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2.
J Pharm Biomed Anal ; 205: 114357, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500237

RESUMO

This study aimed to demonstrate the pharmacological mechanism of total flavonoids extracted from Astragali Radix (AR) on cyclophosphamide (Cy)-induced leucopenia in mice. First, flow cytometry, network pharmacology and plasma metabolomics were integrated to investigate the pharmacological mechanism of total flavonoids, the targets from network pharmacology and metabolites from metabolomics were analyzed by DAVID. Then, the key cytokines were validated to confirm the predicted metabolic pathway results. The results showed that total flavonoids significantly increased body weight, routine blood indices, bone marrow DNA cells, and also markedly caused lymphocyte proliferation by increasing the percentages of CD4+ and CD8+. Using network pharmacology and metabolomics methods, the study identified 13 signal-related pathways regulated by total flavonoids including PI3K-Akt signaling pathway, Jak-STAT signaling pathway, Sphingolipid signaling pathway, and so on. Total flavonoids also reversed changes in serum cytokines IL-2, IL-6, and GM-CSF. Total flavonoids exhibits protective effects against leucopenia probably by modulating immunologic functions, promoting cell proliferation, and regulating related metabolic pathways at the system level.


Assuntos
Medicamentos de Ervas Chinesas , Flavonoides , Animais , Ciclofosfamida/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases , Biologia de Sistemas
3.
Front Neurorobot ; 15: 674322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122035

RESUMO

With the rapid popularity of agent technology, a public opinion early warning agent has attracted wide attention. Furthermore, a deep learning model can make the agent more automatic and efficient. Therefore, for the agency of a public opinion early warning task, the deep learning model is very suitable for completing tasks such as popularity prediction or emergency outbreak. In this context, improving the ability to automatically analyze and predict the virality of information cascades is one of the tasks that deep learning model approaches address. However, most of the existing studies sought to address this task by analyzing cascade underlying network structure. Recent studies proposed cascade virality prediction for agnostic-networks (without network structure), but did not consider the fusion of more effective features. In this paper, we propose an innovative cascade virus prediction model named CasWarn. It can be quickly deployed in intelligent agents to effectively predict the virality of public opinion information for different industries. Inspired by the agnostic-network model, this model extracts the key features (independent of the underlying network structure) of an information cascade, including dissemination scale, emotional polarity ratio, and semantic evolution. We use two improved neural network frameworks to embed these features, and then apply the classification task to predict the cascade virality. We conduct comprehensive experiments on two large social network datasets. Furthermore, the experimental results prove that CasWarn can make timely and effective cascade virality predictions and verify that each feature model of CasWarn is beneficial to improve performance.

4.
Front Neurorobot ; 15: 674428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34045950

RESUMO

With the rapid development of artificial intelligence, Cybernetics, and other High-tech subject technology, robots have been made and used in increasing fields. And studies on robots have attracted growing research interests from different communities. The knowledge graph can act as the brain of a robot and provide intelligence, to support the interaction between the robot and the human beings. Although the large-scale knowledge graphs contain a large amount of information, they are still incomplete compared with real-world knowledge. Most existing methods for knowledge graph completion focus on entity representation learning. However, the importance of relation representation learning is ignored, as well as the cross-interaction between entities and relations. In this paper, we propose an encoder-decoder model which embeds the interaction between entities and relations, and adds a gate mechanism to control the attention mechanism. Experimental results show that our method achieves better link prediction performance than state-of-the-art embedding models on two benchmark datasets, WN18RR and FB15k-237.

5.
Cell Death Discov ; 7(1): 85, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875644

RESUMO

The overexpression of HER2 is associated with a malignant proliferation of breast cancer. In this study, we developed a non-cytotoxic JWA gene activating compound 1 (JAC1) to inhibit the proliferation of HER2-positive breast cancer cells in vitro and in vivo experimental models. JAC1 increased the ubiquitination of HER2 at the K716 site through the E3 ubiquitin ligase SMURF1 which was due to the decreased expression of NEDD4, the E3 ubiquitin ligase of SMURF1. In conclusion, JAC1 suppresses the proliferation of HER2-positive breast cancer cells through the JWA triggered HER2 ubiquitination signaling. JAC1 may serve as a potential therapeutic agent for HER2-positive breast cancer.

6.
J Cancer ; 12(7): 1894-1906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33753987

RESUMO

Background: Cisplatin (DDP) is a highly effective chemotherapeutic agent to most solid tumors including gastric cancer (GC), however, its clinical value is limited due to severe toxic side effects and secondary drug resistance. JP3, a JWA protein based MMP2-targeted polypeptide, known to inhibit the growth of GC in vivo. However, the bidirectional effects of JP3 in DDP-resistant GC and normal cells have not been demonstrated. The present study aims to investigate the actions of JP3 on protecting normal cells from the toxicity of DDP while enhancing its anti-tumor effects on GC cells. Methods: Routine laboratory experimental methods including CCK-8 assay, Western blotting, Hoechst staining, immunofluorescence (IF) and qRT-PCR were used in mechanism investigation; protein docking analysis and coimmunoprecipitation (Co-IP) were used for prediction and confirmation of interactions between JP3 and CK2. Mouse xenograft model was used for screening the treatment of JP3 plus DDP on GC growth. Results: DDP showed similar toxicities to normal cells and DDP-resistant GC cells; JP3 competitively inhibited the binding of XRCC1 to CK2, reduced the DNA repair and anti-apoptosis capacity of DDP-resistant GC cells in combination with DDP treatment; meanwhile, JP3 protected normal cells from DDP-induced oxidative stress and DNA damage through ERK/Nrf2 signaling. JP3 combined with DDP showed similar bidirectional effects in vivo. Conclusions: JP3 enhanced the inhibitory effects of DDP on tumor growth while reduced toxic side effects of DDP on normal cells. The results of this study provide a new insight for the treatment of drug-resistant GC.

7.
Neuroreport ; 32(4): 321-325, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33470768

RESUMO

Studies have found that fibroblast growth factor 9 (FGF9) might have a negative effect in the psychiatric diseases, such as depression or anxiety, but its potential role in the pathophysiology of poststroke depression (PSD) remains uncertain. Here, we set out to investigate the expression changes of FGF9 and its receptors in PSD rats. Middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress was used to establish the PSD rat model. Then, the rats were randomly divided into four groups: control (sham-operation), MCAO, PSD and treated (fluoxetine injection by intraperitoneal). Weight measurement, sucrose preference test, open-field test and forced swim test were performed to evaluate the behavioral changes, and then Western blot and real-time quantitative PCR were used to detect the expression level of FGF9, fibroblast growth factor receptor 1 (FGFR1) and receptor 3 (FGFR3) in the dentate gyrus of rat hippocampus. We found that FGF9 protein and mRNA expression increased significantly in the MCAO and PSD groups; FGFR3 protein and mRNA expression decreased significantly in the MCAO and PSD groups; FGFR1 protein and mRNA expression decreased significantly in the PSD group, but increased in the treated group. Furthermore, the changes mentioned above were reversed obviously by fluoxetine. These results indicated that upregulated FGF9 expression and downregulated FGFR1 and FGFR3 expression may be involved in the pathogenesis of PSD, and the FGF9/FGFR signaling pathway may be considered as an attractive target for further study.

8.
Nanomaterials (Basel) ; 12(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35010094

RESUMO

Tumor invasion/metastasis is still the major cause of death in cancer patients. Membrane type-1 matrix metalloproteinase (MT1-MMP) is directly related to tumor invasion/metastasis. To accurately and quickly distinguish the risk of invasion/metastasis of primary tumor cells, it is urgent to develop a simple and precise quantitative method to distinguish the expression level of MT1-MMP. In this work, we have constructed red fluorescent Au clusters with peroxidase-like properties that could specifically bind to MT1-MMP on human cervical cancer cells. After MT1-MMP was labelled with Au clusters, we could visually see red fluorescence of MT1-MMP on cervical cancer cells via fluorescence microscopy and catalytic color imaging using an ordinary optical microscope. The constructed Au clusters contained 26 Au atoms; thus, the amount of MT1-MMP on cervical cancer cells could be accurately quantified using inductively coupled plasma mass spectrometry (ICP-MS). More importantly, the invasion/metastasis capabilities of the cervical cancer Siha, Caski and Hela cells with different MT1-MMP amounts could be accurately distinguished by fluorescence/catalysis qualitative imaging and ICP-MS quantitative analysis. This method of qualitative/quantitative analysis of tumor-associated proteins on cancer cells has great potential for accurately diagnosing aggressive tumor cells and assessment of their invasion/metastasis risk.

10.
J Pharm Biomed Anal ; 191: 113588, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32927418

RESUMO

Depression is currently the main disease which endangers human health and emotion. However, the existing antidepressants have the disadvantages of slowly taking effect and high recurrence rate. Numerous studies have shown that depression causes disorders in energy metabolism, but the specific metabolic pathways remain unclear. The stable isotope-resolved metabolomics (SIRM) can clarify the specific metabolic pathways of energy metabolism disorders in depression and provide a strong basis for the pathogenesis of depression and new targets for the development of new antidepressants. We applied this method to the chronic unpredictable mild stress (CUMS) model, and the metabolites related to energy metabolism were comprehensively analyzed on HILIC and T3 columns through LC-MS. Conventional untargeted metabolomics found 50 differential metabolites, and most of them were focused on the energy metabolism pathway. SIRM exhibited that 78 metabolites related to energy metabolism were labeled, and 28 of them were observed significantly changed in the model group compared with control. Our results revealed depression inhibited TCA cycle and activated gluconeogenesis pathway, and abnormally increased pyruvic acid may participate in pyrimidine biosynthesis, phospholipid synthesis, and amino acid metabolism pathways. Pyruvate carboxylase (PC), pyruvate dehydrogenase (PDH), aspartate aminotransferase (AST) and phosphoenolpyruvate carboxykinase (PEPC) may be the new targets for depression. We established a SIRM method at animal level. To the best of our knowledge, it is the first time to apply the method for the study of depression. The method is of great significance and value for further explaining the pathogenesis of depression and the development of antidepressants.


Assuntos
Depressão , Metabolômica , Animais , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Metabolismo Energético , Isótopos , Ratos
11.
Phytomedicine ; 77: 153274, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32771537

RESUMO

BACKGROUND: Astragali Radix (AR), a common Traditional Chinese Medicine (TCM), is commonly used for treating nephrotic syndrome (NS) in China. At present, the research on the efficacy of AR against NS is relative clearly, but there are fewer researches on the mechanism. PURPOSE: The aim of this study was to evaluate the potential beneficial effects of AR in an adriamycin-induced nephropathy rat model, as well as investigate the possible mechanisms of action and potential lipid biomarkers. METHODS: In this work, a rat model of NS was established by two injections of ADR (3.5 + 1 mg/kg) into the tail vein. The potential metabolites and targets involved in the anti-NS effects of AR were predicted by lipidomics coupled with the network pharmacology approach, and the crucial metabolite and protein were further validated by western blotting and ELISA. RESULTS: The results showed that 22 metabolites such as l-carnitine, LysoPC (20:3), and SM (d18:1/16:0) were associated with renal injury. Moreover, SMPD1, CPT1A and LCAT were predicted as lipids linked targets of AR against NS, whilst glycerophospholipid, sphingolipid and fatty acids metabolism were involved as key pathways of AR against NS. Besides, AR could play a critical role in NS by improving oxidative stress, inhibiting apoptosis and reducing inflammation. Interestingly, our results indicated that key metabolite l-carnitine and target CPT1 were one of the important metabolites and targets for AR to exert anti-NS effects. CONCLUSION: In summary, this study offered a new understanding of the protection mechanism of AR against NS by network pharmacology and lipidomic method.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Síndrome Nefrótica/tratamento farmacológico , Animais , Astragalus propinquus , Carnitina/metabolismo , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Ácidos Graxos/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Lipidômica , Lisofosfatidilcolinas/metabolismo , Masculino , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/metabolismo , Ratos Sprague-Dawley
12.
Theranostics ; 10(18): 8036-8050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724456

RESUMO

Background: JWA gene is known to down-regulate SP1 and reduces the expression level of Integrin αvß3. Here, we identified a functional polypeptide (JP1) based on the active fragment of the JWA protein to suppress melanoma growth and metastasis by inhibiting the Integrin αvß3. Methods: We conducted a series of melanoma growth and metastasis mouse models to evaluate anti-melanoma effect of JP1 peptide. 18F-labeled JP1 (18F-NFP-JP1) was detected by Micro-PET assay to demonstrate drug biodistribution. Toxicity test in cynomolgus monkeys and pharmacokinetic studies in rats were done to assess the druggability. The expression of MEK1/2, NEDD4L, SP1 and Integrin αvß3 were detected in vitro and vivo models. Results: The peptide JP1 with the best anticancer effect was obtained. Micro-PET assay showed that JP1 specifically targeting to melanoma cells in vivo. JP1 inhibited melanoma growth, metastasis, and prolonged the survival of mouse. JP1 reduced the dosage and toxicity in combination with DTIC in melanoma xenograft and allograft mouse models. Cynomolgus monkey toxicity test showed no observed adverse effect level (NOAEL) of JP1 was 150 mg/kg. Mechanistically, JP1 was shown to activate p-MEK1/2 and triggered SP1 ubiquitination in melanoma cells. NEDD4L, an E3 ubiquitin ligase, was activated by p-MEK1/2 and to ubiquitinate SP1 at K685 site, resulting in subsequent degradation. Conclusions: JP1 was developed as a novel peptide that indicated therapeutic roles on proliferation and metastasis of melanoma through the NEDD4L-SP1-Integrin αvß3 signaling.


Assuntos
Antineoplásicos/administração & dosagem , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Peptídeos/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Proteínas de Choque Térmico/genética , Humanos , Integrina alfaVbeta3/metabolismo , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase 2/metabolismo , Macaca fascicularis , Masculino , Melanoma/secundário , Proteínas de Membrana Transportadoras/genética , Camundongos , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Peptídeos/genética , Peptídeos/farmacocinética , Neoplasias Cutâneas/patologia , Fator de Transcrição Sp1/metabolismo , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Exp Clin Cancer Res ; 39(1): 118, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576271

RESUMO

BACKGROUND: Gastric cancer (GC) is the most prevalent gastrointestinal tumor with an unfavorable clinical prognosis. GC patients are largely threatened owing to metastasis and drug resistance. Tumor angiogenesis plays an important role in the development of gastric cancer and is a challenge in the treatment of gastric cancer. METHODS: Mouse xenograft models were used for screening of therapeutic peptides on GC growth and metastasis. Routine laboratory experimental methods including conditional cell culture, tube formation assay, qRT-PCR, Western blotting, immunohistochemistry (IHC), ubiquitination assay, and immunofluorescence (IF) were used in mechanism investigation; protein docking analysis and coimmunoprecipitation (Co-IP) were used for prediction and confirmation of interactions between JP3/SP1 and TRIM25/MEK1/2. RESULTS: We identified an MMP2-targeted peptide JP3 that plays inhibiting roles in modulating growth and metastasis of GC in vivo and has no observable toxic side effects. JP3 reduced tumor microvessel density (MVD) in vivo and human umbilical vein endothelial cells (HUVECs) tube formation in vitro. Mechanistic studies revealed that JP3 reduces polyubiquitination-mediated degradation of TRIM25 by increasing the stability of TRIM25 through phosphorylating it at Ser12. TRIM25, as an E3 ubiquitin ligase, promoted the ubiquitin of SP1 at K610, further suppressed expression of MMP2 and inhibited angiogenesis in GC. Importantly, the inversely association between TRIM25 and SP1 protein level was further verified in human GC tissues. Decreased TRIM25 expression and increased SP1 expression in tumor tissues were positively correlated with poor prognosis of GC patients. CONCLUSIONS: MMP2-targeted peptide JP3 plays a therapeutic role in GC through anti-angiogenesis by modulating TRIM25/SP1/MMP2.


Assuntos
Biomarcadores Tumorais/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Neovascularização Patológica/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Fator de Transcrição Sp1/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Metaloproteinase 2 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Neovascularização Patológica/patologia , Fator de Transcrição Sp1/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Chin J Nat Med ; 18(6): 460-471, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503737

RESUMO

The quality of Astragali Radix (AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years' wild Astragali Radix (WAR) and transplanted Astragali Radix (TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1-6 growth years root through the methods. The contents of flavonoids and saponins in 2-6 growth years' WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR (4-year-old) and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters (EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.


Assuntos
Astrágalo (Planta)/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Saponinas/farmacologia , Animais , Astragalus propinquus , Modelos Animais de Doenças , Doxorrubicina , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
15.
Alzheimers Res Ther ; 12(1): 47, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32331528

RESUMO

BACKGROUND: Amyloid beta (Aß) which is recognized as a main feature of Alzheimer's disease (AD) has been proposed to "spread" through anatomically and functionally connected brain regions. The entorhinal cortex and perforant path are the earliest affected brain regions in AD. The perforant path is the most vulnerable circuit in the cortex with respect to both aging and AD. Previous data show that the origins and terminations of the perforant path are susceptible to amyloid deposition at the younger age in AD. Nogo receptor (NgR) plays an essential role in limiting injury-induced axonal growth and experience-dependent plasticity in the adult brain. It has been suggested that NgR is involved in AD pathological features, but the results have been conflicting and the detailed mechanism needs further investigation. In this study, the effect of NgR in the perforant path on the pathological and functional phenotype of APP/PS1 transgenic mice was studied. METHODS: To genetically manipulate NgR expression, adeno-associated virus (AAV) with short hairpin (shRNA) against NgR was injected into the perforant path of APP/PS1 transgenic mice, followed by an assessment of behavioral, synaptic plasticity and neuropathological phenotypes. NgR was overexpressed or knockdown in neuroblastoma N2a cells and APPswe/HEK293 cells to investigate the interaction between NgR and amyloid precursor protein (APP). RESULTS: It is shown that reduction of NgR in the perforant path rescued cognitive and synaptic deficits in APP/PS1 transgenic mice. Concurrently, Aß production in the perforant path and levels of soluble Aß and amyloid plaques in the hippocampus were significantly decreased. There was a positive correlation between the total APP protein level and NgR expression both in transgenic mice and in cultured cells, where the α-secretase and ß-secretase cleavage products both changed with APP level in parallel. Finally, NgR might inhibit APP degradation through lysosome by Rho/Rho-associated protein kinases (ROCK) signaling pathway. CONCLUSIONS: Our findings demonstrate that perforant path NgR plays an important role in regulating APP/Aß level and cognitive functions in AD transgenic mice, which might be related to the suppression of APP degradation by NgR. Our study suggests that NgR in the perforant path could be a potential target for modulating AD progression.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Cognição , Modelos Animais de Doenças , Células HEK293 , Humanos , Camundongos , Camundongos Transgênicos , Receptores Nogo , Via Perfurante/metabolismo , Presenilina-1/genética
16.
Chem Biol Interact ; 325: 109096, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32289291

RESUMO

BACKGROUND AND AIMS: Adriamycin nephropathy model (AN), a rodent model of nephrotic syndrome disease that was caused by the nephrotoxicity of adriamycin, has been widely used for pharmacodynamic evaluation of traditional Chinese medicine (TCM) in the treatment of kidney injury. Although some studies have clearly shown the pathological process of AN, the mechanism of kidney injury have not been systematically investigated. METHODS: The reliability of AN was evaluated by weight, urinary protein quantitation, serum biochemical and histopathological examination. Transcriptomic sequencing combined with network pharmacology were used to elucidate the molecular mechanism of AN, and cell experiment combined with real-time quantitative PCR (RT-qPCR) and was used to validate the accuracy of transcriptomic sequencing result and KEGG pathways. RESULTS: Network analysis result showed that Mapk10 and Ptgs2 played important roles in the development of adriamycin-induced kidney injury. KEGG pathway analysis showed that the mechanism of kidney injury may be related to the regulation of biosynthesis of unsaturated fatty acids, complement and coagulation cascades, PPAR signaling pathway and PI3K-AKT signaling pathway. CONCLUSION: These results provide a new insight into the deep research on the mechanism of kidney injury, and provide an experimental basis for finding drug targets for the treatment of AN.


Assuntos
Doxorrubicina/farmacologia , Rim/efeitos dos fármacos , Rim/lesões , Mapeamento de Interação de Proteínas , Transcriptoma/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Rim/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
17.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1279-1286, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281337

RESUMO

The effective material basis of traditional Chinese medicine(TCM) is an indispensable part of studies on TCM, and each technology has its advantages and disadvantages. The target constituent knock-out/knock-in technology has attracted much attention since it was proposed because of its unique advantages of regarding the extract of the formula as a whole, which can better reflect the characteristics of multi-component and multi-target integration and regulation of TCM. This method investigated the contribution of target constituent to the overall efficacy of a TCM by analyzing the changes in efficacy of the remaining formula before and after knock-out/knock-in of the target constitution. The application of this model not only facilitates studies of the effective constituents of TCM, but also help to develop the quality control standard of TCM. However, the application of this model is restricted due to the limitation of target constituent separation technology. By reviewing the literatures in recent years, this study summarized the research process and application of this method for a reference.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Animais , Técnicas de Introdução de Genes , Técnicas de Inativação de Genes , Controle de Qualidade
18.
Food Chem ; 320: 126651, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32220709

RESUMO

Ziziphi Spinosae Folium, the leaf of Ziziphus jujuba Mill. Var. spinosa (Bunge) Hu ex H. F. Chou (LZJS), is currently used as a healthy tea in China. This study evaluated the chemical components and antioxidant activities of LZJS flavonoid (LZJSF) and fermented LZJSF (FLZJSF) using human intestinal bacteria (HIB) through dynamic fermentation. Eighteen flavonoids were simultaneously identified in LZJSF using UHPLC-Q-Orbitrap-MS method, nine of which were targeted for a HIB metabolism study. Seven small phenolic acids were identified in FLZJSF. Not only at chemical level but also at PC12 cell level, FLZJSF samples fermented for 4 and 6 h showed significant positive correlation between their activities and flavonoid aglycones, which were transformed from LZJSF. However, FLZJSF samples (8 h and longer time) mainly contained phenolic acids and indicated weak activities. Thus, LZJSF was found to result in increased antioxidant activity and could be commercially utilized as a novel functional food.


Assuntos
Antioxidantes/metabolismo , Bactérias/metabolismo , Flavonoides/análise , Ziziphus/metabolismo , Adulto , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Flavonoides/metabolismo , Microbioma Gastrointestinal , Humanos , Masculino , Células PC12 , Extratos Vegetais/análise , Extratos Vegetais/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Ratos , Ziziphus/química
19.
J Pharm Biomed Anal ; 185: 113234, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171146

RESUMO

Danggui Buxue Decoction (DBD), a famous traditional Chinese medicine (TCM), is often used to treat anemia in China. However, its underlying therapeutic mechanism is unclear. Through the analysis of body weight, spleen and thymus indexes, peripheral blood routine and pathological section of femur, it was obviously that DBD could significantly improve acetylphenylhydrazine (APH) + cyclophosphamide (CTX) induced anemia mice in the present work. Ultra high performance liquid chromatography coupled with quadrupole - Exactive mass spectrometry (UHPLC Q-Exactive MS) based metabolomics and lipidomics was further utilized to screen out differential spleen metabolites associated with DBD treatment. A total of 26 differential metabolites including 8 polar metabolites and 18 lipids were firstly obtained to relate with anemia mice. 7 polar metabolites and 10 lipids among them were reversed by DBD, which the regulation of pyrimidine metabolism and glycerophospholipid metabolism were mainly associated to the anti-anemia effect of DBD based on MetaboAnalyst analysis. Through random forest analysis (RF), ROC analysis and pearson matrix correlation, three metabolites, cytosine, uracil and PC (o-16:1(9Z)/20:0), were further screened out as the potential pharmacodynamic biomarkers associated with the efficacy of DBD. This study provided a methodological reference for the study of the mechanism of TCM.


Assuntos
Anemia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipidômica/métodos , Baço/efeitos dos fármacos , Anemia/sangue , Animais , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Citosina/sangue , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Masculino , Espectrometria de Massas/métodos , Camundongos , Palmitoilcarnitina/sangue , Baço/metabolismo , Uracila/sangue
20.
J Ethnopharmacol ; 253: 112688, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32101772

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal pair of HuangQi-DanShen (HD) is frequently used for treating brain injury caused by cerebral ischemia (CI) in traditional Chinese medicine (TCM). AIM OF THE STUDY: The present work was designed to reveal the active mechanism of HD against CI. MATERIALS AND METHODS: In our work, an integrated approach combined 1H-NMR based metabonomics and network pharmacology was applied to decipher the protection of HD against MCAO (middle cerebral artery occlusion)-induced CI rats. Meanwhile, the indicator of neurological deficit and TTC staining were used to estimate the efficacy of HD. RESULTS: The results of neurological deficit test and TTC staining suggested HD could improve the brain injury in CI rats. The metabonomic result indicated that HD could significantly ameliorate 8 serum metabolites in CI rats, which were linked 71 corresponding targeted proteins obtained by Metscape. In addition, 84 targets related HD against CI were obtained by network pharmacology. At last, 5 important targets were screened as hopeful targets for the treatment of CI through integrating them. CONCLUSION: The integrated method coupled 1H-NMR based metabonomics with network pharmacology provided the insights into the mechanisms of TCM in treating CI.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/sangue , Animais , Astragalus propinquus , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Masculino , Metabolômica , Mapas de Interação de Proteínas , Ratos Sprague-Dawley , Salvia miltiorrhiza
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