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1.
Small ; 20(22): e2307671, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38221752

RESUMO

The recent groundbreaking achievement in the synthesis of large-sized single crystal C60 monolayer, which is covalently bonded in a plane using C60 as building blocks. The asymmetric lattice structure endows it with anisotropic phonon modes and conductivity. If these C60 are arranged in form of 1D fiber, the improved manipulation of phonon conduction along the fiber axis could be anticipated. Here, thermal properties of C60-fiber, including thermal transfer along the C60-fiber axis and across the interlayer interface are investigated using molecular dynamic simulations. Taking advantage of the distinctively hollow spherical structure of C60 building blocks, the spherical structure deformation and encapsulation induced thermal reduction can be up to 56% and 80%, respectively. By applying external electronic fields in H2O@C60 model, its thermal conductivity decreases up to 60%, which realizes the contactless thermal regulation. ln particular, the thermal rectification phenomenon is discovered by inserting atoms/molecules in C60 with a rational designed mass-gradient, and its maximum thermal rectification factor is predicted to ≈45%. These investigations aim to achieve effective regulation of the thermal conductivity of C60-fibers. This work showcases the potential of C60-fiber in the realms of thermal management and thermal sensing, paving the way to C60-based functional materials.

2.
Stem Cells ; 41(12): 1171-1184, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37659098

RESUMO

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.


Assuntos
Insuficiência Hepática Crônica Agudizada , Células-Tronco Mesenquimais , Camundongos , Animais , Insuficiência Hepática Crônica Agudizada/metabolismo , Proteínas Tirosina Quinases/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo
3.
Genomics ; 115(6): 110737, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37926353

RESUMO

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Insuficiência Hepática Crônica Agudizada/genética , Insuficiência Hepática Crônica Agudizada/terapia , Insuficiência Hepática Crônica Agudizada/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células-Tronco Mesenquimais/metabolismo
4.
FASEB J ; 36(1): e22073, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34847253

RESUMO

Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) are important immune checkpoint receptors that prevent an overreacted maternal immune response to fetal antigens during pregnancy. Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE). Our recent study showed that the Tim-3 pathway was involved in the regulation of decidual macrophage polarization. Decidual macrophages polarized to the M1 phenotype may impair uterine vessel remodeling during placentation, accounting for the occurrence of PE. Co-blockade of the PD-1/Tim-3 pathway was shown to successfully control tumor growth in preclinical cancer models. However, the effects of activating both PD-1 and Tim-3 pathways as a combined intervention strategy in PE are never reported. Herein, we observed the skew of decidual macrophage polarization toward the M1 phenotype in patients with PE and lipopolysaccharide (LPS)-induced PE-like rat model. Moreover, we found that the activation of PD-1/Tim-3 pathway by using PD-L1 and Gal-9 fusion proteins could alleviate the manifestation of the LPS-induced PE-like rats and protect their offspring. Compared with the single intervention, the combination of PD-L1and Gal-9 fusion proteins exhibited obvious advantages in the relief of PE-like symptoms, trophoblast invasion, and fetal vascular development, indicating a synergistic effect of the activated PD-1/Tim-3 pathway. The in vitro study also revealed that the combined intervention using PD-L1 and Gal-9 fusion proteins inhibited the LPS-induced M1 macrophage polarization via the synergic activation of the ERK/GSK3ß/ß-catenin signaling pathway. Together, our findings provide the first evidence that simultaneous activation of PD-1/Tim-3 signaling pathways may have an optimal protective effect and serve as a new potential target for PE intervention.


Assuntos
Decídua/metabolismo , Sistema de Sinalização das MAP Quinases , Macrófagos/metabolismo , Pré-Eclâmpsia/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Decídua/patologia , Modelos Animais de Doenças , Feminino , Humanos , Lipopolissacarídeos/toxicidade , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/patologia , Gravidez , Ratos , Ratos Sprague-Dawley
5.
Org Biomol Chem ; 20(34): 6923-6930, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35979893

RESUMO

An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived Morita-Baylis-Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.


Assuntos
Iminas , Ninidrina , Carbonatos , Catálise , Reação de Cicloadição , Nitrilas , Pirazóis
6.
Int J Mol Sci ; 23(22)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36430914

RESUMO

It is a macro-micro model study for defect initiation, growth and crack propagation of metallic truss structure under high engine temperature and pressure conditions during the reentry atmosphere. Till now, the multi-scale simulation methods for these processes are still unclear. We explore the deformation and failure processes from macroscale to nanoscale using the Gas-Kinetic Unified Algorithm (GKUA) and all-atomic, molecular dynamic (MD) simulation method. The behaviors of the dislocations, defect evolution and crack propagation until failure for Aluminum-Magnesium (Al-Mg) alloy are considered with the different temperature background and strain fields. The results of distributions of temperature and strain field in the aerodynamic environment obtained by molecular dynamics simulations are in good agreement with those obtained from the macroscopic Boltzmann method. Compared to the tensile loading, the alloy structure is more sensitive to compression loading. The polycrystalline Al-Mg alloy has higher yield strength with a larger grain size. It is due to the translation of plastic deformation mode from grain boundary (GB) sliding to dislocation slip and the accumulation of dislocation line. Our findings have paved a new way to analyze and predict the metallic structural failure by micro-scale analysis under the aerodynamic thermal extreme environment of the reentry spacecraft on service expiration.


Assuntos
Ambientes Extremos , Plásticos , Ligas , Cinética , Simulação de Dinâmica Molecular , Antiácidos , Grão Comestível
7.
Sheng Li Xue Bao ; 71(3): 388-394, 2019 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-31218329

RESUMO

The aim of this study was to determine the effects of extremely low frequency electromagnetic field (ELF-EMF) on energy metabolism and oxidative stress in Caenorhabditis elegans (C. elegans). Worms in three adult stages (young adult stage, egg-laying stage and peak egg-laying stage) were investigated under 50 Hz, 3 mT ELF-EMF exposure. ATP levels, ATP synthase activity in vivo, reactive oxygen species (ROS) content, and changes of total antioxidant capacity (TAC) were detected, and worms' oxidative stress responses were also evaluated under ELF-EMF exposure. The results showed that ATP levels were significantly increased under this ELF-EMF exposure, and mitochondrial ATP synthase activity was upregulated simultaneously. In young adult stage, worms' ROS level was significantly elevated, together with upregulated TAC but with a decreased ROS-TAC score indicated by principal component analysis. ROS level and TAC of worms had no significant changes in egg-laying and peak egg-laying stages. Based on these results, we concluded that ELF-EMF can enhance worm energy metabolism and elicit oxidative stress, mainly manifesting as ATP and ROS level elevation together with ATP synthase upregulation and ROS-TAC score decrease in young adult C. elegans.


Assuntos
Caenorhabditis elegans/efeitos da radiação , Radiação Eletromagnética , Metabolismo Energético , Estresse Oxidativo , Trifosfato de Adenosina/metabolismo , Animais , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Espécies Reativas de Oxigênio/análise
8.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4918-4923, 2019 Nov.
Artigo em Zh | MEDLINE | ID: mdl-31872601

RESUMO

Ultra performance liquid chromatography-tandem mass spectrometry( UPLC-MS/MS) was used to establish the simultaneous determination method of eight neurotransmitters in brain,liver,kidney,adrenal gland,serum and urine,including serotonin,5-hydroxyindole acetic acid,epinephrine,norepinephrine,dopamine,glutamic acid,γ-aminobutyric acid,and acetylcholine,and then investigate the distribution characteristics of neurotransmitters in rat tissues,blood and urine. Waters ACQUITY UPLC BEH C_(18) column( 2. 1 mm×100 mm,1. 7 µm) was used,with 0. 3% formic acid solution-acetonitrile as the mobile phase for gradient elution.Multiple reaction monitoring( MRM) scanning method under positive mode by atmospheric pressure electrospray ion source( ESI) was also performed to establish the detection method of neurotransmitters for methodological research. The plasma,urine and tissues of normal rats were pre-treated including homogenization,centrifuging,and protein removal,then the 2 µL supernatant was injected for analysis. The results showed that eight kinds of neurotransmitters could be accurately determined within 7 min,with linear correlation coefficients all greater than 0. 99. This method showed high accuracy and good precision,with specificity,stability,extraction recovery and matrix effects all complying with the biological sample analysis requirements. The most abundant transmitters in the brain,liver,kidney,kidney gland,blood and urine were γ-aminobutyric acid,glutamic acid,glutamic acid,adrenaline,glutamic acid and dopamine.The method is sensitive,rapid,precise,accurate and specific,and can be used for simultaneous quantitative analysis of eight neurotransmitters in biological samples. The investigation of the distribution ratio of transmitters in rats is of important significance to disease prevention and treatment.


Assuntos
Neurotransmissores/metabolismo , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Neurotransmissores/sangue , Neurotransmissores/urina , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(2): 172-175, 2019 Feb.
Artigo em Zh | MEDLINE | ID: mdl-30782282

RESUMO

OBJECTIVE: To explore the value of galactose-deficient IgA1 (Gd-IgA1) in the early diagnosis of Henoch-Schönlein purpura nephritis (HSPN) in children. METHODS: A total of 67 hospitalized children who were definitely diagnosed with HSPN between January and April 2018 and 58 hospitalized children with Henoch-Schönlein purpura (HSP) were enrolled in the study. Twenty children undergoing routine physical examinations served as controls. The levels of serum and urine Gd-IgA1 were determined using ELISA. The receiver operating characteristic curve was used to analyze the value of serum Gd-IgA1 and urine Gd-IgA1/urine creatinine ratio in the diagnosis of HSPN. RESULTS: The level of serum Gd-IgA1 and urine Gd-IgA1/urine creatinine ratio in children with HSP or HSPN were significantly higher than those in healthy control group (P<0.01), with a significantly greater increase observed in children with HSPN (P<0.01). Serum Gd-IgA1 ≥1 485.57 U/mL and/or urine Gd-IgA1/urine creatinine ratio ≥105.74 were of favorable value in the diagnosis of HSPN. During the six-month follow-up of the 49 children with HSP, the incidence of HSPN was 47% (23/49), which included a 100% incidence in children with serum Gd-IgA1 ≥1 485.57 U/mL and a 73% incidence in children with urine Gd-IgA1/urine creatinine ratio ≥105.74. CONCLUSIONS: Serum and urine Gd-IgA1 is of favorable clinical value in the early diagnosis of HSPN.


Assuntos
Glomerulonefrite por IGA , Vasculite por IgA , Criança , Diagnóstico Precoce , Galactose , Humanos , Imunoglobulina A
10.
Kidney Blood Press Res ; 43(4): 1084-1103, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29991025

RESUMO

BACKGROUND/AIMS: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-κB signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. METHODS: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1ß and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. RESULTS: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-α, IL-1ß and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-κB, IL-6, TNF-α and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-κB signaling pathway. CONCLUSION: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-κB signaling pathway in rats with renal I/R injury.


Assuntos
Apoptose , Citocinas/metabolismo , Células Epiteliais/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Animais , Proliferação de Células , Inativação Gênica , Inflamação , Rim/lesões , Túbulos Renais/patologia , Lentivirus , NF-kappa B/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/farmacologia , Ratos , Traumatismo por Reperfusão , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(12): 1055-1062, 2018 Dec.
Artigo em Zh | MEDLINE | ID: mdl-30572998

RESUMO

OBJECTIVE: To study the expression and significance of tight junction proteins (claudin-2, claudin-10, and claudin-17) in a mouse model of renal ischemia-reperfusion injury. METHODS: A total of 152 male C57BL/6 mice were randomly assigned to control group (n=8), sham-operation group (n=72), and model group (n=72). The renal pedicles at both sides were clamped for 30 minutes to establish a mouse model of renal ischemia-reperfusion injury. According to the time points of reperfusion (0, 3, 6, 12, 24, 48, and 72 hours and 5 and 7 days), the sham-operation group and the model group were further divided into 9 subgroups, with 8 mice in each subgroup. RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of claudin-2, claudin-10, and claudin-17 in renal tissue. RESULTS: The control and sham-operation groups had no significant changes in the mRNA and protein expression of claudin-2, claudin-10, and claudin-17 in renal tissue over the time of reperfusion (P>0.05). Compared with the control and sham-operation groups, the model group had decreased mRNA and protein expression of claudin-2 and claudin-10 after reperfusion, and the expression decreased gradually over the time of reperfusion, with the lowest levels at 24 hours of reperfusion (P<0.05). Compared with the control and sham-operation groups, the model group had increased mRNA and protein expression of claudin-17 after reperfusion, and the expression increased gradually over the time of reperfusion, with the highest mRNA level at 12 hours and the highest protein level at 24 hours of reperfusion (P<0.05). CONCLUSIONS: Renal ischemia-reperfusion injury is closely associated with abnormal expression of tight junction proteins claudin-2, claudin-10, and claudin-17.


Assuntos
Rim , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Proteínas de Junções Íntimas
12.
Biochem Biophys Res Commun ; 486(1): 94-100, 2017 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-28274878

RESUMO

In humans, UBXD7 (also called UBXN7), an adaptor of p97 ATPase, can participate in the degradation of misfolded or damaged proteins in the p97-mediated ubiquitin proteasome system (UPS). UBXD7 binds to ubiquitinated substrates via its UBA domain and interacts with p97 N-terminal domain through its UBX domain to recruit p97 or the p97 core complex (p97/NPL4/UFD1). Here, we report the crystal structures of the UBX domain of UBXD7 (UBXD7UBX) at 2.0 Å resolution and its complex with p97 N-terminal domain (p97NTD-UBXD7UBX complex) at 2.4 Å resolution. A structural analysis and isothermal titration calorimetry results provide detailed molecular basis of interaction between UBXD7UBX and p97NTD. Moreover, structural superpositions suggest that dimerization of UBXD7UBX via an intermolecular disulfide bond could interfere with the formation of the p97NTD-UBXD7UBX complex. Interestingly, UBXD7 may have a cooperative effect on p97 interaction with UFD1. Together, these results provide structural and biochemical insights into the interaction between p97NTD and UBXD7UBX.


Assuntos
Adenosina Trifosfatases/química , Proteínas de Transporte/química , Proteínas Nucleares/química , Domínios Proteicos , Proteínas Adaptadoras de Transdução de Sinal , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Sequência de Aminoácidos , Sítios de Ligação/genética , Calorimetria/métodos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cristalização , Cristalografia por Raios X , Dissulfetos/química , Humanos , Modelos Moleculares , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Multimerização Proteica , Homologia de Sequência de Aminoácidos
13.
J Surg Res ; 214: 162-167, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28624039

RESUMO

BACKGROUND: Central lymph node (CLN) metastasis in papillary thyroid carcinoma (PTC) is common and being able to predict CLN metastasis helps surgeons determine individualized therapy. However, the relationship between contralateral CLN metastasis and the total number of positive lymph nodes (LNs) in the combined prelaryngeal and pretracheal region remains unclear. This study aimed to investigate whether the total number of positive LNs in the combined prelaryngeal and pretracheal region has clinical significance as a predictor for contralateral CLN metastasis. METHODS: We prospectively enrolled 153 consecutive patients with unifocal PTC >1.0 cm without ultrasonographic evidence of nodal metastasis who underwent total thyroidectomy and prophylactic bilateral CLN dissection from July 2011-May 2013. Patients were divided into three groups according to the total number of positive LNs in the combined prelaryngeal and pretracheal region. RESULTS: Rates of metastasis to ipsilateral and contralateral central compartments in PTC >1.0 cm were 84.3% and 24.2%, respectively. Multivariate analysis showed that ≥3 positive LNs in the combined prelaryngeal and pretracheal region were an independent predictive factor of contralateral CLN metastasis (P < 0.001; odds ratio, 8.585). After a mean follow-up of 24.1 mo, none of these patients had a recurrence in the central or lateral compartment. CONCLUSIONS: Occult metastasis is highly prevalent in the ipsilateral central neck of patients with PTC >1.0 cm, and the total number of prelaryngeal and pretracheal LNs metastases may be a useful indicator to predict contralateral CLN metastasis in patients with unifocal PTC.


Assuntos
Carcinoma/patologia , Linfonodos/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Carcinoma/cirurgia , Carcinoma Papilar , Criança , Feminino , Seguimentos , Humanos , Laringe , Modelos Logísticos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Traqueia , Adulto Jovem
15.
Drug Metab Dispos ; 44(8): 1193-200, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27271371

RESUMO

Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min per milligram. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822C>T, 2286823G>A, and 3823884A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612A>G, and 10954732G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of P450 isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on P450 activity, was less pronounced. POR transcription was strongly correlated with both hepatocyte nuclear factor 4 alpha and pregnane X receptor mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR single-nucleotide polymorphisms and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 P450s important in drug metabolism.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Fígado/enzimologia , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/metabolismo , China , Sistema Enzimático do Citocromo P-450/genética , Bases de Dados Factuais , Regulação Enzimológica da Expressão Gênica , Frequência do Gene , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Heterozigoto , Homozigoto , Humanos , Isoenzimas , Microssomos Hepáticos/enzimologia , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Fumar/genética , Fumar/metabolismo
16.
Biomed Environ Sci ; 29(5): 379-84, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27353713

RESUMO

Case reports of indium-related lung disease in workers have raised public concern to the human toxicity of indium (In) and its compounds. However, studies evaluating the exposure or health of workers in In smelting plants are rare. Therefore, in this study, we focused on four In smelting plants, with the main objective of characterizing In in smelter plants in China and discussing the potential exposure biomarkers of In exposure. We recruited 494 subjectsat four In smelting plants in China. Personal air samples, first morning urine and spot blood samples were collected. In concentrations in samples were analyzed using inductively coupled plasma mass spectrometry. In concentrations in air samples did not exceed the permissible concentration-time weighed average, but the smelter workers had a higher internal exposure to In. Positive correlations were observed between the air In and urine In concentrations, and between the air In and blood In concentrations. This study provides basic data for the following In exposure and health risk assessment.


Assuntos
Poluentes Ocupacionais do Ar/sangue , Poluentes Ocupacionais do Ar/urina , Índio/sangue , Índio/urina , Metalurgia , Exposição Ocupacional , Adulto , Biomarcadores/sangue , Biomarcadores/urina , China , Monitoramento Ambiental , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto Jovem
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(1): 81-4, 2016 Jan.
Artigo em Zh | MEDLINE | ID: mdl-27062788

RESUMO

OBJECTIVE: To explore the possible risk factors of contralateral central lymph node metastasis (CLNM) in solitary thyroid papillary micro-carcinoma (PTMC). METHODS: Clinicopathologic data of 318 patients with confirmed solitary PTMC by final histological who underwent bilateral centeral lymph node dissection (CLND) from April 2012 to May 2015 in our hospital were retrospectively reviewed. Univariate Χ2 test and multivariate logistic regression analysis were used to determine the risk factors of contralateral CLNM in solitary PTMC. RESULTS: The incidence of ipsilateral CLNM and contralateral CLNM in solitary PTMC patients were 40.57% (129/318), 9.75% (31/318), respectively. Univariate analyses revealed that contralateral CLNM had a correlation with tumor located in lower pole, capsular invasionand underlying ipsilateral CLNM (P < 0.05), and had a correlation with underlying nodular goiter (P < 0.05). Multivariate logistic regression analysis showed that tumor located in lower pole and ipsilateral CLNM were independent risk factors for contralateral CLNM (P < 0.05). CONCLUSIONS: Solitary PTMC patients had a low tendency to contralateral CLNM, it shouldn't undergo contralateral CLND commonly, if the tumor located in lower pole or combine withipsilateral CLNM, it should be consider to undergo bilateral CLND.


Assuntos
Carcinoma Papilar/patologia , Carcinoma/patologia , Metástase Linfática , Neoplasias da Glândula Tireoide/patologia , Humanos , Incidência , Linfonodos/patologia , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(2): 130-5, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-26903059

RESUMO

OBJECTIVE: To compare the therapeutic effects of prednisone combined with mycophenolate mofetil (MMF) versus cyclosporin A (CsA) in children with steroid-resistant nephrotic syndrome (SRNS). METHODS: The clinical data of 164 SRNS children who were treated with prednisone combined with MMF or CsA between January 2004 and December 2013 were collected, and the clinical effect of prednisone combined with MMF (MMF group, 112 children) or CsA (CsA group, 52 children) was analyzed retrospectively. RESULTS: At 1 month after treatment, the CsA group had a significantly higher remission rate than the MMF group (67.3% vs 42.9%; P<0.05). At 3 months after treatment, the CsA group also had a significantly higher remission rate than the MMF group (78.8% vs 63.3%; P<0.05). The 24-hour urinary protein excretion in both groups changed significantly with time (P<0.05) and differed significantly between the two groups (P<0.05). There were no serious adverse events in the two groups. CONCLUSIONS: Prednisone combined with MMF or CsA is effective and safe for the treatment of SRNS in children, and within 3 months of treatment, CsA has a better effect than MMF.


Assuntos
Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Ácido Micofenólico/análogos & derivados , Síndrome Nefrótica/tratamento farmacológico , Prednisona/administração & dosagem , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Ácido Micofenólico/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
19.
Microbiol Immunol ; 59(8): 477-82, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26138857

RESUMO

Enterovirus A71 (EV-A71), one of the most important causative agents of hand, foot and mouth disease (HFMD) in children, can lead to severe clinical outcomes, even death. However, the infection spectrum of EV-A71 in different cell lines remains unknown. Therefore, in this study, the biological characteristics of EV-A71 Subgroup C4 in different cell lines were investigated. To this end, the infectivity of EV-A71Jinan1002 isolated from children with severe HFMD was assessed in 18 different host cell lines. It was found that the MA104 cell line displayed biological characteristics suitable for EV-A71 Subgroup C4 strain isolation and proliferation; indeed, it was found that a broad spectrum of cell lines can be infected by EV-A71Jinan1002. Among the screened cells, four cell lines (HEK293, RD, MA104 and Marc145) produced high 50% tissue culture infective dose (TCID50 ) values calculated in viral proliferations (ranged from 10(7.6) to 10(7.8) ); the TCID50 being negatively associated with the time to appearance of CPE. Proliferation curves demonstrated that EV-A71Jinan1002 amplifies more efficiently in MA104, Hep-2 and RD cells. Remarkably, the virus isolation rate was much higher in MA104 cells than in RD cells. Thus this study, to our knowledge, is for the first to explore the infection spectrum of EV-A71 subgroup C4 in such a large number of different cell lines. Our data provide useful reference data for facilitating further study of EV-A71.


Assuntos
Enterovirus Humano A/crescimento & desenvolvimento , Enterovirus Humano A/isolamento & purificação , Cultura de Vírus/métodos , Animais , Linhagem Celular , Criança , Pré-Escolar , Efeito Citopatogênico Viral , Doença de Mão, Pé e Boca/virologia , Humanos
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(3): 222-6, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-25815488

RESUMO

OBJECTIVE: To study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS). METHODS: One hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants. RESULTS: The incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05). CONCLUSIONS: Trace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.


Assuntos
Mesângio Glomerular/imunologia , Imunoglobulina M/análise , Nefrose Lipoide/imunologia , Adolescente , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Nefrose Lipoide/tratamento farmacológico , Estudos Retrospectivos
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