospho-AKT (Thr308) / ribosomal protein S6 (RPS6) / fatty acid synthase (FASN) signaling both in mice and in vitro. Altogether, this study suggests that osthole exerts its antilipogenic and antiproliferative efficacy by suppressing the AKT/FASN axis and ERK phosphorylation, which contributes to its capacity to delay hepatocarcinogenesis.

3.
Org Lett ; 21(22): 9005-9008, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31689110

RESUMO

An iridium-catalyzed B-H bond insertion reaction between borane adducts and sulfoxonium ylides to afford α-boryl carbonyls has been developed. The starting materials are safe and readily available. In addition, analogues of sulfoxonium ylides, such as sulfonium salts and sulfonium ylides could also be amenable to the reaction.

4.
J Mol Graph Model ; 94: 107488, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31707196

RESUMO

In order to compare the main difference of two diimide derivatives on the modulation of electronic and optical properties of P3HT-based organic solar cell, the density functional theory and molecular dynamics simulations were implemented to achieve elementary data on geometrical structure, molecular orbital, open-circuit voltage, absorption spectra, energetic driving force, and interface parameter of P3HT/D1 and P3HT/D2 systems. According to the investigation, P3HT/D1 system not only exhibits higher open circuit voltage and enough energetic driving force than P3HT/D2 system, but also possesses low-lying LUMO +1 orbital which can favor the exciton separation efficiency. Moreover, on the basis of some typical interface models choose from MD simulation, the estimation of the interface rate manifests that the P3HT/D1 interface possesses the smaller charge recombination rates and larger charge separation rates than those of the P3HT/D2 interface. It is expect that this work can provide certain guidelines for the further develop the performance of organic solar cell. We hope this work can further study on non-fullerene acceptor materials as a certain guides.

5.
Chin J Integr Med ; 25(9): 716-720, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31650488

RESUMO

Chinese medicine (CM) has a good clinical effect on osteoarthritis (OA), but the mechanism is not very clear. Evidence-based medicine researches have shown that intestinal flora plays a role in the pathogenesis and succession of OA. Intestinal flora affects the efficacy of CM, and CM can affect the balance of intestinal flora. This paper focuses on the relationship between intestinal flora, intestinal microenvironment, brain-gut axis, metabolic immunity and OA, and preliminarily expound the significance of intestinal flora in the pathogenesis of OA and the mechanism of CM intervention. The above discussion will be of great significance in the prevention and treatment of OA by CM from the perspective of intestinal flora.

6.
Sci Adv ; 5(10): eaaw8417, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663018

RESUMO

Although nuclear type 2C protein phosphatase (PP2Cδ) has been demonstrated to be pro-oncogenic with an important role in tumorigenesis, the underlying mechanisms that link aberrant PP2Cδ levels with cancer development remain elusive. Here, we found that aberrant PP2Cδ activity decreases p53 acetylation and its transcriptional activity and suppresses doxorubicin-induced cell apoptosis. Mechanistically, we show that BRCA1 facilitates p300-mediated p53 acetylation by complexing with these two proteins and that S1423/1524 phosphorylation is indispensable for this regulatory process. PP2Cδ, via dephosphorylation of ATM, suppresses DNA damage-induced BRCA1 phosphorylation, leading to inhibition of p300-mediated p53 acetylation. Furthermore, PP2Cδ levels correlate with histological grade and are inversely associated with BRCA1 phosphorylation and p53 acetylation in breast cancer specimens. C23, our newly developed PP2Cδ inhibitor, promotes the anticancer effect of doxorubicin in MCF-7 xenograft-bearing nude mice. Together, our data indicate that PP2Cδ impairs p53 acetylation and DNA damage response by compromising BRCA1 function.

7.
J Clin Lab Anal ; : e23032, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31628684

RESUMO

BACKGROUND: Respiratory viruses, such as influenza viruses, initially infect the upper airways but can manifest as severe lower respiratory tract infections in high-risk patients with significant morbidity and mortality. For syndromic diagnosis, several multiplex nucleic acid amplification tests have been developed for clinics, of which SureX 13 Respiratory Pathogen Multiplex Kit (ResP) can simultaneously detect 13 pathogens directly from airway secretion specimens. The organisms identified are influenza virus A, influenza virus A pdmH1N1 (2009), influenza virus A H3N2, influenza virus B, adenovirus, boca virus, rhinovirus, parainfluenza virus, coronavirus, respiratory syncytial virus, human metapneumovirus, Mycoplasma pneumoniae, and Chlamydia. METHODS: This study provides performance evaluation data of this assay by comparing with pathogen-specific PCRs from oropharyngeal swab samples. RESULTS: Ten pathogens were detected in this assay, of which rhinovirus, adenovirus, and influenza virus A pdmH1N1 (2009) were the most common. The overall agreement between the ResP and the comparator tests was 93.8%. The ResP demonstrated 86.5% agreement for positive results and 97.8% agreement for negative results. CONCLUSION: The ResP assay demonstrated a highly concordant performance comparing with pathogen-specific PCRs for detection of respiratory pathogens in oropharyngeal swabs from outpatients and could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.

8.
Chin Med J (Engl) ; 132(21): 2559-2564, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31651518

RESUMO

BACKGROUND: The size of the glenoid bone defect is an important index in selecting the appropriate treatment for anterior shoulder instability. However, the reliability of glenoid bone defect measurement is controversial. The purpose of the present study was to investigate the reliabilities of measurements of the glenoid bone defect on computed tomography and to explore the predisposing factors leading to inconsistency of these measurements. METHODS: The study population comprised 69 consecutive patients who underwent surgery for recurrent anterior shoulder dislocation in Peking University Fourth School of Clinical Medicine from March 2016 to January 2017. The glenoid bone defect was measured by three surgeons on 'self-confirmed' and 'designated' 3-D en-face views, and repeated after an interval of 3 months. Measurements included the ratio of the defect area to the best-fit circle area, and the ratio of the defect width to the diameter of the best-fit circle. The inter- and intra-observer reliabilities of the measurements were evaluated using intraclass correlation coefficients (ICCs). The maximum absolute inter- and intra-observer differences and the cumulative percentages of cases with inter- and intra-observer differences greater than these respective levels were calculated. RESULTS: Almost all linear defect values were bigger than the areal defect values. The inter-observer ICCs for the areal defect were 0.557 and 0.513 in the 'self-confirmed' group and 0.549 and 0.431 in the 'designated' group. The inter-observer reliabilities for the linear defect were moderate or fair in the 'self-confirmed' group (ICC = 0.446, 0.374) and 'designated' group (ICC = 0.402, 0.327). The ICCs for intra-observer measurements were higher than those for inter-observer measurements. The respective maximum inter- and intra-observer absolute differences were 13.9% and 13.2% in the 'self-confirmed' group, and 15.8% and 9.8% in the 'designated' group. CONCLUSIONS: The areal measurement of the glenoid bone defect is more reliable than the linear measurement. The reliability of the glenoid defect areal measurement is moderate or worse, suggesting that a more accurate and objective measurement method is needed in both en-face view and best-fit circle determination. Subjective factors affecting the glenoid bone loss measurement should be minimized.

9.
Toxins (Basel) ; 11(10)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623211

RESUMO

α-Conotoxins (α-CTxs) are small disulfide-rich peptides from venom of Conus species that target nicotinic acetylcholine receptors (nAChRs). The muscle-type nAChRs have been recognized as a potential target for several diseases, such as myogenic disorders, muscle dystrophies, and myasthenia gravis. EI, an α4/7-CTx, mainly blocks α1ß1δε nAChRs and has an extra N-terminal extension of three amino acids. In this study, the alanine scanning (Ala-scan) mutagenesis was applied in order to identify key residues of EI for binding with mouse α1ß1δε nAChR. The Ala-substituted analogues were tested for their abilities of modulating muscle and neuronal nAChRs in Xenopus laevis oocytes using two-electrode voltage clamp (TEVC) recordings. Electrophysiological results indicated that the vital residues for functional activity of EI were His-7, Pro-8, Met-12, and Pro-15. These changes exhibited a significant decrease in potency of EI against mouse α1ß1δε nAChR. Interestingly, replacing the critical serine (Ser) at position 13 with an alanine (Ala) residue resulted in a 2-fold increase in potency at the α1ß1δε nAChR, and showed loss of activity on α3ß2 and α3ß4 nAChRs. Selectivity and potency of [S13A] EI was improved compared with wild-type EI (WT EI). In addition, the structure-activity relationship (SAR) of EI revealed that the "Arg1-Asn2-Hyp3" residues at the N-terminus conferred potency at the muscle-type nAChRs, and the deletion analogue △1-3 EI caused a total loss of activity at the α1ß1δε nAChR. Circular dichroism (CD) spectroscopy studies demonstrated that activity loss of truncated analogue △1-3 EI for α1ß1δε nAChR is attributed to disturbance of the secondary structure. In this report, an Ala-scan mutagenesis strategy is presented to identify crucial residues that are significantly affecting potency of E1 for mouse α1ß1δε nAChR. It may also be important in remodeling of some novel ligands for inhibiting muscle-type nAChRs.

10.
Arch Biochem Biophys ; 676: 108148, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606392

RESUMO

Nickel (Ni) is a silver-white transition metal that is widely used in the production field due to its unique physical and chemical properties. As a toxicant, long-term exposure to Ni can cause rhinitis, pneumonia and other respiratory inflammation. In the present study, we investigated the effect of particles extracted from Ni-refining fumes on cell viability, inflammation-related proteins and mitochondrial damage in human lung epithelial Beas-2B cells. The cells were exposed to Ni-refining fume particles for 24 h at concentrations of 0, 6.25, 12.50 and 25.00 µg/mL. The expression levels of the NACHT-LRR-PYD domains-containing protein 3 (NLRP3), caspase-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α protein in Beas-2B cells exposed to Ni-refining fume particles increased significantly. Downregulation of NLRP3 expression by siRNA decreased the content of IL-1ß. During activation of NLRP3, the mitochondrial membrane potential (MMP) decreased, the opening rate of mitochondrial permeability transition pore (MPTP) increased, and the content of reactive oxygen species (ROS) increased. Using lipopolysaccharide (LPS) intervention as the positive control group, N-acetylcysteine (NAC, an effective ROS remover) acted as an inhibitor. After NAC reduced the level of ROS, activation of the NLRP3 inflammasome was significantly inhibited. Ni-refining fumes caused significant cytotoxicity, inflammation and mitochondrial damage in Beas-2B cells. The present study thus provides experimental support for the hypothesis that Ni-refining fumes cause inflammation by inducing ROS production in Beas-2B cells.

11.
ACS Appl Mater Interfaces ; 11(44): 41506-41515, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31580049

RESUMO

Multicolor fluorescence probes can show fluorescence of different colors when detecting different targets, and the excellent feature can create a highly differentiated multicolor sensing platform. However, most of the previously reported multicolor luminescent materials usually suffer from high toxicity and photobleaching, complex preparation procedures, and poor water solubility, which may not be conducive to bioanalytical applications. Two-dimensional metal organic frameworks (2D MOFs), which have large specific surface areas with long-range fluorescence quenching coupled with biomolecular recognition events, have encouraged innovation in biomolecular probing. Here, we propose a 2D-MOF-based multicolor fluorescent aptamer nanoprobe using a double stirring bar assisted target replacement system for enzyme-free signal amplification. It utilizes the interaction between 2D MOFs and DNA molecules to detect multiple antibiotics quickly, sensitively, and selectively. Since 2D MOFs have excellent quenching efficiency for luminescence of fluorescent-dye-labeled single-strand DNA (ssDNA), the background fluorescence can be largely reduced and the signal-to-noise ratio can be improved. When the adsorbed ssDNA formed double helix double-stranded DNA with its complementary ssDNA, its fluorescence can be almost fully recovered. The assay was tested by detecting chloramphenicol (CAP), oxytocin (OTC), and kanamycin (KANA) in biological samples. The developed aptasensor was sufficiently sensitive to detect the antibiotic residues as low as 1.5 pM CAP, 2.4 pM OTC, and 1 pM KANA (S/N = 3). It has been preliminarily used for multicolor imaging of three different antibiotics in fish tissue slices with satisfactory results.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1607-1611, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607320

RESUMO

OBJECTIVE: To explore the effect of high volume platelet reduction therapy on the white blood cell (WBC) count and hemoglobin (Hb) level in patients with thrombocytosis. METHODS: Thirty-two plateletphoreses were performed for patients with thromocytosis by using ELP or MNC program of blood component isolator of COBE spectra continuous flow concentrifugation and the ACD-A preservation solution for blood as blood anticoagulant. In each treatment of patients, 2.5-3.0 tines total blood volume (TBV) were circulated, then the platelet suspension of 1/5-1/4 time TBV was prepared and collected. RESULTS: A single plateletpheresis took (212.53±41.54) minutes in which (8 812.63±2087.15) ml blood were treated, and (798.84±190.77) ml platelet suspension was collected. In the suspension, the platelet count was 4 486.50 (3 058.50-5 279.50)×109/L, containing 3 455.50 (2 288.68-4 226.71)×109. WBC count was 13.79 (10.21-20.72)×109/L, containing 11.90(7.81-14.40)×109. Hemoglobin concentration was (3.28±1.25) g/L,containing (2.62 ± 1.17) g. Before and after plateletpheresis, the patients' platelet count was 1 263.00 (1 052.50-1 807.50)×109/L and (778.83±247.25)×109/L(Z=4.94, P<0.01), WBC count was 9.96(6.44-14.01)×109/L and 8.59(5.37, 13.12)×109/L (Z=13.31, P<0.05), Hemoglobin concentration was (112.63 ± 24.56)g/L and (109.55 ± 24.46)g/L (t=1.68,P>0.05). CONCLUSION: Using continuous flow centrifugation and blood component separating in plateletpheresis for the patients with thrombocytosis can obviously decrease the high ratio of platelets, and improve the effect of plateletpheresis. The high volume platelet reduction therapy can lead to decrease of WBC count to some alent, degree but WBC count still in the normal range, moreover not affect the hemoglobin level significantly.


Assuntos
Plaquetoferese , Trombocitose , Hemoglobinas , Humanos , Contagem de Leucócitos , Contagem de Plaquetas
13.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3452-3462, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621232

RESUMO

To explore light energy utilization characteristics and yield effect of different legume-gramineae intercropping patterns, we set up five kinds of monocropping patterns including alfalfa, triticale, oats, maize and sorgo as reference in a field experiment. The light energy utilization chara-cteristics and productivity of four kinds of intercropping patterns including alfalfa-triticale, alfalfa-oats, alfalfa-maize and alfalfa-sorgo were examined. The contribution degree of each light energy index to yield formation was analzyed using path analysis method. The results showed that the contribution of each index of light energy to yield from large to small was as follows: leaf area index (LAI)=1.236, net photosynthetic rate (Pn)=0.519, canopy openness (DIFN)=0.302, intercellular CO2 concentration (Ci)=-0.026, stomatal conductance (gs)=-0.116, transpiration rate (Tr)=-0.188, PAR interception rate (FIPAR)=-1.708. Light use efficiency (LUE) as a comprehensive indicator of light energy utilization had the largest value (1.367). Compared with monoculture, the values of LAI, Pn, gs, Tr and FIPAR of four kinds of gramineae grasses increased under intercropping and the values of DIFN and Ci decreased, while alfalfa showed an opposite trend. Compared with monoculture, the LUE of four kinds of gramineae grasses under intercropping was significantly increased. The increase rates of triticale and oats (35.2% and 30.4%) were higher than that of maize and sorgo (28.7% and 26.3%). The decrease rates of alfalfa intercropping with triticale and oats (6.1% and 8.3%) were obviously lower than that of maize and sorgo (21.8% and 24.5%). The values of land equivalent ratio (LER) of four kinds of intercropping patterns was all greater than 1. The LER values of alfalfa-triticale and alfalfa-oat were significantly higher than those of alfalfa-maize and alfalfa-sorgo. It could be seen that LAI had the largest direct contribution to yield, followed by Pn. Among the four intercropping patterns, two patterns, alfalfa-triticale and alfalfa-oats, had greater improvement potential of light energy utilization and yield.


Assuntos
Agricultura , Produtos Agrícolas , Medicago sativa , Fotossíntese , Zea mays
14.
Arch Toxicol ; 93(10): 2993-3003, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31506784

RESUMO

As one of the isoprenoids and widely derived from many fruits and vegetables, ß-ionone (BI) has a potent inhibitory proliferation of cancer cells in vitro and in vivo. However, its exact mechanism is still uncompleted understood and needs to be further verified. Cyclooxygenase-2 (COX-2), as a potential target of cancer chemoprevention, has been played pivotal roles in proliferation of tumor cells and carcinogenesis. Thus, the objective of present study was to determine that BI inhibited the activity of COX-2 in breast cancer and related to cancer cell models. Cell proliferation, DNA synthesis, the distribution of cell cycle, apoptosis induction and the expression of P38-MAPK protein were determined in MCF-7 cells by methylene blue, 3H-thymidine (TdR) incorporation, flow cytometry, TUNEL and Western blotting assays. Quinone reductase (QR) activity was determined in murine hepatoma Hepa1c1c7 cells by enzyme-linked immunosorbent assay (ELISA). The expression of COX-2 in a phorbol-12-myristate-13-acetate (PMA)-induced cell model and mammary tumor tissues was examined by Western blotting and immunohistochemistry. The results showed that BI significantly inhibited cell proliferation and DNA synthesis, arrested the distribution of cell cycle at the S phase or decreased proteins related to cell cycle such as cyclin D1 and CDK4, induced apoptosis and increased the expression of p-P38 in MCF-7 cells. BI at low doses (< 50 µmol/L) significantly increased QR activity, decreased the expression of COX-2 protein and prostaglandin E2 (PEG2) release in cell models. In addition, BI also significantly decreased the expression of COX-2 protein in rat mammary tumor tissues. Therefore, our findings indicate that BI possesses inhibitory proliferation of breast cancer cells through down-regulation of COX-2 activity.

16.
J Exp Clin Cancer Res ; 38(1): 407, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526386

RESUMO

In the publication of this article [1], there are two corrections.

17.
Microbiologyopen ; : e933, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532581

RESUMO

Pseudomonas aeruginosa is commonly found in nosocomial and life-threatening infections in patients. Biofilms formed by P. aeruginosa exhibit much greater resistance to antibiotics than the planktonic form of the bacteria. Few groups have studied the effects of glucose, a major carbon source, and metabolite, on P. aeruginosa biofilm formation and on its metabolic pathways. In this study, we investigated the effect of glucose on the biofilm formation ability of P. aeruginosa and carried out a metabolomic analysis to identify whether glucose alters the metabolic activity of P. aeruginosa in biofilms. We found that glucose efficiently promoted P. aeruginosa biofilm formation by upregulating the expression of the extracellular polysaccharide-related gene pslA. Treatment with glucose caused an increase in 7 metabolites (including 3-hydroxypropionic acid, glucose-6-phosphate, and 2,3-dimethylsuccinic acid) and a decrease in 18 metabolites (including myo-inositol, glutamine, and methoxamedrine) in the biofilm. In addition, there was a synergistic effect between glucose and horse serum on biofilm formation when the two were added in combination, which also increased the resistance of biofilm to levofloxacin therapy. Thus, our work sheds light on the underlying mechanisms by which glucose may enhance biofilm formation and identifies novel targets for developing strategies to counteract biofilm formation.

18.
Chem Commun (Camb) ; 55(76): 11418-11421, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31482875

RESUMO

A water-mediated C-H activation using sulfoxonium ylides is reported, providing a general, green and step-economic approach to construct a C-C bond and varieties of useful N-heterocycle scaffolds. Notably, the "water-mediated" activation, in contrast to that in organic solvents, shows great potential in pharmaceutical, biochemistry and chemical industries.

19.
Eur J Surg Oncol ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31481274

RESUMO

OBJECTIVE: We seek to explore the clinical significance of serum squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting tumor recurrence and survival in operable cervical squamous cell carcinoma patients. METHODS: A total of 3471 patients with cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The cut-off value of serum SCC-Ag for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed. RESULTS: The optimal cut-off value of serum SCC-Ag level for predicting tumor recurrence was calculated and set at 2.75 ng/mL. Compared to the value of 1.5 ng/mL used in clinical practice, our results showed that serum SCC-Ag level >2.75 ng/mL was closely related to extrapelvic metastases in relapsed patients (P = 0.035). Multivariate analysis showed that neither serum SCC-Ag level >1.5 ng/mL nor serum SCC-Ag level >2.75 ng/mL was independent risk factors for PFS and OS in all patients. However, among 964 patients with at least one high-risk factor (parametrial invasion, vaginal margin invasion and lymph node metastasis), serum SCC-Ag level > 2.75 ng/mL, instead of serum SCC-Ag level > 1.5 ng/mL, could be used as an independent factor affecting PFS (P = 0.018). CONCLUSION: Preoperative serum SCC-Ag level > 2.75 ng/mL is closely related to extrapelvic recurrence, and is an independent factor for tumor recurrence and survival in cervical squamous cell carcinoma patients with high-risk factors.

20.
Eur J Med Chem ; 183: 111720, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31553933

RESUMO

At present, chemo- and radiotherapies remain to be the mainstream methods for treating triple-negative breast cancer (TNBC), which is known for poor prognosis and high rate of mortality. Two types of novel dual-targeting TNBC liposomes (Fru-RGD-Lip and Fru+RGD-Lip) that actively recognize both fructose transporter GLUT5 and integrin αvß3 were designed and prepared in this work. Firstly, a Y-shaped Fru-RGD-chol ligand, where a fructose and peptide Arg-Gly-Asp (RGD) were covalently attached to cholesterol, was designed and synthesized. Then, the Fru-RGD-Lip was constructed by inserting Fru-RGD-chol into liposomes, while Fru+RGD-Lip was obtained by inserting both Fru-chol and RGD-chol (with the molar ratio of 1:1) into liposomes. The particle size, zeta potential, encapsulation efficiency and serum stability of the paclitaxel-loaded liposomes were characterized. The results indicated that the paclitaxel-loaded Fru-RGD-Lip had the strongest growth inhibition against GLUT5 and αvß3 overexpressed MDA-MB-231 and 4T1 cells. The cellular uptake of Fru-RGD-Lip on MDA-MB-231 cells and 4T1 cells was 3.19- and 3.23-fold more than that of the uncoated liposomes (Lip). The uptake of Fru+RGD-Lip was slightly lower, giving a 2.81- and 2.90-fold increase than that of Lip in two cell lines, respectively. The mechanism study demonstrated that the cellular uptake of both dual-targeting liposomes was likely to be recognized and mediated by GLUT5 and αvß3 firstly, then endocytosed through comprehensive pathways in an energy-dependent manner. Moreover, Fru-RGD-Lip displayed the maximum accumulation, which was 2.62-fold higher than that of Lip for instance, at the tumor sites compared to other liposomes using in vivo imaging. Collectively, the liposomes co-modified by fructose and RGD have enormous potential in the development of targeted TNBC treatment, especially the covalently modified Fru-RGD-Lip, making it a promising multifunctional liposome.

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