Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 710
Filtrar
Filtros adicionais











Intervalo de ano
1.
Sci Rep ; 9(1): 13176, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511528

RESUMO

Diseases caused by Rickettsiales bacteria are a global public health problem. To better understand the diversity and origins of Rickettsiales infection in humans and animals, we sampled 134 febrile patients, 173 rodents and 43 shrews, as well as 358 ticks, from two cities in Jiangsu and Jiangxi provinces, China. Our data revealed a relatively high prevalence of scrub typhus cases in both localities. In addition, both serological tests and genetic analysis identified three patients infected with Anaplasma bovis, Rickettsia monacensis, and Orientia tsutsugamushi bacteria. Molecular epidemiological investigation revealed the co-circulation of multiple species of Rickettsiales bacteria in small mammals and ticks in both provinces, potentially including novel bacterial species. In sum, these data demonstrate the ongoing importance of Rickettsiales infection in China and highlight the need for the regular surveillance of local arthropods, mammals and humans.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31476577

RESUMO

A novel hydroxyapatite-embedded monolithic column has been facilely prepared in a stainless-steel column with inner diameter of 2.1 mm by the strong adhesion of urea-formaldehyde (UF) resin and exploited as a sorbent for selective on-line solid-phase extraction (on-line SPE) of adenosine triphosphate and its phosphorylated metabolites. The composition for this preparation, including the amount of hydroxyapatite nanopowders and the porogen were investigated to obtain a suitable monolith with large surface area and satisfactory permeability. Owing to anion exchange interaction of hydroxyapatite and hydrophilic interaction of UF monolithic matrix, the prepared monolith showed good extraction efficiency and selectivity towards these phosphorylated analytes. Several parameters for on-line SPE, including ACN percentage in the sampling solution, collection time span, salt concentration of the eluent, sampling and elution flow rate, were optimized with respect to the extraction efficiencies of the target compounds. Under the optimized conditions, the LODs of the analytes were in the range of 0.01-0.04 µg/g, the recoveries in the spiked samples ranged from 78.3%-92.5% with RSDs <4.7%. Due to the excellent extraction ability towards phosphorylated compounds in practical samples, a simple on-line SPE-HPLC method using hydroxyapatite-embedded monolith as sorbent has been proposed for monitoring freshness of grass carp.

3.
Parasit Vectors ; 12(1): 423, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462294

RESUMO

BACKGROUND: Pentatrichomonas hominis is a flagellated protozoan that inhabits the large intestine of humans. Although several protozoans have been proposed to have a role in cancer progression, little is known about the epidemiology of P. hominis infection in cancer patients. METHODS: To determine the prevalence of P. hominis in patients with digestive system malignancies, we collected 195 and 142 fecal samples from gastrointestinal cancer patients and residents without any complaints related to the digestive system, respectively. Each sample was detected for the presence of P. hominis by nested PCR amplifying the internal transcribed spacer (ITS) region and partial 18S rRNA gene. RESULTS: A significantly higher prevalence of P. hominis was found in cancer patients than that in the control population (41.54 vs 9.15%, χ2 = 42.84, df = 1, P < 0.001), resulting in a 6.75-fold risk of gastrointestinal cancers (OR: 6.75, 95% CI: 3.55-12.83, P < 0.001). The highest prevalence of P. hominis infection was detected in small intestine cancer patients (60%, OR: 14.88, 95% CI: 0.82-4.58, P = 0.009) followed by liver (57.14%, χ2 = 10.82, df = 1, P = 0.001) and stomach cancer patients (45.1%, χ2 = 31.95, df = 1, P < 0.001). In addition, phylogenetic analysis provided some evidence supporting that human P. hominis infection might derive from animal sources. CONCLUSIONS: To our knowledge, this study is the first report presenting the high association between P. hominis and gastrointestinal cancers. Nevertheless, whether there is any possible pathological role of P. hominis infection in cancer patients needs to be further elucidated.

4.
Mol Med Rep ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31432167

RESUMO

Studies have revealed that genetic and functional aberrations of oncogenes, tumor­suppressor genes, signaling pathways and receptors are among the most prominent events in pituitary tumorigenesis, and a potent biomarker would be helpful for early diagnosis, subsequent treatment and disease control. The present study investigated the expression signatures of solute carrier family 20 member 1, also known as phosphate transporter 1 (SLC20A1) and the Wnt/ß­catenin signaling pathway in 52 patients with somatotroph adenomas. According to immunohistochemistry analysis, the H­score of SLC20A1 was 222.6±15.2 in invasive tumor samples and 144.5±30.4 in non­invasive tumor samples (P<0.01), while the H­scores of ß­catenin were 210.1±21.4 and 134.9±32.7, respectively (P<0.05). The H­scores of Wnt inhibitory factor 1 (Wif1) exhibited the opposite trend, with scores of 134.5±22.7 and 253.6±14.8, respectively (P<0.01). The H­scores of SLC20A1 were negatively associated with those of Wif1 in somatotroph adenomas (correlation coefficient r=­0.367). The mean progression­free survival in the low SLC20A1 group was longer than that in the group with high SLC20A1 H­scores (P=0.024). Reverse transcription­quantitative PCR (RT­qPCR) and western blotting confirmed the interference efficiency of the segments short hairpin (Sh)­B­SLC20A1 and Sh­C­SLC20A1. Cell proliferation experiments revealed that the cell viability of the Sh­B­SLC20A1 group was 76.3±4.5, 65.7±3.7 and 53.1±3.2% of that of control GH3 cells after 24, 48 and 72 h of transfection, respectively, while the cell viability of the Sh­C­SLC20A1 group was 86.4±5.7, 75.6±4.4 and 67.5±3.8%, respectively (P<0.05). ELISA analysis demonstrated the growth hormone (GH) levels in the Sh­B­SLC20A1 and Sh­C­SLC20A1 groups to be 34.7±10.4 and 54.6±14.4%, respectively, of that of control GH3 cells (P<0.05). The transmembrane invasion assay revealed that knocking down SLC20A1 significantly suppressed cell invasion in the Sh­B­SLC20A1 and Sh­C­SLC20A1 groups. RT­qPCR and western blotting demonstrated that Sh­B­SLC20A1 and Sh­C­SLC20A1 evidently increased the levels of Wif1 and secreted frizzled­related protein 4. The present data suggested that SLC20A1 levels are positively associated with tumor size, invasive behavior and tumor recurrence in somatotroph adenomas. Furthermore, SLC20A1 may be associated with the activation of the Wnt/ß­catenin signaling pathway.

5.
Biomacromolecules ; 20(9): 3425-3434, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31411865

RESUMO

Supraparticles (SPs) assembled from smaller colloidal nanoparticles can serve as depots of therapeutic compounds and are of interest for long-term, sustained drug release in biomedical applications. However, a key challenge to achieving temporal control of drug release from SPs is the occurrence of an initial rapid release of the loaded drug (i.e., "burst" release) that limits sustained release and potentially causes burst release-associated drug toxicity. Herein, a biocoating strategy is presented for silica-SPs (Si-SPs) to reduce the extent of burst release of the loaded model protein lysozyme. Specifically, Si-SPs were coated with a fibrin film, formed by enzymatic conversion of fibrinogen into fibrin. The fibrin-coated Si-SPs, FSi-SPs, which could be loaded with 7.9 ± 0.9 µg of lysozyme per SP, released >60% of cargo protein over a considerably longer period of time of >20 days when compared with the uncoated Si-SPs that released the same amount of the cargo protein, however, within the first 3 days. Neurotrophins that support the survival and differentiation of neurons could also be loaded at ∼7.3 µg per SP, with fibrin coating also delaying neurotrophin release (only 10% of cargo released over 21 days compared with 60% from Si-SPs). In addition, the effects of incorporating a hydrogel-based system for surgical delivery and the opportunity to control drug release kinetics were investigated-an alginate-based hydrogel scaffold was used to encapsulate FSi-SPs. The introduction of the hydrogel further extended the initial release of the encapsulated lysozyme to ∼40 days (for the same amount of cargo released). The results demonstrate the increasing versatility of the SP drug delivery platform, combining large loading capacity with sustained drug release, that is tailorable using different modes of controlled delivery approaches.

6.
Acta Trop ; 198: 105105, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31348896

RESUMO

Trypanosome is considered as one of important parasites in almost all mammalian species, which occurs in Chiroptera throughout the world. Although numerous trypanosome species have been identified in bats in Asia, Africa, South America and Europe, little is known about the genetic diversity and pathogenicity of trypanosomes in Chinese bat. Recently, some human Trypanosoma cruzi infection attributed to a bat-related T. cruzi (TcBat) from the Noctilio spp., Myotis spp. and Artibeus spp was found. Consequently, it is a necessity to know trypanosome species in bats from China. In order to determine the prevalence and genotypes in bat from southwestern China, wehere detected trypanosomes prevalence 227bat brain tissue samples, including 60 Rousettus leschenaultia, 58 Hipposideros Pomona, 69 Rhinolophus pusillus, 40 Myotis daubentonni in Yunnan Province of China using nested PCR based on 18S rRNA. 14 (6.2%) of them were trypanosmes positive including 13 insect-eating bats and 1 fruit bat. The prevalence of trypanosome in R.leschenaultia, H. Pomona, and R.pusillus was 1.67%(1/60), 6.90%(4/58) and 13.0%(9/69), respectively (P < 0.01), suggesting R. pusillus was a main-vector host bat. The positive rate of T.sp, T. dionisii, T.brucei brucei and T.sp ZY-2 was 4.8% (11/227), 0.4%(1/227), 0.4%(1/227), and 0.4% (1/227), resepectively. These results showed that T.sp-Yunnan is the predominant genospecies. To our knowledge, this is the first report about Trypanosome species in bats in Yunnan Province, southwestern China.

7.
Phys Chem Chem Phys ; 21(28): 15623-15629, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31268445

RESUMO

Unlike MoS2, single-layered Ag2S nanoribbons (Ag2SNRs) exhibit a nonmetal-shrouded and a zigzag-shaped buckling structure and possess two distinct edges, S- or Ag-terminated ones. By performing first principle calculations, the spin-dependent electron transport of Ag2SNRs in a ferromagnetic state has been investigated. It is found that the SS- and AgAg-terminated Ag2SNRs exhibit semi-metallic characteristics, but with opposite spin-polarized directions. And AgS-terminated ones show metallic characteristics, but with completely spin-unpolarized transmission. That is to say, all three states, i.e., spin up polarized, spin down polarized and spin unpolarized ones, could be achieved by modulating the edge geometry. Further analysis shows that, the spatial separation on edges of the energy states with different spins around EF is responsible for the switch in the three states. The system could operate as a dual spin-filter, and the direction of the spin polarization can be switched by the edge morphology. Furthermore, calculations show that such a phenomenon is robust to the width of the ribbon and strain, showing great application potential.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31280308

RESUMO

OBJECTIVES: Our objectives were to identify the risk factors for postoperative complications after paediatric cardiac surgery, develop a tool for predicting postoperative complications and compare it with other risk adjustment tools of congenital heart disease. METHODS: A total of 2308 paediatric patients who had undergone cardiac surgeries with cardiopulmonary bypass support in a single centre were included in this study. A univariate analysis was performed to determine the association between perioperative variables and postoperative complications. Statistically significant variables were integrated into a synthetic minority oversampling technique-based XGBoost model which is an implementation of gradient boosted decision trees designed for speed and performance. The 7 traditional risk assessment tools used to generate the logistic regression model as the benchmark in the evaluation included the Aristotle Basic score and category, Risk Adjustment for Congenital Heart Surgery (RACHS-1), Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STS-EACTS) mortality score and category and STS morbidity score and category. RESULTS: Our XGBoost prediction model showed the best prediction performance (area under the receiver operating characteristic curve = 0.82) when compared with these risk adjustment models. However, all of these models exhibited a relatively lower sensitivity due to imbalanced classes. The sensitivity of our optimization approach (synthetic minority oversampling technique-based XGBoost) was 0.74, which was significantly higher than the average sensitivity of the traditional models of 0.26. Furthermore, the postoperative length of hospital stay, length of cardiac intensive care unit stay and length of mechanical ventilation duration were significantly increased for patients who experienced postoperative complications. CONCLUSIONS: Postoperative complications of paediatric cardiac surgery can be predicted based on perioperative data using our synthetic minority oversampling technique-based XGBoost model before deleterious outcomes ensue.

9.
Kidney Int ; 96(3): 642-655, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31171376

RESUMO

The essential role of membrane associated guanylate kinase 2 (MAGI2) in podocytes is indicated by the phenotypes of severe glomerulosclerosis of both MAGI2 knockout mice and in patients with congenital nephrotic syndrome (CNS) caused by mutations in MAGI2. Here, we show that MAGI2 forms a complex with the Rap1 guanine nucleotide exchange factor, RapGEF2, and that this complex is lost when expressing MAGI2 CNS variants. Co-expression of RapGEF2 with wild-type MAGI2, but not MAGI2 CNS variants, enhanced activation of the small GTPase Rap1, a central signaling node in podocytes. In mice, podocyte-specific RapGEF2 deletion resulted in spontaneous glomerulosclerosis, with qualitative glomerular features comparable to MAGI2 knockout mice. Knockdown of RapGEF2 or MAGI2 in human podocytes caused similar reductions in levels of Rap1 activation and Rap1-mediated downstream signaling. Furthermore, human podocytes expressing MAGI2 CNS variants show severe abnormalities of cellular morphology and dramatic loss of actin cytoskeletal organization, features completely rescued by pharmacological activation of Rap1 via a non-MAGI2 dependent upstream pathway. Finally, immunostaining of kidney sections from patients with congenital nephrotic syndrome and MAGI2 mutations showed reduced podocyte Rap1-mediated signaling. Thus, MAGI2-RapGEF2-Rap1 signaling is essential for normal podocyte function. Hence, disruption of this pathway is an important cause of the renal phenotype induced by MAGI2 CNS mutations.

10.
Acta Trop ; 197: 105044, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31173736

RESUMO

Neospora caninum is an intracellular protozoan infecting many domestic and wild animals. In the present study, the brain tissues of wild birds collected in Hunan province of China were examined by N. caninum specific nested PCR, targeting the Nc-5 gene and the internal transcribed spacer 1 (ITS-1) region of the nuclear ribosomal DNA. The prevalence of N. caninum was detected in 15.5% (37/239) of wild birds, including 20.5% (9/44) of the examined olive-backed pipit Anthus hodgsoni, 18.3% (24/131) of the examined tree sparrows Passer montanus, 7.9% (3/38) of the examined chestnut bunting Emberiza rutila and 3.8% (1/26) of the examined yellow-breasted bunting E. aureola. Phylogenetic analyses showed that N. caninum from different hosts and geographical origins are genetically diverse and can be further classified into two distinct groups. Our findings indicated that wild birds are potential source of N. caninum for other animals. To our knowledge, this is the first report of N. caninum infection in wild birds in China, which provides a foundation for the prevention and control of this parasite in China and elsewhere.

11.
Biochem Biophys Res Commun ; 516(2): 357-364, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31208717

RESUMO

Esophageal cancer is one of the most malignant tumors in digestive system, but the pathogenesis of esophageal cancer is still unclear. It has been verified that circular RNAs (circRNAs) play critical roles in development and progression of tumors. However, little research concentrates on the role of circRNAs in the pathogenesis of esophageal cancer. In the present study, we found that circular RNA-RAD23B (circRAD23B) was upregulated in specimens of patients with esophageal cancer. Further investigation revealed that circRAD23B promoted proliferation and invasion of esophageal cancer cells. Next, we identified microRNA-5095 (miR-5095) as a target of circRAD23B, and found that miR-5095 was negatively correlated to the expression of circRAD23B in esophageal cancer. In addition, circRAD23B facilitated expression of PARP2 and AKT2 by sponging miR-5095, which might underlie the growth of esophageal cancer. In summary, these data displayed the crucial role of circRAD23B/miR-5095 regulating PARP2 and AKT2 in esophageal cancer, and provided a novel mechanism in the pathogenesis of esophageal cancer.

12.
Epigenetics ; : 1-15, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31232159

RESUMO

Histone methyltransferase KMT2D has diverse functions and distinct mechanisms in different cancers. Although we have previously found KMT2D serves as an oncogene that promotes tumor growth and metastasis in prostate cancer (PCa), the functions and mechanisms of KMT2D are complicated and most remain undefined. Here, the function of KMT2D regarding DNA damage in PCa and the underlying mechanisms of KMT2D in epigenetic regulation were explored in a series of studies. Knockdown of KMT2D sensitized cells to DNA damage through the disturbance of antioxidative gene expression and increased levels of intracellular reactive oxygen species, which led to cell apoptosis and senescence. The loss of KMT2D reduced the abundance of enhancer activity markers H3K4me1 and H3K27ac, which blocked the DNA binding of FOXO3, a critical mediator of the cellular response to oxidative stress, and suppressed antioxidative gene transcription. Moreover, KMT2D deletion in PCa cells also increased their sensitivity to genotoxic anticancer drugs and a PARP inhibitor, which suggested that lower levels of KMT2D may mediate the response of PCa to particular treatments. These findings further highlighted the important role of KMT2D in PCa progression and suggested that targeting KMT2D might be therapeutically beneficial for advanced PCa treatment.

13.
BMJ ; 365: l2211, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171523

RESUMO

OBJECTIVE: To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. DESIGN: Open label, blinded endpoint, randomised controlled phase II trial. SETTING: Prospective studies conducted at 26 centres in China, August 2015 to March 2017. PARTICIPANTS: 675 patients with acute minor stroke or transient ischaemic attack. INTERVENTION: Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. RESULTS: At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). CONCLUSION: Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02506140.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/uso terapêutico , Adulto , Idoso , Plaquetas/efeitos dos fármacos , China , Quimioterapia Combinada , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
14.
Environ Int ; 128: 343-352, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31078003

RESUMO

Despite of the ubiquity of organophosphate esters (OPEs) in various environmental matrices, information regarding the dietary intakes of OPEs is currently limited. To better understand dietary exposure and intake, the present study investigated 11 OPE flame retardants (FRs) in 105 composite food samples divided into 9 food categories, collected in 2018 and based on the contents of a typical Chinese food market basket. Nine OPEs, including triethyl phosphate (TEP), tributyl phosphate (TNBP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), 2-ethylhexyl-diphenyl phosphate (EHDPP), tris(2-butoxyethyl) phosphate (TBOEP), tris(2-ethylhexyl) phosphate (TEHP) and tris(methyl-phenyl) phosphate (TMPP), were measurable above the method limits of quantifications (MLOQs) in at least one of the analyzed samples. Among the 9 food categories, sweets were contaminated most severely with a mean sum (Σ) OPE concentration of 10.34 ng/g wet weight (ww). Regardless the food categories, EHDPP and TEP were the predominant OPEs with mean concentrations of 1.12 and 0.95 ng/g ww, respectively. In addition, the levels of OPEs in "processed foods" were significantly (unpaired t-test, p < 0.01) higher than those in "non-processed foods". Based on the measured OPE concentrations, we estimated daily per capita dietary intakes of ΣOPEs for Chinese adult population to be 44.3 ng/kg bw/day, that was mainly contributed by TCEP (14.3 ng/kg bw/day), TEP (12.7 ng/kg bw/day) and EHDPP (8.4 ng/kg bw/day). In addition to these 9 detected OPEs, further suspect screening in the combined extracts of foodstuffs by use of high-resolution spectrometry revealed a novel OP-FR, triphenyl phosphine oxide (TPPO). The highlight findings in this study were: 1) the amount of OPE via dietary intakes for the Chinese population is generally in the same order of magnitude as for other countries, i.e. the Swedish, Belgian and Australian adult population, and far less than the reference dosage value of each OPE (hazard index ≪ 1); 2) the total dietary intakes of OPEs were dominated by cereals, approximately accounting for 52.2%; and 3) the first reported detection of the novel OP-FR, TPPO, in foodstuff samples.

15.
Acta Trop ; 197: 105040, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31145875

RESUMO

Toxoplasma gondii is an important intracellular parasite that is distributed worldwide and can infect almost all warm-blooded animals. The Chinese I genotype Wh3 strain is the most common in China and has unique pathogenicity compared with other strains of T. gondii. Bicoid-interacting protein (Bin3) is predicted to be involved in the development and polarity of T. gondii, and the localization of this protein is necessary for studying the biological characteristics of the Chinese I genotypeWh3 strain of T. gondii. In this study, we established an in vitro the method of transforming the tachyzoites into bradyzoites to lay the foundations for further experimental studies. Parasites were induced by culturing in alkaline conditions, then the changes in parasites morphology were evaluated. SAG2C, BAG1 and SAG1 were used to identify parasites. The results show that the Chinese I genotype Wh3 strain exhibited pseudocysts and cysts in the alkaline conditions after being induced, and the bradyzoite stage expressed specific proteins at the same time. Bradyzoites, induced using an alkaline medium (pH = 8.2), had higher expression levels of the Bin3 protein than tachyzoites. The results of indirect immunofluorescence, using a Bin3 monoclonal antibody showed that the Bin3 protein is expressed in both free-state and pseudocysts tachyzoites, and in the cysts of the Chinese I genotype Wh3 strain. The Bin3 protein is located in the cytoplasm of free-state tachyzoites, secreted between the parasite and the pseudocyst membrane in pseudocysts, and distributed inside the cyst wall of cysts. These findings provide a basis for further study on the biological characteristics of the Chinese I genotype Wh3 strain.

17.
Mol Med ; 25(1): 13, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975096

RESUMO

BACKGROUND: Extracellular high mobility group box 1 protein  (HMGB1) serves a central role in inflammation as a transporter protein, which binds other immune-activating molecules that are endocytosed via the receptor for advanced glycation end-products (RAGE). These pro-inflammatory complexes are targeted to the endolysosomal compartment, where HMGB1 permeabilizes the lysosomes. This enables HMGB1-partner molecules to avoid degradation, to leak into the cytosol, and to reach cognate immune-activating sensors. Lipopolysaccharide (LPS) requires this pathway to generate pyroptosis by accessing its key cytosolic receptors, murine caspase 11, or the human caspases 4 and 5. This lytic, pro-inflammatory cell death plays a fundamental pathogenic role in gram-negative sepsis. The aim of the study was to identify molecules inhibiting HMGB1 or HMGB1/LPS cellular internalization. METHODS: Endocytosis was studied in cultured macrophages using Alexa Fluor-labeled HMGB1 or complexes of HMGB1 and Alexa Fluor-labeled LPS in the presence of an anti-HMGB1 monoclonal antibody (mAb), recombinant HMGB1 box A protein, acetylcholine, the nicotinic acetylcholine receptor subtype alpha 7 (α7 nAChR) agonist GTS-21, or a dynamin-specific inhibitor of endocytosis. Images were obtained by fluorescence microscopy and quantified by the ImageJ processing program (NIH). Data were analyzed using student's t test or one-way ANOVA followed by the least significant difference or Tukey's tests. RESULTS: Anti-HMGB1 mAb, recombinant HMGB1 antagonist box A protein, acetylcholine, GTS-21, and the dynamin-specific inhibitor of endocytosis inhibited internalization of HMGB1 or HMGB1-LPS complexes in cultured macrophages. These agents prevented macrophage activation in response to HMGB1 and/or HMGB1-LPS complexes. CONCLUSION: These results demonstrate that therapies based on HMGB1 antagonists and the cholinergic anti-inflammatory pathway share a previously unrecognized molecular mechanism of substantial clinical relevance.


Assuntos
Proteína HMGB1/metabolismo , Lipopolissacarídeos/farmacologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Acetilcolina/farmacologia , Animais , Células Cultivadas , Agonistas Colinérgicos/farmacologia , Endocitose/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Células RAW 264.7
18.
Sci Total Environ ; 673: 726-733, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31003100

RESUMO

As a typical nanomaterial, graphene oxide (GO) can be easily dispersed in water and may affect the aqueous environment. In this paper, the degradation of triclosan (TCS) in a Fenton-like system Fe3+/H2O2 in GO aqueous solution was investigated. Interestingly, it was observed that GO at low concentration (2.0 mg/L) could exhibit significant catalytic effect on TCS removal. Meanwhile, results of XPS, Raman and TEM spectroscopy suggested the structure and chemical composition of GO did not exhibit significant change after the oxidation process within 30 min. As per the radical quenching experiments and ESR tests, hydroxyl radical (·OH) was mainly responsible for the decomposition of TCS. Further mechanism study indicated that the reaction activation energy (Ea) could be lowered and the production of ·OH be promoted in the presence of GO, respectively. A total of nine intermediates of TCS degradation were detected by TOF-LC-MS after SPE procedure. Finally, ecotoxicity assessment revealed that degradation of TCS by Fe3+/H2O2 system in GO aqueous solution could yield by-products of smaller toxicity compared with parent compounds.

19.
Med Sci Monit ; 25: 2452-2478, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30945699

RESUMO

BACKGROUND As an important aspect of tumor heterogeneity, genetic variation may influence susceptibility and prognosis in different types of cancer. By exploring the prognostic value of genetic variation, this study aimed to establish a model for predicting postoperative survival and assessing the impact of variation on clinical outcomes in patients with hepatocellular carcinoma (HCC). MATERIAL AND METHODS A genome-wide association study of 367 patients with HCC was conducted to identify single nucleotide polymorphisms (SNPs) associated with prognosis. Identified predictors were further evaluated in 758 patients. Two prognostic models were established using Cox proportional hazards regression and Nomogram strategy, and validated in another 316 patients. The effect of the SNP rs2431 was analyzed in detail. RESULTS A prognostic model including 5 SNPs (rs10893585, rs2431, rs34675408, rs6078460, and rs6766361) was established and exhibited high predictive accuracy for HCC prognosis. The panel combined with tumor node metastasis (TNM) stage resulted in a significantly higher c-index (0.723) than the individual c-index values. Stratified by the Nomogram prediction model, the median overall survival for the low-risk and high-risk groups were 100.1 versus 30.8 months (P<0.001) in the training set and 82.2 versus 22.5 months (P<0.001) in the validation set. A closer examination of rs2431 revealed that it may regulate the expression of FNDC3B by disrupting a microRNA-binding site. CONCLUSIONS This study established prediction models based on genetic factors alone or in combination with TNM stage for postoperative survival in patients with HCC, and identified FNDC3B as a potential therapeutic target for combating HCC metastasis.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Testes Genéticos/métodos , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Linhagem Celular Tumoral , China , Feminino , Fibronectinas/genética , Fibronectinas/metabolismo , Estudo de Associação Genômica Ampla/métodos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Nomogramas , Polimorfismo de Nucleotídeo Único/genética , Período Pós-Operatório , Prognóstico , Fatores de Risco
20.
Vet Parasitol ; 268: 16-20, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30981301

RESUMO

Neospora caninum is an intracellular parasite that causes neosporosis in cattle. Bovine neosporosis is considered a major cause of bovine abortion worldwide. Rapid replication of N. caninum tachyzoites within host cells is responsible for the acute phase of N. caninum infection. Evidence shows that the host immune response plays an essential role in recognizing and regulating the replication of invading pathogens. Nucleotide-binding oligomerization domain receptors (NLRs) are a class of cytoplasmic sensors that can sense pathogens and induce the formation of the inflammasome complex. Activation of the inflammasome promotes restriction of microbial replication. Our previous study revealed NLRP3 inflammasome activation in N. caninum-infected murine macrophages. However, the role of inflammasome activity in N. caninum-infected bovine cells is unknown. To address this question, a bovine peritoneal macrophage cell line was used to investigate the role of inflammasome activation in regulating intracellular N. caninum replication. The results showed that inflammasome mediated activation of caspase-1 occurs in N. caninum-infected bovine macrophages, and caspase-1-dependent cell death was considered to be induced in N. caninum-infected bovine macrophages because N. caninum induced cell death decreased following pretreatment with zVAD-fmk and VX765. Meanwhile, the inhibition of caspase-1 in N. caninum-infected bovine macrophages led to the presence of more parasites in the parasitophorous vacuole. In contrast, inflammasome activation induced by ATP treatment in N. caninum-infected bovine macrophages contributed to the clearance of N. caninum. In addition, pyroptotic cell supernatant collected from ATP-stimulated bovine macrophages also impaired the ability of this parasite to infect new cells. In conclusion, this study is the first report on the role of the bovine inflammasome in restraining intracellular N. caninum replication and suggests that the bovine inflammasome may be a potential target for future development of drugs or vaccines against N. caninum infection in cattle.


Assuntos
Doenças dos Bovinos/imunologia , Coccidiose/imunologia , Inflamassomos/imunologia , Macrófagos Peritoneais/parasitologia , Trifosfato de Adenosina/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Caspase 1/metabolismo , Bovinos , Proliferação de Células , Células Cultivadas , Citoplasma/parasitologia , Dipeptídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Neospora , para-Aminobenzoatos/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA