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1.
Int J Anal Chem ; 2022: 8279839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35027928

RESUMO

In this study, the effects of different processing techniques on the chemical components of Raphani Semen (RS) were evaluated. An established high-performance liquid chromatography (HPLC) method was adopted for the simultaneous determination of glucoraphanin, sinapine thiocyanate, raphanin, and erucic acid in the fried products of Raphani Semen to evaluate the chemical changes during frying processing as well as optimize the best frying technology of Raphani Semen. Then, the chemical components in the fried Raphani Semen were identified by ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A total of 54 compounds in processed Raphani Semen were identified by UPLC-Q-TOF-MS. The results showed that the content of glucoraphanin and sinapine thiocyanate was the highest in the fried products at 130°C for 10 min, and the effect of "Enzyme Killing and Glycosides Preserving" was the best. Therefore, this condition was chosen as the best frying technology of Raphani Semen. This study provided a more scientific basis for evaluation of the quality of Raphani Semen fried products and optimization of the frying technology of Raphani Semen.

2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 28-34, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35048596

RESUMO

Gut microbiota-derived metabolites play vital roles in the regulation of host-gut microbiota mutualism, gut homeostasis and the pathogenesis of multiple human diseases. Fermentation of indigestible dietary fibers by gut microbiota produces a variety of short-chain fatty acids (SCFAs) consisting mainly of acetate, propionate and butyrate. Despite high concentrations of SCFAs in the gut, it has been reported in a large number of studies that SCFAs are involved in the onset and development of multiple diseases, including colitis, diabetes mellitus, hepatic steatosis, and obesity. Recent studies including our work found that SCFAs regulates allergic immune reactions and the pathogenesis of allergic diseases via their action on allergic effector immune cells, including T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), eosinophils, mast cells and basophils. Herein, we reviewed the association of SCFAs with human allergic diseases, their role in regulating the animal model of allergic diseases and the effects of different SCFAs in regulating the functions of allergic effectors cells and the underlying mechanisms, aiming to provide research clues for in-depth investigation in the role played by SCFAs in regulating various allergic diseases.


Assuntos
Hipersensibilidade , Imunidade Inata , Animais , Butiratos , Ácidos Graxos Voláteis , Humanos , Linfócitos
3.
Ultrasonics ; 120: 106639, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34953343

RESUMO

The Rayleigh wave excited by the electromagnetic acoustic transducer (EMAT) is an effective selection for surface plane stress measurement. However, the propagation velocity of Rayleigh wave on the metal surface is easily affected by the original rolling process. Besides, the direction of the plane stress state is usually unknown, which means that the propagation velocity cannot be expressed linearly by the stress. As a result, the traditional measurement model of one transmitter and one receiver can only realize the decouple of plane stress components by rotating method, which not only brings position error but also low measurement efficiency. Therefore, this paper focuses on a novel Rayleigh wave-EMAT for plane stress ultrasonic measurement. Firstly, the Rayleigh wave measurement model is established based on the acoustoelastic equation and displacement expression. Furthermore, an array Rayleigh wave-EMATintegrating three transmitters and three receivers is designed. Finally, the typical plane stress state of 5052 aluminum alloy plate after friction stir welding (FSW) is measured. The experimental results show good agreement compared with the hole-drilling method, which verifies the effectiveness of proposed method and designed EMAT.

4.
Front Immunol ; 12: 754208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733286

RESUMO

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that ß2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, ß2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow-derived macrophages revealed that macrophages from Adrb2-/- mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+ . This study provides a better understanding of the mechanisms by which the ß2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.

5.
Cytometry A ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34173319

RESUMO

Human basophils are terminally differentiated granulocytes that are least abundant in the peripheral blood but play important roles in allergic diseases. Studies on human basophils are limited by the high cost on the isolation of human basophils by magnetic-activated cell sorting (MACS) for negative depletion of non-basophils, followed by CD123-based positive selection of basophils. Moreover, such CD123-based purification of basophils may be limited by blocking of the binding of IL-3/anti-CD123 to the surface CD123. Here we identified SSClow CD4- CD127- HLA-DR- CRTH2high as unique markers for the identification of human basophils through stringent flow cytometric analysis of leukocytes from buffy coat. We established an efficient and cost-effective method for isolating human basophils from buffy coat based on positive magnetic selection of CRTH2+ cells followed by flow cytometric sorting of SSClow CD4- CD127- HLA-DR- CRTH2high cells. Approximately 1 to 1.5 million basophils were isolated from one buffy coat with a purity of >97%. Basophils purified by this method were viable and efficiently responded to key regulators of basophils including IL-3 and anti-IgE. This method can be used for purifying human basophils for subsequent functional studies.

6.
Immunology ; 164(2): 292-304, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33999409

RESUMO

Allergic diseases are caused by dysregulated Th2 immune responses involving multiple effector cells including basophils. Short chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, exert immunomodulatory functions via activation of its receptors GPR41 and GPR43, and inhibition of the histone deacetylases (HDACs) activity. In allergic diseases, SCFAs suppress the activity of mast cells, eosinophils and type 2 innate lymphoid cells (ILC2) but enhance the function of Th2 cells. Here, we aimed to elucidate the function of SCFAs on human basophils. Human basophils were purified from healthy donors by flow cytometric sorting. The surface proteins, apoptosis and degranulation of basophils were analyzed by flow cytometric analysis. The mRNA expression was assayed using real-time PCR. Interleukin 4 (IL-4) and IL-13 were measured by ELISA. Histone acetylation was examined by western blot. GPR41 was expressed by basophils and was enhanced by IL-3. Acetate induced intracellular calcium influx in basophils which was suppressed by blocking GPR41. Propionate and butyrate, but not acetate, induced the expression of CD69 and IL-13. In addition, propionate and butyrate enhanced IgE-mediated basophil degranulation but inhibited basophil survival and IL-4 secretion. Propionate and butyrate induced histone acetylation of basophils and suppression of HDACs activity mimicked the effects of propionate and butyrate on human basophils. Our findings demonstrate that propionate and butyrate may play a complex role in regulating basophil apoptosis, activation and degranulation via inhibiting HDACs activity. The in vivo effects of SCFAs on the regulation of basophil-associated allergic diseases need to be further explored.


Assuntos
Apoptose/efeitos dos fármacos , Basófilos/efeitos dos fármacos , Butiratos/farmacologia , Histonas/metabolismo , Interleucina-13/metabolismo , Propionatos/farmacologia , Apoptose/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Células Cultivadas , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/metabolismo , Ácidos Graxos Voláteis , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo
7.
Dev Comp Immunol ; 121: 104097, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33831480

RESUMO

ß-Thymosin is a multifunctional peptide ubiquitously expressed in vertebrates and invertebrates. Many studies have found ß-thymosin is critical for wound healing, angiogenesis, cardiac repair, hair regrowth, and anti-fibrosis in vertebrates, and plays an important role in antimicrobial immunity in invertebrates. However, whether ß-thymosin participates in the regeneration of organisms is still poorly understood. In this study, we identified a ß-thymosin gene in Dugesia japonica which played an important role in stem cell proliferation and neuron regeneration during the tissue repair process in D. japonica. Sequencing analysis showed that ß-thymosin contained two conserved ß-thymosin domains and two actin-binding motifs, and had a high similarity with other ß-thymosins of invertebrates. In situ or fluorescence in situ hybridization analysis revealed that Djß-thymosin was co-localized with DjPiWi in the neoblast cells of intact adult planarians and the blastema of regenerating planarians, suggesting Djß-thymosin has a potential function of regeneration. Disruption Djß-thymosin by RNA interference results in a slightly curled up head of planarian and stem cell proliferation defects. Additionally, we found that, upon amputation, Djß-thymosin RNAi-treated animals had impaired regeneration ability, including impaired blastema formation, delayed eyespot formation, decreased brain area, and disrupted central CNS formation, implying Djß-thymosin is an essential regulator of stem cell proliferation and neuron regeneration.

8.
Nano Lett ; 21(4): 1722-1728, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33528254

RESUMO

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.


Assuntos
Escherichia coli , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Biofilmes , Escherichia coli/genética , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia
10.
Protein Pept Lett ; 28(6): 612-622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33319655

RESUMO

Apoptosis, also named programmed cell death, is a highly conserved physiological mechanism. Apoptosis plays crucial roles in many life processes, such as tissue development, organ formation, homeostasis maintenance, resistance against external aggression, and immune responses. Apoptosis is regulated by many genes, among which Apoptosis Inhibitor-5 (API5) is an effective inhibitor, though the structure of API5 is completely different from the other known Inhibitors of Apoptosis Proteins (IAPs). Due to its high expression in many types of tumors, API5 has received extensive attention, and may be an effective target for cancer treatment. In order to comprehensively and systematically understand the biological roles of API5, we summarized the evolution and structure of API5 and its roles in anti-apoptosis in this review.


Assuntos
Proteínas Reguladoras de Apoptose , Apoptose , Proteínas Nucleares , Animais , Apoptose/genética , Apoptose/fisiologia , Humanos , Camundongos , Modelos Moleculares , Conformação Proteica , Ratos
11.
Sci Rep ; 10(1): 20280, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219247

RESUMO

The righting reflex (RR) is frequently used to assess level of arousal and applied to animal models of a range of neurological disorders. RR produces a binary result that, when positive, is used to infer restoration of consciousness, often without further behavioral corroboration. We find that RR is an unreliable metric for arousal/recovery of consciousness. Instead, cortical activity and motor behavior that accompany RR are a non-binary, superior criterion that accurately calibrates and establishes level of arousal in rodents.


Assuntos
Nível de Alerta/fisiologia , Técnicas de Observação do Comportamento/métodos , Doenças do Sistema Nervoso/diagnóstico , Reflexo de Endireitamento/fisiologia , Animais , Estado de Consciência/fisiologia , Modelos Animais de Doenças , Eletroencefalografia , Feminino , Humanos , Masculino , Camundongos , Doenças do Sistema Nervoso/fisiopatologia , Reprodutibilidade dos Testes , Técnicas Estereotáxicas
12.
Zootaxa ; 4834(2): zootaxa.4834.2.1, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-33056119

RESUMO

According to the Orthoptera species file, there are 765 genera of the infraorder Gryllidea in the world, belonging to 2 superfamilies, 8 families, 37 subfamilies and 6159 species or subspecies in total. A complete list of all genera in the world is provided, including type species, synonyms and species richness. Through statistical analysis, there are 26 extant subfamilies, accounting for 70.27%, 692 extant genera, accounting for 90.46%, 6010 extant species or subspecies, accounting for 97.58%. At the same time, the composition characteristics of the extant genera and species or subspecies in all subfamilies: subfamily Gryllinae has the largest number of genera and species or subspecies, reaching 125 genera and 1221 species or subspecies, with the proportion of 16.34% and 20.34%, followed by subfamily Podoscrtinae, with the number of 99 genera, 770 species or subspecies, with the proportion of 12.94% and 12.83%; subfamily Gryllomiminae with the least number, the number and ratio is 1 genus, 2 species and 0.13%, 0.03%. Among all fossil genera, subfamily †Cearagryllinae is the largest, with 7 genera, 15 species. There are 21 free genera in infraorder Gryllidea, accounting for 2.75%, and 268 monotypic genera (only 1 species), accounting for 35.03%. The largest genus is Hapithus Uhler, 1864, with 209 species or subspecies.


Assuntos
Biodiversidade , Gryllidae , Distribuição Animal , Animais , Fósseis
13.
Eur Spine J ; 29(12): 3187-3193, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33078268

RESUMO

PURPOSE: Some atypical vertebral hemangiomas (VHs) may mimic metastases on routine MRI and can result in misdiagnosis and ultimately to additional imaging, biopsy and unnecessary costs. The purpose of this study is to assess the utility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) on account of field-of-view optimized and constrained undistorted single shot (FOCUS) in distinguishing atypical VHs and vertebral metastases. METHODS: A total of 25 patients with vertebral metastases and 25 patients with atypical VHs were confirmed by clinical follow-up or pathology. IVIM-DWI imaging was performed at different b values (0, 30, 50, 100, 150, 200, 400, 600, 800, 1000 mm2/s). IVIM parameters [the true diffusion coefficient (D), pseudodiffusion coefficient (D*), standard apparent diffusion coefficient (ADC), and perfusion fraction (f)] were calculated and compared between two groups by using Student's t test. A receiver operating characteristic analysis was performed. RESULTS: Quantitative analysis of standard ADC and D parameters showed significantly lower values in vertebral metastases when compared to atypical hemangiomas [ADC value: (0.70 ± 0.12) × 10-3 mm2/s vs (1.14 ± 0.28) × 10-3 mm2/s; D value: (0.47 ± 0.07) × 10-3 mm2/s vs (0.76 ± 0.14) × 10-3 mm2/s, all P < 0.01]. The sensitivity and specificity of D value were 93.8% and 92.3%, respectively. CONCLUSION: The standard ADC value and D value may be used as an indicator to distinguish vertebral metastases from atypical VHs. FOCUS IVIM-derived parameters provide potential value in the quantitatively differentiating vertebral metastases from vertebral atypical hemangiomas.


Assuntos
Imagem de Difusão por Ressonância Magnética , Hemangioma , Hemangioma/diagnóstico por imagem , Humanos , Movimento (Física) , Sensibilidade e Especificidade , Coluna Vertebral
14.
Cytokine ; 136: 155268, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32889153

RESUMO

Human basophils regulate allergic reactions by secreting histamine, interleukin 4 (IL-4) and IL-13 through key surface receptors FcεRI as well as IL-3R, which are constitutively expressed on basophils. IL-3/IL-3R signaling axis plays key roles in regulating the development and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2, IL-17RB and IL-2 receptors regulate the biology of basophils. However, the expression and function of IL-3-induced surface proteins on human basophils remain to be elucidated. We in this study aimed to identify new basophil activation regulators by transcriptomic analysis of IL-3-stimulated basophils. Gene expression microarray analysis of IL-3-treated basophils revealed 2050 differentially expressed genes, of which 323 genes encoded surface proteins including GITR. We identified that GITR was preferentially induced by IL-3 rather than anti-IgE, IL-33, fMLP and C5a. IL-3-induced GITR was suppressed by inhibitors targeting JAK2, PI3K and MEK1/2. Stimulation of IL-3-treated basophils by GITR enhanced the expression of IL-4 and IL-13. Moreover, IgE-mediated degranulation was enhanced by GITRL in the presence of IL-3. This transcriptomic analysis of IL-3-activated basophils helps to identify novel activation regulator. IL-3-induced GITR promoted the activation of basophils, adding new evidence supporting GITR as an important player in Th2-associated immune responses.


Assuntos
Basófilos/imunologia , Regulação da Expressão Gênica/imunologia , Proteína Relacionada a TNFR Induzida por Glucocorticoide/imunologia , Interleucina-3/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Feminino , Humanos , Masculino
15.
ACS Appl Mater Interfaces ; 12(12): 13731-13738, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32155326

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) biofilms are associated with a wide range of infections, from chronic tissue diseases to implanted medical devices. In a biofilm, the extracellular polymeric substance (EPS) causes an inhibited penetration of antibacterial agents, leading to a 100-1000 times tolerance of the bacteria. In view of the water-filled channels in biofilms and the highly negative charge of EPS, we design a chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) in this study. The CS-PEG-LK13 prefers a neutrally charged assembly at a size of ∼100 nm in aqueous environment, while undergoes disassembly to expose the α-helical peptide at the bacterial cell membrane. This behavior provides CS-PEG-LK13 superiorities in both penetrating the biofilms and inactivating the bacteria. At a concentration of 8 times the minimum inhibitory concentration, CS-PEG-LK13 has a much higher antibacterial efficiency (72.70%) than LK13 peptide (15.24%) and tobramycin (33.57%) in an in vitro P. aeruginosa biofilm. Moreover, CS-PEG-LK13 behaves comparable capability of combating an implanted P. aeruginosa biofilm to highly excess tobramycin. This work has implications for the design of new antibacterial agents in biofilm combating.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Quitosana/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos , Infecções Bacterianas/microbiologia , Quitosana/análogos & derivados , Quitosana/química , Humanos , Testes de Sensibilidade Microbiana , Peptídeos/química , Peptídeos/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Pseudomonas aeruginosa/patogenicidade
16.
Int J Anal Chem ; 2019: 3497045, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885590

RESUMO

This study aimed to develop a selective, simple, and sensitive HPLC-MS/MS method for the simultaneous determination of schisandrin and promethazine (PMZ) with its metabolite in rat plasma, which was further used for a pharmacokinetic herb-drug interaction study. HPLC-MS/MS analyses were performed on an Agilent Technologies 1290 LC and a 6410 triple quadrupole mass spectrometer. The following parameters, the lower limit of quantification (LLOQ), calibration curve, accuracy, precision, stability, matrix effect, and recovery, were validated. The linear range of the developed method for PMZ, its metabolite promethazine sulfoxide (PMZSO), and schisandrin in rat plasma was 0.5-200 ng/mL (R 2 > 0.995), with an LLOQ of 0.5 ng/mL, which completely met the determination requirements of biosamples. The intra- and interday precision (RSD, %) was below 13.31% (below 16.67% for the LLOQ) in various plasma, whose accuracy (bias, %) was from -8.52% to 11.40%, which were both within an acceptable range. This method was successfully applied to a pharmacokinetic herb-drug interaction study after oral administration of PMZ with or without S. chinensis water extract. The results demonstrated that coadministration with the S. chinensis water extract might affect the pharmacokinetic behaviors of PMZ. In turn, when taken together with PMZ, the pharmacokinetic parameters of schisandrin, the main active component of S. chinensis, were also affected. The method established in the current study was selective, simple, sensitive, and widely available with good linearity, high accuracy and precision, and a stable sample preparation process. Moreover, this analytical method provides a significant approach for the investigation of herb-drug interaction between S. chinensis and PMZ. The potential pharmacokinetic herb-drug interaction of PMZ- and schisandrin-containing preparations should be noted.

17.
Proc Natl Acad Sci U S A ; 116(47): 23437-23443, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31685638

RESUMO

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.


Assuntos
Ácidos Acíclicos/farmacologia , Antibacterianos/farmacologia , Proteínas do Capsídeo/farmacologia , Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Produtos do Gene tat/farmacologia , Compostos Organoplatínicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Estilbenos/farmacologia , Ácidos Acíclicos/química , Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/efeitos da radiação , Escherichia coli/ultraestrutura , Microscopia Eletrônica , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio , Staphylococcus aureus/efeitos da radiação , Staphylococcus aureus/ultraestrutura , Eletricidade Estática , Vírus do Mosaico do Tabaco
18.
Chin Med ; 14: 30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467589

RESUMO

Background: Astragali Radix (AR) is widely-used for improving liver fibrosis, but, the mechanism of action has not been systematically explained. This study aims to investigate the mechanism of AR intervention in liver fibrosis based on comprehensive metabolomics combined with network pharmacology approach. Materials and methods: UPLC-Q-TOF/MS based metabolomics technique was used to explore the specific metabolites and possible pathways of AR affecting the pathological process of liver fibrosis. Network pharmacology analysis was introduced to explore the key targets of AR regarding the mechanisms on liver fibrosis. Results: AR significantly reduced the levels of ALT, AST and AKP in serum, and improved pathological characteristics. Metabolomics analysis showed that the therapeutic effect of AR was mainly related to the regulation of nine metabolites, including sphingosine, 6-keto-prostaglandin F1a, LysoPC (O-18:0), 3-dehydrosphinganine, 5,6-epoxy-8,11,14-eicosatrienoic acid, leukotriene C4, taurochenodesoxycholic acid, LysoPC (18:1 (9Z)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine. Pathway analysis indicated that the treatment of AR on liver fibrosis was related to arachidonic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis. Validation of the key targets by network pharmacology analysis of potential metabolic markers showed that AR significantly down-regulated the expression of CYP1B1 and up-regulated the expression of CYP1A2 and PCYT1A. Conclusion: Metabolomics combined with network pharmacology was used for the first time to clarify that the treatment of AR on liver fibrosis, which is related to the regulation of arachidonic acid metabolism and ether lipid metabolism by modulating the expression of CYP1A2, CYP1B1 and PCYT1A. And the integrated approach can provide new strategies and ideas for the study of molecular mechanisms of traditional Chinese medicines in the treatment of liver fibrosis.

19.
J Pharm Pharmacol ; 70(12): 1675-1687, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30277564

RESUMO

OBJECTIVES: Cholestasis is a critical risk factor for severe hepatic disease or cirrhosis. The anti-inflammatory effect of Paeonia lactiflora Pall. (PLP), named Chishao in traditional Chinese medicine (TCM), on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model was tried to be elucidated in this research. METHODS: Therapeutic effect indices on hepatic function, including ALT, AST, TBIL, DBIL, ALP, TBA and γ-GT, were measured. To further investigate the protective mechanism of PLP, the mRNA and protein expression levels of NF-κB-NLRP3 inflammasome pathway were detected. RESULTS: Our results showed that compared with the model group, PLP could significantly reduce the increased serum indices such as ALT, AST, TBIL, DBIL, ALP, TBA and γ-GT induced by ANIT in a dose-dependent way. Moreover, we found that PLP downregulated the mRNA expression levels including IKK, p65, NLRP3, caspase-1 and IL-1ß, especially at the large dose. Furthermore, PLP also significantly inhibited NF-κB-NLRP3 inflammasome pathway by decreasing the protein levels of p65, p-p65, p-IKK, NLRP3, caspase-1 and IL-1ß. CONCLUSIONS: The results indicated that PLP could ameliorate ANIT-induced cholestasis in rats and the anti-inflammatory effect of PLP might be related to regulating NF-κB-NLRP3 inflammasome pathway. This study will provide scientific evidence for PLP as a potential drug candidate for cholestasis.


Assuntos
Inflamassomos/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , NF-kappa B/biossíntese , Paeonia , Extratos Vegetais/farmacologia , 1-Naftilisotiocianato/farmacologia , Animais , Biomarcadores , Colestase/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Testes de Função Hepática , Medicina Tradicional Chinesa , RNA Mensageiro , Ratos , Ratos Sprague-Dawley
20.
Nano Lett ; 18(9): 5453-5460, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30091612

RESUMO

Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.


Assuntos
Peptídeos Penetradores de Células/química , Portadores de Fármacos/química , Nanopartículas/química , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Vírus do Mosaico do Tabaco/química , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Feminino , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , Terapêutica com RNAi
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