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1.
Asian J Androl ; 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33402547

RESUMO

This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg-1) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.

2.
Huan Jing Ke Xue ; 41(2): 702-712, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608729

RESUMO

The Wenyu River is an important ecological corridor of Beijing. In this study, the spatio-temporal dynamics of water quality and phytoplankton community in the Wenyu River in 2006, 2011, and 2018, as well as their relationship were thoroughly analyzed by historical data analysis and field surveys. Results show that the water quality in the Wenyu River improved significantly from serious pollution owing to pollution containment. The major water pollutant has shifted from ammonia nitrogen (NH4+-N) to total nitrogen (TN). Compared with 2011, the average multiple of NH4+-N and total nitrogen TN exceeding the national standard were reduced by factors of 0.29-0.33 and 2.77-2.39, respectively, in 2018. The average concentration of NH4+-N and TN decreased from 15.52-19.16 mg·L-1 and 20.21-19.58 mg·L-1 in 2011 to 1.93-2.66 mg·L-1 and 5.66-6.79 mg·L-1 in 2018. Moreover, dissolved oxygen (DO) and NH4+-N concentrations in the Wenyu River and its tributaries, the Qinghe River, almost met requirements of their water function zoning target. Corresponding with the water quality improvement, the phytoplankton and community species increased dramatically. Phytoplankton species increased from 6 to 8 phyla, as well as community species. The dominant species changed from Chlorophyta in 2006 to the Cyanophyta in 2011, then to Bacillariophyta in 2018. The Shannon-Wiener diversity index (H') and evenness Pielou index (J) had improved. However, the major dominant species such as Cyclotella and Melosira persisted, and the Wenyu River was still in the eutrophication state in 2018. Statistical analysis results indicated that Cyanophyta, Bacillariophyta, and other algae abundance were significantly correlated with DO, pH, NH4+-N, TN, and TP.


Assuntos
Fitoplâncton/classificação , Rios , Poluição da Água/análise , Qualidade da Água , Pequim , China , Estações do Ano , Análise Espaço-Temporal
3.
Vector Borne Zoonotic Dis ; 20(10): 755-762, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679008

RESUMO

As one of the important tick-borne zoonotic pathogens, Anaplasma has both veterinary and public health significance. Here, we performed a survey of Anaplasma infection in the goats from a farm in Beijing, China, and found 44.6% (41/92) were infected with Anaplasma capra, and 22.8% (21/92) were infected with Anaplasma sp. This Anaplasma sp. bacterium was close to a recently emerging Anaplasma platys strain based on gltA and groEL gene phylogenetic analysis. As to further understand the characteristics of Anaplasma sp., we raised a couple of positive goats (n = 2) in the laboratory with tick-free settings. We observed inappetence, vomiting, high fever, and weakness of limbs in the goat's offspring (n = 3). In addition, the blood samples from all offspring were all positive of this Anaplasma spp. We did not see any intracellular morulae in neutrophils, monocytes, and erythrocytes, but we identified some in the platelets of the blood smears from the positive goats by light microscopy. We named it A. platys-like and suggested it may infect platelets and be transmitted vertically through the placenta of goats. These findings deserve further evaluation.

4.
Infect Immun ; 88(4)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31907196

RESUMO

Spotted fever group rickettsia (SFGR) can cause mild to fatal illness. The early interaction between the host and rickettsia in skin is largely unknown, and the pathogenesis of severe rickettsiosis remains an important topic. A surveillance of SFGR infection by PCR of blood and skin biopsy specimens followed by sequencing and immunohistochemical (IHC) detection was performed on patients with a recent tick bite between 2013 and 2016. Humoral and cutaneous immunoprofiles were evaluated in different SFGR cases by serum cytokine and chemokine detection, skin IHC staining, and transcriptome sequencing (RNA-seq). A total of 111 SFGR cases were identified, including 79 "Candidatus Rickettsia tarasevichiae," 22 Rickettsia raoultii, 8 Rickettsia sibirica, and 2 Rickettsia heilongjiangensis cases. The sensitivity to detect SFGR in skin biopsy specimens (9/24, 37.5%) was significantly higher than that in blood samples (105/2,671, 3.9%) (P < 0.05). As early as 1 day after the tick bite, rickettsiae could be detected in the skin. R. sibirica infection was more severe than "Ca Rickettsia" and R. raoultii infections. Increased levels of serum interleukin-18 (IL-18), IP10, and monokine induced by gamma interferon (MIG) and decreased levels of IL-2 were observed in febrile patients infected with R. sibirica compared to those infected with "Ca Rickettsia." RNA-seq and IHC staining could not discriminate between SFGR-infected and uninfected tick bite skin lesions. However, the type I interferon (IFN) response was differently expressed between R. sibirica and R. raoultii infections at the cutaneous interface. It is concluded that skin biopsy specimens were more reliable for the detection of SFGR infection in human patients although the immunoprofile may be complicated by immunomodulators induced by the tick bite.


Assuntos
Fatores Imunológicos/análise , Rickettsia/crescimento & desenvolvimento , Pele/patologia , Rickettsiose do Grupo da Febre Maculosa/patologia , Picadas de Carrapatos/complicações , Biópsia , Citocinas/sangue , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Pele/imunologia , Pele/microbiologia , Rickettsiose do Grupo da Febre Maculosa/imunologia , Rickettsiose do Grupo da Febre Maculosa/microbiologia
5.
Ticks Tick Borne Dis ; 11(1): 101316, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677968

RESUMO

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause human granulocytic anaplasmosis, human monocytic ehrlichiosis, and are severe threats to livestock economies like Mongolia. In this study, ticks were collected, identified, and pooled (n = 299) from three distinct environments across central Mongolia. Each pool was initially tested for Anaplasma/Ehrlichia using a 16S rRNA PCR assay that detects both genera, and specific PCR testing was done to identify those positive samples. Maximum likelihood estimation (MLE) of infection rates of ticks collected from the environment in Selenge aimag (province) found infection rates of Ixodes persulcatus ticks to be 2.0% (95% CI: 0.7, 4.3%) for A. phagocytophilum and 0.8% (95% CI: 0.1, 2.5%) for both nonspecific Ehrlichia and Anaplasma. Ehrlichia muris was only detected in I. persulcatus ticks collected from the Selenge aimag, where the MLE was 1.2% (95% CI: 0.1, 2.5%). The calculated MLE infection rate of Anaplasma spp. in questing Dermacentor nuttalli ticks ranged from 1.9% (95% CI: 1.1, 9.1%) in the Tov aimag to 2.3% (95% CI: 1.3, 10.8%) in the Selenge aimag. However, when examining MLE in ticks removed from livestock, estimates increase substantially, ranging from 7.8% (95% CI: 4.2, 13.3%) in Dornogovi to 22.5% (95% CI: 14.3, 34.3%) in Selenge, suggesting that livestock play a key role in disease maintenance. Considering the collective economic losses that can result from these pathogens and the potential for illness in nomadic herdsmen, these results highlight the need for enhanced TBD surveillance and prevention measures within Mongolia.

6.
Clin Sci (Lond) ; 133(3): 515-530, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30683734

RESUMO

The de novo synthesis of serum amyloid A1 (SAA1) is augmented in human fetal membranes at parturition. However, its role in parturition remains largely unknown. Here, we investigated whether SAA1 was involved in the rupture of fetal membranes, a crucial event in parturition accompanied with extensive degradation of collagens. Results showed that SAA1 decreased both intracellular and extracellular COL1A1 and COL1A2 abundance, the two subunits of collagen I, without affecting their mRNA levels in human amnion fibroblasts. These reductions were completely blocked only with inhibition of both matrix metalloproteases (MMPs) and autophagy. Consistently, SAA1 increased MMP-2/9 abundance and the markers for autophagic activation including autophagy related (ATG) 7 (ATG7) and the microtubule-associated protein light chain 3 ß (LC3B) II/I ratio with the formation of LC3 punctas and autophagic vacuoles in the fibroblasts. Moreover, the autophagic degradation of COL1A1/COL1A2 and activation of MMP-2/9 by SAA1 were blocked by inhibitors for the toll-like receptors 2/4 (TLR2/4) or NF-κB. Finally, reciprocal corresponding changes of SAA1 and collagen I were observed in the amnion following spontaneous rupture of membranes (ROM) at parturition. Conclusively, SAA1 may participate in membrane rupture at parturition by degradating collagen I via both autophagic and MMP pathways. These effects of SAA1 appear to be mediated by the TLR2/4 receptors and the NF-κB pathway.


Assuntos
Âmnio/metabolismo , Colágeno Tipo I/metabolismo , Parto/metabolismo , Proteína Amiloide A Sérica/metabolismo , Autofagia , Colágeno Tipo I/genética , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Parto/genética , Proteólise , Proteína Amiloide A Sérica/genética , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
7.
Am J Reprod Immunol ; 81(1): e13073, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30461130

RESUMO

PROBLEM: Rupture of fetal membranes is a crucial event at parturition, which is preceded by extensive extracellular matrix (ECM) remodeling. Our recent studies have demonstrated that the human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute phase protein, and the abundance of SAA1 in the amnion was increased at parturition. However, the exact role of SAA1 in human parturition remains to be established. METHOD OF STUDY: The effects of SAA1 on the abundance of collagenases and lysyl oxidase, the enzyme that cross-links collagens, were investigated in culture primary human amnion fibroblasts and tissue explants with an aim to examine the involvement of SAA1 in the ECM remodeling in the amnion. RESULTS: Serum amyloid A1 (SAA1) time- and dose-dependently increased the abundance of collagenases MMP-1, MMP-8, and MMP-13, while decreased the abundance of lysyl oxidase-like 1 (LOXL1). These effects of SAA1 were attenuated by siRNA-mediated knockdown of the Toll-like receptor (TLR) 4 and its antagonist CLI-095, but not by siRNA-mediated knockdown of TLR2. Furthermore, the inhibitors for NF-κB (JSH-23) and mitogen-activated protein kinases (MAPKs) p38 (SB203580) and JNK (SP600125) could also attenuate the effects of SAA1, while the inhibitor for MAPK ERK1/2 (PD 98059) could block the effects of SAA1 only on MMP-1, MMP-8, and LOXL1 but not on MMP-13. CONCLUSION: These data highlight a possible role for SAA1 in ECM remodeling preceding membrane rupture by regulating the expression of collagenases MMP-1, MMP-8, MMP-13, and LOXL1 through TLR4-mediated activation of the NF-κB and MAPK pathways in amnion fibroblasts.


Assuntos
Âmnio/fisiologia , Matriz Extracelular/metabolismo , Membranas Extraembrionárias/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Fibroblastos/fisiologia , Parto/metabolismo , Proteína Amiloide A Sérica/metabolismo , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Membranas Extraembrionárias/patologia , Feminino , Ruptura Prematura de Membranas Fetais/patologia , Humanos , NF-kappa B/metabolismo , Parto/genética , Gravidez , RNA Interferente Pequeno/genética , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
8.
FASEB J ; 33(2): 2770-2781, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30303742

RESUMO

Preterm premature rupture of fetal membranes precedes 30-40% of preterm births. Activation of matrix metalloproteases (MMPs) is the one of the major causes of extracellular matrix (ECM) degradation in membrane rupture. Increased cortisol, regenerated by 11ß-hydroxysteroid dehydrogenase 1 in the amnion at parturition, is known to participate in a number of parturition-pertinent events. However, whether cortisol has a role in the regulation of MMPs in the membranes is not known. Here, we addressed this issue using human amnion tissue, the most tensile layer of the membranes. RNA-sequencing revealed that cortisol induced MMP7 expression dramatically in amnion fibroblasts, which was confirmed by real-time quantitative RT-PCR and Western blotting analysis in cortisol-treated amnion explants and fibroblasts. Measurement of collagen IV α5 chain (COL4A5), a substrate for MMP-7, showed that cortisol reduced its extracellular abundance, which was blocked by an antibody against MMP-7. Moreover, increased MMP-7 but decreased COL4A5 abundance was observed in the amnion tissue following labor-initiated spontaneous rupture of membranes. Mechanistic studies showed that cortisol increased the phosphorylation of c-Jun and the expression of c-Fos, the 2 major components of activated protein 1 (AP-1), respectively. The knocking down of c-Fos or c-Jun significantly attenuated the induction of MMP7 expression by cortisol. Chromatin immunoprecipitation assays showed that cortisol stimulated the enrichment of c-Fos and c-Jun at the AP-1 binding site in the MMP7 promoter. The data suggest that induction of MMP7 by cortisol via AP-1 may be a contributing factor to ECM degradation in membrane rupture at parturition.-Wang, L.-Y., Wang, W.-S., Wang, Y.-W., Lu, J.-W., Lu, Y., Zhang, C.-Y., Li, W.-J., Sun, K., Ying, H. Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition.


Assuntos
Âmnio/enzimologia , Ruptura Prematura de Membranas Fetais/patologia , Fibroblastos/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hidrocortisona/efeitos adversos , Metaloproteinase 7 da Matriz/metabolismo , Parto , Âmnio/efeitos dos fármacos , Anti-Inflamatórios/efeitos adversos , Células Cultivadas , Ativação Enzimática , Feminino , Ruptura Prematura de Membranas Fetais/induzido quimicamente , Ruptura Prematura de Membranas Fetais/enzimologia , Fibroblastos/efeitos dos fármacos , Humanos , Gravidez
9.
Biomed Res Int ; 2018: 4651639, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850520

RESUMO

This paper presents a rapid label-free method for the identification of morphological characteristics of biological cells. Based on quantitative phase microscopy as well as the connotation of phase value, the gradient operator of phase and the associated analytic processing are employed to determine the edge of different parts of the samples. A heterogeneous biological cell model is established by simulation to show the mechanism of this method and a polystyrene bead is selected as a sample to confirm its validity by optical experiment. The result agrees well with the actual situation and this approach is proved to have good antinoise ability. Furthermore, a neutrophil is investigated by this method. Based on the optical experiment and the related analysis, the basic structure characteristics of the cell are obtained. It is indicated that the method presented in this paper could be applied to rapid identification and classification of living cells.


Assuntos
Forma Celular , Células/citologia , Imagem Molecular/métodos , Animais , Humanos , Processamento de Imagem Assistida por Computador , Microesferas , Modelos Biológicos , Neutrófilos/citologia , Poliestirenos/química
10.
Clin Infect Dis ; 67(7): 1110-1119, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-29538646

RESUMO

Background: Human babesiosis is an emerging health problem in China. Methods: Babesia were identified in ticks, sheep, and humans in northeastern China using polymerase chain reaction (PCR) followed by genetic sequencing. We enrolled residents who experienced a viral-like illness after recent tick bite or were healthy residents. We defined a case using the definition for babesiosis developed by the US Centers for Disease Control and Prevention. Results: A Babesia crassa-like agent was identified in Ixodes persulcatus and Haemaphysalis concinna ticks using PCR followed by sequencing. The agent was characterized through phylogenetic analyses of the 18S rRNA gene, the ß-tubulin gene, and the internal transcribed spacer region. We tested sheep as a possible reservoir and found that 1.1% were infected with the B. crassa-like agent. We screened 1125 human participants following tick bites using B. crassa-specific PCR and identified 31 confirmed and 27 suspected cases. All the patients were previously healthy except for 1 with an ovarian tumor. Headache (74%), nausea or vomiting (52%), and fever (48%) were the most common clinical manifestations of confirmed cases. Six of 10 cases remained PCR positive for B. crassa-like infection 9 months after initial diagnosis. Asymptomatic infections were detected in 7.5% of 160 local residents. Conclusions: We identified B. crassa-like infection in people in northeastern China that caused mild to moderate symptoms. The possibility of more severe disease in immunocompromised patients and of transmission through the blood supply due to asymptomatic infections justifies further investigation of this reported infection.


Assuntos
Babesia/genética , Babesiose/epidemiologia , Babesiose/microbiologia , Adolescente , Adulto , Idoso , Babesia/classificação , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Bacteriano/genética , RNA Ribossômico 18S/genética , Adulto Jovem
11.
Emerg Infect Dis ; 24(2): 236-241, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29350133

RESUMO

We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3.0% (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a nearly entire 16s rRNA gene, a partial flagellin gene, and the glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi identified in patients and ticks were clustered in the group of the Siberian type. These findings indicate that B. miyamotoi is endemic in northeastern China and its public health significance deserves further investigation.


Assuntos
Infecções por Borrelia/epidemiologia , Infecções por Borrelia/microbiologia , Borrelia/isolamento & purificação , Ixodes/microbiologia , Adulto , Idoso , Animais , Borrelia/genética , Criança , China/epidemiologia , DNA Bacteriano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Picadas de Carrapatos
12.
Parasit Vectors ; 10(1): 61, 2017 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-28153052

RESUMO

BACKGROUND: Little is known regarding tick-borne diseases in Mongolia, despite having 26% of the population still living nomadic pastoral lifestyles. A total of 1497 adult unfed ticks: 261 Ixodes persulcatus, 795 Dermacentor nuttalli, and 441 Hyalomma asiaticum, were collected from three ecologically distinct regions in Central Mongolia. Tick pools (n = 299) containing ~5 ticks each, were tested for Rickettsia and Tick-borne encephalitis virus (TBEV) using nested polymerase chain reaction, reverse transcription-PCR, and quantitative real-time RT-PCR. RESULTS: Assays yielded pooled prevalence of 92.5% (49/53) and 1.9% (1/53) for pooled I. persulcatus testing positive for "Candidatus Rickettsia tarasevichiae" and TBEV, respectively, while Rickettsia raoultii was found in 72.8% (115/158) of pooled D. nuttalli samples. When calculating a maximum likelihood estimation, an estimated 46.6% (95% CI: 35.2-63.6%) of I. persulcatus ticks in the pooled sample were infected with "Candidatus R. tarasevichiae". CONCLUSIONS: Both "Candidatus R. tarasevichiae" and R. raoultii are recognized as emerging tick-borne pathogens, with this being one of the first reports of "Candidatus R. tarasevichiae" in Mongolia. Given that "Candidatus R. tarasevichiae" shares the same vector (I. persulcatus) as TBEV, and infections may present with similar symptoms, Mongolian physicians treating suspected cases of TBEV should include "Candidatus R. tarasevichiae" infection in their differential diagnosis and consider prescribing antimicrobial therapy.


Assuntos
Ixodidae/microbiologia , Rickettsiaceae/classificação , Rickettsiaceae/isolamento & purificação , Animais , Vírus da Encefalite Transmitidos por Carrapatos/genética , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Ixodidae/classificação , Ixodidae/virologia , Mongólia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rickettsiaceae/genética
13.
Chem Biodivers ; 14(3)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27696725

RESUMO

An acquired T798M gatekeeper mutation in human epidermal growth factor receptor 2 (HER2) kinase can cause drug resistance to anti-HER2 chemotherapy drugs in lung cancer. Previously, the reversible pan-kinase inhibitor staurosporine has been found to selectively inhibit the HER2 T798M mutant over wild-type kinase, suggesting that the staurosporine scaffold is potentially to develop mutant-selective inhibitors. Here, we systematically evaluated the chemical space of staurosporine scaffold-based compounds in response to HER2 T798M mutation at structural, energetic and molecular levels by using an integrated analysis strategy. With this strategy, we were able to identify several novel wild-type sparing inhibitors with high or moderate selectivity, which are comparable to or even better than that of the parent compound staurosporine. Molecular modeling and structural analysis revealed that noncovalent contacts can form between the side chain of mutated residue Met798 and selective inhibitor ligands, which may improve the favorable interaction energy between the kinase and inhibitor and reduce the unfavorable desolvation penalty upon the kinase-inhibitor binding.


Assuntos
Inibidores de Proteínas Quinases/química , Receptor ErbB-2/metabolismo , Sítios de Ligação , Carbazóis/química , Carbazóis/metabolismo , Domínio Catalítico , Humanos , Cinética , Ligantes , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Simulação de Acoplamento Molecular , Mutação , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Estaurosporina/química , Estaurosporina/metabolismo , Termodinâmica
14.
Proc Natl Acad Sci U S A ; 113(16): 4488-93, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27035948

RESUMO

Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission.


Assuntos
Bases de Dados Factuais , Ebolavirus , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/transmissão , Modelos Biológicos , Feminino , Humanos , Masculino , Serra Leoa/epidemiologia
15.
Ann Intern Med ; 164(10): 641-8, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27019406

RESUMO

BACKGROUND: Human infection with Candidatus Rickettsia tarasevichiae (CRT) was first reported in northeastern China in 2012. OBJECTIVE: To describe the clinical spectrum and laboratory findings of patients infected with CRT in eastern central China. DESIGN: Case series. SETTING: A sentinel hospital for severe fever with thrombocytopenia syndrome (SFTS) in eastern central China in 2014. PARTICIPANTS: Hospitalized patients with SFTS-like illness. MEASUREMENTS: Molecular and serologic tests were performed to diagnose CRT infection. Data about clinical manifestations and laboratory findings were retrieved from medical records. RESULTS: 56 of 733 assessed patients had CRT based on polymerase chain reaction and sequencing. All patients presented with nonspecific manifestations, including fever (96%), malaise (88%), myalgia (57%), cough (25%), and dizziness (14%). Only 2 patients had rash. Further, 16% had eschar, 29% had lymphadenopathy, 100% had gastrointestinal symptoms, 34% had neurologic symptoms, 43% had hemorrhagic manifestations, and 23% had signs of plasma leakage. Thrombocytopenia was observed in 70%, leukopenia in 59%; lymphopenia in 45%; and elevated levels of lactate dehydrogenase in 82%, aspartate aminotransferase in 70%, alanine aminotransferase in 54%, and creatinine kinase in 46%. Co-infection with SFTS virus was documented in 66% patients, and 8 of the 56 patients died. LIMITATIONS: Patients with CRT were not treated for infection because they were retrospectively identified. This was not a population-based study, and the results cannot be generalized to all patients with CRT. CONCLUSION: Candidatus R tarasevichiae infection should be considered in the differential diagnosis of febrile patients with SFTS-like illness in endemic areas. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.


Assuntos
Infecção Hospitalar/diagnóstico , Infecções por Rickettsia/diagnóstico , Rickettsia/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/epidemiologia , China/epidemiologia , Comorbidade , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-Idade , Phlebovirus , Filogenia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-26360502

RESUMO

Renal angiomyolipoma may sometimes require surgical intervention. In this paper, we present a case of renal angiomyolipoma which infiltrated the sinus and extended into the inferior vena cava. He was successfully treated with a combined approach of laparoscopic radical nephrectomy, extracorporeal workbench tumor resection, and autotransplantation. Three months postoperatively, no evidence of tumor recurrence or presence of thrombus in the inferior vena cava was noted. Our experience represents the successful application of a combined nephron-sparing approach in the management of angiomyolipoma with extension into a major blood vessel.


Assuntos
Angiomiolipoma/patologia , Angiomiolipoma/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Veia Cava Inferior/patologia , Adulto , Circulação Extracorpórea , Humanos , Laparoscopia/métodos , Masculino , Nefrectomia/métodos , Transplante Autólogo
17.
Lancet Infect Dis ; 15(6): 663-70, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25833289

RESUMO

BACKGROUND: Anaplasma phagocytophilum and Anaplasma ovis cause human infections. We investigated the potential for human pathogenicity of a newly discovered Anaplasma species infecting goats in China. METHODS: We collected blood samples from patients with a history of tick bite in the preceding 2 months at Mudanjiang Forestry Central Hospital of Heilongjiang Province from May 1, to June 10, 2014, to detect the novel Anaplasma species by PCR. We inoculated positive samples into cell cultures. We characterised the isolated pathogen by morphological and phylogenetic analyses. We tested serum antibodies by indirect immunofluorescence assay. FINDINGS: 28 (6%) of 477 patients assessed were infected with the novel Anaplasma species according to PCR and sequencing. We isolated the pathogen in vitro from three patients. Phylogenetic analyses of rrs, gltA, groEL, msp2, and msp4 showed that the pathogen was distinct from all known Anaplasma species. We provisionally nominate it "Anaplasma capra". 22 (92%) of 24 patients with data available had seroconversion or a four-fold increase in antibody titres. All 28 patients developed non-specific febrile manifestations, including fever in 23 (82%), headache in 14 (50%), malaise in 13 (46%), dizziness in nine (32%), myalgia in four (14%), and chills in four (14%). Additionally, ten (36%) of 28 patients had rash or eschar, eight (29%) had lymphadenopathy, eight (29%) had gastrointestinal symptoms, and three (11%) had stiff neck. Five patients were admitted to hospital because of severe disease. Six (35%) of 17 patients with data available had high hepatic aminotransferase concentrations. INTERPRETATION: The emergence of "A capra" as a cause of human disease suggests that individuals living in or travelling to endemic regions in northern China should take precautions to reduce their risk of exposure to this novel tick-borne pathogen. FUNDING: Natural Science Foundation of China and the US National Institutes of Health.


Assuntos
Anaplasma/classificação , Anaplasma/isolamento & purificação , Ehrlichiose/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Adolescente , Adulto , Idoso , Anaplasma/genética , Animais , Técnicas de Cultura de Células , Criança , China/epidemiologia , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Adulto Jovem
18.
Lancet Infect Dis ; 15(2): 196-203, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25539588

RESUMO

BACKGROUND: Human babesiosis is an emerging zoonosis. "Babesia venatorum" has been identified in only four asplenic men and a child so far. We aimed to describe the epidemiological, clinical, and laboratory characteristics of a series of cases with "B venatorum" infection identified in a sentinel hospital in China. METHODS: We recruited participants with a recent tick bite at Mudanjiang Forestry Central Hospital, Heilongjiang province, China. Cases were diagnosed through PCR followed by sequencing, microscopic identification, or isolation by animal inoculation, or both. FINDINGS: 48 individuals (30 women or girls; median age 45 years, range 7 months to 75 years) with "B venatorum" infection were identified. 32 of these individuals were confirmed cases and 16 were probable cases. None of the 48 cases had received a blood transfusion or had a splenectomy. Geographically, cases were distributed diffusely throughout the hospital catchment area. Of the 32 confirmed cases, 21 (66%) presented with a fever, 13 (41%) with a headache, 12 (38%) with myalgia or arthralgia, and three (9%) with chills. 14 (44%) patients had fatigue, eight (25%) had dizziness, and eight (25%) had hypersomnia. Six (19%) patients had an erythematous non-pruritic rash around the tick-bite site and two (6%) had lymphadenopathy. Seven (22%) and four (13%) patients had anaemia and thrombocytopenia, respectively, and seven (50%) of 14 patients with confirmed infection had increased hepatic transaminase concentrations. In the confirmed cases, concentrations of intercellular adhesion molecule 3 (p<0·001), P-selectin (p<0·05), and platelet endothelial cell adhesion molecule 1 (p<0·001) were significantly reduced, whereas tumour necrosis factor α (p<0·01) and vascular cell adhesion molecule 1 (p<0·001) were significantly increased. INTERPRETATION: "B venatorum" infection should be included in the differential diagnosis of patients with a tick-exposure history in areas where this pathogen has previously been identified in ticks or people. FUNDING: Natural Science Foundation of China and Mega-Project for Infectious Diseases.


Assuntos
Babesia/isolamento & purificação , Babesiose/epidemiologia , Babesiose/patologia , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/patologia , Adolescente , Adulto , Idoso , Animais , Babesiose/diagnóstico , Babesiose/parasitologia , Criança , Pré-Escolar , China/epidemiologia , Técnicas de Laboratório Clínico , Feminino , Humanos , Lactente , Masculino , Microscopia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Picadas de Carrapatos/complicações , Doenças Transmitidas por Carrapatos/diagnóstico , Doenças Transmitidas por Carrapatos/parasitologia , Adulto Jovem
19.
Huan Jing Ke Xue ; 35(9): 3455-60, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25518665

RESUMO

To improve anaerobic digestion and dewatering of sludge, impacts of sludge pretreated by microwave (MW) and its combined processes on sludge anaerobic digestion and dewatering were investigated. The results showed that microwave and its combined processes could effectively enhance anaerobic sludge digestion. Not only the cumulative methane production in the test of the MW-H2O2-alkaline (0. 2) was increased by 13. 34% compared with the control, but also its methane production rate was much higher than that of the control. Compared with the single MW process, the addition of both H2O2 and alkaline enhanced the solubilization of particle COD( >0. 45 micron) , indicating that synergistically generated soluble organics were faster to biodegrade which resulted in the enhancement of anaerobic digestion. The MW-acid process was effective in improving sludge dewaterability, e. g. , Capillary Suction Time (CST) at only 9. 85 s. The improvement of sludge dewatering was significantly correlated with sludge physical properties such as zeta potential, surface charge density and particle size. Under different sludge pretreatment conditions, the sludge dewatering after anaerobic digestion was similar, though the difference of sludge dewatering to some degrees was observed for pretreated sludge.


Assuntos
Micro-Ondas , Esgotos , Eliminação de Resíduos Líquidos/métodos , Biodegradação Ambiental , Peróxido de Hidrogênio/química , Metano/química , Tamanho da Partícula
20.
Huan Jing Ke Xue ; 35(5): 1955-61, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25055692

RESUMO

Seafood samples were collected from Dalian, China to study the accumulation and distribution characteristics of short chain chlorinated paraffins (SCCPs) by GC/ECNI-LRMS. Sum of SCCPs (dry weight) were in the range of 77-8 250 ng.g-1, with the lowest value in Scapharca subcrenata and highest concentration in Neptunea cumingi. The concentrations of sum of SCCPs (dry weight) in fish, shrimp/crab and shellfish were in the ranges of 100-3 510, 394-5 440, and 77-8 250 ng.g-1 , respectively. Overall, the C10 and C11 homologues were the most predominant carbon groups of SCCPs in seafood from this area,and a relatively higher proportion of C12-13 was observed in seafood with higher concentrations of sum of SCCPs . With regard to chlorine content, Cl1,, CI8 and CI6 were the major groups. Significant correlations were found among concentrations of different SCCP homologues (except C1, vs. Cl10 ) , which indicated that they might share the same sources and/or have similar accumulation, migration and transformation processes.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Clorados/análise , Parafina/análise , Alimentos Marinhos/análise , Animais , China , Peixes , Contaminação de Alimentos/análise , Moluscos
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