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1.
Anal Chem ; 96(12): 4783-4790, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38471066

RESUMO

The 2019 coronavirus disease (COVID-19) outbreak created an unprecedented need for rapid, sensitive, and cost-effective point-of-care diagnostic tests to prevent and mitigate the spread of the SARS-CoV-2 virus. Herein, we demonstrated an advanced lateral flow immunoassay (LFIA) platform with dual-functional [colorimetric and surface-enhanced Raman scattering (SERS)] detection of the spike 1 (S1) protein of SARS-CoV-2. The nanosensor was integrated with a specially designed core-gap-shell morphology consisting of a gold shell decorated with external nanospheres, a structure referred to as gold nanocrown (GNC), labeled with a Raman reporter molecule 1,3,3,1',3',3'-hexamethyl-2,2'-indotricarbocyanine iodide (HITC) to produce a strong colorimetric signal as well as an enhanced SERS signal. Among the different plasmonics-active GNC nanostructures, the GNC-2 morphology, which has a shell decorated with an optimum number and size of nanospheres, produces an intense dark-blue colorimetric signal and ultrahigh SERS signal. The limit of detection (LOD) of the S1 protein via colorimetric detection LFIA was determined to be 91.24 pg/mL. On the other hand, the LOD for the SERS LFIA method was more than three orders of magnitude lower at 57.21 fg/mL. Furthermore, we analyzed the performance of the GNC-2 nanosensor for directly analyzing the S1 protein spiked in saliva samples without any sample pretreatment and achieving the LOD as low as 39.65 fg/mL using SERS-based plasmonics-enhanced LFIA, indicating ultrahigh detection sensitivity. Overall, our GNC nanosensor showed excellent sensitivity, reproducibility, and rapid detection of the SARS-CoV-2 S1 protein, demonstrating excellent potential as a promising point-of-care platform for the early detection of respiratory virus infections.


Assuntos
COVID-19 , Nanopartículas Metálicas , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Análise Espectral Raman/métodos , Ouro/química , Reprodutibilidade dos Testes , Colorimetria , Imunoensaio/métodos , Nanopartículas Metálicas/química
2.
Small ; 20(16): e2307366, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38039446

RESUMO

Restoring immune tolerance is the ultimate goal for rheumatoid arthritis (RA) treatment. The most reported oral or intravenous injection routes for the immunization of autoantigens cause gastrointestinal side effects, low patient compliance, and unsatisfied immune tolerance induction. Herein, the use of a transdermal microneedle patch is for the first time investigated to codeliver CII peptide autoantigen and rapamycin for reversing immune disorders of RA. The immunized microneedles efficiently recruit antigen-presenting cells particularly Langerhans cells, and induce tolerogenic dendritic cells at the administration skin site. The tolerogenic dendritic cells further homing to lymph nodes to activate systemic Treg cell differentiation, which upregulates the expression of anti-inflammatory mediators while inhibiting the polarization of Th1/2 and Th17 T cell phenotypes and the expression of inflammatory profiles. As a result, the optimized microneedles nearly completely eliminate RA symptoms and inflammatory infiltrations. Furthermore, it is demonstrated that a low dose of rapamycin is crucial for the successful induction of immune tolerance. The results indicate that a rationally designed microneedle patch is a promising strategy for immune balance restoration with increased immune tolerance induction efficiency and patient compliance.


Assuntos
Artrite Reumatoide , Células de Langerhans , Humanos , Células Th17 , Artrite Reumatoide/terapia , Tolerância Imunológica , Sirolimo/farmacologia
3.
Bioorg Med Chem ; 105: 117725, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38640588

RESUMO

Enhancer of zeste homolog 2 (EZH2) is a promising therapeutic target for diffuse large B-cell lymphoma. In this study, based on the binding model of 1 (tazemetostat) with polycomb repressive complex 2 (PRC2), we designed and synthesized a series of tazemetostat analogs bearing a 1-methyl-2-benzimidazolinone moiety to improve the inhibitory activity of EZH2 wild-type (WT) and Y641 mutants and enhance metabolic stability. After the assessment of the structure-activity relationship at enzymatic and cellular levels, compound N40 was identified. Biochemical assays showed that compound N40 (IC50 = 0.32 nM) exhibited superior inhibitory activity against EZH2 WT, compared with 1 (IC50 = 1.20 nM), and high potency against EZH2 Y641 mutants (EZH2 Y641F, IC50 = 0.03 nM; EZH2 Y641N, IC50 = 0.08 nM), which were approximately 10-fold more active than those of 1 (EZH2 Y641F, IC50 = 0.37 nM; EZH2 Y641N, IC50 = 0.85 nM). Furthermore, compound N40 (IC50 = 3.52 ±â€¯1.23 nM) effectively inhibited the proliferation of Karpas-422 cells and was more potent than 1 (IC50 = 35.01 ±â€¯1.28 nM). Further cellular experiments showed that N40 arrested Karpas-422 cells in the G1 phase and induced apoptosis in a dose-dependent manner. Moreover, N40 inhibited the trimethylation of lysine 27 on histone H3 (H3K27Me3) in Karpas-422 cells bearing the EZH2 Y641N mutant. Additionally, N40 (T1/2 = 177.69 min) showed improved metabolic stability in human liver microsomes compared with 1 (T1/2 = 7.97 min). Our findings suggest N40 as a promising EZH2 inhibitor; further investigation remains warranted to confirm our findings and further develop N40.


Assuntos
Antineoplásicos , Benzamidas , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Proteína Potenciadora do Homólogo 2 de Zeste , Piridonas , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Relação Estrutura-Atividade , Benzamidas/química , Benzamidas/farmacologia , Benzamidas/síntese química , Piridonas/farmacologia , Piridonas/química , Piridonas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Descoberta de Drogas , Benzimidazóis/química , Benzimidazóis/farmacologia , Benzimidazóis/síntese química
4.
J Gastroenterol Hepatol ; 39(1): 121-132, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037531

RESUMO

BACKGROUND: Gastric cancer (GC) is a common malignancy with high incidence and mortality, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the molecular mechanism of circTMEM87A in GC malignant progression is uncertain. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of circTMEM87A, miR-1276, and solute carrier family 7 membrane 11 (SLC7A11). Western blot was applied to detect protein expression levels of EMT-related proteins (vimentin and E-cadherin) and SLC7A11. Cell counting kit-8 assay (CCK8) and thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) were performed to assess cell proliferation. Apoptosis was investigated using flow cytometry. Transwell assay and wound healing assay were carried out to examine the migration of MKN-7 and AGS cells. The Cellular ROS Assay Kit, Iron Assay Kit, and GSH/GSSG Ratio Detection Assay Kit were utilized to monitor lipid ROS level, iron level, and GSH/GSSG ratio, respectively. The interaction between miR-1276 and circTMEM87A or SLC7A11 was investigated using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft mouse model was constructed to explore the function of circTMEM87A in tumor formation in vivo. RESULTS: CircTMEM87A and SLC7A11 were upregulated, while miR-1276 was downregulated in GC tissues and cells. Knockdown of circTMEM87A suppressed the proliferation and migration and promoted apoptosis and ferroptosis of GC cells. CircTMEM87A served as a sponge for miR-1276, and miR-1276 inhibitor relieved the circTMEM87A knockdown-induced effects on GC cell phenotypes. Similarly, SLC7A11, a downstream gene of miR-1276, rescued miR-1276 overexpression-induced effects on GC cell function. Furthermore, circTMEM87A knockdown inhibited GC cell tumor phenotypes in vivo. CONCLUSION: CircTMEM87A promoted the proliferation and migration and inhibited apoptosis and ferroptosis of GC cells by increasing SLC7A11 expression through binding to miR-1276.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/genética , Dissulfeto de Glutationa , Espécies Reativas de Oxigênio , Carcinogênese/genética , Transformação Celular Neoplásica , Proliferação de Células/genética , Modelos Animais de Doenças , Ferro , MicroRNAs/genética , Linhagem Celular Tumoral , Sistema y+ de Transporte de Aminoácidos/genética
5.
Respir Res ; 24(1): 276, 2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-37953225

RESUMO

BACKGROUND: Lung cancer represents a significant public health issue in China, given its high incidence and mortality rates. Circular RNAs (circRNAs) have been recently proposed to participate in the development and progression of tumors. Nevertheless, their particular roles in the pathogenesis of lung adenocarcinoma (LUAD), the tumor microenvironment (TME), and the underlying molecular mechanisms are still not well understood. METHODS: High-throughput sequencing was used to analyze the circRNAs expression profiles in 7 pairs of human LUAD tissues. shRNA was used to knockdown the YAP1 and FGB genes. RNA sequencing and RT-qPCR were performed to classify the regulatory effects of circ_16601 in LUAD cells. The progression effect of circ_16601 on lung cancer was investigated in vitro and in vivo. RESULTS: The circ_16601 is significantly elevated in LUAD tissues compared to adjacent normal lung tissues, and its high expression is positively associated with poor prognosis in LUAD patients. Additionally, circ_16601 overexpression promotes LUAD cell proliferation in vitro and increases xenograft tissue growth in mice in vivo; circ_16601 also could recruit fibroblasts to cancer associate fibroblasts. Mechanistically, circ_16601 can directly bind to miR-5580-5p, preventing its ability to degrade FGB mRNA and enhancing its stability. Subsequently, circ_16601 promotes the activation of the Hippo pathway in a YAP1-dependent manner, leading to LUAD progression. CONCLUSIONS: Our findings shed valuable insights into the regulatory role of circ_16601 in LUAD progression and highlight its potential as a diagnostic and therapeutic target in LUAD. Overall, this study provides theoretical support to improve the prognosis and quality of life of patients suffering from this devastating disease.


Assuntos
Adenocarcinoma de Pulmão , Via de Sinalização Hippo , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Fibrinogênio , Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA Circular/genética , Microambiente Tumoral
6.
Proteins ; 89(6): 614-622, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33426726

RESUMO

Puromycin-hydrolizing peptidases have been described as members of the prolyl oligopeptidase peptidase family. These enzymes are present across all domains of life but still little is known of the homologs found in the pathogenic bacterium Mycobacterium tuberculosis. The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved prolyl oligopeptidase fold, defined by α/ß-hydrolase and ß-propeller domains with two distinctive loops that occlude access of large substrates to the active site. The enzyme displayed amino peptidase activity with a substrate specificity preference for hydrophobic residues in the decreasing order of phenylalanine, leucine, alanine and proline. The enzyme's active site is lined by residues Glu564 for the coordination of the substrates amino terminal moiety and His561, Val608, Tyr78, Trp306, Phe563 and Ty567 for the accommodation of hydrophobic substrates. The availability of a crystal structure for puromycin hydrolase of M. tuberculosis shall facilitate the development of inhibitors with therapeutic applications.


Assuntos
Aminopeptidases/química , Proteínas de Bactérias/química , Hidrolases/química , Mycobacterium tuberculosis/enzimologia , Prolil Oligopeptidases/química , Puromicina/química , Alanina/química , Alanina/metabolismo , Aminopeptidases/genética , Aminopeptidases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Hidrolases/genética , Hidrolases/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Cinética , Leucina/química , Leucina/metabolismo , Modelos Moleculares , Mycobacterium tuberculosis/química , Fenilalanina/química , Fenilalanina/metabolismo , Prolina/química , Prolina/metabolismo , Prolil Oligopeptidases/genética , Prolil Oligopeptidases/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Puromicina/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
7.
J Control Release ; 366: 637-649, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38215983

RESUMO

Induction of antigen-specific immune tolerance for the treatment of allergic or autoimmune diseases is an attractive strategy. Herein, we investigated the protective effect of a transdermal microneedle patch against allergic asthma by stimulating allergen-specific immune tolerance. We fabricated biodegradable tolerogenic nanoparticles (tNPs) that are loaded with a model allergen ovalbumin (OVA) and an immunomodulator rapamycin, and filled the tNPs into microneedle tips by centrifugation to form sustained-release microneedles. After intradermal immunization, the microneedles successfully delivered the cargos into the skin and sustainedly released them for over 96 h. Importantly, the microneedles induced allergen-specific regulatory T cells (Treg), decreased the levels of pro-inflammatory cytokines and antibodies while increased anti-inflammation cytokines, finally leading to restored immune homeostasis. The lung tissue analysis illustrated that the sustained-release microneedles significantly reduced the infiltration of eosinophils, decreased the accumulation of mucus and collagen, and significantly relived asthma symptoms. Our results suggested that the sustained-release microneedle-based transdermal delivery system can induce antigen-specific immune tolerance with improved compliance and efficacy, providing a new therapeutic strategy for the treatment of allergic and autoimmune diseases.


Assuntos
Asma , Doenças Autoimunes , Hipersensibilidade , Nanopartículas , Humanos , Preparações de Ação Retardada , Asma/tratamento farmacológico , Tolerância Imunológica , Alérgenos , Citocinas
8.
Am J Transl Res ; 15(12): 6949-6958, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38186981

RESUMO

BACKGROUND: Viral pneumonias, such as SARS and MERS, have been a recurrent challenge for the public healthcare system. COVID-19 posed an unprecedented global crisis. The primary impact of viral pneumonia is pathologic changes of lung tissue. However, the effect of SP-B site gene polymorphism on alveolar surface tension in viral pneumonia remains unexplored. OBJECTIVE: To explore the molecular mechanism of how the gene polymorphism at SP-B 1580 site regulates the pulmonary surfactant tension of viral pneumonia through the cellular pyroptosis signaling pathway using an in vivo animal experiment and a clinical trial. METHODS: We constructed a genetically modified mouse model of viral pneumonia and administered H5N1 influenza virus through intratracheal injection. After 48 hours, the survival rate of each mouse group was evaluated. Lung tissue, blood, and bronchoalveolar lavage fluid samples were collected for histopathologic analysis. Inflammatory factor concentrations were measured using ELISA. The level of apoptosis was determined using TUNEL assay. Changes in the expression of cell death-related factors were assessed using qRT-PCR and protein blotting. Additionally, blood samples from patients with viral pneumonia were analyzed to detect single nucleotide polymorphisms and explore their correlation with disease severity, inflammatory factor levels, and pulmonary surfactant protein expression. RESULTS: Following H5N1 infection of mice, the model group and hSP-B-C group showed high mortality rates within 24 hours. The survival rates in the blank control group, virus model group, hSP-B-C group, and hSP-B-T group were 100%, 50%, 37.5%, and 75%, respectively. Histologic analysis revealed significant lung tissue damage, congestion, alveolar destruction, and thickened alveolar septa in the model and hSP-B-C groups. However, these pulmonary lesions were significantly alleviated in the hSP-B-T group. Inflammatory factor levels were elevated in the model and hSP-B-C groups but reduced in the hSP-B-T group. TUNEL assay demonstrated a decrease in apoptotic cells in the lungs of the hSP-B-T group. Furthermore, the expression of SP-B and cell death-related proteins was downregulated in all three groups, with the lowest expression observed in the hSP-B-C group. The clinical trial found that patients with severe viral pneumonia exhibited a higher frequency of CC genotype and C allele in, along with increased inflammatory factor levels and decreased SP-B expression compared to those with mild-to-moderate viral pneumonia. CONCLUSION: SP-B polymorphism at the 1580 site regulates lung surfactant tension through the cell pyroptosis signaling pathway, thus affecting the progression of viral pneumonia.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35742335

RESUMO

Source apportionment of PM2.5 in Lanzhou, China, was carried out using positive matrix factorization (PMF). Seventeen elements (Ca, Fe, K, Ti, Ba, Mn, Sr, Cd, Se, Pb, Cu, Zn, As, Ni, Co, Cr, V), water-soluble ions (Na+, NH4+, K+, Mg2+, Ca2, Cl-, NO3-, SO42-), and organic carbon (OC) and elemental carbon (EC) were analyzed. The results indicated that the mean concentration of PM2.5 was 178.63 ± 96.99 µg/m3. In winter, the PM2.5 concentration was higher during the day than at night, and the opposite was the case in summer, and the nighttime PM2.5 concentration was 1.3 times higher than during the day. Water-soluble ions were the dominant component of PM2.5 during the study. PMF source analysis revealed six sources in winter, during the day and night: salt lakes, coal combustion, vehicle emissions, secondary aerosols, soil dust, and industrial emissions. In summer, eight sources during the day and night were identified: soil dust, coal combustion, industrial emissions, vehicle emissions, secondary sulfate, salt lakes, secondary aerosols, and biomass burning. Secondary aerosols, coal combustion, and vehicle emissions were the dominant sources of PM2.5. In winter, the proportions of secondary aerosols and soil dust sources were greater during the day than at night, and the opposite was the case in summer. The coal source, industrial emissions source, and motor vehicle emissions source were greater at night than during the day in winter. This work can serve as a case study for further in-depth research on PM2.5 pollution and source apportionment in Lanzhou, China.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Carbono/análise , China , Carvão Mineral/análise , Poeira/análise , Monitoramento Ambiental/métodos , Íons/análise , Material Particulado/análise , Estações do Ano , Solo , Emissões de Veículos/análise , Água/análise
10.
Nanomaterials (Basel) ; 12(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35159801

RESUMO

We demonstrated a passively Q-switched Er:Ca0.8Sr0.2F2 laser with indium tin oxide nanowire arrays as an optical modulator in the mid-infrared region. In the Q-switched regime, the maximum output power of 58 mW with a slope efficiency of 18.3% was acquired. Meanwhile, the minimum pulse duration and highest repetition rate of the stable pulse trains were 490 ns and 17.09 kHz, corresponding to single pulse energy of 3.4 µJ and peak power of 6.93 W, respectively. To the best of our knowledge it was the first time that indium tin oxide nanowire arrays were employed as a saturable absorber to make pulse lasers carried out at 2.8 µm. The experimental data show that indium tin oxide nanowire arrays can be employed as a competitive candidate for saturable absorber in the field of mid-infrared solid-state lasers.

11.
J Control Release ; 349: 699-711, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35907590

RESUMO

As two of the most widely used adjuvants, aluminum hydroxide and the oil-in-water emulsion MF59 have their intrinsic limitations: classical aluminum gel induces only weak cellular immune responses while MF59 cannot be used as an antigen delivery system due to its poor physical interaction with antigen molecules. Herein, we combined these two adjuvants and constructed a novel nano-vaccine delivery system by inserting aluminum hydroxide into the surface of a modified MF59 nano-emulsion (AlNEs). A model antigen ovalbumin (OVA) and an immune potentiator CpG were adsorbed on the surface of AlNEs (hereinafter AlNEs-OVA-CpG) through a facile mixing step. After subcutaneous injection, AlNEs-OVA-CpG effectively drained to lymph nodes, delivered both cargos into lymph node-resident antigen presenting cells (APCs), and escaped from lysosomes into the cytoplasm, resulting in enhanced antigen cross-presentation. Finally, AlNEs-OVA-CpG induced potent antigen-specific humoral and cellular immune responses, which significantly inhibited tumor growth and prolonged mice survival in a EG7-OVA tumor model. In sum, our results suggested that AlNEs have a great prospect to induce CD8+ T cell responses for subunit antigens.


Assuntos
Hidróxido de Alumínio , Neoplasias , Adjuvantes Imunológicos , Alumínio/farmacologia , Animais , Antígenos , Imunidade Celular , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina , Polissorbatos , Esqualeno , Água
12.
Acta Biomater ; 146: 357-369, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35577045

RESUMO

Photodynamic therapy (PDT) is an emerging therapeutic approach that can inhibit tumor growth by destroying local tumors and activating systemic antitumor immune responses. However, PDT can be ineffective because of photosensitizer aggregation, tumor-induced dendritic cells (DCS) dysfunction and PDT-mediated immunosuppression. Therefore, we designed chondroitin sulfate-based prodrug nanoparticles for the co-delivery of the photosensitizer chlorin e6 (Ce6) and retinoic acid (RA), which can reduce PDT-mediated immunosuppression by disrupting the Golgi apparatus and blocking the production of immunosuppressive cytokines. Moreover, CpG oligodeoxynucleotide was combined as immunoadjuvant to promote the maturation of DCs. As expected, the strategy of Golgi apparatus targeting immunotherapy combined PDT was confirmed to relieve PDT-induced immunosuppression, showed excellent PDT antitumor efficacy in B16F10-subcutaneous bearing mice model. Thus, our finding offers a promising approach for photodynamic immunotherapy of advanced cancers. STATEMENT OF SIGNIFICANCE: Golgi apparatus has been shown to be a potential target of immunosuppression for producing several immunosuppressive cytokines. In this work, a Golgi apparatus-targeted prodrug nanoparticle was developed to enhance the immune response in photodynamic immunotherapy. The nanoparticle can target and disrupt the Golgi apparatus in tumor cells, which reduced PDT-mediated immunosuppression by blocking the production of immunosuppressive cytokines. This work provides an effective strategy of PDT in combination with the Golgi apparatus-targeted nanovesicle for enhanced cancer therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Pró-Fármacos , Animais , Linhagem Celular Tumoral , Sulfatos de Condroitina , Citocinas , Complexo de Golgi , Fatores Imunológicos , Imunoterapia , Camundongos , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Pró-Fármacos/farmacologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-33572484

RESUMO

The characteristics of spatial-temporal distribution and sources for multiple environmental carriers (surface soil, soil profiles, atmospheric dustfall) from the typical industrial city of Baiyin in Northwestern China were studied by means of environmental magnetism. This study aims to contribute to the potential application of magnetic measurements in the case of multiple environmental carriers, for the evaluation and differentiation of urban pollution sources. Results show that background magnetic susceptibility of soil is 37 × 10-8 m3 kg-1, and that magnetite and hematite carry the magnetic properties. However, magnetic properties of urban soil and atmospheric dustfall are dominated by PSD magnetite. Magnetite content in soil samples is anomalously high surrounding metallurgical plant and slag dump (major industry district), of moderate value in the center of the city (major commercial district), and of low value in the west of city (Baiyin new zone). Vertical distribution of magnetite content in soil profile of waste land suggests that the pollutants are mostly enriched in the top 0-2 cm soil layers, while planting of crops near the industrial area may accelerate the transfer of contaminants deeper in the soil (2-30 cm); accordingly, reducing detrimental soil tillage practices can alleviate the vertical migration of pollution. Measurements of magnetic variations of atmospheric dustfall indicate that industrial emissions by factory chimneys and blowing dust from slag heap and mineral transport control the magnetic properties of dust, with slag heaps being the main pollution source since 2014. Governance of slag pollution is a primary task in resource-exhausted urban contexts. The combination of several magnetic parameters arising from multiple environmental carriers, such as soil and atmospheric dustfall, can provide comprehensive spatio-temporal information on environmental pollution.


Assuntos
Metais Pesados , Poluentes do Solo , China , Cidades , Poeira/análise , Monitoramento Ambiental , Poluição Ambiental/análise , Fenômenos Magnéticos , Metais Pesados/análise , Solo , Poluentes do Solo/análise
14.
Artigo em Inglês | MEDLINE | ID: mdl-34831718

RESUMO

Studies on the variation in the particulate matter (PM) content, Saturation Isothermal Remanent Magnetization (SIRM), and particle grain-size distribution at a high spatial resolution are helpful in evaluating the important role of urban forests in PM removal. In this study, the trees located in dense urban forests (T0) retained more PM than trees located in open spaces (T1-T4); the SIRM and PM weight of T0 were 1.54-2.53 and 1.04-1.47 times more than those of T1-T4, respectively. In addition, the SIRM and PM weight decreased with increasing distance to the road, suggesting that distance from pollution sources plays a key role in reducing the air concentration of PM. The different grain-size components were determined from frequency curve plots using a laser particle-size analyzer. A unimodal spectrum with a major peak of approximately 20 µm and a minor peak between 0.1 and 1 µm was observed, indicating that a large proportion of fine air PM was retained by the needles of the study trees. Additionally, more <2.5 µm size fraction particles were observed at the sampling site near the traffic source but, compared to a tree in a row of trees, the percentage of the >10 µm size fraction for the tree in the dense urban forest was higher, indicating that the particles deposited on the needle surface originating from traffic sources were finer than those from natural atmospheric dust. The exploration of the variation in the PM weight, SIRM, and grain size of the particles deposited on the needle surface facilitates monitoring the removal of PM by urban forests under different environmental conditions (e.g., in closed dense urban forests and in open roadside spaces), different distances to roads, and different sampling heights above the ground.


Assuntos
Poluentes Atmosféricos , Árvores , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise , Folhas de Planta/química
15.
Biomed Pharmacother ; 130: 110580, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32745913

RESUMO

The increased resistance of Candida to conventional antifungals brings great challenges for the clinical treatment of Candida infections. Recently, more attention has been paid to the research on combination therapy, which is a potential therapeutic approach for overcoming Candida resistance. In the present study, we first investigated the interaction between gypenosides (Gyp) and fluconazole (FLC) against Candida albicans (C. albicans) in vitro and in vivo. The in vitro test revealed a synergistic antifungal activity between Gyp and FLC against FLC-resistant (FLCR) C. albicans and indifferent effects for FLC-susceptible (FLCS) C. albicans, with the fractional inhibitory concentration index of 0.2539-0.2578 and 1-1.5, respectively. Besides, Gyp displayed synergistic interaction with FLC against FLCRC. albicans performed biofilm over 4 h, with the fractional inhibitory concentration index <0.5. In vivo, the combined antifungal efficacy of Gyp with FLC was evaluated by Galleria mellonella (G. mellonella) larvae. Gyp plus FLC prolonged the survival rate and reduced tissue invasion of larvae infected with FLCRC. albicans. Further experiments to get a first hint at what antifungal mechanisms might be inhibition of early biofilm formation, suppression of drug efflux, and inhibition of yeast-hyphal conversion. These findings will provide a new approach for the treatment of C. albicans infection.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Animais , Biofilmes/efeitos dos fármacos , Candida albicans/fisiologia , Candidíase/tratamento farmacológico , Sinergismo Farmacológico , Gynostemma , Larva/microbiologia , Lepidópteros/microbiologia , Extratos Vegetais/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-28439502

RESUMO

In this study, we found that ambroxol hydrochloride (128 µg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 µg/mL) against resistant planktonic Candida albicans (C. albicans) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans. With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans, increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans. The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.


Assuntos
Ambroxol/farmacologia , Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Sinergismo Farmacológico , Fluconazol/farmacologia , Animais , Candida albicans/fisiologia , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Lepidópteros , Testes de Sensibilidade Microbiana , Resultado do Tratamento
17.
Appl Bionics Biomech ; 2015: 145040, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27018226

RESUMO

In order to increase the workspace and the carrying capacity of biomimetic robotics hip joint, a novel biomimetic robotics hip joint was developed. The biomimetic robotics hip joint is mainly composed of a moving platform, frame, and 3-RRR orthogonal spherical parallel mechanism branched chains, and has the characteristics of compact structure, large bearing capacity, high positioning accuracy, and good controllability. The functions of the biomimetic robotics hip joint are introduced, such as the technical parameters, the structure and the driving mode. The biomimetic robotics hip joint model of the robot is established, the kinematics equation is described, and then the dynamics are analyzed and simulated with ADAMS software. The proposed analysis methodology can be provided a theoretical base for biomimetic robotics hip joint of the servo motor selection and structural design. The designed hip joint can be applied in serial and parallel robots or any other mechanisms.

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