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1.
Mol Brain ; 12(1): 76, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484535

RESUMO

Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. This study was designed to examine the role of anterior insular cortex (aIC) in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). Abdomen hyperalgesia and anxiety were assessed by von Frey filament and open field tests, respectively. Two weeks after surgery, the activation of aIC was indicated by FOS immunohistochemical staining and electrophysiological recordings. Expressions of VGluT1, NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings. The regulatory roles of aIC in hyperalgesia and pain-related anxiety were detected via pharmacological approach and chemogenetics in CP rats. Our results showed that TNBS treatment resulted in long-term hyperalgesia and anxiety-like behavior in rats. CP rats exhibited increased FOS expression and potentiated excitatory synaptic transmission within aIC. CP rats also showed up-regulated expression of VGluT1, and increased membrane trafficking and phosphorylation of NR2B and GluR1 within aIC. Blocking excitatory synaptic transmission significantly attenuated abdomen mechanical hyperalgesia. Specifically inhibiting the excitability of insular pyramidal cells reduced both abdomen hyperalgesia and pain-related anxiety. In conclusion, our findings emphasize a key role for aIC in hyperalgesia and anxiety of painful CP, providing a novel insight into cortical modulation of painful CP and shedding light on aIC as a potential target for neuromodulation interventions in the treatment of CP.

2.
Org Lett ; 21(16): 6548-6551, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31373503

RESUMO

Evolvulins I and II (1 and 2), representing a new class of resin glycosides with an unprecedented trihydroxy aglycone unit, 3S,11R,14R-trihydroxyhexadecanoic acid (4), were isolated from the whole plants of Evolvulus alsinoides. Their structures were thoroughly characterized by extensive spectroscopic analyses as well as chemical evidence. Compound 1 exhibited the most potent cytotoxic activity against MCF-7 cells, with an IC50 value of 3.12 µM.

3.
Environ Pollut ; 254(Pt A): 112956, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31362255

RESUMO

Triclocarban (TCC) is used as a broad-spectrum antimicrobial agent, the intensive detection of TCC in aquatic environments and its potential risks to aquatic organisms are concerned worldwide. In this study, 8 Chinese resident aquatic organisms from 3 phyla and 8 families were used for the toxicity tests, and four methods were employed to derive the aquatic life criteria (ALC). A criterion maximum concentration (CMC) of 1.46 µg/L and a criterion continuous concentration (CCC) of 0.21 µg/L were derived according to the USEPA guidelines. The acute predicted no effect concentrations (PNECs) derived by species sensitivity distribution (SSD) methods based on log-normal, log-logistic and Burr Type Ⅲ models were 2.64, 1.88 and 3.09 µg/L, respectively. The comparisons of ALCs derived with resident and non-resident species showed that the CMC and CCC of TCC derived with Chinese resident species could provide a sufficient protection for non-resident species. The higher toxicity of TCC on aquatic organisms was found compared with other antimicrobial agents (except for Clotrimazole) in aquatic environment. The strong positive linear correlation was observed between the TCC and TCS concentrations in aquatic environment with a correlation coefficient (R2) of 0.8104, it is of great significance in environmental monitoring and risk assessment for TCC and TCS. Finally, the ecological risk assessment showed that the TCC in Yellow River basin and Pearl River basin had higher risk with the mean potential affected fractions (PAFs) of 9.27% and 7.09%, and 22.10% and 15.00% waters may pose potential risk for 5% aquatic organisms, respectively. In general, the risk of TCC in Asian waters was higher than that in Europe and North America.

4.
Breast Cancer Res ; 21(1): 81, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337427

RESUMO

BACKGROUND: Mammographic density (MD) is a strong breast cancer risk factor that reflects fibroglandular and adipose tissue composition, but its biologic underpinnings are poorly understood. Insulin-like growth factor binding proteins (IGFBPs) are markers that may be associated with MD given their hypothesized role in breast carcinogenesis. IGFBPs sequester IGF-I, limiting its bioavailability. Prior studies have found positive associations between circulating IGF-I and the IGF-I:IGFBP-3 ratio and breast cancer risk. We evaluated the associations of IGF-I, IGFBP-3, and six other IGFBPs with MD. METHODS: Serum IGF measures were quantified in 296 women, ages 40-65, undergoing diagnostic image-guided breast biopsy. Volumetric density measures (MD-V) were assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Area density measures (MD-A) were estimated by computer-assisted thresholding software. Age, body mass index (BMI), and BMI2-adjusted linear regression models were used to examine associations of serum IGF measures with MD. Effect modification by BMI was also assessed. RESULTS: IGF-I and IGFBP-3 were not strongly associated with MD after BMI adjustment. In multivariable analyses among premenopausal women, IGFBP-2 was positively associated with both percent MD-V (ß = 1.49, p value = 0.02) and MD-A (ß = 1.55, p value = 0.05). Among postmenopausal women, positive relationships between IGFBP-2 and percent MD-V (ß = 2.04, p = 0.003) were observed; the positive associations between IGFBP-2 and percent MD-V were stronger among lean women (BMI < 25 kg/m2) (ß = 5.32, p = 0.0002; p interaction = 0.0003). CONCLUSIONS: In this comprehensive study of IGFBPs and MD, we observed a novel positive association between IGFBP-2 and MD, particularly among women with lower BMI. In concert with in vitro studies suggesting a dual role of IGFBP-2 on breast tissue, promoting cell proliferation as well as inhibiting tumorigenesis, our findings suggest that further studies assessing the role of IGFBP-2 in breast tissue composition, in addition to IGF-1 and IGFBP-3, are warranted.

5.
BMC Cancer ; 19(1): 534, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159774

RESUMO

BACKGROUND: FBXO11, a member of the F-box protein family, regulates the cell-cycle by promoting the degradation of Bcl-6 and p53. This protein has been implicated in the progression of several cancers, including renal cell carcinoma (RCC). The aim of this study was to determine the prognostic role of FBXO11 in the clinical outcome of RCC patients. METHODS: FBXO11 mRNA expression was analysed in normal and RCC tissue microarrays of the Oncomine database. In addition, the in situ expression levels of stromal FBXO11 protein were assessed in primary RCC tissues from 227 patients (training and validation cohorts) using immunohistochemistry (IHC). Kaplan Meier and Cox regression analyses were used to determine the association between FBXO11 expression and cliniopathological factors. A nomogram was established using the significant prognostic factors to predict overall survival (OS) of RCC patients after one, three and 5 years. RESULTS: In the Oncomine database, FBXO11 mRNA levels were lower in normal tissues than in cancer tissues, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), hereditary ccRCC, non-hereditary ccRCC, VHL mutant ccRCC and VHL wild-type ccRCC. In addition, FBXO11 expression was also significantly higher in metastatic kidney cancer than in primary cancer. Immunohistochemical analysis reported that 57.3% (86 of 150) of the training cohort and 57.1% (44 of 77) of the validation cohort were scored as having high FBXO11 staining density. FBXO11 expression was significantly associated with Fuhrman grade (p = 0.003), UISS score (p = 0.021) and age (p = 0.048) in the training cohort. Furthermore, Kaplan-Meier survival analysis showed that higher FBXO11 levels, T stage, UISS scores and SSIGN score were associated with poor OS in ccRCC patients. Multivariate Cox analysis demonstrated that higher FBXO11 levels and higher UISS score were independent prognostic indicators for OS. Nomogram, calibration plots, AUC values and the C-index showed that the predictive accuracy of conventional prognostic models, including UISS score and SSIGN score, was improved when FBXO11 expression was added. CONCLUSIONS: FBXO11 expression was closely related to RCC malignancy and poor prognosis, indicating its potential as a prognostic marker as well as a therapeutic target for RCC.

6.
J Nat Prod ; 82(6): 1593-1598, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31181918

RESUMO

Six new glycosidic acids, arvensic acids E-J (1-6), were obtained from a glycosidic acid fraction afforded by alkaline hydrolysis of the crude resin glycosides from Convolvulus arvensis whole plants. Their structures were established from the spectroscopic data obtained and by chemical evidence. They were defined as heptasaccharides or hexasaccharides, comprising d-fucose, d-glucose, and l-rhamnose units. Compounds 1, 3, and 5 were assigned the 11 S-hydroxyheptadecanoic acid as the aglycone, while compounds 2, 4, and 6 were found to possess 11 S-hydroxyhexadecanoic acid as the aglycone. Compounds 1, 3, and 5 are the first representatives of resin glycosides with 11 S-hydroxyheptadecanoic acid as the aglycone.

7.
Cancer Imaging ; 19(1): 41, 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228956

RESUMO

BACKGROUND: To determine if mammographic features from deep learning networks can be applied in breast cancer to identify groups at interval invasive cancer risk due to masking beyond using traditional breast density measures. METHODS: Full-field digital screening mammograms acquired in our clinics between 2006 and 2015 were reviewed. Transfer learning of a deep learning network with weights initialized from ImageNet was performed to classify mammograms that were followed by an invasive interval or screen-detected cancer within 12 months of the mammogram. Hyperparameter optimization was performed and the network was visualized through saliency maps. Prediction loss and accuracy were calculated using this deep learning network. Receiver operating characteristic (ROC) curves and area under the curve (AUC) values were generated with the outcome of interval cancer using the deep learning network and compared to predictions from conditional logistic regression with errors quantified through contingency tables. RESULTS: Pre-cancer mammograms of 182 interval and 173 screen-detected cancers were split into training/test cases at an 80/20 ratio. Using Breast Imaging-Reporting and Data System (BI-RADS) density alone, the ability to correctly classify interval cancers was moderate (AUC = 0.65). The optimized deep learning model achieved an AUC of 0.82. Contingency table analysis showed the network was correctly classifying 75.2% of the mammograms and that incorrect classifications were slightly more common for the interval cancer mammograms. Saliency maps of each cancer case found that local information could highly drive classification of cases more than global image information. CONCLUSIONS: Pre-cancerous mammograms contain imaging information beyond breast density that can be identified with deep learning networks to predict the probability of breast cancer detection.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Mamografia/métodos , Detecção Precoce de Câncer , Feminino , Humanos , Processamento de Imagem Assistida por Computador/normas , Limite de Detecção , Mamografia/normas
8.
Artigo em Inglês | MEDLINE | ID: mdl-31095501

RESUMO

The coaxial-rotor micro-aerial vehicles (CRMAVs) have been proven to be a powerful tool in forming small and agile manned-unmanned hybrid applications. However, the operation of them is usually subject to unpredictable time-varying aerodynamic disturbances and model uncertainties. In this paper, an adaptive robust controller based on a neural network (NN) approach is proposed to reject such perturbations and track both the desired position and orientation trajectories. A complete dynamic model of a CRMAV is first constructed. When all system states are assumed to be available, an NN-based state-feedback controller is proposed through feedback linearization and Lyapunov analysis. Furthermore, to overcome the practical challenge that certain states are not measurable, a high-gain observer is introduced to estimate the unavailable states, and then, an output-feedback controller is developed. Rigorous theoretical analysis verifies the stability of the entire closed-loop system. In addition, extensive simulation studies are conducted to validate the feasibility of the proposed scheme.

9.
Huan Jing Ke Xue ; 40(5): 2101-2114, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087846

RESUMO

The concentrations and spatial distribution characteristics of 16 US EPA priority Polycyclic Aromatic Hydrocarbons (PAHs) in water bodies in seven basins in China were systematically analyzed and summarized. The acute ecological risks of 8 PAHs to aquatic organisms were evaluated by means of species sensitivity distribution (SSD). The joint acute ecological risks of ΣPAH8 to aquatic organisms were evaluated by concentration addition model and response addition model. The health risks of PAHs ingestion were estimated by hazard quotients. The results showed that the 2-, 3-, and 4 ringed-PAHs had higher-than-average concentrations in the water bodies from the seven basins, and the mean concentration of ΣPAH16 was 2596.25 ng·L-1, which is higher than in most foreign water bodies. The composition characteristics and sources of PAHs in water bodies of China and other countries were similar. The pollution of ΣPAH16 in northern water bodies was more serious compared with that of southern water bodies. The potentially affected fraction (PAF) values of naphthalene, acenaphthene, fluorene, phenanthrene, fluoranthene, pyrene, and anthracene to aquatic organisms in the seven basins were less than 4%. Except for the Haihe River and Yangtze River basins, the PAF values of benzo (a) pyrene to aquatic organisms exceeded 5%, which indicates that benzo (a) pyrene had high acute ecological risks to aquatic organisms. The concentration addition model was not suitable for water ecological risk assessments of PAHs. The results of risk assessments based on response addition model showed that except for the Haihe River, the multisubstance PAF (msPAF) values of ΣPAH8 to aquatic organisms in other basins exceeded 5%, which indicates that ΣPAH8 constitutes high joint acute ecological risks to aquatic organisms. The health risks through ingestion of carcinogenic PAHs from water bodies of the seven basins were at 10-5 level, which is higher than the baseline value of acceptable risk (10-6) from the US EPA. The health risks through the ingestion of non-carcinogenic PAHs were at 10-9 level, which is far lower than the baseline value of acceptable risk. The results indicate that there are potential carcinogenic risks to human health through ingestion of PAHs from seven basins in China.

10.
Int J Biol Macromol ; 135: 373-378, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31108143

RESUMO

A phenolic-UDP-glycosyltransferase Bs-PUGT from Bacillus subtilis PI18 was cloned and expressed in Escherichia coli BL21 (DE3). The purified Bs-PUGT could catalyze the glycosylation of tyrosol, 4-hydroxybenzyl alcohol, 2-hydroxybenzyl alcohol, caffeic acid, cinnamic alcohol, ferulic acid, and so on. This enzyme showed a high activity and stability over a broad pH range and was sensitive to temperature. Studies on the kinetic parameters indicated that the affinity of Bs-PUGT to UDP-G (Km) and its catalytic efficiency (Kcat) increased by 1.5-fold and 1.7-fold, respectively, with the addition of 10 mM Ca2+. The most effective glycosylation of caffeic acid catalyzed by whole-cell E. coli/Bs-PUGT was achieved with a molar yield of 78.3% in a system with pH 8.0, 30 °C, 25 g/L sucrose, 10 mM Ca2+, and 0.5 g/L substrate concentration. The addition of Ca2+ increased the molar yield of caffeic acid glucosides and shortened the reaction. This work proposes a strategy for the efficient glycosylation of phenolic compounds by microbe-derived glycosyltransferase assisted by metal ions.

11.
Sci Total Environ ; 681: 488-496, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31121399

RESUMO

The polycyclic musk galaxolide (HHCB) is widely used as fragrances in personal care products (PCPs) and has been detected in various environmental media. There is an urgent need to derive aquatic life criteria (ALC) of HHCB for the protection of aquatic organisms. Toxicity tests with 8 Chinese resident aquatic organisms from 3 phyla and 8 families were conducted, and three methods were used for deriving the ALC. A criterion maximum concentration (CMC) of 8.33 µg/L and a criterion continuous concentration (CCC) of 2.20 µg/L were derived according to the USEPA guidelines. The acute predicted no effect concentrations (PNECs) values derived by log-normal species sensitivity distribution (SSD) and log-logistic SSD method were 77.41 and 66.47 µg/L, respectively. In addition, a significant sensitivity difference was observed between the planktonic crustacean and benthic crustacean, and there was no significant difference (p > 0.05) among SSDs based on resident and non-resident species. A comparison of chronic SSDs between HHCB, tonalide (AHTN) and musk ketone (MK) showed that nitro musk (MK) was more toxic to aquatic organisms than polycyclic musks (HHCB and AHTN). Finally, an assessment of risk to aquatic organisms in surface waters and effluents of wastewater treatment plants (WWTPs) worldwide showed that potential risk may exist at several locations. HHCB concentrations in 4.08 and 46.17% of the WWTP effluents in China and 1.71 and 16.13% of the WWTP effluents in other countries exceed the hazard concentration for 5% and 1% aquatic species.


Assuntos
Benzopiranos/toxicidade , Odorantes/análise , Poluentes Químicos da Água/toxicidade , Qualidade da Água/normas , Organismos Aquáticos/fisiologia , Benzopiranos/normas , Poluentes Químicos da Água/normas
12.
ACS Nano ; 13(6): 6760-6769, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31145851

RESUMO

Thiol-polystyrene (SH-PS)-capped plasmonic nanoparticles can be fabricated into free-standing, one-nanoparticle-thick superlattice sheets (termed plasmene) based on physical entanglement between ligands, which, however, suffer from irreversible dissociation in organic solvents. To address this issue, we introduce coumarin-based photo-cross-linkable moieties to the SH-PS ligands to stabilize gold nanoparticles. Once cross-linked, the obtained plasmene nanosheets consisting of chemically locked nanoparticles can well maintain structural integrity in organic solvents. Particularly, arising from ligand-swelling-induced enlargement of the interparticle spacing, these plasmene nanosheets show significant optical responses to various solvents in a specific as well as reversible manner, which may offer an excellent material for solvent sensing and dynamic plasmonic display.

13.
Gynecol Endocrinol ; 35(9): 825-828, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30990090

RESUMO

The aim of this study is to review the natural course, clinical features, and reproductive prognosis of ovarian tumors associated with hyperandrogenemia. We retrospect 33 patients of ovarian tumors with hyperandrogenemia. Thirty cases (91%) were sex cord-stromal tumors. Sertoli-Leydig cell tumors, Leydig cell tumors, and steroid cell tumors were the most common types. It is not possible, to predict the pathological subtypes based on androgen levels alone. Most of these tumors were solid masses, with an average diameter of 3.9 cm. These tumors are soft or fragile, no clear boundary with normal tissue, thus excision is superior to exfoliation. The average disease course of the top three tumors was 32.6, 35.4, and 67.7 months, respectively. Among 11 married women with a desire to get pregnant, nine cases resumed menstrual periods after surgery and became pregnant naturally. Hyperandrogenemia might predict a better prognosis. The asynchronism of hyperandrogenemia and undetectable tumor may cause irreversible change and emotional depress, the methods of early diagnosis need further study.

14.
Nanoscale ; 11(13): 6285-6296, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30882835

RESUMO

Multimodality therapy under imaging-guidance is significant to improve the accuracy of cancer treatment. In this study, a photoacoustic imaging (PAI)-guided anticancer strategy based on poly-l-lysine functionalized melanin nanoparticles (MNP-PLL) was developed to treat laryngeal squamous cell carcinoma (LSCC). As a promising alternative to traditional therapies for LSCC, MNP-PLL/miRNA nanoparticles were combined with photothermal ablation against primary tumors and miR-145-5p mediated gene therapy for depleting the metastatic potential of tumor cells. Furthermore, taking advantage of the photoacoustic properties of melanin, PAI guided therapy could optimize the time point of NIR irradiation to maximize the efficacy of photothermal therapy (PTT). The in vitro and in vivo results proved that the combined treatments displayed the most significant tumor suppression compared with monotherapy. By integrating thermo-gene therapies into a theranostic nanoplatform, the MNP-PLL/miR-145-5p nanoparticles significantly suppressed the LSCC progression, indicating their great potential use for cancer therapy.


Assuntos
Carcinoma de Células Escamosas/terapia , Terapia Genética , Neoplasias Laríngeas/terapia , Melaninas/química , Nanopartículas/química , Animais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada , Humanos , Raios Infravermelhos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/química , MicroRNAs/metabolismo , Microscopia Confocal , Nanopartículas/uso terapêutico , Nanopartículas/toxicidade , Fototerapia , Polilisina/química , Nanomedicina Teranóstica
15.
Oncol Rep ; 41(5): 2753-2761, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896861

RESUMO

As a core kinase in the Hippo pathway, large tumor suppressor kinase 2 (LATS2) regulates cell proliferation, migration and invasion through numerous signaling pathways. However, its functions on cell proliferation, migration and invasion in glioma have yet to be elucidated. The present study revealed that LATS2 was downregulated in glioma tissues and cells, as determined by reverse transcription­quantitative polymerase chain reaction and immunohistochemistry. In addition, Cell Counting Kit­8, scratch wound healing and Transwell assays revealed that overexpression of LATS2 in U­372 MG cells inhibited cell proliferation, migration and invasion. Furthermore, western blot analysis indicated that the expression levels of phosphorylated (p)­yes­associated protein and p­tafazzin were increased in cells with LATS2 overexpression. These results indicated that LATS2 is a potential tumor suppressor, and downregulation of LATS2 in glioma may contribute to cancer progression.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/cirurgia , Linhagem Celular Tumoral , Proliferação de Células , Criança , Progressão da Doença , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Adulto Jovem
16.
Clin Infect Dis ; 69(1): 144-146, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-30924492

RESUMO

In a randomized, double-blind, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) use from 28 weeks gestational age to 2 months postpartum to prevent mother-to-child transmission of hepatitis B virus, there was no significant effect of maternal TDF use on maternal or infant bone mineral density 1 year after delivery/birth. Clinical Trials Registration. NCT01745822.

17.
Biomed Res Int ; 2019: 4390839, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30915355

RESUMO

Gastric cancer (GC) is one of the most malignant tumors, accounting for 10% of deaths caused by all cancers. Chemotherapy is often necessary for treatment of GC; the FOLFOX regimen is extensively applied. However, multidrug resistance (MDR) of GC cells prevents wider application of this treatment. Ubenimex, an inhibitor of CD13, is used as an immune adjuvant to treat hematological malignancies. Here, we demonstrate that CD13 expression positively correlates with MDR development in GC cells. Moreover, Ubenimex reverses the MDR of SGC7901/X and MKN45/X cells and enhances their sensitivity to FOLFOX, in part by decreasing CD13 expression, which is accompanied by downregulation of Bcl-xl, Bcl-2, and survivin expression; increased expression of Bax; and activation of the caspase-3-mediated apoptotic cascade. In addition, Ubenimex downregulates expression of membrane transport proteins, such as P-gp and MRP1, by inhibiting phosphorylation in the PI3K/AKT/mTOR pathway to increase intracellular accumulations of 5-fluorouracil and oxaliplatin, a process for which downregulation of CD13 expression is essential. Therefore, the present results reveal a previously uncharacterized function of CD13 in promoting MDR development in GC cells and suggest that Ubenimex is a candidate for reversing the MDR of GC cells.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leucina/análogos & derivados , Proteínas de Neoplasias/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Apoptose/genética , Antígenos CD13/biossíntese , Antígenos CD13/genética , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Leucina/farmacologia , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Neoplasias/genética
18.
Eur Radiol ; 29(10): 5607-5616, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30888479

RESUMO

OBJECTIVES: To evaluate the safety and efficacy of microwave ablation (MWA) with the assistance of continuous cool saline injection (CCSI) in patients with primary hyperparathyroidism (PHPT). METHODS: Between November 1, 2014, and February 29, 2016, 22 patients with PHPT were enrolled and treated with ultrasound-guided MWA assisted by CCSI. The levels of parathyroid hormone (PTH) and serum calcium were recorded before and after the MWA. Patients were divided into two groups (normalized and unnormalized groups) according to treatment efficacy. Fisher's exact test and the Mann-Whitney test were used to compare data between the two groups. Timing differences in serum PTH and calcium levels were analyzed with repeated measures analysis of variance. RESULTS: Normalized outcomes for both PTH and calcium levels were achieved in 19 of 22 (86.36%) patients with PHPT. In the normalized group, PTH levels remained normal for 12 months after MWA. PTH levels in the unnormalized group were outside the reference range at six of seven follow-ups within 12 months following MWA. By contrast, serum calcium levels gradually decreased in all patients in both groups. The mean serum PTH and mean calcium levels at 6 months after therapy were significantly lower than those before MWA (both p < 0.05). A transient voice change developed in eight patients. One patient experienced hypocalcaemia, which was corrected by oral calcium supplementation within 2 months. CONCLUSIONS: US-guided MWA assisted by CCSI is safe and effective for destroying parathyroid gland tissue and may serve as a therapeutic alternative for patients with PHPT. KEY POINTS: • Microwave ablation is a new option for patients with hypercalcemic or normocalcemic primary hyperparathyroidism. • Microwave ablation can decrease PTH and calcium levels with sustained efficacy in most patients. • Treatment is safe and causes only transient side effects.

19.
Invest New Drugs ; 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30734202

RESUMO

Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators in tumor development. This study aims to investigate the potential role oflncRNALEF1-AS1, in the progression of lung cancer. Quantitative real-time PCR (qRT-PCR) and western blot assays showed that LEF1-AS1 was upregulated while miR-544a was downregulated in lung cancer specimens and cells. Overexpression of LEF1-AS1 led to the enhancement of cell proliferation and invasion, revealed by CCK-8 assay and transwell assay. A negative correlation was found between LEF1-AS1 and miR-544a. BLAST analysis and dual-luciferase assay confirmed that FOXP1 is a downstream effector of miR-544a. Therefore, the LEF1-AS1/miR-544a/FOXP1 axis is an important contributor to lung cancer progression. Collectively, our novel data uncovers a new mechanism that governs tumor progression in lung cancer and provides new targets that may be used for disease monitoring and therapeutic intervention of lung cancer.

20.
Medicine (Baltimore) ; 98(1): e13933, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608422

RESUMO

This study was aimed to explore the correlation between catechol-O-methyltransferase (COMT) gene polymorphisms and endometriosis susceptibility in Chinese Han population.This case-control study recruited 134 endometriosis patients and 139 healthy individuals. COMT gene rs4680, rs2020917, and rs4646312 polymorphisms in the subjects were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Association between COMT polymorphisms and endometriosis susceptibility was evaluated by χ test and adjusted by Logistic regression. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to present the relative risk of endometriosis.A allele of rs4680 was distinctly correlated with increased susceptibility of endometriosis (OR = 1.450, 95% CI = 1.012-2.076). However, when adjusted by the confounding factors, these associations become not significant. We failed to find any significant association between rs2020917 and endometriosis risk in the crude results. The adjusted results suggested that rs2020917 TT genotype and T allele were distinctly correlated with enhanced endometriosis risk (TT vs CC: P = .038, OR = 2.894, 95% CI = 1.060-7.903; T vs C: P = .039, OR = 1.481, 95% CI = 1.021-2.149). Besides, rs4646312 C allele was significantly correlated with endometriosis risk both in the crude (P = .027, OR = 1.502, 95% CI = 1.047-2.154) and adjusted (P = .019, OR = 1.564, 95% CI = 1.078-2.269) results.COMT polymorphisms might predict the occurrence of endometriosis.


Assuntos
Catecol O-Metiltransferase/genética , Endometriose/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Reação em Cadeia da Polimerase/métodos
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