Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
One Health ; 13: 100344, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34805474

RESUMO

Prohibiting the unsafe sale of livestock that have died in production and harmlessly disposing of them are key measures to control and prevent outbreaks of zoonotic diseases and exert a great significance for maintaining meat-derived food and public health safety. However, under the strict implementation of governmental initiatives, some farmers still choose to sell dead livestock unsafely in developing countries such as China, Brazil, Mexico, and Kenya, which have become an important hidden danger in preventing and controlling zoonotic diseases. Based on data from 496 pig farmers in Hebei, Henan, and Hubei, China, the Double Hurdle Model was employed to explore the impact of governmental initiatives on the willingness and proportion of dead pigs sold unsafely by farmers. Besides, based on the heterogeneity of organization participation and breeding scale, the impact of governmental initiatives on different scale farmers' unsafely selling behaviors is also discussed. The results showed that the harmless disposal subsidy significantly reduces farmers' willingness to unsafely sell dead pigs (SW, RC = -0.0666, and SE = 0.0261). Still, the impact on the proportion is weak (SP, RC = -0.0502, and SE = 0.0474). Though the effect of supervision punishment is greatly weakened (SW, RC =-0.0381, and SE = 0.0324; SP, RC = -0.0204 and SE = 0.0263), it can significantly enhance the effect of harmless disposal subsidy by creating a good law-abiding environment (SW, RC = -0.1370, and SE = 0.0374; SP, RC = -0.0820, and SE = 0.0431). Governmental initiatives have an undue impact on the unsafe sale of dead livestock by farmers participating in cooperatives. The effects of these measures on different scale farmers' unsafe sale of dead pigs are highly heterogeneous. In addition, the study also found that food and public health safety risk perceptions are important endogenous drivers for curbing farmers selling dead pigs. This research can also provide important inspiration for other countries. The government should raise farmers' risk perception level of food and public safety, optimize governmental initiatives, play the key role of cooperative organization, increase the proportion of dead pigs harmlessly disposed of, and finally eliminate new hidden dangers in the prevention and control of zoonotic diseases.

3.
Sci Rep ; 11(1): 16293, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381119

RESUMO

That the high frequency and good replication capacity of strains with reduced susceptibility to neuraminidase inhibitors (NAIs) in highly pathogenic avian influenza H7N9 (HPAI H7N9) virus made it a significance to further study its drug resistance. HPAI H7N9 viruses bearing NA I222L or E119V substitution and two mutations of I222L-E119V as well as their NAIs-sensitive counterpart were generated by reverse genetics for NA inhibition test and replication capability evaluation in vitro. The attenuated H7N9/PR8 recombinant viruses were developed to study the pathogenicity and drug resistance brought by the above substitutions to mice. The IC50 fold change of oseltamivir to HPAI H7N9 with NA222L-119V is 306.34 times than that of its susceptible strain, and 3.5 times than the E119V mutant virus. HPAI H7N9 bearing NA222L-119V had good replication ability with peak value of more than 6log10 TCID50/ml in MDCK cells. H7N9/PR8 virus bearing NA222L-119V substitutions leaded to diffuse pneumonia, significant weight loss and fatality in mice. NA E119V made H7N9/PR8 virus resistant to oseltamivir, and I222L-E119V had synergistic resistance to oseltamivir in mice. Due to the good fitness of drug resistant strains of HPAI H7N9 virus, it is necessary to strengthen drug resistance surveillance and new drug research.


Assuntos
Substituição de Aminoácidos/genética , Farmacorresistência Viral/genética , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Subtipo H7N9 do Vírus da Influenza A/genética , Neuraminidase/genética , Oseltamivir/farmacologia , Substituição de Aminoácidos/efeitos dos fármacos , Animais , Antivirais/farmacologia , Aves/virologia , Linhagem Celular , Cães , Inibidores Enzimáticos/farmacologia , Feminino , Células HEK293 , Humanos , Influenza Aviária/tratamento farmacológico , Influenza Aviária/virologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Proteínas Virais/genética , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética
4.
Mol Cancer ; 20(1): 98, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325714

RESUMO

BACKGROUND: Breast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown. METHODS: Bone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays. RESULTS: We identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKß-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively. CONCLUSION: We revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.

5.
Cancer Res ; 81(14): 3835-3848, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34049973

RESUMO

Mitochondrial dynamics play vital roles in the tumorigenicity and malignancy of various types of cancers by promoting the tumor-initiating potential of cancer cells, suggesting that targeting crucial factors that drive mitochondrial dynamics may lead to promising anticancer therapies. In the current study, we report that overexpression of mitochondrial fission factor (MFF), which is upregulated significantly in liver cancer-initiating cells (LCIC), promotes mitochondrial fission and enhances stemness and tumor-initiating capability in non-LCICs. MFF-induced mitochondrial fission evoked mitophagy and asymmetric stem cell division and promoted a metabolic shift from oxidative phosphorylation to glycolysis that decreased mitochondrial reactive oxygen species (ROS) production, which prevented ROS-mediated degradation of the pluripotency transcription factor OCT4. CRISPR affinity purification in situ of regulatory elements showed that T-box transcription factor 19 (TBX19), which is overexpressed uniquely in LCICs compared with non-LCICs and liver progenitor cells, forms a complex with PRMT1 on the MFF promoter in LCICs, eliciting epigenetic histone H4R3me2a/H3K9ac-mediated transactivation of MFF. Targeting PRMT1 using furamidine, a selective pharmacologic inhibitor, suppressed TBX19-induced mitochondrial fission, leading to a profound loss of self-renewal potential and tumor-initiating capacity of LCICs. These findings unveil a novel mechanism underlying mitochondrial fission-mediated cancer stemness and suggest that regulation of mitochondrial fission via inhibition of PRMT1 may be an attractive therapeutic option for liver cancer treatment. SIGNIFICANCE: These findings show that TBX19/PRMT1 complex-mediated upregulation of MFF promotes mitochondrial fission and tumor-initiating capacity in liver cancer cells, identifying PRMT1 as a viable therapeutic target in liver cancer.

6.
Adv Sci (Weinh) ; 8(4): 2001961, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33643786

RESUMO

The incidence of bone metastases in hepatocellular carcinoma (HCC) has increased prominently over the past decade owing to the prolonged overall survival of HCC patients. However, the mechanisms underlying HCC bone-metastasis remain largely unknown. In the current study, HCC-secreted lectin galactoside-binding soluble 3 (LGALS3) is found to be significantly upregulated and correlates with shorter bone-metastasis-free survival of HCC patients. Overexpression of LGALS3 enhances the metastatic capability of HCC cells to bone and induces skeletal-related events by forming a bone pre-metastatic niche via promoting osteoclast fusion and podosome formation. Mechanically, ubiquitin ligaseRNF219-meidated α-catenin degradation prompts YAP1/ß-catenin complex-dependent epigenetic modifications of LGALS3 promoter, resulting in LGALS3 upregulation and metastatic bone diseases. Importantly, treatment with verteporfin, a clinical drug for macular degeneration, decreases LGALS3 expression and effectively inhibits skeletal complications of HCC. These findings unveil a plausible role for HCC-secreted LGALS3 in pre-metastatic niche and can suggest a promising strategy for clinical intervention in HCC bone-metastasis.

7.
Health Sci Rep ; 4(1): e230, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33437876

RESUMO

Background and Aims: H9N2 subtype avian influenza virus (AIV) has low-pathogenicity but causes respiratory symptoms and drop in egg production in chicken with long-term virus shedding, resulting in great economic losses due to high mortality related to secondary infection with other pathogens. In recent years, H9N2 viruses have been posing a threat to public health, causing human infection in China. Compared to studies on other AIV subtypes, there are relatively few studies on the pathogenic mechanism of the H9N2 virus in mammals. H9N2 subtype AIV has been circulating worldwide in many avian species and transmitting with high efficiency in poultry. It can provide internal genes for other subtypes to produce new viruses, causing a pandemic risk. It is important to carry out long-term surveillance and pathogenic characteristics of the H9N2 virus. In this study, we conducted environmental surveillance of live poultry markets in Anhui province from 2013 to 2018, and 33 representative environmental isolates were selected and studied systematically. Methods: The genomic RNA of Anhui H9N2 isolates was subjected to RT-PCR amplification followed by sequencing analysis. Results: Thirty-three strains were isolated from the embryonated eggs of specific-pathogen-free chickens. Phylogenetic analysis indicated that h9.4.2.5-like H9N2 viruses were predominant during 2013-2018 and acquired multiple specific amino acid mutations that may have increased their affinity for mammals and enhanced their infectivity and transmissibility. Additionally, six internal genes of H9N2 clustered together with the novel human-lethal reassortant viruses, such as the low-pathogenicity H7N9, H10N8, and Anhui H5N6 viruses, and even HPAI H7N9. Conclusion: Because H9N2 viruses may be the donors of internal genes that lead to the generation of novel reassortant viruses with enhanced pathogenicity in Anhui province, continuous environmental surveillance of live poultry markets, a key source of reassorted H9N2 and other avian influenza viruses, is of great importance.

8.
Biomed Chromatogr ; 35(4): e5020, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33159321

RESUMO

Chronic inflammation pain is a debilitating disease, and its mechanism still remains poorly understood. This study attempted to illuminate the metabolic mechanism of chronic inflammation pain induced by complete Freund's adjuvant (CFA) injection, especially at spinal level. The chronic inflammation pain model was established by CFA administration. Behavioral testing including mechanical allodynia and thermal hyperalgesia was performed. Meanwhile, a liquid chromatography-mass spectrometry-based metabolomics approach was applied to analyze potential metabolic biomarkers. The orthogonal partial least squares discrimination analysis mode was employed for determining metabolic changes, and a western blot was performed to detect the protein expression change. The results showed that 27 metabolites showed obviously abnormal expression and seven metabolic pathways were significantly enriched, comprising aminoacyl-tRNA biosynthesis, arginine and proline metabolism, histidine metabolism, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism, and phenylalanine metabolism. Meanwhile, the results showed that the expression of arginase I and nitric oxide levels were elevated in the CFA group compared with the control group, while the argininosuccinate synthetase and argininosuccinatelyase proteins were not significantly different between the groups. These findings demonstrate that metabolic changes of the spinal cord may be implicated in neurotransmitter release and pain conductivity following CFA administration.


Assuntos
Adjuvante de Freund , Inflamação , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Dor , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Adjuvante de Freund/efeitos adversos , Adjuvante de Freund/farmacologia , Hiperalgesia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Dor/induzido quimicamente , Dor/metabolismo , Medula Espinal/química , Medula Espinal/metabolismo
9.
Pediatr Infect Dis J ; 40(1): 70-73, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33284252

RESUMO

After following 141 children with likely asymptomatic congenital cytomegalovirus infection in a highly immune population in China, four children (2.8%) were found to have late-onset hearing loss. No maternal or childhood factors, except higher saliva cytomegalovirus viral load at birth (P = 0.03), were associated with increased risk of developing a hearing loss.


Assuntos
Infecções por Citomegalovirus , Perda Auditiva , Adolescente , Adulto , Pré-Escolar , China , Estudos de Coortes , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/epidemiologia , Feminino , Perda Auditiva/epidemiologia , Perda Auditiva/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Saliva/virologia , Carga Viral , Adulto Jovem
10.
Neuropsychiatr Dis Treat ; 16: 2519-2528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149593

RESUMO

Purpose: Temporal lobe epilepsy (TLE) is a common neurological disorder, which is characterized by recurrent spontaneous seizures. Exploring the mechanisms of epileptogenesis has been considered as a priority. The aim of this study is to investigate the effects of LncRNA MEG3 in spontaneous recurrent epileptiform discharges (SREDs) and rats with TLE. Methods: Rat model of TLE was produced by intraperitoneal injection of lithium chloride and pilocarpine. Rat hippocampal neuronal model of SREDs was established by Mg2+-free treatment. MEG3 was overexpressed by transfection of AAV-MEG3 in TLE and SREDs model. The expression of MEG3, interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and recombinant human tumor necrosis factor-alpha (TNF-α) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected by corresponding kit. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase transfer­mediated dUTP nick end­labeling (TUNEL) assay and flow cytometry. The expression of proteins related to apoptosis (Caspase-3, Bax, and Bcl-2) and the PI3K/AKT/mTOR pathway was detected by Western blot. Results: MEG3 expression was downregulated in SREDs and rats with TLE. Overexpression of MEG3 reduced the expression of IL-1ß, IL-6, and TNF-α, MDA content, apoptosis rate of hippocampal neuron, increased SOD activity, and inhibited the PI3K/AKT/mTOR pathway in rats with TLE. In addition, overexpression of MEG3 enhanced cell viability and inhibited apoptosis through the activation of the PI3K/AKT/mTOR pathway in SREDs. Conclusion: MEG3 reduced proinflammatory cytokines, oxidative stress, and apoptosis rate of hippocampal neuron and enhanced cell viability through the activation of the PI3K/AKT/mTOR pathway in SREDs and rats with TLE. Our findings may contribute to find a new therapeutic target for the treatment of epilepsy.

11.
Oncol Lett ; 20(6): 358, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33133258

RESUMO

Pseudolaric acid B (PAB) is a diterpene-type acid isolated from the root and trunk bark of Pseudolarix kaempferi Gordon of the Pinaceae family that has been demonstrated to induce apoptosis in various cell lines and autophagy in certain cell lines including murine fibrosarcoma L929, human thyroid squamous cell carcinoma SW579 and human lung fibroblast MRC5 cells. However, in human rhabdomyosarcoma RD cells, which are derived from the most common soft tissue sarcoma in children and represent a high-grade neoplasm of a skeletal myoblast type, it is not clear whether PAB induces apoptosis or autophagy. The identification of the exact mechanism of PAB is important for studying its antitumor effects and its potential application in the treatment of human rhabdomyosarcoma. To confirm the inhibitory ability of PAB on RD cells, the inhibitory ratio of PAB was analyzed, and the results of MTT assay demonstrated that PAB inhibited RD cell proliferation. Meanwhile aggregation of the microtubule fibers was found in PAB-treated RD cells compared with that in control-treated cells, which was consistent with previous studies. In addition, PAB inhibited RD cell migration, induced apoptosis and cell cycle arrest at the G2/M phase. These results suggested that the mechanism of PAB-mediated growth inhibition in RD was similar to that reported in the human breast cancer cell line MCF-7 and the neuroglioma cell line A172; however, it was different from that reported in the L929, MRC5 and SW579 cell lines. Additional experiments demonstrated that PAB regulated the activation of caspase-8 and caspase-9 to induce apoptosis and caused an upregulation of phosphorylated H2A histone family member X and cyclin B1 expression in order to induce cell cycle arrest. Therefore, PAB may be considered a potential treatment agent for human rhabdomyosarcoma.

12.
Appl Microbiol Biotechnol ; 104(21): 9343-9361, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32965561

RESUMO

The human body is almost always facing the oxidative stress caused by foodborne aldehydes such as glyoxal (GO) and methylglyoxal (MGO), 4-hydroxyhexenal (HHE), and 4-hydroxynonenal (HNE). When these aldehydes build up, they can cause a range of harm. However, a probiotic, Clostridium butyricum, can increase nuclear factor erythroid-2 related factor 2 (Nrf2) and may have the potential to relieve oxidative stress. If C. butyricum is indeed resistant to aldehydes, the advantages (accessibility, convenience, and safety) will be of great significance compared with drugs. Unfortunately, whether C. butyricum can play a role in alleviating toxic effects of foodborne aldehydes in the intestine (the first line of defense against food-derived toxin) was unclear. To investigate these, we measured the viability, ROS, autophagy, and inflammatory cytokine expression of Caco-2 which were co-cultured with C. butyricum and stimulated by the four aldehydes via Nrf2 pathway (Staphylococcus aureus and Enterococcus faecium as controls). Then, we explored the link among C. butyricum, NLRP6, and Nrf2 signaling pathways when facing the stimuli. In the present study, we demonstrated that Clostridium butyricum relieved the oxidative stress induced by the aldehydes in Caco-2. Most interestingly, we found a "complementary" relationship between NLRP6 and Nrf2 in C. butyricum treatment under aldehyde stress. Our research not only makes a contribution to the popularization of C. butyricum as a probiotic-rich food instead of medicines but also sheds new light on the application of subsequent microecological formulation of C. butyricum. KEY POINTS: • The adverse effects are caused in a dose-dependent manner by foodborne aldehydes. • Clostridium butyricum can significantly ameliorate oxidative stress. • There is a "complementary" relationship between the NLRP6 and Nrf2 signaling pathways. • Using Clostridium butyricum foods to alleviate oxidative stress shows great prospects.


Assuntos
Clostridium butyricum , Aldeídos/toxicidade , Células CACO-2 , Manipulação de Alimentos , Humanos , Lipídeos , Estresse Oxidativo
13.
J Microbiol ; 58(9): 812-820, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32870487

RESUMO

Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.


Assuntos
Antivirais/farmacologia , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Enterovirus Humano D/efeitos dos fármacos , Enterovirus Humano D/crescimento & desenvolvimento , Apoptose/fisiologia , Linhagem Celular Tumoral , Infecções por Enterovirus/patologia , Infecções por Enterovirus/prevenção & controle , Infecções por Enterovirus/virologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Hidrazonas/farmacologia , Oligopeptídeos/farmacologia , Piperazinas/farmacologia
14.
Virology ; 549: 77-84, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32853849

RESUMO

Human infections with highly pathogenic avian influenza (HPAI) H7N9 virus were detected in late 2016. We examined the drug resistance profile of 30 HPAI H7N9 isolates from Mainland of China (2016-2019). Altogether, 23% (7/30) carried neuraminidase inhibitors (NAIs) - resistance mutations, and 13% (4/30) displayed reduced susceptibility to NAIs in neuraminidase (NA) inhibition test. An HPAI H7N9 reassortment virus we prepared was passaged with NAIs for 10 passages. Passage with zanamivir induced an E119G substitution in NA, whereas passage with oseltamivir induced R292K and E119V substitutions that simulated that seen in oseltamivir -treated HPAI H7N9 cases, indicating that the high frequency of resistant strains in the HPAI H7N9 isolates is related to NAIs use. In presence of NAIs, R238I, A146E, G151E and G234T substitutions were found in HA1 region of HA. No amino acid mutations were found in the internal genes of the recombinant virus.


Assuntos
Farmacorresistência Viral/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Mutação , Neuraminidase/genética , Vírus Reordenados/genética , Proteínas Virais/genética , Substituição de Aminoácidos , Animais , Antivirais/farmacologia , Aves/virologia , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Subtipo H7N9 do Vírus da Influenza A/metabolismo , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Influenza Aviária/patologia , Influenza Aviária/transmissão , Influenza Aviária/virologia , Influenza Humana/patologia , Influenza Humana/transmissão , Influenza Humana/virologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Neuraminidase/metabolismo , Oseltamivir/farmacologia , Conformação Proteica , Vírus Reordenados/efeitos dos fármacos , Vírus Reordenados/metabolismo , Vírus Reordenados/patogenicidade , Proteínas Virais/metabolismo , Zanamivir/farmacologia
15.
Poult Sci ; 99(7): 3374-3384, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32616231

RESUMO

Newcastle disease is a kind of avian infectious disease caused by Newcastle disease virus (NDV). The virulence of NDV is dependent mainly on the fusion (F) protein and hemagglutinin-neuraminidase (HN) protein. The genomes of 2 viruses, NDV-Blackbird and NDV-Dove, are 99.9% similar, while NDV-Blackbird is a velogenic virus, and NDV-Dove is a lentogenic virus. Further analysis revealed that the F proteins of the 2 strains were identical, and only 5 amino acid sites on the HN proteins were inconsistent. Five different HN mutant plasmids were constructed and analyzed in this study. The results showed that the mutation F110L caused a significant increase in fusion-promotion activity caused by an increase in neuraminidase activity. Because of the increase in receptor-binding activity caused by G116R, there was a significant increase in fusion-promotion activity. The mutation G54S resulted in a slight decrease in the fusion-promotion activity caused by a slight decrease in receptor-binding activity. The slight increase in the fusion-promotion activity caused by A469V was associated with a significant increase in neuraminidase activity. Therefore, the amino acids L110 and R116 played a key role in determining the virulence difference between NDV-Blackbird and NDV-Dove, which could lay a foundation for illuminating the virulence differences of NDV strains, as well as the development of attenuated vaccines.


Assuntos
Galinhas , Proteína HN/genética , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/patogenicidade , Doenças das Aves Domésticas/virologia , Animais , Proteína HN/metabolismo , Vírus da Doença de Newcastle/genética , Virulência/genética
16.
Chem Commun (Camb) ; 56(52): 7116-7119, 2020 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32458867

RESUMO

We successfully developed a photoelectrochemical enzymatic fuel cell (PEFC)-based self-powered biosensing platform for microRNA detection via DNA conformation change-controlled co-sensitization behavior, which could offer ultrasensitive detection of microRNA down to 0.05 fM and realize microRNA determination in human serum.


Assuntos
DNA/química , MicroRNAs/sangue , Técnicas Biossensoriais , Materiais Revestidos Biocompatíveis/química , Técnicas Eletroquímicas , Eletrodos , Ouro/química , Humanos , Lacase/química , Limite de Detecção , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Conformação de Ácido Nucleico , Processos Fotoquímicos , Semicondutores , Propriedades de Superfície
17.
Front Chem ; 8: 185, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32296677

RESUMO

Adipic acid is one of the most important feedstocks for producing resins, nylons, lubricants, plasticizers. Current industrial petrochemical process, producing adipic acid from KA oil, catalyzed by nitric acid, has a serious pollution to the environment, due to the formation of waste nitrous oxide. Hence, developing cleaner methods to produce adipic acid has attracted much attention of both industry and academia. This mini-review article discussed advances on adipic acid synthesis from bio-renewable feedstocks, as well as most recent progress on cleaner technology from fossil fuels over novel catalytic materials. This work on recent advances in green adipic acid production will provide insights and guidance to further study of various other industrial processes for producing nylon precursors.

18.
Fish Shellfish Immunol ; 100: 476-488, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32209398

RESUMO

Retinol-binding protein 4 (RBP4) is known as a highly conserved adipokine for immune activation. Aeromonas hydrophila (A. hydrophila) is the most common zoonotic pathogen in aquaculture, which causes serious economic losses to aquaculture, especially to bighead carp (Hypophthalmichthys nobilis, H. nobilis) and silver carp (Hypophthalmichthys molitrix, H. molitrix). Recent studies along with our previous findings have shown that synthetic oligodeoxynucleotides containing CpG motifs (CpG ODN) can play a good role in aquatic animals against infection. In order to clarify the relationship between CpG ODN and RBP4 under A. hydrophila infection, firstly, full-length RBP4 cDNAs from H. nobilis and H. molitrix were cloned. And characteristics of RBP4, including sequence and structure, tissue distribution and genetic evolution were analyzed. In addition, mRNA expression levels of RBP4, cytokine, toll-like receptors (TLRs), morbidity and survival rates of H. nobilis and H. molitrix were observed post CpG ODN immunization or following challenge. The results indicated that hn/hm_RBP4 (RBP4 genes obtained from H. nobilis and H. molitrix) had the highest homology with Megalobrama amblycephala. Distribution data showed that the expression level of hn_RBP4 mRNA was higher than that of hm_RBP4. After CpG ODN immunization followed by A.hydrophila challenge, significantly higher survival was observed in both carps, together with up-regulated RBP4 expression. Meanwhile, hn/hm_IL-1ß level was relatively flat (and decreased), hn/hm_IFN-γ, hn/hm_TLR4 and hn/hm_TLR9 levels increased significantly, but hn/hm_STRA6 showed no significant change, compared with control. Moreover, CpG ODN immunization could induce stronger immune protective responses (higher IFN-γ/gentle IL-1ß level and lower morbidity/higher survival rate) against A. hydrophila in H. nobilis, along with higher RBP4 level, when compared with that in H. molitrix. These results demonstrated that RBP4 was well involved in the immune protection of CpG ODN. Based on the results, we speculated that in the case of A. hydrophila infection, TLR9 signaling pathway was activated by CpG ODN. Subsequently, CpG ODN up-regulated RBP4, and RBP4 activated TLR4 signaling pathway. Then TLR4 and TLR9 synergistically improved the anti-infection responses. Our findings have good significance for improving resistance to pathogen infection in freshwater fish.


Assuntos
Carpas/genética , Carpas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunização/veterinária , Oligodesoxirribonucleotídeos/administração & dosagem , Proteínas Celulares de Ligação ao Retinol/genética , Aeromonas hydrophila/patogenicidade , Animais , Carpas/imunologia , DNA Complementar , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Oligodesoxirribonucleotídeos/imunologia , Proteínas Celulares de Ligação ao Retinol/química , Proteínas Celulares de Ligação ao Retinol/imunologia , Regulação para Cima
19.
Front Microbiol ; 11: 42, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117097

RESUMO

Hand, foot, and mouth disease (HFMD) is a febrile exanthematous disease with typical or atypical symptoms. Typical HFMD is usually caused by enterovirus 71 (EV71) or coxsackievirus A16, while atypical HFMD is usually caused by coxsackievirus A6 (CA6). In recent years, worldwide outbreaks of CA6-associated HFMD have dramatically increased, although the pathogenic mechanism of CA6 is still unclear. EV71 has been established to induce caspase-dependent apoptosis, but in this study, we demonstrate that CA6 infection promotes a distinct pathway of cell death that involves loss of cell membrane integrity. Necrostatin-1, an inhibitor of necroptosis, blocks the cell death induced by CA6 infection, but Z-DEVD-FMK, an inhibitor of caspase-3, has no effect on CA6-induced cell death. Furthermore, CA6 infection up-regulates the expression of the necroptosis signaling molecule RIPK3. Importantly, necrostatin-1 inhibits CA6 viral production, as assessed by its ability to inhibit levels of VP1 protein and genomic RNA and infectious particles. CA6-induced necroptosis is not dependent on the generation of reactive oxygen species; however, viral 3D protein can directly bind RIPK3, which is suggestive of a direct mechanism of necroptosis induction. Therefore, these results indicate that CA6 induces a mechanism of RIPK3-dependent necroptosis for viral production that is distinct from the mechanism of apoptosis induced by typical HFMD viruses.

20.
Microb Cell Fact ; 19(1): 35, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070347

RESUMO

Porcine growth hormone (pGH) is a class of peptide hormones secreted from the pituitary gland, which can significantly improve growth and feed utilization of pigs. However, it is unstable and volatile in vitro. It needs to be encapsulated in liposomes when feeding livestock, whose high cost greatly limits its application in pig industry. Therefore we attempted to express pGH as intracellular soluble protein in Pichia pastoris and feed these yeasts with partial wall-breaking for swine, which could release directly pGH in intestine tract in case of being degraded in intestinal tract with low cost. In order to improve the intracellular soluble expression of pGH protein in Pichia pastoris and stability in vitro, we optimized the pGH gene, and screened molecular chaperones from E. coli and Pichia pastoris respectively for co-expressing with pGH. In addition, we had also explored conditions of mechanical crushing and fermentation. The results showed that the expression of intracellular soluble pGH protein was significantly increased after gene optimized and co-expressed with Ssa1-Sis1 chaperone from Pichia pastoris. Meanwhile, the optimal conditions of partial wall-breaking and fermentation of Pichia pastoris were confirmed, the data showed that the intracellular expression of the optimized pGH protein co-expressed with Ssa1-Sis1 could reach 340 mg/L with optimal conditions of partial wall-breaking and fermentation. Animal experiments verified that the optimized pGH protein co-expression with Ssa1-Sis1 had the best promoting effects on the growth of piglets. Our study demonstrated that Ssa1-Sis1 could enhance the intracellular soluble expression of pGH protein in Pichia pastoris and that partial wall-breaking of yeast could prevent pGH from degradation in vitro, release targetedly in the intestine and play its biological function effectively. Our study could provide a new idea to cut the cost effectively, establishing a theoretical basis for the clinic application of unstable substances in vitro.


Assuntos
Proteínas Fúngicas/metabolismo , Hormônio do Crescimento/biossíntese , Chaperonas Moleculares/metabolismo , Pichia/metabolismo , Suínos/crescimento & desenvolvimento , Animais , Clonagem Molecular , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fermentação , Pichia/genética , Proteínas Recombinantes/biossíntese
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...