Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
1.
Quant Imaging Med Surg ; 14(6): 4141-4154, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38846278

RESUMO

Background: Bone erosion in the sacroiliac joint (SIJ) is highly specific for the diagnosis of axial spondyloarthritis (axSpA) and may indicate early disease progression. The 3D ultrashort echo time (3D-UTE) technique excels in providing clear contrast between the articular cartilage and the bone cortex interface. Additionally, it is emerging as a promising quantitative tool for detecting early cartilage changes. Therefore, this study aimed to evaluate the diagnostic performance of 3D-UTE sequences in identifying bone erosion in the SIJ of patients with axSpA and to clarify the potential of cartilage T2* values as a quantitative biomarker for axSpA. Methods: This prospective study employed convenience and consecutive sampling methods to recruit patients diagnosed with axSpA in Peking University Third Hospital who met the Assessment of Spondyloarthritis International Society (ASAS) criteria and also an equal number of healthy volunteers. After providing informed consent, all participants underwent 3D-UTE sequences and conventional T2* mapping of the SIJs. Two radiologists separately interpreted the bone erosion of each SIJ on 3D-UTE sequences. Erosion detection of SIJs via computed tomography (CT) served as the standard of reference. The T2* values of the cartilage were measured and compared, and the diagnostic efficacy of the T2* value for axSpA diagnosis was evaluated. Results: A total of 32 patients and 32 healthy volunteers were included. The 3D-UTE sequence, as separately assessed by two reviewers in terms of its ability to detect erosions, exhibited a notable level of accuracy. For the two reviewers, the respective diagnostic sensitivities were 94.7% and 92.9%, the specificities were 97.4% and 96.5%, positive predictive values were 96.7% and 95.4%, the negative predictive values were 95.9% and 94.5%, the accuracies were 96.2% and 94.9%, and the areas under the curve (AUCs) were 96.1% and 94.7%. For the detection of erosions, the interreader κ value was 0.949. The T2* values of the SIJ cartilage were significantly higher in patients with axSpA than in healthy volunteers. The intraobserver intraclass correlation coefficients (ICCs) for T2* measurements ranged between 80.5% and 82.2%. Meanwhile, the interobserver ICCs for UTE-T2* and gradient echo T2* measurements were 81.5% and 80.8%, respectively. The AUCs of the UTE-T2* values for discriminating patients with axSpA from the healthy volunteers of the two readers were 73.3% and 71.6%, respectively. Conclusions: 3D-UTE sequences can be used as a reliable morphological imaging technique for detecting bone erosion in the SIJ. Additionally, UTE-T2* values of the cartilage may offer a quantitative method for identifying patients with axSpA.

2.
Environ Sci Technol ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317381

RESUMO

Ammonium-related pathways are important for groundwater arsenic (As) enrichment, especially via microbial Fe(III) reduction coupled with anaerobic ammonium oxidation; however, the key pathways (and microorganisms) underpinning ammonium-induced Fe(III) reduction and their contributions to As mobilization in groundwater are still unknown. To address this gap, aquifer sediments hosting high As groundwater from the western Hetao Basin were incubated with 15N-labeled ammonium and external organic carbon sources (including glucose, lactate, and lactate/acetate). Decreases in ammonium concentrations were positively correlated with increases in the total produced Fe(II) (Fe(II)tot) and released As. The molar ratios of Fe(II)tot to oxidized ammonium ranged from 3.1 to 3.7 for all incubations, and the δ15N values of N2 from the headspace increased in 15N-labeled ammonium-treated series, suggesting N2 as the key end product of ammonium oxidation. The addition of ammonium increased the As release by 16.1% to 49.6%, which was more pronounced when copresented with organic electron donors. Genome-resolved metagenomic analyses (326 good-quality MAGs) suggested that ammonium-induced Fe(III) reduction in this system required syntrophic metabolic interactions between bacterial Fe(III) reduction and archaeal ammonium oxidation. The current results highlight the significance of syntrophic ammonium-stimulated Fe(III) reduction in driving As mobilization, which is underestimated in high As groundwater.

3.
Arthritis Res Ther ; 25(1): 227, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001465

RESUMO

BACKGROUND: Identifying axial spondyloarthritis (axSpA) activity early and accurately is essential for treating physicians to adjust treatment plans and guide clinical decisions promptly. The current literature is mostly focused on axSpA diagnosis, and there has been thus far, no study that reported the use of a radiomics approach for differentiating axSpA disease activity. In this study, the aim was to develop a radiomics model for differentiating active from non-active axSpA based on fat-suppressed (FS) T2-weighted (T2w) magnetic resonance imaging (MRI) of sacroiliac joints. METHODS: This retrospective study included 109 patients diagnosed with non-active axSpA (n = 68) and active axSpA (n = 41); patients were divided into training and testing cohorts at a ratio of 8:2. Radiomics features were extracted from 3.0 T sacroiliac MRI using two different heterogeneous regions of interest (ROIs, Circle and Facet). Various methods were used to select relevant and robust features, and different classifiers were used to build Circle-based, Facet-based, and a fusion prediction model. Their performance was compared using various statistical parameters. p < 0.05 is considered statistically significant. RESULTS: For both Circle- and Facet-based models, 2284 radiomics features were extracted. The combined fusion ROI model accurately differentiated between active and non-active axSpA, with high accuracy (0.90 vs.0.81), sensitivity (0.90 vs. 0.75), and specificity (0.90 vs. 0.85) in both training and testing cohorts. CONCLUSION: The multi-ROI fusion radiomics model developed in this study differentiated between active and non-active axSpA using sacroiliac FS T2w-MRI. The results suggest MRI-based radiomics of the SIJ can distinguish axSpA activity, which can improve the therapeutic result and patient prognosis. To our knowledge, this is the only study in the literature that used a radiomics approach to determine axSpA activity.


Assuntos
Espondiloartrite Axial , Espondilartrite , Humanos , Espondilartrite/tratamento farmacológico , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia
4.
Am J Cancer Res ; 13(6): 2572-2587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424805

RESUMO

Due to the lack of sensitive biomarkers, cancer disease kill 9.6 million individuals each year around the globe. The present study aimed to explore the association between ELL Associated Factor 2 (EAF2) expression and its diagnostic and prognostic landscape across different human cancers using an in silico and in vitro approach. To achieve the defined goals of this study, we used the following online sources: UALCAN, KM plotter, TNMplot, cBioPortal, STRING, DAVID, MuTarget, Cytoscape, and CTD. In addition to this, we also used additional The Cancer Genome Atlas (TCGA) datasets via TIMER2, GENT2, and GEPIA to confirm the expression of EAF2 on additional cohorts. Finally, we performed RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques-based analysis using A549, ABC-1, EBC-1, LK-2 lung cancer cell lines, and MRC-9 normal control lung cell line for further validation of the results. On balance, EAF2 was elevated in 19 types of human cancers and its up-regulation was significantly correlated with shorter overall survival (OS), relapse-free survival (RFS), and metastasis in Liver Hepatocellular Carcinoma (LIHC) and Lung Squamous Cell Carcinoma (LUSC) patients. We further evaluated that EAF2 expression was also elevated across LIHC and LUSC patients belonging to different clinicopathological features. Through pathway analysis, EAF2 associations were observed with four important pathways. Moreover, some worth noticing correlations were also documented between EAF2 expression and its promoter methylation level, genetic alterations, other mutant genes, tumor purity, and different immune cells infiltration. The higher EAF2 expression contributes significantly to the tumorigenesis and metastasis of LIHC and LUSC. Therefore, it can be used as a common biomarker in these cancers.

5.
Pathogens ; 12(1)2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36678450

RESUMO

The mosquito Aedes albopictus can transmit various arboviral diseases, posing a severe threat to human health. As an environmentally friendly method, sterile insect technology (SIT) is considered an alternative to traditional methods such as chemical pesticides to control Ae. albopictus. In SIT, the sterility of male mosquitoes can be achieved by γ-ray or X-ray radiation. Compared with γ-rays, X-rays are easier to obtain, cheaper, and less harmful. However, there is a lack of comparative assessment of these two types of radiation for SIT under the same controlled conditions. Here, we compared the effects of X-ray and γ-ray radiation on the sterility of Ae. albopictus males under laboratory-controlled conditions. Neither type of radiation affected the number of eggs but significantly reduced the survival time and hatch rate. The same dose of γ-rays caused a higher sterility effect on males than X-rays but had a more significant impact on survival. However, X-rays could achieve the same sterility effect as γ-rays by increasing the radiation dose. For example, X-rays of 60 Gy induced 99% sterility, similar to γ-rays of 40 Gy. In the test of male mating competitiveness, the induced sterility and the male mating competitiveness index were also identical at the same release ratio (sterile males/fertile males). At a release ratio of 7:1, nearly 80% of eggs failed to hatch. Sterile males produced by X-ray and γ-ray radiation had similar male competitiveness in competition with field males. In conclusion, a higher dose of X-rays is required to achieve the same sterility effect, compared to γ-rays. When γ-rays are not readily available, high-dose X-rays can be used instead. This study provides data supporting the selection of more suitable radiation for the field release of sterile male mosquitoes.

6.
Sci Total Environ ; 858(Pt 3): 160066, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36356776

RESUMO

Sulfide-induced reduction (sulfidization) of arsenic (As)-bearing Fe(III) (oxyhydro)oxides may lead to As mobilization in aquifer systems. However, little is known about the relative contributions of sulfidization and non-sulfidization of Fe(III) (oxyhydro)oxides reduction to As mobilization. To address this issue, high As groundwater with low sulfide (LS) and high sulfide (HS) concentrations were pumped through As(V)-bearing ferrihydrite-coated sand columns (LS-column and HS-column, respectively) being settled within wells in the western Hetao Basin, China. Sulfidization of As(V)-bearing ferrihydrite was evidenced by the increase in dissolved Fe(II) and the presence of solid Fe(II) and elemental sulfur (S0) in both the columns. A conceptual model was built using accumulated S0 and Fe(II) produced in the columns to calculate the proportions of sulfidization-induced Fe(III) (oxyhydro)oxide reduction and non-sulfidization-induced Fe(III) (oxyhydro)oxide reduction. Fe(III) reduction via sulfidization occurred preferentially in the inlet ends (LS-column, 31 %; HS-column, 86 %), while Fe(III) reduction via non-sulfidization processes predominated in the outlet ends (LS-column, 96 %; HS-column, 86 %), and was attributed to the metabolism of genera associated with Fe(III) reduction (including Shewanella, Ferribacterium, and Desulfuromonas). Arsenic was mobilized in the columns via sulfidization and non-sulfidization processes. More As was released from the solid of the HS-column than that of the LS-column due to the higher intensity of sulfidization in the presence of higher concentrations of dissolved S(-II). Overall, this study highlights the sulfidization of As-bearing Fe(III) (oxyhydro)oxides as an important As-mobilizing pathway in complex As-Fe-S bio-hydrogeochemical networks.


Assuntos
Arsênio , Compostos Férricos , Areia , Sulfetos , Óxidos , Compostos Ferrosos
7.
Sci Adv ; 8(49): eabo5686, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36475802

RESUMO

High-melting point alloy catalysts have been reported to be effective for the structure-controlled growth of single-wall carbon nanotubes (SWCNTs). However, some fundamental issues remain unclear because of the complex catalytic growth environment. Here, we directly investigated the active catalytic phase of Co-W-C alloy catalyst, the growth kinetics of CNTs, and their interfacial dynamics using closed-cell environmental transmission electron microscopy at atmospheric pressure. The alloy catalyst was precisely identified as a cubic η-carbide phase that remained unchanged during the whole CNT growth process. Rotations of the catalyst nanoparticles during CNT growth were observed, implying a weak interfacial interaction and undefined orientation dependence for the solid catalyst. Theoretical calculations suggested that the growth kinetics are determined by the diffusion of carbon atoms on the surface of the η-carbide catalyst and through the interface of the catalyst-CNT wall.

9.
Quant Imaging Med Surg ; 11(6): 2499-2508, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34079719

RESUMO

BACKGROUND: Our study aimed to characterize the imaging appearance of spinal fractures in ankylosing spondylitis (AS) and identify situations in which the use of magnetic resonance imaging (MRI) is necessary. METHODS: A total of 70 cases of spinal fractures associated with AS were retrospectively enrolled. Two radiologists independently reviewed the preoperative images. The location, type, ligament injury, neurological injury, and epidural hematoma following spinal fractures were assessed. RESULTS: Only one patient had a vertebral compression fracture, and 69 patients had 77 transverse fractures involving three columns. The most frequent injuries in AS patients were type B3 (N=32, 43.8%) spine fractures, followed by type C (N= 20, 27.4%) spine fractures. There were significant differences in fracture types of the different spine regions (H=14.1, P<0.0001). Most type C spine fractures were located in the lower cervical spine, while most of the type B2 spine fractures were located in the thoracic spine. Transverse fractures were classified as shear or stress type fractures. In total, there were 62 shear fractures and 15 stress fractures. All of the transverse fractures were detected by computed tomography (CT). The accuracy of CT in the diagnosis of the exact anatomic involvement of transverse fractures was significantly higher than that of MRI (χ2=8.36, P=0.014). The anterior longitudinal ligament (ALL) was the most frequently torn ligament. Tears of ossified ligaments were best visualized by sagittal reformatted CT. Lower cervical fractures were more likely to be associated with neurological injury compared with fractures to other regions of the spine (χ2=7.24, P=0.025). There were six epidural hematoma cases, which were only detected by MRI, were found to have fractures of the lower cervical spine. CONCLUSIONS: We recommend a whole-spine CT examination with three-dimensional reconstruction for detecting a suspected fracture in AS patients. In cases with neurological injury, MRI examinations are always mandatory. AS patients with lower cervical spine fractures require further investigation by MRI. Patients with non-lower cervical spine fractures without any neurological deficits do not need to undergo an immediate MRI.

10.
J Nanopart Res ; 23(6): 130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149308

RESUMO

Tumor vaccine has shown outstanding advantages and good therapeutic effects in tumor immunotherapy. However, antigens in tumor vaccines can be easily cleared by the reticuloendothelium system in advance, which leads to poor therapeutic effect of tumor vaccines. Moreover, it was still hard to monitor the fate and distribution of antigens. To address these limitations, we synthesized a traceable nanovaccine based on gold nanocluster-labeled antigens and upconversion nanoparticles (UCNPs) for the treatment of melanoma in this study. PH-sensitive Schiff base bond is introduced between UCNPs and gold nanocluster-labeled ovalbumin antigens for monitoring antigens release. Our studies demonstrated that UCNPs conjugated metallic antigen showed excellent biocompatibility, pH-sensitive and therapeutic effect.

11.
Life Sci ; 270: 119141, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33529672

RESUMO

Although the proteins in bromodomain and extra-terminal domain (BET) family are promising therapy drug targets for numerous human diseases, the binding effectiveness is interfered by the competition from non-BET protein BRD9. In this study, molecular docking, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition methods were employed to clarify the selective inhibition mechanism of nitroxoline. The results showed that the different cavity volume of effective embedding inhibitor and the changes in conserved residues were associated with the significant higher selectivity of inhibitor nitroxoline for BET family than non-BET protein (BRD9). In addition, the non-polar interactions occurred in Phe83, Val87 at ZA loop, and the polar interaction appeared in Met132, Asn135 at BC loop. Therefore, when designing a new inhibitor, it could better improve the inhibitor activity by introducing the heteroatom conjugated pyridine-like moiety and the strong electron-withdrawing nitro-like moiety. Overall, this study not only clarified the molecular mechanism of the selective inhibition of nitroxoline, but also provided insight into designing more effective BET inhibitors in next step.


Assuntos
Nitroquinolinas/metabolismo , Nitroquinolinas/farmacologia , Proteínas/metabolismo , Sítios de Ligação , Desenho de Fármacos , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Nitroquinolinas/química , Proteínas Nucleares/metabolismo , Ligação Proteica , Domínios Proteicos , Proteínas/antagonistas & inibidores , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo
13.
Molecules ; 25(24)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302335

RESUMO

Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., 13C NMR, 1H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC50) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties.


Assuntos
Compostos de Bifenilo/síntese química , Compostos de Bifenilo/farmacologia , Técnicas de Química Sintética , Lignanas/síntese química , Lignanas/farmacologia , Metformina/química , Triazinas/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclização , Citocinas/biossíntese , Regulação da Expressão Gênica , Humanos , Lignanas/química , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Células RAW 264.7 , Relação Estrutura-Atividade
14.
Artigo em Inglês | MEDLINE | ID: mdl-33246279

RESUMO

Sandalwood is one of the most valuable woods in the world. However, today's counterfeits are widespread, it is difficult to distinguish authenticity. In this paper, similar genus (Dalbergia and Pterocarpus) and confused species (Gluta sp.) of sandalwood were quickly and efficiently identified. Rapid identification model based on 1H NMR and decision tree (DT) algorithm was firstly developed for the identification of sandalwood, and the accuracy was improved by introducing the AdaBoost algorithm. The accuracy of the final model was above 95%. And the feature components between different species of sandalwood were further explored using UHPLC-QTOFMS and NMR spectrometry. The results showed that 183 compounds were identified, among which 99 were known components, 84 were unknown components. The 1H NMR and 13C NMR signals of 505 samples were assigned, among them, 14 compounds were attributed, characteristic chemical shift intervals with great differences in the model were analysed. Furthermore, the fragmentation pattern of different compounds from sandalwood, in both positive and negative ion ESI modes, was summarized. The results showed a potential and rapid tool based on DT, NMR spectroscopy and UHPLC-QTOFMS, which had performed great potential for rapid identification and feature analysis of sandalwood.


Assuntos
Algoritmos , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Santalum/química , Árvores de Decisões , Flavonoides/análise , Flavonoides/química , Glicosídeos/análise , Glicosídeos/química
15.
ACS Appl Mater Interfaces ; 12(31): 34667-34677, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32610896

RESUMO

Efficient drug delivery into tumor cells while bypassing many biological barriers is still a challenge for cancer therapy. By taking advantage of the palladium (Pd)-mediated in situ activation of a prodrug and the glucose oxidase (GOD)-based ß-d-glucose oxidation reaction, we developed a multisynergistic cancer therapeutic platform that combined doxorubicin (DOX)-induced chemotherapy with GOD-mediated cancer-orchestrated oxidation therapy and cancer starvation therapy. In the present work, we first synthesized DOX prodrugs (pDOXs) and temporarily assembled them with ß-cyclodextrins to reduce their toxic side effects. Then, a nanoreactor was constructed by synthesizing Pd0 nanoparticles in situ within the pores of mesoporous silica nanoparticles for the conversion of pDOX into the active anticancer drug. Furthermore, GOD was introduced to decrease the pH of the tumor microenvironment and induce cancer-orchestrated oxidation/starvation therapy by catalyzing ß-d-glucose oxidation to form hydrogen peroxide (H2O2) and gluconic acid. Our study provides a new strategy that employs a cascade chemical reaction to achieve combined orchestrated oxidation/starvation/chemotherapy for the synergistic killing of cancer cells and the suppression of tumor growth.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Nanopartículas/química , Pró-Fármacos/uso terapêutico , Animais , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Doxorrubicina/síntese química , Doxorrubicina/química , Feminino , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Nus , Estrutura Molecular , Paládio/química , Tamanho da Partícula , Pró-Fármacos/síntese química , Pró-Fármacos/química , Propriedades de Superfície
16.
Clin Exp Pharmacol Physiol ; 47(8): 1382-1392, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32155673

RESUMO

In this study, we investigated the lipid metabolism regulatory activity of a novel metformin derivative (MD568) and its potential mechanism of action in obese rats with type 2 diabetes mellitus (T2 DM). Previous gene chip analysis of 3T3-L1 cells have shown that MD568 regulates the transcription of genes involved in the peroxisome proliferator-activated receptor (PPAR) signalling pathway, fatty acid metabolism, and glycerolipid metabolism. In this study, obese T2 DM rats were treated with MD568 (200 mg/kg) for 8 weeks. Results showed that MD568 significantly reduced the body weight gain, plasma glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. MD568 treatment also improved the insulin resistance of obese T2 DM model rats. In particular, in white adipose tissue, MD568 inhibited the excessive volume increment of adipose cells by down-regulating the protein levels of CCAAT/enhancer-binding protein-α (C/EBP-α) and PPAR-γ, as well as the transcription of their target lipid metabolism-related genes. In the liver, MD568 inhibited hepatic fatty lesions and interfered with hepatic gluconeogenesis by regulating the expression of lipid metabolism-related genes and glycogen-related kinases. In conclusion, our results suggest that the newly synthesized MD568 affects the maintenance of lipid homeostasis in obese type 2 diabetic rats.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metformina/química , Metformina/farmacologia , Obesidade/complicações , Animais , Masculino , Ratos
17.
Int J Biol Macromol ; 150: 509-518, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32057851

RESUMO

Nitroreductase (NTR), a member of the flavoenzyme family, could react with nicotinamide adenine dinucleotide by reducing nitro to amino at hypoxic tumor, which can be monitored by some fluorescent probes in vivo. Here, molecular docking and molecular dynamics simulation techniques were used to explore the molecular mechanisms between NTR and probes. The results showed that formation of hydrogen bond in 1F5V-13 between A@His215 and B@Ser41 with 74.53% occupancy might be the main reason for the decrease of probe fluorescence emission in experiment. Moreover, Probe 16 was rotated by nearly 60 degrees with respect to the position of other probes in protein binding pocket, deforming the protein active pocket, changing the hydrogen bond formation, which leads to the fluorescence performance of 16 with electron donor and electron acceptor groups was superior to other probes in experiment. The deformation of protein active pocket and the formation of intramolecular hydrogen bonds revealed the difference in performance of NTR fluorescent probe at molecular level, which provide theoretical guidance for latter design of fluorescent probes with better performance.


Assuntos
Corantes Fluorescentes/química , Ligação de Hidrogênio , Nitrorredutases/química , Aminoácidos/química , Sítios de Ligação , Humanos , Ligantes , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
18.
Chem Biodivers ; 17(4): e1900684, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32064755

RESUMO

Anemarrhena asphodeloides Bunge is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides Bunge. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet ß cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides Bunge by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic ß cells through reducing IL-1ß (interleukin-1ß) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.


Assuntos
Anemarrhena/química , Glicolipídeos/toxicidade , Substâncias Protetoras/química , Saponinas/química , Esteroides/química , Anemarrhena/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Análise Discriminante , Glutationa/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Interleucina-1beta/metabolismo , Lipidômica/métodos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Malondialdeído/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Análise de Componente Principal , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Células RAW 264.7 , Saponinas/isolamento & purificação , Saponinas/farmacologia , Saponinas/uso terapêutico , Esteroides/isolamento & purificação , Esteroides/farmacologia , Esteroides/uso terapêutico
19.
Environ Int ; 136: 105489, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31991235

RESUMO

Various functional groups of microorganisms and related biogeochemical processes are likely to control arsenic (As) mobilization in groundwater systems. However, spatially-dependent correlations between microbial community composition and geochemical zonation along groundwater flow paths are not fully understood, especially with respect to arsenic mobility. The western Hetao Basin was selected as the study area to address this limitation, where groundwater flows from a proximal fan (geochemical-group I: low As, oxidizing), through a transition area (geochemical-group II: moderate As, moderately-reducing) and then to a flat plain (geochemical-group III: high As, reducing). High-throughput Illumina 16S rRNA gene sequencing showed that the microbial community structure in the proximal fan included bacteria affiliated with organic carbon degradation and nitrate-reduction or even nitrate-dependant Fe(II)-oxidation, mainly resulting in As immobilization. In contrast, for the flat plain, high As groundwater contained Fe(III)- and As(V)-reducing bacteria, consistent with current models on As mobilization driven via reductive dissolution of Fe(III)/As(V) mineral assemblages. However, Spearman correlations between hydrogeochemical data and microbial community compositions indicated that ammonium as a possible electron donor induced reduction of Fe oxide minerals, suggesting a wider range of metabolic pathways (including ammonium oxidation coupled with Fe(III) reduction) driving As mobilization in high As groundwater systems.


Assuntos
Compostos de Amônio , Arsênio , Água Subterrânea , Microbiota , Poluentes Químicos da Água , Elétrons , Compostos Férricos , Sedimentos Geológicos , RNA Ribossômico 16S
20.
Med Sci Monit ; 25: 9319-9326, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31811711

RESUMO

BACKGROUND Schistosomiasis is one of the most important infectious parasitic diseases in the world. The most important was to control schistosomiasis is through a combination of medical therapy and immunization. The membrane antigens Tsp2 and 29 from Schistosoma are promising anti-schistosomiasis vaccine candidates. MATERIAL AND METHODS In this study, the pcDNA3.1(+)-SjTsp2, pcDNA3.1(+)-Sj29, and pcDNA3.1 (+)-SjTsp2-29 eukaryotic expression vectors were successfully constructed as DNA vaccines, and the protective abilities of these vaccines were evaluated in mice. RESULTS The results showed that vaccination with SjTsp2, Sj29, and SjTsp2-29 reduced parasite burden and hepatic pathology compared to the control group, and the protective effect of the bivalent SjTsp2-29 DNA vaccine was better than that of the univalent SjTsp2 or Sj29 DNA vaccines. We also found high levels of IgG, IgG1, and IgG2a against SjTsp2, Sj29, and SjTsp2-29 DNA vaccines, with high expression of IFN-γ and no IL-4 in the mice. CONCLUSIONS The double-membrane antigen DNA vaccine SjTsp2-29 elicited protection against Schistosoma infection and might serve as a vaccine candidate.


Assuntos
Schistosoma japonicum/imunologia , Esquistossomose/terapia , Vacinas de DNA/farmacologia , Animais , Anticorpos Anti-Helmínticos , China , Feminino , Imunização , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos , Schistosoma japonicum/metabolismo , Esquistossomose/imunologia , Trombospondinas/imunologia , Vacinação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...