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1.
J Am Chem Soc ; 145(25): 13663-13673, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37329320

RESUMO

The development of photo-responsive ferroelectrics whose polarization may be remotely controlled by optical means is of fundamental importance for basic research and technological applications. Herein, we report the design and synthesis of a new metal-nitrosyl ferroelectric crystal (DMA)(PIP)[Fe(CN)5(NO)] (1) (DMA = dimethylammonium, PIP = piperidinium) with potential phototunable polarization via a dual-organic-cation molecular design strategy. Compared to the parent non-ferroelectric (MA)2[Fe(CN)5(NO)] (MA = methylammonium) material with a phase transition at 207 K, the introduction of larger dual organic cations both lowers the crystal symmetry affording robust ferroelectricity and increases the energy barrier of molecular motions, endowing 1 with a large polarization of up to 7.6 µC cm-2 and a high Curie temperature (Tc) of 316 K. Infrared spectroscopy shows that the reversible photoisomerization of the nitrosyl ligand is accomplished by light irradiation. Specifically, the ground state with the N-bound nitrosyl ligand conformation can be reversibly switched to both the metastable state I (MSI) with isonitrosyl conformation and the metastable state II (MSII) with side-on nitrosyl conformation. Quantum chemistry calculations suggest that the photoisomerization significantly changes the dipole moment of the [Fe(CN)5(NO)]2- anion, thus leading to three ferroelectric states with different values of macroscopic polarization. Such optical accessibility and controllability of different ferroelectric states via photoinduced nitrosyl linkage isomerization open up a new and attractive route to optically controllable macroscopic polarization.

2.
Eur Radiol ; 32(9): 5964-5973, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35357535

RESUMO

OBJECTIVES: To explore added value of diffusion-weighted imaging (DWI) as an adjunct to Kaiser score (KS) for differentiation of benign from malignant lesions on breast magnetic resonance imaging (MRI). METHODS: Two hundred forty-six patients with 273 lesions (155 malignancies) were included in this retrospective study from January 2015 to December 2019. All lesions were proved by pathology. Two radiologists blind to pathological results evaluated lesions according to KS. Lesions with score > 4 were considered malignant. Four thresholds of ADC values -1.3 × 10-3mm2/s, 1.4 × 10-3mm2/s, 1.53 × 10-3mm2/s, and 1.6 × 10-3mm2/s were used to distinguish benign from malignant lesions. For combined diagnosis, a lesion with KS > 4 and ADC values below the preset cutoffs was considered as malignant; otherwise, it was benign. Sensitivity, specificity, and area under the curve (AUC) were compared between KS, DWI, and combined diagnosis. RESULTS: The AUC of KS was significantly higher than that of DWI alone (0.941 vs 0.901, p = 0.04). The sensitivity of KS (96.8%) and DWI (97.4 - 99.4%) was comparable (p > 0.05) while the specificity of KS (83.9%) was significantly higher than that of DWI (19.5-56.8%) (p < 0.05). Adding DWI as an adjunct to KS resulted in a 0-2.5% increase of specificity and a 0.1-1.3% decrease of sensitivity; however, the difference did not reach statistical significance (p > 0.05). CONCLUSION: KS showed higher diagnostic performance than DWI alone for discrimination of breast benign and malignant lesions. DWI showed no additional value to KS for characterizing breast lesions. KEY POINTS: • KS showed higher diagnostic performance than DWI alone for differentiation of benign from breast malignant lesions. • DWI alone showed a high sensitivity but a low specificity for characterizing breast lesions. • Diagnostic performance did not improve using DWI as an adjunct to KS.


Assuntos
Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade
3.
Fish Shellfish Immunol ; 125: 84-89, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35537672

RESUMO

The hemoglobin (Hb) is identified in Tegillarca granosa and its derived peptides have been proved to possess antibacterial activity against gram-positive and gram-negative bacteria. In this study, we identified a series of novel antimicrobial peptides (AMPs) and artificially mutated AMPs derived from subunits of T. granosa Hbs, among which, a mutant T. granosa hemoglobin peptide (mTgHbP) mTgHbP7, was proved to possess predominant antibacterial activity against three bacteria strains (Vibrio alginolyticus, V. parahaemolyticus and Escherichia coli). Besides, mTgHbP7 was predicted to form α-helical structure, which was known to be an important feature of bactericidal AMPs. Furthermore, upon contact with HEK293 cell line, we confirmed that mTgHbP7 had no cytotoxicity to mammalian cell even at a high concentration of 160 µM. Therefore, the findings reported here provide a rationalization for antimicrobial peptide prediction and optimization from mollusk hemoglobin, which will be useful for future development of antimicrobial agents.


Assuntos
Antibacterianos , Arcidae , Animais , Arcidae/genética , Arcidae/microbiologia , Escherichia coli , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Células HEK293 , Hemoglobinas/química , Humanos , Mamíferos , Testes de Sensibilidade Microbiana , Peptídeos/química
4.
Fish Shellfish Immunol ; 122: 495-500, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35202805

RESUMO

Serum amyloid protein (SAA) is known as an acute reactive protein of innate immunity in mammals. However, in invertebrates, the role of SAA in innate immunity is still unclear. In this study, a full-length cDNA of the SAA gene (named TcSAA) was cloned from Tridacna crocea, mollusca. The gene includes a 193 bp 5' untranslated region (UTR) and a 129 bp 3' UTR sequence, and the open reading frame (ORF) with 393 bp nucleotides encodes a polypeptide of 130 amino acids. TcSAA contains a typical signal peptide and an SAA functional domain. The mRNA expression of TcSAA was detected in all 12 selected tissues and 7 different developmental stages. Furthermore, the expression of TcSAA was increased quickly in hemocytes after challenge with V. coralliilyticus or LPS. Furthermore, rTcSAA could bind V. coralliilyticus and V. alginolyticus, and the protein could reduce the lethality rate of the clams from 80% to 55% which caused by V. coralliilyticus about 48 h after injection. In summary, these results indicate that TcSAA may act as a marker for monitoring health and protecting T. crocea.


Assuntos
Perciformes , Sequência de Aminoácidos , Proteínas Amiloidogênicas/genética , Proteínas Amiloidogênicas/metabolismo , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Proteínas de Peixes/genética , Regulação da Expressão Gênica , Imunidade Inata/genética , Mamíferos/genética , Mamíferos/metabolismo , Filogenia
5.
Popul Health Metr ; 20(1): 20, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333770

RESUMO

BACKGROUND: Chronic pain is a common disease; about 20% of people worldwide suffer from it. While compared with the research on the prevalence and management of chronic pain in developed countries, there is a relative lack of research in this field in China. This research aims to construct the China Pain Health Index (CPHI) to evaluate the current status of the prevalence and management of chronic pain in the Chinese population. METHODS: The dimensions and indicators of CPHI were determined through literature review, Delphi method, and analytical hierarchy process model, and the original values ​​of relevant indicators were obtained by collecting multi-source data. National and sub-provincial scores of CPHI (2020) were calculated by co-directional transformation, standardization, percentage transformation of the aggregate, and weighted summation. RESULTS: The highest CPHI score in 2020 is Beijing, and the lowest is Tibet. The top five provinces are Beijing (67.64 points), Shanghai (67.04 points), Zhejiang (65.74 points), Shandong (61.16 points), and Tianjin (59.99 points). The last five provinces are Tibet (33.10 points), Ningxia (37.24 points), Guizhou (39.85 points), Xinjiang (39.92 points), and Hainan (40.38 points). The prevalence of chronic pain is severe in Heilongjiang, Chongqing, Guizhou, Sichuan, and Fujian. Guizhou, Hainan, Xinjiang, Beijing, and Guangdong display a high burden of chronic pain. The five provinces of Guangdong, Shanghai, Beijing, Jiangsu, and Zhejiang have better treatment for chronic pain, while Tibet, Qinghai, Jilin, Ningxia, and Xinjiang have a lower quality of treatment. Beijing, Shanghai, Qinghai, Guangxi, and Hunan have relatively good development of chronic pain disciplines, while Tibet, Sichuan, Inner Mongolia, Hebei, and Guizhou are relatively poor. CONCLUSION: The economically developed provinces in China have higher CPHI scores, while economically underdeveloped areas have lower scores. The current pain diagnosis and treatment situation in economically developed regions is relatively good, while that in financially underdeveloped areas is rather poor. According to the variations in the prevalence and management of chronic pain among populations in different provinces in China, it is necessary to implement chronic pain intervention measures adapted to local conditions.


Assuntos
Dor Crônica , Humanos , China/epidemiologia , Prevalência , Dor Crônica/epidemiologia , Dor Crônica/terapia
6.
Mar Drugs ; 20(7)2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35877752

RESUMO

Hemocyanins present in the hemolymph of invertebrates are multifunctional proteins that are responsible for oxygen transport and play crucial roles in the immune system. They have also been identified as a source of antimicrobial peptides during infection in mollusks. Hemocyanin has also been identified in the cephalopod ancestor Nautilus, but antimicrobial peptides derived from the hemocyanin of Nautilus pompilius have not been reported. Here, the bactericidal activity of six predicted peptides from N. pompilius hemocyanin and seven mutant peptides was analyzed. Among those peptides, a mutant peptide with 15 amino acids (1RVFAGFLRHGIKRSR15), NpHM4, showed relatively high antibacterial activity. NpHM4 was determined to have typical antimicrobial peptide characteristics, including a positive charge (+5.25) and a high hydrophobic residue ratio (40%), and it was predicted to form an alpha-helical structure. In addition, NpHM4 exhibited significant antibacterial activity against Gram-negative bacteria (MBC = 30 µM for Vibrio alginolyticus), with no cytotoxicity to mammalian cells even at a high concentration of 180 µM. Upon contact with V. alginolyticus cells, we confirmed that the bactericidal activity of NpHM4 was coupled with membrane permeabilization, which was further confirmed via ultrastructural images using a scanning electron microscope. Therefore, our study provides a rationalization for the development and optimization of antimicrobial peptide from the cephalopod ancestor Nautilus, paving the way for future novel AMP development with broad applications.


Assuntos
Hemocianinas , Nautilus , Animais , Antibacterianos/farmacologia , Hemocianinas/química , Hemocianinas/metabolismo , Hemocianinas/farmacologia , Mamíferos/metabolismo , Moluscos/metabolismo , Nautilus/química , Nautilus/metabolismo , Peptídeos/química
7.
BMC Med Imaging ; 21(1): 4, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407222

RESUMO

BACKGROUND: The aim of the present study was to explore the brain active characteristics of patients with irritable bowel syndrome with diarrhea (IBS-D) using resting-state functional magnetic resonance imaging technology. METHODS: Thirteen IBS-D patients and fourteen healthy controls (HC) were enrolled. All subjects underwent head MRI examination during resting state. A voxel-based analysis of fractional amplitude of low frequency fluctuation (fALFF) maps between IBS-D and HC was performed using a two-sample t-test. The relationship between the fALFF values in abnormal brain regions and the scores of Symptom Severity Scale (IBS-SSS) were analyzed using Pearson correlation analysis. RESULTS: Compared with HC, IBS-D patients had lower fALFF values in the left medial superior frontal gyrus and higher fALFF values in the left hippocampus and right precuneus. There was a positive correlation between the duration scores of IBS-SSS and fALFF values in the right precuneus. CONCLUSION: The altered fALFF values in the medial superior frontal gyri, left hippocampus and right precuneus revealed changes of intrinsic neuronal activity, further revealing the abnormality of gut-brain axis of IBS-D.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Diarreia/fisiopatologia , Síndrome do Intestino Irritável/diagnóstico por imagem , Síndrome do Intestino Irritável/fisiopatologia , Imageamento por Ressonância Magnética , Dor Abdominal/fisiopatologia , Adulto , Estudos de Casos e Controles , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Diarreia/etiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/psicologia , Masculino , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/fisiopatologia , Adulto Jovem
8.
Mar Drugs ; 19(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436258

RESUMO

Antimicrobial peptides are a fundamental component of mollusks' defense systems, though they remain a thinly investigated subject. Here, infection by Vibrio parahemolyticus triggered a significant increase in antimicrobial activity in oyster plasma. By using PBS-challenged oysters as a control, plasma peptides from immunologically challenged oysters were subjected to peptidomic profiling and in silico data mining to identify bioactive peptides. Thirty-five identified plasma peptides were up-regulated post infection, among which, six up-regulated peptides (URPs) showed a relatively high positive charge. URP20 was validated with significant antibacterial activity. Virtually, URP20 triggered aggregation of bacterial cells, accompanied by their membrane permeabilization. Interestingly, URP20 was found to be active against Gram-positive and Gram-negative foodborne pathogens as well as Candida albicans, with no cytotoxicity to mammalian cells and mice. Our study provides the first large-scale plasma peptidomic dataset that identifies novel bioactive peptides in marine mollusks. Further exploration of peptide diversity in marine invertebrates should prove a fruitful pursuit for designing novel AMPs with broad applications.


Assuntos
Antibacterianos/farmacologia , Peptídeos Antimicrobianos/farmacologia , Crassostrea , Animais , Organismos Aquáticos , Candida albicans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos
9.
Fish Shellfish Immunol ; 93: 416-427, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374314

RESUMO

Phagocytosis is one of the fundamental cellular immune defense parameter that helps in the elimination of the invading pathogens in both vertebrates and invertebrates, which require plenty of energy for functioning. In the present study, we identified the critical energy regulator AMP-activated protein kinase (AMPK) in Crassostrea hongkongensis which is composed of three subunits, named ChAMPK-α, ChAMPK-ß, and ChAMPK-γ, and then analyzed the function of AMPK in regulating hemocyte phagocytosis. All the three ChAMPK subunits mRNA were detected to be expressed at various embryological stages, and also constitutively expressed in multiple tissues with high expression in gill and mantle. The phylogenetic tree showed that the three subunits of AMPK were correspondingly clustered with its orthologue branches. Furthermore Western Blot analysis revealed that the AMPK pharmacological inhibitors Compound C could effectively down-regulate the Thr172 phosphorylation level of AMPK-α, and the hemocyte phagocytosis was inhibited by Compound C (CC), which indicate its existence in the oyster. Our results showed that treatment of AMPK inhibitors significantly attenuated the capacity of hemocytes phagocytosis. Moreover, Compound C could also change the organization of actin cytoskeleton in the oyster hemocytes, demonstrating the crucial role of AMPK signaling in control of phagocytosis.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/imunologia , Crassostrea/genética , Crassostrea/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteínas Quinases Ativadas por AMP/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Perfilação da Expressão Gênica , Hemócitos , Fagocitose , Alinhamento de Sequência , Transdução de Sinais
10.
Fish Shellfish Immunol ; 75: 190-197, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29407615

RESUMO

Cystatins are a large family of the proteins that function as reversible and tight-binding inhibitors of cysteine proteases, which consequently regulate multiple physiological activities including apoptosis and innate immunity. In the present study, we cloned a gene from Crassostrea gigas encoding cystatin, which is related to cystatin A superfamily. CgCytA was comprised of a cystatin-like domain with two conserved glycine residues (GG) near the N-terminal and a highly conserved glutamine-valine-glycine (Q-X-V-X-G) motif in the form of QVVAG loop. Transcription analysis of CgCytA indicated its constitutive expression in all tissues including mantle, gill, digestive tract, hemocytes, heart, adductor muscle, and gonads. Immune challenge with Vibrio alginolyticus, resulted in significant down-regulation of CgCytA expression at the initial stages of infection (till 12 h post infection) and the expression of cystatin increased 48 h post infection. Protease assay demonstrated the concentration of cystatin needed to inhibit half of the maximum biological response of cysteine protease is 14.4 µg/L (IC50). Furthermore, RNAi of CgCytA resulted in increase of apoptotic cell population in hemocytes of C. gigas, suggesting protection role of CgCytA from hemocytes apoptosis. Unexpectedly, knockdown of CgCytA leaded to enhancement of bacterial clearance in vivo, implying that CgCytA may negatively regulate immune defense by suppressing endogenous cysteine protease. Therefore, CgCytA plays dual roles in protection of host hemocytes from apoptosis and control of bacterial clearance, which may server as one of key endogenous balancer between apoptosis and innate immunity in oyster.


Assuntos
Crassostrea/genética , Crassostrea/imunologia , Cistatina A/genética , Cistatina A/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Cistatina A/química , Perfilação da Expressão Gênica , Filogenia , Interferência de RNA , Alinhamento de Sequência , Vibrio alginolyticus
11.
Fish Shellfish Immunol ; 81: 423-429, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29864587

RESUMO

Hemocytes are the first line of defence of the innate immune system of molluscs. For the first time hemocytes of Crassostrea hongkongensis were morphologically and functionally characterized, identifying circulating cell types and studying their involvement in immune responses. In the present study, two main populations, hyalinocytes and granulocytes, were characterized based on the presence or absence of cytoplasmic granules, using light and electron microscopy (TEM), and flow cytometry analyses. Granulocytes are 7-13 µm in diameter and present evident cytoplasmic granules, and hyalinocytes, 6-15 µm in diameter, with a few or no granules. The mean number of circulating hemocytes in the hemolymph was 2.52 × 106 cells/mL. Flow cytometry indicated that both granulocytes and hyalinocytes showed cell phagocytosis and reactive oxygen species (ROS) production. However, phagocytosis and spontaneous production of reactive oxygen species (ROS) in granulocytes are much more active compared with hyalinocytes, which demonstrated that the granulocytes are the main hemocytes involved in the immune response of Hong Kong oyster. Moreover, the cell-free hemolymph showed antibacterial activity against Vibrio alginolyticus. Our results provide the basic information of hemocytes population of Hong Kong oyster for further investigations associated with innate immunity.


Assuntos
Crassostrea/imunologia , Hemócitos/citologia , Hemócitos/imunologia , Animais , Contagem de Células , Hemolinfa/imunologia , Fagocitose , Espécies Reativas de Oxigênio/metabolismo , Vibrio alginolyticus
12.
BMC Public Health ; 18(1): 937, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-30064389

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is not only the primary cause of death in developed western countries, but also its disease burden is increasing in China. The purpose of constructing population cardiovascular health index is to monitor, compare and evaluate disease burden, influencing factors and prevention and control levels of Chinese population cardiovascular disease in order to provide evidence to improve population cardiovascular health. METHODS: This study collected multi-source data and constructed China Cardiovascular Health Index (CHI) using literature review, questionnaire surveys, Delphi method and Analytical Hierarchy Process (AHP) model. RESULTS: China CHI system included 52 indices of 5 dimensions, which were prevalence status of CVD, exposure of risk factors, prevention and control of risk factors, treatment situation and public health policy and service ability. The weights of 5 dimensions from high to low were successively prevention and control of risk factors 0.3656, prevalence status of CVD 0.2070, treatment situation 0.1812, public health policy and service ability 0.1458, and exposure of risk factors 0.1004. CONCLUSION: China CHI is a comprehensive evaluation system raised to effectively control the prevalence of CVD. In the future, we should strengthen and improve CVD monitoring and big data usage, to ensure these indices to reflect the practical situations and to become utility of controlling CVD.


Assuntos
Doenças Cardiovasculares/epidemiologia , Indicadores Básicos de Saúde , Vigilância da População/métodos , Adulto , China/epidemiologia , Técnica Delphi , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Inquéritos e Questionários
13.
Molecules ; 23(5)2018 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-29783787

RESUMO

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was established and applied to pharmacokinetics in a type 2 diabetic rat model. We firstly investigated the pharmacokinetic changes of canagliflozin and its metabolites in type 2 diabetic rats in order to use canagliflozin more safely, reasonably and effectively. We identified three types of O-glucuronide metabolites (M5, M7 and M17), two kinds of oxidation metabolites (M8 and M9) and one oxidation and glucuronide metabolite (M16) using API 5600 triple-TOF-MS/MS. Following liquid⁻liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin and its metabolites were performed on a Waters XBridge BEH C18 column (100 × 2.1 mm, 2.5 µm) using 0.1% acetonitrile⁻formic acid (75:15, v/v) as the mobile phase at a flow rate of 0.7 mL/min. Selected ion monitoring transitions of m/z 462.00→191.10, 451.20→153.10, 638.10→191.10 and 478.00→267.00 were chosen to quantify canagliflozin, empagliflozin (IS), O-glucuronide metabolites (M5, M7 and M17), and oxidation metabolites (M9) using an API 5500-triple-MS/MS in the positive electrospray ionization mode. The validation of the method was found to be of sufficient specificity, accuracy and precision. The pathological condition of diabetes could result in altered pharmacokinetic behaviors of canagliflozin and its metabolites. The pharmacokinetic parameters (AUC0⁻t, AUC0⁻∞, CLz/F, and Vz/F) of canagliflozin were significantly different between the CTRL and DM group rats (p < 0.05 or p < 0.01), which may subsequently cause different therapeutic effects.


Assuntos
Canagliflozina/farmacocinética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Hipoglicemiantes/farmacocinética , Administração Oral , Animais , Canagliflozina/administração & dosagem , Canagliflozina/sangue , Canagliflozina/química , Cromatografia Líquida de Alta Pressão/métodos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Hipoglicemiantes/química , Limite de Detecção , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Estreptozocina , Espectrometria de Massas em Tandem/métodos
14.
Circulation ; 134(14): 1025-1038, 2016 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-27576776

RESUMO

BACKGROUND: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown. METHODS: Parabiosis and ICH models combined with in vivo and in vitro experiments were used to investigate the roles of hepcidin in brain iron metabolism after ICH. RESULTS: Increased hepcidin-25 was found in serum and primarily in astrocytes after ICH. The brain iron efflux, oxidative brain injury, and cognition impairment were improved in Hepc-/- ICH mice but aggravated by the human hepcidin-25 peptide in C57BL/6 ICH mice. Data obtained in in vitro studies showed that increased hepcidin inhibited the intracellular iron efflux of brain microvascular endothelial cells but was rescued by a hepcidin antagonist, fursultiamine. Using parabiosis ICH models also shows that increased serum hepcidin prevents brain iron efflux. In addition, Toll-like receptor 4 (TLR4)/MyD88 signaling pathway increased hepcidin expression by promoting interleukin-6 expression and signal transducer and activator of transcription 3 phosphorylation. TLR4-/- and MyD88-/- mice exhibited improvement in brain iron efflux at 7, 14, and 28 days after ICH, and the TLR4 antagonist (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate significantly decreased brain iron levels at days 14 and 28 after ICH and improved cognition impairment at day 28. CONCLUSIONS: The results presented here show that increased hepcidin expression caused by inflammation prevents brain iron efflux via inhibition of the intracellular iron efflux of brain microvascular endothelial cells entering into circulation and aggravating oxidative brain injury and cognition impairment, which identifies a mechanistic target for muting inflammation to promote brain iron efflux and to attenuate oxidative brain injury after ICH.


Assuntos
Lesões Encefálicas/metabolismo , Hemorragia Cerebral/metabolismo , Disfunção Cognitiva/metabolismo , Hepcidinas/metabolismo , Ferro/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Lesões Encefálicas/complicações , Disfunção Cognitiva/etiologia , Células Endoteliais/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/genética
15.
Fish Shellfish Immunol ; 68: 37-45, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28648883

RESUMO

Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been demonstrated to be a key signaling molecule involved in adaptive and innate immunity. In this study, we obtained the full length CgTRAF6 cDNA and analyzed the characteristics of the ORF and the peptide sequence in Crassostrea gigas. The deduced protein sequence of CgTRAF6 includes a conserved C-terminal TRAF domain following the RING and the zinc finger domain. The TRAF domain is composed of coiled-coil TRAF-N and MATH (meprin and TRAF-C homology) subdomains. Furthermore, phylogenetic analysis revealed that CgTRAF6 is clustered together with other members TRAF6 family and is placed in a sub-cluster singly which had a close relationship with Drosophila melanogaster. Expression analysis of CgTRAF6 indicated its constitutive expression in all tissues including mantle, adductor muscle, digestive tract, gonads, heart, gill, and hemocyte. Immune challenge with Vibrio alginolyticus and poly I:C resulted in significant up-regulation of CgTRAF6 expression. Dual-luciferase reporter assays showed that CgTRAF6 could activate both pNF-κB-Luc and pISRE-Luc expression, suggesting CgTRAF6 is potentially involved in NF-κB and the interferon signaling pathway. Furthermore, RNAi mediated knockdown of CgTRAF6 resulted in the down-regulation of several putative anti-viral signaling (IRF) and effector (PKR & Viperin) molecules coding genes, 7 days post-injection. These results collectively indicate that CgTRAF6 is a member of TRAF6 sub-family and is potentially involved in immune defense system against invading bacteria and viruses in Crassostrea gigas.


Assuntos
Crassostrea/genética , Crassostrea/imunologia , Imunidade Inata , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Crassostrea/microbiologia , Regulação para Baixo , Especificidade de Órgãos , Filogenia , Poli I-C/imunologia , Fator 6 Associado a Receptor de TNF/química , Regulação para Cima , Vibrio alginolyticus/fisiologia
16.
Fish Shellfish Immunol ; 62: 311-319, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28159693

RESUMO

Extracellular signal-regulated kinases (ERKs) are a group of highly conserved serine/threonine-specific protein kinases that function as important signaling intermediates in mitogen-activated protein kinase (MAPK) pathways, which are involved in a wide variety of cellular activities, including proliferation, inflammation and cytokine production. However, little is known about the roles of this kinase in mollusk immunity. In this study, we identified a molluscan ERK homolog (ChERK) in the Hong Kong oyster (Crassostrea hongkongensis) and investigated its biological functions. The open reading frame (ORF) of ChERK encoded a polypeptide of 365 amino acids, with a predicted molecular weight of 41.96 kDa and pI of 6.43. The predicted ChERK protein contained typical characteristic motifs of the ERK family, including a dual threonine-glutamate-tyrosine (TEY) phosphorylation motif and an ATRW substrate binding site. Phylogenetic analysis revealed that ChERK belonged to the mollusk cluster and shared a close evolutionary relationship with ERK from Crassostrea gigas. In addition, quantitative real-time PCR analysis revealed that ChERK expression was detected in all of the examined tissues and stages of embryonic development; its transcript level was significantly induced upon challenge with bacterial pathogens (Vibrio alginolyticus and Staphylococcus haemolyticus) in vivo and PAMPs (lipopolysaccharide and peptidoglycan) in vitro. Moreover, ChERK was mainly located in the cytoplasm of HEK293T cells. Taken together, these findings may provide novel insights into the functions of molluscan ERKs, especially their roles in response to immune challenge in oyster.


Assuntos
Crassostrea/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Regulação da Expressão Gênica , Moléculas com Motivos Associados a Patógenos/farmacologia , Staphylococcus haemolyticus/fisiologia , Vibrio alginolyticus/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Crassostrea/imunologia , Crassostrea/microbiologia , DNA Complementar/genética , DNA Complementar/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , Humanos , Imunidade Inata , Lipopolissacarídeos/farmacologia , Peptidoglicano/farmacologia , Filogenia , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência
17.
Fish Shellfish Immunol ; 56: 106-110, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27393236

RESUMO

TRIM proteins are a group of highly conserved proteins participating in a variety of biological processes such as regulation of development, apoptosis, and innate immunity. However, the functions of these proteins in the mollusk are still poorly understood. In the present study, a TRIM9 homolog (named ChTRIM9) was first identified from a transcript-ome library in the Hong Kong oyster Crassostrea hongkongensis. The full-length cDNA of ChTRIM9 is 2928 bp and has a predicted Open Reading Frame ORF) encoding 721 amino acids, encoding a putative 80.2 kDa protein. SMART analysis indicated that ChTRIM9 contains the three typical TRIM domains, a RING finger, two B-boxes, and a coiled-coil domain in the N-terminal region, whereas the C-terminal region contains a SPRY domain. qRT-PCR analysis revealed a ubiquitous presence of ChTRIM9, with the highest expression in the gills. Upon bacterial challenge in vivo, the ChTRIM9 transcripts in hemocytes were significantly down-regulated, indicating its involvement in signal transduction in immune response of oysters. Furthermore, ChTRIM9 was found to be localized mainly in the cytoplasm, and its over-expression inhibited the transcriptional activity of the NF-κB gene in HEK293T cells, demonstrating its negative role in regulating NF-κB signaling.


Assuntos
Crassostrea/genética , Crassostrea/imunologia , Proteínas com Motivo Tripartido/genética , Animais , Clonagem Molecular , Crassostrea/metabolismo , Crassostrea/microbiologia , DNA Complementar/genética , DNA Complementar/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Imunidade Inata , NF-kappa B , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de Proteína , Proteínas com Motivo Tripartido/química , Proteínas com Motivo Tripartido/metabolismo , Vibrio alginolyticus/fisiologia
18.
Health Qual Life Outcomes ; 14: 5, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26753922

RESUMO

BACKGROUND: Self-rated health (SRH) and health-related quality of life (HRQOL) are two outcome measures used to assess health status. However, little is known about population-based SRH and HRQOL in China. METHODS: Data from the 2010 China Chronic Disease and Risk Factor Surveillance, a nationally representative sample of 98,658 adults (≥18-year-old) residing in China, were analyzed. SRH was assessed by asking "Would you say that, in general, your health is very good, good, general, poor, or very poor?" HRQOL was assessed by asking "For about how many days during the past 30 days was your health not good due to physical illnesses, injuries, or mental unhealthy?". RESULTS: Overall, 6.3 % of participants rated their health as poor or very poor. The prevalence of poor/very poor health increased with advancing age ranging from 2.0 % in the 18-24 year-olds to 14.9 % in those ≥75 years-old, while it decreased with education levels from 13.0 % in illiterates/those with some primary school education to 2.2 % in college graduates or above. Additionally, women were more likely than men to rate their health as poor or very poor (7.2 % vs. 5.4 %). The reported rate of poor/very poor health was higher in western region residents compared to those in the east (7.4 % vs. 5.3 %). The mean numbers of self-reported physically unhealthy days, injury-caused unhealthy days, or mentally unhealthy days during the past 30 days were 1.48, 0.20, and 0.54, respectively. Older adults had more physically unhealthy days than the younger ones ranging from 2.92 days in those ≥ 75 year-old to 0.95 days in 18-24 year-olds. Women had more physically unhealthy days and mentally unhealthy days than men (1.72 vs. 1.23; 0.62 vs. 0.46, respectively). The highest mean number of physically unhealthy days (2.32) was reported by illiterates or those with some primary school education. The highest mean number of mentally unhealthy days (0.86) reported by college graduates or above. CONCLUSIONS: Substantial variations existed in SRH and HRQOL among age groups, gender groups, education groups, and across regions in China. Considering these disparities will be important when developing health policies and allocating resources.


Assuntos
Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , Atitude Frente a Saúde , Nível de Saúde , Avaliação de Resultados da Assistência ao Paciente , Qualidade de Vida/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Autorrelato , Fatores Socioeconômicos , Adulto Jovem
19.
Molecules ; 19(8): 12065-77, 2014 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-25120057

RESUMO

Various products containing sinomenine monomer and extracts of Sinomenium acutum have been widely applied in clinical treatments. The goal of the present study was to compare the pharmacokinetics of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract, and to attempt to explore potential component-component interactions between the constituents of this traditional Chinese herbal medicine. A reliable and specific reversed phase high performance liquid chromatography method was developed to analyze sinomenine in rat plasma. Pharmacokinetic parameters for sinomenine were processed by non-compartmental analysis. The results showed that the maximum concentration, the area under the concentration-time curve, clearance and the apparent volume of distribution of sinomenine in the Sinomenium acutum extract statistically differed from those of sinomenine monomer (p < 0.05); however, the mean residence time, time of peak concentration, and half-life did not show significant differences between the two groups. These findings suggested that some additional components in the Sinomenium acutum extract may decrease the absorption of sinomenine. The complex interactions between sinomenine and other components of the herbal extract could result in the altered pharmacokinetic behavior of sinomenine, which may subsequently cause different therapeutic and detoxification effects.


Assuntos
Morfinanos/farmacocinética , Extratos Vegetais/farmacocinética , Sinomenium/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Inativação Metabólica , Morfinanos/administração & dosagem , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 48(8): 710-4, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25388468

RESUMO

OBJECTIVE: To investigate the status quo and influence factors of self monitoring of blood glucose (SMBG) and self-efficacy of diabetes patients' that participated in community diabetes self management group. METHODS: Beijing, Shanghai, Chongqing, Jiangsu, Guangdong, and Zhejiang were selected as the study sites considering patients management experiences they had. 1 401 adult diabetes patients were recruited from communities via health records system screening, telephone notification, poster advertisement, letters invitation ways. Face to face questionnaire survey was applied to obtain patients' general information, diabetes history, diabetes knowledge awareness, SMBG, and self-efficacy information. Multiple linear regression was used to analyze the relationship between factors and self efficacy. RESULTS: There were 519 male patients (37.0%) and 882 female patients (63.0%) with an average age of (64.9 ± 8.9) years old. Patients lived in city accounted for 48.0% (672/1 401) and rural patients accounted for 52.0% (729/1 401). Patients who conducted SMBG accounted for 79.9% (1 120/1 401) and 33.3% (446/1 401) patients conducted blood glucose monitoring 1-3 times per month. Rural patients, primary school educated, and new rural cooperative medical system (NCMS) covered patients had a higher proportion of never conducting SMBG which were 21.9% (160/729), 24.2% (160/662), and 26.3% (125/475) , respectively. Scores of self-efficacy was (69.24 ± 16.30) (hundred-mark system) with a relative lower score in monitoring of blood glucose (64.09 ± 20.08) and foot care (63.63 ± 21.40), as well as a highest score in taking medicine and insulin injections (76.10 ± 22.00). Multiple regression analysis on self-efficacy and its related factors show a negative correlation between patients' place of residence and self-efficacy (ß' = -0.076) and a positive correlation between education and self-efficacy (ß' = 0.114) as well as between diabetes knowledge awareness and self-efficacy (ß' = 0.193)(t = -2.46, 3.71, 7.18, P < 0.05). CONCLUSION: Community diabetes patients had a low self-efficacy and it was even lower among low economic and education degree patients. The worst parts were SMBG and foot care. Place of residence, education, and diabetes knowledge awareness are factors that influence patients' self efficacy.


Assuntos
Automonitorização da Glicemia/estatística & dados numéricos , Diabetes Mellitus/terapia , Adesão à Medicação/estatística & dados numéricos , Autoeficácia , Idoso , Idoso de 80 Anos ou mais , Glicemia , China/epidemiologia , Feminino , , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Inquéritos e Questionários
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