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1.
J Cell Mol Med ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32410294

RESUMO

Non-alcoholic fatty liver disease is a public health problem worldwide associated with high morbidity and hepatic steatosis, but no effective therapeutic interventions. Magnesium isoglycyrrhizinate (MGIG), a derivative of an active component of Glycyrrhiza glabra, is widely used for the treatment of inflammatory liver diseases due to its potent anti-inflammatory and hepatoprotective activities. Hence, this study aimed to study the effects of MGIG on hepatic steatosis in mice fed a high-fat diet (HFD). Oil Red O staining and transmission electron microscopy revealed a decrease in lipid accumulation in the liver after MGIG treatment along with improved mitochondrial ultramicrostructures. Metabonomic analysis demonstrated that MGIG intervention increased glutamate utilization in mitochondria by promoting the uptake of glutamate into the tricarboxylic acid (TCA) cycle. The NAD+ /NADH ratio and the expression of other lipid-metabolism-related genes were increased in MGIG-treated livers. Transcriptome sequencing showed that the expression of TLR4, an isoform of the innate immunity Toll-like receptors (TLRs), was significantly decreased after MGIG treatment, suggesting a link between the anti-inflammatory effects of MGIG and its suppression of lipidation. Our results reveal the potent effects of MGIG on lipid metabolism and suggest that hepatic TLR4 might be a crucial therapeutic target to regulate energy homeostasis in hepatic steatosis.

2.
J Infect Public Health ; 13(5): 730-736, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32005617

RESUMO

BACKGROUND: Candida auris can form long-lasting colonies in the hospital environment and on human skin. There is limited evidence regarding the efficacy of different methods and products for disinfecting hospitals and colonized patients to prevent the spread of C. auris. METHODS: The minimum inhibitory concentration of three disinfectant products ("84" disinfectant, IodineTincture disinfectant, and quaternary ammonium) and 75% ethanol against C. auris and other Candida species were measured. A pig skin model was used to evaluate the efficacy of three hand hygiene products in killing pathogens. The killing effect of ultraviolet-C (253.7 nm) and the LK/CXD bed unit ozone disinfection machine on C. auris was also evaluated. RESULTS: Thirty seconds of pig skin washing with bacteriostatic hand sanitizer followed by drying and 15 s of ethanol-based gel can completely eradicate the colonization of C. auris (3.00 log10 CFU). The antifungal activity of ultraviolet-C to C. auris inoculated on bed sheets was significantly reduced (P < 0.01) at a distance of 1 m. Candida glabrata and C. auris showed greater resistance to ozone than other Candida species. The ozone could completely eradicate C. auris (3.60 log10 CFU) on bed sheets at dosage of 300 mg/m3 for 40 min of exposure. CONCLUSIONS: We recommend extending the disinfection times of ultraviolet-C and ozone and emphasizing the effectiveness of washing skin with soap, drying skin, and then applying an ethanol-based gel to remove C. auris from skin.

3.
J Virol Methods ; 276: 113791, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31778678

RESUMO

Following the recommended use of the inactivated poliovirus vaccine from Sabin strains (sIPV) by the WHO, a D antigen-specific neutralizing monoclonal antibody (mAb) 1G10 that recognized the human poliovirus type 1 Sabin strain (PV-I Sabin) was produced for D-antigen potency evaluation on sIPV. Study of the mAb 1G10 showed that it recognized a discontinuous conformational epitope of PV-I Sabin antigen. To identify this epitope quickly, easily and cost-effectively, clues to the epitope's identity were first obtained by employing a novel mimotope strategy based on a phage display library and "in silico" prediction. Then, the conformation of the epitope region, including the amino acid sequence, neutralizing sites, and location of this epitope, was identified using several classic epitope-mapping methods such as synthesized peptides analysis, neutralization assay and site-directed mutagenesis. The mimotope strategy may offer some guidance for achieving epitope identification in a more feasible and effective way. This mAb could be used in an in-house or national and international standard IPV D-antigen potency ELISA kit in the future.

4.
Dentomaxillofac Radiol ; 49(2): 20190295, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31617748

RESUMO

OBJECTIVE: To date, imaging and non-invasive examination methods for evaluating the oral tissue of patients who with oral chronic graft-versus-host disease (GVHD) are still lacking. Herein, we assessed the ultrasonography imaging characteristics of chronic GVHD patients' buccal soft tissue and evaluated the response to treatment using gray-scale and power Doppler (PD) ultrasound. The overall objective of the study was to determine the potential of ultrasonography to provide an early and objective indication of a therapeutic response to treatment intervention in oral chronic GVHD. METHODS: Buccal mucosa in 21 patients with clinically diagnosis of oral chronic GVHD were assessed before and after 14 day treatment between 2016 and 2018. Ultrasonography assessment included thickness and echogenicity evaluation, and PD. Echogenicity and PD were measured and scored according to a semi-quantitative method. Ultrasonography parameters were compared with clinical activity assessments of disease activity and patient-reported measures. RESULTS: Following 14 day therapy, a significant decrease in PD scores and patient-reported measures was observed (p < 0.01), and clinical assessment scores also decreased (p < 0.05). Changes from baseline PD scores correlated significantly with patient-reported measures (r = 0.85, p < 0.01). Changes in PD scores correlated moderately with the changes in the clinical assessments from baseline (r = 0.46, p < 0.05). A significant decrease in PD scores was observed in the buccal soft tissue of patients that responded clinically to the treatment. A significant decrease in PD scores was also observed in patients that were failed to show clinical improvement (p < 0.05). CONCLUSION: Ultrasonography is a novel and feasible imaging technique for measurement of the response of oral chronic GVHD to therapy. Ultrasonography yields additional information about buccal mucosa and is a complementaty to clinical examination.


Assuntos
Doença Enxerto-Hospedeiro , Doenças da Boca , Ultrassonografia Doppler , Doença Crônica , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Humanos , Doenças da Boca/diagnóstico por imagem , Mucosa Bucal , Estudos Prospectivos
5.
J Innate Immun ; : 1-17, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31865314

RESUMO

Toll-like receptor 3 (TLR3) is a sensor of endogenous cell necrosis during the process of acute inflammation. Interleukin (IL)-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine and can negatively regulate the pathogenesis of inflammation. However, whether and how activation of TLR3 can regulate IL-1Ra expression has not been clarified. Here, we show that poly(I:C) induces IL-1Ra expression in primarily cultured human fibroblast-like synoviocytes and other types of cells. Induction of IL-1Ra by poly(I:C) was dependent on TLR3, but was independent of melanoma differentiation--associated protein 5 or retinoic acid-inducible gene I. Interferon regulatory factor 3 (IRF3) directly binds to the IL-1Ra promoter and promotes IL-1Ra expression in response to poly(I:C) stimulation. Induction of IL-1Ra by poly(I:C) was abolished by the inhibition of the NF-κB signaling, attenuated by the inhibition of the PI3K-Akt signaling, enhanced by inhibition of the ERK1/2 or MSK1/2 activation, but was independent of the p38 MAPK signaling. Treatment with poly(I:C) or Sendai virus elevated the levels of serum IL-1Ra in wild-type, but not in TLR3-/- or IRF3-/- mice. Our findings may provide new insights into the intrinsic anti-inflammatory function of TLR3 and double-stranded RNA-induced IL-Ra expression by TLR3 and its regulation.

6.
Br J Pharmacol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724152

RESUMO

BACKGROUND AND PURPOSE: Immunosuppressive drugs have shown great promise in treating autoimmune diseases in recent years. A series of novel oxazole derivatives were screened for their immunosuppressive activity. PO-322 [1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)] was identified as the most effective of these compounds. Here, we have investigated the mechanism(s) underlying the inhibition of T-cell proliferation in vitro by PO-322, as well as its effects on the delayed-type hypersensitivity (DTH) response and imiquimod-induced dermatitis in vivo. EXPERIMENTAL APPROACH: T-cell proliferation and apoptosis were analysed with flow cytometry. Cell viability was assessed with a CCK-8 assay. Protein kinase activity was assessed by SelectScreen Kinase Profiling Services. The phosphorylation of signal-regulated molecules was measured by Western blot. Cytokine levels were determined by elisa. The effect of PO-322 on DTH and imiquimod-induced dermatitis was evaluated in BALB/c mice. KEY RESULTS: PO-322 inhibited human T-cell proliferation with anti-CD3/anti-CD28 mAbs or alloantigen without significant cytotoxicity. Importantly, PO-322 was a selective inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1) and decreased NDRG1 phosphorylation but not p70S6K, STAT5, Akt, or ERK1/2 phosphorylation. Furthermore, PO-322 inhibited IFN-γ, IL-6, and IL-17 expression but not IL-10 expression. Finally, treatment with PO-322 was safe and effective for ameliorating the DTH response and imiquimod-induced dermatitis in mice. CONCLUSIONS AND IMPLICATIONS: PO-322 exerted immunosuppressive activity in vitro and in vivo by selectively inhibiting SGK1 activity. PO-322 represents a potential lead compound for the design and development of new drugs for the treatment of autoimmune diseases.

7.
Int Immunopharmacol ; 75: 105774, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351363

RESUMO

BACKGROUND: The purpose of the present study was to evaluate the protective effect of Magnesium Isoglycyrrhizinate (MI) on Epirubicin (EPI)-induced hepatic encephalopathy (HE) and explore its underlying mechanism. METHODS: Mice were divided randomly into groups for treatments as follows: control group, EPI group (Model group), EPI + MI (25, 50 mg/kg) group. Morris water maze test were conducted to evaluate the spatial learning and memory ability. The serum and hippocampus levels of oxidative stress or inflammation were uncovered with the detection of superoxide dismutase (SOD), malondialdehyde (MDA), and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α). RESULTS: As a result, treatment with MI effectively ameliorated the EPI-induced decline in the ability of spatial learning and memory. MI also significantly relieved the severity of oxidative stress or inflammation in serum and hippocampus, which was accompanied with regulating liver functional parameters. Western blot data demonstrated that administration of MI could regulate the redox-related expressions of Txnip, Trx, Nrf2, HO-1, p-IκB-α, p-NF-κB, Caspase-3, Caspase-9, Bax and Bcl-2 in EPI-stimulated hepatic encephalopathy (HE). And the potency of MI treatments on Nrf2, NF-κB expression was also confirmed with immunohistochemical analysis. CONCLUSIONS: Taken together, the protective effect of Magnesium Isoglycyrrhizinate on EPI-induced hepatic encephalopathy might be mediated via the Txnip/Nrf2/NF-κB signaling pathway.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Epirubicina/efeitos adversos , Encefalopatia Hepática/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Proteínas de Transporte/imunologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/imunologia , Citocinas/sangue , Citocinas/imunologia , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/imunologia , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Masculino , Malondialdeído/sangue , Malondialdeído/imunologia , Memória/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Fármacos Neuroprotetores/farmacologia , Saponinas/farmacologia , Aprendizagem Espacial/efeitos dos fármacos , Superóxido Dismutase/sangue , Superóxido Dismutase/imunologia , Tiorredoxinas/imunologia , Triterpenos/farmacologia
8.
J Chem Phys ; 150(22): 224305, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31202252

RESUMO

The possibility of laser cooling of bismuth hydride (BiH) molecules has been investigated based on high-level ab initio calculations by considering the core-valence and the spin-orbit coupling (SOC) effects. The potential energy curves of the 12 Λ-S states as well as the 25 Ω states that split from them via SOC are obtained by multireference configuration interaction plus the Davidson correction. The properties of b-X transition are investigated. Based on our calculations, we show that the transition between Ω states b0+-X10+ of BiH is a possible candidate for laser cooling, with consideration of the intermediate Ω state X21. An optical cycling scheme is proposed by utilizing four lasers at wavelengths around 471 and 601 nm with 5400 cycles for photon absorption/emission and a sub-microkelvin temperature. Our study should shed some light on searching for possible molecular candidates for laser cooling with the existence of an intermediate electronic state.

9.
J Phys Chem A ; 123(16): 3435-3440, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30951309

RESUMO

HS2 molecules play an important role in the photochemical processes in combustion, atmosphere, and interstellar medium, yet our knowledge about the electronic excited states in the UV region is limited. In this study, we perform high-level ab initio calculations on electronic states of HS2 using the internally contracted multireference configuration interaction method including the Davidson correction (icMRCI + Q) method. The vertical transition energies, oscillator strengths, electron configurations, and transitions of thirteen electronic states of HS2 with energy up to 8 eV are calculated at the icMRCI + Q/aug-cc-pv(5 + d)Z level. Based on the calculated potential energy curves, we investigate the interaction and photodissociation mechanism of the electronic states, which should shed some light on the decomposition processes of the gas-phase HS2 molecules in the ultraviolet region.

10.
Ultrasound Med Biol ; 45(5): 1297-1305, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826154

RESUMO

The aim of the work described here was to compare intra-oral and transcutaneous ultrasonography (US) scanning and to determine the normal values of buccal mucosa thickness and echogenicity. A total of 190 volunteers underwent US examination of the buccal mucosa. The thickness of the buccal epithelial layer was recorded in 19 subjects via both intra-oral and transcutaneous methods. Overall, 171 healthy adults were examined through intra-oral US. Buccal epithelial layer measurement was unreliable via the transcutaneous method (p = 0.001). The mean time required for visualizing the buccal mucosa was 75 and 171s with intra-oral and transcutaneous US, respectively (p < 0.001). The thickness of the buccal epithelial layers significantly differed with age and sex (p < 0.001), and was positively correlated with height, weight and body surface area. Intra-oral US was proposed as a conventional method for examination of the buccal mucosa. Normal buccal epithelial thickness in adults is associated with age, sex, height, weight and body surface area.


Assuntos
Mucosa Bucal/anatomia & histologia , Ultrassonografia/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estatura , Índice de Massa Corporal , Superfície Corporal , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/diagnóstico por imagem , Estudos Prospectivos , Valores de Referência , Fatores Sexuais , Adulto Jovem
11.
Microb Drug Resist ; 25(6): 855-864, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30767721

RESUMO

Aquatic animals are now recognized to be major hosts of potentially pathogenic Laribacter hongkongensis. A comparative study was carried out among extended-spectrum ß-lactamase (ESBL)-producing L. hongkongensis isolated from frogs (47 isolates) and fish (41 isolates) to examine phenotypic and genotypic antimicrobial resistance profiles, integrons, virulence factors, and genetic relatedness. Isolates from frogs showed a higher incidence of antibiotic resistance compared with those from fish for most of the antimicrobials tested, especially trimethoprim-sulfamethoxazole, tetracycline, ciprofloxacin, levofloxacin, and streptomycin. Multidrug-resistant strains were also found more frequently among frog isolates (5.44 traits on average) than among fish isolates (3.29 traits). In frog isolates, class 1 integrons and the resistance genes sul1, sul2, tetA, tetR, and aac(6')-Ib-cr showed a clearly higher incidence compared with isolates from fish. In contrast, blaTEM-1 was higher in fish isolates than in frog isolates. Correlation analysis showed that sul1, sul2, tetA, and tetR were significantly associated with class 1 integrons in frog isolates. The correlations indicated a potential co-selection risk of bacterial resistance to antibiotics. In addition, the distribution of three virulence-associated determinants for the type IV bundle-forming pili gene (bfpA), ferric aerobactin receptor gene (iucD), and iron-responsive element gene (ireA) was markedly higher in strains isolated from frogs than in those isolated from fish. No obvious genetic relatedness was observed between both populations. The large differences found in the incidence of antibiotic resistance, integrons along with the multiple resistance genes, virulence factors, and genetic fingerprints determined by pulsed-field gel electrophoresis suggest a high degree of antibiotic resistance and pathogenicity potential of ESBL-producing L. hongkongensis from isolates found in frogs.


Assuntos
Anuros/microbiologia , Betaproteobacteria/genética , Farmacorresistência Bacteriana Múltipla/genética , Peixes/microbiologia , Integrons/genética , Virulência/genética , beta-Lactamases/genética , Animais , Antibacterianos/farmacologia , Betaproteobacteria/efeitos dos fármacos , Água Doce/microbiologia , Fatores de Virulência/genética
12.
Cell Stress Chaperones ; 24(1): 105-113, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30421325

RESUMO

Autophagy plays an important role in maintaining cell function. Abnormal autophagy leads to cell dysfunction and is associated with many diseases such as tumors, immunodeficiency diseases, lysosomal storage disorders, and neurodegenerative diseases. Autophagy is precisely regulated, and PTEN plays an important role in regulating autophagy. As noncoding small RNAs, miRNAs play an important role in the fine regulation of cellular processes. However, the mechanism of the miRNA regulation of PTEN-related autophagy has not been fully elucidated. In this study, our results showed that miR-4465 significantly inhibited the expression of PTEN, upregulated phosphorylated AKT, and thereby inhibited autophagy by activating mTOR in HEK293, HeLa, and SH-SY5Y cells. Further studies indicated that miR-4465 reduced PTEN mRNA levels through posttranscriptional regulation via directly targeting the 3'-UTR. Our novel findings provide useful hints for the comprehensive elucidation of the molecular mechanism of miRNA-regulated PTEN-related autophagy and may also provide some new insights for the exploration of miRNAs in the treatment of PTEN-related diseases.


Assuntos
Autofagia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Regiões 3' não Traduzidas/genética , Autofagia/genética , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Transdução de Sinais , Transcrição Genética
13.
J Cell Biochem ; 120(6): 9193-9202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30506723

RESUMO

Immunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO-296 [2-(6-chlorobenzo[d]oxazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO-296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO-296 did not affect the expression of cluster of differentiation (CD)-25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO-296 inhibited interleukin (IL)-6, IL-17, and interferon gamma expression but had no effect on IL-2, IL-4, or IL-10. Yet, importantly, PO-296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mitogen-activated protein kinase pathway. In conclusion, these findings indicate that PO-296 inhibits human activated T-lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO-296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.

14.
Sci Rep ; 8(1): 1051, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29348538

RESUMO

Although metamaterials wave-plates have been demonstrated previously, many of them suffer from the issue of narrow bandwidth since they typically rely on resonance principles and thus exhibit inevitable frequency dispersions. Here, we show that the dispersion of spoof surface plasmon (SSP) mode supported by a fishbone structure can be freely modulated by varying the structural parameters. This motivates us to establish a general strategy of building broadband wave-plates by cascading two fishbone structures with different propagation constants of SSP modes. We derive a criterion under which the cross-polarization phase-difference across the whole device can maintain at a nearly constant value over a wide frequency band, with frequency dispersions in the two fishbone structures cancelled out. As an illustration, we design and fabricate an efficient microwave quarter-wave plate and experimentally characterize its excellent polarization-control performances over a broad frequency band (7-9.2 GHz). Our findings can stimulate making dispersion-controlled high-performance optical functional devices in different frequency domains.

15.
J Cell Biochem ; 119(7): 5382-5390, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29345351

RESUMO

Benzoxazole and its derivatives have been widely studied in recent years due to their various biological properties. A previous study has demonstrated that K313 (1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole derivative, inhibits T cell proliferation to yield immunosuppressive effects. However, there are no related reports about its anti-inflammatory effects. In the present study, we investigated the anti-inflammatory properties and the underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. K313 dose-dependently (5, 10, and 20 µM) inhibited LPS-stimulated nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 3-nitrotyrosine (3-NT) production and significantly decreased the gene transcription levels of inducible nitric oxide (iNOS), IL-6, and TNF-α. In addition, the results showed that the inflammatory cytokines suppressed by K313 were not regulated by p65 NF-κB, ERK1/2, AKT, or p38 MAPK. Instead, K313 increased phosphorylation of glycogen synthase kinase-3 beta (GSK-3ß) (Ser9) resulting in GSK-3ß deactivation. Moreover, in LPS-stimulated RAW264.7 macrophages, K313 and lithium chloride (LiCl) had a synergistic effect on the anti-inflammatory response. These results indicated that K313 exhibited anti-inflammatory properties and revealed the potential mechanism. K313 can increase GSK-3ß (Ser9) phosphorylation to decrease GSK-3ß activation in LPS-induced RAW264.7 macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Benzoxazóis/farmacologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Benzoxazóis/química , Células Cultivadas , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
J Med Virol ; 89(12): 2075-2083, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28786502

RESUMO

With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunoensaio/métodos , Poliovirus/genética , Poliovirus/imunologia , Animais , Saúde Global , Células HEK293 , Humanos , Poliomielite/imunologia , Poliovirus/isolamento & purificação , Poliovirus/fisiologia , Vacina Antipólio Oral , Ratos , Replicação Viral
17.
Sci Rep ; 7(1): 1354, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28465543

RESUMO

Efficiently exciting surface plasmon polaritons (SPP) is highly desired in many photonic applications, but most approaches (such as prism and grating couplers) cannot control flexibly their SPP excitation directions. While Pancharatnam-Berry (PB) metasurfaces were recently proposed to achieve direction-controllable SPP excitations, such scheme suffers from low-efficiency issue due to both direct reflections at the coupler surface and the mode mismatch between the coupler and the guiding-out plasmonic structure. In this article, we solve these issues via imposing two criterions to guide design both the metasurface and the plasmonic metal, based on which a direction-controllable SPP excitation with very high efficiency can be realized. As a proof of concept, we designed/fabricated a realistic device working in the microwave regime, and performed both near-field and far-field measurements to demonstrate that it can achieve an spoof SPP conversion efficiency ~78%, much higher than previous devices. Full-wave simulations are in good agreement with experiments, showing that the efficiency can be further pushed to 92% with optimized designs. Our findings can stimulate spoof SPP-related applications, particularly can help enhance the spin-dependent light-matter interactions in low frequency regime.

18.
J Immunol Res ; 2016: 5021537, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28070525

RESUMO

It is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG-) specific experimental autoimmune encephalomyelitis (EAE) model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS). Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT) disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs). Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/transplante , Encefalomielite Autoimune Experimental/terapia , Tolerância Imunológica/imunologia , Imunoterapia Adotiva , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Linfócitos T Reguladores/citologia , Células Th17/citologia , Animais , Contagem de Linfócito CD4 , Células Cultivadas , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Inibidores de Proteínas Quinases/farmacologia , Células Th1/citologia
19.
Mol Carcinog ; 55(1): 77-89, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25557841

RESUMO

Glioblastoma multiforme (GBM) cancer stem cells (GSCs) are responsible for the progression and recurrence of GBM after conventional therapy. Morusin possesses anti-cancer activity in vitro. The purpose of this study is to confirm the growth inhibition effect of morusin on human GSCs growth in vitro and in vivo and to explore the possible mechanism of its activity. Human GSCs were enriched under nonadhesive culture system, and characterized through neurosphere formation, toluidine blue staining, immunofluorescence staining, Western blotting analysis of stemness markers of CD133, nestin, Sox2 and Oct4, and tumorigenecity in vivo; the growth inhibition effect of morusin on human GSCs in vitro and in vivo were tested by cell cytotoxicity, neurosphere formation inhibition, adipogenic differentiation, apoptosis induction, and tumor growth inhibition in vivo assays. The potential molecular mechanisms underlying the growth inhibition effect of morusin on GSCs in vitro and in vivo were investigated with Western blotting evaluation of stemness, adipogenic, and apoptotic proteins in morusin treated GSCs and tumor tissues. GSCs enriched under nonadhesive culture system possess stemness characterstics; Morusin inhibited GSCs growth in vitro and in vivo, it reduced stemness of GSCs, induced them adipocyte-like transdifferention and apoptosis. Morusin has the potential to inhibit human GSCs growth in vitro and in vivo through stemness attenuation, adipocyte transdifferentiation, and apoptosis induction.


Assuntos
Apoptose/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Transdiferenciação Celular/efeitos dos fármacos , Flavonoides/farmacologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Animais , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Expressão Gênica , Glioblastoma/genética , Humanos , Camundongos , Esferoides Celulares , Carga Tumoral , Células Tumorais Cultivadas
20.
Chin Med J (Engl) ; 127(18): 3254-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25266523

RESUMO

BACKGROUND: Apical abscess is an inflammatory process in the peri-radicular tissues caused by biofilms in the necrotic root canal systems. Therefore, a comprehensive analysis of the bacterial colonization is required for a better understanding of the pathogenesis. This study aimed to investigate the patterns of bacterial infection of root canals of teeth with apical abscesses and to determine whether histological and microbiological findings correlated with clinical conditions. METHODS: Eighteen samples from 18 teeth with apical pathological lesions were analyzed. Nine patients with acute apical abscesses experienced severe pain, and nine patients were asymptomatic with a sinus tract. After extraction, each affected root was divided into two halves. One half was processed for histobacteriologic analysis and examined using light microscopy, and the other half was analyzed using scanning electron microscopy (SEM) to determine the patterns of microbial colonization of the root canals. RESULTS: The appearance of each sample subjected to SEM was consistent with the histobacteriologic findings despite the presence or absence of clinical symptoms. Intraradicular biofilms comprising cocci, rods, and/or filaments of amorphous materials were observed in the apical third of the main root canals in all samples. The bacterial biofilms covering the main root canal walls also penetrated the dentinal tubules to varying depths. The morphologies of biofilms varied, and a unique pattern of intraradicular infection was not identified. CONCLUSION: Intraradicular infections formed complex and variable multispecies biofilms and their presence did not correlate with clinical symptoms.


Assuntos
Abscesso/microbiologia , Cavidade Pulpar/microbiologia , Idoso , Infecções Bacterianas/microbiologia , Biofilmes/crescimento & desenvolvimento , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade
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