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1.
Food Res Int ; 162(Pt B): 112082, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461331

RESUMO

Chinese wild rice (Zizania latifolia) is rich in flavonoids and the characteristic colour of its pericarp is attributed to the flavonoids. In this study, the molecular basis of the colour change in the pericarp of Chinese wild rice was studied using metabolomics and proteomics. Whole seeds in three developmental stages (10, 20, and 30 days after flowering) were characterised based on phenolic contents, free amino acids (FAAs), and the expression level and activities of enzymes critical in flavonoid biosynthesis. The total phenolic and proanthocyanidin contents of Chinese wild rice increased gradually, whereas total flavonoid and FAA contents decreased during seed development. Metabolomic analysis revealed gradual upward trends for 57 flavonoids (sub classes 1, 3, and 10) related to colour change in the pericarp. Proteomic analysis showed that the phenylpropanoid biosynthesis metabolic pathway was enriched with differentially expressed proteins and was associated with flavonoid biosynthesis. Proteomic data suggested that leucoanthocyanidin reductase and WD40 repeat protein may be involved in flavonoid biosynthesis in Chinese wild rice, which was also verified by real-time quantitative PCR. Our results provide new insights into the understanding of the colour formation in the pericarp of Chinese wild rice.


Assuntos
Oryza , Oryza/genética , Proteômica , Cor , Poaceae , Excipientes , Flavonoides , Fenóis , China
2.
Chem Sci ; 13(42): 12577-12587, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36382274

RESUMO

In the present study, norbornene-tetrazine ligation chemistry is harnessed for developing clickable RNA switches in biological contexts. This RNA control strategy is explored with a variety of applications. We further demonstrate the application of RNA-based norbornene-tetrazine ligation chemistry for controlling CRISPR systems. Moreover, the manipulation of gene editing in human cells is accomplished.

3.
Front Immunol ; 13: 1043293, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389808

RESUMO

During the past decades, with the implementation of pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCVs), a dramatic reduction in vaccine type diseases and transmissions has occurred. However, it is necessary to develop a less expensive, serotype-independent pneumococcal vaccine due to the emergence of nonvaccine-type pneumococcal diseases and the limited effect of vaccines on colonization. As next-generation vaccines, conserved proteins, such as neuraminidase A (NanA), elongation factor Tu (Tuf), and pneumolysin (Ply), are promising targets against pneumococcal infections. Here, we designed and constructed a novel fusion protein, NanAT1-TufT1-PlyD4, using the structural and functional domains of full-length NanA, Tuf and Ply proteins with suitable linkers based on bioinformatics analysis and molecular cloning technology. Then, we tested whether the protein protected against focal and lethal pneumococcal infections and examined its potential protective mechanisms. The fusion protein NanAT1-TufT1-PlyD4 consists of 627 amino acids, which exhibits a relatively high level of thermostability, high stability, solubility and a high antigenic index without allergenicity. The purified fusion protein was used to subcutaneously immunize C57BL/6 mice, and NanAT1-TufT1-PlyD4 induced a strong and significant humoral immune response. The anti-NanAT1-TufT1-PlyD4 specific IgG antibody assays increased after the first immunization and reached the highest value at the 35th day. The results from in vitro experiments showed that anti-NanAT1-TufT1-PlyD4 antisera could inhibit the adhesion of Streptococcus pneumoniae (S. pneumoniae) to A549 cells. In addition, immunization with NanAT1-TufT1-PlyD4 significantly reduced S. pneumoniae colonization in the lung and decreased the damage to the lung tissues induced by S. pneumoniae infection. After challenge with a lethal dose of serotype 3 (NC_WCSUH32403), a better protection effect was observed with NanAT1-TufT1-PlyD4-immunized mice than with the separate full-length proteins and the adjuvant control; the survival rate was 50%, which met the standard of the marketed vaccine. Moreover, we showed that the humoral immune response and the Th1, Th2 and Th17-cellular immune pathways are involved in the immune protection of NanAT1-TufT1-PlyD4 to the host. Collectively, our results support that the novel fusion protein NanAT1-TufT1-PlyD4 exhibits extensive immune stimulation and is effective against pneumococcal challenges, and these properties are partially attributed to humoral and cellular-mediated immune responses.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Camundongos , Animais , Anticorpos Antibacterianos , Camundongos Endogâmicos C57BL , Vacinas Pneumocócicas , Infecções Pneumocócicas/prevenção & controle
4.
Nucleic Acids Res ; 50(19): 11387-11400, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36263801

RESUMO

It is important to develop small moelcule-based methods to modulate gene editing and expression in human cells. The roles of the G-quadruplex (G4) in biological systems have been widely studied. Here, G4-guided RNA engineering is performed to generate guide RNA with G4-forming units (G4-gRNA). We further demonstrate that chemical targeting of G4-gRNAs holds promise as a general approach for modulating gene editing and expression in human cells. The rich structural diversity of RNAs offers a reservoir of targets for small molecules to bind, thus creating the potential to modulate RNA biology.


Assuntos
Sistemas CRISPR-Cas , RNA Guia , Humanos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Genômica , RNA/genética , RNA Guia/genética , RNA Guia/metabolismo , Quadruplex G
5.
Front Endocrinol (Lausanne) ; 13: 970122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992100

RESUMO

Objective: To investigate the relations of Triglyceride glucose (TyG) index with cerebral small vessel disease (CSVD) burden and cognitive function in aged patients with type 2 diabetes mellitus (T2DM). Methods: A total of 308 elderly patients with T2DM were included in this retrospective study. The standardized Chinese version of Mini-Mental State Examination was used to assess cognitive function. The total CSVD burden score was assessed by combining four imaging markers of CSVD, including the presence of white matter hyperintensity, cerebral microbleeds in the deep, lacunes and enlarged perivascular spaces in the basal ganglia. The TyG index was calculated as the formula of ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. We used logistic regression analysis and mediation analysis to investigate the relations of TyG index with CSVD and cognitive function. Results: Multivariate binary logistic regression analysis showed that increased TyG index (OR: 2.241; 95% Confidence Interval(CI): 1.439 to 3.490; P <0.001), or severe CSVD burden (OR: 2.198; 95% CI: 1.283 to 3.763; P = 0.004) was associated with an increased risk of cognitive impairment in elderly patients with T2DM after adjusting for potential confounders. In addition, TyG index was an independent risk factor of severe CSVD burden (OR: 1.472; 95% CI: 1.003 to 2.160; P = 0.048) after controlling for potential confounders. Compared with the lowest TyG index tertile, the multivariable-adjusted OR of the highest tertile was 3.298 (95% CI: 1.685 to 6.452; P for trend <0.001) for cognitive impairment, 1.933 (95% CI: 1.010 to 3.698; P for trend = 0.047) for severe CSVD burden. Mediation analysis found a significant moderating effect of the severe CSVD burden on the association between higher TyG index levels and cognitive impairment. Conclusions: The increased TyG index is an independent risk factor for cognitive impairment and severe CSVD burden in clinical practice. A proportion of the effect of increased TyG index on cognitive impairment may be due to the aggravation of CSVD burden.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Idoso , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Glucose , Humanos , Estudos Retrospectivos , Triglicerídeos
6.
FEBS Open Bio ; 12(8): 1542-1557, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35674216

RESUMO

Glucocorticoid-induced TNF receptor-related (GITR) can act as a co-stimulatory receptor, representing a potential target for safely enhancing immunotherapy efficacy. GITR is triggered by a GITR ligand or an agonist antibody and activates CD8+ and CD4+ effector T cells, reducing tumor-infiltrating Treg numbers and resulting in activation of immune responses and tumor cell destruction by effector T cells. GITR is an attractive target for immunotherapy, especially in combination therapy with immune checkpoint inhibitors, as is being explored in clinical trials. Using H2L2 transgenic mice encoding the human immunoglobulin variable region and hybridoma technology, we generated a panel of fully human antibodies that showed excellent specific affinity and strong activation of human T cells. After conversion to fully human antibodies and engineering modification, we obtained an anti-GITR antibody hab019e2 with enhanced antitumor activity in a B-hGITR MC38 mouse model compared to Tab9H6V3, an anti-GITR antibody that activates T cells and inhibits Treg suppression from XenoMouse. As a fully human antibody with its posttranslational modification hot spot removed, the hab019e2 antibody exerted more potent therapeutic effects, and may have potential as a novel and developable antibody targeting GITR for follow-up drug studies.


Assuntos
Glucocorticoides , Receptores do Fator de Necrose Tumoral , Animais , Anticorpos , Linhagem Celular Tumoral , Proteína Relacionada a TNFR Induzida por Glucocorticoide/agonistas , Humanos , Imunoterapia/métodos , Camundongos , Receptores do Fator de Necrose Tumoral/agonistas
7.
Polymers (Basel) ; 14(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35567088

RESUMO

The rapid development of the polymeric materials market has created an urgent demand for the thermoplastic polyamide elastomer (TPAE) owing to its greater functionality, and ability to be synthesized via a facile and industrial route. In this work, a series of novel silicone-containing polyamides (PA1212/Si12) were successfully synthesized from 1,12-dodecarboxylic acid (LA), 1,12-dodecarbondiamine (DMDA), and 1,3-bis (amino-propyl) tetramethyldisiloxane (BATS), via a one-pot melt polycondensation method in the absence of a catalyst. FTIR, 1H-NMR, GPC and inherent viscosity results cohesively prove that the polymerization of monomers was well conducted, and the chemical structure was in high accordance with the design. As expected, the Si12 unit-content of the copolymers regulate the properties of the series. As the feeding ratio of BATS in the diamines increases from 5 mol% to 40 mol%, the thermal transition temperatures, Tg and Tm, decline steadily before finally stabilizing at ~6 °C and 160 °C, respectively, indicating that the co-polyamides possess improved chain flexibility but restricted crystallization ability. The conspicuous evolution in crystalline morphology of the series was observed by XRD and AFM. The increased PA Si12 phase induces the crystallized PA 1212 phase to transit from a thermally-favorable large and rigid crystal structure (α phase) to a kinetically-favorable small and ductile crystal structure (γ phase). Reflected in their stress-strain behavior, PA1212/Si12 copolymers are successfully tailored from rigid plastic to ductile elastomer. The tensile strength mildly drops from above 40 MPa to ~30 MPa while the reversible elongation increases from ~50% to approximately 350%. Accordingly, the moderate surface tension differences in the monomers facilitate the efficient conduction of the co-polymerization process, and the distributed short siloxane unit in the backbone fulfills the copolymer with desirable elasticity. Interestingly, the novel silicone-containing polyamides also display Si12 unit-content dependent flame retardancy, humidity stability, and unconventional solid-state fluorescence properties. The elastomers exhibit a low bibulous rate and anti-fouling characteristics to dye droplets and mud contamination, pass the V-1 rating (UL 94) with a constantly declining PHRR value, and emit blue luminescence under a 365 nm light source. Herein, we propose a new facile strategy for developing a high-performance and multifunctional silicone-modified polyamide, which bears promising industrialization potential. In addition, this first reported silicone-containing thermoplastic polyamide elastomer, which is self-extinguishing, anti-fouling and blue-luminescent, will further broaden the application potential of thermoplastic polyamide elastomers.

8.
Nucleic Acids Res ; 50(8): 4769-4783, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35446403

RESUMO

It is important to control CRISPR/Cas9 when sufficient editing is obtained. In the current study, rational engineering of guide RNAs (gRNAs) is performed to develop small-molecule-responsive CRISPR/Cas9. For our purpose, the sequence of gRNAs are modified to introduce ligand binding sites based on the rational design of ligand-RNA pairs. Using short target sequences, we demonstrate that the engineered RNA provides an excellent scaffold for binding small molecule ligands. Although the 'stem-loop 1' variants of gRNA induced variable cleavage activity for different target sequences, all 'stem-loop 3' variants are well tolerated for CRISPR/Cas9. We further demonstrate that this specific ligand-RNA interaction can be utilized for functional control of CRISPR/Cas9 in vitro and in human cells. Moreover, chemogenetic control of gene editing in human cells transfected with all-in-one plasmids encoding Cas9 and designer gRNAs is demonstrated. The strategy may become a general approach for generating switchable RNA or DNA for controlling other biological processes.


Assuntos
Edição de Genes , RNA Guia , Humanos , RNA Guia/genética , RNA Guia/metabolismo , Sistemas CRISPR-Cas/genética , Ligantes , Plasmídeos
10.
Comput Biol Med ; 141: 105182, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34979404

RESUMO

BACKGROUND: Chest computed tomography (CT) is crucial in the diagnosis of coronavirus disease 2019 (COVID-19). However, the persistent pandemic and similar CT manifestations between COVID-19 and community-acquired pneumonia (CAP) raise methodological requirements. METHODS: A fully automatic pipeline of deep learning is proposed for distinguishing COVID-19 from CAP using CT images. Inspired by the diagnostic process of radiologists, the pipeline comprises four connected modules for lung segmentation, selection of slices with lesions, slice-level prediction, and patient-level prediction. The roles of the first and second modules and the effectiveness of the capsule network for slice-level prediction were investigated. A dataset of 326 CT scans was collected to train and test the pipeline. Another public dataset of 110 patients was used to evaluate the generalization capability. RESULTS: LinkNet exhibited the largest intersection over union (0.967) and Dice coefficient (0.983) for lung segmentation. For the selection of slices with lesions, the capsule network with the ResNet50 block achieved an accuracy of 92.5% and an area under the curve (AUC) of 0.933. The capsule network using the DenseNet121 block demonstrated better performance for slice-level prediction, with an accuracy of 97.1% and AUC of 0.992. For both datasets, the prediction accuracy of our pipeline was 100% at the patient level. CONCLUSIONS: The proposed fully automatic deep learning pipeline of deep learning can distinguish COVID-19 from CAP via CT images rapidly and accurately, thereby accelerating diagnosis and augmenting the performance of radiologists. This pipeline is convenient for use by radiologists and provides explainable predictions.


Assuntos
COVID-19 , Aprendizado Profundo , Pneumonia , Humanos , Redes Neurais de Computação , Pneumonia/diagnóstico por imagem , SARS-CoV-2 , Tomografia Computadorizada por Raios X
11.
Nucleic Acids Res ; 50(3): 1241-1255, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35100423

RESUMO

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) technology is a powerful tool in biology and medicine. However, the safety and application of this technology is hampered by excessive activity of CRISPR machinery. It is particularly important to develop methods for switching off CRISPR activity in human cells. The current study demonstrates the concept of supramolecular CRISPR-OFF switches by employing host-guest chemistry. We demonstrate that the CRISPR systems show considerable tolerance to adamantoylation on guide RNAs (gRNAs), whereas supramolecular complexation tremendously affects the function of adamantoyl gRNAs. Host-guest chemistry is demonstrated to be novel and effective tools to reduce unwanted excessive activities of CRISPR complexes in human cells. This work indicates considerable potential of supramolecular strategy for controlling and enhancing CRISPR systems.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Edição de Genes/métodos , Humanos , RNA Guia/genética
12.
Commun Biol ; 5(1): 36, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017643

RESUMO

Chinese wild rice (Zizania latifolia; family: Gramineae) is a valuable medicinal homologous grain in East and Southeast Asia. Here, using Nanopore sequencing and Hi-C scaffolding, we generated a 547.38 Mb chromosome-level genome assembly comprising 332 contigs and 164 scaffolds (contig N50 = 4.48 Mb; scaffold N50 = 32.79 Mb). The genome harbors 38,852 genes, with 52.89% of the genome comprising repetitive sequences. Phylogenetic analyses revealed close relation of Z. latifolia to Leersia perrieri and Oryza species, with a divergence time of 19.7-31.0 million years. Collinearity and transcriptome analyses revealed candidate genes related to seed shattering, providing basic information on abscission layer formation and degradation in Z. latifolia. Moreover, two genomic blocks in the Z. latifolia genome showed good synteny with the rice phytocassane biosynthetic gene cluster. The updated genome will support future studies on the genetic improvement of Chinese wild rice and comparative analyses between Z. latifolia and other plants.


Assuntos
Cromossomos de Plantas/genética , Genoma de Planta/genética , Poaceae/genética , Sementes/genética , China , Oryza/genética , Filogenia , Poaceae/metabolismo
13.
Front Aging Neurosci ; 13: 773797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776938

RESUMO

Objective: Type 2 diabetes (T2D) is a risk factor for cognitive impairment and cerebral small vessel disease (CSVD). The relation of metformin use and cognitive impairment or CSVD is not clear. The objective of this study was to investigate the cross-sectional effects of long-term use of metformin on total CSVD burden and cognitive function in patients with T2D. Methods: A total of 234 participants with T2D from the memory clinic in Hebei General Hospital were enrolled in this retrospective study. Duration of metformin use and dosage were recorded. Along with cerebral magnetic resonance imaging (MRI) examination, Mini-Mental State Examination (MMSE) was also performed to assess their cognitive status. We determined the validated total CSVD score (ranging from 0-4) by combining four markers of CSVD that were visually rated. We used binary logistic regression analysis, ordinal logistic regression analysis and mediation analysis to assess the relation of long-term use of metformin with CSVD burden and cognitive function. Results: Binary logistic regression analysis showed long-term use of metformin was associated with reducing the risk of cognitive impairment (OR: 0.446; 95% Confidence Interval (CI): 0.249 to 0.800; P = 0.007), after adjustment of potential confounders, such as total CSVD burden score, age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Ordinal logistic regression analysis suggested that long-term use of metformin was associated with alleviation of total CSVD burden score (OR: 0.583; 95% CI: 0.359 to 0.943; P = 0.027), after adjusting for age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Mediation analysis showed significant mediation by the presence of severe CSVD burden score for long-term use of metformin in relation to cognitive impairment. Conclusion: Long-term use of metformin was associated with lower rates of cognitive impairment and lower total CSVD burden score in patients with T2D. A proportion of the relation between long-term use of metformin and cognitive impairment may be attributable to alleviation of CSVD burden.

14.
Environ Pollut ; 290: 118022, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492527

RESUMO

Volatile brominated compounds are important trace gases for stratospheric ozone chemistry. In this study, the spatial variations of dibromomethane (CH2Br2), bromodichloromethane (CHBrCl2), dibromochloromethane (CHBr2Cl) and bromoform (CHBr3) in the seawater and overlying atmosphere were measured in the Yellow Sea (YS) and the East China Sea (ECS) in winter. The air-sea fluxes of CH2Br2, CHBrCl2, CHBr2Cl and CHBr3 ranged from -11.46 to 25.33, -4.68 to 7.91, -8.60 to 4.08 and -88.57 to 8.84 nmol m-2·d-1, respectively. In order to understand the mechanism of halocarbons production, we measured bromoperoxidase (BrPO) activity (39.18-186.74 µU·L-1) in the YS and ECS for the first time using an aminophenyl fluorescein (APF) method and performed in-situ incubation experiments in BrPO-treated seawater. The production rates of CH2Br2, CHBrCl2, CHBr2Cl and CHBr3 ranged from 14.21 to 94.74, 0.00 to 19.74, 0.00 to 30.62 and 6.18-72.75 pmol L-1·h-1, respectively, in BrPO-treated seawater. There were significantly higher production rates in coastal waters compared with the open sea (P = 0.016) because of higher DOC levels near the coast. Moreover, the production rates of halocarbons increased with BrPO activity and H2O2 concentration. The results showed that enzyme-mediated reaction was an important source for the production of halocarbons in seawater. The present research is of great significance for understanding the production mechanisms of halocarbons in seawater and global oceanic halocarbons emissions.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Poluentes Atmosféricos/análise , China , Peróxido de Hidrogênio , Oceanos e Mares , Peroxidases , Água do Mar
15.
ACS Appl Mater Interfaces ; 13(33): 39806-39818, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387459

RESUMO

Silver nanomaterials have attracted a great deal of interest due to their broad-spectrum antimicrobial activity. However, it is still challenging to balance the high antibacterial efficiency with low damage to biological cells of silver nanostructures, especially when the diameter decreases to less than 10 nm. Here, we developed a new type of Ag nanohybrid material via a unimolecular micelle template method, which presents amazing antibacterial activities and almost noncytotoxicity. First, water-soluble multiarm star-shaped brushlike copolymer α-CD-g-[(PEO40-g-PAA50)-b-PEO5]18 was precisely synthesized and its micelle behavior in different solvents was revealed. Then, nanocrystal clusters assembled by Ag grains (Ag@Template NCs) were prepared through an in situ redox route using the unimolecular micelle of α-CD-g-[(PEO40-g-PAA50)-b-PEO5]18 as the soft template, AgNO3 as a precursor, and tetrabutylammonium borohydride (TBAB) as the reducing agent. The overall size of the achieved Ag@Template NCs is controlled by the template structure at around 40 nm (Dh in DMF), and the size of the Ag grain can be easily regulated from ∼1 to ∼5 nm by adjusting the feeding ratio of AgNO3/acrylic acid (AA) units in the template from 1:10 to 1:1. Benefitting from the structural design of the template, all Ag@Template NCs prepared here exhibit excellent dispersibility and chemical stability in different aqueous environments (neutral, pH = 5.5, and 0.9% NaCl physiological saline solution), which play a crucial role in the long-term storage and potential application in a complex physiological environment. The antibacterial and cytotoxicity tests indicate that Ag@Template NCs display much better performance than Ag nanoparticles (Ag NPs), which have a comparable overall size of ∼25 nm. The inhibitory capability of Ag@Template NCs to bacteria strongly depends on the grain size. Specifically, the Ag@Template-1 NC assembled by the smallest grains (1.6 ± 0.3 nm) presents the best antibacterial activity. For E. coli (-), the MIC value is as low as 5 µg/mL (0.36 µg/mL of Ag), while for S. aureus (+), the value is around 10 µg/mL (0.72 µg/mL of Ag). The survival rate of L02 cells and lactate dehydrogenase assay together illustrate the low cytotoxicity possessed by the prepared Ag@Template NCs. Therefore, the proposed Ag@Template NC structure successfully resolves the high reactivity, instability, and fast oxidation issues of the ultrasmall Ag nanoparticles, and integrates high antibacterial efficiency and nontoxicity to biological cells into one platform, which implies its broad potential application in biomedicine.


Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/química , Nanopartículas Metálicas/química , Prata/química , Antibacterianos/metabolismo , Boroidretos/química , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Polímeros/química , Compostos de Amônio Quaternário/química , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Nanomedicina Teranóstica
16.
Chem Biodivers ; 18(2): e2000804, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33346933

RESUMO

A series of (E)-1-(substituted benzylidene)-4-(3-isopropylphenyl)thiosemicarbazone derivatives were synthesized and characterized by FT-IR spectrum, elemental analysis, NMR spectrum, HR-MS spectrum, and X-ray single crystal diffraction technology. The crystal structures and packing of (E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone and (E)-1-(3-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone were maintained through the intramolecular hydrogen bond (N3-H6⋅⋅⋅N1) and intermolecular hydrogen bonds (N2-H4⋅⋅⋅S1, C14-H14⋅⋅⋅F1 and C7-H7⋅⋅⋅S1). The results obtained by employing the DPPH free radicals scavenging assay indicated that (E)-1-(4-methoxylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had a more significant antioxidant activity compared with other compounds. The results measured by adopting the disc diffusion method elucidated that (E)-1-(4-trifluoromethylbenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone possessed a more prominent antifungal activity than other compounds. Molecular docking showed that (E)-1-(4-chlorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had the highest affinity with receptor protein (1NMT). Moreover, the drug-likeness characteristic, physicochemical properties, pharmacokinetic profiles, and bioactivity scores of all the compounds were predicted through in silico studies. The results illustrated that (E)-1-(4-fluorobenzylidene)-4-(3-isopropylphenyl)thiosemicarbazone had the drug-likeness characteristic and all the compounds were considered as moderately biological active molecules.


Assuntos
Compostos de Benzilideno/química , Compostos de Benzilideno/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Benzilideno/síntese química , Cristalografia por Raios X , Fungos/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Micoses/tratamento farmacológico , Tiossemicarbazonas/síntese química
17.
Food Chem ; 344: 128600, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33221101

RESUMO

The contents of phenolic compounds, especially flavonoids, and antioxidant activity of rice (Oryza sativa, Os) and Chinese wild rice (Zizania latifolia, Zl) harvested in China were compared. Zl possessed significantly higher contents of total phenolics, flavonoids, and proanthocyanidins and exhibited higher antioxidant activity than in the Os Xian group, the Os Geng group, and red rice. The flavonoid contents of Os and Zl were compared using a UHPLC-QqQ-MS-based metabolomics approach. A total of 159 flavonoids were identified, among which 78 showed differential expression (72 up-regulated and six down-regulated in the Zl group). The Kyoto Encyclopaedia of Genes and Genomes annotation and classification indicated that the differentially expressed flavonoids were mainly related to anthocyanin biosynthesis. Moreover, candidate genes for flavonoid biosynthesis in Os and Zl were identified in this study. Compared with non-pigmented and red rice, Zl may be more nutritious and is thus considered a better source of natural antioxidants.


Assuntos
Antioxidantes/química , Flavonoides/análise , Oryza/química , Fenóis/análise , Extratos Vegetais/química , Poaceae/química , Área Sob a Curva , China , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Flavonoides/química , Humanos , Análise dos Mínimos Quadrados , Metabolômica/métodos , Oryza/metabolismo , Fenóis/química , Poaceae/metabolismo , Análise de Componente Principal , Curva ROC , Espectrometria de Massas em Tandem
18.
Immunology ; 162(3): 328-338, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33283278

RESUMO

Schistosomiasis is a neglected tropical disease with over 250 million people infected worldwide. The main clinically important species Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum) cause inflammatory responses against tissue-trapped eggs, resulting in formation of granulomas mainly in host liver. Persistent granulomatous response results in severe fibrosis in the liver, leading to irreversible impairment of the liver and even death of the host. CD1d, a highly conserved MHC class I-like molecule, is expressed by both haematopoietic and non-haematopoietic cells. CD1d on antigen-presenting cells (APCs) of haematopoietic origin presents pathogen-derived lipid antigens to natural killer T (NKT) cells, which enables them to rapidly produce large amounts of various cytokines and facilitate CD4+ T helper (Th) cell differentiation upon invading pathogens. Noteworthy, hepatocytes of non-haematopoietic origin have recently been shown to be involved in maintaining liver NKT cell homeostasis through a CD1d-dependent manner. However, whether hepatocyte CD1d-dependent regulation of NKT cell homeostasis also modulates CD4+ Th cell responses and liver immunopathology in murine schistosomiasis remains to be addressed. Here, we show in mice that CD1d expression on hepatocytes was decreased dramatically upon S. japonicum infection, accompanied by increased NKT cells, as well as upregulated Th1 and Th2 responses. Overexpression of CD1d in hepatocytes significantly decreased local NKT numbers and cytokines (IFN-γ, IL-4, IL-13), concomitantly with downregulation of both Th1 and Th2 responses and alleviation in pathological damage in livers of S. japonicum-infected mice. These findings highlight the potential of hepatocyte CD1d-targeted therapies for liver immunopathology control in schistosomiasis.


Assuntos
Antígenos CD1d/metabolismo , Hepatócitos/imunologia , Fígado/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Animais , Antígenos CD1d/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatócitos/patologia , Interações Hospedeiro-Parasita , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/parasitologia , Schistosoma japonicum/patogenicidade , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/parasitologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/parasitologia , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/parasitologia
19.
Nat Commun ; 11(1): 4792, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963238

RESUMO

Natural biomolecules have been used extensively as chiral scaffolds that bind/surround metal complexes to achieve stereoselectivity in catalytic reactions. ATP is ubiquitously found in nature as an energy-storing molecule and can complex diverse metal cations. However, in biotic reactions ATP-metal complexes are thought to function mostly as co-substrates undergoing phosphoanhydride bond cleavage reactions rather than participating in catalytic mechanisms. Here, we report that a specific Cu(II)-ATP complex (Cu2+·ATP) efficiently catalyses Diels-Alder reactions with high reactivity and enantioselectivity. We investigate the substrates and stereoselectivity of the reaction, characterise the catalyst by a range of physicochemical experiments and propose the reaction mechanism based on density functional theory (DFT) calculations. It is found that three key residues (N7, ß-phosphate and γ-phosphate) in ATP are important for the efficient catalytic activity and stereocontrol via complexation of the Cu(II) ion. In addition to the potential technological uses, these findings could have general implications for the chemical selection of complex mixtures in prebiotic scenarios.

20.
Exp Ther Med ; 20(4): 3679-3686, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32855720

RESUMO

Hepatitis B virus (HBV) can establish a lifelong chronic infection in humans, leading to liver cirrhosis, liver failure and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) exhibit a weak virus-specific immune response. Regulatory T cells (Tregs) play a key role in regulating the immune response in patients with CHB. Patients with hepatitis B envelope antigen (HBeAg)-positive CHB harbored a higher percentage of Tregs in their peripheral blood than those with HBeAg-negative CHB. However, whether and how HBeAg manipulates the host immune system to increase the population of Tregs remains to be elucidated. The present manuscript describes a preliminary immunological study of HBeAg in a mouse model. Multiple potential CD4+ T cell epitopes in HBeAg were identified using Immune Epitope Database consensus binding prediction. It was demonstrated that HBeAg treatment increased the numbers of Tregs in mouse spleens in vitro and in vivo. Furthermore, it was indicated that the HBeAg-mediated increase in Tregs occurred through the conversion of CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs. Additionally, in vitro study illustrated that HBeAg stimulated murine spleen cells to produce increased transforming growth factor-ß, which is required to enable HBeAg to convert T cells into Tregs. The results of the present study may provide further evidence of the effect of HBeAg on Tregs and aid in the development of novel HBeAg-based immunotherapy for CHB.

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