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1.
Opt Express ; 32(1): 313-324, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175058

RESUMO

Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10 mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.

2.
World J Clin Cases ; 11(29): 7156-7161, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37946754

RESUMO

BACKGROUND: Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia. In recent years, with platelet transfusion increasing, ineffective platelet transfusion has become increasingly prominent. Generally speaking, platelet antibodies can be produced after repeated transfusion, thus rendering subsequent platelet transfusion ineffective. We report a case of first platelet transfusion refractoriness (PTR) in a patient with acute myelocytic leukemia (AML). Due to the rarity of such cases in clinical practice, there have been no relevant case reports so far. CASE SUMMARY: A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d. Her diagnosis was acute myelocytic leukemia [M2 type Fms related receptor tyrosine kinase 3, Isocitrate Dehydrogenase 1, Nucleophosmin 1, Neuroblastoma RAS viral oncogene homolog (+) high-risk group]. She was treated with "IA" (IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5) chemotherapy. When her condition improved, the patient was discharged from the hospital, instructed to take medicine as prescribed by the doctor after discharge, and returned to the hospital for further chemotherapy on time. CONCLUSION: We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy, which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load. This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML. When platelet antibodies are produced, immunoglobulins can be used to block antibodies, thereby reducing platelet destruction. For patients with PTR, both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem.

3.
Front Oncol ; 12: 872503, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646675

RESUMO

Purpose: To establish and verify the ability of a radiomics prediction model to distinguish invasive adenocarcinoma (IAC) and minimal invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs). Methods: We retrospectively analyzed 118 lung GGN images and clinical data from 106 patients in our hospital from March 2016 to April 2019. All pathological classifications of lung GGN were confirmed as IAC or MIA by two pathologists. R language software (version 3.5.1) was used for the statistical analysis of the general clinical data. ITK-SNAP (version 3.6) and A.K. software (Analysis Kit, American GE Company) were used to manually outline the regions of interest of lung GGNs and collect three-dimensional radiomics features. Patients were randomly divided into training and verification groups (ratio, 7:3). Random forest combined with hyperparameter tuning was used for feature selection and prediction modeling. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate model prediction efficacy. The calibration curve was used to evaluate the calibration effect. Results: There was no significant difference between IAC and MIA in terms of age, gender, smoking history, tumor history, and lung GGN location in both the training and verification groups (P>0.05). For each lung GGN, the collected data included 396 three-dimensional radiomics features in six categories. Based on the training cohort, nine optimal radiomics features in three categories were finally screened out, and a prediction model was established. We found that the training group had a high diagnostic efficacy [accuracy, sensitivity, specificity, and AUC of the training group were 0.89 (95%CI, 0.73 - 0.99), 0.98 (95%CI, 0.78 - 1.00), 0.81 (95%CI, 0.59 - 1.00), and 0.97 (95%CI, 0.92-1.00), respectively; those of the validation group were 0.80 (95%CI, 0.58 - 0.93), 0.82 (95%CI, 0.55 - 1.00), 0.78 (95%CI, 0.57 - 1.00), and 0.92 (95%CI, 0.83 - 1.00), respectively]. The model calibration curve showed good consistency between the predicted and actual probabilities. Conclusions: The radiomics prediction model established by combining random forest with hyperparameter tuning effectively distinguished IAC from MIA presenting as GGNs and represents a noninvasive, low-cost, rapid, and reproducible preoperative prediction method for clinical application.

4.
Cell Chem Biol ; 29(8): 1260-1272.e8, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35732177

RESUMO

Programmed cell death protein 1 (PD-1) checkpoint blockade therapy requires the CD28 co-stimulatory receptor for CD8+ T cell expansion and cytotoxicity. However, CD28 expression is frequently lost in exhausted T cells and during immune senescence, limiting the clinical benefits of PD-1 immunotherapy in individuals with cancer. Here, using a cereblon knockin mouse model that regains in vivo T cell response to lenalidomide, an immunomodulatory imide drug, we show that lenalidomide reinstates the anti-tumor activity of CD28-deficient CD8+ T cells after PD-1 blockade. Lenalidomide redirects the CRL4Crbn ubiquitin ligase to degrade Ikzf1 and Ikzf3 in T cells and unleashes paracrine interleukin-2 (IL-2) and intracellular Notch signaling, which collectively bypass the CD28 requirement for activation of intratumoral CD8+ T cells and inhibition of tumor growth by PD-1 blockade. Our results suggest that PD-1 immunotherapy can benefit from a lenalidomide combination when treating solid tumors infiltrated with abundant CD28- T cells.


Assuntos
Antígenos CD28 , Receptor de Morte Celular Programada 1 , Animais , Linfócitos T CD8-Positivos , Fatores Imunológicos , Imunoterapia/métodos , Lenalidomida/farmacologia , Camundongos
5.
Nat Commun ; 12(1): 7003, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853298

RESUMO

Cancer cells acquire genetic heterogeneity to escape from immune surveillance during tumor evolution, but a systematic approach to distinguish driver from passenger mutations is lacking. Here we investigate the impact of different immune pressure on tumor clonal dynamics and immune evasion mechanism, by combining massive parallel sequencing of immune edited tumors and CRISPR library screens in syngeneic mouse tumor model and co-culture system. We find that the core microRNA (miRNA) biogenesis and targeting machinery maintains the sensitivity of cancer cells to PD-1-independent T cell-mediated cytotoxicity. Genetic inactivation of the machinery or re-introduction of ANKRD52 frequent patient mutations dampens the JAK-STAT-interferon-γ signaling and antigen presentation in cancer cells, largely by abolishing miR-155-targeted silencing of suppressor of cytokine signaling 1 (SOCS1). Expression of each miRNA machinery component strongly correlates with intratumoral T cell infiltration in nearly all human cancer types. Our data indicate that the evolutionarily conserved miRNA pathway can be exploited by cancer cells to escape from T cell-mediated elimination and immunotherapy.


Assuntos
Evasão da Resposta Imune , MicroRNAs/metabolismo , Neoplasias , Animais , Linhagem Celular Tumoral , Quimiocinas/metabolismo , Heterogeneidade Genética , Humanos , Imunoterapia , Interferon gama , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Neoplasias/genética , Fosfoproteínas Fosfatases , Receptor de Morte Celular Programada 1 , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina , Linfócitos T
6.
Medicine (Baltimore) ; 98(10): e14566, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30855440

RESUMO

The aim of the present study was to investigate factors affecting ablation effect and safety of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids (UFs).A retrospective analysis of 346 patients with symptomatic UFs who were treated with USgHIFU was performed. All UFs was grouped based on magnetic resonance imaging (MRI) characteristics before HIFU; all adverse events and treatment data were recorded during and after HIFU. One-way analysis of variance and multiple linear regression analysis were used to evaluate the effect of USgHIFU treatment and affecting factors.The results showed that the mean age of patients was 38.3 ±â€Š6.1 years, with the mean nonperfusion volume rate of 74.4 ±â€Š14.7% and the mean energy efficiency factor (EEF) of 7.2 ±â€Š4.8 J/mm. Except for the size group, the ablation rate was significantly different (P < .001); and the anterior, intramural, hypointense (T2WI), and mild enhancement (T1WI contrast enhancement) UFs had the highest ablation rate. The EEF of the anterior, intramural, hypointense (T2WI), mild enhancement (T1WI contrast enhancement), and >5 cm UFs had minimum value, with a statistically significant difference (P < .01). According to multiple linear regression model, the distance from the UFs ventral side to the skin, enhancement type on T1WI, size of UFs, signal intensity on T2WI, location of UFs, type and volume of fibroids all had a line relationship with EEF, and the enhancement type on T1WI was the greatest factor affecting the ablation effect. Some patients (37.6%) had thermal injury of the sacrum on MRI, but no serious adverse events were observed.Our results suggest that USgHIFU can be safely used and have a promising prospect for treating UFs, even though its effect may be affected by anatomical features, tissue characteristics, and blood supply.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma/diagnóstico por imagem , Leiomioma/terapia , Ultrassonografia de Intervenção , Adulto , Feminino , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia de Intervenção/métodos , Útero/diagnóstico por imagem , Adulto Jovem
7.
Int J Hyperthermia ; 36(1): 21-28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30428744

RESUMO

PURPOSE: We investigated the risk factors influencing MR changes associated with sacral injury from ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. METHODS: We retrospectively analyzed a total of 346 patients with symptomatic uterine fibroids who received USgHIFU ablation. All of the patients underwent contrast-enhanced magnetic resonance imaging (CE-MRI) before and after treatment. Injury to the sacrum was set as the dependent variable, while fibroid features and the treatment parameters were set as independent variables. These variables were used to assess respectively their correlation with sacral injury by using univariate and multivariate analyses. RESULTS: The results of univariate analysis revealed that the volume, distance from the fibroid to the skin, maximal diameter, distance from the fibroid to the sacrum, fibroid types, degree of enhancement, therapeutic dosimetry (TD), energy efficiency factor (EEF) and non-perfused volume (NPV) ratio manifested significant correlations with the sacral injury (p < .05). Multivariate analysis showed that the degree of enhancement, TD and EEF were independent risk factors for sacral injury (p < .05), while the distance from fibroid to sacrum and intramural or subserosal types were protective factors (p < .05). The incidence of sacral tail pain and leg pain showed a significant positive correlation with sacral injury (p < .05). CONCLUSION: As important affecting factors, the degree of enhancement, distance from fibroid to sacrum and fibroid types all possess significant correlations with MR changes associated with sacral injury.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Leiomioma/complicações , Leiomioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sacro/diagnóstico por imagem , Sacro/fisiopatologia , Adulto , Feminino , Humanos , Leiomioma/patologia , Estudos Retrospectivos
8.
Int J Hyperthermia ; 35(1): 534-540, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30428735

RESUMO

OBJECTIVE: To investigate factors affecting effects of ultrasound guided high intensity focused ultrasound (USgHIFU) in the treatment of single uterine fibroids (UFs) with different magnetic resonance imaging (MRI) features. METHODS: A total of 207 patients with single symptomatic UFs who were treated with HIFU were retrospectively analyzed. All UFs were grouped according to MRI features, and factors affecting HIFU ablation were set as independent variables. Non-perfusion volume ratio (NPVR) and energy efficiency factor (EEF) were set as dependent variables to establish multiple linear regression models with a stepwise method. RESULTS: All patients had successful HIFU treatment, with the mean NPVR of 74.7 ± 15.1% and the mean EEF of 7.4 ± 5.2 j/mm3. The NPVR was negatively correlated with transmural type of UFs, hyperintense on T2 weighted image (T2WI), enhancement type on T1 weighted image (T1WI), distance from UFs ventral side to skin and posterior location of UFs, but positively correlated with anterior location of UFs, hypointense on T2WI and anteverted uterus (uterine location). The EEF was negatively correlated with size, anterior location of UFs and hypointense on T2WI, but positively correlated with distance from UFs ventral side to skin, enhancement type on T1WI and transmural type of UFs. The UFs size and enhancement type on T1WI were the greatest factors affecting the ablation effect. CONCLUSIONS: The effect of HIFU treatment for single UFs is affected by multiple factors, and the UFs of hypointense on T2WI, large size, mild enhancement on T1WI and anteverted uterus can be easily ablated with high ablation efficiency.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Leiomioma/cirurgia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
Oncotarget ; 7(46): 75064-75080, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27634894

RESUMO

Porcine epidemic diarrhea is a devastating swine enteric disease, which is caused by porcine epidemic diarrhea virus (PEDV) infection. Our studies demonstrated that PEDV infection resulted in the up-regulation of proinflammatory cytokines. Meanwhile, PEDV infection and overexpression of viral nucleoprotein resulted in the acetylation and release of high mobility group box 1 proteins in vitro, an important proinflammatory response mediator, which contributes to the pathogenesis of various inflammatory diseases. Our studies also showed that SIRT1, histone acetyltransferase, and NF-κB regulated the acetylation and release of HMGB1. Chromatin immunoprecipitation, dual-luciferase reporter gene assay, and co-immunoprecipitation experiments illustrated that PEDV-N could induce HMGB1 transcription by interacting with C/EBP-ß, which could bind to C/EBP motif in HMGB1 promotor region. Collectively, our data indicate PEDV-N contributes to HMGB1 transcription and the subsequent release/acetylation of HMGB1 during PEDV infection.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Regulação da Expressão Gênica , Proteína HMGB1/genética , Nucleoproteínas/metabolismo , Vírus da Diarreia Epidêmica Suína/fisiologia , Transcrição Gênica , Acetilação , Animais , Sítios de Ligação , Biomarcadores , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/genética , Citocinas/metabolismo , Proteína HMGB1/metabolismo , Histona Acetiltransferases/metabolismo , Mediadores da Inflamação/metabolismo , NF-kappa B/metabolismo , Motivos de Nucleotídeos , Regiões Promotoras Genéticas , Ligação Proteica , Sirtuína 1/metabolismo , Células Vero
10.
Arch Virol ; 161(9): 2491-501, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27357231

RESUMO

Newcastle disease (ND) is a contagious disease that affects most species of birds. Its causative pathogen, Newcastle disease virus (NDV), also exhibits considerable oncolytic activity against mammalian cancers. A better understanding of the pathogenesis of NDV will help us design efficient vaccines and novel anticancer strategies. GW3965, a widely used synthetic ligand of liver X receptor (LXR), induces the expression of LXRs and its downstream genes, including ATP-binding cassette transporter A1 (ABCA1). ABCA1 regulates cellular cholesterol homeostasis. Here, we found that GW3965 inhibited NDV infection in DF-1 cells. It also inhibited NF-κB activation and reduced the upregulation of proinflammatory cytokines induced by the infection. Further studies showed that GW3965 exerted its inhibitory effects on virus entry and replication. NDV infection increased the mRNA levels of several lipogenic genes but decreased the ABCA1 mRNA level. Overexpression of ABCA1 inhibited NDV infection and reduced the cholesterol content in DF-1 cells, but when the cholesterol was replenished, NDV infection was restored. GW3965 treatment prevented cholesterol accumulation in the perinuclear area of the infected cells. In summary, our studies suggest that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis.


Assuntos
Benzoatos/farmacologia , Benzilaminas/farmacologia , Colesterol/metabolismo , Fibroblastos/virologia , Homeostase/efeitos dos fármacos , Vírus da Doença de Newcastle/efeitos dos fármacos , Animais , Antivirais/farmacologia , Linhagem Celular , Galinhas , Citocinas/genética , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
11.
Biochem Biophys Res Commun ; 475(2): 230-7, 2016 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-27208778

RESUMO

The causative agent of porcine reproductive and respiratory syndrome is the PRRS virus (PRRSV), an enveloped, single-stranded and positive-sense RNA virus. The host factors and mechanisms that are involved in PRRSV entry are still largely unknown. In our present studies, we found that syndecan-4, one of the heparan sulfate proteoglycans, plays a critical role in PRRSV entry, especially in PRRSV attachment. Moreover, EGFR interacts with syndecan-4 in MACR-145 cells and disruption of their interaction impaired PRRSV entry. Furthermore, EGFR inhibitor AG1478 or syndecan-4 derived peptide SSTN87-131 inhibited syndecan-4 endocytosis induced by PRRSV entry. Altogether, syndecan-4, a PRRSV attachment factor, mediated PRRSV entry by interacting with EGFR.


Assuntos
Receptores ErbB/metabolismo , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Suínos/virologia , Sindecana-4/metabolismo , Animais , Linhagem Celular , Endocitose , Interações Hospedeiro-Patógeno , Síndrome Respiratória e Reprodutiva Suína/fisiopatologia , Mapas de Interação de Proteínas , Suínos/metabolismo , Ligação Viral , Internalização do Vírus
12.
Vet Res ; 47: 50, 2016 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-27089967

RESUMO

Streptococcus equi ssp. zooepidemicus (S. equi spp. zooepidemicus) is an opportunistic pathogen that causes major economic losses in the swine industry in China and is also a threat for human health. Biofilm formation by this bacterium has been previously reported. In this study, we used an immunoproteomic approach to search for immunogenic proteins expressed by biofilm-grown S. equi spp. zooepidemicus. Seventeen immunoreactive proteins were found, of which nine common immunoreactive proteins were identified in planktonic and biofilm-grown bacteria. The immunogenicity and protective efficacy of the S. equi spp. zooepidemicus immunoreactive GroEL chaperone protein was further investigated in mice. The protein was expressed in vivo and elicited high antibody titers following S. equi spp. zooepidemicus infections of mice. An animal challenge experiment with S. equi spp. zooepidemicus showed that 75% of mice immunized with the GroEL protein were protected. Using in vitro biofilm inhibition assays, evidence was obtained that the chaperonin GroEL may represent a promising target for the prevention and treatment of persistent S. equi spp. zooepidemicus biofilm infections. In summary, our results suggest that the recombinant GroEL protein, which is involved in biofilm formation, may efficiently stimulate an immune response, which protects against S. equi spp. zooepidemicus infections. It may therefore be a candidate of interest to be included in vaccines against S. equi spp. zooepidemicus infections.


Assuntos
Proteínas de Bactérias/genética , Biofilmes , Chaperonina 60/genética , Streptococcus equi/fisiologia , Animais , Anticorpos Antibacterianos , Proteínas de Bactérias/imunologia , Chaperonina 60/imunologia , Feminino , Imunização , Imunoproteínas/genética , Imunoproteínas/imunologia , Camundongos , Camundongos Endogâmicos ICR , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Streptococcus equi/genética , Streptococcus equi/imunologia
13.
Methods Mol Biol ; 1349: 163-75, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26458836

RESUMO

Poxvirus-vectors have been widely used in vaccine development for several important human and animal diseases; some of these vaccines have been licensed and used extensively. Swinepox virus (SPV) is well suited to develop recombinant vaccines because of its large packaging capacity for recombinant DNA, its host range specificity, and its ability to induce appropriate immune responses.


Assuntos
Suipoxvirus/genética , Vacinação/métodos , Vacinas Sintéticas/genética , Animais , DNA Recombinante/genética , DNA Recombinante/imunologia , Vetores Genéticos , Humanos , Suipoxvirus/imunologia , Vacinação/veterinária , Vacinas Sintéticas/biossíntese
14.
Appl Microbiol Biotechnol ; 99(24): 10639-54, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26278540

RESUMO

Autotransporters (ATs) are associated with pathogenesis of Avian Pathogenic Escherichia coli (APEC). The molecular characterization of APEC ATs can provide insights about their relevance to APEC pathogenesis. Here, we characterized a conventional autotransporter UpaB in APEC DE205B genome. The upaB existed in 41.9 % of 236 APEC isolates and was predominantly associated with ECOR B2 and D. Our studies showed that UpaB mediates the DE205B adhesion in DF-1 cells, and enhances autoaggregation and biofilm formation of fimbria-negative E. coli AAEC189 (MG1655Δfim) in vitro. Deletion of upaB of DE205B attenuates the virulence in duck model and early colonization in the duck lungs during APEC systemic infection. Furthermore, double and triple deletion of upaB, aatA, and aatB genes cumulatively attenuated DE205B adhesion in DF-1 cells, accompanying with decreased 50 % lethal dose (LD50) in duck model and the early colonization in the duck lungs. However, DE205BΔupaB/ΔaatA/ΔaatB might "compensate" the influence of gene deletion by upregulating the expression of fimbrial adhesin genes yqiL, yadN, and vacuolating autotransporter vat during early colonization of APEC. Finally, we demonstrated that vaccination with recombinant UpaB, AatA, and AatB proteins conferred protection against colisepticemia caused by DE205B infection in duck model.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Doenças das Aves/patologia , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Escherichia coli/patogenicidade , Deleção de Genes , Proteínas de Membrana Transportadoras/genética , Fatores de Virulência/genética , Animais , Aderência Bacteriana , Proteínas da Membrana Bacteriana Externa/metabolismo , Doenças das Aves/microbiologia , Patos , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/metabolismo , Dose Letal Mediana , Pulmão/microbiologia , Proteínas de Membrana Transportadoras/metabolismo , Virulência
15.
Arch Virol ; 160(7): 1621-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25896095

RESUMO

It is well known that many viruses use heparan sulfate as the initial attachment factor. In the present study, we determined whether porcine epidemic diarrhea virus (PEDV), an emerging veterinary virus, infects Vero cells by attaching to heparan sulfate. Western blot analysis, real-time PCR, and plaque formation assay revealed that PEDV infection was inhibited when the virus was pretreated with heparin (an analogue of heparan sulfate). There was no inhibitory effect when the cells were pre-incubated with heparin. We next demonstrated that enzymatic removal of the highly sulfated domain of heparan sulfate by heparinase I treatment inhibited PEDV infection. We also confirmed that sodium chlorate, which interferes with heparan sulfate biosynthesis, also inhibited PEDV infection. Furthermore, we examined the effect of two heparin derivatives with different types of sulfation on PEDV infection. The data suggested de-N-sulfated heparin, but not N-acetyl-de-O-sulfated heparin, inhibits PEDV infection. In summary, our studies revealed that heparan sulfate acts as the attachment factor of PEDV in Vero cells.


Assuntos
Infecções por Coronavirus/veterinária , Heparitina Sulfato/metabolismo , Vírus da Diarreia Epidêmica Suína/fisiologia , Receptores Virais/metabolismo , Doenças dos Suínos/virologia , Ligação Viral , Animais , Chlorocebus aethiops , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Vírus da Diarreia Epidêmica Suína/genética , Suínos , Doenças dos Suínos/metabolismo , Células Vero
16.
Antiviral Res ; 117: 99-109, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25746333

RESUMO

Lithium chloride (LiCl) has been used as a mood stabilizer in the manic depressive disorders treatment. Recent studies show that LiCl is also a potent inhibitor for some DNA and RNA viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) is an important viral pathogen in modern pig industry. In this study, we assessed the inhibitory effect of LiCl on PRRSV infection using plaque-formation assay, Q-PCR and Western blot analysis. Our results showed that LiCl could inhibit PRRSV infection in MARC-145 and PAM-CD163 cells. Previous reports have shown that LiCl could induce the Wnt pathway in the absence of Wnt ligands. In our studies, we demonstrated that LiCl activates the Wnt pathway in PRRSV infected cells. Additionally, the knockdown of ß-catenin or the Wnt/ß-catenin pathway inhibitor PNU74654 was able to reverse the antiviral effect of LiCl, which suggested that the inhibitory effect of LiCl against PRRSV replication might be associated with the activation of the Wnt/ß-catenin pathway. We also found that lower viral replication after LiCl treatment was associated with the reduced mRNA levels of pro-inflammatory IL-8, IL-6, IL-1 ß, tumor necrosis factor α and decreased NF-κB nuclear translocation. Collectively, our data demonstrated that LiCl inhibited PRRSV infection by enhancing Wnt/ß-catenin pathway and suppressing pro-inflammatory responses.


Assuntos
Antivirais/farmacologia , Cloreto de Lítio/farmacologia , Macrófagos Alveolares/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Vírus da Síndrome Respiratória e Reprodutiva Suína/crescimento & desenvolvimento , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Western Blotting , Linhagem Celular , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/ultraestrutura , Transporte Proteico/efeitos dos fármacos , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacos , Via de Sinalização Wnt/genética , beta Catenina/genética
17.
Biochem Biophys Res Commun ; 458(2): 392-8, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25660453

RESUMO

CD163 and sialoadhesin had been reported as the two receptors for porcine reproductive and respiratory syndrome virus (PRRSV) infection. The signaling pathway activated by PRRSV entry was seldom reported. In our studies, we demonstrated that PRRSV entry triggers FAK, PI3K, AKT and Rac1 activation. The signaling pathway FAK-PI3K-AKT-Rac1 is essential for PRRSV entry. Blocking FAK by PF573228 attenuates the activation of PI3K, AKT, Rac1 and the cytoskeleton remodeling induced by virus entry. Inhibitors to FAK, PI3K, AKT and Rac1 can significantly inhibit the virus entry. In conclusion, our observations reveal that PRRSV triggers the activation of FAK-PI3K-AKT-Rac1 signaling pathway to facilitate its entry into cells.


Assuntos
Fosfotransferases/metabolismo , Síndrome Respiratória e Reprodutiva Suína/enzimologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Suínos/metabolismo , Suínos/virologia , Internalização do Vírus , Animais , Quinase 1 de Adesão Focal/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo
18.
Microbiol Res ; 169(9-10): 666-74, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24813303

RESUMO

Streptococcus suis (SS) is an important zoonotic pathogen causing a variety of life-threatening infections in pigs and humans. Tran, a novel transcriptional regulator which was identified to be an infection-related factor in S. suis serotype 2 using suppression subtractive hybridization (SSH), has been reported by our group. In this study, a tran deletion mutant was constructed to compare with the wild-type ZY05719 in some biological characteristics. It is suggested that longer chains and relatively slower growth could be observed in tran deletion mutants. In order to identify gene transcription profiles, microarray analysis was performed. It indicated that the inactivation of Tran led to 130 differentially expressed genes spread throughout the genome. Among these, 21 genes were upregulated, and 109 genes were downregulated. Most of the differentially expressed genes were involved in bacterial metabolism, such as the phosphotransferase system (PTS), and heat shock proteins. In the case of glucose scarcity, the growth characteristics of tran deletion mutants were impacted significantly, meanwhile Δtran mutant was highly sensitive to environmental stresses. Moreover, cell adherence decreased by 22.2%, and virulence in zebrafish declined to more than five times in Δtran mutants. These data demonstrate the role of Tran in regulation in S. suis serotype 2, that is affect bacterial virulence by influencing bacterial metabolism and stress tolerance of external environment.


Assuntos
Regulação Bacteriana da Expressão Gênica , Redes e Vias Metabólicas , Streptococcus suis/fisiologia , Streptococcus suis/patogenicidade , Estresse Fisiológico , Fatores de Transcrição/metabolismo , Animais , Aderência Bacteriana , Modelos Animais de Doenças , Deleção de Genes , Perfilação da Expressão Gênica , Células Hep G2 , Humanos , Análise em Microsséries , Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Streptococcus suis/metabolismo , Fatores de Transcrição/genética , Virulência , Peixe-Zebra/microbiologia
19.
Acta Crystallogr C Struct Chem ; 70(Pt 5): 502-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24816022

RESUMO

Two novel polymers exhibiting metal-organic frameworks (MOFs) have been synthesized by the combination of a metal ion with a benzene-1,3,5-tricarboxylate ligand (BTC) and 1,10-phenanthroline (phen) under hydrothermal conditions. The first compound, poly[[(µ4-benzene-1,3,5-tricarboxylato-κ(4)O:O':O'':O''')(µ-hydroxido-κ(2)O:O)bis(1,10-phenanthroline-κ(2)N,N')dizinc(II)] 0.32-hydrate], {[Zn2(C9H3O6)(OH)(C12H8N2)2]·0.32H2O}n, denoted Zn-MOF, forms a two-dimensional network in which a binuclear Zn2 cluster serves as a 3-connecting node; the BTC trianion also acts as a 3-connecting centre. The overall topology is that of a 6(3) net. The phen ligands serve as appendages to the network and interdigitate with phen ligands belonging to adjacent parallel sheets. The second compound, poly[[(µ6-benzene-1,3,5-tricarboxylato-κ(7)O(1),O(1'):O(1):O(3):O(3'):O(5):O(5'))(µ3-hydroxido-κ(2)O:O:O)(1,10-phenanthroline-κ(2)N,N')dimanganese(II)] 1.26-hydrate], {[Mn2(C9H3O6)(OH)(C12H8N2)]·1.26H2O}n, denoted Mn-MOF, exists as a three-dimensional network in which an Mn4 cluster serves as a 6-connecting unit, while the BTC trianion again plays the role of a 3-connecting centre. The overall topology is that of the rutile net. Phen ligands act as appendages to the network and form the `S-shaped' packing mode.

20.
Vet Microbiol ; 171(1-2): 198-205, 2014 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-24726504

RESUMO

To develop a vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection, the genes of porcine IL-18, capsid protein (Cap) of PCV2 and M-like protein (SzP) of SEZ were inserted into the swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox virus rSPV-ICS was verified by PCR and indirect immunofluorescence assays. To evaluate the immunogenicity of rSPV-ICS, 28 PCV2 and SEZ seronegative Bama minipigs were immunized with rSPV-ICS (n=8), commercial PCV2 vaccine and SEZ vaccine (n=8) or wild type SPV (n=8). The results showed that SzP-specific antibody and PCV2 neutralizing antibody of the rSPV-ICS immunized group increased significantly compared to the wild type SPV treated group after vaccination and increased continuously over time. The levels of IL-4 and IFN-γ in the rSPV-ICS immunized group were significantly higher than the other three groups, respectively. After been co-challenged with PCV2 and SEZ, 87.5% piglets in rSPV-ICS immunized group were survived. Significant reductions in gross lung lesion score, histopathological lung lesion score, and lymph node lesion score were noticed in the rSPV-ICS immunized group compared with the wtSPV treated group. The results suggested that the recombinant rSPV-ICS provided piglets with significant protection against PCV2-SEZ co-infection; thus, it offers proof-of-principle for the development of a vaccine for the prevention of these swine diseases.


Assuntos
Vacinas Bacterianas , Infecções por Circoviridae/veterinária , Imunização/veterinária , Infecções Estreptocócicas/veterinária , Doenças dos Suínos/prevenção & controle , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/normas , Infecções por Circoviridae/complicações , Infecções por Circoviridae/patologia , Infecções por Circoviridae/prevenção & controle , Circovirus/genética , Circovirus/imunologia , Coinfecção , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/patologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus equi/genética , Streptococcus equi/imunologia , Suipoxvirus/genética , Suínos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas Virais/genética , Vacinas Virais/imunologia , Vacinas Virais/normas
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