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1.
J Nanosci Nanotechnol ; 20(2): 719-730, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383067

RESUMO

The efficient removal of toxic metal ions from waste water is of critical importance in environmental protection. In this study, we report the incorporation of graphene oxide (GO) into bacterial cellulose (BC) and the effect on the removal of metal ions from waste water. The as-prepared BC/GO adsorbents have a three-dimensional (3D) network structure with interconnected pores and high porosity. The adsorption capacities and efficiencies of the BC/GO adsorbents with varying GO contents were compared by using Cu2+, Cd2+, and Pb2+ as model heavy metal ions. The incorporated GO into the BC/GO adsorbents plays a critical role in removing metal ions through strong electrostatic interactions between the positive metal ions and the negative functional groups on GO. In addition, the effects of pH, contact time, adsorbent dose, and ion concentration on the adsorption behavior of the BC/GO adsorbents were investigated. The data from adsorption kinetics indicate that the adsorption of Cu2+, Cd2+, and Pb2+ on BC/GO obeys a pseudo-second-order model, while the adsorption isotherms vary with the type of metal ions. The desorption and readsorption experiments of the BC/GO adsorbents demonstrate good recyclability. It has been demonstrated that incorporating GO into BC is an effective way to improve the adsorption behavior of BC.

2.
Med Sci Monit ; 25: 6539-6546, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472071

RESUMO

BACKGROUND Long non-coding RNAs (lncRNAs) have been shown to play an important regulatory role in many tumors. This study was designed to investigate the expression of lncRNA ENST00000429227.1 in hepatocellular carcinoma (HCC) and to determine whether the expression of lncRNA ENST00000429227.1 affects the prognosis of HCC. MATERIAL AND METHODS lncRNA ENST00000429227.1 showing differences in expression between M1 and M2 was screened by microarray expression measurements. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA ENST00000429227.1 in 161 HCC patients. The chi-square test was used to evaluate the relationship between the expression of ENST00000429227.1 and clinicopathological parameters. A survival curve was drawn and analyzed by Kaplan-Meier method. Cox regression was used for univariate and multivariate analysis to determine whether lncRNA ENST00000429227.1 is an independent factor of the occurrence and prognosis of HCC. RESULTS A total of 3703 differentially expressed lncRNAs were obtained, of which 1777 were upregulated and 1926 were downregulated, with multiple change >1.5. The expression of lncRNA ENST00000429227.1 was upregulated in M2 cells. The expression of lncRNA ENST00000429227.1 in HCC tissues was higher than that in adjacent normal tissues (p<0.05), which was correlated with pathological parameters such as surgical margin (p=0.042), AFP (p=0.022) and Barcelona Clinic Liver Cancer (BCLC) stage (p=0.008). Survival analysis showed that high expression of lncRNA ENST00000429227.1 was associated with a decrease in overall survival (OS) rate of HCC patients. Cox regression analysis showed that high expression of ENST00000429227.1 may be an independent risk factor affecting the prognosis of HCC patients. CONCLUSIONS The results suggest that upregulation of ENST00000429227.1 is associated with poor prognosis of HCC patients, and may be a new biomarker for the diagnosis of HCC.

3.
Parasit Vectors ; 12(1): 358, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337442

RESUMO

BACKGROUND: Excretory/secretory products (ESPs) released by parasites influence the development and functions of host dendritic cells (DCs). However, little is known about changes of DNA (hydroxy)methylation on DC development during Fasciola gigantica infection. The present study aimed to investigate whether F. gigantica ESPs (FgESPs) affects the development and functions of buffalo DCs through altering the DNA (hydroxy)methylation of DCs. METHODS: Buffalo DCs were prepared from peripheral blood mononuclear cells (PBMCs) and characterized using scanning and transmission electron microscopy (SEM/TEM) and quantitative reverse transcriptional PCR (qRT-RCR). DCs were treated with 200 µg/ml of FgESPs in vitro, following DNA extraction. The DNA methylome and hydroxymethylome were profiled based on (hydroxy)methylated DNA immunoprecipitation sequencing [(h)MeDIP-Seq] and bioinformatics analyses. qRT-RCR was also performed to assess the gene transcription levels of interest. RESULTS: FgESPs markedly suppressed DC maturation evidenced by morphological changes and downregulated gene expression of CD1a and MHC II. Totals of 5432 and 360 genes with significant changes in the 5-methylcytosine (5-mC) and the 5-hydroxymethylcytosine (5-hmC) levels, respectively, were identified in buffalo DCs in response to FgESPs challenge. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these differentially expressed genes were highly enriched in pathways associated with immune response. Some cancer-related pathways were also indicated. There were 111 genes demonstrating changes in both 5-mC and 5-hmC levels, 12 of which were interconnected and enriched in 12 pathways. The transcription of hypermethylated genes TLR2, TLR4 and IL-12B were downregulated or in a decreasing trend, while the mRNA level of high-hydroxymethylated TNF gene was upregulated in buffalo DCs post-exposure to FgESPs in vitro. CONCLUSIONS: To our knowledge, the present study provides for the first time a unique genome-wide profile of DNA (hydroxy)methylation for DCs that interact with FgESPs, and suggests a possible mechanism of FgESPs in suppressing DC maturation and functions that are involved in TLR signaling.

4.
Fungal Genet Biol ; 130: 54-61, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31075360

RESUMO

Talaromyces marneffei (T. marneffei) is a medically important opportunistic dimorphic fungus that infects both humans and bamboo rats. However, the mechanisms of transmission and pathogenicity of T. marneffei are poorly understood. In our study, we combined Illumina and PacBio sequencing technologies to sequence and assemble a complete genome of T. marneffei. To elucidate the transmission route and source, we sequenced three additional T. marneffei isolates using Illumina sequencing technology. Variations among isolates were used to develop a multilocus sequence typing (MLST) system comprising five housekeeping genes that can be used to discriminate between isolates derived from different sources. Our analysis revealed that human and bamboo rat share identical genotypes in these five loci. Thus, we hypothesized that T. marneffei is transmitted to humans through inhalation of spores in the surrounding environment into the lungs and that the bamboo rat can serve as an important natural reservoir for pathogens. Furthermore, we also identified temperature-dependent polyketide synthases, non-ribosomal peptide synthetases and secreted proteins as putative pathogenicity-related factors. In addition, we identified antifungal drug targets that can be investigated in future studies to elucidate the mechanisms underlying drug resistance. In summary, our study presents the basic features of the T. marneffei genome and provides insights into the transmission and pathogenicity of T. marneffei, which warrant fundamental experimental research.

5.
Vet Parasitol ; 268: 73-80, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30981309

RESUMO

The infection of ruminants by Fasciola spp. always induces a non-protective Th2-type immune response. However, little is known about changes in the local and systemic immune environment during F. gigantica migration in buffalo. In this study, native swamp buffaloes were each infected with 500 viable F. gigantica metacercariae. Mesenteric lymph node (MLN), hepatic lymph node (HLN), spleen, and serum samples were collected from control and infected buffaloes at 3, 10, 28, 42, 70, and 98 days post-infection (DPI). The mRNA expression levels of the Th1- and Th2-related cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IFN-γ, TNF-α, and CD4 were measured during different infection stages in the MLNs, spleens, and HLNs using quantitative real-time PCR (qRT-PCR). Levels of the specific anti-ESP isotype antibodies IgG, IgG1, and IgG2 were used to reflect changes in humoral immunity. The results of this study indicated that swamp buffaloes were susceptible to F. gigantica infection, and that susceptibility to this infection was closely related to the cytokine environment associated with the Th2-type immune response. The MLNs showed a mixed Th1- and Th2-type immune response during the acute infection stages, after which the production of these cytokines returned to normal. Cytokine expression in the HLNs also expressed a mixed Th1- and Th2-type immune response during the early infection stages. When the infection became chronic, the typical Th2 immune response was induced in the HLNs. At the acute infection stages, the spleen exhibited a Th2 immune response. Nevertheless, cytokines associated with the Th1 and Th2 immune responses were upregulated at 98 DPI. In addition, the total IgG and IgG1 of the parasite-specific antibodies increased. This suggested that the Th2-related cytokines and IgG1 induced by F. gigantica infection might mediate successful F. gigantica infection in the natural host, swamp buffalo.


Assuntos
Búfalos/imunologia , Doenças dos Bovinos/imunologia , Citocinas/imunologia , Fasciolíase/veterinária , Evasão da Resposta Imune , Células Th2/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Búfalos/parasitologia , Bovinos , Doenças dos Bovinos/parasitologia , Citocinas/genética , Fasciola , Fasciolíase/imunologia , Imunidade Humoral , Imunoglobulina G/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Linfonodos/imunologia , Linfonodos/parasitologia , Metacercárias/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Baço/imunologia , Baço/parasitologia , Células Th1/imunologia
6.
Nanomicro Lett ; 10(3): 42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30393691

RESUMO

Uniform dispersion of two-dimensional (2D) graphene materials in polymer matrices remains challenging. In this work, a novel layer-by-layer assembly strategy was developed to prepare a sophisticated nanostructure with highly dispersed 2D graphene oxide in a three-dimensional matrix consisting of one-dimensional bacterial cellulose (BC) nanofibers. This method is a breakthrough, with respect to the conventional static culture method for BC that involves multiple in situ layer-by-layer assembly steps at the interface between previously grown BC and the culture medium. In the as-prepared BC/GO nanocomposites, the GO nanosheets are mechanically bundled and chemically bonded with BC nanofibers via hydrogen bonding, forming an intriguing nanostructure. The sophisticated nanostructure of the BC/GO leads to greatly enhanced mechanical properties compared to those of bare BC. This strategy is versatile, facile, scalable, and can be promising for the development of high-performance BC-based nanocomposite hydrogels.

7.
Virulence ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30475087

RESUMO

Enteroviruses (EVs) are the most common human pathogens worldwide. Recent international outbreaks in North America and South East Asia have emphasized the need for more effective anti-viral therapies. As obligate parasites, EVs rely on the host cellular machinery for effective viral propagation. Accumulating evidence has indicated that EVs subvert and disrupt the cellular autophagy pathway to facilitate productive infection, and consequently leading to host pathogenesis. Given that defective autophagy is a common factor in various human diseases, including neurodegeneration, cardiomyopathy, and metabolic disorders, a clear understanding of the relationship between EV infection and autophagy is warranted. In this review, we highlight recent advances in understanding the molecular mechanisms by which EVs exploit the autophagy pathway during different steps of viral life cycle, from entry, replication, and maturation to release. We also provide an overview of recent progress in EV subversion of the autophagy for immune evasion.

8.
Am J Pathol ; 188(12): 2853-2862, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30273599

RESUMO

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons in the cerebral cortex, brainstem, and spinal cord, leading to progressive paralysis and eventual death. Approximately 95% of all ALS cases are sporadic without known causes. Enteroviruses have been suspected to play a role in ALS because of their ability to target motor neurons and to cause muscle weakness and paralysis. In vitro enteroviral infection results in cytoplasmic aggregation and cleavage of transactive response DNA binding protein-43, a pathologic hallmark of ALS. However, whether enteroviral infection can induce ALS-like pathologies in vivo remains to be characterized. In this study, neonatal BALB/C mice were intracranially inoculated with either a recombinant coxsackievirus B3 expressing enhanced green fluorescent protein or mock-infected for 2, 5, 10, 30, and 90 days. Histologic and immunohistochemical analysis of brain tissues demonstrated sustained inflammation (microglia and astrogliosis) and lesions in multiple regions of the brain (hippocampus, cerebral cortex, striatum, olfactory bulb, and putamen) in parallel with virus detection as early as 2 days for up to 90 days after infection. Most notably, ALS-like pathologies, including cytoplasmic mislocalization of transactive response DNA binding protein-43, p62-, and ubiquitin-positive inclusions, were observed in the areas of infection. These data provide the first pathologic evidence to support a possible link between enteroviral infection and ALS.

9.
ChemSusChem ; 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376216

RESUMO

Conducting polyaniline (PANI) exhibits momentous properties, such as high conductivity, reversible convertibility between redox states and advantageous structural feature and therefore receives ever-increasing attention for various applications. This paper extensively reviews recent studies on applications of polyaniline for Li-ion batteries (LIBs), Li-sulfur batteries (LSBs) and supercapacitors (SCPs). The flexible polyaniline is crucial for cyclability especially for buffering the volumetric changes of electrode materials, in addition to enhancing the electron/ions transport. Besides, polyaniline can be directly used as an electroactive component of electrode materials for LIBs or SCPs. Also it is widely applied in LSBs due to its physically and chemically strong affinity for sulfur and polysulfides. Herein, substantial studies demonstrate the significant improvements of electrochemical performance by the physical/chemical modification and incorporation of polyaniline.

10.
FASEB J ; : fj201800301RRR, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30080445

RESUMO

The role for the NOD-like receptor (NLR) P3 inflammasome in enterovirus infection remains controversial. Available data suggest that the NLRP3 inflammasome is protective against enterovirus A71 but detrimental to the host during coxsackievirus B3 (CVB3) infection. CVB3 is a common etiologic agent associated with myocarditis and pancreatitis. Previous findings on the role of NLRP3 in CVB3 were based primarily on indirect evidence. Here, we utilized NLRP3 knockout mice as well as immune and cardiac cells to investigate the direct interplay between CVB3 infection and NLRP3 activation. We demonstrated that NLRP3 knockout mice exhibited more severe disease phenotype after CVB3 infection (significantly higher virus titers), increased myocardial, and pancreatic damage, as well as markedly impaired cardiac function compared to nontransgenic control mice. We further showed that NLRP3 activity was enhanced during early stage of CVB3 infection, as evidenced by increased gene expression and/or secretion of IL-1ß and caspase-1. Finally, we demonstrated that CVB3 inactivates the NLRP3 inflammasome by degrading NLRP3 and its upstream serine/threonine-protein kinase receptor-interacting protein 1/3 via the proteolytic activity of virus-encoded proteinases. Taken together, our results reveal the functional significance of NLRP3 in host antiviral immunity against CVB3 infection and the mechanisms by which CVB3 has evolved to counteract the host defense response.-Wang, C., Fung, G., Deng, H., Jagdeo, J., Mohamud, Y., Xue, Y. C., Jan, E., Hirota, J. A., Luo, H. NLRP3 deficiency exacerbates enterovirus infection in mice.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30096907

RESUMO

The rapid urbanization in China has brought with it some health benefits, but it also brought about a negative influence on the lifestyle of residents. We conducted this study to assess the change in hypertension-related knowledge and behavior from 2013 to 2016 among recently urbanized residents and determine their association with socioeconomic status (SES). This research used data from two cross-sectional studies conducted in Hezuo community in Chengdu, Sichuan province of China. A total of 2268 and 2601 individuals, respectively, participated and completed standard questionnaires. According to the results, the median (IQR) scores of health knowledge was 1 (0,3) and 3 (1,5), respectively, (p < 0.001) and the median (IQR) scores of health behavior was 6 (5,6) and 5 (5,6), respectively, (p < 0.001) in 2013 and 2016. The rate of sufficient knowledge increased from 8.8% to 18.1% (p < 0.001), while the rate of correct behavior decreased from 54.5% to 45.5% (p < 0.001) in three years. Logistic regression analysis showed that higher education was associated with sufficient hypertension-related knowledge (p < 0.05), and those with higher education, unemployment, and retirement were more likely to have sufficient behavior (p < 0.05). The impact of SES on knowledge was stable between 2013 and 2016. The behavior difference between the middle school educated and the illiterate increased from 2013 to 2016 (p < 0.05), and the behavior difference between the unemployed and manual workers decreased from 2013 to 2016 (p < 0.05). Our results revealed that hypertension-related knowledge improved with no corresponding improvement in self-reported behavior among recently urbanized residents from 2013 to 2016. Organizational strategy should be implemented to improve health education on knowledge, and what is more, translate knowledge into behavior. All these measures should be given more attention to the lower educated and manual workers among recently urbanized residents to eliminate the SES disparity.

12.
Cell Death Differ ; 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30154446

RESUMO

Cell autonomous immunity is the ability of individual cells to initiate a first line of host defense against invading microbes, such as viruses. Autophagy receptors, a diverse family of multivalent proteins, play a key role in this host response by detecting, sequestering, and eliminating virus in a process termed virophagy. To counteract this, positive-stranded RNA viruses, such as enteroviruses, have evolved strategies to circumvent the host autophagic machinery in an effort to promote viral propagation; however, the underlying mechanisms remain largely unclear. Here we studied the interaction between coxsackievirus B3 (CVB3) and the autophagy receptor SQSTM1 (sequestosome 1)/p62 and CALCOCO2/NDP52 (calcium binding and coiled-coil domain-containing protein 2/nuclear dot 10 protein 52). We demonstrated that SQSTM1 and CALCOCO2 differentially regulate CVB3 infection. We showed that knockdown of SQSTM1 causes increased viral protein production and elevated viral titers, whereas depletion of CALCOCO2 results in a significant inhibition of viral growth. Both receptors appear to have a role in virophagy through direct interaction with the viral capsid protein VP1 that undergoes ubiquitination during infection. Further investigation of the proviral mechanism of CALCOCO2 revealed that CALCOCO2, but not SQSTM1, suppresses the antiviral type I interferon signaling by promoting autophagy-mediated degradation of the mitochondrial antiviral signaling (MAVS) protein. Moreover, we demonstrated that viral proteinase 2A-mediated cleavage of SQSTM1 at glycine 241 impairs its capacity to associate with viral capsid, whereas cleavage of CALCOCO2 by viral proteinase 3C at glutamine 139, generates a stable C-terminal fragment that retains the proviral function of full-length CALCOCO2. Altogether, our study reveals a mechanism by which CVB3 targets selective autophagy receptors to evade host virophagy.

13.
Autophagy ; 14(8): 1469-1471, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30032704

RESUMO

Picornaviruses, one of the major causes of human diseases ranging from the common cold to acute flaccid paralysis, have a short cytosolic lifecycle that, in cultured cells, ends in cell lysis. For years, the prevailing model was that these viruses exit from cells exclusively through cell lysis. However, over the last several years it has become apparent that for some picornaviruses, a macroautophagy/autophagy-related pathway can result in release of virus particles wrapped in a membrane containing autophagic markers. It has been proposed that this enveloped release predominates within hosts, allowing cell-to-cell movement of virus while minimizing exposure to the immune system. One reason that picornaviruses induce the autophagy pathway is to provide membrane scaffolds for RNA replication complexes. Perhaps more importantly, acidified autophagosomes (known as amphisomes) provide havens for maturation of new viral particles into infectious viruses. In back-to-back papers recently published in Cell Reports, our labs investigated a basic question: if picornavirus particles are maturing inside amphisomes, then how are they avoiding the typical degradative fate of autophagic cargo and exiting the cell intact?

14.
Cell Physiol Biochem ; 47(2): 505-522, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794463

RESUMO

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. METHODS: F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. RESULTS: In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. CONCLUSIONS: This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Fasciola/metabolismo , Proteínas de Helminto/farmacologia , RNA Longo não Codificante/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Células Cultivadas , Redes Reguladoras de Genes/efeitos dos fármacos , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
15.
Cell Rep ; 22(12): 3292-3303, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29562184

RESUMO

Picornaviruses have evolved to hijack host cellular machinery, including the autophagic pathway. However, the mechanisms remain largely unclear. We use coxsackievirus B3 (CVB3) as a model organism to explore the possible role of picornavirus subversion of the autophagic pathway in viral infection. Our in vivo and in vitro experiments demonstrate that CVB3 infection causes a significant, albeit incomplete, inhibition of autophagic flux by limiting the fusion of autophagosomes with lysosomes and/or late endosomes. Furthermore, we show that CVB3 specifically targets SNARE protein SNAP29 and adaptor protein PLEKHM1, two critical proteins known to regulate autophagosome fusion, for cleavage through the catalytic activity of viral proteinase 3C, ultimately impairing the formation of SNARE complexes. Finally, we demonstrate that loss of SNAP29/PLEKHM1 inhibits autophagic flux, resulting in increased viral replication. Collectively, our study reveals a mechanism that supports an emerging model whereby CVB3 hijacks the autophagic machinery to facilitate its own propagation.

16.
Front Mol Neurosci ; 11: 63, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29593492

RESUMO

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily attacks motor neurons in the brain and spinal cord, leading to progressive paralysis and ultimately death. Currently there is no effective therapy. The majority of ALS cases are sporadic, with no known family history; unfortunately the etiology remains largely unknown. Contribution of Enteroviruses (EVs), a family of positive-stranded RNA viruses including poliovirus, coxsackievirus, echovirus, enterovirus-A71 and enterovirus-D68, to the development of ALS has been suspected as they can target motor neurons, and patients with prior poliomyelitis show a higher risk of motor neuron disease. Multiple efforts have been made to detect enteroviral genome in ALS patient tissues over the past two decades; however the clinical data are controversial and a causal relationship has not yet been established. Recent evidence from in vitro and animal studies suggests that enterovirus-induced pathology remarkably resembles the cellular and molecular phenotype of ALS, indicating a possible link between enteroviral infection and ALS pathogenesis. In this review, we summarize the nature of enteroviral infection, including route of infection, cells targeted, and viral persistence within the central nervous system (CNS). We review the molecular mechanisms underlying viral infection and highlight the similarity between viral pathogenesis and the molecular and pathological features of ALS, and finally, discuss the potential role of enteroviral infection in frontotemporal dementia (FTD), a disease that shares common clinical, genetic, and pathological features with ALS, and the significance of anti-viral therapy as an option for the treatment of ALS.

17.
J Virol ; 92(8)2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29437971

RESUMO

Enteroviruses encode proteinases that are essential for processing of the translated viral polyprotein. In addition, viral proteinases also target host proteins to manipulate cellular processes and evade innate antiviral responses to promote replication and infection. Although some host protein substrates of enterovirus proteinases have been identified, the full repertoire of targets remains unknown. We used a novel quantitative in vitro proteomics-based approach, termed terminal amine isotopic labeling of substrates (TAILS), to identify with high confidence 72 and 34 new host protein targets of poliovirus and coxsackievirus B3 (CVB3) 3C proteinases (3Cpros) in HeLa cell and cardiomyocyte HL-1 cell lysates, respectively. We validated a subset of candidate substrates that are targets of poliovirus 3Cproin vitro including three common protein targets, phosphoribosylformylglycinamidine synthetase (PFAS), hnRNP K, and hnRNP M, of both proteinases. 3Cpro-targeted substrates were also cleaved in virus-infected cells but not noncleavable mutant proteins designed from the TAILS-identified cleavage sites. Knockdown of TAILS-identified target proteins modulated infection both negatively and positively, suggesting that cleavage by 3Cpro promotes infection. Indeed, expression of a cleavage-resistant mutant form of the endoplasmic reticulum (ER)-Golgi vesicle-tethering protein p115 decreased viral replication and yield. As the first comprehensive study to identify and validate functional enterovirus 3Cpro substrates in vivo, we conclude that N-terminomics by TAILS is an effective strategy to identify host targets of viral proteinases in a nonbiased manner.IMPORTANCE Enteroviruses are positive-strand RNA viruses that encode proteases that cleave the viral polyprotein into the individual mature viral proteins. In addition, viral proteases target host proteins in order to modulate cellular pathways and block antiviral responses in order to facilitate virus infection. Although several host protein targets have been identified, the entire list of proteins that are targeted is not known. In this study, we used a novel unbiased proteomics approach to identify ∼100 novel host targets of the enterovirus 3C protease, thus providing further insights into the network of cellular pathways that are modulated to promote virus infection.


Assuntos
Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida/metabolismo , Cisteína Endopeptidases/metabolismo , Enterovirus Humano B/enzimologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Poliovirus/enzimologia , Proteínas Virais/metabolismo , Células HeLa , Humanos , Marcação por Isótopo/métodos , Especificidade por Substrato/fisiologia
18.
J Nanosci Nanotechnol ; 18(8): 5314-5319, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29458582

RESUMO

Compared to two-dimensional (2D) conditions, investigation on gene transfection in three-dimensional (3D) conditions is much less extensive. In this work, lamellar nano-hydroxyapatite (L-HAp) with and without magnetism were used as the vectors and gene transfection in 2D and 3D cell culture was carried out and compared. We found that the transfection efficiency in 3D conditions was much higher than 2D cell culture. Additionally, magnetism enhanced transfection efficiency under both 2D and 3D conditions. The findings presented in this study demonstrated that the magnetic L-HAp could be a promising vector in 3D gene transfection.


Assuntos
Durapatita , Nanopartículas , Transfecção , Técnicas de Cultura de Células
19.
Oncotarget ; 8(58): 98455-98470, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228702

RESUMO

Objectives: To investigate the lncRNA profiling during tilapia peritoneal macrophages (TPMs) activation and discuss the relationship between lncRNA and mRNA. Materials and Methods: RNA sequencing was used to investigate the lncRNA and mRNA profiles of TPMs activation following stimulation with Streptococcus agalactiae (Sa) antigen, heat shock protein 70 (HSP70) and HSP70+Sa. The expressions of lncRNA and mRNA were confirmed by qPCR. 356 lncRNA, 10173 mRNA and 1782 transcripts of uncertain coding potential (TUCP) were differentially expressed by pairwise comparison. These lncRNAs were shorter in length, fewer in exon number and higher in expression levels as compared with mRNAs. 683 lncRNAs and 4320 mRNAs were co-located, while 316 lncRNAs and 9997 mRNAs were in co-expression networks. Seven mRNAs (ANKRD34A, FMODA, GJA3, CNTN5, BMP10, BAI2 and HS3ST6) were involved in both networks of LNC_00035 and LNC_000466. Differentially expressed genes were involved in signaling pathways, such as "phosphorylation", "cytokine-cytokine receptor interaction", "endocytosis" and "MHC protein complex". LNC_000792, LNC_000215, LNC_000035 and LNC_000310, with cis and/or trans relationships with mRNAs, were also involved in ceRNA network. Conclusions: These results might represent the first identified expression profile of lncRNAs and mRNAs in tilapia macrophages activated by HSP70 and Sa.

20.
ACS Nano ; 11(12): 12849-12862, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29236476

RESUMO

Hypoxia as one characteristic hallmark of solid tumors has been demonstrated to be involved in cancer metastasis and progression, induce severe resistance to oxygen-dependent therapies, and hamper the transportation of theranostic agents. To address these issues, an oxygen-self-produced sonodynamic therapy (SDT) nanoplatform involving a modified fluorocarbon (FC)-chain-mediated oxygen delivery protocol has been established to realize highly efficient SDT against hypoxic pancreatic cancer. In this nanoplatform, mesopores and FC chains of FC-chain-functionalized hollow mesoporous organosilica nanoparticle carriers can provide sufficient storage capacity and binding sites for sonosensitizers (IR780) and oxygen, respectively. In vitro and in vivo experiments demonstrate the nanoplatform involving this distinctive oxygen delivery protocol indeed breaks the hypoxia-specific transportation barriers, supplies sufficient oxygen to hypoxic PANC-1 cells especially upon exposure to ultrasound irradiation, and relieves hypoxia. Consequently, hypoxia-induced resistance to SDT is inhibited and sufficient highly reactive oxygen species (ROS) are produced to kill PANC-1 cells and shrink hypoxic PANC-1 pancreatic cancer. This distinctive FC-chain-mediated oxygen delivery method provides an avenue to hypoxia oxygenation and holds great potential in mitigating hypoxia-induced resistance to those oxygen-depleted therapies, e.g., photodynamic therapy, radiotherapy, and chemotherapy.

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