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1.
Am J Physiol Lung Cell Mol Physiol ; 326(6): L754-L769, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38625125

RESUMO

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates procellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.


Assuntos
Mitocôndrias , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Animais , Mucosa Respiratória/patologia , Mucosa Respiratória/metabolismo , Células Epiteliais/patologia , Células Epiteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Opt Lett ; 49(2): 318-321, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38194558

RESUMO

Multi-focusing of light is a crucial capability for photonic devices that can be effectively achieved by precisely modulating the phase delay on the incident wavefront. However, integrating functional structures into optical fibers for remote light focusing remains challenging due to the complex device design and limited fabrication approaches. Here, we present the design and fabrication of metalens array on the end-face of a tailored single-mode step-index fiber for focusing light field into closely packed focal spot array. The metalenses are configured based on the fractional Talbot effect and benefit a modular design capability. Light passing through the optical fiber can be focused into different focal planes. With a synergistic 3D laser nanoprinting technique based on two-photon polymerization, high-quality meta-fibers are demonstrated for focusing light parallelly with a uniform numerical aperture (NA) as high as approximately 0.77. This may facilitate various applications such as optical trapping, generation of sophisticated beam profiles, and boosting light coupling efficiencies.

3.
J Immunol ; 209(4): 820-828, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35906000

RESUMO

Pyroptosis is a key inflammatory form of cell death participating in the progression of many inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE) and sepsis. Identification of small molecules to inhibit pyroptosis is emerging as an attractive strategy. In this study, we performed a screening based on in silico docking of compounds on the reported Gasdermin D (GSDMD) three-dimensional structure and found C202-2729 demonstrated strong anti-inflammatory effects in both endotoxin shock and EAE mouse models. Oral administration of C202-2729 was capable of attenuating EAE disease severity significantly and has the comparable effects to teriflunomide, the first-line clinical drug of multiple sclerosis. We found C202-2729 remarkably suppressed macrophage and T cell-associated immune inflammation. Mechanistically, C202-2729 neither impact GSDMD cleavage nor the upstream inflammasome activation in mouse immortalized bone marrow-derived macrophages. However, C202-2729 exposure significantly repressed the IL-1ß secretion and cell pyroptosis. We found C202-2729 directly bonds to the N terminus of GSDMD and blocks the migration of the N-terminal GSDMD fragment to cell membrane, restraining the pore-forming and mature IL-1ß release. Collectively, our findings provide a new molecule with the potential for translational application in GSDMD-associated inflammatory diseases.


Assuntos
Encefalomielite Autoimune Experimental , Sepse , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Inflamassomos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Proteínas de Ligação a Fosfato/metabolismo , Piroptose , Sepse/tratamento farmacológico
4.
Opt Lett ; 48(10): 2523-2526, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37186698

RESUMO

The supercritical lens has shown a remarkable capability of achieving far-field sub-diffraction limited focusing through elaborating a modulated interference effect. Benefiting from the relative high energy utilization efficiency and weak sidelobe properties, the supercritical lens holds significant advantage in a series of application scenarios. However, all of the demonstrated supercritical lenses mainly work in the on-axis illumination condition, so the off-axis aberration effect will severely deteriorate its sub-diffraction limit focusing capability for the illuminating beam with an oblique angle. In this work, an aberration-compensated supercritical lens with single-layer configuration is proposed and experimentally demonstrated. Such a single-layer supercritical lens consists of multilevel phase configurations patterned with the two-photon polymerization lithography technique. The simulation and experimental recorded results show that the aberration-compensated supercritical lens with a numerical aperture value of 0.63 could achieve a far-field sub-diffraction limited focusing property within 20° field of view at a wavelength of λ = 633 nm. This monochromatic aberration-compensated supercritical lens with single-layer configuration indicates excellent potential in the development of laser scanning ultrahigh optical storage and label free super-resolution imaging.

5.
Clin Exp Pharmacol Physiol ; 50(10): 806-814, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37452725

RESUMO

Filtration surgery is commonly performed for glaucoma treatment to reduce intraocular pressure (IOP); however, scarring of the filtering bleb is the main cause of failure. In this study, we evaluated the effects of the chloride channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) on scar formation in filtering blebs. A glaucoma filtering surgery model was generated using Sprague-Dawley rats, divided into the control and NPPB groups receiving injections of different NPPB concentrations. The IOP of all rats decreased 1-day post-surgery and gradually increased afterward. However, IOP in rats from the NPPB groups recovered more slowly than that of the control group rats. In addition, the area and survival times of filtering blebs in rats from the NPPB groups were substantially larger and longer than those in the control group. Twenty-eight days after surgery, the protein and mRNA expression of collagen I, fibronectin and α-smooth muscle actin in the filtering area of rats from the NPPB groups were significantly lower than that in the control group rats. Collectively, our study demonstrates that NPPB inhibits filtering bleb scar formation, maintains filtering bleb morphology and prolongs filtering bleb survival time by inhibiting the differentiation of conjunctival fibroblasts and extracellular matrix synthesis.


Assuntos
Cicatriz , Glaucoma , Ratos , Animais , Cicatriz/prevenção & controle , Cloretos , Ratos Sprague-Dawley , Glaucoma/cirurgia , Pressão Intraocular , Canais de Cloreto
6.
Nano Lett ; 22(4): 1649-1655, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35107290

RESUMO

Integrating two-dimensional (2D) transition-metal dichalcogenides (TMDCs) into dielectric plasmonic nanostructures enables the miniaturization of on-chip nanophotonic devices. Here we report on a high-quality light emitter based on the newly designed 2D h-BN/WS2 heterostructure integrated with an array of TiO2 nanostripes. Different from a traditional strongly coupled system such as the TMDCs/metallic plasmonic nanostructure, we first employ dielectric nanocavities and achieve a Purcell enhancement on the nanoscale at room temperature. Furthermore, we demonstrate that the light emission strength can be effectively controlled by tuning the polarization configuration. Such a polarization dependence meanwhile could be proof of the resonant energy transfer theory of dipole-dipole coupling between TMDCs and a dielectric nanostructure. This work gains experimental and simulated insights into modified spontaneous emission with dielectric nanoplasmonic platforms, presenting a promising route toward practical applications of 2D semiconducting photonic emitters on a silica-based chip.

7.
J Immunol ; 204(7): 1736-1745, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32111731

RESUMO

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.


Assuntos
Autoimunidade/imunologia , Linfócitos B/imunologia , Interleucina-1/imunologia , Miastenia Gravis/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th17/imunologia , Adulto , Autoanticorpos/imunologia , Células Cultivadas , Feminino , Humanos , Imunidade Humoral/imunologia , Masculino , Pessoa de Meia-Idade
8.
J Environ Manage ; 321: 115960, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36104881

RESUMO

Based on the study's thorough logging records from 74 wells, grain size analysis, spatial analysis of sand thickness and sand ratio, and pertinent regional geological data, a sedimentary microfacies analysis of the Bayanchagan area is conducted using one sand layer as a unit. In addition, the reservoir's microscopic characteristics are summarized, and the location of advantageous reservoir areas is predicted. The principal reservoir rock types in the research region are determined to be lithic arkose and feldspathic lithic sandstone, and reservoir physical attributes are also quite poor. Intergranular dissolution pores make up the bulk of reservoir space types, which also include primary pores, secondary dissolution pores, and micro-fractures. Additionally, the delta front and delta plain subfacies are recognized. Eight more sedimentary microfacies are found: sheet sand, estuary bar, underwater distributary channel, underwater distributary bay, overflow thin sand, floodplain, and distributary channel under water. In a sedimentary environment with water penetration, the entire reservoir was produced. The delta diversion plain deposit makes up the lower portion of the FIII, FII, and FI oil layer groups, while the delta front deposit makes up the top portion of the FI oil layer group. The reservoirs may be divided into three groups: type I reservoirs, type II reservoirs, and type III reservoirs by thorough examination of the facies, microstructure, mercury intrusion characteristics, and other criteria. Among these, type I and type II reservoirs with substantial thicknesses, which are favorable for hydrocarbon accumulation, are the main focus of favorable oil and gas area exploration. The investigation's conclusions are instructive for future research.


Assuntos
Geologia , Areia , Fácies , Humanos , Água , Poços de Água
9.
Opt Lett ; 46(2): 356-359, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449028

RESUMO

Here, we demonstrate a flat nanofocalizer for converging light field into a uniform subwavelength light spot array based on the fractional Talbot effect by developing a direct laser writing technique with 3D fabrication precision. The fractional Talbot effect endows the device with the merits of high compression ratio and modular design capability for transforming a plane wave into arrayed light focal spots. By combining a synergistic laser printing technique, we introduce a buffer layer for improving the fabrication precision of structural height in favor of accurately manipulating the phase delay. For a given light wavelength at 750 nm, by precisely producing a nanofocalizer consisting of periodic unit elements with the dimensions of 300(width)×600(length)×585(height)nm, we have achieved 5×6 light spot array with modular design, while the full width at half-maximum of a single focused light spot can be reduced to ∼0.82λ. Our research may pave the way for realizing subwavelength optical devices capable of being readily integrated to existing optical systems.

10.
Small ; 16(2): e1905202, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814302

RESUMO

Graphene has attracted great interests in various areas including optoelectronics, spintronics, and nanomechanics due to its unique electronic structure, a linear dispersion with a zero bandgap around the Dirac point. Shifts of Dirac cones in graphene creates pseudo-magnetic field, which generates an energy gap and brings a zero-magnetic-field analogue of the quantum Hall effect. Recent studies have demonstrated that graphene pseudo-magnetic effects can be generated by vacancy defects, atom adsorption, zigzag or armchair edges, and external strain. Here, a larger than 100 T pseudo-magnetic field is reported that generated on the step area of graphene; and with the ultrahigh vacuum scanning tunneling microscopy, the observed Landau levels can be effectively tailored by graphene phonons. The zero pseudo-Landau level is suppressed due to the phonon-mediated inelastic tunneling, and this is observed by the scanning tunneling spectroscopy spectrum and confirmed by the Vienna ab initio simulation package calculation, where graphene phonons modulate the flow of tunneling electrons and further mediate pseudo-Landau levels. These observations demonstrate a viable approach for the control of pseudo-Landau levels, which tailors the electronic structure of graphene, and further ignites applications in graphene valley electronics.

11.
Microb Pathog ; 138: 103847, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704464

RESUMO

Helicobacter pylori (H. pylori) infection is highly prevalent, and has developed antimicrobial resistance to virtually all existing antibiotics. Currently, treatment of H. pylori infection (involving proton pump inhibitors and broad-spectrum antibiotics) is suboptimal, with high failure rates. Thus, there is a pressing need to develop new anti-H. pylori therapies. Cbf-K16, a cathelicidin-like antimicrobial peptide, presented broad antimicrobial activity during our previous research. This study further evaluated the therapeutic potential and the mode of action underlying Cbf-K16 against clarithromycin- and amoxicillin-resistant H. pylori SS1. The MIC and MBC of Cbf-K16 against the tested H. pylori were 16 and 32 µg/ml, respectively, and its killing kinetics was time-dependent, reflecting the thorough elimination of drug-resistant bacteria within 24 h. This peptide also protected H. pylori-infected gastric epithelial cells (GES-1) from death by reducing the cell supernatant and intracellular bacterial counts by 1.9 and 2.9-log10 units, respectively. These data indicated the powerful antimicrobial effects of Cbf-K16in vitro. Meanwhile, notable antimicrobial activity in the mouse gastritis model was observed, with decreasing bacterial counts by 3.9-log10 units in stomach tissues and Cbf-K16 could effectively suppress the secretion of inflammatory cytokine IL-8. For its mode of action, Cbf-K16 not only neutralized the negative potential and increased the membrane uptake of NPN and PI by 78.5% and 85.1%, respectively, but also bound to genomic DNA, which in turn downregulated the expression of adhesion genes (alpA and alpB) and virulence gene (cagA), indicating its effective activities on membrane disruption, DNA-binding and gene expression. The data above demonstrated that Cbf-K16 possessed effective antimicrobial and anti-inflammatory activities and downregulated the expression of adhesion- and cytotoxin-associated genes of drug-resistant H. pylori SS1, making it a potential candidate for anti-infective therapy.


Assuntos
Adesinas Bacterianas/efeitos dos fármacos , Catelicidinas/farmacologia , Infecções por Helicobacter , Helicobacter pylori/efeitos dos fármacos , Interleucina-8/efeitos dos fármacos , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antígenos de Bactérias/efeitos dos fármacos , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/efeitos dos fármacos , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Farmacorresistência Bacteriana , Genes Bacterianos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Humanos , Interleucina-8/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Virulência/efeitos dos fármacos , Virulência/genética
12.
Nano Lett ; 19(2): 775-780, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30596507

RESUMO

Chiral light-matter interactions as an emerging aspect of quantum optics enable exceptional physical phenomena and advanced applications in nanophotonics through the nanoscale exploitation of photon-emitter interactions. The chiral radiative properties of quantum emitters strongly depend on the photonic environment, which can be drastically altered by plasmonic nanostructures with a high local density of states (LDOS). Hence, precise knowledge of the chiral photonic environment is essential for manipulating the chirality of light-matter interactions, which requires high resolution chiral characterization techniques. In this work, chiral radiative LDOS distributions of single plasmonic nanostructures that directly govern the chiral radiative spontaneous decay of quantum emitters are imaged at the nanoscale by using cathodoluminescence nanoscopy, enabling precise and highly efficient control of chiral photon emission for chiroptical technologies. Radiative LDOS hot-spots with the chirality larger than 93% are obtained by properly designing chiral plasmonic modes of Au nanoantennas. After fabricating monolayered WSe2 nanodisks (NDs) at chiral radiative LDOS hot-spots and forming ND/Au hybrid nanostructures, the chiral radiative properties of WSe2 NDs are significantly modified, leading to chiral photoluminescence. Our experimental concept and method provide an effective way to characterize and manipulate chiral light-matter interactions at the nanoscale, facilitating future applications in chiral quantum nanophotonics such as single-photon sources and light emission devices.

13.
Phys Rev Lett ; 123(21): 213902, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809151

RESUMO

Optical chirality occurs when materials interact differently with light in a specific circular polarization state. Chiroptical phenomena inspire wide interdisciplinary investigations, which require advanced designs to reach strong chirality for practical applications. The development of artificial intelligence provides a new vision for the manipulation of light-matter interaction beyond the theoretical interpretation. Here, we report a self-consistent framework named the Bayesian optimization and convolutional neural network that combines Bayesian optimization and deep convolutional neural network algorithms to calculate and optimize optical properties of metallic nanostructures. Both electric-field distributions at the near field and reflection spectra at the far field are calculated and self-learned to suggest better structure designs and provide possible explanations for the origin of the optimized properties, which enables wide applications for future nanostructure analysis and design.

14.
Proc Natl Acad Sci U S A ; 113(52): 15000-15005, 2016 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-27956612

RESUMO

Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and to control their cell sizes. Growth of Escherichia coli, in particular, follows a relation known as Schaechter's growth law. This law says that the average cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate. Here, we sought to test the robustness of the growth law to systematic perturbations in cell dimensions achieved by varying the expression levels of mreB and ftsZ We found that decreasing the mreB level resulted in increased cell width, with little change in cell length, whereas decreasing the ftsZ level resulted in increased cell length. Furthermore, the time from replication termination to cell division increased with the perturbed dimension in both cases. Moreover, the growth law remained valid over a range of growth conditions and dimension perturbations. The growth law can be quantitatively interpreted as a consequence of a tight coupling of cell division to replication initiation. Thus, its robustness to perturbations in cell dimensions strongly supports models in which the timing of replication initiation governs that of cell division, and cell volume is the key phenomenological variable governing the timing of replication initiation. These conclusions are discussed in the context of our recently proposed "adder-per-origin" model, in which cells add a constant volume per origin between initiations and divide a constant time after initiation.


Assuntos
Ciclo Celular , Replicação do DNA , Escherichia coli/citologia , Escherichia coli/genética , Proteínas de Bactérias/metabolismo , Divisão Celular , Parede Celular/metabolismo , Cromossomos Bacterianos , Proteínas do Citoesqueleto/metabolismo , DNA Bacteriano/biossíntese , Proteínas de Escherichia coli/metabolismo , Plasmídeos
15.
Nano Lett ; 18(1): 567-572, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29261313

RESUMO

Circularly polarized light is crucial for the modern physics research. Highly integrated nanophotonic device further requires the control of circularly polarized light at subnanoscale. Here, we report the tuning of chiral cathodoluminescence (CL) on single Au nanostructure under electron stimulation. The detected CL helicity is found ultrasensitive with the electron impinging position on the structure, and a helicity switch is achieved within a 1.86 nm electron-beam movement, which is applied to construct ternary notation sequence. The proposed configuration provides a delicate platform for the CL helicity control, which opens a way for the future chiral applications at subnanoscale like information coding and quantum communication.

16.
Biochem Biophys Res Commun ; 496(2): 387-393, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29326045

RESUMO

The inhibitor of growth 5 (ING5) is a new candidate tumor suppressor gene (TSG) of the ING family. So far, there have been many reports about its functions related to cancer development. However, the biological roles of ING5 in esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we demonstrated that ING5 was lowly expressed in ESCC tissues and cell lines. Overexpression of ING5 inhibited ESCC cell proliferation and invasion in vitro as well as suppressed tumor growth and metastasis in vivo. We also found that overexpression of ING5 significantly decreased the levels of p-AKT, NF-κB and MMP-9 in ECA109 cells. Taken together, these findings demonstrated that ING5 inhibited cell proliferation and invasion in ESCC through regulation of the Akt/NF-κB/MMP-9 signaling pathway. Thus, ING5 might be considered a promising target for ESCC treatment.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Metaloproteinase 9 da Matriz/genética , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Invasividade Neoplásica , Transplante de Neoplasias , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
17.
Fungal Genet Biol ; 110: 38-47, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29221882

RESUMO

Cbf-14 (RLLRKFFRKLKKSV), a designed peptide derived from cathelicidin family AMP, has proven to be potent against drug-resistant bacteria. In the present study, we investigated the anti-cryptococcal activity of Cbf-14 in vitro and in a pulmonary infection mouse model. Sensitivity test indicated that Cbf-14 possessed effective antifungal activity against Cryptococcus neoformans with an MIC of 4-16 µg/ml, and killing experiments showed that fungicidal activity was achieved after only 4 h treatment with Cbf-14 at 4× MIC concentrations in vitro. Meanwhile, Cbf-14 was effective at prolonging the survival of infected mice when compared with controls, and significantly inhibited the secretion of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6, suggesting its anti-inflammatory activity against fungal infections. As a positively charged peptide, Cbf-14 was proven to neutralize the negative zeta potential of the fungal cell surface, disrupt the capsule polysaccharide of fungi, and further damage cell membrane integrity. These results were confirmed by flow cytometry analysis of the fluorescence intensity after PI staining, while cell membrane damage could be clearly observed by transmission electron microscopy after Cbf-14 (4× MIC) treatment for 1 h. In addition, Cbf-14 increased the IL-10 levels in cultured RAW 264.7 cells, which were stimulated by C. neoformans infection. The obtained data demonstrated that Cbf-14 could rapidly kill C. neoformans cells in vitro, effectively inhibit C. neoformans induced-infection in mice, and inhibit inflammation in vitro / vivo. Therefore, Cbf-14 could potentially be used for the treatment of fungal infections clinically.


Assuntos
Criptococose/tratamento farmacológico , Cryptococcus neoformans/patogenicidade , Peptídeos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antifúngicos/uso terapêutico , Criptococose/metabolismo , Cryptococcus neoformans/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Fator de Necrose Tumoral alfa/metabolismo
18.
J Dairy Sci ; 99(3): 1736-1746, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26805974

RESUMO

Lactobacillus plantarum WLPL04, a specific strain isolated from human breast milk, was investigated for its survival capacity (acid and bile salt tolerance, survival in simulated gastrointestinal tract, inhibition of pathogens, antibiotic susceptibility, yield of exopolysaccharides) and probiotic properties (antiadhesion of pathogens, protection from harmful effect of sodium dodecyl sulfate, and antiinflammatory stress on Caco-2 cells). The results showed that Lb. plantarum WLPL04 had broad-spectrum activity against gram-positive strains (Listeria monocytogenes CMCC54007, Bacillus cereus ATCC14579, and Staphylococcus aureus CMCC26003) and gram-negative strains (Pseudomonas aeruginosa MCC10104, Shigella sonnei ATCC25931, Enterobacter sakazakii ATCC29544, Salmonella typhimurium ATCC13311, and Escherichia coli O157:H7). Antibiotic susceptibility tests showed that Lb. plantarum WLPL04 was susceptible to 8 of 14 antibiotics (e.g., erythromycin and nitrofurantoin) and resistant to 6 of 14 antibiotics (e.g., kanamycin and bacitracin). Lactobacillus plantarum WLPL04 was able to survive at pH 2.5 for 3h and at 0.45% bile salt for 12h, suggesting that it can survive well in the gastrointestinal tract. In addition, the exopolysaccharide yield of Lb. plantarum WLPL04 reached 426.73 ± 65.56 mg/L at 24h. With strategies of competition, inhibition, and displacement, Lb. plantarum WLPL04 reduced the adhesion of E. coli O157:H7 (35.51%), Sal. typhimurium ATCC 13311 (8.10%), and Staph. aureus CMCC 26003 (40.30%) on Caco-2 cells by competition, and subsequently by 59.80, 62.50, and 42.60%, respectively, for the 3 pathogens through inhibition, and by 75.23, 39.97, and 52.88%, respectively, through displacement. Lactobacillus plantarum WLPL04 attenuated the acute stress induced by sodium dodecyl sulfate on Caco-2 cells and significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor-α) on Caco-2 cells but increased IL-10 expression in vitro compared with the Salmonella-treated group. In summary, Lb. plantarum WLPL04 from breast milk could be considered as a probiotic candidate for dairy products to promote human health.


Assuntos
Citocinas/imunologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Lactobacillus plantarum/fisiologia , Leite Humano/microbiologia , Probióticos , Animais , Células CACO-2 , Feminino , Humanos , Lactobacillus plantarum/isolamento & purificação
19.
J Dairy Sci ; 99(6): 4282-4290, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26995141

RESUMO

The aim of this study was to evaluate the safety of enterococci isolated from Chinese infants and screen out potential probiotic candidates. One hundred eight strains were isolated from feces of 34 healthy infants, and 38 strains of Enterococcus spp. were categorized as follows: E. faecalis (22), E. faecium (10), E. hirae (3), E. durans (2), and E. casseliflavus (1). Of these, 72.7% of E. faecalis came from infants delivered by cesarean and 62.5% of E. faecium from infants delivered vaginally. For safety evaluation of strains, we determined presence of virulence genes; production of hemolysin, gelatinase, and biofilm; and antimicrobial susceptibility of enterococci. Six out of 14 virulence genes were detected with a distribution of gelE (26.3%), cylA (39.4%), esp (15.8%), efaA (63.2%), asa1 (50.0%), and ace (50.0%). In phenotype analysis, 36.8% of the strains exhibited positive hemolytic activity and 17.5% were positive for production of gelatinase. Results of antimicrobial susceptibility showed that different percentages of the strains were resistant to ciprofloxacin (5.2%), vancomycin (7.8%), rifampicin (10.5%), erythromycin (52.6%), and gentamycin (52.6%); remarkably, none of the strains were resistant to ampicillin or chloramphenicol. In total, 10 strains, including 6 E. faecium, which are free of virulence determinants and sensitive to common antimicrobial agents (e.g., ampicillin and vancomycin), were further assessed for their probiotic properties. All strains survived well in simulated gastric fluid and intestinal tract, with maximum reductions of 0.600 and 0.887 log cfu/mL, respectively. Six strains of E. faecium could resist 0.3 to 1.0% bile salt, of which E. faecium WEFA23 presented the highest growth (75.06%) at 1.0% bile salt. All strains showed bile salt hydrolase activity on glycodeoxycholic acid, but only 3 of E. faecium showed activity on taurodeoxycholic acid. These results deliver useful information on the safety of enterococci in infants in China, and provide a protocol to screen probiotics for absence of virulence and antimicrobial susceptibility of enterococci.


Assuntos
Enterococcus/isolamento & purificação , Probióticos , Animais , Antibacterianos , Anti-Infecciosos , Testes de Sensibilidade Microbiana , Virulência , Fatores de Virulência/genética
20.
Psicol Reflex Crit ; 37(1): 7, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411796

RESUMO

BACKGROUND: This study explored the effects of attention shifting on Chinese children's word reading. OBJECTIVE: The sample consisted of 87 fourth-grade children from Shaoxing City, China. METHODS: The students completed measures of the attention shifting task, reading accuracy test, reading fluency test, and rapid automatized naming test. RESULTS: The results showed that reading fluency was significantly correlated with attention shifting scores, specifically with tag1 and tag6 (ps < 0.05). The reading accuracy score was also significantly correlated with tag6 (p < 0.05). According to the regression analysis of attention shifting on word reading, even when controlling for rapid automatic naming, attention shifting significantly affected word reading fluency at approximately 600 ms (p = .011). Attention shifting did not affect children's word reading accuracy. SHORT CONCLUSION: These findings suggest that attention shifting is significantly associated with children's word reading. Educators should focus on developing children's attention shifting to improve their word reading ability.

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