Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 138
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Cell Mol Med ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164044

RESUMO

The role of IL-6 signalling in hypertensive heart disease and its sequelae is controversial. Our group demonstrated that Bazedoxifene suppressed IL-6/gp130 signalling in cancer cells but its effect on myocardial pathology induced by pressure overload is still unknown. We explored whether Bazedoxifene could confer benefits in wild-type C57BL/6J mice suffering from transverse aortic constriction (TAC) and the potential mechanisms in H9c2 myoblasts. Mice were randomized into three groups (Sham, TAC, TAC+Bazedoxifene, n = 10). Morphological and histological observations suggested TAC aggravated myocardial remodelling while long-term intake of Bazedoxifene (5 mg/kg, intragastric) attenuated pressure overload-induced pathology. Echocardiographic results indicated Bazedoxifene rescued cardiac function in part. We found Bazedoxifene decreased the mRNA expression of IL-6, MMP2, Col1A1, Col3A1 and periostin in murine hearts after 8-week surgery. By Western blot detection, we found Bazedoxifene exhibited an inhibition of STAT3 activation in mice three hours and 8 weeks after TAC. Acute TAC stress (3 hours) led to down-regulated ratio of LC3-Ⅱ/LC3-Ⅰ, while in mice after long-term (8 weeks) TAC this ratio becomes higher than that in Sham mice. Bazedoxifene inverted the autophagic alteration induced by TAC at both two time-points. In H9c2 myoblasts, Bazedoxifene suppressed the IL-6-induced STAT3 activation. Moreover, IL-6 reduced the ratio of LC3-Ⅱ/LC3-Ⅰ, promoted P62 expression but Bazedoxifene reversed both changes in H9c2 cells. Our data suggested Bazedoxifene inhibited IL-6/gp130 signalling and protected against cardiac remodelling together with function deterioration in TAC mice.

2.
Methods Appl Fluoresc ; 8(2): 025005, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32069448

RESUMO

An eco-friendly fluorescence polymer nanoparticle based on carbon quantum dots and poly(methyl methacrylate) nanoparticles is successfully fabricated to detect sulfadiazine. By making use of the abundant functional group of carbon quantum dots and poly(methyl methacrylate) nanoparticles, without any extra modification, the synthetic process of the fluorescence nanoparticles is reduced and the unnecessary chemical molecules are avoided being brought into the reaction system. The investigation of the fluorescence property of carbon quantum dots shows that the prepared carbon quantum dots are the excitation independent. In addition, the morphology of the synthesized fluorescence polymer nanoparticle is tested by the scanning electron microscope and shows that the fluorescence sensor possesses a good spherical core-shell structure. Moreover, under the optimized condition, the prepared fluorescence polymer nanoparticle possesses a good selectivity in the detection of sulfadiazine under a mixture solution. Moreover, the limit of detection is 4 µmol.l-1 within the detective range from 10 µmol.l-1 to 60 µmol.l-1. Meanwhile, the fluorescence quenching mechanism is considered with the photoinduced electron transfer mechanism. Finally, the practical research on the detection of sulfadiazine in tap water shows that the recovery range and relative standard deviation are 97.5% - 105.1% and 2.1%-4.5%, respectively.

3.
Prostate ; 80(6): 481-490, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32104919

RESUMO

OBJECTIVE: To investigate the potential mechanism of the effect of metabolic syndrome (MetS) on prostate volume (PV) and the risk of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and the relationships of MetS and the major pathogenic factors of MetS with the clinical progression of BPH/LUTS in older Chinese men. SUBJECTS AND METHODS: We analyzed clinical data obtained from 506 ostensibly healthy men who underwent routine health check-ups and recruited 415 subjects from a group of previously studied men after 4 years. We evaluated the associations of major pathological factors of MetS, including insulin resistance, subclinical inflammatory state, and sex hormone changes, with PV, the risk of BPH and the clinical progression of BPH/LUTS by using multiple linear regression and logistic regression. RESULTS: After adjustment for age, insulin, HOMA (homeostatic model assessment) index, leptin, resistin, adiponectin, C-reactive protein, tumor necrosis factor-α (TNF-α), sex hormone-binding globulin, and testosterone levels were significantly associated with PV (all P < .05), and in the age-adjusted logistic regression model, positive associations of resistin and TNF-α with BPH/LUTS were found (OR, 1.662, P = .007 and OR, 1.044, P < .001, respectively). Predictors of BPH/LUTS clinical progression were significantly correlated with MetS and TNF-α. The group with higher TNF-α levels had a higher rate of newly diagnosed BPH (9.5% vs 19.1%, P = .006) and a greater increase in PV levels (0.61 ± 0.08 vs 1.09 ± 0.35 cm3 , P <.001) after 4 years. CONCLUSIONS: MetS and its pathological factors were associated with an increased PV and an increased risk of BPH/LUTS that is more prone to clinical progression. TNF-α may serve as an early biological indicator to identify which patients with BPH/LUTS are at higher risk of unfavorable outcomes.

4.
J Cell Physiol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048287

RESUMO

High-throughput messenger RNA (mRNA) analysis has become a powerful tool for exploring tumor recurrence or metastasis mechanisms. Here, we constructed a signature to predict the recurrence risk of Stages II and III gastric cancer (GC) patients. A least absolute shrinkage and selection operator method Cox regression model was utilized to construct the signature. Using this method, a 16-mRNA signature was identified to be associated with the relapse-free survival of Stages II and III GCs in training dataset GSE62254 (n = 194). Then this signature was validated in an independent Gene Expression Omnibus cohort GSE26253 (n = 297) and a dataset of The Cancer Genome Atlas (TCGA; n = 235). This classifier could successfully screen out the high-risk Stages II and III GCs in the training cohort (hazard ratio [HR] = 40.91; 95% confidence interval [CI] = 5.58-299.7; p < .0001). Analysis in two independent validation cohorts yielded consistent results (GSE26253: HR = 1.69, 95% CI = 1.17-2.43,; p = .0045; TCGA: HR = 2.01, 95% CI = 1.13-3.56, p = .0146). Cox regression analyses revealed that the risk score derived from this signature was an independent risk factor in Stages II and III GCs. Besides, a nomogram was constructed to serve clinical practice. Through gene set variation analysis, we found several gene sets associated with chemotherapeutic drug resistance and tumor metastasis significantly enriched in high-risk patients. In summary, this 16-mRNA signature can be used as a powerful tool for prognostic evaluation and help clinicians identify high-risk patients.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31900959

RESUMO

BACKGROUND AND AIM: In the phase 3 CONCUR trial (NCT01584830), regorafenib improved overall survival (OS) versus placebo in Asian patients with treatment-refractory metastatic colorectal cancer (mCRC). We conducted a post hoc subgroup analysis of Chinese patients in CONCUR. METHODS: Adults with mCRC progressing despite at least two prior treatment regimens and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:1 to regorafenib 160 mg once daily or placebo for the first 3 weeks of each 4-week cycle. Dose modifications were permitted. The primary endpoint was OS. Secondary endpoints included progression-free survival, objective overall response, disease control rate, and safety. RESULTS: A total of 172 Chinese patients were randomized and treated (regorafenib n = 112, placebo n = 60). OS was significantly improved with regorafenib versus placebo (8.4 vs 6.2 months, respectively; hazard ratio [HR] 0.56, 95% CI 0.39-0.80; one-sided P = 0.000632), as was progression-free survival (HR 0.32, 95% CI 0.22-0.47; one-sided P < 0.000001). The most common drug-related grade ≥ 3 treatment-emergent adverse events (TEAEs; regorafenib, placebo) were hand-foot skin reaction (19%, 0%), hypertension (13%, 3%), hypophosphatemia (7%, 0%), increased alanine aminotransferase (6%, 0%), and increased aspartate aminotransferase (5%, 0%). In patients receiving regorafenib and placebo, respectively, TEAEs led to treatment discontinuation in 14% and 7%, dose reduction in 39% and 0%, and dose interruption in 64% and 20%. CONCLUSIONS: This retrospective analysis showed that regorafenib provided an OS benefit over placebo for Chinese patients with previously treated mCRC. TEAEs were consistent with the regorafenib safety profile and manageable with treatment modifications.

6.
Food Chem ; 314: 126160, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31958749

RESUMO

Lipolysis products released during digestion exert positive metabolic impacts on the nutrition of newborns. However, the lipolysis behavior of yak milk lipids during digestion remains unknown. In this study, the simulated in vitro infant gastrointestinal digestion of cow, yak and standardized yak milk fat globules the same size as those from cow milk (Cow MF, Yak MF and Yak SMF) were compared. Although Cow MF showed a higher lipolysis rate at the beginning of gastric digestion, Yak MF and Yak SMF exhibited a higher lipolysis level during later gastrointestinal digestion. Higher hydrolysis efficiency of yak milk lipids was due to their lipid properties, including their composition and structure. Furthermore, yak milk lipids released more unsaturated fatty acids than Cow MF throughout digestion. This study highlights the crucial role of lipid characteristics in the efficient digestion of milk lipids and provides new insight for the design of yak milk infant diets.

7.
J Cancer Res Clin Oncol ; 146(1): 287-295, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31667572

RESUMO

PURPOSE: Trastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the optimal maintenance treatment in patients benefited from the first line therapy remains unclear. METHODS: In this prospective observational study, patients with HER2 positive AGC who received six cycles of trastuzumab-based first line chemotherapy were divided into two arms according to the maintenance strategy: trastuzumab monotherapy (arm A) and trastuzumab plus mono-chemo-agent derived from the initial chemotherapy (arm B). The primary end point was overall survival (OS), the secondary end points were first line progression free survival (PFS), maintenance PFS, cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs) and safety. RESULTS: 30 patients were in arm A received trastuzumab monotherapy and 48 were in arm B. The clinical and pathological characteristics of two arms were well balanced. There was no significant difference of median OS (16.5 vs 20.0 months, HR 0.71 P = 0.169) or PFS (7.9 vs 11.0, HR 1.06, P = 0.892) between two arms, however, adding chemo-agent could lead to a 29% reduction in mortality risk. Adverse effects including cardiac safety were also similar. Subgroup analysis showed chemotherapy additional to trastuzumab benefited on OS in patients who had stable disease (SD) of response (HR: 0.084, P = 0.004), elder than 65 years old (HR: 0.4, P = 0.015), without liver metastasis (HR: 0.271, P = 0.008) or less than two organs of distance metastasis (HR: 0.263, P = 0.005). The average cost per patients in arm A was 153,137 RMB and 165,195 RMB in arm B. While, ICER in arm A was 1.29 times higher than arm B (CERs of two arms were 19,384 vs 15,018 RMB). CONCLUSION: Mono-chemo-agent combined with trastuzumab showed an advantage of absolute value and hazard ratio on OS, in addition to ICER of PFS for patients who benefit from the initial six cycles of trastuzumab-based first line therapy, especially in patients with certain clinical or treatment-related characterisitics. A large sample randomized trial is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Trastuzumab/administração & dosagem , Adulto Jovem
8.
J Sep Sci ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31788943

RESUMO

A highly sensitive and convenient electrochemical sensor, based on surface molecularly imprinted polymers and multiwalled carbon nanotubes, was successfully developed to detect chlorpyrifos in real samples. In order to solve the problems like uneven shapes, poor size accessibility, and low imprinting capacity, the layer of the molecularly imprinted polymer was prepared on the surface of silica nanospheres. Moreover, the doping of multiwalled carbon nanotubes greatly improved the electrical properties of developed sensor. Under the optimal conductions, the electrochemical response of the sensor is linearly proportional to the concentration of chlorpyrifos in the range of 5.0 × 10-12 -5.0 × 10-8  mol/L with a low detection limit of 8.1 × 10-13  mol/L. The prepared sensor exhibited multiple advantages such as low cost, simple preparation, convenient use, excellent selectivity, and good reproducibility. Finally, the prepared sensor was successfully used to detect chlorpyrifos in vegetable and fruit.

9.
Chin Med J (Engl) ; 132(24): 2941-2949, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31855962

RESUMO

BACKGROUND: X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC). However, the mechanism through which XIAP regulates DNA damage repair is unknown. This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression. METHODS: The two cell lines were established using RNA interference technology. The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach. Proteomic analysis revealed 255, 375, 362, and 5 differentially expressed proteins after 0, 0.5, 3, and 12 h of drug stimulation, respectively, between the two cell lines. The identified differentially expressed proteins were involved in numerous biological processes. In addition, the expression of histone proteins (H1.4, H2AX, H3.1, H3.2, and H3.3) was drastically altered, and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX. Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses. RESULTS: The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins, such as H2AX, and influences the DNA repair process. CONCLUSIONS: Given these functions, XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents.

10.
Aging (Albany NY) ; 11(22): 10052-10060, 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31739285

RESUMO

Dual block HER2 assessment can effectively increase the HER2 positive rate in resected specimens of gastric cancer (GC). The aim of this study is to explore whether GC patients with extra gained HER2 positivity by dual block assessment can benefit from trastuzumab therapy. Twenty-eight GC patients receiving gastrectomy prior to trastuzumab treatment were retrospectively analyzed. All the cases routinely accepted dual block HER2 assessment. The cases were divided into 2 cohorts based on HER2 status: cohort A with concordant HER2 results and cohort B with discordant HER2 results between the two blocks (cases with extra gained HER2 positivity). Response rate (RR), progress free survival (PFS) and overall survival (OS) were compared between the two cohorts. The results showed that no significant differences were found between the two cohorts in main clinicopathologic characteristics. No statistical difference was found in response rate (47.6% vs 57.1%) (P=1.0), either. The two cohorts did not demonstrate statistical differences in the PFS (10.5 months (95%CI 6.4-14.6) vs 8.0 months (95%CI 3.2-12.8), P=0.686) and the OS (23.3 months (95%CI 12.1-34.5) vs 20.0 months (95%CI 10.1-29.9), P=0.776). In conclusion, our study suggests that patients with extra gained HER2 positivity may not show compromised efficacy to trastuzumab treatment.

11.
BMC Urol ; 19(1): 119, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752806

RESUMO

BACKGROUND: Metabolic syndrome (MetS) and serum prostate-specific antigen (PSA) levels are correlated. To investigate the underlying effect of MetS on PSA levels, the relationship between the major pathogenic factors of MetS and serum PSA levels was studied. METHODS: A total of 506 ostensibly healthy men who underwent routine health check-ups were recruited to this study. We evaluated the effect of the major pathogenic factors of MetS, which included insulin resistance, a subclinical inflammatory state and sexual hormone changes, on serum PSA levels by using linear regression analysis and multivariate analysis after adjusting for age, BMI and prostate volume. RESULTS: When simultaneously adjusting for age, BMI, prostate volume and high-density lipoprotein cholesterol, serum insulin levels and SHBG levels were inversely correlated with serum PSA levels (P = 0.049 and P = 0.004, respectively), and testosterone levels were positively correlated with serum PSA levels (P = 0.039). In multivariate regression models, serum insulin levels and serum SHBG levels were significantly associated with serum PSA levels (both P < 0.001). CONCLUSIONS: Among the major pathogenic factors of metabolic syndrome, insulin resistance and sexual hormone changes may be the most significant contributors to the decline in serum PSA levels.

12.
J Sex Med ; 16(12): 1874-1884, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31585805

RESUMO

INTRODUCTION: Modulating tissue-resident stem and progenitor cells with a non-invasive, mechanobiological intervention is an optimal approach for tissue regeneration. Stem cell antigen-1 (Sca-1) has been identified as a stem cell marker within many organs but never within the penis. AIM: To localize and isolate penile stem/progenitor cells (PSPCs) and to evaluate cellular differentiation after exposure to induction medium and microenergy acoustic pulse (MAP) therapy. METHODS: Six male Sprague-Dawley rats were used to isolate PSPCs. Isolation was followed by stem cell characterization and differentiation assays. The PSPCs were then treated with MAP (0.033 mJ/mm2, 1 Hz) at various dosages (25, 50, 100, and 200 pulses) and for different durations (1, 2, 4, 6, or 8 hours) in vitro. MAIN OUTCOME MEASURE: The PSPCs (Sca-1-positive cells) were isolated using the magnetic-activated cell sorting system. PSPC cellular differentiation was assessed after induction with induction medium and with MAP in vitro. Wnt/ß-catenin signaling was also assayed. RESULTS: The PSPCs were successfully localized within the penile subtunic and perisinusoidal spaces, and they were successfully isolated using magnetic-activated cell sorting. The stemness of the cells was confirmed by stem cell marker characterization and by multiple differentiation into smooth muscle cells, endothelial cells, adipocytes, and neurons. MAP-induced PSPCs differentiated into smooth muscle cells by activating the Wnt/ß-catenin signaling pathway in a time- and dosage-dependent manner. CLINICAL IMPLICATIONS: By modulating resident PSPCs, MAP may have utility in the treatment of erectile dysfunction (ED). STRENGTHS & LIMITATIONS: This study provides solid evidence in support of microenergy therapies, including both MAP and low-intensity extracorporeal shock wave therapy, for the treatment of ED. Additional studies are needed and should include additional stem cells markers. Furthermore, studies exploring the underling mechanisms for PSPC activation and differentiation are required. CONCLUSION: PSPCs were successfully identified, localized, and isolated. Additionally, MAP provoked PSPCs to differentiate into smooth muscle cells via the Wnt/ß-catenin signaling pathway. As such, MAP provides a novel method for activating endogenous tissue-resident stem/progenitor cells and might facilitate stem cell regenerative therapy targeting ED. Peng D, Yuan H, Liu T, et al. Smooth Muscle Differentiation of Penile Stem/Progenitor Cells Induced by Microenergy Acoustic Pulses In Vitro. J Sex Med 2019; 16:1874-1884.

13.
Aging (Albany NY) ; 11(18): 7473-7491, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527303

RESUMO

Gastric cancer (GC) is a common disease globally with high mortality rate. It is therefore necessary to develop novel therapies targeting specific events in the pathogenesis of GC. Some hnRNP family members are involved in multiple cancer biological behaviors. However, the potential function and mechanism of hnRNPR, a new molecule of hnRNP family in GC remains unknown. We found that the expression of hnRNPR was significantly overexpressed in multiple cancers compared to the normal tissues. Functionally, hnRNPR promoted cancer cell proliferation, migration, and invasion. Knockdown of hnRNPR in two type mice models, with two types of tumors models decreased the tumor aggressiveness and metastasis. Mechanistically, hnRNPR targeted oncogenic pathways by stabilizing the expression of CCNB1 and CENPF mRNA level. Knockdown of CCNB1 and CENPF abolished the hnRNPR-induced cell growth and invasion, respectively. Furthermore, the protein level of hnRNPR in the tumor was positively correlated with the expression of CCNB1 and CENPF in clinical samples. Together, these results indicate that overexpression of hnRNPR promoted the aggressiveness of GC by increasing the mRNA expression of CCNB1 and CENPF. HnRNPR-CCNB1/CENPF axis may be a potential therapeutic target for GC treatment.

14.
BMC Cancer ; 19(1): 790, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395059

RESUMO

BACKGROUND: This study aimed to investigate the prognostic value of volumetric parameters on 18F- fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in gastric-cancer patients, according to the expression status of c-MET (MET proto-oncogene, receptor tyrosine kinase), which was previously unclear. METHODS: The study included 61 patients with advanced gastric cancer. Data on the baseline 18F-FDG PET/CT, clinical-pathological information, progression-free survival (PFS), and overall survival (OS) were collected. The maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of gastric tumors in situ were measured on PET/CT. The expression status of c-MET was recorded based on immunohistochemical staining. Associations between the parameters on PET/CT and patients' survival outcomes were analyzed in relation to expression status of c-MET. RESULTS: Patients with positive c-MET expression had significantly shorter PFS (11.5 vs. 17.6 months, P = 0.039) and OS (17.0 vs. 24.3 months, P = 0.043), and had gastric tumors with a larger MTV (70.8 ± 53.11 vs. 41.1 ± 52.32, P = 0.034) and TLG (428.39 ± 442.95 vs. 205.7 ± 354.40, P = 0.039), compared with those with negative c-MET expression. However, SUVmax (9.6 ± 7.40 vs. 8.0 ± 4.91, P = 0.335) and SUVpeak (7.7 ± 5.99 vs. 6.62 ± 4.08, P = 0.438) were similar between these two patient groups. In patients with c-MET-positive tumors, MTV and TLG were independent factors in predicting patient OS after correction by distant metastasis (hazards ratio = 1.014 and 1.002, respectively; P = 0.024 and 0.027, respectively), while these associations were not significant in patients with c-MET-negative tumors. CONCLUSIONS: Patients with c-MET-positive gastric cancer had higher MTV and TLG values compared to those with c-MET-negative gastric cancer. In patients with c-MET-positive gastric cancer, volumetric parameters on 18F-FDG PET/CT have prognostic value for patient overall survival.


Assuntos
Expressão Gênica , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas c-met/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Idoso , Terapia Combinada , Feminino , Fluordesoxiglucose F18 , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Resultado do Tratamento , Carga Tumoral
15.
Mikrochim Acta ; 186(9): 625, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414214

RESUMO

The surface of poly(methyl methacrylate) nanospheres (PMMA-NSs) was molecularly imprinted with sulfadiazine by a surface imprinting method. Simultaneously, Mn(II)-doped ZnS quantum dots were incorporated into the imprinted PMMA-NSs. The morphology of the fluorescent nanoprobe was characterized by transmission electron microscopy which revealed good spheroidal core-shell structure and a homogeneous distribution of the QDs. Following binding of sulfadiazine, fluorescence (best measured at excitation/emission maxima of 335/592 nm) is increasingly quenched. The detection range is 5-40 µmol·L-1 of sulfadiazine, and the detection limit is 0.24 µmol·L-1. The fluorescence quenching mechanism is discussed, and a photo-induced electron transfer process is shown to account for quenching. The fluorescent probe was applied to the determination of sulfadiazine in spiked tap water with recoveries and RSDs of 96.6-100.2% and 2.7-3.9%, respectively. The detection of sulfadiazine in spiked lake water exhibited the recoveries and RSDs with 99.3-104.8% and 1.8-4.2%, respectively. Graphical abstract Schematic presentation of synthesis of PMMA-Ns, Mn-doped ZnS QDs, MQPs, and the elution diagram of SD from MQPs, and the relative reagents including: sodium dodecyl benzene sulfonate(SDBS), (3-aminopropyl)triethoxysilane(APTES), 3-mercaptopropionic acid (MPA), tetraethylorthosilicate(TEOS)and sulfadiazine(SD), and nanoparticles including: polymer(methyl methacrylate) nanospheres(PMMANs), MIPs@QDs@PMMANs(MQPs) and carbon quantum dots(CQDs).

16.
Food Funct ; 10(9): 5656-5668, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433414

RESUMO

Schisandra chinensis (Turcz.) Baill (S. chinensis), a functional food, is used as a tonic and sedative agent in traditional Chinese medicine. Modern pharmacological research has proved that S. chinensis could prevent and treat age-related neurodegenerative diseases. The presence of bioactive lignans in S. chinensis is the main reason for its neuroprotective and cognitive enhancement effects. This study aimed to clarify the mechanism of lignans in S. chinensis in ameliorating learning and memory deficits in Alzheimer's disease (AD) animals. The step-down test and Morris water maze (MWM) test were used to verify the effects of lignans in S. chinensis on learning and memory in AD animals. Then, metabolomics approaches based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) were used to clarify the mechanism of lignans in S. chinensis in treating AD. Finally, quantitative analysis of AD-related neurotransmitters in the brain was conducted after treatment with lignans in S. chinensis. In the MWM and step-down tests, lignans in S. chinensis showed a clear ability to ameliorate the impaired learning and memory of AD animals. A total of 31 endogenous metabolites were identified after treatment with lignans in S. chinensis, which were associated with lignans ameliorating learning and memory. These biomarkers were mainly associated with polyunsaturated fatty acid metabolism and amino acid and vitamin metabolism. Moreover, lignans in S. chinensis upregulated the levels of γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), acetylcholine (Ach), norepinephrine (NE) and glycine (Gly) and downregulate the level of aspartic acid (Asp). Lignans in S. chinensis might alleviate the neurotoxic effects of neurological inflammation and oxidative stress, Aß deposition, and tau phosphorylation via the regulation of multiple endogenous metabolic pathways during pathological AD. The research might provide useful support for the further study of pharmacology and new drug development of lignans in S. chinensis.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Lignanas/administração & dosagem , Schisandra/química , Doença de Alzheimer/sangue , Doença de Alzheimer/psicologia , Doença de Alzheimer/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Humanos , Lignanas/química , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metabolômica , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Plasma/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Urina/química
17.
Clin Chem Lab Med ; 57(10): 1501-1510, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31339850

RESUMO

Background Evaluating the tumor RAS/BRAF status is important for treatment selection and prognosis assessment in metastatic colorectal cancer (mCRC) patients. Correction of artifacts from library preparation and sequencing is essential for accurately analyzing circulating tumor DNA (ctDNA) mutations. Here, we assessed the analytical and clinical performance of a novel amplicon-based next-generation sequencing (NGS) assay, Firefly™, which employs a concatemer-based error correction strategy. Methods Firefly assay targeting KRAS/NRAS/BRAF/PIK3CA was evaluated using cell-free DNA (cfDNA) reference standards and cfDNA samples from 184 mCRC patients. Plasma results were compared to the mutation status determined by ARMS-based PCR from matched tissue. Samples with a mutation abundance below the limit of detection (LOD) were retested again by droplet digital polymerase chain reaction (ddPCR) or NGS. Results The Firefly assay demonstrated superior sensitivity and specificity with a 98.89% detection rate at an allele frequency (AF) of 0.2% for 20 ng cfDNA. Generally, 40.76% and 48.37% of the patients were reported to be positive by NGS of plasma cfDNA and ARMS of FFPE tissue, respectively. The concordance rate between the two platforms was 80.11%. In the pre-treatment cohort, the concordance rate between plasma and tissue was 93.33%, based on the 17 common exons that Firefly™ and ARMS genotyped, and the positive percent agreement (PPA) and negative percent agreement (NPA) for KRAS/NRAS/BRAF/PIK3CA were 100% and 99.60%, respectively. Conclusions Total plasma cfDNA detected by Firefly offers a viable complement for mutation profiling in CRC patients, given the high agreement with matched tumor samples. Together, these data demonstrate that Firefly could be routinely applied for clinical applications in mCRC patients.

18.
Cancer Manag Res ; 11: 6029-6041, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303797

RESUMO

Background: For patients with locally advanced gastric cancer (LAGC) after D2 gastrectomy, the survival benefits of receiving adjuvant chemoradiotherapy versus adjuvant chemotherapy are unclear. This study aimed to compare the 5- and 7-year overall survival (OS) in the two groups and to identify which patients can benefit more from adjuvant chemoradiotherapy. Methods: Retrospective data were collected from January 2009 to December 2014. The 5- and 7-year OS and disease-free survival (DFS) were compared between the two groups using the Chi-square test. The association of OS with prognostic factors was identified using the Cox's proportional hazard model, which was then adjusted for survival coparison using propensity score-matching (PSM) analysis. The association of OS with each clinical/demographic factor was compared between the two groups using the Kaplan-Meier analysis. Results: A total of 415 eligible patients were identified (135 adjuvant chemoradiotherapy, 280 adjuvant chemotherapy). Significant 5- and 7-year OS and DFS benefits were found in the adjuvant chemoradiotherapy group versus chemotherapy group. Multivariate analysis showed that age, TNM stage, lymph node (LN) ratio, tumor deposits, and total/subtotal gastrectomy were independent prognostic factors. When the PSM analysis was adjusting by these factors, 135 patients were matched with an improved survival benefit from adjuvant chemoradiotherapy. Patients in the adjuvant chemoradiotherapy group had a lower locoregional relapse. Subset analysis also identified significant OS benefits of adjuvant chemoradiotherapy in patients with LN ratio <50%, pIIIA, and pIIIB stage disease, while OS benefits were not observed in patients with tumor deposits, pN3b classification, or pIIIC stage disease. Conclusion: Adjuvant chemoradiotherapy was shown to be superior in improving the OS in a certain population of patients compared with adjuvant chemotherapy. This finding may help to better guide the individualized treatments of patients with stage III LAGC after D2 gastrectomy.

19.
Oncologist ; 24(10): 1311-e989, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31239311

RESUMO

LESSONS LEARNED: The NEO-CLASSIC study provided valuable insight for the clinical efficacy and tolerability profiles of perioperative chemotherapy with oxaliplatin and capecitabine, plus gastrectomy, in patients with localized resectable gastric cancer.The study was designed to explore the potential survival benefits of an eight-cycle, perioperative oxaliplatin and capecitabine (XELOX) schedule in the above-mentioned setting and to explore the feasibility of prolonging the cycles of preoperative chemotherapy. The projected endpoint was not met. BACKGROUND: This multicenter, open-label study (NEO-CLASSIC) evaluated the efficacy and safety of oxaliplatin and capecitabine (XELOX), plus D2 gastrectomy, in localized resectable gastric cancer. METHODS: Patients aged 18-75 years with histologically-confirmed gastric adenocarcinoma (stage T2-4a/N+M0) were given eight cycles of XELOX (four preoperatively, four postoperatively). Each 3-week cycle comprised capecitabine 1,000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1. Curative D2 gastrectomy was scheduled 2-4 weeks after the last preoperative cycle. The primary objective of the study was to determine the objective response rate (ORR) of XELOX in the preoperative setting. Sample size was calculated by assuming that a minimum of 47 cases would be required to increase the ORR by 15% (from 40% to 55%). With an estimated 10% dropout rate, 55 patients would have to be recruited. RESULTS: Fifty-five patients were enrolled, and one was excluded because of screening failure. R0 resections were achieved in 45 of 54 intent-to-treat patients (83.3%), and four patients received R1 resections (Fig. 1). There were no complete responses, 27 (50.0%) partial responses, 22 cases (40.7%) of stable disease, and 4 (7.4%) of progressive disease. The objective response rate was 50.0%. Median follow-up was 52.97 months; 30 patients (55.6%) had disease progression (Table 1), and median progression-free survival was 20.10 (95% confidence interval: 4.31-35.89) months; median overall survival was 30.77 months (95% confidence interval was not yet available) (Fig. 2). Fifty-four patients completed 209 cycles of preoperative chemotherapy; 42 patients received 133 cycles of postoperative chemotherapy (Table 3). The rate of grade 3-4 adverse events was 8.5% (29/342 cycles); the most frequent events were neutropenia (9/342 cycles) and leukopenia (4/342 cycles). CONCLUSION: These findings suggest that combination therapy with capecitabine and oxaliplatin as perioperative chemotherapy, followed by D2 gastrectomy, is effective and safe in late-stage, locally advanced gastric cancer. Although enrollment exceeded the 47 patients required to identify an increase in the ORR by 15% (from 40% to 55%), results did not meet the primary endpoint.

20.
J Transl Med ; 17(1): 203, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215439

RESUMO

BACKGROUND: Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients' prognosis. We aim to identify new prognostic markers for resected HCC patients. METHODS: 274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a "9-gene signature" associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80). RESULTS: We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P < 0.001). CONCLUSIONS: The 9-gene signature, in which four were upregulated (ZC2HC1A, MARCKSL1, PTGS1, CDKN2B) and five (CLEC10A, PRDX3, PRKCH, MPEG1, LMO2) were downregulated in HCC with poor prognosis, stratified HCC patients into low and high risk group significantly in different clinical settings, including receiving adjuvant transarterial chemoembolization and especially in early stage disease. This new signature should be validated in prospective studies to stratify patients in clinical decisions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA