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1.
Mol Immunol ; 127: 136-145, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32971400

RESUMO

Sepsis-induced inflammatory damage is a crucial cause of acute kidney injury (AKI), and AKI is an ecumenical fearful complication in approximately half of patients with sepsis. CCAAT/enhancer-binding protein ß (C/EBPß) plays roles in regulating acute phase responses and inflammation. However, the role and mechanism of C/EBPß in AKI are unclear. LPS combined with ATP-treated renal epithelial cells HK2 and cecal ligation-peferation (CLP)-mice were used as models of AKI in vitro and in vivo. Cell damage, the secretion of interleukin-1 beta (IL-1ß), IL-18 and cysteinyl aspartate specific proteinase 1 (caspase-1) activity were tested by LDH, ELISA assay and flow cytometry analysis, respectively. The expression levels of TFAM, C/EBPß, and pyroptosis-related molecules were tested by qRT-PCR and Western blotting. Chromatin immunoprecipitation (ChIP) assessed the interaction between C/EBPß with TFAM. Hematoxylin-Eosin (H&E) staining detected pathological changes of kidney tissues, and immunohistochemistry measured TFAM and C/EBPß in mice kidney tissues. C/EBPß or TFAM were up-regulated in LPS combined with ATP -induced HK2 cells. Knockdown of C/EBPß could suppress cell injury and the secretion of IL-1ß and IL-18 induced by LPS combined with ATP. Furthermore, C/EBPß up-regulated the expression levels of TFAM via directly binding to TFAM promoter. Overexpression of TFAM reversed the effects of C/EBPß deficiency on pyroptosis. Knockdown of C/EBPß could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway by inactivating TFAM/RAGE pathway. It was further confirmed in the AKI mice that C/EBPß and TFAM promoted AKI by activating NLRP3-mediated pyroptosis. The interaction of between C/EBPß and TFAM facilitated pyroptosis by activating NLRP3/caspase-1 signal axis, thereby promoting the occurrence of AKI.


Assuntos
Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Inflamassomos/metabolismo , Proteínas Mitocondriais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Fatores de Transcrição/metabolismo , Trifosfato de Adenosina , Animais , Caspase 1/metabolismo , Linhagem Celular , Humanos , Inflamação/patologia , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , Ligação Proteica , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais
2.
Front Pharmacol ; 11: 996, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719603

RESUMO

Renal fibrosis is the final common pathological manifestation of almost all progressive chronic kidney diseases (CKD). Transient receptor potential canonical (TRPC) channels, especially TRPC3/6, were proposed to be essential therapeutic targets for kidney injury. Huangkui capsule (HKC), an important adjuvant therapy for CKD, showed superior efficacy for CKD at stages 1-2 in clinical practice. However, its anti-fibrotic effect and the underlying mechanisms remain to be investigated. In the present study, we evaluated the efficacy of HKC on renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and explored the potential underlying mechanism. Administration of HKC by intragastric gavage dose-dependently suppressed UUO-induced kidney injury and tubulointerstitial fibrosis. Similarly, HKC suppressed the expression level of α-smooth muscle actin (α-SMA), increased the expression of E-cadherin, and suppressed the mRNA expression of a plethora of proinflammatory mediators that are necessary for the progression of renal fibrosis. Mechanistically, HKC suppressed both canonical and non-canonical TGF-ß signaling pathways in UUO mice as well as the TRPC6/calcineurin A (CnA)/nuclear factor of activated T cells (NFAT) signaling axis. In addition, TRPC6 knockout mice and HKC treated wild type mice displayed comparable protection on UUO-triggered kidney tubulointerstitial injury, interstitial fibrosis, and α-SMA expression. More importantly, HKC had no additional protective effect on UUO-triggered kidney tubulointerstitial injury and interstitial fibrosis in TRPC6 knockout mouse. Further investigation demonstrated that HKC could directly suppress TRPC3/6 channel activities. Considered together, these data demonstrated that the protective effect of HKC on renal injury and interstitial fibrosis is dependent on TRPC6, possibly through direct inhibition of TRPC6 channel activity and indirect suppression of TRPC6 expression.

3.
J Ophthalmol ; 2020: 7516286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676204

RESUMO

Purpose: In vivo confocal laser scanning microscopy (CLSM) is an emerging diagnostic tool allowing fast and easy microscopic tissue examination. For the diagnostics of pathological eyelid margin lesions, the knowledge of the normal eyelid margin is essential. Methods: We examined 18 eyelid margins of healthy humans using the in vivo CLSM device and 10 samples of healthy eyelid margins from donor sites with ex vivo CLSM and compared the findings to the corresponding histological sections of donor sites. Cross-section images of different depths and depths of different skin appendages were measured. Results: The depth observed by in vivo CLSM is less than 150 µm into the eyelid. Images of the epidermis and superficial dermis skin, appendages including hair follicle, and sebaceous catheters can be captured associated with histopathology and ex vivo confocal microscopy. In correlation with histopathology, we identified different layers of the eyelid margin, different layers of the epidermis, and skin appendages by ex vivo confocal microscopy. Conclusions: The study offers an overview of the in vivo confocal microscopy human eyelid margin characteristics in comparison to the standard histological examination and confirms that in vivo CLSM could not observe the meibomian gland acini structure.

4.
Int J Syst Evol Microbiol ; 70(4): 2907-2911, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32242795

RESUMO

The Gram-stain-negative, rod-shaped, yellow-pigmented and facultative anaerobic bacterial strain, designated H164T, was isolated from seawater collected from the Caroline Seamounts in the Pacific Ocean. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain H164T was related to the genus Algibacter and had highest 16S rRNA gene sequence similarity to Algibacter wandonensis WS-MY22T (97.4 %). The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. The predominant menaquinone was MK-6. The polar lipid profile contained phosphatidylethanolamine, one unidentified aminolipid and two unidentified lipids. The genomic DNA G+C content of strain H164T was 33.2 mol%. The values of in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) between strain H164T and A. wandonensis KCTC 32381T were 26.10 and 81.88 %. The isDDH and ANI values between strain H164T and Algibacter lectus DSM 15365T were 25.40 and 81.79 %. Combined data from phenotypic, phylogenetic, isDDH and ANI analyses demonstrated that strain H164T represents a novel species of the genus Algibacter, for which we propose the name Algibacter pacificus sp. nov. (type strain H164T=KCTC 72432T=CGMCC 1.17117T).


Assuntos
Flavobacteriaceae/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Oceano Pacífico , Fosfatidiletanolaminas/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Nat Commun ; 11(1): 79, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911589

RESUMO

Mice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93-95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Camundongos/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Ceco/microbiologia , China , Bases de Dados Factuais , Genoma Bacteriano , Masculino , Camundongos Endogâmicos C57BL , Filogenia
6.
Appl Environ Microbiol ; 85(22)2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31492670

RESUMO

Soil bacteria adapt to diverse and rapidly changing environmental conditions by sensing and responding to environmental cues using a variety of sensory systems. Two-component systems are a widespread type of signal transduction system present in all three domains of life and typically are comprised of a sensor kinase and a response regulator. Many two-component systems function by regulating gene expression in response to environmental stimuli. The bacterial chemotaxis system is a modified two-component system with additional protein components and a response that, rather than regulating gene expression, involves behavioral adaptation and results in net movement toward or away from a chemical stimulus. Soil bacteria generally have 20 to 40 or more chemoreceptors encoded in their genomes. To simplify the identification of chemoeffectors (ligands) sensed by bacterial chemoreceptors, we constructed hybrid sensor proteins by fusing the sensor domains of Pseudomonas putida chemoreceptors to the signaling domains of the Escherichia coli NarX/NarQ nitrate sensors. Responses to potential attractants were monitored by ß-galactosidase assays using an E. coli reporter strain in which the nitrate-responsive narG promoter was fused to lacZ Hybrid receptors constructed from PcaY, McfR, and NahY, which are chemoreceptors for aromatic acids, tricarboxylic acid cycle intermediates, and naphthalene, respectively, were sensitive and specific for detecting known attractants, and the ß-galactosidase activities measured in E. coli correlated well with results of chemotaxis assays in the native P. putida strain. In addition, a screen of the hybrid receptors successfully identified new ligands for chemoreceptor proteins and resulted in the identification of six receptors that detect propionate.IMPORTANCE Relatively few of the thousands of chemoreceptors encoded in bacterial genomes have been functionally characterized. More importantly, although methyl-accepting chemotaxis proteins, the major type of chemoreceptors present in bacteria, are easily identified bioinformatically, it is not currently possible to predict what chemicals will bind to a particular chemoreceptor. Chemotaxis is known to play roles in biodegradation as well as in host-pathogen and host-symbiont interactions, but many studies are currently limited by the inability to identify relevant chemoreceptor ligands. The use of hybrid receptors and this simple E. coli reporter system allowed rapid and sensitive screening for potential chemoeffectors. The fusion site chosen for this study resulted in a high percentage of functional hybrids, indicating that it could be used to broadly test chemoreceptor responses from phylogenetically diverse samples. Considering the wide range of chemical attractants detected by soil bacteria, hybrid receptors may also be useful as sensitive biosensors.


Assuntos
Proteínas de Bactérias/genética , Quimiotaxia/genética , Escherichia coli/genética , Pseudomonas putida/genética , Transdução de Sinais , Proteínas de Escherichia coli/genética , Expressão Gênica , Genoma Bacteriano , Proteínas Quimiotáticas Aceptoras de Metil/genética
7.
Pathobiology ; 86(5-6): 263-273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430762

RESUMO

BACKGROUND: Mitochondrial transcription factor A (TFAM) plays multiple pathophysiologic roles in mitochondrial DNA (mtDNA) maintenance. However, the role of TFAM in sepsis-induced acute kidney injury (AKI) remains largely unknown. METHODS: Lipopolysaccharide (LPS) treatment of HK-2 cells mimics the in vitro model of AKI inflammation. pcDNA3.1 plasmid was used to construct pcDNA3.1-TFAM. sh-TFAM-543, sh-TFAM-717, sh-TFAM-765, sh-TFAM-904 and pcDNA3.1-TFAM were transfected into HK-2 cells using Lipofectamine 2000. MtDNA transcriptional levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was performed to assess the cell viability. Changes in reactive oxygen species (ROS) and mitochondrial membrane potential in HK-2 cells were detected using the corresponding kits. Immunofluorescence experiment was used to investigate the displacement of TFAM. mRNA and protein expression levels of TFAM and its related genes were measured by qRT-PCR and western blot respectively. Mice in sepsis were administered cecal ligation and puncture surgery. RESULTS: LPS treatment was a non-lethal influencing factor, leading to the upregulation of ROS levels and downregulation of mtDNA copy number and NADH dehydrogenase subunit-1 (ND1) expression, and caused damage to the mitochondria. As the LPS treatment time increased, TFAM was displaced from the periphery of the nucleus to cytoplasm. TFAM reduced ROS and P38MAPK levels by inhibiting toll-like receptor 4 (TLR4) expression, ultimately inhibiting inflammation and repairing mtDNA. CONCLUSIONS: Our results indicate that TFAM repairs mtDNA by blocking the TLR4/ROS/P38MAPK signaling pathway in inflammatory cells, thereby repairing septic tubular epithelial cells, and TFAM may serve as a new target for sepsis therapy.


Assuntos
Proteínas de Ligação a DNA/genética , Células Epiteliais/patologia , Proteínas Mitocondriais/genética , Espécies Reativas de Oxigênio/metabolismo , Sepse/genética , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Fatores de Transcrição/genética , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Linhagem Celular , Humanos , Túbulos Renais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Sepse/patologia
8.
Am J Ophthalmol ; 203: 46-52, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30849348

RESUMO

PURPOSE: We sought to determine the diagnostic accuracy of in vivo confocal microscopy (IVCM) for ocular demodicosis. DESIGN: Reliability and validity analysis. METHODS: This was a single-center study of consecutive patients presenting to Zhongnan Hospital of Wuhan University, Hubei, China, between February 2017 and February 2018 with blepharitis. After examination, the blepharitis was scanned by IVCM. The regrading of the shuffled image set was performed by grader 1 (experienced) and grader 2 (inexperienced). The regrading of the shuffled image set was performed by 2 graders 3 weeks later. Eyelash samples were collected for light microscopy. The main outcome measures were sensitivity, specificity, and positive and negative predictive values of IVCM compared with those of positive light microscopy under 2 definitions. Sensitivities and specificities for multiple graders were pooled and 95% confidence intervals (CIs) were calculated. RESULTS: Sensitivity of IVCM grader 1 and grader 2 based on the definition of "light microscopy-positive demodex" was 100% (95% CI 94.84-100%) and 98.8% (95% CI 93.02-99.94%), respectively. Sensitivity of IVCM grader 1, grader 2, and light microscopy to the definition of "definite diagnosis demodex" definition was 100% (95% CI 97.02-100%), 93.63% (95% CI 88.28-96.73%), and 56.69% (95% CI 48.55-64.49%). CONCLUSIONS: IVCM is better than traditional methods in detecting the number and sensitivity of demodex, and it is both highly sensitive and specific when performed by an experienced operator.


Assuntos
Blefarite/diagnóstico , Infecções Oculares Parasitárias/diagnóstico , Pálpebras/patologia , Microscopia Confocal/métodos , Infestações por Ácaros/diagnóstico , Ácaros , Adulto , Animais , Blefarite/parasitologia , Infecções Oculares Parasitárias/parasitologia , Pálpebras/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infestações por Ácaros/parasitologia , Estudos Prospectivos , Reprodutibilidade dos Testes
9.
Int J Syst Evol Microbiol ; 69(3): 761-766, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30652964

RESUMO

A polyphasic taxonomic approach was applied to characterize an anaerobic bacterial strain, 426-9T, that was isolated from human faeces. The strain was Gram-stain-negative, non-motile, non-spore-forming, non-pigmented and rod-shaped. Strain 426-9T grew anaerobically at 20-45 °C (optimally at 37-40 °C) and at pH 6.0-10.0 (optimally at pH 6.0-8.0). The major polar lipids were phosphatidylethanolamine, seven amino phospholipids and three phospholipids. The major fatty acids of strain 426-9T were anteiso-C15 : 0 and iso-C17 : 0 3-OH, and the predominant respiratory quinones were menaquinones MK-9 and MK-10. End-products of glucose fermentation were acetate, propionate, iso-butyrate and iso-pentanoate. 16S rRNA gene sequence analysis showed that strain 426-9T was a member of the genus Parabacteroides. The level of 16S rRNA gene sequence similarity of strain 426-9T to the type species of the genus, Parabacteroides distasonis ATCC 8503T, was 91.0 %. Within the genus Parabacteroides, strain 426-9T was phylogenetically closely related to Parabacteroides johnsonii M-165T (96.0 % 16S rRNA gene sequence similarity). The draft genome of strain 426-9T comprised 5.15 Mb with a DNA G+C content of 45.9 mol%. A total of 4088 genes were predicted and, of those, 3744 were annotated. On the basis of phenotypic, chemotaxonomic and phylogenetic characterization, strain 426-9T represents a novel species within the genus Parabacteroides, for which the name Parabacteroides acidifaciens sp. nov. is proposed. The type strain is 426-9T (=CGMCC 1.13558T=NBRC 113433T).


Assuntos
Bacteroidetes/classificação , Fezes/microbiologia , Filogenia , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fermentação , Humanos , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
10.
Biochemistry ; 56(34): 4559-4567, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28767234

RESUMO

Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an "open" conformation (apo) obtained in the absence of ligands and a "closed" conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in solution, X-ray solution scattering data were collected from AdK in the apo form and with progressively increasing concentrations of five different ligands. Scattering data from apo AdK are consistent with scattering predicted from the crystal structure of AdK in the open conformation. In contrast, data from AdK samples saturated with Ap5A do not agree with that calculated from AdK in the closed conformation. Using cluster analysis of available structures, we selected representative structures in five conformational states: open, partially open, intermediate, partially closed, and closed. We used these structures to estimate the relative abundances of these states for each experimental condition. X-ray solution scattering data obtained from AdK with AMP are dominated by scattering from AdK in the open conformation. For AdK in the presence of high concentrations of ATP and ADP, the conformational ensemble shifts to a mixture of partially open and closed states. Even when AdK is saturated with Ap5A, a significant proportion of AdK remains in a partially open conformation. These results are consistent with an induced-fit model in which the transition of AdK from an open state to a closed state is initiated by ATP binding.


Assuntos
Difosfato de Adenosina/química , Trifosfato de Adenosina/química , Adenilato Quinase/química , Fosfatos de Dinucleosídeos/química , Proteínas de Escherichia coli/química , Escherichia coli/enzimologia , Adenilato Quinase/genética , Domínio Catalítico , Cristalografia por Raios X , Escherichia coli/genética , Proteínas de Escherichia coli/genética
11.
Cell Mol Neurobiol ; 37(5): 919-929, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27678140

RESUMO

The CD4+CD25+ regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model. Tregs treatment reduced the content of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and malondialdehyde, while increasing the superoxide dismutase (SOD) enzymatic activity at day (1, 3 and 7) following ICH. Furthermore, Tregs treatment obviously reduced the number of NF-κB+, IL-6+, TUNEL+ and active caspase-3+ cells at day 3 after ICH. These results indicate that adoptive transfer of Tregs may provide neuroprotection following ICH in mouse models.


Assuntos
Transferência Adotiva , Hemorragia Cerebral/imunologia , Hemorragia Cerebral/terapia , Hematoma/imunologia , Hematoma/terapia , Inflamação/patologia , Linfócitos T Reguladores/imunologia , Animais , Apoptose , Barreira Hematoencefálica/patologia , Hemorragia Cerebral/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Hematoma/complicações , Hematoma/patologia , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismo
12.
J Ophthalmol ; 2016: 3071036, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27293874

RESUMO

Background. To evaluate the optical quality and related factors in patients with ocular hypertension (OHT). Methods. This was a prospective case-control study. A total of 12 eyes with OHT and 20 control eyes underwent testing with Optical Quality Analysis System II (OQAS II) to evaluate the modulation transfer function cut off frequency (MTF cutoff), the Strehl 2D ratio (SR), objective scatter index (OSI), tear-film mean OSI (TFOSI), and the OQAS values (OV100%,OV20%, and OV9%). Results. The optical quality of patients with OHT declined, with lower MTF cutoff (OHT 36.86 ± 7.11 cpd , controls 48.50 ± 4.04 cpd, t = -4.60, P < 0.05), lower SR (OHT 0.22 ± 0.04, controls 0.27 ± 0.05, t = -2.72, P < 0.05), lower OV100% (OHT 1.26 ± 0.25, controls 1.61 ± 0.14, t = -4.03, P < 0.05), lower OV20% (OHT 1.27 ± 0.27, controls 1.72 ± 0.20, t = -4.00, P < 0.05), and lower OV9% (OHT 1.30 ± 0.25, controls 1.69 ± 0.32, t = -2.28, P < 0.05). There were not any statistically significant differences in OSI and TFOSI. The MTF cutoff in patients with OHT was correlated significantly with age (r = -0.59, P < 0.05). Conclusions. Optical quality of patients with OHT is reduced, with lower MTF cutoff, SR, OV100%, OV20%, and OV9%. MTF cutoff is negatively related to age.

13.
J Huazhong Univ Sci Technolog Med Sci ; 36(1): 95-98, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26838747

RESUMO

Both open and closed loop self-expandable stents were used in carotid artery stenting (CAS) for carotid bifurcation stenosis. We sought to compare the efficacy of two types of stents in CAS. The data of 212 patients treated with CAS (42 and 170 cases implanted with closed and open loop stents, respectively) for carotid bifurcation stenosis and distal filtration protection devices were retrospectively analyzed. Between closed and open loop stents, there were no significant differences in hospitalization duration, NIHSS score before and after the treatment, stenosis at 12th month, and cumulative incidence of primary endpoint events within 30 days or from the 31st day to the 12th month; while there were significant differences in hemodynamic changes and rate of difficulty in recycling distal filtration protection devices. Use of open vs. closed loop stents for carotid bifurcation stenosis seems to be associated with similar incidence of complications, except for greater rate of hemodynamic changes and lower rate of difficulty in recycling the distal filtration protection devices.


Assuntos
Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Procedimentos Endovasculares/instrumentação , Stents Metálicos Autoexpansíveis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias
14.
Parasite ; 23: 4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26842927

RESUMO

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that affects humans and various vertebrate livestock and causes serious economic losses. To develop an effective vaccine against T. gondii infection, we constructed a DNA vaccine encoding the T. gondii rhoptry protein 17 (TgROP17) and evaluated its immune protective efficacy against acute T. gondii infection in mice. The DNA vaccine (p3×Flag-CMV-14-ROP17) was intramuscularly injected to BALB/c mice and the immune responses of the vaccinated mice were determined. Compared to control mice treated with empty vector or PBS, mice immunized with the ROP17 vaccine showed a relatively high level of specific anti-T. gondii antibodies, and a mixed IgG1/IgG2a response with predominance of IgG2a production. The immunized mice also displayed a specific lymphocyte proliferative response, a Th1-type cellular immune response with production of IFN-γ and interleukin-2, and increased number of CD8(+) T cells. Immunization with the ROP17 DNA significantly prolonged the survival time (15.6 ± 5.4 days, P < 0.05) of mice after challenge infection with the virulent T. gondii RH strain (Type I), compared with the control groups which died within 8 days. Therefore, our data suggest that DNA vaccination with TgROP17 triggers significant humoral and cellular responses and induces effective protection in mice against acute T. gondii infection, indicating that TgROP17 is a promising vaccine candidate against acute toxoplasmosis.


Assuntos
DNA de Protozoário/genética , Proteínas de Protozoários/imunologia , Toxoplasma/imunologia , Toxoplasmose Animal/prevenção & controle , Vacinas de DNA/imunologia , Fatores de Virulência/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Linfócitos T CD8-Positivos/imunologia , Citocinas/metabolismo , DNA de Protozoário/imunologia , DNA Recombinante/genética , DNA Recombinante/imunologia , Feminino , Imunoglobulina G/sangue , Injeções Intramusculares , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Células Th1/imunologia , Toxoplasmose Animal/imunologia , Vacinação , Vacinas Sintéticas/imunologia , Fatores de Virulência/genética
15.
J Renin Angiotensin Aldosterone Syst ; 15(3): 294-300, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23283824

RESUMO

OBJECTIVE: The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI), but previous studies have been inconsistent. The present study aimed at assessing the association of M235T polymorphism in the AGT gene with MI using a meta-analysis. METHODS: We retrieved literature in Google Scholar, PubMed, Cochrane Library and the China National Knowledge Infrastructure database (January 1990-December 2011) for the relevant studies on the AGT polymorphism M235T and risk of MI. Statistical analyses were carried out using Stata 10.0 for combining all the relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Begg's test was used to measure publication bias. RESULTS: A total of 21 case-control studies containing 5887 patients and 6164 controls were enrolled into this meta-analysis. Overall, significant association was found between the AGT gene M235T polymorphism and risk of MI in the subgroup analysis for TT vs MT in Asians (OR 1.47, 95% CI: 1.01-2.12; p = 0.04). No associations were detected between AGT M235T and the risk of MI in total population and Caucasians. CONCLUSIONS: This meta-analysis demonstrated that the AGT M235T polymorphism could be a prediction marker for risk of MI in Asians. Conclusive evidence on the effects of the variants in MI should be addressed in further studies.


Assuntos
Angiotensinogênio/genética , Predisposição Genética para Doença , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Humanos , Razão de Chances , Viés de Publicação , Fatores de Risco
16.
Zhonghua Er Ke Za Zhi ; 50(6): 435-9, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22931941

RESUMO

OBJECTIVE: To investigate the characteristics of circulatory disturbance and treatment of severe hand-foot-and-mouth disease (HFMD). METHOD: The clinical characteristics, laboratory findings, therapy and outcome of 22 severe HFMD patients were retrospectively analyzed. RESULT: All the 22 severe HFMD patients came from the countryside. All these patients had encephalitis. Fifteen cases had myocardial injury. All had symptoms of sympathetic excitation and 17 cases had hypertension [(128 ± 16)/(81 ± 14) mm Hg (1 mm Hg = 0.133 kPa)]. Fourteen cases had exacerbation with rapid decline of blood pressure [(61 ± 12)/(33 ± 12) mm Hg]. In cardiorespiratory failure stage, 13 patients had neurogenic pulmonary edema accompanied by circulatory failure and 12 cases had a lower glasgow scores (less than 7). Myocardial injury and ECG change were found in some cases. Inotropic and pressor drugs were given in patients with circulatory collapse. Five cases received fluid resuscitation due to refractoriness to inotropic drugs. Nine patients received blood purification. Seventeen survived and 5 cases died due to circulatory failure. CONCLUSION: Circulation failure of severe HFMD is the main cause of death. Early and appropriate circulation support is very important to reduce mortality.


Assuntos
Doença de Mão, Pé e Boca/mortalidade , Doença de Mão, Pé e Boca/terapia , Milrinona/administração & dosagem , Insuficiência de Múltiplos Órgãos/mortalidade , Edema Pulmonar/mortalidade , Pré-Escolar , China/epidemiologia , Terapia Combinada , Feminino , Doença de Mão, Pé e Boca/complicações , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Milrinona/uso terapêutico , Insuficiência de Múltiplos Órgãos/etiologia , Edema Pulmonar/etiologia , Respiração Artificial , Estudos Retrospectivos , Choque/etiologia , Choque/mortalidade , Resultado do Tratamento
17.
Anal Chem ; 84(15): 6312-6, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22816618

RESUMO

Transmission electron microscopy (TEM) is a unique and powerful tool for observation of nanoparticles. However, due to the uneven spatial distribution of particles conventionally dried on copper grids, TEM is rarely employed to evaluate the spatial distribution of nanoparticles in aqueous solutions. Here, we present a microchip nanopipet with a narrow chamber width for sorting nanoparticles from blood and preventing the aggregation of the particles during the drying process, enabling quantitative analysis of their aggregation/agglomeration states and the particle concentration in aqueous solutions. This microchip is adaptable to all commercial TEM holders. Such a nanopipet proves to be a simple and convenient sampling device for TEM image-based quantitative characterization.


Assuntos
Microscopia Eletrônica de Transmissão , Nanopartículas/análise , Ouro/química , Humanos , Dispositivos Lab-On-A-Chip , Nanotecnologia/instrumentação , Plasma/química , Polietilenoglicóis/química
18.
Mol Med Rep ; 6(4): 884-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22842872

RESUMO

The angiotensinogen (AGT) gene M235T polymorphism has been suggested to be linked with susceptibility to coronary artery disease (CAD). In the present study, a meta-analysis was performed to assess the correlation between the M235T polymorphism and CAD. Nine studies with a total of 2281 subjects were selected for inclusion in the analysis. The references were retrieved via PubMed, China National Knowledge Infrastructure, Wanfang and VIP database (1995.1-2012.1). The analyses were performed using STATA 10.0 software. Odds ratios (OR) with 95% confidence intervals (CIs) were assessed after the collected data were pooled for analysis. A significant association was detected between M235T gene polymorphism and CAD in the population studied. The estimates (OR) of CAD risk were calculated in a homozygote comparison (OR=1.54; 95% CI, 1.09-2.16), a heterozygote comparison (OR=1.30; 95% CI, 1.07-1.58), a dominant model (OR=0.72; 95% CI, 0.55-0.94) and a recessive model (OR=1.37; 95% CI, 0.98-1.91). The current meta-analysis suggests that the M235T polymorphism is associated to an increased risk of CAD.


Assuntos
Angiotensinogênio/genética , Doença da Artéria Coronariana/genética , Bases de Dados Factuais , Heterozigoto , Homozigoto , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco
19.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 4): o1272, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22606199

RESUMO

In the title compound, C(24)H(30)N(6)O(5), the cyclo-hexyl ring adopts a chair conformation, while the remainder of the mol-ecule adopts a U-shape. The dihedral angles between the pyridine ring and the pendant pyrimidine rings are 69.04 (12) and 75.99 (9)°. The two pyrimidine rings, however, are nearly parallel to one another, with a dihedral angle of 8.56 (15)° between them. They are also involved in an intra-molecular π-π stacking inter-action with a distance of 3.6627 (18) Šbetween the ring centroids. In the crystal, C-H⋯O contacts link the mol-ecules into chains along the b axis.

20.
J Chromatogr B Analyt Technol Biomed Life Sci ; 895-896: 178-81, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22483396

RESUMO

Nanoparticles were designed to encapsulate drugs to alter their pharmacological behaviors, therefore, it is very essential to monitor the pharmacokinetic profile of drug encapsulated in nanoparticles in order to clarify and predict their efficacy and side effects. In this paper, we reported a simple, rapid µ-elution 96-well solid phase extraction (µSPE) method combining with ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for determination of nanoformulated drug in rat plasma. This method presented satisfactory results in terms of sensitivity, precision, accuracy, and recovery, for the first time, of quantitatively analyzing clarithromycin (CLA) in rat plasma after intravenous administration CLA-loaded ultrafine PLGA nanoparticles for pharmacokinetic study. This method has been proved to be fast, reliable and reproducible to accurately analyze drug encapsulated in polymeric nanoparticles sample for a pharmacokinetic study.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Claritromicina/sangue , Ácido Láctico/administração & dosagem , Nanopartículas/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Espectrometria de Massas em Tandem/métodos , Animais , Claritromicina/administração & dosagem , Claritromicina/farmacocinética , Injeções Intravenosas , Ácido Láctico/química , Modelos Lineares , Masculino , Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Microextração em Fase Sólida
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