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1.
Ther Drug Monit ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33560100

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease. Initial therapy is based on etoposide, dexamethasone, and cyclosporine (CSA). The pharmacokinetics (PKs) of CSA and other drugs are sometimes altered in patients with HLH complicated by diabetes insipidus (DI) but the precise mechanisms remain unknown. METHODS: In this study, the authors present a case of a 4-year-old boy with HLH complicated by DI. CSA concentrations were determined by enzyme multiplied immunosaasy technique (EMIT), non-compartmental PK analysis of the plasma concentration-time data was performed using PKSolver, linear regression analysis was performed to determine linearity of relationship between urine output and C0 levels of CSA. RESULTS: Although C0 values of CSA were lower than the target levels, the patient was successfully treated and a good clinical outcome was achieved. Linear regression analysis showed a strong negative correlation between urine output and the serum trough concentration (C0) of CSA, pharmacokinetic analysis showed the main PK parameters of CSA as follows: C0, 50.2 µg/L; peak concentration (Cmax), 723.4 µg/L; area under the curve (AUC)0-24, 7478.2 µg·h/L; clearance, 0.77 L/h/kg, elimination half-life, 5.3 h, and volume of distribution, 6.0 L/kg. CONCLUSIONS: To the best of the authors' knowledge, this is the first report of the CSA PK profile in a patient with HLH complicated by DI. The authors suppose that a large fluid output and input leads to extensive CSA distribution. These results suggest that the monitoring of the Cmax and AUC of CSA might be more clinically and pharmacokinetically significant than that of C0 in patients with HLH complicated by DI. This case highlights the importance of Therapeutic drug monitoring (TDM) and demonstrates PK parameters of CSA in a pediatric patient with HLH complicated by DI.

2.
J Exp Clin Cancer Res ; 39(1): 269, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33256799

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is a common urological cancer. circular RNAs (circRNAs) is involved in the development of various types of cancers. However, the roles and underlying mechanisms of circRNAs in RCC are not fully elucidated. Herein, we aimed to examine the potential effect of circ_001287 on RCC progression. MATERIALS AND METHODS: Microarray-based gene expression profiling of RCC was initially employed in order to identify differentially expressed genes. Next, the expression of circ_001287 was examined, and the cell line with the highest circ_001287 expression was selected for subsequent investigation. The interaction among circ_001287, miR-144, and CEP55 was identified by conducting luciferase reporter assay, RNA-pull down, RIP, RT-qPCR and FISH. The effect of circ_001287 on proliferative, invasive and migratory capacities as well as tumorigenicity of transfected cells in mice was examined using gain- and loss-of-function experiments. RESULTS: circ_001287 and CEP55 were highly expressed while miR-144 was decreased in RCC tissues and cell lines. circ_001287 can up-regulate CEP55 by binding to miR-144, which resulted in increased proliferative, invasive and migratory capacities and tumor growth in vivo. In addition, down-regulation of miR-144 was also observed to promote these biological activities. CONCLUSIONS: Overall, these results elucidate a new mechanism for circ_001287 in RCC development and provide a potential therapeutic target for RCC patients.

3.
Oncol Lett ; 20(6): 382, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33154780

RESUMO

Hepatocellular carcinoma is a serious public health problem in China. The mortality rate associated with the majority of cancer types has decreased as a result of targeted therapy. However, the mortality rates associated with hepatocellular carcinoma have not improved; therefore, the identification of new molecular targets is required for the development of novel targeted therapies. In the present study, a new molecular target, Rhophilin Rho GTPase-binding protein 2 (RHPN2), was identified. The levels of RHPN2 protein in tumor tissues were assessed via immunohistochemistry, while the mRNA levels were analyzed via reverse transcription-quantitative PCR. Additionally, cell viability was tested via MTT analysis. RHPN2 expression was upregulated in hepatocellular carcinoma tissues compared with that of matched adjacent normal tissues. More importantly, low expression of RHPN2 in patients with hepatocellular carcinoma was associated with an improved prognosis rate compared with patients with high expression. Downregulation of RHPN2 reduced the proliferation of hepatocellular carcinoma cells and increased the rate of apoptosis, whereas overexpression of RHPN2 demonstrated the opposite effects. Hepatocyte nuclear factor 1α was implicated in the mechanism of RHPN2. Overall, these data indicated that overexpression of RHPN2 may promote hepatocellular carcinoma.

4.
J Trace Elem Med Biol ; 62: 126629, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32745979

RESUMO

BACKGROUND: More and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis. MATERIALS AND METHODS: Studies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls. RESULTS: Thirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies. CONCLUSION: The results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.

5.
J Cell Mol Med ; 24(17): 9712-9725, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32729666

RESUMO

Renal cell carcinoma (RCC) is a common urologic malignancy, and up to 30% of RCC patients present with locally advanced or metastatic disease at the time of initial diagnosis. Increasing evidence suggests that circular RNAs (circRNAs) serve as genomic regulatory molecules in various human cancers. Our initial in silico microarray-based analysis identified that circRNA circ_001842 was highly expressed in RCC. Such up-regulation of circ_001842 in RCC was experimentally validated in tissues and cell lines using RT-qPCR. Thereafter, we attempted to identify the role of circ_001842 in the pathogenesis of RCC. Through a series of gain- and loss-of function assays, cell biological functions were examined using colony formation assay, Transwell assay, annexin V-FITC/PI-labelled flow cytometry and scratch test. A high expression of circ_001842 in tissues was observed as associated with poor prognosis of RCC patients. circ_001842 was found to elevate SLC39A14 expression by binding to miR-502-5p, consequently resulting in augmented RCC cell proliferation, migration and invasion, as well as EMT in vitro and tumour growth in vivo. These observations imply the involvement of circ_001842 in RCC pathogenesis through a miR-502-5p-dependent SLC39A14 mechanism, suggesting circ_001842 is a potential target for RCC treatment.

6.
Int J Mol Med ; 46(3): 1118-1134, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32582980

RESUMO

The SAM and SH3 domain­containing 1 (SASH1) genes have been identified as the causal genes of dyschromatosis universalis hereditaria (DUH); these genes cause the pathological phenotypes of DUH, and SASH1 variants have been shown to regulate the abnormal pigmentation phenotype in human skin in various genodermatoses. However, investigations into the mutated SASH1 gene have been limited to in vitro studies. In the present study, to recapitulate the molecular pathological phenotypes of individuals with DUH induced by SASH1 mutations, a heterozygous BALB/c mouse model, in which the human SASH1 c.1654 T>G (p. Tyr 551Asp, Y551D) mutation was knocked in was first generated. The in vivo functional experiments on Y551D SASH1 indicated that the increased expression of microphthalmia­associated transcription factor (Mitf) was uniformly induced in the tails of heterozygous BALB/c mice, and an increased quantity of Mitf­positive epithelial cells was also detected. An increased expression of Mitf­ and Mitf­positive cells was also demonstrated in the epithelial tissues of Y551D­SASH1 affected individuals. In the present study, Mitf expression was also found to be increased by Y551D SASH1 in vitro. Taken together, these findings indicate that the upregulation of Mitf is the bona fide effector of the Y551D SASH1­mediated melanogenesis signaling pathway in vivo. SASH1 may function as a scaffold molecule for the assembly of a SASH1­Mitf molecular complex to regulate Mitf expression in the cell nucleus and thus to promote the hyperpigmented phenotype in the pathogenesis of DUH and other genodermatoses related to pigment abnormalities.

7.
Oxid Med Cell Longev ; 2020: 5737289, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308805

RESUMO

Background: Previous studies have demonstrated that lncRNAs play functional roles in regulating cancer cell proliferation, invasion, and apoptosis. Recent studies confirmed that lncRNA 00312 has important biological functions in lung and colorectal cancer. However, the role of lncRNA 00312 in renal cell carcinoma (RCC) remains unclear. Our aim was to explore the function of lncRNA 00312 in RCC and its potential molecular mechanism. Methods: RCC cell lines A498 and ACHN were used as in vitro models in this study. RT-PCR was performed to determine lncRNA 00312, miR-34a-5p, and ASS1 mRNA expression. Proliferation and invasion were examined by CCK-8 and Transwell assay to confirm the function role of lncRNA 00312. Western blot analysis was used to examine the expression of apoptotic proteins Bax and Bcl-2. Results: lncRNA was significantly downregulated in RCC cells such as A498 and ACHN; the expression of lncRNA 00312 in RCC tissues was significantly lower than that in adjacent normal tissues. Patients with low expression of lncRNA 00312 have worse prognosis regarding pathological grade, tumor size, and TNM stage. Overexpression of lncRNA 00312 suppressed A498 and ACHN cell proliferation and invasion, while promoting apoptosis. Our study found that miR-34a-5p had the potential binding site with lncRNA 00312 and revealed the role of miR-34a-5p in RCC. Furthermore, we confirmed that lncRNA 00312 played its role with the participation of ASS1 and miR-34a-5p. Conclusion: lncRNA 00312 can inhibit RCC proliferation and invasion and promote apoptosis in vitro by suppressing miR-34a-5p and overexpressing ASS1. Our study demonstrated that the lncRNA 00312/miR-34a-5p/ASS1 axis may play a functional role in the progression of RCC; lncRNA 00312 abundance is a prognostic factor candidate for RCC survival, which provides new insights for RCC clinical treatment.in vitro models in this study. RT-PCR was performed to determine lncRNA 00312, miR-34a-5p, and ASS1 mRNA expression. Proliferation and invasion were examined by CCK-8 and Transwell assay to confirm the function role of lncRNA 00312. Western blot analysis was used to examine the expression of apoptotic proteins Bax and Bcl-2.

8.
Phytother Res ; 34(7): 1570-1577, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32072706

RESUMO

A low insulin-like growth factor 1 (IGF-1) level is known to be associated with many disorders. Several studies have shown that soy consumption may influence IGF-1, but the findings remain inconclusive. In this work, we conducted a systematic review and meta-analysis to provide a more accurate estimation of the effect of soy consumption on plasma IGF-1. A comprehensive systematic search was performed in Scopus, Embase, Web of Science, and PubMed/MEDLINE databases from inception until October 2019. Eight studies fulfilled the eligibility criteria. The pooled weighted mean difference (WMD) of the eligible studies was calculated with random-effects approach. Overall, a significant increment in plasma IGF-1 was observed following soy intervention (WMD: 13.5 ng/ml, 95% CI: 5.2, 21.8, I2 = 97%). Subgroup analyses demonstrated a significantly greater increase in IGF-1, when soy was administered at a dosage of ≤40 g/day (WMD: 11.7 ng/ml, 95% CI: 10.9 to 12.6, I2 = 98%), and when the intervention duration was <12 weeks (WMD: 26.6 ng/ml, 95% CI: 9.1 to 44.1, I2 = 0.0%). In addition, soy intervention resulted in a greater increase in IGF-1 among non-healthy subjects (WMD: 36 ng/ml, 95% CI: 32.7 to 39.4, I2 = 84%) than healthy subjects (WMD: 9.8 ng/ml, 95% CI: 8.9 to 10.7, I2 = 90%). In conclusion, this study provided the first meta-analytical evidence that soy intake may increase IGF-1 levels, but the magnitude of the increase is dependent on the intervention dosage, duration, and health status of the participants.


Assuntos
Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Soja/efeitos adversos , Humanos , Adulto Jovem
9.
Nat Commun ; 11(1): 262, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937768

RESUMO

Navigation requires not only the execution of locomotor programs but also high arousal and real-time retrieval of spatial memory that is often associated with hippocampal theta oscillations. However, the neural circuits for coordinately controlling these important processes remain to be fully dissected. Here we show that the activity of the neuromedin B (NMB) neurons in the nucleus incertus (NI) is tightly correlated with mouse locomotor speed, arousal level, and hippocampal theta power. These processes are reversibly suppressed by optogenetic inhibition and rapidly promoted by optogenetic stimulation of NI NMB neurons. These neurons form reciprocal connections with several subcortical areas associated with arousal, theta oscillation, and premotor processing. Their projections to multiple downstream stations regulate locomotion and hippocampal theta, with the projection to the medial septum being particularly important for promoting arousal. Therefore, NI NMB neurons functionally impact the neural circuit for navigation control according to particular brains states.


Assuntos
Nível de Alerta/fisiologia , Hipocampo/fisiologia , Locomoção/fisiologia , Núcleos da Rafe/fisiologia , Animais , Feminino , Masculino , Camundongos , Vias Neurais/fisiologia , Neurocinina B/análogos & derivados , Neurocinina B/metabolismo , Neurônios/metabolismo , Optogenética , Núcleos da Rafe/citologia , Septo do Cérebro/fisiologia , Navegação Espacial/fisiologia , Ritmo Teta
10.
Environ Sci Pollut Res Int ; 27(2): 1224-1233, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30155638

RESUMO

In this work, sludge-derived carbon (SC) was innovatively integrated with copper oxide (CuO) on macroporous silicon carbide foams to construct a distinctive catalyst (CuO/SC) with strong catalytic activity, which can effectively activate persulfate (PS) for the removal of methyl mercaptan (CH3SH). The structure and morphology of CuO/SC were investigated by means of XRD, SEM, and EDS. The effects of initial pH values, copper contents, PS dosages, and flow rates on CH3SH removal were also investigated. Under optimal condition, more than 90% of CH3SH was removed by CuO/SC-PS combined system within 10-min reaction due to the synergistic function of CuO and SC. More importantly, on the basis of reactive species trapping and ESR spectroscopy, it is revealed that the responsible reactive species for catalytic CH3SH composition were ·SO4-, ·OH, 1O2, and ·O2- in CuO/SC-PS system. Finally, the possible PS activation scheme of CuO/SC samples was proposed.


Assuntos
Compostos Inorgânicos de Carbono/química , Carbono , Cobre/química , Esgotos , Compostos de Silício/química , Espécies Reativas de Oxigênio , Compostos de Sulfidrila/química
11.
Elife ; 82019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647409

RESUMO

Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed diverse and segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.


Assuntos
Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , Neurônios Serotoninérgicos/citologia , Neurônios Serotoninérgicos/fisiologia , Transcriptoma , Animais , Mapeamento Encefálico , Camundongos , Análise de Sequência de RNA , Análise de Célula Única
12.
Oncol Lett ; 18(5): 5332-5340, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612043

RESUMO

The Wnt/ß-catenin signaling pathway is a well-studied pathway that drives the carcinogenesis and metastasis of colorectal cancer (CRC). The secretion of Wnt proteins is essential for the continuous activation of Wnt/ß-catenin signaling in CRC. The secretion of Drosophila wingless, which is homologous to the human Wnt protein, is mediated by sorting nexin 3 (SNX3) in Drosophila; however, the role of SNX3 in CRC remains unknown. In the present study it was demonstrated that SNX3 reduced the migratory and invasive ability of HCT116 human CRC cells, and reversed epithelial-mesenchymal transition (EMT). Conversely, in the HT29 CRC cell line, which endogenously expresses high levels of SNX3, short hairpin RNA or siRNA-mediated knockdown of SNX3 induced EMT, and enhanced cell migration and invasion. In addition, upregulation of SNX3 significantly inhibited metastasis of HCT116 cells to the lungs of mice. These SNX3-mediated effects were associated with downregulation of ß-catenin. Taken together, by downregulating ß-catenin, SNX3 may mediate EMT and reverse CRC metastasis.

13.
Free Radic Biol Med ; 143: 288-299, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445205

RESUMO

Transient Receptor Potential Melastatin-2 (TRPM2) is a nonselective cation channel mediating Ca2+ influx in response to oxidative stress. Given that insulin resistance-related endothelial dysfunction in obesity attributes to fatty-acid-induced reactive oxygen species (ROS) overproduction, in this study, we addressed the possible role of TRPM2 in obesity-related endothelial insulin resistance and the underlying mechanisms. Whole-cell patch clamp technique, intracellular Ca2+ concentration measurement, western blot, vasorelaxation assay, and high-fat diet (HFD)-induced obese model were employed to assess the relationship between TRPM2 and endothelial insulin response. We found that both the expression and activity of TRPM2 were higher in endothelial cells of obese mice. Palmitate rose a cationic current in endothelial cells which was inhibited or enlarged by TRPM2 knockdown or overexpression. Silencing of TRPM2 remarkably improved insulin-induced endothelial Akt activation, nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production, while TRPM2 overexpression resulted in the opposite effects. Furthermore, TRPM2-mediated Ca2+ entry, CaMKII activation and the following activation of PERK/ATF4/TRB3 cascade were involved in the mechanism of obesity or palmitate-induced endothelial insulin resistance. Notably, in vivo study, knockdown of TRPM2 with adeno-associated virus harboring short-hairpin RNA (shRNA) against TRPM2 alleviated endothelial insulin resistance and ameliorated endothelium-dependent vasodilatation in obese mice. Thus, these results suggest that TRPM2-activated Ca2+ signaling is necessary to induce insulin resistance-related endothelial dysfunction in obesity. Downregulation or pharmacological inhibition of TRPM2 channels may lead to the development of effective drugs for treatment of endothelial dysfunction associated with oxidative stress state.


Assuntos
Cálcio/metabolismo , Endotélio Vascular/patologia , Ácidos Graxos não Esterificados/toxicidade , Peróxido de Hidrogênio/toxicidade , Resistência à Insulina , Obesidade/fisiopatologia , Canais de Cátion TRPM/metabolismo , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Oxidantes/toxicidade , Estresse Oxidativo , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Canais de Cátion TRPM/genética , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
14.
Medicine (Baltimore) ; 97(46): e13169, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30431590

RESUMO

BACKGROUND: While liposomal cisplatin has shown enhanced drug tolerability and higher targeting property as compared with the conventional cisplatin, the doubt remains whether lipoplatin could improve its anticancer efficacy. What's more, there is still no systematic evaluation of the safety profiles of lipoplatin comparing with original cisplatin. Thus, we performed a systematic literature search for randomized clinical trials directly comparing efficacy and safety of liposomal cisplatin versus its conventional nonliposomal cisplatin. METHODS: The electronic search was conducted in PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov from inception to February 10, 2018. The pooled odds ratio (OR) and 95% confidence intervals (CIs) of progressive disease (PD), partial response (PR), stable disease (SD), and adverse events (AEs) were obtained to assess the efficacy and safety. Heterogeneity was estimated using the I test (I > 50%, significant heterogeneity). RESULTS: The search yielded 5 clinical trials that meet inclusion criteria, with a total of 523 patients. We found that the liposome encapsulated cisplatin was more clinical efficacious than cisplatin as assessed by PD rate (OR, 0.46; 95% CI, 0.28-0.74; P = .002), while subgroup analysis of the only nonsmall cell lung cancer (NSCLC) patients showed higher response rates in PR (OR, 0.46; 95% CI, 0.28-0.74; P = .002) and PD (OR, 0.46; 95% CI, 0.28-0.74; P = .002) simultaneously. In addition, the toxicity meta-analysis revealed lipoplatin was much less toxic than the original cisplatin, with respect to grade 3 to 4 neurotoxicity (OR, 0.18; 95% CI, 0.04-0.74; P = .02), grade 3 to 4 leukopenia (OR, 0.47; 95% CI, 0.26-0.85; P = .01), grade 3 to 4 neutropenia (OR, 0.26; 95% CI, 0.09-0.71; P = .009), grade 1 and 2 nausea/vomiting (OR, 0.50; 95% CI, 0.32-0.77; P = .002), and grade 3 and 4 asthenia (OR, 0.11; 95% CI, 0.03-0.42; P = .001). CONCLUSIONS: This meta-analysis revealed that with both NSCLC and squamous cell carcinoma of the head and neck (SCCHN) patients, liposomal cisplatin-based chemotherapy offers significant advantages regarding the PD and reduced toxicities relative to conventional cisplatin.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Resultado do Tratamento
15.
Sensors (Basel) ; 18(9)2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30177608

RESUMO

The rapid development of electronic techniques in automobile has led to an increase of potential safety hazards, thus, a strong on-board diagnostic (OBD) system is desperately needed. To solve the problem of OBD insensitivity to manufacture errors or aging faults, the paper proposes a novel multi information fusion method. The diagnostic model is composed of a data fusion layer, feature fusion layer, and decision fusion layer. They are based on the back propagation (BP) neural network, support vector machine (SVM), and evidence theory, respectively. Algorithms are mainly focused on the reliability allocation of diagnostic results, which come from the data fusion layer and feature fusion layer. A fault simulator system was developed to simulate bias and drift faults of the intake pressure sensor. The real vehicle experiment was carried out to acquire data that are used to verify the availability of the method. Diagnostic results show that the multi-information fusion method improves diagnostic accuracy and reliability effectively. The study will be a promising approach for the diagnosis bias and drift fault of sensors in electronic control systems.

16.
Br J Pharmacol ; 175(18): 3669-3684, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29968377

RESUMO

BACKGROUND AND PURPOSE: Transmembrane member 16A (TMEM16A), an intrinsic constituent of the Ca2+ -activated Cl- channel, is involved in vascular smooth muscle cell (VSMC) proliferation and hypertension-induced cerebrovascular remodelling. However, the functional significance of TMEM16A for apoptosis in basilar artery smooth muscle cells (BASMCs) remains elusive. Here, we investigated whether and how TMEM16A contributes to apoptosis in BASMCs. EXPERIMENTAL APPROACH: Cell viability assay, flow cytometry, Western blot, mitochondrial membrane potential assay, immunogold labelling and co-immunoprecipitation (co-IP) were performed. KEY RESULTS: Hydrogen peroxide (H2 O2 ) induced BASMC apoptosis through a mitochondria-dependent pathway, including by increasing the apoptosis rate, down-regulating the ratio of Bcl-2/Bax and potentiating the loss of the mitochondrial membrane potential and release of cytochrome c from the mitochondria to the cytoplasm. These effects were all reversed by the silencing of TMEM16A and were further potentiated by the overexpression of TMEM16A. Endogenous TMEM16A was detected in the mitochondrial fraction. Co-IP revealed an interaction between TMEM16A and cyclophilin D, a component of the mitochondrial permeability transition pore (mPTP). This interaction was up-regulated by H2 O2 but restricted by cyclosporin A, an inhibitor of cyclophilin D. TMEM16A increased mPTP opening, resulting in the activation of caspase-9 and caspase-3. The results obtained with cultured BASMCs from TMEM16A smooth muscle-specific knock-in mice were consistent with those from rat BASMCs. CONCLUSIONS AND IMPLICATIONS: These results suggest that TMEM16A participates in H2 O2 -induced apoptosis via modulation of mitochondrial membrane permeability in VSMCs. This study establishes TMEM16A as a target for therapy of several remodelling-related diseases.


Assuntos
Anoctamina-1/fisiologia , Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Animais , Apoptose/fisiologia , Células Cultivadas , Ciclofilina D , Ciclofilinas/metabolismo , Citocromos c/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias Musculares/enzimologia , Mitocôndrias Musculares/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/metabolismo , Ratos , Ratos Sprague-Dawley
17.
Neuron ; 97(4): 911-924.e5, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29398361

RESUMO

The interactions between predator and prey represent some of the most dramatic events in nature and constitute a matter of life and death for both sides. The hypothalamus has been implicated in driving predation and evasion; however, the exact hypothalamic neural circuits underlying these behaviors remain poorly defined. Here, we demonstrate that inhibitory and excitatory projections from the mouse lateral hypothalamus (LH) to the periaqueductal gray (PAG) in the midbrain drive, respectively, predation and evasion. LH GABA neurons were activated during predation. Optogenetically stimulating PAG-projecting LH GABA neurons drove strong predatory attack, and inhibiting these cells reversibly blocked predation. In contrast, LH glutamate neurons were activated during evasion. Stimulating PAG-projecting LH glutamate neurons drove evasion and inhibiting them impeded predictive evasion. Therefore, the seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the LH to the PAG. VIDEO ABSTRACT.


Assuntos
Neurônios GABAérgicos/fisiologia , Região Hipotalâmica Lateral/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Comportamento Predatório/fisiologia , Animais , Comportamento Animal , Feminino , Masculino , Camundongos Endogâmicos C57BL , Vias Neurais/fisiologia
18.
J Hazard Mater ; 344: 1198-1208, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29162299

RESUMO

A heterogeneous catalytic ozonation/membrane filtration (HCOMF) system was fabricated by integrating a flat-plate polyvinylidene fluoride (PVDF) membrane module along with a slurry catalytic ozonation reactor. The performance and catalytic activity of HCOMF was evaluated for degradation of model wastewater containing bisphenol A (BPA) and humid acid (HA) under different permeation flux in long-term continuous experiments. The membrane fouling was investigated by trans-membranous pressure (TMP), membrane filtration resistance, scanning electronic microscopy (SEM), and fluorescence spectra. The results showed that HCOMF system exhibited an excellent and stable catalytic activity in long-term continuous experiments owning to integration of 3D MnO2 hollow microsphere ozone-catalysis with flat-plate membrane filtration. The TMP of HCOMF system didn't increase significantly, and the membrane resistance Rp and Rc declined from 4% and 16% to 1% and 4%, respectively, thus, the membrane fouling of HCOMF system was mitigated compared to MF system. The mitigation of membrane fouling in HCOMF system was attributed to the increase of hydrophilicity of membrane surface and change of HA fractions.

19.
Int J Infect Dis ; 61: 23-26, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28572073

RESUMO

The successful use of tigecycline in a 12-month old liver transplant recipient with extensively drug-resistant Acinetobacter baumannii bacteremia is presented. Tigecycline serum concentrations were monitored to help improve antibiotic efficacy and minimize side effects. A literature review identified 11 additional pediatric cases of A. baumannii infection treated with tigecycline since 2011. Tigecycline treatment should be considered in children with extensively drug-resistant bacterial infections.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Minociclina/análogos & derivados , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Bacteriemia/microbiologia , Farmacorresistência Bacteriana , Humanos , Lactente , Transplante de Fígado , Masculino , Minociclina/uso terapêutico , Tigeciclina
20.
J Cell Mol Med ; 21(10): 2465-2480, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28382689

RESUMO

We previously reported that three point mutations in SASH1 and mutated SASH1 promote melanocyte migration in dyschromatosis universalis hereditaria (DUH) and a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. However, the underlying mechanism of molecular regulation to cause this hyperpigmentation disorder still remains unclear. In this study, we aimed to investigate the molecular mechanism undergirding hyperpigmentation in the dyschromatosis disorder. Our results revealed that SASH1 binds with MAP2K2 and is induced by p53-POMC-MC1R signal cascade to enhance the phosphorylation level of ERK1/2 and CREB. Moreover, increase in phosphorylated ERK1/2 and CREB levels and melanogenesis-specific molecules is induced by mutated SASH1 alleles. Together, our results suggest that a novel SASH1/MAP2K2 crosstalk connects ERK1/2/CREB cascade with p53-POMC-MC1R cascade to cause hyperpigmentation phenotype of DUH.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hiperpigmentação/metabolismo , MAP Quinase Quinase 2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Células HEK293 , Humanos , Hiperpigmentação/genética , MAP Quinase Quinase 2/genética , Modelos Biológicos , Mutação , Transtornos da Pigmentação/congênito , Transtornos da Pigmentação/genética , Transtornos da Pigmentação/metabolismo , Ligação Proteica , Interferência de RNA , Transdução de Sinais/genética , Dermatopatias Genéticas/genética , Dermatopatias Genéticas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética
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