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1.
Dev Comp Immunol ; 103: 103497, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31518591

RESUMO

The lectin pathway of complement activation is an important component of the innate immune response, which must be tightly controlled to maintain immune homeostasis. However, its control mechanisms have not been investigated in detail in bony fish. In this study, we identified and characterized two novel, phylogenetically conserved mannan-binding lectin (MBL)-associated proteins (MAps) of grass carp (Ctenopharyngodon idella), CiMAp27 and CiMAp39, which were truncated, alternatively-spliced forms of grass carp MBL-associated serine proteases (MASPs), CiMASP1 and CiMASP2, respectively. Gene expression profiling showed that both CiMAp27 and CiMAp39 were upregulated by low doses of Aeromonas hydrophila, and inhibited by high doses, which lead to the inference that these genes acted as immune factors in antibacterial defense. Sequence analysis showed that CiMAp27 lack a catalytic domain but retains two domains (CUB1-EGF) involved in the association with MBL, while CiMAp39 retained four domains (CUB1-EGF-CUB2-CCP1). Not only the two CiMASPs but also the CiMAps were detected in grass carp serum. Furthermore, both recombinant CiMASPs (rCiMASPs) and recombinant rCiMAps (rCiMAps) interacted with recombinant MBL and the two CiMAps competed with CiMASPs for binding to MBL, and hence inhibited downstream C4 binding. These results indicated that CiMAps acted as competitive inhibitors in the lectin complement pathway of grass carp.

2.
Food Chem ; 308: 125650, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31655477

RESUMO

This study aimed at investigating the formation and accumulation of 16 reactive aldehydes in clam (Ruditapes philippinarum) during oil frying in both the tissue and the oil using an HPLC-ESI-MS/MS methodology. After processing, the accumulation of acrolein, crotonaldehyde, pentanal, trans-2-hexenal, hexanal, trans, trans-2,4-heptadienal, heptanal, nonanal, trans, trans-2,4-decadienal and 4-hydroxy-2-nonenal was most noticeable in both fried clam and frying oil. Most of the aldehyde species showed a time- and temperature-dependent manner of formation and accumulation during frying due to continuous oxidative degradation under conditions employed. However, several species of aldehyde such as acrolein and trans-2-pentenal slightly decreased at higher temperatures and/or longer frying times, which may be due to the imbalance toward disappearance of aldehydes resulting from their evaporation under the extreme conditions. Presence of natural polyphenols in bamboo leaves significantly prevented the formation of aldehydes in both fried clam and frying oil due to their antioxidant activity (P < 0.05).

4.
Bioresour Technol ; 295: 122313, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670203

RESUMO

Sludge rheology is an essential factor for anaerobic digestion (AD) processes to control the agitation energy consumption. In this study, the sludge rheology was characterized for an osmotic membrane bioreactor and a conventional sludge anaerobic digestion reactor as the solid content being increased from 3.5-3.7% to 7.5-7.7%. The flow curves were fitted using different rheological models and the mechanism was discussed. The sludge from the osmotic membrane bioreactor exhibited obviously better rheological properties than that of the conventional reactor at a solid content of 7.5-7.7%. Larger particles induced by less negative zeta potential and higher extracellular polymeric substances, together with the higher conductivity resulted by reverse salt flux in the osmotic membrane bioreactor, improved the sludge rheology due to reduced interactions between particles. As a result, the agitation energy consumption of the osmotic membrane bioreactor can save up to 34-39% compared with the conventional one at total solid content of 7.5-7.7%.


Assuntos
Reatores Biológicos , Esgotos , Anaerobiose , Membranas Artificiais , Osmose , Reologia , Eliminação de Resíduos Líquidos
5.
Talanta ; 206: 120179, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514881

RESUMO

In this work, the magnetic amino-functionalized microporous organic network composites (Fe3O4@MON-NH2) were rational designed and facile synthesized for magnetic solid phase extraction (MSPE) of endocrine disrupting chemicals (EDCs), followed by their analysis with high-performance liquid chromatography. The incorporation of amino groups (hydrogen bonding sites) into hydrophobic MON-NH2 networks led to their good enrichment for four typical EDCs bisphenol A (BPA), 4-alpha-cumylphenol (4-α-CP), 4-tert-octylphenol (4-t-OP) and 4-nonylphenol (4-NP) relying on the pre-designed hydrogen bonding, π-π and hydrophobic interactions. The combination of MON-NH2 shell and magnetic Fe3O4 core provided a fast extraction of BPA, 4-α-CP, 4-t-OP and 4-NP from matrix solution. Under the optimal conditions, the developed method offered good linearity (R2 > 0.990) in the range of 0.05-1000 µg L-1, low limits of detection (S/N = 3) of 0.015-0.030 µg L-1 and large enrichment factors of 172-197 for the studied EDCs. The maximum adsorption capacities of BPA, 4-α-CP, 4-t-OP and 4-NP were 124.1, 105.6, 116.6 and 117.9 mg g-1, respectively. The Fe3O4@MON-NH2 gave larger selectivity for other polar phenols than non-polar polycyclic aromatic hydrocarbons, revealing the dominant role of hydrogen bonding interaction during the extraction and the potential of Fe3O4@MON-NH2 for other polar phenols. The developed method was successfully applied for the analysis of EDCs in water, orange juice and beverage bottle samples with the recoveries of 80.3-109.5%. These results revealed the potential of functional MONs as efficient adsorbents in sample pretreatment.

6.
Sci Total Environ ; 698: 134289, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514034

RESUMO

Microeukaryotes are the key ecosystem drivers mediating marine productivity, the food web and biogeochemical cycles. The northwestern Pacific Ocean (NWPO), as one of the world's largest oligotrophic regions, remains largely unexplored regarding diversity and biogeography of microeukaryotes. Here, we investigated the community composition and geographical distribution of microeukaryotes collected from the euphotic zone of three different regions in the NWPO using high-throughput sequencing of the 18S rRNA gene and quantified the contributions of environmental factors on the distributions of microeukaryotes. The relative abundance of different group taxa, except for Ciliophora, presented distinct patterns in each region, and Metazoa and Dinoflagellata dominated the community, contributing approximately half of reads abundance. Spatial and environmental factors explained 66.01% of community variation in the NWPO. Temperature was the most important environmental factor significantly correlated with community structure. Bacterial biomass was also significantly correlated with microeukaryotic distribution, especially for Dinoflagellata and Diatomea. Network analysis showed strong correlations between microeukaryotic groups and free-living bacteria and different bacterial taxa were correlated with specific microeukaryotic groups, indicating that their interactions enabled microeukaryotic groups to adapt to diverse environments. This study provides a first glance at the diversity and geographical distribution of microeukaryotes in the NWPO and sheds light on the biotic and abiotic factors in shaping the microeukaryotic community in the ocean.

7.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117413, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31369990

RESUMO

The twelve Λ-S electronic states of the first four dissociation limits of the MgSb molecule have been examined at the icMRCI+Q level employing basis sets of quintuple-ζ quality. The potential energy curves, vibrational levels and spectroscopic constants of the species have been investigated. The permanent dipole moments of the interested states are derived, and the transition dipole moments, Einstein emission coefficients, radiation lifetimes and Franck-Condon factors between selected states are also determined. Four Λ-S states of the first two dissociation limits split into seven Ω states under the effect of spin-orbit coupling. Characterizations of the MgSb low-lying Ω states are performed for the first time. In addition, the results and relevant data provided in this work on MgSb are compared with the antimony-IIA group and magnesium-VA group diatomic species. It is anticipated that this work will shed some light on further investigations of MgSb and other antimony-IIA group systems.

9.
PLoS One ; 14(11): e0224726, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693690

RESUMO

The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34-0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41-0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33-23.1 and HR 8.0, 95% CI 1.53-41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01-1.16 and HR 1.05, 95% CI 1.00-1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.

10.
J Transl Med ; 17(1): 363, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703694

RESUMO

BACKGROUND: Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. METHODS: A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. RESULTS: Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p < 0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC = 0.823; OS, AUC = 0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK-STAT3, inflammatory response and TNF-alpha signaling pathways. CONCLUSION: Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31730029

RESUMO

A Gram-stain-negative, strictly aerobic, gliding-motile, rod-shaped and orange-pigmented bacterium, designated 1494T, was isolated from marine sediment collected off the coast of Weihai, PR China. Strain 1494T was found to grow at 4-37 °C (optimum, 30 °C), at pH 6.0-9.0 (pH 7.0) and in the presence of 0-8 % (w/v) NaCl (2 %). Cells were positive for oxidase and catalase activity. The results of 16S rRNA gene based phylogenetic analysis revealed that strain 1494T belonged to the genus Formosa and exhibited the highest sequence similarity to Formosa spongicola KCTC 22662 T (98.4 %). Menaquinone-6 (MK-6) was detected as the major respiratory quinone. The dominant cellular fatty acids were iso-C15 : 1 G and iso-C15  :  0. The DNA G+C content of strain 1494T was 31.1 mol%. The major polar lipids included phosphatidylethanolamine, one unidentified phospholipid and one unidentified lipid. Based on its phylogenetic and phenotypic characteristics, strain 1494T is considered to represent a novel species from the genus Formosa, for which the name Formosa maritima sp. nov. is proposed. The type strain is 1494T (=KCTC 72531T=MCCC 1H00385T).

12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 581-588, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699186

RESUMO

Objective To evaluate the effect of miR-145 on migration and invasion of ovarian cancer cells.Methods The effect of miR-145 overexpression on the expression levels of miR-145 and zeb-2 were detected with qRT-PCR and Western blotting.The changes of in vitro migration and invasion were examined using Transwell assay.Target genes of miR-145 were predicted by bioinformatics software.Dual-luciferase reporter assay were used to verify zeb-2 as a direct target of miR-145.zeb-2 siRNA was transiently transfected in SKOV3 and 3AO cells,Transwell was used to examine in vitro migration and invasion abilities.Results The migration and proliferation of SKOV3(t=10.752,P=0.000;t=5.617,P=0.005)and 3AO cells(t=10.111,P=0.001;t=21.746,P=0.000)decreased significantly after overexpression of miR-145.The results of dual-luciferase reporter assay showed that the relative luciferase activity of co-transfected miR-145 mimic and WT 3'UTR expression vectors was significantly lower than that of co-transfected mimic control and WT 3'UTR expression vectors(SKOV3:t=4.572,P=0.010;3AO:t=3.528,P=0.024).There was no significant difference in relative luciferase activity between co-transfected miR-145 mimic/MUT 3'UTR expression vector cells and co-transfected mimic control/MUT 3'UTR expression vector cells(SKOV3:t=0.227,P=0.831;3AO:t=0.040,P=0.970).Real-time quantitative PCR showed that the zeb-2 expressions in SKOV3(t=1.490,P=0.211)and 3AO cells(t=0.114,P=0.914)were not significantly different from negative control after 48 h of miR-145 overexpression.Western blot analysis showed that the expression of zeb-2 protein in SKOV3(t=3.769,P=0.020)and 3AO cells(t=4.452,P=0.011)decreased significantly compared with negative control after 72 h of miR-145 overexpression.Seventy-two hours after transfection of zeb-2 siRNA,Western blotting showed that the expression of zeb-2 protein in SKOV3(t=4.660,P=0.010)and 3AO cells(t=4.594,P=0.010)was significantly down-regulated.Transwell assay showed that the migration and invasion abilities of SKOV3(t=18.655,P=0.000;t=18.026,P=0.000)and 3AO cells(t=5.500,P=0.005;t=8.780,P=0.001)were significantly decreased.Conclusion miR-145 may inhibit the migration and invasion of ovarian cancer cells by targeting zeb-2.


Assuntos
Movimento Celular , MicroRNAs/genética , Invasividade Neoplásica , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 308-311, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701712

RESUMO

OBJECTIVE: To observe the expressions of sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 2 (S1PR2) in hippocampus of epileptic rats and to investigate the pathogenesis of SphK1 and S1PR2 in epilepsy. METHODS: One hundred and eight male Sprague-Dawley (SD) rats were randomly divided into control group (n=48) and pilocarpine (PILO) group (n=60). A robust convulsive status epilepticus (SE) was induced in PILO group rats by the application of pilocarpine. Control group rats were injected with respective of physiological saline. Pilocarpine group was randomly divided into 6 subgroups (n=8): acute group (E6 h, E1 d, E3 d), latent group (E7 d) and chronic group (E30 d, E56 d). Each subgroup has 8 control rats and 8 epileptic rats. Hippocampal tissue and brain slices were obtained from control rats and rats subjected to the Li-PILO model of epilepsy at 6 h, 1 d, 3 d,7 d,30 d and 56 d after status epilepticus (SE). Western blot technique was used to determine the expressions of SphK1 and S1PR2 in hippocampus at different point of time after pilocarpine treatment. Immunofluorescence was applied to detect the activation and proliferation of hippocampal astrocytes and the localization of SphK1 and S1PR2 in rat hippocampal astrocytes. RESULTS: Compared with control group, the levels of SphK1 in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d) were significantly increased while the expressions of S1PR2 were decreased in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d)(P<0.05 or P<0.01). Immunofluorescence results showed astrocyte activation and proliferation in hippocampus of epileptic (E7 d) rats (P<0.05). Confocal microscopy confirmed the preferential expressions of SphK1 and S1PR2 in epileptic rat(E7 d)hippocampal astrocytes. CONCLUSION: The results indicate that SphK1 and S1PR2 may play an important role in the pathogenesis of epilepsy by regulating the activation and proliferation of hippocampal astrocytes and altering neuronal excitability.


Assuntos
Epilepsia/enzimologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Animais , Astrócitos/enzimologia , Epilepsia/fisiopatologia , Hipocampo/citologia , Hipocampo/enzimologia , Masculino , Pilocarpina , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
14.
Breast Cancer Res ; 21(1): 119, 2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703728

RESUMO

BACKGROUND: Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC. METHODS: The primary objective of this study was to evaluate the safety and toxicities of the combination. Patients with metastatic TNBC who had up to four lines of prior chemotherapies were enrolled. The combination of eribulin and everolimus was tested using three dosing levels: A1 (everolimus 5 mg daily; eribulin 1.4 mg/m2 days 1 and 8 every 3 weeks), A2 (everolimus 7.5 mg daily; eribulin 1.4 mg/m2, days 1 and 8 every 3 weeks), and B1 (everolimus 5 mg daily; eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks). RESULTS: Twenty-seven patients with median age 55 years were enrolled. Among 8 evaluable patients who received dose level A1, 4 had dose-limiting toxicities (DLTs). Among 3 evaluable patients treated with dose level A2, 2 had DLTs. Among 12 evaluable patients who received dose level B1, 4 had DLTs. The DLTs were neutropenia, stomatitis, and hyperglycemia. Over the study period, 59% had a ≥ grade 3 toxicity, 44% had ≥ grade 3 hematologic toxicities, and 22% had grade 4 hematologic toxicities. The most common hematological toxicities were neutropenia, leukopenia, and lymphopenia. Thirty-three percent had grade 3 non-hematologic toxicities. The most common non-hematological toxicities were stomatitis, hyperglycemia, and fatigue. The median number of cycles completed was 4 (range 0-8). Among 25 eligible patients, 9 patients (36%) achieved the best response as partial response, 9 (36%) had stable disease, and 7 (28%) had progression. The median time to progression was 2.6 months (95% CI [2.1, 4.0]), and median overall survival (OS) was 8.3 months (95% CI [5.5, undefined]). CONCLUSION: Eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks with everolimus 5 mg daily was defined as the highest dose with acceptable toxicity (RP2D). The combination is safe, and efficacy is modest. A post hoc analysis showed that participants that used dexamethasone mouthwash stayed on treatment for one additional cycle. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02120469. Registered 18 April 2014.

15.
Braz J Microbiol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667800

RESUMO

NADPH oxidases are enzymes that have been reported to generate reactive oxygen species (ROS) in animals, plants and many multicellular fungi in response to environmental stresses. Six genes of the NADPH oxidase complex components, including vvnoxa, vvnoxb, vvnoxr, vvbema, vvrac1 and vvcdc24, were identified based on the complete genomic sequence of the edible fungus Volvariella volvacea. The number of vvnoxa, vvrac1, vvbema and vvcdc24 transcripts fluctuated with ageing, and the gene expression patterns of vvnoxa, vvrac1 and vvbema were significantly positively correlated. However, the expression of vvnoxb and vvnoxr showed no significant difference during ageing. In hyphae subjected to mechanical injury stress, both O2- and H2O2 concentrations were increased. The expression of vvnoxa, vvrac1, vvbema and vvcdc24 was substantially upregulated, but vvnoxb and vvnoxr showed no response to mechanical injury stress at the transcriptional level. Additionally, the transcription of vvnoxa, vvrac1, vvbema and vvcdc24 could be repressed when the intracellular ROS were eliminated by diphenyleneiodonium (DPI) chloride and reduced glutathione (GSH) treatments. These results indicated a positive feedback loop involving NADPH oxidase and intracellular ROS, which might be the reason for the oxidative burst during injury stress.

16.
Cancer Sci ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677335

RESUMO

The tripartite motif containing 23 (TRIM23) gene is a member of the tripartite motif (TRIM) family that participate in many pathophysiological processes. However, the role of TRIM23 in lung adenocarcinoma (LUAD) remains unclear. In the present study, TRIM23 was firstly screened by next-generation sequencing between cisplatin (DDP)-resistant A549/DDP cell line and parental A549 cell line, combined with integrated analysis of the Gene Expression Omnibus (GEO) data (E-GEOD-43493 and E-GEOD-43494). The expression of TRIM23 was then verified to be upregulated in the DDP-resistant LUAD cells and tissues. The knockdown of TRIM23 expression in A549/DDP cells caused increased apoptosis, decreased IC50 values of DDP, NF-κB nuclear translocation, inhibition of cell proliferation in vitro and in vivo, inhibition of GLUT1/3 expression, glucose uptake, lactate and ATP production. While TRIM23 overexpression resulted in opposite effects in A549 cells. Additionally, the inhibition of proliferation in A549 cells caused by NF-κB signaling inhibitor PTDC or glycolysis inhibitor 3-BrPA could be weakened by TRIM23 overexpression. Furthermore, immunohistochemical analysis revealed that TRIM23 was upregulated in 46.1% (70/152) LUAD cases, and elevated TRIM23 expression was correlated with high expression of NF-κB, poor cellular differentiation, and adverse overall survival (OS) and disease-free survival (DFS). In conclusion, our study demonstrates that TRIM23 acts as an oncogene in LUAD and promotes DDP resistance by regulating glucose metabolism via TRIM23/NF-κB/ GLUT1/3 axis.

17.
Nanotoxicology ; : 1-19, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703536

RESUMO

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

18.
Psychiatry Res ; : 112591, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31703981

RESUMO

This study examines the prevalence and risk factors for postpartum hypomania in women after childbirth as well as examining the potential influence of personality traits in relation to experiencing symptoms of postpartum hypomania. A total of 1022 women no later than 1 month post-birth were recruited in Suzhou, China, between March 2017 and December 2018. Hypomanic symptoms were assessed with the Hypomania Checklist-32 (HCL-32), and a total score of 14 or higher was defined as having hypomanic symptoms. We found 43.6% of the women in our sample had hypomanic symptoms. The results of multiple logistic regression showed that rural residence [p = 0.01, odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.5-0.9], education background (p = 0.005, OR = 0.6, 95% CI = 0.5-0.9), marriage satisfaction (p = 0.048, OR = 0.9, 95% CI =0.8-1.0), Pittsburgh Sleep Quality Index (PSQI) (p = 0.001, OR = 0.9, 95% CI = 0.9-1.0), Eysenck Personality Questionnaire-Extraversion (p < 0.001, OR = 1.2, 95% CI = 1.1-1.2), Eysenck Personality Questionnaire-Lie (p = 0.01, OR = 0.9, 95% CI = 0.9-1.0), and General Anxiety Disorder-7 (p = 0.02, OR = 1.1, 95% CI = 1.0-1.1) were independently associated with exhibiting hypomanic symptoms. The current study provided insights into hypomanic symptoms in Chinese postpartum women. We also found that extraversion and lie personality were significantly associated with an increased risk of hypomanic symptoms in postpartum women. It is urgent to arrange screening for women at risk of developing postpartum hypomania as soon as possible after giving birth and at regular intervals in the first 6 months to prevent the women developing psychological disorders such as depression and bipolar disorder later on.

19.
Eur Radiol ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705255

RESUMO

OBJECTIVES: The purpose of this study was to investigate the correlation of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with the Ki67 proliferation index in a murine model of rhabdomyosarcoma. METHODS: The rhabdomyosarcoma model was established by injecting RD cells into the right hind flank of nude mice. The mice underwent 3.0T magnetic resonance imaging (MRI), including DWI and IVIM. The apparent diffusion coefficient (ADC), D, D*, and f were calculated with the ADW4.7 workstation. A specialized method was employed to ensure the pathological sections corresponded to the correct MRI slices. The Ki67 proliferation index was analyzed by immunohistochemistry, and any possible correlations were assessed between the DWI and IVIM parameters and Ki67 proliferation index. RESULTS: Twenty-seven rhabdomyosarcoma mice were established successfully. After 46 days, the average tumor volume reached 1094.78 ± 678.77 mm3. The average ADC, D, and D* values were 1.0470 ± 0.2036 × 10-3 mm2/s, 0.7237 ± 0.0971 × 10-3 mm2/s, and 4.8497 ± 1.6293 × 10-3 mm2/s, respectively. The range in f values was 0.102-0.229. The ADC and D values showed a moderate negative correlation with the Ki67 proliferation indexes (r = - 0.543, p = 0.003; r = - 0.491, p = 0.009, respectively). In addition, the f value showed a weak negative correlation with the Ki67 proliferation indexes (r = - 0.151, p = 0.451), while the D* value showed no association with the Ki67 proliferation indexes (r = - 0.037, p = 0.853). CONCLUSIONS: The ADC value of DWI, along with the D value of IVIM, may be reflective of Ki67 proliferation indexes in murine models of rhabdomyosarcoma. KEY POINTS: • DWI and IVIM parameters are correlated with Ki67 proliferation indexes in rhabdomyosarcoma mouse models. • A specialized method ensured a strong correlation between pathological sections and MRI slices, resulting in a robust radiological-pathological correlation.

20.
Int Immunopharmacol ; 77: 105911, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31671330

RESUMO

Liver fibrosis results from sustained liver injury and is characterized by inflammation, hepatic stellate cell (HSC) activation, extracellular matrix (ECM) accumulation and liver structure destruction. The Farnesoid-X receptor (FXR) antagonizes toxic liver injury and fibrosis, yet the mechanism in liver fibrosis remains unclear. We investigated the effects of FXR agonist obeticholic acid (OCA) on liver fibrosis in mice. Mice were injected with carbon tetrachloride (CCl4) for 3 weeks or 6 weeks to induce liver fibrosis. OCA (5 mg/kg) or PBS is administered daily during CCl4-treatment. At sacrifice, biochemical parameters and fibrosis were assessed. Pretreatment with OCA alleviated hepatic injury in 6 weeks group but not in 3 weeks group of CCl4 liver cirrhosis. At same time, pretreatment with OCA exhibit a dramatic protection of liver fibrosis in both 3 weeks group and 6 weeks group. Further experiments found that OCA pretreatment inhibited α-SMA expression and the activation of hepatic pSmad3 in 3 weeks group and 6 weeks group of CCl4-induced liver cirrhosis. Moreover, OCA activated FXR nuclear translocation and increased the interaction between liver FXR and pSmad3. This led to the discovery of a novel role for FXR in regulating fibrosis through interaction with pSmad3. Our data suggest that CCl4-induced liver fibrosis is protected by OCA through interaction between farnesoid X receptor and Smad3.

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