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1.
J Asian Nat Prod Res ; : 1-10, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33550877

RESUMO

Eighteen novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives were prepared, and their structures well characterized by 1H NMR, HRMS, and mp. Due to the steric hindrance, the substituents on the C = N double bond of all hydrazine compounds (except E/Z = 4/1 for IV-1g, IV-1l, IV-2b, and E/Z = 3/2 for IV-1n, IV-3a) adopted E configuration. Among all compounds, four compounds 2, 4, IV-1j, and IV-1n exhibited potent nematicidal activity than their precursor paeonol, especially 5-nitropaeonol (2) and 3,5-dinitropaeonol (4) displayed the most potent nematicidal activity Heterodera glycines in vivo with LC50 values of 32.3307 and 36.7074 mg/L, respectively.

2.
FASEB J ; 34(10): 13609-13625, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32786030

RESUMO

Bacterial pore-forming toxin aerolysin-like proteins are widely distributed in animals and plants. Emerging evidence supports their roles in host innate immunity, but their direct actions in adaptive immunity remain elusive. In this study, we found that ßγ-CAT, an aerolysin-like protein and trefoil factor complex identified in the frog Bombina maxima, modulated several steps of endocytic pathways during dendritic cell antigen presentation. The protein augmented the antigen uptake of dendritic cells and actively neutralized the acidification of cellular endocytic organelles to favor antigen presentation. In addition, the release of functional exosome-like extracellular vesicles was largely enhanced in the presence of ßγ-CAT. The cellular action of ßγ-CAT increased the number of major histocompatibility complex (MHC) I-ovalbumin and MHC II molecules on dendritic cell surfaces and the released exosome-like extracellular vesicles. An enhanced antigen presentation capacity of dendritic cell for priming of naive T cells was detected in the presence of ßγ-CAT. Collectively, these effects led to strong cytotoxic T lymphocyte responses and antigen-specific antibody responses. Our findings provide evidence that a vertebrate-secreted pore-forming protein can augment antigen presentation by directly modulating cellular endocytic and exocytic pathways, leading to robust activation of adaptive immunity.

4.
Clin Oral Investig ; 23(12): 4433-4439, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30982180

RESUMO

OBJECTIVES: This study aimed to investigate the effect of fracture orientation on the detection accuracy of vertical root fractures (VRFs) in non-endodontically treated teeth using four different cone beam computed tomography (CBCT) units. MATERIALS AND METHODS: Thirty eight out of 148 extracted human permanent teeth were chosen randomly, and VRFs were artificially induced to result in 20 mesiodistally and 18 buccolingually oriented root fractures. The fracture width was subsequently measured. All the teeth were scanned with four CBCT units. CBCT images were evaluated independently by two observers. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated for each observer and fracture orientation. The AUC between the two fracture orientations was compared using Z test. RESULTS: The mean fracture width was 140 µm (standard deviation 26.8 µm). A statistically significant difference was found between the mesiodistal and buccolingual VRFs for the AUC from the CBCT unit 3D Accuitomo 170 (p = 0.02). There were no statistically significant differences between the mesiodistal and buccolingual VRFs for AUCs from the CBCT units NewTom VGi (p = 0.21), ProMax 3D Mid (p = 0.23), and i-CAT FLX (p = 0.21). CONCLUSION: Fracture orientations of teeth with VRFs in non-endodontically treated teeth may play a role in the detection accuracy of CBCT images, but this effect seems to be dependent on the CBCT unit used. CLINICAL RELEVANCE: Although for most of the CBCT units tested, the fracture orientation of VRF in non-endodontically treated teeth seems not to play a role for the diagnosis, clinical data is needed to further assess the impact of different devices on VRF detection.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Fraturas dos Dentes/diagnóstico por imagem , Raiz Dentária/diagnóstico por imagem , Dente não Vital , Dente Pré-Molar , Humanos
5.
J Colloid Interface Sci ; 544: 155-163, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30836257

RESUMO

Natural diatomite with abundant pores was used as a biotemplate for the massive production of three-dimensional (3D) porous graphene by chemical vapor deposition method. Subsequent template removal and nitrogen doping treatment yield nitrogen doped 3D graphene with preserved shape and complex internal features of the diatomite. After further deposition with MnO2 nanosheets, the N-doped 3D graphene@MnO2 (N-G@MnO2) hybrid exhibited excellent supercapacitor and good oxygen reduction reaction (ORR) performance. Accordingly, the porous N-G@MnO2 electrode exhibited a high specific capacitance (411.5 F g-1) and a good cycling performance (88.3% capacitance retention after 4000 charge/discharge cycling test). When tested in a two-electrode configuration, N-G@MnO2 achieved a wide potential window up to 1.8 V with a high energy density of 46.1 Wh kg-1. Furthermore, the as-prepared N-G@MnO2 showed good performance in oxygen reduction reaction, which is comparable to those of commercially available Pt/C electrode. The enhanced capacitive and electrocatalytic properties and stability is due to the synergistic interactions between the porous 3D graphene and MnO2 nanosheets. The results indicate that the 3D N-G@MnO2 could be useful for supercapacitor and ORR catalyst.

6.
Commun Biol ; 2: 59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30775460

RESUMO

Bacterial pore-forming toxin aerolysin-like proteins (ALPs) are widely distributed in animals and plants. However, functional studies on these ALPs remain in their infancy. ßγ-CAT is the first example of a secreted pore-forming protein that functions to modulate the endolysosome pathway via endocytosis and pore formation on endolysosomes. However, the specific cell surface molecules mediating the action of ßγ-CAT remain elusive. Here, the actions of ßγ-CAT were largely attenuated by either addition or elimination of acidic glycosphingolipids (AGSLs). Further study revealed that the ALP and trefoil factor (TFF) subunits of ßγ-CAT bind to gangliosides and sulfatides, respectively. Additionally, disruption of lipid rafts largely impaired the actions of ßγ-CAT. Finally, the ability of ßγ-CAT to clear pathogens was attenuated in AGSL-eliminated frogs. These findings revealed a previously unknown double binding pattern of an animal-secreted ALP in complex with TFF that initiates ALP-induced endolysosomal pathway regulation, ultimately leading to effective antimicrobial responses.


Assuntos
Glicoesfingolipídeos Acídicos/química , Proteínas de Anfíbios/imunologia , Toxinas Bacterianas/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Lisossomos/imunologia , Complexos Multiproteicos/imunologia , Proteínas Citotóxicas Formadoras de Poros/imunologia , Fator Trefoil-3/imunologia , Glicoesfingolipídeos Acídicos/antagonistas & inibidores , Glicoesfingolipídeos Acídicos/biossíntese , Aeromonas hydrophila/crescimento & desenvolvimento , Aeromonas hydrophila/patogenicidade , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/metabolismo , Animais , Anuros , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Ceramidas/antagonistas & inibidores , Ceramidas/biossíntese , Ceramidas/química , Cerebrosídeos/antagonistas & inibidores , Cerebrosídeos/biossíntese , Cerebrosídeos/química , Gangliosídeos/antagonistas & inibidores , Gangliosídeos/biossíntese , Gangliosídeos/química , Expressão Gênica , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Interleucina-1beta/biossíntese , Lisossomos/efeitos dos fármacos , Lisossomos/microbiologia , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/imunologia , Microdomínios da Membrana/microbiologia , Meperidina/análogos & derivados , Meperidina/farmacologia , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Esfingosina/antagonistas & inibidores , Esfingosina/biossíntese , Esfingosina/química , Células THP-1 , Fator Trefoil-3/genética , Fator Trefoil-3/metabolismo
7.
FASEB J ; 33(1): 782-795, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30063438

RESUMO

Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore-forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear. ßγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (ß-subunit) complex (ßγ-CAT) is a complex of a bacterial pore-forming toxin aerolysin-like protein and trefoil factor identified in the frog Bombina maxima. In this study, we established mouse cutaneous wound models to explore the effects of ßγ-CAT on skin wound healing. ßγ-CAT accelerated the healing of full-thickness wounds by improving re-epithelialization. This complex relieved dermal edema and promoted scarless healing. ßγ-CAT treatment resulted in a rapid release of IL-1ß, which initiated an acute inflammation response in the early stage of healing. Meanwhile, the expression levels of TGF-ß1, VEGF, and bFGF and the recruitment of M2 macrophages around the wound significantly increased after ßγ-CAT treatment. ßγ-CAT protected skin wounds against methicillin-resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound. Overall, our results suggest that ßγ-CAT can promote tissue repair and protect skin wounds against antibiotic-resistant bacterial infection by triggering the acute inflammatory response. This is the first example that aerolysin-like pore-forming proteins widely existing in plants and animals may act in wound healing and tissue repair.-Gao, Z.-H., Deng, C.-J., Xie, Y.-Y., Guo, X.-L., Wang, Q.-Q., Liu, L.-Z., Lee, W.-H., Li, S.-A., Zhang, Y. Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.


Assuntos
Proteínas Citotóxicas Formadoras de Poros/metabolismo , Toxinas Biológicas/metabolismo , Cicatrização , Animais , Anuros , Linhagem Celular , Colágeno/metabolismo , Cristalinas/metabolismo , Células Epiteliais/citologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/citologia , Humanos , Interleucina-1beta/metabolismo , Macrófagos/citologia , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Neutrófilos/citologia , Coelhos , Pele/lesões , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Fator de Crescimento Transformador beta1/metabolismo , Fatores Trefoil/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Genes Dis ; 5(1): 16-23, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30258930

RESUMO

Circular RNAs (circRNAs) with a covalently closed loop structure which was different with linear RNAs, recently re-merged as novel regulator and exerted function in multiple biological processes. Through deep RNA sequencing (RNA-seq) technology coupled with bioinformatic analyses, a number of circRNAs has been identified. Moreover, circRNAs exhibit tissue- and development-specific expression indicating their potential biological significance. Actually, function of circRNAs as miRNA sponge has been well demonstrated in some diseases, besides, circRNAs also could function as RNA binding protein sponge and regulate alternative splicing and gene transcription. Notably, Emerging evidences showed that circRNAs played a pivotal role on the development of diseases including atherosclerotic vascular disease, neurological disorders and liver diseases, and served as diagnostic or predictive biomarkers of some diseases. This review mainly discusses the current advance of circRNAs as regulator involved in many diseases, and highlights circRNAs which have been well elucidated biological and pathogenic mechanism.

9.
Cytotechnology ; 70(1): 313-320, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28965287

RESUMO

Dimethyl sulfoxide (DMSO) is widely used in the laboratory and in clinical situations because it is soluble in both aqueous and organic media and can be used to treat many types of diseases. Thus, it is meaningful to assess the comprehensive and in-depth biological activities of DMSO. Here, we showed that a high concentration of DMSO induced pro-inflammatory cytokine interleukin-1ß (IL-1ß) secretion from the monocytic cell line THP-1. DMSO-induced IL-1ß secretion was dependent on intracellular caspase-1 activation. Further study revealed that the activation of caspase-1 by DMSO relied on NLRP3 inflammasome formation. It is generally accepted that the NLRP3 inflammasome is activated by reactive oxygen species generation or potassium efflux; however, the common NLRP3 inflammasome trigger remains controversial. Here, we showed that although DMSO is a ROS scavenger, this chemical increases membrane permeability and potassium efflux, and the formation of the NLRP3 inflammasome reflects the increased membrane permeability and potassium efflux induced by DMSO. The present study reveals a new characteristic of DMSO, which should be considered when using this chemical in either the laboratory or the clinic.

10.
J Infect Dis ; 215(11): 1753-1763, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28419297

RESUMO

Many intracellular pathogens invade cells via endocytic organelles and have adapted to the drop in pH along the endocytic pathway. However, the strategy by which the host cell counteracts this pathogen adaptation remains unclear. ßγ-CAT is an aerolysin-like pore-forming protein and trefoil factor complex in the frog Bombina maxima. We report here that ßγ-CAT, as a host-secreted factor with an intrinsic channel-forming property, is the first example of a molecule that actively neutralizes the acidification of endocytic organelles to counteract Listeria monocytogenes infection. Immunodepletion of endogenous ßγ-CAT largely impaired the control of L. monocytogenes by frog cells. ßγ-CAT elevates the pH of L. monocytogenes-containing vacuoles to limit the vacuole escape of L. monocytogenes to cytosol. Furthermore, ßγ-CAT promotes intracellular L. monocytogenes clearance via autophagy and by that the nonlytic expulsion of the bacteria from host cells. Finally, ßγ-CAT attenuated the dissemination of L. monocytogenes in vivo. These findings reveal a novel host strategy and effectors that combat pathogen adaptation to acidic conditions along the endocytic pathway.


Assuntos
Lisossomos/imunologia , Proteínas Citotóxicas Formadoras de Poros/imunologia , Fatores Trefoil/imunologia , Animais , Anuros , Autofagia/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Listeriose/microbiologia , Lisossomos/microbiologia , Proteínas Citotóxicas Formadoras de Poros/metabolismo
11.
Dalton Trans ; 45(26): 10530-8, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27005689

RESUMO

MnOx-decorated MgAl layered double oxide (M-LDO) was fabricated via merging of memory effect and anion intercalation, accompanied by the reduction/calcination process. The as-obtained nanocomposites were characterized by scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (XRD) and N2 adsorption-desorption. To clarify the detailed formation mechanism, optimized calcination temperature/time and temperature for methyl orange (MO) adsorption were investigated. Adsorption experiments showed that the adsorption behaviour fitted well with a Langmuir isotherm and pseudo-second-order model, and the maximum adsorption capacity calculated from the Langmuir model was 555.55 mg g(-1). The adsorption process was exothermic and spontaneous in nature. Moreover, the used adsorbent could be regenerated for at least five cycles (94% removal retained) through a thermal procedure, indicating that the M-LDO hybrid is a promising adsorbent with promising ability to remove anionic dye pollutants from wastewater.

12.
Biochim Biophys Acta ; 1843(7): 1393-401, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24732013

RESUMO

The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is irreversibly activated by either thrombin or metalloprotease 1. Due this irrevocable activation, activated internalization and degradation are critical for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved, ubiquitously expressed, pleiotropic protein and belongs to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family. In a previous study, we found that PHB localized on the platelet membrane and participated in PAR1-mediated human platelet aggregation, suggesting that PHB likely regulates the signaling of PAR1. Unfortunately, PHB's exact function in PAR1 internalization and degradation is unclear. In the current study, flow cytometry revealed that PHB expressed on the surface of endothelial cells (HUVECs) but not cancer cells (MDA-MB-231). Further confocal microscopy revealed that PHB dynamically associates with PAR1 in a time-dependent manner following induction with PAR1-activated peptide (PAR1-AP), though differently between HUVECs and MDA-MB-231 cells. Depletion of PHB by RNA interference significantly inhibited PAR1 activated internalization and led to sustained Erk1/2 phosphorylation in the HUVECs; however, a similar effect was not observed in MDA-MB-231 cells. For both the endothelial and cancel cells, PHB repressed PAR1 degradation, while knockdown of PHB led to increased PAR1 degradation, and PHB overexpression inhibited PAR1 degradation. These results suggest that persistent PAR1 signaling due to the absence of membrane PHB and decreased PAR1 degradation caused by the upregulation of intracellular PHB in cancer cells (such as MDA-MB-231 cells) may render cells highly invasive. As such, PHB may be a novel target in future anti-cancer therapeutics, or in more refined cancer malignancy diagnostics.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Receptor PAR-1/genética , Proteínas Repressoras/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Microscopia Confocal , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Especificidade de Órgãos , Peptídeos/farmacologia , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor PAR-1/antagonistas & inibidores , Receptor PAR-1/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Transdução de Sinais
13.
J Biomed Mater Res A ; 102(11): 3903-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24338974

RESUMO

Poly(glycerol-sebacate) (PGS) is an elastomeric biodegradable polyester. Our previous series of studies have showed that PGS has good biocompatibility. In view of the potential use of PGS in bioengineering, we attempt to characterize the PGS polymer with different ratio of glycerol and sebacic acid, and the cell adhesion and growth on these polymers. PGSs with different proportion of glycerol and sebacic acid were synthesized by polycondensation reaction. The microstructure of the series PGSs were characterized by infrared spectroscopy and X-ray diffraction analysis (XRD). Results showed that, with the increase of the ratio of sebacic acid in PGS from 1:0.8, 1:1, to 1:1.2 (ratio of glycerol to sebacic acid), the main diffraction peak in XRD, the sol content and gel swelling increased but then decreased, suggesting that the degree of crosslinking and the inherent degree of order of the series PGS increased and then decreased. With the increase of sebacic acid proportion, water absorption increased and then decreased, and the water absorption ranged from 9.62% to 10.66%. The mass loss of the series of samples in degradation experiments ranged from 24.63% to 40.06% on the 32nd day of degradation. Cell culture data suggested that the polymer with the ratio of 1:0.8 for glycerol and sebacate was suitable for cell adhesion and growth. In conclusion, PGS can be used as the cell culture matrix by modifying the composition ratio of glycerol and sebacic acid to improve the properties of cell adhesion and growth.


Assuntos
Plásticos Biodegradáveis , Técnicas de Cultura de Células , Decanoatos , Elastômeros , Glicerol/análogos & derivados , Glicerol/química , Polímeros , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Decanoatos/síntese química , Decanoatos/química , Elastômeros/síntese química , Elastômeros/química , Glicerol/síntese química , Células HeLa , Humanos , Polímeros/síntese química , Polímeros/química
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