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1.
Front Immunol ; 13: 935454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837399

RESUMO

Duck plague virus (DPV), a member of the alphaherpesvirus subfamily, can cause severe damage and immunosuppression in ducks and geese in China. Since lacking an available cell model, the antiviral signal transduction pathways induction and regulation mechanisms related to DPV infection in duck cells are still enigmatic. Our previous study developed a monocyte/macrophages cell model, which has been applied to study innate immunity with DPV. In the present study, we compared and analyzed transcriptome associated with the DPV infection of CHv (virulent strain) and CHa (avirulent strain) at 48hpi based on the duck monocyte/macrophages cell model and RNA-seq technology. Differentially expressed genes (DEGs) analysis showed 2,909 and 2,438 genes altered in CHv and CHa infected cells compared with control cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the DEGs were mainly involved in biological processes such as metabolic pathways, viral infectious diseases, immune system, and signal transduction. The CHv and CHa virus differentially regulated MAPK, NF-κB, and IFN signaling pathways based on transcriptome sequencing data and RT-qPCR results. The JNK inhibitor SP600125 enhanced the IFN signaling, but potentially reduced the VSV and DPV titers in the cell culture supernatant, indicating that JNK negatively regulates the IFN pathway and the inflammatory pathway to promote virus proliferation. The research results may provide promising information to understand the pathogenesis of DPV and provide a novel mechanism by which DPV modulates antiviral signaling and facilitate virus proliferation through hijacking the JNK pathway, which provides a new means for the prevention and control of DPV infection.


Assuntos
Fenômenos Biológicos , Patos , Animais , Antivirais/metabolismo , Proliferação de Células , Sistema de Sinalização das MAP Quinases , Mardivirus , Transdução de Sinais
2.
Poult Sci ; 101(9): 102017, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35901648

RESUMO

Flavivirus RNA cap-methylation plays an important role in viral infection, proliferation, and escape from innate immunity. The methyltransferase (MTase) of the flavivirus NS5 protein catalyzes viral RNA methylation. The E218 amino acid of the NS5 protein MTase domain is one of the active sites of flavivirus methyltransferase. In flaviviruses, the E218A mutation abolished 2'-O methylation activity and significantly reduced N-7 methylation activity. Tembusu virus (TMUV, genus Flavivirus) was a pathogen that caused neurological symptoms in ducklings and decreased egg production in laying ducks. In this study, we focused on a comprehensive understanding of the effects of the E218A mutation on TMUV characteristics and the host immune response. E218A mutation reduced TMUV replication and proliferation, but did not affect viral adsorption and entry. Based on a TMUV replicon system, we found that the E218A mutation impaired viral translation. In addition, E218A mutant virus might be more readily recognized by RIG-I-like receptors to activate the corresponding antiviral immune signaling than WT virus. Together, our data suggest that the E218A mutation of TMUV MTase domain impairs viral replication and translation and may activates RIG-I-like receptor signaling, ultimately leading to a reduction in viral proliferation.

3.
World J Surg Oncol ; 20(1): 227, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804390

RESUMO

BACKGROUND: With low response to present immunotherapy, it is imperative to identify new immune-related biomarkers for more effective immunotherapies for oral cancer. METHODS: RNA profiles for 390 oral cancer patients and 32 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database and differentially expressed genes (DEGs) were analyzed. Immune genesets from ImmPort repository were overlapped with DEGs. After implementing univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, key immune-related gene pairs (IRGPs) among the overlapped DEGs for predicting the survival risk were obtained. Then, the cutoff of risk score was calculated by the receiver operating characteristic (ROC) curve to stratify oral cancer patients into high and low-risk groups. Multivariate Cox analysis was used to analyze independent prognostic indicators for oral cancer. Besides, infiltration of immune cells, functional annotation, and mutation analysis of IRGPs were conducted. Biological functions correlated with IRGPs were enriched by Gene Set Enrichment Analysis (GSEA) method. RESULTS: We identified 698 differentially expressed genes (DEGs) in response to oral cancer. 17 IRGPs among the DEGs were identified and integrated into a risk score model. Patients in the high-risk group have a significantly worse prognosis than those in the low-risk group in both training (P<0.001) and test (P=0.019) cohorts. Meanwhile, the IRGP model was identified as an independent prognostic factor for oral cancer. Different infiltration patterns of immune cells were found between the high- and low-risk groups that more types of T and B cells were enriched in the low-risk group. More immune-related signaling pathways were highly enriched in the low-risk group and Tenascin C (TNC) was the most frequently mutated gene. We have developed a novel 17-IRGPs signature for risk stratification and prognostic prediction of oral cancer. CONCLUSION: Our study provides a foundation for improved immunotherapy and prognosis and is beneficial to the individualized management of oral cancer patients.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias Bucais/genética , Prognóstico , Medição de Risco/métodos
4.
Virol J ; 19(1): 111, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761382

RESUMO

BACKGROUND: Duck hepatitis A virus type 1 (DHAV-1) is one of the most serious pathogens endangering the duck industry. However, there are few studies on the regulation of the cell cycle by DHAV-1. METHODS: In this study, flow cytometry was applied to analyze the effect of DHAV-1 infection on the cell cycle of duck embryo fibroblasts (DEFs). Subsequently, we analyzed the effects of cell cycle phases on DHAV-1 replication by real-time reverse transcriptase quantitative PCR (real-time RT-qPCR). RESULTS: Flow cytometry data analysis found that DEFs in the S phase increased by 25.85% and 54.21% at 24 h and 48 h after DHAV-1 infection, respectively. The levels of viral RNA detected by real-time RT-qPCR were higher in the DEFs with synchronization in the S phase or G0/G1 phase than in the control group. However, there was no difference in viral copy number between the G2/M phase arrest and control groups. In addition, non-structural protein 3D of DHAV-1 significantly increased cells in the S phase, indicating that 3D protein is one of the reasons for the cell cycle arrest in the S phase. CONCLUSIONS: In summary, DHAV-1 infection induces the cell cycle arrest of DEFs in the S phase. Both S phase and G0/G1 phase synchronization facilitate the replication of DHAV-1, and 3D protein is one of the reasons for the S phase arrest.


Assuntos
Vírus da Hepatite do Pato , Hepatite Viral Animal , Animais , Pontos de Checagem do Ciclo Celular , Patos , Vírus da Hepatite do Pato/genética , Fase S
5.
China CDC Wkly ; 4(3): 41-46, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35586458

RESUMO

What is already known about this topic?: The association of diabetes mellitus (DM) with both increased risk of tuberculosis (TB) and unfavorable treatment outcomes has been identified by many studies (1). However, epidemic data for TB cases in DM patients is absent in China. What is added by this report?: This current population-based prospective cohort study, conducted in ten counties located in eastern, central, and western China during 2013-2015, revealed a high prevalence and incidence of TB in known DM patients. Most TB cases were captured by active case-finding and a much higher presence of being asymptomatic among TB/DM patients was obtained. What are the implications for public health practice?: Active case-finding should be carried out in DM patients and populations at high risk for developing TB. A TB symptom screening-based case-finding strategy is not enough; chest radiography check should be done once a year for these patients.

6.
Front Psychol ; 13: 842378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418921

RESUMO

Mental health issues are becoming increasingly prevalent amongst university students. However, research on the psychological profile of the general university population is relatively limited. Thus, this study analyses the current state of university students' psychological conditions; the demographic differences in depression, anxiety, and stress and the influencing factors. The objectives are to provide additional appropriate guidance in mental health for university students with different demographic characteristics. A cross-sectional study of 6,032 university students nationwide was conducted from October 2020 to January 2021. A randomized whole-group sampling method was used to select the study participants, and the 21-item Depression, Anxiety, and Stress Scale (DASS) was used. P < 0.05 in the final model were considered statistically significant. The number of university students with no complain of depression, anxiety, or stress was 3,751 (62.2%). The odds of developing complain of depression were higher amongst anxious respondents (AOR = 23.417, 95% CI: 19.706, 27.826) and senior year (AOR = 2.210, 95% CI: 1.657, 2.947) than their counterparts. Students with "myopia" were 1.263 times more likely to be anxious (AOR = 1.263, 95% CI: 1.042-1.530). In terms of "impaired" or not, impaired is defined as any injury, such as sprain, strain, and fracture, "impaired" university students were 1.321 times more likely to be anxious (AOR = 1.321, 95% CI: 1.064-1.641). Furthermore, history of impairment and myopia increased the odds of stress by 1.305 (AOR = 1.305, 95% CI: 1.022-1.667) and 1.305 (AOR = 1.305, 95% CI: 1.012-1.683), respectively. Myopia, physical-activity-related injury (PARI) and irrational eating habits are risk factors for complain of anxiety and stress. Males, upper grades, low parental education, and irrational eating habits are risk factors for complain of depression. Low physical activity levels are also an influential factor for complain of depression. DASS consists of interchangeable risk factors and multiple complains of DASS may coexist.

7.
Vet Res ; 53(1): 22, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303942

RESUMO

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are cytosolic pattern recognition receptors that initiate innate antiviral immunity. Recent reports found that duck RLRs significantly restrict duck plague virus (DPV) infection. However, the molecular mechanism by which DPV evades immune responses is unknown. In this study, we first found that the DPV UL41 protein inhibited duck interferon-ß (IFN-ß) production mediated by RIG-I and melanoma differentiation-associated gene 5 (MDA5) by broadly downregulating the mRNA levels of important adaptor molecules, such as RIG-I, MDA5, mitochondrial antiviral signalling protein (MAVS), stimulator of interferon gene (STING), TANK-binding kinase 1 (TBK1), and interferon regulatory factor (IRF) 7. The conserved sites of the UL41 protein, E229, D231, and D232, were responsible for this activity. Furthermore, the DPV CHv-BAC-ΔUL41 mutant virus induced more duck IFN-ß and IFN-stimulated genes (Mx, OASL) production in duck embryo fibroblasts (DEFs) than DPV CHv-BAC parent virus. Our findings provide insights into the molecular mechanism underlying DPV immune evasion.


Assuntos
Patos , Interferon beta , Animais , Imunidade Inata , Interferon beta/genética , Interferons , Estabilidade de RNA
8.
Front Behav Neurosci ; 16: 808789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35283740

RESUMO

Background: The use of transcranial magnetic stimulation combined with electromyography for the functional evaluation of the cerebral cortex in both clinical and non-clinical populations is becoming increasingly common. Numerous studies have shown that electro-acupuncture (EA) can regulate cerebral cortical excitability. However, the effect of EA on the lateralization of the human swallowing motor cortex excitability is not yet fully understood. Objective: The aim of this study was to assess whether lateralization is present in the swallowing motor cortex of healthy subjects, and to investigate the impact of EA at Lianquan (CV23) and Fengfu (GV16) on lateralization. Methods: Forty subjects were randomized 1:1 into the EA group and the sham-EA group. The bilateral swallowing motor cortices was located by a neuroimaging navigation system. Then, the resting motor threshold (RMT) and motor evoked potential (MEP) of the mylohyoid of healthy subjects were recorded while applying combined transcranial magnetic stimulation and electromyography before and after EA or sham-EA. Results: First, the RMT and MEP latency of the contralateral mylohyoid innervated by the right swallowing cortex (71.50 ± 1.67%, 8.30 ± 0.06 ms) were lower than those innervated by the left (79.38 ± 1.27%, 8.40 ± 0.06 ms). Second, EA at CV23 and GV16 reduced the bilateral RMT and enhanced the bilateral MEP latency and amplitude (P = 0.005, P < 0.001; P = 0.002, P = 0.001; P = 0.002, P = 0.009), while sham-EA did not (P > 0.05). Third, EA had an effect on the RMT and MEP latency in terms of lateralization changes, but this was not significant (P = 0.067, P = 0.156). Conclusion: The right swallowing motor cortex of healthy subjects is more excitable than that of the left at resting state. Thus, we found that lateralization is present in the swallowing motor cortex of healthy people, which might indicate a hemispheric dominance of swallowing predominates in the right swallowing motor cortex. In addition, EA at CV23 and GV16 can instantly promote the excitability of the bilateral swallowing motor cortices. But there was no significant difference in EA stimulation in terms of lateralization.

9.
Front Bioeng Biotechnol ; 10: 842014, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35284417

RESUMO

Objective: To investigate the effect of osseointegration of kaempferol loaded on the surface of micro-nanomorphic implants in ovariectomized rats. Methods: Titanium flakes were polished to obtain the PT group, anodized and acid-etched to obtain the NT and WNT groups, loaded with kaempferol to obtain the KNT and KWNT groups, and spin-coated on chitosan-gelatin composite film to obtain the KNT-CG and KWNT-CG groups. In vitro experiments were performed to observe the physicochemical properties of the titanium tablets in each group through scanning electron microscopy and contact angle experiments. The cytotoxicity and drug release pattern were observed using CCK-8 and drug release assays. An osteoporosis rat model was established. Pure titanium implants were divided into PT, NT, WNT, KNT-CG, and KWNT-CG groups after the same treatment and used in the in vivo experiments and then implanted in the femur of mice in each group. After 4 weeks, all samples were collected for toluidine blue staining, micro-computed tomography scanning, and bone morphometry analysis to evaluate their osteogenic properties. Results: According to scanning electron microscopy, the surface of the titanium flakes had a micro-nano morphology in the WNT group and the KNT and KWNT groups were functionally loaded with kaempferol. In CCK-8 and drug release experiments, the loaded kaempferol and gelatin composite membranes showed no significant toxic effects on cells. The drug release time in the KNT-CG and KWNT-CG groups was significantly longer than that in the KNT and KWNT groups, with the release time in the KWNT-CG group reaching 15 days. In vivo experiments micro-computed tomography and bone morphometry analysis showed that the osteoporosis model had been successfully constructed. The bone volume fraction around the implant increased. Toluidine blue staining showed new bone formation and a significantly increased number of bone trabeculae. Conclusion: Kaempferol micro-nanocomposite coating improved the osseointegration ability of implants in osteoporotic rats.

10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(2): 254-259, 2022 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-35184493

RESUMO

Objective: To analyze the effects of unsafe sexual behavior and sexual orientation on previous HIV testing and HIV testing willingness among college students in Harbin, to provide a theoretical basis for promoting and promoting HIV testing among them. Methods: A cross-sectional survey design was used to place the automatic vending machine of HIV urine test kit in 9 universities in Harbin from December 2017 to January 2018. The questionnaire star was used to design and recruit college students to carry out an anonymous online survey. The estimated sample size was 6 659. A multivariate logistic regression model was used to analyze the effects of unsafe sexual behavior and sexual orientation on previous HIV testing and HIV testing willingness among college students. WPS 2016 was used to sort out the database, and SPSS 21.0 software was used for statistical analysis. Results: A total of 60 849 valid questionnaires were collected. 19.1% (11 189/58 605) of college students reported having sex. College students who used condoms correctly every time, occasionally or never during sex in the past six months 58.5% (6 206/10 603), 25.2%(2 669/10 603)and 16.3% (1 728/10 603), respectively. Heterosexuality, homosexuality and bisexuality accounted for 94.1% (54 393/57 823), 2.4% (1 369/57 823) and 3.5% (2 061/57 823), respectively. The HIV testing willingness of college students was 73.3% (44 572/60 849). The proportion of previous HIV testing was 10.3% (951/9 241). Results of the multivariate logistic analysis showed that compared with the college students who used condoms correctly whenever they had sex in the past six months, there was no significant difference in the proportion of previous HIV testing among college students who sometimes/occasionally used or never used condoms (OR=0.94,95%CI:0.69-1.29; OR=1.11,95%CI:0.73-1.67), but their willingness to HIV testing was lower (OR=0.79, 95%CI:0.71-0.89; OR=0.48, 95%CI:0.42-0.55); Compared with heterosexual college students, homosexual or bisexual college students have a higher proportion of previous HIV testing (OR=2.62, 95%CI:1.62-4.24; OR=2.04, 95%CI:1.25-3.32), but have lower HIV testing willingness (OR=0.76, 95%CI: 0.62-0.93; OR=0.64, 95%CI: 0.53-0.77). Conclusions: Unsafe sexual behavior existed among college students in Harbin, and college students with weak awareness of HIV prevention also have weak awareness of testing. Behavioral intervention should be strengthened and HIV testing promoted. Compared with heterosexuals, homosexual or bisexual college students had a higher proportion of previous HIV testing, but their willingness to test was lower. The HIV detection mode with better concealment, accuracy, and convenience should be promoted on the college's campus.


Assuntos
Infecções por HIV , Comportamento Sexual , Preservativos , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Teste de HIV , Humanos , Masculino , Estudantes , Inquéritos e Questionários
11.
Bioengineered ; 13(1): 1758-1766, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35034554

RESUMO

Asthma is a chronic inflammatory disease of the airways, and IL-35 has been found to be involved in the pathogenesis of inflammatory diseases by mediating the inhibition of effector T cells. But the role of IL-35 on cell pyroptosis, which frequently occurs in inflammatory diseases, has not been elucidated. Therefore, the present study used a TNF-α-induced bronchial epithelial cell injury model to investigate the mechanism of IL-35 action on cell pyroptosis and asthma injury. The effects of IL-35 on cell activity, inflammatory factor levels, cell barrier damage and cell pyroptosis-related proteins were examined by CCK-8, ELISA, lucifer yellow permeability and Western blotting assay, respectively. Subsequently, following the activation of p38 MAPK signaling pathway by adding p38 agonist, the effect of IL-35 on TNF-α-induced bronchial epithelial cell injury was investigated. The results showed that IL-35 reduced TNF-α-induced cell injury, decreased inflammatory factors, improved cell permeability, and inhibited cell pyroptosis. More importantly, the effect of IL-35 on injured cells was reversed after p38 MAPK pathway was activated. In summary, IL-35 inhibited p38 MAPK pathway to suppress cell pyroptosis and thereby reduce asthma injury.


Assuntos
Brônquios/metabolismo , Células Epiteliais/metabolismo , Interleucinas/metabolismo , Sistema de Sinalização das MAP Quinases , Piroptose , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular , Humanos
12.
Inorg Chem ; 61(1): 605-612, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34919395

RESUMO

Carbide clusterfullerenes (CCFs) have been of great concern due to their potential applications in materials science, in which the internal carbide cluster plays vital roles in the stability and properties of CCF. However, there still remains a debate about what configuration is ideal for the internal carbide cluster. In this work, we isolated two isomers (I and II) of Ho2C94 and studied them by means of mass spectrometry, UV-vis-NIR spectroscopy, and cyclic/differential pulse voltammetry. A combined study of single-crystal X-ray diffraction (SC-XRD) and density functional theory (DFT) computation ascertains isomer-I as Ho2C2@C2(61)-C92, in which the Ho2C2 cluster displays variable configurations from planar zigzag to folded butterfly with very small distortion energy (∼10 kJ/mol). This study hence confirms that the internal carbide cluster is intrinsically flexible over a broad geometrical range in a relatively large fullerene cage, where the nanoscale compression effect is almost negligible.

13.
Vet Microbiol ; 264: 109300, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34922149

RESUMO

The duck hepatitis A virus 1 (DHAV-1) 2C protein was predicted to be a superfamily III helicase member and includes nucleotide binding (NTB) and putative RNA helicase activity motifs. To study whether DHAV-1 2C protein has NTB activity, we expressed DHAV-1 2C protein with maltose binding protein (MBP) to solve its poor solubility in a prokaryotic expression system. We showed that the DHAV-1 2C protein has nucleoside triphosphatase (NTPase) activity by measuring the released phosphate. The NTPase of the DHAV-1 2C protein is Mg2+ indispensable and affected by other biochemical characteristics such as Mn2+, Ca2+, Zn2+, Na+ and pH. Guanidine hydrochloride (GdnHCl), a potent inhibitor of viral RNA replication, inhibited ATPase activity of the DHAV-1 2C protein in a dose-dependent manner. Finally, we constructed three mutants to identify the key site for the ATPase activity of the DHAV-1 2C protein. These results indicate that lysine at position 151 of the DHAV-1 2C protein is very important for NTPase activity. Here, we demonstrated and partially characterized that the DHAV-1 2C protein has NTPase activity and showed that mutation of the lysine in the conserved Walker A impairs that activity. The results serve to confirm what is readily predicted from previous work on picornavirus 2C proteins. It also provides a basis for further study of the 2C protein and the function of NTPase activity on the viral life cycle.


Assuntos
Proteínas de Transporte , Vírus da Hepatite do Pato , Lisina , Nucleosídeo-Trifosfatase , Proteínas não Estruturais Virais , Animais , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Patos , Vírus da Hepatite do Pato/genética , Lisina/metabolismo , Nucleosídeo-Trifosfatase/genética , Nucleosídeo-Trifosfatase/metabolismo , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/genética
14.
Vet Microbiol ; 265: 109312, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34953307

RESUMO

Our previous studies revealed that duck Tembusu virus (DTMUV) NS2A inhibited IFNß signaling pathway by competitively binding to STING with TBK1, leading to reducing the phosphorylation of TBK1. Herein, we found that the 114-143 aa region of NS2A is critical for its interaction with STING and suppression of STING-mediated IFNß signaling. We further identified the amino acids at positions L129, N130, L139, R140 and F143 of NS2A critical for NS2A-STING interaction. Subsequently, single residue substitution in the NS2A protein was introduced into the DTMUV replicon and infectious clone. The replicons with NS2A L129A and L130A mutations significantly inhibited viral genome RNA replication. The rDTMUV NS2A L129A, L139A and R140A mutant viruses yielded significantly lower titer levels than WT in both BHK-21 and DEF cells, with much more obvious effect on the viral genome level, and infectious virions formed outside of infected cells. Especially, the rDTMUV L129A mutant showed a significantly lower mortality in both embryos and ducks than WT. All NS2A-mutants decreased the weight gain of infected ducklings and reduced the viral loads in the spleen relative to WT. However, no significant differences of viral loads were observed in the blood, thymus, or liver. Our findings extend our previous study on the immune evasion role of flavivirus NS2A protein. The targeted therapy of disabling the viral strategies developed for evading innate defense can be applied to the development of attenuated flaviviruses.


Assuntos
Infecções por Flavivirus , Flavivirus , Doenças das Aves Domésticas , Animais , Patos , Flavivirus/genética , Infecções por Flavivirus/veterinária , Proteínas não Estruturais Virais/metabolismo , Virulência/genética
15.
Toxicology ; 466: 153079, 2022 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-34942272

RESUMO

Long-term excessive exposure to fluoride from environmental sources can cause serious public health problems such as dental fluorosis and skeletal fluorosis. The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis and canonical Wnt signaling pathway participate in the progress. However, the specific mechanism that how canonical Wnt signaling pathway was mediated is not yet clear. In this study, we found that miR-21-5p induced the activation of canonical Wnt signaling pathway via targeting PTEN and DKK2 during fluoride induced osteoblasts activation and firstly demonstrated the forward loop between canonical Wnt signaling and miR-21-5p in the process. These findings suggested an important regulatory role of miR-21-5p on canonical Wnt signaling pathway during skeletal fluorosis and miR-21-5p might be a potential therapeutic target for skeletal fluorosis.


Assuntos
Fluoretos/toxicidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MicroRNAs/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Via de Sinalização Wnt , Doenças Ósseas Metabólicas/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos
16.
Front Microbiol ; 12: 700434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867836

RESUMO

Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-ß by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-ß-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.

18.
Front Microbiol ; 12: 744408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925260

RESUMO

Duck plague virus (DPV) can cause high morbidity and mortality in many waterfowl species within the order Anseriformes. The DPV genome contains 78 open reading frames (ORFs), among which the LORF2, LORF3, LORF4, LORF5, and SORF3 genes are unique genes of avian herpesvirus. In this study, to investigate the role of this unique LORF5 gene in DPV proliferation, we generated a recombinant virus that lacks the LORF5 gene by a two-step red recombination system, which cloned the DPV Chinese virulent strain (DPV CHv) genome into a bacterial artificial chromosome (DPV CHv-BAC); the proliferation law of LORF5-deleted mutant virus on DEF cells and the effect of LORF5 gene on the life cycle stages of DPV compared with the parent strain were tested. Our data revealed that the LORF5 gene contributes to the cell-to-cell transmission of DPV but is not relevant to virus invasion, replication, assembly, and release formation. Taken together, this study sheds light on the role of the avian herpesvirus-specific gene LORF5 in the DPV proliferation life cycle. These findings lay the foundation for in-depth functional studies of the LORF5 gene in DPV or other avian herpesviruses.

19.
Front Cell Dev Biol ; 9: 728821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733844

RESUMO

Precise regulation of angiogenesis is required for organ development, wound repair, and tumor progression. Here, we identified a novel gene, nxhl (New XingHuo light), that is conserved in vertebrates and that plays a crucial role in vascular integrity and angiogenesis. Bioinformatic analysis uncovered its essential roles in development based on co-expression with several key developmental genes. Knockdown of nxhl in zebrafish causes global and pericardial edema, loss of blood circulation, and vascular defects characterized by both reduced vascularization in intersegmental vessels and decreased sprouting in the caudal vein plexus. The nxhl gene also affects human endothelial cell behavior in vitro. We found that nxhl functions in part by targeting VE-PTP through interaction with NCL (nucleolin). Loss of ptprb (a VE-PTP ortholo) in zebrafish resulted in defects similar to nxhl knockdown. Moreover, nxhl deficiency attenuates tumor invasion and proteins (including VE-PTP and NCL) associated with angiogenesis and EMT. These findings illustrate that nxhl can regulate angiogenesis via a novel nxhl-NCL-VE-PTP axis, providing a new therapeutic target for modulating vascular formation and function, especially for cancer treatment.

20.
Front Immunol ; 12: 751688, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691066

RESUMO

The 5' end of the flavivirus genome contains a type 1 cap structure formed by sequential N-7 and 2'-O methylations by viral methyltransferase (MTase). Cap methylation of flavivirus genome is an essential structural modification to ensure the normal proliferation of the virus. Tembusu virus (TMUV) (genus Flavivirus) is a causative agent of duck egg drop syndrome and has zoonotic potential. Here, we identified the in vitro activity of TMUV MTase and determined the effect of K61-D146-K182-E218 enzymatic tetrad on N-7 and 2'-O methylation. The entire K61-D146-K182-E218 motif is essential for 2'-O MTase activity, whereas N-7 MTase activity requires only D146. To investigate its phenotype, the single point mutation (K61A, D146A, K182A or E218A) was introduced into TMUV replicon (pCMV-Rep-NanoLuc) and TMUV infectious cDNA clone (pACYC-TMUV). K-D-K-E mutations reduced the replication ability of replicon. K61A, K182A and E218A viruses were genetically stable, whereas D146A virus was unstable and reverted to WT virus. Mutant viruses were replication and virulence impaired, showing reduced growth and attenuated cytopathic effects and reduced mortality of duck embryos. Molecular mechanism studies showed that the translation efficiency of mutant viruses was inhibited and a higher host innate immunity was induced. Furthermore, we found that the translation inhibition of MTase-deficient viruses was caused by a defect in N-7 methylation, whereas the absence of 2'-O methylation did not affect viral translation. Taken together, our data validate the debilitating mechanism of MTase-deficient avian flavivirus and reveal an important role for cap-methylation in viral translation, proliferation, and escape from innate immunity.


Assuntos
Fibroblastos/imunologia , Flavivirus/genética , Metiltransferases/deficiência , RNA Viral , Animais , Células Cultivadas , Patos , Embrião não Mamífero , Fibroblastos/virologia , Imunidade Inata , Mesocricetus , Metilação , Metiltransferases/genética , Mutação , Proteínas Virais/genética
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