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1.
Blood ; 142(12): 1071-1081, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37294924

RESUMO

Rebalance of coagulation and anticoagulation to achieve a hemostatic effect has recently gained attention as an alternative therapeutic strategy for hemophilia. We engineered a humanized chimeric antibody, SR604, based on a previously published murine antibody, HAPC1573, which selectively blocks the anticoagulant activity of human activated protein C (APC). SR604 effectively blocked the anticoagulation activities of APC in human plasma deficient in various coagulation factors in vitro with affinities ∼60 times greater than that of HAPC1573. SR604 exhibited prophylactic and therapeutic efficacy in the tail-bleeding and knee-injury models of hemophilia A and B mice expressing human APC (humanized hemophilic mice). SR604 did not interfere with the cytoprotection and endothelial barrier function of APC, nor were there obvious toxicity effects in humanized hemophilic mice. Pharmacokinetic study showed a high bioavailability (106%) of subcutaneously injected SR604 in cynomolgus monkeys. These results demonstrate that SR604 is expected to be a safe and effective therapeutic and/or prophylactic agent with a prolonged half-life for patients with congenital factor deficiencies including hemophilia A and B.


Assuntos
Hemofilia A , Proteína C , Humanos , Camundongos , Animais , Proteína C/uso terapêutico , Hemofilia A/tratamento farmacológico , Modelos Animais de Doenças , Coagulação Sanguínea , Anticoagulantes/uso terapêutico
2.
Small ; 19(16): e2207066, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36683236

RESUMO

Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of corona vireus disease 2019 (COVID-19). Here, a dual-function circular aptamer-ASO chimera (circSApt-NASO) is designed to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibits high serum stability by artificial cyclization. It is also demonstrated that the SApt binding to spike protein enables the chimera to be efficiently delivered into the host cells expressing ACE2 along with the infection of SARS-CoV-2. Among them, the SApt potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Overall, benefiting from the high stability of the cyclization, antispike aptamer-dependent, and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron, providing a promising specific anti-inflammatory and antiproliferative reagent for therapeutic COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Inflamação , Proliferação de Células
3.
Entropy (Basel) ; 25(2)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36832548

RESUMO

Currently, the implementation of water resource spatial equilibrium strategy is a fundamental policy of water resource integrated management in China; it is also a considerable challenge to explore the relationship structure features of water resources, society, economy and ecological environment (WSEE) complex system. For this purpose, firstly, we applied information entropy, ordered degree and connection number coupling method to reveal the membership characteristics between different evaluation indicators and grade criterion. Secondly, the system dynamics approach was introduced to describe the relationship features among different equilibrium subsystems. Finally, the ordered degree, connection number, information entropy and system dynamics integrated model was established to conduct relationship structure simulation and evolution trend evaluation of the WSEE system. The application results in Hefei city, Anhui Province, China, demonstrated that: (1) the variation of overall equilibrium conditions of WSEE system in Hefei city, 2020-2029 was higher compared to that of 2010-2019, though the increasing rate of ordered degree and connection number entropy (ODCNE) became slower after 2019; and (2) the annual ODCNE value from 2020 to 2029 of WSEE system under dry year scenarios increased about 0.0812, which indicated that the construction of Yangtze-Huaihe Diversion (YHD) project could play significant positive role in mitigating the equilibrium situation of WSEE system in Hefei city in the future. On the whole, this study is capable of providing the guidance basis for constructing a theoretical framework of structure simulation and equilibrium evaluation analysis of WSEE complex system.

4.
Environ Res ; 210: 112913, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35151656

RESUMO

The comprehensive evaluation analysis of water resource spatial equilibrium (WRSE) system is a fundamental and crucial facet to construct national water resource network system and implement socio-economy equilibrium development strategy in China. To clearly understanding of the structural relationship of WRSE system, we firstly proposed the definition of WRSE system from the perspective of coordination variation between water resource carrying pressure and support force subsystems in this study, then, the multi-dimensional connection cloud and coupling coordination degree approaches were applied to construct integrated evaluation model (MCCD) of WRSE system, and finally, the obstacle degree model was utilized as well to recognize the primary influence factors which resulted in the variation of WRSE system. Eventually, it can be revealed from the application results of MCCD model that, the overall situation of WRSE system in Anhui Province, China was improved obviously during the past 10 years, with the average coupling coordination degree (CCD) increased from 0.58 in 2011 to 0.68 in 2018. In addition, water resources availability per capita (S1) and agricultural irrigation quota (P8) were the two primary indicators causing the variation of water resource carrying support and pressure force subsystems. The above application analysis results were reliable and consistent with the evolution trend of actual historical observed statistics, and could also provide scientific decision-making basis for the implementation of prediction and regulation schemes of WRSE system.


Assuntos
Conservação dos Recursos Naturais , Recursos Hídricos , China , Cidades , Desenvolvimento Econômico , Análise Fatorial
5.
Neoplasma ; 69(3): 700-707, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35188402

RESUMO

The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value. Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study. All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy. In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved. A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group). We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups. In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS. Multivariate analyses showed that the primary site (p=0.011) and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS. In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor. So, we think PCNI for stage I ENKTCL patients is not necessary. Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis. And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.


Assuntos
Linfoma Extranodal de Células T-NK , Intervalo Livre de Doença , Humanos , Células Matadoras Naturais , Linfoma Extranodal de Células T-NK/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
6.
Entropy (Basel) ; 24(7)2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35885096

RESUMO

To promote the application of entropy concepts in uncertainty analysis of water resources complex system, a quantitative evaluation and obstacle factor diagnosis model of agricultural drought disaster risk was proposed using connection number and information entropy. The results applied to Suzhou City showed that the agricultural drought disaster risks in Suzhou during 2007-2017 were all in middle-risk status, while it presented a decreasing trend from 2010. The information entropy values of the difference degree item bI were markedly lower than those of the difference degree b, indicating that bI provided more information in the evaluation process. Furthermore, the status of drought damage sensitivity and drought hazard were improved significantly. Nevertheless, high exposure to drought and weak drought resistance capacity seriously impeded the reduction of risk. Thus, the key to decreasing risk was to maintain the level of damage sensitivity, while the difficulties were to reduce exposure and enhance resistance. In addition, the percentage of the agricultural population, population density, and percentage of effective irrigation area were the main obstacle factors of risk and also the key points of risk control in Suzhou. In short, the results suggest that the evaluation and diagnosis method is effective and conducive to regional drought disaster risk management.

7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 600-605, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36065692

RESUMO

Objective To explore the impact of pressure and social support on the quality of life of non-surgical gastric cancer patients. Methods A total of 158 non-surgical patients diagnosed with gastric cancer by gastroscopy from June to August in 2021 were included in this study.The perceived stress scale,multidimensional scale of perceived social support,and the 36-item short form health survey questionnaire [including the physical composite score (PCS) and mental composite score (MCS)] were used for the evaluation of perceived stress,social support,and quality of life,respectively.Spearman correlation analysis was conducted.Mann-Whitney U test,Kruskal-Wallis H test or one-way analysis of variance was employed for the comparison between groups.Bivariate Logistic regression was employed for multiple comparisons. Results Gender (P<0.001),marriage (P=0.022),age (P=0.022),and sickness symptoms (P=0.009) affected the PCS of non-surgical gastric cancer patients.Gender (P=0.016),income (P=0.012),and sickness symptoms (P=0.038) influenced the MCS of non-surgical gastric cancer patients.Perceived pressure was negatively correlated with PCS and MCS (all P<0.001).The three factors of social support were positively correlated with PCS and MCS (all P<0.001).The PCS was associated with gender (OR=0.219,95%CI=0.091-0.525,P=0.001),age (OR=0.969,95%CI=0.942-0.998,P=0.035),sickness symptoms (OR=1.142,95%CI=1.013-1.287,P=0.030),perceived stress (OR=0.921,95%CI=0.860-0.987,P=0.019),and family support (OR=1.195,95%CI=1.064-1.343,P=0.003).The MCS was associated with gender (OR=0.169,95%CI=0.062-0.459,P<0.001),perceived pressure (OR=0.910,95%CI=0.844-0.981,P=0.013),and other support (OR=1.136,95%CI=1.002-1.288,P=0.046). Conclusions The quality of life of the patients with non-surgical gastric cancer was related to perceived pressure and social support.Female and elderly patients have lower quality of life,which requires more attention in clinical work.


Assuntos
Qualidade de Vida , Neoplasias Gástricas , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Qualidade de Vida/psicologia , Apoio Social , Inquéritos e Questionários
8.
Haematologica ; 106(3): 759-769, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32303557

RESUMO

Sialic acid is a common terminal residue of glycans on proteins and acidic sphingolipids such as gangliosides and has important biological functions. The sialylation process is controlled by more than 20 different sialyltransferases, many of which exhibit overlapping functions. Thus, it is difficult to determine the overall biological function of sialylation by targeted deletion of individual sialyltransferases. To address this issue, we established a mouse line with the Slc35a1 gene flanked by loxP sites. Slc35a1 encodes the cytidine-5'-monophosphate (CMP)-sialic acid transporter that transports CMP-sialic acid from the cytoplasm into the Golgi apparatus for sialylation. Here we report our study regarding the role of sialylation on megakaryocytes and platelets using a mouse line with significantly reduced sialylation in megakaryocytes and platelets (Plt Slc35a1­ /­). The major phenotype of Plt Slc35a1­/­ mice was thrombocytopenia. The number of bone marrow megakaryocytes in Plt Slc35a1­/­ mice was reduced, and megakaryocyte maturation was also impaired. In addition, an increased number of desialylated platelets was cleared by Küpffer cells in the liver of Plt Slc35a1­/­ mice. This study provides new insights into the role of sialylation in platelet homeostasis and the mechanisms of thrombocytopenia in diseases associated with platelet desialylation, such as immune thrombocytopenia and a rare congenital disorder of glycosylation (CDG), SLC35A1-CDG, which is caused by SLC35A1 mutations.


Assuntos
Proteínas de Transporte de Nucleotídeos , Trombocitopenia , Plaquetas , Humanos , Fígado , Ácido N-Acetilneuramínico , Proteínas de Transporte de Nucleotídeos/genética , Trombocitopenia/genética , Trombopoese
9.
J Cell Mol Med ; 24(7): 4356-4361, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073234

RESUMO

Hereditary thrombotic thrombocytopenic purpura (TTP) is an autosomal recessive thrombosis disorder, caused by loss-of-function mutations in ADAMTS13. Mutations in the CUB domains of ADAMTS13 are rare, and the exact mechanisms through which these mutations result in the development of TTP have not yet been fully elucidated. In this study, we identified two novel mutations in the CUB domains in a TTP family with an acceptor splice-site mutation (c.3569-1, G>A, intron 25) and a point missense mutation (c.3923, G>A, exon 28), resulting in a glycine to aspartic acid substitution (p.G1308D). In vitro splicing analysis revealed that the intronic mutation resulted in abnormal pre-mRNA splicing, and an in vitro expression assay revealed that the missense mutation significantly impaired ADAMTS13 secretion. Although both the patient and her brother displayed significantly reduced ADAMTS13 activity and increased levels of ultra-large VWF (ULVWF) multimers in plasma, only the female developed acute episodes of TTP. Our findings indicate the importance of the CUB domains for the protein stability and extracellular secretion of ADAMTS13.


Assuntos
Proteína ADAMTS13/genética , Multimerização Proteica/genética , Púrpura Trombocitopênica Trombótica/genética , Precursores de RNA/sangue , Proteína ADAMTS13/sangue , Adulto , Feminino , Humanos , Mutação com Perda de Função/genética , Mutação de Sentido Incorreto/genética , Estabilidade Proteica , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/patologia , Precursores de RNA/genética , Splicing de RNA/genética , Fator de von Willebrand/genética
10.
Neurochem Res ; 45(5): 1202-1214, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32125561

RESUMO

Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), which may be related to mitophagy failure. Previous reports suggest that treadmill exercise protects against mitochondrial dysfunction in AD. However, few studies have investigated the relationship between mitophagy and mitochondrial adaptation caused by treadmill exercise in AD. The current study aimed to investigate whether exercise-ameliorated AD is associated with changes in mitophagy activity. Both Wild-type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 9 for each group). WTE and ADE mice were subjected to treadmill exercise for 12 weeks, followed by evaluating the effect of treadmill exercise on learning and memory ability, Aß plaques, mitochondrial Aß peptide level, synaptic activity and mitochondrial function. Meanwhile, mitophagy-related proteins PINK1, Parkin, LC3II and P62 were measured in the hippocampal mitochondrial fractions. The results indicated that exercise not only restored learning and memory ability, but also reduced Aß plaque area, mitochondrial Aß peptide level, and increased levels of synaptic markers SYN and GAP43, as well as reversed mitochondrial dysfunction (defective mitochondrial ultrastructure, decreased PGC-1α, TFAM and ATP levels) in APP/PS1 transgenic mice. Moreover, exercise increased mitophagy activity as evidenced by a significant decrease in levels of P62 and PINK1 as well as an increase in levels of LC3II and Parkin in ADE mice. These findings suggest that treadmill exercise can enhance mitophagy activity in the hippocampus, which is efficient in ameliorating pathological phenotypes of APP/PS1 transgenic mice.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Mitocôndrias/metabolismo , Mitofagia/fisiologia , Condicionamento Físico Animal/fisiologia , Presenilina-1 , Peptídeos beta-Amiloides/antagonistas & inibidores , Precursor de Proteína beta-Amiloide/genética , Animais , Teste de Esforço/métodos , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/patologia , Condicionamento Físico Animal/métodos , Presenilina-1/genética
11.
Echocardiography ; 37(10): 1678-1681, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32944966

RESUMO

We present a patient with breast cancer with multiple metastases who had an unusual cardiac mass in the right atrium. The cardiac mass was initially diagnosed as malignant metastasis by transthoracic echocardiogram (TTE) but subsequently diagnosed as benign by contrast-enhanced ultrasonography, cardiac magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). TTE is the preferred imaging method for examination of cardiac masses. However, this case demonstrates that contrast-enhanced ultrasonography, MRI, and PET/CT are useful to differentiate between diagnoses of benign and malignant tumor. The combination of multiple diagnostic imaging modalities is necessary to confirm the diagnosis of cardiac tumors.


Assuntos
Neoplasias Cardíacas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Erros de Diagnóstico , Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons
12.
Proc Natl Acad Sci U S A ; 114(31): 8360-8365, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28716912

RESUMO

Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1-/- ). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1-/- mice show reduced levels of α-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets. The preferential accumulation of HC C1galt1-/- platelets in the liver was reduced in mice lacking the hepatic asialoglycoprotein receptor [Ashwell-Morell receptor (AMR)]. However, we found that Kupffer cells are the primary cells phagocytosing HC C1galt1-/- platelets in the liver. Our results demonstrate that hepatic AMR promotes preferential adherence to and phagocytosis of desialylated and/or HC C1galt1-/- platelets by the Kupffer cell through its C-type lectin receptor CLEC4F. These findings provide insights into an essential role for core 1 O-glycosylation of platelets in their clearance in the liver.


Assuntos
Plaquetas/metabolismo , Galactosiltransferases/genética , Células de Kupffer/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Animais , Receptor de Asialoglicoproteína/metabolismo , Hepatócitos/metabolismo , Homeostase/fisiologia , Lectinas Tipo C/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Trombocitopenia/patologia
13.
Entropy (Basel) ; 22(1)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33285881

RESUMO

Drought is one of the most typical and serious natural disasters, which occurs frequently in most of mainland China, and it is crucial to explore the evolution characteristics of drought for developing effective schemes and strategies of drought disaster risk management. Based on the application of Cloud theory in the drought evolution research field, the cloud transformation algorithm, and the conception zooming coupling model was proposed to re-fit the distribution pattern of SPI instead of the Pearson-III distribution. Then the spatio-temporal evolution features of drought were further summarized utilizing the cloud characteristics, average, entropy, and hyper-entropy. Lastly, the application results in Northern Anhui province revealed that the drought condition was the most serious during the period from 1957 to 1970 with the SPI12 index in 49 months being less than -0.5 and 12 months with an extreme drought level. The overall drought intensity varied with the highest certainty level but lowest stability level in winter, but this was opposite in the summer. Moreover, drought hazard would be more significantly intensified along the elevation of latitude in Northern Anhui province. The overall drought hazard in Suzhou and Huaibei were the most serious, which is followed by Bozhou, Bengbu, and Fuyang. Drought intensity in Huainan was the lightest. The exploration results of drought evolution analysis were reasonable and reliable, which would supply an effective decision-making basis for establishing drought risk management strategies.

14.
Anal Bioanal Chem ; 411(17): 3857-3870, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31073732

RESUMO

The present paper describes a novel two-dimensional liquid chromatography (2D-LC) system, which is comprised of a first-dimensional ion exchange chromatography (IEX1) column, trap column, and second-dimensional reversed-phase chromatography (RP2) column system. The biological sample is separated by the first-dimensional LC using an IEX column to remove interferences. The analytes are transferred to the trap column after heart-cutting. Then, the analytes are transferred to the second-dimensional LC using an RP2 column for further separation and ultraviolet detection. This 2D-LC system can offer a large injection volume to provide sufficient sensitivity and exhibits a strong capacity for removing interferences. Here, the determination of three monoterpene indole alkaloids (MIAs; gelsemine, koumine, and humantenmine) from Gelsemium in biological matrices (plasma, tissue, and urine) was used this 2D-LC system. After a rapid and easy sample preparation method based on protein precipitation, the sample was injected into the 2D-LC. The method was developed and validated in terms of the selectivity, LOD, LOQ, linearity, precision, accuracy, and stability. The sample preparation time for the three MIAs was 15 min. The LOD for these compounds was 10 ng/mL, which was lower than the developed HPLC methods. The results showed that this method had good quantitation performance and allowed the determination of gelsemine, koumine, and humantenmine in biological matrices. The method is rapid, exhibits high selectivity, has good sensitivity, and is low-cost, thus making it well-suited for application in the pharmaceutical and toxicological analysis of Gelsemium. Graphical abstract.


Assuntos
Alcaloides/análise , Cromatografia por Troca Iônica/instrumentação , Cromatografia de Fase Reversa/instrumentação , Alcaloides Indólicos/análise , Alcaloides/sangue , Alcaloides/normas , Alcaloides/urina , Cromatografia por Troca Iônica/métodos , Cromatografia de Fase Reversa/métodos , Alcaloides Indólicos/sangue , Alcaloides Indólicos/normas , Alcaloides Indólicos/urina , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta/métodos
15.
Rapid Commun Mass Spectrom ; 32(23): 2047-2054, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30252168

RESUMO

RATIONALE: N-Methylcanadine and N-methylstylopine are two types of isoquinoline alkaloids which are considered to be the main medicinally active constituents of the genus Papaveraceae. However, to date, no metabolism studies of N-methylcanadine and N-methylstylopine have been reported. Therefore, the purpose of the present study was to investigate the in vitro metabolism of these two alkaloids in rat liver S9. METHODS: N-Methylcanadine or N-methylstylopine was incubated with rat liver S9 for 1 h, and then the incubation mixture was processed with 15% trichloroacetic acid. High-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS) as a reliable analytical method was used. The structural characterization of these metabolites was performed by the combination of the accurate MS/MS spectra and the known elemental composition. RESULTS: As a result, a total of four metabolites of N-methylcanadine and five metabolites of N-methylstylopine in rat liver S9 were tentatively identified. The cleavage of the methylenedioxy group of the drugs was the main metabolic pathway of N-methylcanadine and N-methylstylopine. CONCLUSIONS: The present study is the first in vitro metabolic investigation of N-methylcanadine and N-methylstylopine in rat liver S9 using a reliable HPLC/QqTOF-MS method. The metabolic pathways of N-methylcanadine and N-methylstylopine are tentatively proposed. This work lays the foundation for the in vivo metabolism of the two compounds in animals.


Assuntos
Alcaloides/química , Alcaloides de Berberina/química , Cromatografia Líquida de Alta Pressão/métodos , Microssomos Hepáticos/química , Papaveraceae/química , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Alcaloides/metabolismo , Animais , Alcaloides de Berberina/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Extratos Vegetais/metabolismo , Ratos , Ratos Sprague-Dawley
16.
Platelets ; 29(3): 288-291, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28504079

RESUMO

Gray platelet syndrome (GPS) is a rare, inherited bleeding disorder characterized by the defect of platelet α-granule. Up to date, these are only four studies identifying NBEAL2 gene correlated with GPS. In the current report, we present a Chinese GPS patient who had severe bleeding tendency, abnormalities of platelet functions, and absence of platelet α-granules. Genomic DNA sequencing for the patient identified a nonsense mutation (g.27713C>A) of NBEAL2 gene (g.NG__031914.1) resulting in a premature protein (p.Glu1726*). In comparison with the reported patients, we conclude that homozygotes with nonsense or deletion mutation leading to a premature stop codon exhibit more serious bleeding problem than those with missense mutations.


Assuntos
Proteínas Sanguíneas/genética , Códon sem Sentido , Síndrome da Plaqueta Cinza/complicações , Síndrome da Plaqueta Cinza/genética , Hemorragia/diagnóstico , Hemorragia/etiologia , Adulto , Biomarcadores , Plaquetas/metabolismo , Plaquetas/ultraestrutura , Grânulos Citoplasmáticos/metabolismo , Análise Mutacional de DNA , Feminino , Homozigoto , Humanos , Linhagem , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária , Análise de Sequência de DNA , Índice de Gravidade de Doença
17.
Ophthalmic Res ; 57(3): 173-185, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28076855

RESUMO

To evaluate the role of microRNA-126 (miR-126) in maintaining the integrity of the blood-retina barrier (BRB), we established a mouse model of oxygen-induced retinopathy (OIR) and measured the retinal levels of miR-126 using recombinant plasmid pCMV-MIR or pCMV-MIR-126 intravitreal injections. We also detected VCAM-1 and BCL2L11 levels. Retinal vaso-obliteration, VCAM-1 localization on retinal endothelial cells, the blood-retina vascular permeability or albumin leakage in retinas, TUNEL histology, Evans blue assays, or Western blotting for detecting albumin or tight junction levels in the retina was performed. We also detected the effect of miR-126 on the survival of Müller cells in a mouse model using vimentin fluorescence staining. Our results suggested that miR-126 may not only regulate the overexpression of VCAM-1 or BCL2L11 and lead to the reduction of retinal endothelial cell apoptosis, retinal vascular leakage, or retinal permeability in the OIR mouse model, but may also protect hypoxic retinal Müller cells via the STAT3 signaling pathway. We believe that miR-126 could also be a potential therapeutic agent to maintain the stability of the BRB in ischemic retinopathy.


Assuntos
Proteína 11 Semelhante a Bcl-2/metabolismo , Barreira Hematorretiniana/fisiologia , Isquemia/metabolismo , MicroRNAs/fisiologia , Doenças Retinianas/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/fisiologia , Western Blotting , Permeabilidade Capilar/fisiologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Retina/citologia , Doenças Retinianas/patologia , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia
18.
ORL J Otorhinolaryngol Relat Spec ; 78(6): 303-307, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27978529

RESUMO

BACKGROUND: The repair of large nasal septal perforations (NSPs) is one of the most challenging procedures in nasal surgery. The aim of this prospective clinical study was to determine the efficacy of using a pedicle inferior turbinate mucosal flap combined with temporal fascia to repair a large NSP. METHOD: Between January 2008 and December 2015, 17 consecutive patients with large NSPs underwent septal perforation repair via an endoscopic approach using a pedicle inferior turbinate mucosal flap combined with temporal fascia. RESULTS: Complete closure of the perforation was achieved in all patients. CONCLUSION: The pedicle inferior turbinate mucosal flap combined with the temporal fascia technique can easily solve this challenging problem, and the current data from this prospective study suggest that this technique shows promising results.


Assuntos
Endoscopia , Perfuração do Septo Nasal/cirurgia , Rinoplastia/métodos , Retalhos Cirúrgicos , Adulto , Fáscia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfuração do Septo Nasal/diagnóstico por imagem , Perfuração do Septo Nasal/etiologia , Estudos Prospectivos , Resultado do Tratamento , Conchas Nasais
19.
Int J Mol Sci ; 17(10)2016 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-27735849

RESUMO

During the past decades, there have been continuous attempts in the prediction of metabolism mediated by cytochrome P450s (CYP450s) 3A4, 2D6, and 2C9. However, it has indeed remained a huge challenge to accurately predict the metabolism of xenobiotics mediated by these enzymes. To address this issue, microsomal metabolic reaction system (MMRS)-a novel concept, which integrates information about site of metabolism (SOM) and enzyme-was introduced. By incorporating the use of multiple feature selection (FS) techniques (ChiSquared (CHI), InfoGain (IG), GainRatio (GR), Relief) and hybrid classification procedures (Kstar, Bayes (BN), K-nearest neighbours (IBK), C4.5 decision tree (J48), RandomForest (RF), Support vector machines (SVM), AdaBoostM1, Bagging), metabolism prediction models were established based on metabolism data released by Sheridan et al. Four major biotransformations, including aliphatic C-hydroxylation, aromatic C-hydroxylation, N-dealkylation and O-dealkylation, were involved. For validation, the overall accuracies of all four biotransformations exceeded 0.95. For receiver operating characteristic (ROC) analysis, each of these models gave a significant area under curve (AUC) value >0.98. In addition, an external test was performed based on dataset published previously. As a result, 87.7% of the potential SOMs were correctly identified by our four models. In summary, four MMRS-based models were established, which can be used to predict the metabolism mediated by CYP3A4, 2D6, and 2C9 with high accuracy.


Assuntos
Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Modelos Teóricos , Preparações Farmacêuticas/metabolismo , Área Sob a Curva , Biotransformação , Humanos , Microssomos Hepáticos/enzimologia , Curva ROC , Máquina de Vetores de Suporte
20.
ScientificWorldJournal ; 2015: 291680, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26495421

RESUMO

Due to the proved clinical efficacy, Shuang-Huang-Lian (SHL) has developed a variety of dosage forms. However, the in-depth research on targets and pharmacological mechanisms of SHL preparations was scarce. In the presented study, the bioinformatics approaches were adopted to integrate relevant data and biological information. As a result, a PPI network was built and the common topological parameters were characterized. The results suggested that the PPI network of SHL exhibited a scale-free property and modular architecture. The drug target network of SHL was structured with 21 functional modules. According to certain modules and pharmacological effects distribution, an antitumor effect and potential drug targets were predicted. A biological network which contained 26 subnetworks was constructed to elucidate the antipneumonia mechanism of SHL. We also extracted the subnetwork to explicitly display the pathway where one effective component acts on the pneumonia related targets. In conclusions, a bioinformatics approach was established for exploring the drug targets, pharmacological activity distribution, effective components of SHL, and its mechanism of antipneumonia. Above all, we identified the effective components and disclosed the mechanism of SHL from the view of system.


Assuntos
Biologia Computacional/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonas/farmacologia , Flavonoides/farmacologia , Glucosídeos/farmacologia , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Mapas de Interação de Proteínas/efeitos dos fármacos
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