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1.
Int J Mol Sci ; 21(9)2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32392795

RESUMO

In antibiotics, ß-lactam is one kind of major concern acknowledged as an unavoidable contaminant in milk. Thus, a facile and sensitive method is essential for rapid ß-lactam antibiotics detection. In our work, a specific electrochemical receptor sensor based on the graphene/thionine (GO/TH) composite was established. The mechanism of the electrochemical receptor sensor was a direct competitive inhibition of the binding of horseradish peroxidase-labeled ampicillin (HRP-AMP) to the mutant BlaR-CTD protein by free ß-lactam antibiotics. Then, horseradish peroxidase (HRP) catalyzed the hydrolysis of the substrate hydrogen peroxide (H2O2), which produced an electrochemical signal. Under optimal experimental conditions, this method could quantitatively detect cefquinome from 0.1 to 8 µg L-1 and with the limit of detection (LOD) of 0.16 µg L-1, much lower than the maximum residue limit (MRL) of 5 µg L-1 set by the European Union. In addition, the LOD of spiked milk samples with cefalexin, cefquinoxime, cefotafur, penicillin G and ampicillin were 14.88 µg L-1, 2.46 µg L-1, 17.16 µg L-1, 0.06 µg L-1, 0.21 µg L-1 and the limits of quantitation (LOQ) were 36.09 µg L-1, 5.40 µg L-1, 41.45 µg L-1, 0.13 µg L-1, 0.42 µg L-1, respectively. The sensor showed a favorable recovery of 84.89-102.44%. Moreover, the electrochemical receptor sensor was successfully applied to assay ß-lactam antibiotics in milk, which showed good correlation with the results obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS).

2.
Chin Med J (Engl) ; 133(10): 1175-1181, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433049

RESUMO

BACKGROUND: Patients carrying the HongKongαα (HKαα) allele and -α/ααα could be misdiagnosed as -α/αα by the current conventional thalassemia detection methods, leading to inaccurate genetic counseling and an incorrect prenatal diagnosis. This study was aimed to accurately analyze the genotypes of HKαα carriers and -α/ααα. METHODS: Samples were collected in our hospital from July 2017 to October 2019. Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB). Anti-4.2 multiplex-PCR was used to confirm carriers of the ααα duplication with -α deletion. Two-round nested PCR and multiplex ligation-dependent probe amplification (MLPA) were applied to accurately identify and confirm their genotypes. For data analysis, we used descriptive statistics and Fisher's exact tests. RESULTS: Two thousand five hundred and forty-four cases were identified as thalassemia in 5488 peripheral blood samples. The results showed that α, ß, and αß compound thalassemia were identified in 1190 (46.78%), 1286 (50.55%), and 68 (2.67%) cases, respectively. A total of 227 samples from thalassemia patients were identified as -α/αα by Gap-PCR, and the genotypes of two samples were uncertain. There was a difference between Gap-PCR and combined groups (Gap-PCR combined with nested PCR and MLPA) in detecting HKαα (P < 0.05). Among the 229 patients, 20 patients were identified as HKαα carriers and one was identified as -α/ααα by two-round nested PCR and MLPA, including 15 patients with HKαα/αα, three with HKαα/αα and ß-thalassemia coinheritance, one with HKαα/--, one with HKαα/-α and ß-thalassemia coinheritance, and one with -α/ααα and ß-thalassemia coinheritance. CONCLUSIONS: ααα and HKαα genotypes of patients carrying -α need to be detected to reduce the misdiagnosis rate of patients carrying HKαα and -α3.7/ααα alleles. More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA.

3.
J Pineal Res ; : e12665, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358852

RESUMO

Death-associated protein kinase 1 (DAPK1) is upregulated in the brains of human Alzheimer's disease (AD) patients compared with normal subjects, and aberrant DAPK1 regulation is implicated in the development of AD. However, little is known about whether and how DAPK1 function is regulated in AD. Here, we identified melatonin as a critical regulator of DAPK1 levels and function. Melatonin significantly decreases DAPK1 expression in a post-transcriptional manner in neuronal cell lines and mouse primary cortical neurons. Moreover, melatonin directly binds to DAPK1 and promotes its ubiquitination, resulting in increased DAPK1 protein degradation through a proteasome-dependent pathway. Furthermore, in tau-overexpressing mouse brain slices, melatonin treatment and the inhibition of DAPK1 kinase activity synergistically decrease tau phosphorylation at multiple sites related to AD. In addition, melatonin and DAPK1 inhibitor dramatically accelerate neurite outgrowth and increase the assembly of microtubules. Mechanistically, melatonin-mediated DAPK1 degradation increases the activity of Pin1, a prolyl isomerase known to play a protective role against tau hyperphosphorylation and tau-related pathologies. Finally, elevated DAPK1 expression shows a strong correlation with the decrease in melatonin levels in human AD brains. Combined, these results suggest that DAPK1 regulation by melatonin is a novel mechanism that control tau phosphorylation and function and offers new therapeutic options for treating human AD.

4.
Chin Med J (Engl) ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32345813

RESUMO

BACKGROUND: Patients carrying the HongKongαα (HKαα) allele and -α/ααα could be misdiagnosed as -α/αα by the current conventional thalassemia detection methods, leading to inaccurate genetic counseling and an incorrect prenatal diagnosis. This study was aimed to accurately analyze the genotypes of HKαα carriers and -α/ααα. METHODS: Samples were collected in our hospital from July 2017 to October 2019. Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB). Anti-4.2 multiplex-PCR was used to confirm carriers of the ααα duplication with -α deletion. Two-round nested PCR and multiplex ligation-dependent probe amplification (MLPA) were applied to accurately identify and confirm their genotypes. For data analysis, we used descriptive statistics and Fisher's exact tests. RESULTS: 2,544 cases were identified as thalassemia in 5488 peripheral blood samples. The results showed that α, ß, and αß compound thalassemia were identified in 1190 (46.78%), 1286 (50.55%), and 68 (2.67%) cases, respectively. A total of 227 samples from thalassemia patients were identified as -α/αα by Gap-PCR, and the genotypes of two samples were uncertain. There was a difference between Gap-PCR and combined groups (Gap-PCR combined with nested PCR and MLPA) in detecting HKαα (P < 0.05). Among the 229 patients, 20 patients were identified as HKαα carriers and one patient was identified as -α/ααα by two-round nested PCR and MLPA, including 15 patients with HKαα/αα, three patients with HKαα/αα and ß-thalassemia coinheritance, one patient with HKαα/--, one patient with HKαα/-α and ß-thalassemia coinheritance, and one patient with -α/ααα and ß-thalassemia coinheritance. CONCLUSIONS: ααα and HKαα genotypes of patients carrying -α need to be detected to reduce the misdiagnosis rate of patients carrying HKαα and -α3.7/ααα alleles. More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA.

5.
BMC Pediatr ; 20(1): 146, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241251

RESUMO

BACKGROUND: Group B streptococcus (GBS)-induced invasive disease is a major cause of illness and death among infants aged under 90 days in China; however, invasive GBS infection remains unknown in China. We aimed to describe the serotype and genotype distributions of early-onset disease (EOD) and late-onset disease (LOD), and to show the clinical correlations among various GBS serotypes and genotypes obtained from infants with invasive GBS infections. METHODS: Between June 1, 2016 and June 1, 2018, 84 GBS strains were collected from patients younger than 90 days at seven Chinese hospitals. Clinical data were retrospectively reviewed. GBS serotyping was conducted and multi-locus sequence typing was performed. RESULTS: Serotypes Ia, Ib, II, III, and V were detected. Serotype III (60.71%) was the most common, followed by Ia (16.67%) and Ib (14.29%). Intrapartum temperature ≥ 37.5 °C, chorioamnionitis, and mortality were noted in 28.57, 42.86, and 28.57% of patients with serotype Ia, respectively, and these rates were higher than those in patients with serotypes Ib and III (P = 0.041, P = 0.031, and P = 0.023, respectively). The incidence of respiratory distress was lower (P = 0.039) while that of purulent meningitis was higher (P = 0.026) in the serotype III group. Eighteen sequence types were detected among isolates, and ST17 [42.86% (36/84)] was the most prevalent. CONCLUSIONS: GBS isolates belonging to serotypes Ia, Ib, and III are common in southern mainland China, and ST17 is highly prevalent. Differences were found in the clinical manifestations of invasive GBS disease induced by serotypes Ia and III.

6.
J Hazard Mater ; 395: 122672, 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32305716

RESUMO

Duckweeds are widely recognized for the heavy metal phytoremediation. However, the intraspecific variations in biological responses of duckweeds to heavy metal remain largely unknown. Here, the toxicity and phytoaccumulation of cadmium (Cd) were synchronously evaluated in 30 accessions of giant duckweed (Spirodela polyrhiza) collected from different provenances in Southern China. Exposure to 1 µM Cd decreased relative growth rates of dry weight, fronds number and fronds area, as well as photosynthetic pigment contents, while it increased H2O2 accumulation, lipid peroxidation and activities of anti-oxidant enzymes in the majority of accessions. Cd treatment led to remarkable Cd accumulation but little changes in the starch content in giant duckweed. The biological responses to Cd varied among the accessions. Further correlation analysis indicated that growth traits and Cd concentration were positively correlated with Cd accumulation, while the contents of chlorophyll, H2O2 and MDA were negatively associated with Cd accumulation. Our results proved the great intraspecific variation in Cd tolerance of giant duckweed, suggesting a valuable natural resource for Cd phytoremediation. Moreover, different mechanisms may be exploited by S. polyrhiza for phytoaccumulation, but growth maintenance, Cd uptake and antioxidative enzyme-independent ROS-scavenging under Cd exposure are the common mechanisms contributing to Cd accumulation ability.

7.
Chemosphere ; 249: 126016, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32062561

RESUMO

The tissue distribution and bioaccumulation of 8:2 fluorotelomer alcohol (8:2 FTOH) were evaluated in pigs after oral exposure of a dose of 5 mg/kg.b.w.d. for 7 d. The bioaccumulation of 8:2 FTOH and its metabolites showed significant differences among the various tissues. The parent compound was quickly depleted, and the main metabolites perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), and 3-perfluoroheptyl propanoic acid (7:3 FTCA) were detected in all tissues examined. The relative elimination half-life (T1/2re) calculated by compound concentration of 7:3 FTCA and PFOA was longest in kidney tissue (8.60 and 23.9 d, respectively), while their absolute elimination half-life (T1/2ab) of 7:3 FTCA and PFOA calculated by compound amount was longest in kidney tissue (10.41 and 64.1 d, respectively). The T1/2re and T1/2ab for PFHpA was longest in heart tissue (19.3 d and 30.26 d, respectively).The accumulated PFOA in kidney and liver tissues was still above the detection limit (LOD) at 21 d postdosing. These results indicate that PFOA and the kidneys are the ideal biomonitoring marker and target tissue, respectively, for 8:2 FTOH pollution. The T1/2 values of the main metabolites were of long duration compared to the growth cycle of farmed pigs (approximately 180 d) before slaughter; therefore, pigs contaminated with 8:2 FTOH present a potential risk to humans.


Assuntos
Fluorcarbonetos/metabolismo , Animais , Bioacumulação , Caprilatos , Etanol/metabolismo , Fluorcarbonetos/administração & dosagem , Ácidos Heptanoicos , Hidrocarbonetos Fluorados/metabolismo , Fígado/metabolismo , Suínos , Distribuição Tecidual
8.
Med Sci Monit ; 26: e921580, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32049955

RESUMO

BACKGROUND Codonopsis pilosula is a traditional Chinese medicine that has an anti-aging effect. However, the anti-aging effect of Codonopsis pilosula on the lungs remains largely unknown, and the molecular mechanism also needs to be further studied. Thus, we investigated the protective effect of Codonopsis pilosula on the lungs of aging mice, and explored the underlying molecular mechanism. MATERIAL AND METHODS We established an aging mouse model and then treated the mice with Codonopsis pilosula. Microarray analysis and bioinformatics methods were used to comprehensively analyze the lncRNA-miRNA-mRNA (ceRNA) network. RESULTS Our results showed that we successfully established the aging mouse model. The microarray analysis showed that 138 lncRNAs, 128 mRNAs, and 7 miRNAs were significantly changed after aging, and 282 lncRNAs, 283 mRNAs, and 19 miRNAs were dysregulated after treatment with Codonopsis pilosula. To explore the signaling pathways involved, KEGG pathway analysis was performed. Compared with the ceRNA network in aging mice and after treatment with Codonopsis pilosula, we found that 3 mRNAs (Hif3a, Zbtb16, Plxna2) and 1 lncRNA (NONMMUT063872) were associated with the anti-aging effect of Codonopsis pilosula and they were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CONCLUSIONS Our results showed that Codonopsis pilosula has a protective effect on the aging lung, and the ceRNA network plays an important role in the anti-aging effect of Codonopsis pilosula.

9.
Arch Pharm Res ; 43(2): 187-203, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31956964

RESUMO

Glioma is the most common type of primary brain tumor, and it has a high mortality rate. Currently, there are only a few therapeutic approaches for gliomas, and their effects are unsatisfactory. Therefore, uncovering the pathogenesis and exploring more therapeutic strategies for the treatment of gliomas are urgently needed to overcome the ongoing challenges. Cellular redox imbalance has been shown to be associated with the initiation and progression of gliomas. Among reactive oxygen species (ROS), hydrogen peroxide (H2O2) is considered the most suitable for redox signaling and is a potential candidate as a key molecule that determines the fate of cancer cells. In this review, we discuss the potential cellular and molecular roles of H2O2 in gliomagenesis and explore the potential implications of H2O2 in radiotherapy and chemotherapy and in the ongoing challenges of current glioma treatment. Moreover, we evaluate H2O2 as a potential redox sensor and potential driver molecule of nanocatalytic therapeutic strategies for glioma treatment.

10.
J Vet Pharmacol Ther ; 43(2): 97-107, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31912519

RESUMO

Cyadox (CYX) is a synthetic antibacterial agent of quinoxaline with much lower toxic effects. A safety criterion of CYX for clinical use was established by studying the pharmacokinetics and metabolism of CYX after oral (PO), intramuscular (IM), and intravenous (IV) administration. CYX was administered in six domesticated cats (three males and three females) by PO (40 mg/kg.b.w.), IM (10 mg/kg.b.w.), and IV (10 mg/kg.b.w.) routes in a crossover pattern. Highly sensitive liquid chromatography with ultraviolet detection (HPLC-UV) method was developed for detection of CYX and its metabolites present in plasma, urine, and feces. The bioavailability of CYX after PO and IM routes was 4.37% and 84.4%. The area under curves (AUC), mean resident time (MRT), and clearance (CL) of CYX and its metabolites revealed that CYX quickly metabolized into its metabolites. The total recovery of CYX and its main metabolites was >60% after each route. PO delivery suggesting first pass effect in cats that might make this route suitable for intestinal infection and IM injection could be better choice for systemic infections. Less ability of glucuronidation did not show any impact on CYX metabolism. The findings of present study provide detailed information for evaluation of CYX.

11.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 31-36, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948521

RESUMO

OBJECTIVE: To study the clinical effect and complications of continuous blood purification (CBP) in the treatment of multiple organ dysfunction syndrome (MODS) in neonates. METHODS: A retrospective analysis was performed for the clinical data of 21 neonates with MODS who were admitted to the neonatal intensive care unit from November 2015 to April 2019 and were treated with CBP. Clinical indices were observed before treatment, at 6, 12, 24, and 36 hours of CBP treatment, and at the end of treatment to evaluate the clinical effect and safety of CBP treatment. RESULTS: Among the 21 neonates with MODS undergoing CBP, 17 (81%) had response to treatment. The neonates with response to CBP treatment had a significant improvement in oxygenation index at 6 hours of treatment, a significant increase in urine volume at 24 hours of treatment, a stable blood pressure within the normal range at 24 hours of treatment, and significant reductions in the doses of the vasoactive agents epinephrine and dopamine at 6 hours of treatment (P<0.05), as well as a significant reduction in serum K+ level at 6 hours of treatment, a significant improvement in blood pH at 12 hours of treatment, and significant reductions in blood lactic acid, blood creatinine, and blood urea nitrogen at 12 hours of treatment (P<0.05). Among the 21 neonates during CBP treatment, 6 experienced thrombocytopenia, 1 had membrane occlusion, and 1 experienced bleeding, and no hypothermia, hypotension, or infection was observed. CONCLUSIONS: CBP is a safe, feasible, and effective method for the treatment of MODS in neonates, with few complications.


Assuntos
Insuficiência de Múltiplos Órgãos , Gasometria , Nitrogênio da Ureia Sanguínea , Hemofiltração , Humanos , Recém-Nascido , Estudos Retrospectivos
12.
Clin Exp Hypertens ; 42(2): 181-189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30957546

RESUMO

Aim: We explored the role of histone modification in the association of depression-hypertension by comparing norepinephrine transporter (NET) gene levels in different depression-hypertensive patients. Then, we analyzed the expression of NET correlation with inflammatory cytokines to provide a new direction for detecting the association mechanism between depression and hypertension.Methods: NE expression levels in serum of diverse groups were detected by enzyme-linked immunosorbent assay. Then histone acetyltransferase (HAT), histone deacetylase (HDAC), H3K27ac, NET, TNF-α, and interleukin-6 (IL-6) were detected by western blot in nine female subjects in different depression and hypertension groups, and Chromatin immunoprecipitation-polymerase chain reaction (Chip-PCR) were used to confirm the degree of acetylation affecting on the transcription level of NET gene. Meanwhile, correlation between NET with TNF/IL-6 was analyzed by SPSS19.0 software program. Finally, Quantitative real-time polymerase chain reaction (qPCR) and western blot were used to detect TNF-α and IL-6 expression levels after NET overexpression or interference treatment in human umbilical vein endothelial cells and Neuro-2a cells.Results: The expression of HAT and H3K27ac had lower levels in D-H and nonD-H group than nonD-nonH group. The results showed that higher acetylation could promote expression of NET genes. Meanwhile, the expression of NET had a significant negative correlation with IL-6 (R = -0.933, p < 0.01) and tumor necrosis factor (TNF) (R = -0.817, p < 0.01) in subjects. In addition, the results confirmed that TNF-α and IL-6 mRNA and protein partial expressions could be inhibited by NET in both HUVECs and Neuronal cells (p < 0.01).Conclusion: In conclusion, differential expression of NET gene might function as an important factor in interaction between depression and hypertension by partially targeting TNF-α and IL-6.

13.
Food Chem ; 311: 125924, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865112

RESUMO

LC-MS/MS method was developed for the efficient identification and quantification of 21 banned substances including various nitroimidazoles, nitrofurans, pharmacologically-active dyes and chloramphenicol, respectively in aquaculture products. The sample preparation was started by acid-treatment with 2-nitrobenzaldehyde (NBA) to liberate matrix-bound residues of nitrofurans. A modified QuEChERS method was optimized for the extraction and clean-up of the target analytes. The metabolites of the four conventional nitrofurans (nitrofurantoin, furazolidone, nitrofurazone and furaltadone) and of three other nitrofurans (nifursol, nifuroxazide, and nitrovin), and an underivatizable nitrofuran (nifurpirinol) were simultaneously detected. Furthermore, 21 banned substances were quantified by LC-MS/MS with ESI using one single injection. To evaluate and validate the performance of the method, the criteria of the Decision (EC) no 2002/657 were applied. Decision limit (CCα) of target analytes ranged 0.067-1.655 µg/kg in aquaculture products. The recovery ranged 77.2%-125.6%, and the relative standard deviations of inter-day analyses (RSD) were less than 25%.


Assuntos
Antibacterianos/análise , Cloranfenicol/análise , Cromatografia Líquida/métodos , Corantes/análise , Nitroimidazóis/análise , Espectrometria de Massas em Tandem/métodos , Animais , Aquicultura , Resíduos de Drogas/análise , Peixes/crescimento & desenvolvimento , Contaminação de Alimentos/análise , Furazolidona/análise
14.
Food Chem ; 302: 124623, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408774

RESUMO

To monitor the illegal use of olaquindox in animals, a monoclonal antibody-based surface plasmon resonance (SPR) biosensor method has been developed to detect 3-methyl-quinoxaline-2-carboxylic acid, the marker residues of olaquindox, in swine tissues. The limit of detection was 1.4 µg kg-1 in swine muscle and 2.7 µg kg-1 in swine liver, which are lower than the EU recommended concentration (10 µg kg-1). The recoveries were from 82% to 104.6%, with coefficients of variation of less than 12.2%. Good correlations between SPR and HPLC results (r = 0.9806, muscle; r = 0.9698, liver) and between SPR and ic-ELISA results (r = 0.9918, muscle; r = 0.9873, liver) were observed in the affected tissues, which demonstrated the reliability of the SPR method. This method would be a rapid and reliable tool for the screening of the residues of olaquindox in the edible tissues of animals.


Assuntos
Resíduos de Drogas/metabolismo , Quinoxalinas/análise , Quinoxalinas/metabolismo , Ressonância de Plasmônio de Superfície , Animais , Limite de Detecção , Fígado/química , Músculos/química , Reprodutibilidade dos Testes , Suínos
15.
Onco Targets Ther ; 12: 10427-10439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819524

RESUMO

Purpose: To determine the oncogenic role of the sixth subunit of chaperonin-containing tailless complex polypeptide 1 (CCT6A) in hepatocellular carcinoma (HCC) and address the correlation of CCT6A with clinicopathological characteristics and survival. Additionally, this study aimed to explore the effect of CCT6A on HCC cells and the underlying mechanisms. Methods: We searched for levels of CCT6A expression in the Oncomine database and GEPIA database, which was then validated by analyzing cancer and adjacent non-cancerous tissues of HCC patients using quantitative PCR, Western blot, and immunohistochemistry assays. The relationship between CCT6A expression and survival was analyzed from the GEPIA database and confirmed by immunohistochemistry assays of 133 HCC tissue sections. In addition, the effect of depleting CCT6A on cell proliferation was assessed by CCK-8 and colony formation assays. Cell cycle analysis, immunofluorescence assays, GSEA analysis, and cyclin D expression analyzed by Western blot were used to explore the possible underlying mechanism how dysregulated CCT6A affect the proliferation of HCC. Results: Both mRNA and protein levels of CCT6A were increased in HCC tissues. Higher CCT6A expression was significantly associated with reduced overall survival (P = 0.023). CCT6A depletion inhibited cell proliferation and downregulated cyclin D, hindering the G1-to-S phase arrest. Conclusion: CCT6A may contribute to HCC cell proliferation by accelerating the G1-to-S transition, as it maintains the expression of cyclin D. CCT6A could be considered an oncogene of HCC and could be used as a prognostic biomarker for HCC.

17.
J Hematol Oncol ; 12(1): 117, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747962

RESUMO

The original article [1] contains an error in authorship whereby author, Robert Weinkove's name is mistakenly inverted. The configuration noted in this Correction article should be considered instead along with author's updated affiliation.

18.
J Opt Soc Am A Opt Image Sci Vis ; 36(10): 1669-1674, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674432

RESUMO

X-ray luminescence tomography (XLT) is a promising imaging technology based on x-ray beams, with high-resolution capability. We developed a fan-beam XLT system, where the x-ray beam scans the object at predefined directions and positions. As the scanning at one position needs to cover the object, the data acquisition time is usually long. To improve spatial resolution, we propose a three-dimensional multiple-beam x-ray luminescence imaging method, in which the x rays are modulated by an x-ray fence-modulation component. The proposed method can produce multiple x-ray beams and ensure spatial resolution along the longitudinal direction as well as the transverse plane. The proposed methods of single-source experiments can achieve 0.62 mm in location error and 0.87 in the dice coefficient while 1.32 mm in location error and 0.63 in the dice coefficient in the double-source experiment. The simulation experiments show that our proposed method can achieve better results at different depths than the traditional scanning method. It is also demonstrated that the best simulation results can be achieved with the smallest x-ray width.

19.
Oxid Med Cell Longev ; 2019: 4957878, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687081

RESUMO

Bovine herpesvirus type 1 (BoHV-1) is a significant cofactor for bovine respiratory disease complex (BRDC), the most important inflammatory disease in cattle. BoHV-1 infection in cell cultures induces overproduction of pathogenic reactive oxygen species (ROS) and the depletion of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a master transcriptional factor regulating a panel of antioxidant and cellular defense genes in response to oxidative stress. In this study, we reported that the virus productive infection in MDBK cells at the later stage significantly decreased the expression levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1) proteins, the canonical downstream targets regulated by Nrf2, inhibited Nrf2 acetylation, reduced the accumulation of Nrf2 proteins in the nucleus, and relocalized nuclear Nrf2 proteins to form dot-like staining patterns in confocal microscope assay. The differential expression of Kelch-like ECH associated protein 1 (KEAP1) and DJ-1 proteins as well as the decreased association between KEAP1 and DJ-1 promoted Nrf2 degradation through the ubiquitin proteasome pathway. These data indicated that the BoHV-1 infection may significantly suppress the Nrf2 signaling pathway. Moreover, we found that there was an association between Nrf2 and LaminA/C, H3K9ac, and H3K18ac, and the binding ratios were altered following the virus infection. Taken together, for the first time, we provided evidence showing that BoHV-1 infection inhibited the Nrf2 signaling pathway by complicated mechanisms including promoting Nrf2 degradation, relocalization of nuclear Nrf2, and inhibition of Nrf2 acetylation.

20.
Theranostics ; 9(26): 8392-8408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754404

RESUMO

Calcyclin-binding protein (CACYBP) is a multi-ligand protein implicated in the progression of various human cancers. However, its function in hepatocellular carcinoma (HCC) remains unknown. Methods: The expression of CACYBP and RNF41 (RING finger protein 41) in HCC cancer and adjacent non-tumor tissues was detected by immunohistochemistry. CCK-8 assays, colony formation assays, flow cytometry detection and xenograft models were used to evaluate the impact of CACYBP expression on HCC cell growth, apoptosis and cell cycle regulation. Immunoprecipitation and ubiquitination assays were performed to determine how RNF41 regulates CACYBP. The regulatory mechanism of RNF41-CACYBP signaling axis on P27Kip1 was investigated by western blotting and immunofluorescence. Results: CACYBP was highly expressed and associated with poor prognosis in HCC. CACYBP expression was required for HCC cell growth in vitro and in vivo. Moreover, we identified RNF41 as a specific binding partner of CACYBP at exogenous and endogenous levels. RNF41 recruited CACYBP by its C-terminal substrate binding domain, subsequently ubiquitinating CACYBP and promoting its degradation in both proteasome- and lysosome-dependent pathways. In HCC tissues, RNF41 expression was reduced and conferred a negative correlation with CACYBP expression. Mechanistically, CACYBP overexpression stimulated the Ser10, Thr157 and Thr198 phosphorylation of P27Kip1 and its cytoplasmic retention, and RNF41 co-expression attenuated this phenomenon. CACYBP depletion led to decreased levels of cyclin D1, cyclin A2, CDK2 and CDK4, causing a typical cell cycle arrest at G1/S phase and increasing apoptosis in HCC cells. P27Kip1-S10D but not P27Kip1-S10A reconstitution rescued partially the cell cycle function and apoptotic feature after CACYBP depletion. Conclusion: Our findings provide novel insights into the functional role and regulatory mechanism of CACYBP in HCC.

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