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1.
Int J Mol Sci ; 20(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484301

RESUMO

The G-protein-coupled receptor (GPCR) regulated intracellular signaling pathway is known to be involved in the development of insecticide resistance in the mosquito, Culex quinquefasciatus. To elucidate the specific role of each effector in the GPCR regulating pathway, we initially expressed a GPCR, G-protein alpha subunit (Gαs), adenylate cyclase (AC), and protein kinase A (PKA) in insect Spodoptera frugiperda (Sf9) cells and investigated their regulation function on cyclic AMP (cAMP) production and PKA activity. GPCR, Gαs, and AC individually expressed Sf9 cells showed higher cAMP production as the expression of each effector increased. All the effector-expressed cell lines showed increased PKA activity however. Moreover, Sf9 cytochrome P450 gene expression and cell tolerance to permethrin were examined. The relative expression of CYP9A32gene in Sf9 cells tested was significantly increased in all effector-expressed cell lines compared to a control cell line; these effector-expressed cell lines also showed significantly higher tolerance to permethrin. Inhibitor treatments on each effector-expressed cell line revealed that Bupivacaine HCl and H89 2HCl robustly inhibited cAMP production and PKA activity, respectively, resulting in decreased tolerance to permethrin in all cell lines. The synergistic functions of Bupivacaine HCl and H89 2HCl with permethrin were further examined in Culex mosquito larvae, providing a valuable new information for mosquito control strategies.

2.
Hum Mutat ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479177

RESUMO

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma-glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low-GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in-vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.

3.
J Hazard Mater ; 381: 120997, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31476708

RESUMO

Soil washing is a rapid and efficient remediation technique for soil contaminated by heavy metals. In this study, Cd, Pb, and Zn were removed from contaminated soil by ethylenediamine tetra (methylene phosphonic acid) (EDTMP) and polyacrylic acid (PAA). We then investigated the effect of varying the concentration, pH and duration of the washing processes. Single-factor experiments suggest that the PAA washing process may be dominated by electrostatic adsorption, and is suitable for remediation under weak acid and neutral conditions. Meanwhile, EDTMP remediation might be dominated by chelation, which is favorable in strong acid and alkaline environments. In a quadratic saturation D-optimization design (QSDD), we optimized the washing parameters and further explored the washing mechanism including primary factor, principal effect, interaction effect, and the optimal washing conditions, with simultaneously changing multiple influencing factors. The optimum efficiencies of Cd, Pb, and Zn removal were 92.74%, 96.14%, and 50.76% respectively in EDTMP remediation, and 84.62, 79.24, and 41.66% respectively in PAA remediation. The washing processes effectively reduced the availability of Cd, Pb, and Zn in contaminated soil, without noticeably affecting soil chemical properties. Therefore, the washing incurred little ecological risk. EDTMP and PAA are suitable remediation agents of soil contaminated by heavy metals.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31479744

RESUMO

The obligate intracellular parasite Toxoplasma gondii can infect nearly all warm-blooded animals including humans. Although infection with this parasite is generally benign, severe illness may occur in the infected individuals if their immunity becomes less competent, such as AIDS patients. In this study, we determined the inhibitory activity of 44 commonly used antiretroviral compounds against T. gondii in vitro. Fourteen of the 44 tested antiretroviral compounds showed potency against T. gondii at IC50 concentrations that ranged from 1.18 ± 2.21 µM (nelfinavir) to 18.89 ± 1.87 µM (trovirdine). Seven of the 14 potent antiretroviral compounds are HIV-1 protease inhibitors. We investigated whether co-administration of these 14 antiretroviral compounds interferes with the anti-T. gondii activity of the existing anti-T. gondii drugs, sulfadiazine or pyrimethamine. Results showed no significant interaction between any of the tested 14 antiretroviral compounds and pyrimethamine or sulfadiazine. These results warrant the investigation of whether the administration of the lead antiretroviral drugs with highly potent anti-T. gondii activity to AIDS patients may help in limiting the occurrence of toxoplasmic encephalitis.

5.
Pharmacol Res ; : 104440, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31479750

RESUMO

Targeting on the IKKß to discover anti-inflammatory drugs has been launched for ten years, due to its predominant role in canonical NF-κB signaling. In the current study, we identified a novel IKKß inhibitor, ellipticine (ELL), an alkaloid isolated from Ochrosia elliptica and Rauvolfia sandwicensis. We found that ELL reduced the secretion and mRNA expression of TNF-α and IL-6 and decreased the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in bone marrow derived macrophages (BMDMs) stimulated with LPS. In coincided with the results, ELL suppressed PGE2 and NO production in BMDMs. Underlying mechanistic study showed that ELL inhibited IκBα phosphorylation and degradation as well as NF-κB nuclear translocation, which was attributed to suppression of IKKα/ß activation. Furthermore, kinase assay and binding assay results indicated that ELL inhibited IKKß activity via directly binding to IKKß and in turn resulted in suppression of NF-κB signaling. To identify the binding sites of ELL on IKKß, IKKßC46A plasmid was prepared and the kinase assay was performed. The results demonstrated that the inhibitory effect of ELL on IKKß activity was impaired in the mutation, implying that anti-inflammatory effect of ELL was partially attributed to binding on cysteine 46. Furthermore, ELL up-regulated LC3 II expression and reduced p62 expression, suggesting that autophagy induction contributed to the anti-inflammatory effect of ELL as well. In coincided with the in vitro results, ELL increased the survival and antagonized the hypothermia in the mice with LPS-induced septic shock. Consistently, ELL reduced TNF-α and IL-6 production in the serum of the mice treated with LPS. Collectively, our study provides evidence that ELL is an IKKß inhibitor and has potential to be developed as a lead compound for treatment inflammatory diseases in the future.

6.
Plant Sci ; 287: 110206, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31481203

RESUMO

A pot experiment was conducted to evaluate how nitrogen (N) availability influences cadmium (Cd) absorption, translocation and stress tolerance in roots of Populus euramericana. Seedling growth was sensitive to N deficiency, but it was unaltered by Cd exposure. Cadmium absorption by roots was promoted by N deficiency, resulting in a higher root Cd concentration compared to the N-sufficient condition. Fine-root length was tightly correlated (R2 = 0.73) with Cd concentration in roots, indicating that vigorous fine-root proliferation under N deficiency contributed to active absorption and accumulation of Cd in roots. Despite accumulation in roots, Cd translocation from roots to shoots was less active under N deficiency compared to N sufficiency. This was related to elevated glutathione reductase (GR) activity and glutathione (GSH) levels in roots after N application, which may not only promote antioxidant defence, but also facilitate the formation of GSH-Cd complexes that are uploaded into root cylinders. Nitrogen application also promoted antioxidant defense in roots via increased production of phytohormones and the level of enzymatic and non-enzymatic antioxidants. Transcript levels for genes responsible for antioxidant defense, Cd detoxification and Cd uploading were increased in roots by N application. The N-stimulated Cd tolerance, detoxification and uploading in roots are factors likely to promote Cd translocation from roots to shoots, which may enhance the biological capacity of this poplar species for phytoremediation of Cd pollution.

7.
Plant Dis ; : PDIS01190179RE, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31483183

RESUMO

Brown root rot (BRR), caused by the white rot fungus Phellinus noxius (syn. Phellinus noxius), is an epidemic disease of diverse broadleaved and coniferous tree species in many tropical and subtropical regions. Flooding and trenching control measures are difficult to implement, and chemical controls can have an adverse impact on ecosystems. Previous studies have provided in vitro evidence for the potential use of Trichoderma spp. for biocontrol of BRR. Here, we analyzed the in vitro antagonistic and mycoparasitic abilities of four Trichoderma spp. isolates against four P. noxius isolates in dual culture and Ficus microcarpa wood blocks. A convenient inoculation system based on root inoculation of a highly susceptible loquat (Eriobotrya japonica) with P. noxius-colonized wheat-oat grains was developed to examine the effect of Trichoderma treatment in planta. Preventive application of Trichoderma asperellum TA, the isolate showing high antagonistic activity in vitro, was effective in preventing and delaying the wilting of P. noxius-inoculated loquat cuttings in greenhouse trials. To understand the specific niche in which T. asperellum TA interacts with P. noxius, KOH-aniline blue fluorescence microscopy was used to investigate the colonization of loquat roots by P. noxius and/or T. asperellum TA. Dilution plating assays were also conducted to quantify Trichoderma populations in the rhizosphere and potting mix. T. asperellum TA was able to robustly establish in the rhizosphere and potting mix but with scarce root penetration limited to the superficial layer. We discuss the timing and strategy for applying antagonistic Trichodema sp. on living trees or in BRR-infested areas for BRR management.

8.
EMBO Mol Med ; : e10168, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475771

RESUMO

Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA-based signature that could improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA-seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four-circRNA-based cirScore to classify patients into high-risk and low-risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease-free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss-of-function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four-circRNA-based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31490648

RESUMO

Carbon nanotube (CNT) buckypapers, or films, have the potential for wide applications for their unique properties. Neat buckypapers or pristine CNT (PCNT) films have relatively large elongation but low strength and low modulus due to the weak interaction between CNTs. Chemical modifications of PCNT films can significantly strengthen the interaction between CNTs, resulting in high strength and high modulus but usually accompanied by low elongation. Here, we report the functionalization of pristine CNT films by thiol-ended hyperbranched polymers (THBP-n) via a thiol-ene click reaction that can introduce simultaneous improvements on the strength, modulus and elongation to the PCNT film by 689 %, 812 % and 32.4 %, respectively. The high thiol content of THBP-n enables the formation of a high degree cross-linking network between carbon nanotubes, which provides high efficiency load transfer that increases the tensile strength and modulus of the resulting films, and at the same time a compressible hyperbranched structure that allows for deformation and slip between CNTs and consequently improved elongation. The main factors affecting the mechanical performance of the functionalized CNT film are also investigated.

10.
BMC Vet Res ; 15(1): 313, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477093

RESUMO

BACKGROUND: Bovine ephemeral fever virus (BEFV) causes fever and muscle stiffness in cattle, resulting in negative economic impact for cattle and dairy farms. During the manufacturing process of inactivated vaccine for virus control, it is important to determine the virus titer, but traditional methods such as plaque assay and TCID50 assay require days of waiting time. We sought to develop a quick dot blot assay for BEFV titering. RESULTS: Three different kinds of BEFV antigens were prepared to raise primary antibodies for BEFV detection in dot blot assays: 1) purified BEFV particles, 2) Escherichia coli (E. coli)-expressed BEFV G1 region, and 3) E. coli-expressed BEFV N protein. Results showed that antibodies raised against purified BEFV particles can detect BEFV particles, but it also showed a high background level from the proteins of BHK-21 cells. Antibodies raised against E.coli-expressed BEFV G1 region could not detect BEFV particles in dot blot assays. Finally, antibodies raised against E.coli-expressed BEFV N protein detected BEFV particles with a high signal-to-noise ratio in dot blot assays. CONCLUSIONS: E.coli-expressed N protein is a suitable antigen for the production of antiserum that can detect BEFV particles with a high signal-to-noise ratio. A dot blot assay kit using this antiserum can be developed as a quick and economical way for BEFV titering.

11.
Phys Chem Chem Phys ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490519

RESUMO

Mg-M (M = Li, Na and K) dual-metal-ion batteries featuring a dendrite-free Mg anode and an alkali-metal-ion storage cathode are promising safe energy storage systems. However, the compatibility between cathode materials and insertion cations might largely limit the electrochemical performance of the cathodes. In this work, three types of Mg-M (M = Li, Na and K) dual-metal-ion batteries are constructed with a Berlin green (FeFe(CN)6) cathode. The FeFe(CN)6 cathode is compatible with the dual-salt Mg2+/M+ (M = Li, Na and K) electrolytes, and delivers a high reversible capacity of 120 mA h g-1 at 50 mA g-1, with no capacity fading over 50 cycles in Mg-Na batteries. The Mg-Na battery also shows an outstanding rate capability, providing 85 mA h g-1 at 1000 mA g-1 and superior long-term cyclability over 800 cycles. The electrochemical performance comparison between Mg-Li, Mg-Na and Mg-K dual-metal-ion batteries demonstrates the significance of the appropriate hydrated ionic radius and dehydrated ionic radius for the insertion of cations with the FeFe(CN)6 cathode. This work provides new design strategies for stable and high energy density cathodes, and opens a new avenue for building safe and high-performance Mg-M (M = Li, Na and K) dual-metal-ion batteries for practical applications.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31508929

RESUMO

Industrial production of NH3 heavily depends on the conventional Haber-Bosch process under rigorous conditions with a large amount of energy consumption and carbon emissions. Electrocatalysis exhibits an intriguing prospect for the N2 reduction reaction (NRR) at ambient conditions. Wherein, a high-efficiency and low-cost catalyst is paramount. In this letter, Cr3C2 nanoparticles and carbon nanofiber composite (Cr3C2@C NF) is proposed as a noble metal-free NRR electrocatalyst for converting N2 to NH3 c with an excellent selectivity. The optimal faradic efficiency and NH3 yield rate achieve as high as 8.6% and 23.9 µg h-1 mgcat.-1 at -0.3 V vs. reversible hydrogen electrode (RHE) in 0.1 M HCl. Theoretical calculations show a low reaction barrier of merely 0.53 eV in the enzymatic route for this catalyst.

13.
Am J Cardiol ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31514966

RESUMO

Some previous literature indicated an association between cardiovascular diseases and erectile dysfunction (ED). This case-control study purposed to evaluate the association between prior mitral valve prolapse (MVP) and ED using data from the Taiwan National Health Insurance Research Dataset. In this study, 48,755 patients with ED were identified as cases, and 195,020 propensity score-matched patients without ED were selected as controls. Conditional logistic regressions were conducted to evaluate the odds ratios (ORs) for previous MVP between cases and the matched controls. In all sampled patients, 4,565 (1.87%) patients had MVP before the index date. MVP was found in 1,304 (2.67%) cases and in 3,261 (1.67%) matched controls. Patients with ED had a significantly higher occurrence of MVP than the controls. In addition, after propensity score matching, a conditional logistic regression analysis showed that the OR of previous MVP for patients with ED was 1.63 (95% confidence interval [CI] 1.52 to 1.74) compared to the matched controls. The ORs of previous MVP for patients with ED aged ≤65 years and those >65 years were 1.68 (95% CI 1.56 to 1.81) and 1.49 (95% CI 1.30 to 1.70), respectively, compared with the matched controls. We found that patients with erectile dysfunction had significantly higher odds of previous MVP compared with matched control subjects without ED regardless of the age group.

14.
Eur J Pharmacol ; 862: 172639, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31491406

RESUMO

This study investigated the effect of dextromethorphan (DXM) against Parkinson's disease (PD) in rats and explored the association between DXM dose and PD risk in elderly patients 65 years and older using a population-based database. The PD rat model (Sprague Dawley rats) was induced by injecting 6-hydroxydopamine (6-OHDA) into the unilateral medial forebrain bundle of the rat brain. DXM (20 mg/kg) was administered intraperitoneally twice daily from 7 days before the appearance of a 6-OHDA lesion to 28 days after the lesion appeared. The availability of dopamine transporter (DAT) and serotonin transporter (SERT) in the striatum of the rat brain was measured using positron emission tomography. The apomorphine-induced rotation test was performed to study the hypersensitivity of the brain regions with lesions. This animal study demonstrated that DXM significantly attenuated 6-OHDA-induced DAT and SERT loss, correlating to rotational behaviors. The population-based human study analyzed the data from the Taiwan Longitudinal Health Insurance Database 2005 between January 2005 and December 2013 and then used the DXM dose-response curve to investigate the trend of its protective effect against PD. In the human study, low cumulative doses of DXM may potentially achieve a protective effect for PD; however, high cumulative doses seem to be a risk for PD.

15.
Phytomedicine ; 64: 153084, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31514083

RESUMO

BACKGROUND: Metastasized melanoma is extremely difficult to treat. Activation of C-C chemokine receptor type 7 (CCR7) has been linked to melanoma metastasis. CCR7 can be directly regulated by miR-let-7. We have previously shown that an ethanolic extract of an herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos (SLE) inhibits melanoma cell migration and invasion. PURPOSE: In this study, we determined whether SLE suppresses melanoma metastasis, and whether regulation of miR-let-7a/f-CCR7 signaling is involved in the effect. STUDY DESIGN AND METHODS: Small RNA sequencing was conducted to compare miRNA expression profiles of B16F10 tumors dissected from SLE-treated or untreated mice. Western blot and RT-qPCR analyses were employed to examine protein and miRNA levels, respectively. A B16F10 melanoma lung metastasis mouse model was used to evaluate the effects of SLE on melanoma metastasis. MiR-let-7a/f-knockdown and CCR7-overexpression cell models were used to investigate the involvement of miR-let-7a/f-CCR7 signaling in the anti-metastatic effects of SLE. RESULTS: It was found that SLE upregulated levels of miR-let-7a/f in B16F10 melanoma tissues. SLE significantly elevated levels of miR-let-7a/f, lowered the protein level of CCR7, inhibited the phosphorylation of CCR7 downstream molecules p38 and JNK in B16F10 and A375 melanoma cells. SLE inhibited B16F10 melanoma lung metastasis in mice. SLE upregulated levels of miR-let-7a/f, and lowered protein levels of CCR7, MMP-2, MMP-9, phospho-p38 (Thr180/Tyr182) and phospho-JNK (Thr183/Tyr185) in melanoma-invaded lung tissues. Knockdown of miR-let-7a/f diminished the effects of SLE on CCR7 signaling in, and invasion of, melanoma cells. Overexpression of CCR7 lessened the effects of SLE in inhibiting the phosphorylation of p38 and JNK in, and the invasive capability of, melanoma cells. CONCLUSION: We for the first time demonstrated that SLE inhibits melanoma metastasis in mice, and that regulation of the miR-let-7a/f-CCR7 pathway contributes to the anti-metastatic mechanisms of SLE. These findings provide a pharmacological basis for developing SLE as a modern agent for treating metastatic melanoma. Additionally and importantly, this study suggests that regulating the miR-let-7a/f-CCR7 pathway is a novel strategy for controlling melanoma metastasis.

16.
New Phytol ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514232

RESUMO

Arabidopsis CRY1 and phyB are the primary blue and red light photoreceptors mediating blue and red light inhibition of hypocotyl elongation, respectively. Auxin is a pivotal phytohormone involved in promoting hypocotyl elongation. CRY1 and phyB interact with and stabilize Aux/IAA proteins (Aux/IAAs) to inhibit auxin signaling. Here, we investigated whether photoreceptors might interact directly with Auxin Response Factors (ARFs) to regulate auxin signaling. We demonstrated by protein-protein interaction studies that CRY1 and phyB physically interact with ARF6 and ARF8 through their N-terminal domains in a blue and red light-dependent manner, respectively. Moreover, the N-terminal DNA-binding domain of ARF6 and ARF8 is involved in mediating their interactions with CRY1. Genetic studies showed that ARF6 and ARF8 act partially downstream from CRY1 and PHYB to regulate hypocotyl elongation under blue and red light, respectively. ChIP-PCR assays demonstrated that CRY1 and phyB mediate blue and red light repression of the DNA-binding activity of ARF6 and ARF6-target gene expression, respectively. Altogether, our results suggest that the direct repression of auxin-responsive gene expression mediated by the interactions of CRY1 and phyB with ARFs constitutes a new layer of the regulatory mechanisms by which light inhibits auxin-induced hypocotyl elongation.

17.
Dalton Trans ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508626

RESUMO

Rechargeable Mg batteries are promising candidates for highly safe, large-scale energy storage batteries due to the low-cost and non-dendritic metallic Mg anode. However, exploring high-performance cathodes remains a great challenge blocking their development. Herein, a rechargeable Mg battery is established with a Ag2S conversion cathode, providing a highly reversible capacity of 120 mA h g-1 at 50 mA g-1, a superior rate capability of 70 mA h g-1 at 500 mA g-1, and an outstanding long-term cyclability over 400 cycles. The mechanism was investigated using XRD, TEM and XPS in addition to electrochemical measurements, and indicated a two-stage magnesiation: first, Mg2+ intercalation into Ag2S and then a conversion reaction to form metallic Ag0 and MgS. The solid-state Mg2+ diffusion coefficients are as high as 3.6 × 10-9 and 3.1 × 10-10 cm2 s-1 for the intercalation and conversion reactions, respectively, which explains the high performance of the Ag2S cathode. This work provides scientific insights for the selection of a promising conversion cathode by the combination of soft anions and soft transition metal cations.

18.
BMC Cancer ; 19(1): 908, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511059

RESUMO

BACKGROUND: This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. METHODS: From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. RESULT: Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. CONCLUSION: In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.

19.
AAPS PharmSciTech ; 20(7): 280, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399832

RESUMO

Sarsasapogenin derivative 5n (SGD 5n) is a new compound with potent antitumor efficacy, but the low solubility severely affects its absorption and bioavailability. Therefore, the SGD 5n-loaded mPEG-PLGA block copolymer micelles were developed to improve the value of SGD 5n in clinical application. The polymeric micelles were prepared by an organic solvent evaporation method, and the encapsulation efficiency (EE), drug loading (DL), critical micelle concentrations (CMC), morphology, particle size, and zeta potential were determined. The cytotoxicity was examined by the MTT assay, and the cellular uptake study was performed by confocal laser scanning microscopy. A model of tumor-bearing mouse was established to study the antitumor activity in vivo. The results demonstrated that the particle size of the prepared micelle was 124.6 ± 9.6 nm, the encapsulation efficiency was 82.0 ± 2.9%, and the drug loading was 8.3 ± 0.4%. The results of cytotoxicity and cellular uptake demonstrated that the SGD 5n-loaded micelles could efficiently enter tumor cells, and the cellular uptake of SGD 5n presented concentration and time dependence. This study demonstrated that the prepared SGD 5n-loaded polymeric micelles had significant antitumor activity and provided a basis for clinical development of new compound SGD 5n.

20.
Parasit Vectors ; 12(1): 423, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462294

RESUMO

BACKGROUND: Pentatrichomonas hominis is a flagellated protozoan that inhabits the large intestine of humans. Although several protozoans have been proposed to have a role in cancer progression, little is known about the epidemiology of P. hominis infection in cancer patients. METHODS: To determine the prevalence of P. hominis in patients with digestive system malignancies, we collected 195 and 142 fecal samples from gastrointestinal cancer patients and residents without any complaints related to the digestive system, respectively. Each sample was detected for the presence of P. hominis by nested PCR amplifying the internal transcribed spacer (ITS) region and partial 18S rRNA gene. RESULTS: A significantly higher prevalence of P. hominis was found in cancer patients than that in the control population (41.54 vs 9.15%, χ2 = 42.84, df = 1, P < 0.001), resulting in a 6.75-fold risk of gastrointestinal cancers (OR: 6.75, 95% CI: 3.55-12.83, P < 0.001). The highest prevalence of P. hominis infection was detected in small intestine cancer patients (60%, OR: 14.88, 95% CI: 0.82-4.58, P = 0.009) followed by liver (57.14%, χ2 = 10.82, df = 1, P = 0.001) and stomach cancer patients (45.1%, χ2 = 31.95, df = 1, P < 0.001). In addition, phylogenetic analysis provided some evidence supporting that human P. hominis infection might derive from animal sources. CONCLUSIONS: To our knowledge, this study is the first report presenting the high association between P. hominis and gastrointestinal cancers. Nevertheless, whether there is any possible pathological role of P. hominis infection in cancer patients needs to be further elucidated.

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