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1.
Immunity ; 52(1): 109-122.e6, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31882361

RESUMO

Recent work suggests that cholesterol metabolism impacts innate immune responses against infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we have shown that upon DNA and RNA viral infection, macrophages reduced 7-dehydrocholesterol reductase (DHCR7) expression. DHCR7 deficiency or treatment with the natural product 7-dehydrocholesterol (7-DHC) could specifically promote phosphorylation of IRF3 (not TBK1) and enhance type I interferon (IFN-I) production in macrophages. We further elucidated that viral infection or 7-DHC treatment enhanced AKT3 expression and activation. AKT3 directly bound and phosphorylated IRF3 at Ser385, together with TBK1-induced phosphorylation of IRF3 Ser386, to achieve IRF3 dimerization. Deletion of DHCR7 and the DHCR7 inhibitors including AY9944 and the chemotherapy drug tamoxifen promoted clearance of Zika virus and multiple viruses in vitro or in vivo. Taken together, we propose that the DHCR7 inhibitors and 7-DHC are potential therapeutics against emerging or highly pathogenic viruses.


Assuntos
Desidrocolesteróis/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/biossíntese , Macrófagos/imunologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Estomatite Vesicular/imunologia , Células A549 , Animais , Linhagem Celular , Colesterol/metabolismo , Ativação Enzimática/imunologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/genética , Vírus da Estomatite Vesicular Indiana/imunologia
2.
Small ; : e2403070, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770743

RESUMO

Among silicon-based anode family for Li-ion battery technology, SiOx, a nonstoichiometric silicon suboxide holds the potential for significant near-term commercial impact. In this context, this study mainly focuses on demonstrating an innovative SiOx@C anode design that adopts a pre-lithiation strategy based on in situ pyrolysis of Li-salt of silsesquioxane trisilanolate without the need for lithium metal or active lithium compounds and creates dual carbon encapsulation of SiOC nanodomains by simply one-step thermal treatment. This ingenious design ensures the pre-lithiation process and pre-lithiation material with high-environmental stability. Moreover, phenyl-rich organosiloxane clusters and polyacrylonitrile polymers are expected to serve as internal and external carbon source, respectively. The formation of an interpenetrating and continuous carbon matrix network would not only synergistically offer an improved electrochemical accessibility of active sites but also alleviate the volume expansion effect during cycling. As a result, this new type of anode delivered a high reversible capacity, remarkable cycle stability as well as excellent high-rate capability. In particular, the L2-SiOx@C material has a high initial coulomb efficienc of 80.4% and, after 500 cycles, a capacity retention as high as 97.5% at 0.5 A g-1 with a reversible specific capacity of 654.5 mA h g-1.

3.
Plant Cell Environ ; 47(7): 2693-2709, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38576334

RESUMO

As a well-conserved histone variant, H2A.Z epigenetically regulates plant growth and development as well as the interaction with environmental factors. However, the role of H2A.Z in response to salt stress remains unclear, and whether nucleosomal H2A.Z occupancy work on the gene responsiveness upon salinity is obscure. Here, we elucidate the involvement of H2A.Z in salt response by analysing H2A.Z disorder plants with impaired or overloaded H2A.Z deposition. The salt tolerance is dramatically accompanied by H2A.Z deficiency and reacquired in H2A.Z OE lines. H2A.Z disorder changes the expression profiles of large-scale of salt responsive genes, announcing that H2A.Z is required for plant salt response. Genome-wide H2A.Z mapping shows that H2A.Z level is induced by salt condition across promoter, transcriptional start site (TSS) and transcription ending sites (-1 kb to +1 kb), the peaks preferentially enrich at promoter regions near TSS. We further show that H2A.Z deposition within TSS provides a direct role on transcriptional control, which has both repressive and activating effects, while it is found generally H2A.Z enrichment negatively correlate with gene expression level response to salt stress. This study shed light on the H2A.Z function in salt tolerance, highlighting the complex regulatory mechanisms of H2A.Z on transcriptional activity for yielding appropriate responses to particularly environmental stress.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Histonas , Histonas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Transcrição Gênica/efeitos dos fármacos , Estresse Salino/genética , Tolerância ao Sal/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regiões Promotoras Genéticas/genética , Nucleossomos/metabolismo
4.
Environ Res ; 252(Pt 1): 118826, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579999

RESUMO

Nitration of allergenic proteins caused by atmospheric pollutants O3 and NO2 may enhance their allergenic potential. In the study, the influence of nitration was investigated on the allergenicity of Der p 2, which is a main allergen from house dust mites and plays an important role in allergenic rhinitis and asthma. The results reveal that nitrated Der p 2 enhanced the IgE-binding capacity, upregulated the mRNA expression and release of IL-6 and IL-8 from bronchial epithelial cells, and induced higher levels of specific-IgE, TH2 cytokines and white blood cells in mice. Besides, nitrated Der p 2 caused more severe oxidative stress and allergenic symptoms in mice. It is concluded that nitration enhanced the allergenicity of Der p 2 through not only directly inducing higher amount of specific-IgE and stronger responses of TH2 cytokines, but also indirectly aggravating allergic symptoms by oxidative stress and adjuvant-like activation airway epithelial cells. The study suggests that the contribution of nitration to the promotion in allergenicity should not be ignored when precisely assessing the risk of house dust mite allergens in real environment.


Assuntos
Antígenos de Dermatophagoides , Proteínas de Artrópodes , Animais , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Camundongos , Tirosina , Cisteína Endopeptidases/imunologia , Camundongos Endogâmicos BALB C , Humanos , Imunoglobulina E/imunologia , Alérgenos/imunologia , Feminino , Citocinas/imunologia , Citocinas/metabolismo , Estresse Oxidativo
5.
Plant Cell Rep ; 43(2): 33, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38200226

RESUMO

KEY MESSAGE: The study on melatonin biosynthesis mutant snat1snat2 revealed that endogenous melatonin plays an important role in salt responsiveness by mediating auxin signaling. Melatonin is a pleiotropic signaling molecule, which, besides being involved in multiple growth and developmental processes, also mediates environmental stress responses. However, whether and how endogenous melatonin is involved in salt response has not been determined. In this study, we elucidated the involvement of endogenous melatonin in salt response by investigatiing the impact of salt stress on a double mutant of Arabidopsis (snat1snat2) defective in melatonin biosynthesis genes SNAT1 and SNAT2. This mutant was found to exhibit salt sensitivity, manifested by unhealthy growth, ion imbalance and ROS accumulation under salt stress. Transcriptomic profiles of snat1snat2 revealed that the expression of a large number of salt-responsive genes was affected by SNAT defect, and these genes were closely related to the synthesis of auxin and several signaling pathways. In addition, the salt-sensitive growth phenotype of snat1snat2 was alleviated by the application of exogenous auxin. Our results show that endogenous melatonin may be essential for plant salt tolerance, a function that could be correlated with diverse activity in mediating auxin signaling.


Assuntos
Arabidopsis , Melatonina , Arabidopsis/genética , Ácidos Indolacéticos , Fenótipo , Estresse Salino/genética
6.
Neurocrit Care ; 40(2): 612-620, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37498458

RESUMO

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.


Assuntos
Ventriculite Cerebral , Infecção Hospitalar , Meningites Bacterianas , Meningite , Humanos , Antibacterianos , Ventriculite Cerebral/tratamento farmacológico , Estudos Retrospectivos , Mortalidade Hospitalar , Infecção Hospitalar/tratamento farmacológico , Meningite/tratamento farmacológico , Hospitais , Meningites Bacterianas/tratamento farmacológico
7.
Ecotoxicol Environ Saf ; 279: 116448, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38754199

RESUMO

Evodiae Fructus (EF), an herbal medicine, possesses remarkable anti-inflammatory and analgesic properties. It exhibits insecticidal activity as a potent insecticide candidate. However, the toxic characteristics of EF and the underlying mechanisms have not been comprehensively elucidated comprehensively. Thus, we comprehensively explored the toxic components of EF and established the relationship between the therapeutic and toxic effects of EF, encouraging its therapeutic use. We found that evodiamine (EVO), one of the main ingredients of EF, can truly reflect its analgesic properties. In phenotype observation trials, low doses of EVO (< 35 ng/mL) exhibited distinct analgesic activity without any adverse effects in zebrafish. However, EVO dose-dependently led to gross morphological abnormalities in the liver, followed by pericardial edema, and increased myocardial concentrations. Furthermore, the toxic effects of EVO decreased after processing in liver microsomes but increased after administering CYP450 inhibitors in zebrafish, highlighting the prominent effect of CYP450s in EVO-mediated hepatotoxicity. EVO significantly changed the expression of genes enriched in multiple pathways and biological processes, including lipid metabolism, inflammatory response, tight junction damage, and cell apoptosis. Importantly, the PPAR/PI3K/AKT/NF-кB/tight junction-mediated apoptosis pathway was confirmed as a critical functional signaling pathway inducing EVO-mediated hepatotoxicity. This study provided a typical example of the overall systematic evaluation of traditional Chinese medicine (TCM) and its active ingredients with significant therapeutic effects and simultaneous toxicities, especially metabolic toxicities.


Assuntos
Apoptose , Evodia , NF-kappa B , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Quinazolinas , Peixe-Zebra , Animais , Quinazolinas/toxicidade , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Evodia/química , Transdução de Sinais/efeitos dos fármacos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia
8.
Geriatr Nurs ; 57: 224-231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696880

RESUMO

The factors that affect resident satisfaction with emerging residential integrated care for older people in China have been unclear due to a lack of validated instruments. Based on psychometric assessment procedures, we developed a new scale for older resident satisfaction with residential integrated care (SORSRIC). The scale was developed using a two-step process and a sample of 16 Chinese institutions and 333 residents. Exploratory and confirmatory factor analysis was used to evaluate reliability and validity. Principal component analysis and maximum variance methods were used to orthogonally rotate the items to extract seven factors. These were: resident expectations, perceived quality (physical care), perceived quality (mental care), perceived value, resident satisfaction, resident complaints, and resident loyalty. The CR value of each dimension of the pre-tested, formal scale was greater than 0.80, and the AVE value was greater than 0.50. This 24-item instrument showed good reliability and structural validity and can be applied to improve the experience and outcomes for older people in residential care.


Assuntos
Psicometria , Humanos , China , Masculino , Feminino , Idoso , Reprodutibilidade dos Testes , Inquéritos e Questionários , Satisfação do Paciente , Idoso de 80 Anos ou mais
9.
Small ; 19(40): e2303742, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37267931

RESUMO

The hierarchical Cu2 S@NC@MoS3 heterostructures have been firstly constructed by the high-capacity MoS3 and high-conductive N-doped carbon to co-decorate the Cu2 S hollow nanospheres. During the heterostructure, the middle N-doped carbon layer as the linker facilitates the uniform deposition of MoS3 and enhances the structural stability and electronic conductivity. The popular hollow/porous structures largely restrain the big volume changes of active materials. Due to the cooperative effect of three components, the new Cu2 S@NC@MoS3 heterostructures with dual heterogenous interfaces and small voltage hysteresis for sodium ion storage display a high charge capacity (545 mAh g-1 for 200 cycles at 0.5 A g-1 ), excellent rate capability (424 mAh g-1 at 15 A g-1 ) and ultra-long cyclic life (491 mAh g-1 for 2000 cycles at 3 A g-1 ). Except for the performance test, the reaction mechanism, kinetics analysis, and theoretical calculation have been performed to explain the reason of excellent electrochemical performance of Cu2 S@NC@MoS3 . The rich active sites and rapid Na+ diffusion kinetics of this ternary heterostructure is beneficial to the high efficient sodium storage. The assembled full cell matched with Na3 V2 (PO4 )3 @rGO cathode likewise displays remarkable electrochemical properties. The outstanding sodium storage performances of Cu2 S@NC@MoS3 heterostructures indicate the potential applications in energy storage fields.

10.
Opt Express ; 31(3): 3520-3535, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785343

RESUMO

Hyperbolic metamaterial (HMM) based sensors can achieve superior sensing performance than conventional surface plasmon resonance sensors. In this work, the operator approach to effective medium approximation (OEMA) is used to characterize the HMM dielectric constant properties of metal-dielectric multilayer structures, which are classified into short-range (SR) mode and long-range (LR) mode according to the propagation length of the bulk high K waves in HMM. The dispersion relations of SR modes are derived, and a high-sensitivity refractive index sensor is designed for the near-infrared SR mode resonance. The effects of the number of periods, cell thickness, metal fill rate and incidence angle on the SR mode resonance were analyzed for the multilayer structured HMM. Our designed sensing structure achieves a maximum sensitivity of 330 µm/RIU in the near-infrared band with a quality factor of 492 RIU-1. In addition, the simulations show that the SR mode resonance wavelength is flexible and tunable. We believe that the study of HMM-based SR mode resonance sensors offers potential applications for high-sensitivity biochemical detection.

11.
Zhongguo Zhong Yao Za Zhi ; 48(1): 140-147, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36725266

RESUMO

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 µg·mL~(-1) of the absolute lethal concentration and 448 µg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Peixe-Zebra , Animais , Peixe-Zebra/genética , Apoptose , Larva
12.
Opt Express ; 30(18): 32483-32500, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242309

RESUMO

The optical sensor based on lossy mode resonance can overcome the limitations of traditional surface plasmon resonance sensors and work under TE and TM polarized light. In this paper, an LMR sensor theoretical model with the configuration of prism/matching layer/lossy layer/sensing layer is proposed, which is based on the principle of attenuated total reflection. By using TiO2 film as the lossy layer and LiF film as the matching layer, the resonance signal under angle interrogation is effectively improved. One of the advantages of the proposed sensor is that the detection range and detection accuracy are dynamically adjustable, which provides additional degrees of freedom in the design and use of the device. The structural parameters (film thickness, layer refractive index) affecting the resonance signal have been investigated based on the electric field distribution at resonance and the coupled mode theory. The LMR signal under TE and TM polarization can be switched by changing the thickness ratio of the matching layer and the lossy layer. All possible combinations of film thicknesses are given as a reference for the design of the LMR prism sensor based on TiO2 film. Under proper thickness combination, the proposed sensor is capable of detecting the medium with refractive index ranging from 1.32 ∼ 1.47, with a sensitivity range of 34 ∼ 148 °/RIU under angle interrogation and a maximum value of 192 RIU-1 for FOM under TM polarization. We hope these investigations can prove the advantages of LMR prism sensors and provide guidance for the experimental implementation of LMR prism sensors in the future.

13.
Molecules ; 27(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36364187

RESUMO

This study optimized the laminate structure of a composite cylinder under the constraint of minimum layup thickness. Based on the progressive damage theory, a finite element model of the cylinder was established, and the NOL ring tensile test was used to verify the accuracy of the damage theory. The winding angle, the number of layers, and the helical/hoop ratio (the stacking sequence) were selected as the optimization factors, and the burst pressure value was used to evaluate the quality of the laminate structure. Then the orthogonal experiments were designed by RSM. Combined with FEA, the function model of the burst pressure of the gas cylinder and each optimization factor was established to obtain the optimal layering scheme, satisfying the minimum burst pressure. In addition, finite element analysis was used to verify the optimal scheme, demonstrating that the error of the burst pressure predicted by the quadratic model established by the response surface design was not more than 5%. This study provides a faster and more efficient optimization method for the optimization design of composite gas cylinder layers.


Assuntos
Análise de Elementos Finitos
14.
J Sci Food Agric ; 102(2): 461-471, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34487550

RESUMO

Food contamination caused by foodborne pathogens is one of the most important concerns in public health worldwide, and accounts for a significant portion of food loss every year. The emergence of antimicrobial resistant bacteria has turned the attention of researchers back to the potential of bacteriophages as antibacterial agents, and their use has been attempted in various pre-and post-harvest food production settings. The application of phage-based antibacterial products has achieved considerable success but a number of technical, environmental and administrative challenges remain unaddressed. In this review, we summarize the current status of bacteriophage application in the food industry. We discuss the obstacles facing the further development of phage-based antibacterial products from the aspects of technology, environmental safety, and administrative policy. We also advance some possible solutions to these challenges. © 2021 Society of Chemical Industry.


Assuntos
Bactérias/virologia , Bacteriófagos/fisiologia , Inocuidade dos Alimentos/métodos , Indústria de Processamento de Alimentos/tendências , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bacteriófagos/genética , Contaminação de Alimentos/prevenção & controle , Indústria de Processamento de Alimentos/métodos , Humanos
15.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2712-2720, 2022 May.
Artigo em Zh | MEDLINE | ID: mdl-35718491

RESUMO

This study aims to evaluate the anti-tumor and analgesic activities of Compound Kushen Injection(CKI) based on zebrafish model in vivo and investigate the anti-tumor mechanism. To be specific, zebrafish tumor xenotransplantation model was established by microinjection of murine LPC H12 cells into yolk sac. Then the high-dose CKI(H-CKI), medium-dose CKI(M-CKI), low-dose CKI(L-CKI) groups, and the model group were set. The anti-tumor activity of CKI was evaluated with the tumor area growth fold and integral absorbance(IA) growth fold 72 h after administration. The peripheral pain and central pain in zebrafish were respectively induced with acetic acid(AA) and phorbol myristate acetate(PMA). Zebralab ViewPoint system was employed to monitor behavioral trajectory of zebrafish, and movement times, movement time, movement distance, and movement velocity were used to evaluate the analgesic activity of CKI. Finally, real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression levels of apoptosis-related B lymphocyte tumor-2(Bcl-2) and phosphatidylinositol-3-kinase(PI3 K)/protein kinase B(Akt or PKB) pathway-related genes, for the verification of the anti-tumor mechanism. Compared with the model group, M-CKI and H-CKI significantly reduced the growth folds of tumor area and IA, relief the peripheral pain and central pain. The mechanism was that CKI can up-regulate the expression of cysteine aspartic acid specific protease-3(caspase-3, Casp3) and caspase-9(Casp9), down-regulate the expression of phosphoinositide 3-kinase(PI3 K) and Akt, and significantly reduce the expression of Bcl-2, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF). In conclusion, CKI has significant inhibitory effect on tumor growth and pain, which is related to the PI3 K/Akt signaling pathway. The pathway mediates cell apoptosis, suppresses tumor growth, and alleviates tumor pain.


Assuntos
Antineoplásicos , Neoplasias , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos , Neoplasias/tratamento farmacológico , Dor/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-bcl-2 , Fator A de Crescimento do Endotélio Vascular , Peixe-Zebra
16.
Zhongguo Zhong Yao Za Zhi ; 46(2): 320-332, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33645118

RESUMO

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.


Assuntos
Hepatopatias , Peixe-Zebra , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Fígado , Hepatopatias/genética , Medicina Tradicional Chinesa , Peixe-Zebra/genética
17.
Neurochem Res ; 45(12): 3021-3033, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33095440

RESUMO

Treatment for epilepsy, particularly temporal lobe epilepsy, is challenging. Baicalein has multiple effects, including anti-inflammatory action. However, little is known about its efficacy in treatment of epilepsy. In this study, we established a pilocarpine-induced rat model and used it for assessment of baicalein efficacy in vivo. We predicted the pharmacological mechanism of baicalein by network pharmacology and RNA sequencing analyses. Pilocarpine epileptic rats treated with baicalein exhibited improved average seizure severity, seizure frequency, seizure duration, and survival time. Network pharmacology and RNA sequencing identified the differentially expressed genes between the baicalein treatment and epileptic groups. Insulin-like growth factor 1 receptor (IGF1R) was chosen as the top candidate target because of its overlapping findings in RNA sequencing and network pharmacology data. Western blotting, immunofluorescence, and polymerase chain reaction analyses showed that baicalein inhibited microglial proliferation, IGF1R, and inflammatory cytokine expression. Moreover, baicalein improved epilepsy symptoms. Inhibition of IGF1R function by blocking with AXL1717 enhanced baicalein treatment efficacy both in vivo and in vitro. In conclusion, baicalein exerted antiepileptic effects by regulation of IGF1R in a pilocarpine-induced rat model.


Assuntos
Epilepsia/tratamento farmacológico , Flavanonas/uso terapêutico , Receptor IGF Tipo 1/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Epilepsia/induzido quimicamente , Epilepsia/complicações , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Microglia/metabolismo , Pilocarpina , Ratos Sprague-Dawley
18.
BMC Musculoskelet Disord ; 21(1): 548, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32799840

RESUMO

BACKGROUND: The prognostic value of Neutrophil-to-Lymphocyte Ratio (NLR) for the outcome of acute cervical traumatic spinal cord injury (tSCI) patients has rarely been studied by now throughout the world. METHODS: We performed a single-center retrospective cohort study to evaluate the prognostic value of NLR from peripheral whole blood count in patients with acute cervical tSCI. Patients within 6 h of acute cervical tSCI treated between Dec 2008 and May 2018 in Huashan Hospital of Fudan University were enrolled. Outcomes of patients with tSCI were assessed using American spinal injury association Impairment Scale (AIS). 6-month outcomes were dichotomized into poor outcome group (AIS A to C) and good outcome group (AIS D and E). Uni- and multivariate analyses were performed to assess the independent predictors of 6-month outcome. Two prediction models based on admission characteristics were built to evaluate the prognostic value of NLR. The discriminative ability of predictive models was evaluated using the area under the curve (AUC). RESULTS: A total of 377 patients were identified from our single center in China PR. Multivariate analysis showed that age, AIS grade at admission, NLR (p < 0.001) and coagulopathy (p = 0.003) were independent predictors of the 6-months outcome for acute cervical tSCI patients. The model combing NLR and standard variables (AUC = 0.944; 95% CI, 0.923-0.964) showed a more favorable prognostic value than that without NLR (AUC = 0.841; 95% CI, 0.798-0.885) in terms of 6-month outcome. CONCLUSIONS: NLR is firstly identified as an independent predictor of the 6-month outcome in acute cervical tSCI patients worldwide. The prognostic value of NLR is favorable, and a high NLR is associated with poor outcome in patients with acute cervical tSCI.


Assuntos
Medula Cervical , Traumatismos da Medula Espinal , China , Humanos , Recém-Nascido , Linfócitos , Neutrófilos , Estudos Retrospectivos , Traumatismos da Medula Espinal/diagnóstico
19.
Small ; 15(1): e1804692, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30480365

RESUMO

To overcome the zigzag pathway transport of the electron diffusion process and eliminate the surface trap states of phenyl-C61-butyric acid methyl ester (PCBM) nanofilms in inverted perovskite solar cells, novel 1D N-type doped carbon nanorods (CNRs) are developed by a stibonium (Sb) auxiliary ball milling method and introduced into the PCBM film to prepare the PCBM:Sb-CNRs hybrid transport layer. In this way, the N-type doped Sb-CNRs can extend the built-in electric field between CH3 NH3 PbI3 and PCBM to facilitate the separation of electron/hole pairs. The discontinuous band with the built-in potential in the PCBM/Sb-CNRs heterojunction can boost interfacial charge redistribution and promote electrons diffusion from PCBM to electrode through 1D Sb-CNRs network. As a result, the high device efficiency of 19.26% with enhanced air stability and little hysteresis are achieved. This work demonstrates a simple strategy to improve the efficiency and stability of perovskite photovoltaic devices using low-cost carbon nanomaterials.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33528352

RESUMO

A novel actinobacterium, designated strain NEAU-D428T, was isolated from rhizosphere soil of wheat and characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics of the strain coincided with members of the genus Microbispora. The 16S rRNA gene sequence analysis showed that the isolate was most closely related to Microbispora bryophytorum NEAU-TX2-2T (99.2 %). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that the strain clustered with Microbispora clausenae CLES2T (99.1 %), but formed a separate subclade in the phylogenomic tree within the genus Microbispora. The menaquinones were identified as MK-9(H4), MK-9(H2) and MK-9(H0). The phospholipid profile was found to consist of diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, ninhydrin-positive glycophospholipid, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were identified as iso-C16 : 0, C16 : 0, 10-methyl C17 : 0 and C18 : 0. Digital DNA-DNA hybridization and average nucleotide identity values between strain NEAU-D428T and M. bryophytorum NEAU-TX2-2T, Microbispora camponoti 2C-HV3T, M. clausenae CLES2T, 'Microbispora cellulosiformans' Gxj-6T and Microbispora fusca NEAU-HEGS1-5T were 47.6 and 92.2 %, 47.5 and 92.2 %, 55.9 and 94.0 %, 33.1 and 86.8 %, and 33.6 and 87.1 %, respectively. These results and some physiological and biochemical properties demonstrated that the strain could be distinguished from its closest relatives. Therefore, it is proposed that strain NEAU-D428T should be classified as representative of a novel species of the genus Microbispora, for which the name Microbispora sitophila sp. nov. is proposed. The type strain is NEAU-D428T (=CGMCC 4.7523T=DSM 109822T).

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