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Book ; Online: DAN-Net

Wang, Tao / Xia, Wenjun / Huang, Yongqiang / Sun, Huaiqiang / Liu, Yan / Chen, Hu / Zhou, Jiliu / Zhang, Yi

Dual-Domain Adaptive-Scaling Non-local Network for CT Metal Artifact Reduction

2021

Abstract: ... performance. In this paper, a novel Dual-domain Adaptive-scaling Non-local network (DAN-Net) for MAR ... module are leveraged in the proposed network model. In the experiments, the proposed DAN-Net demonstrates ...

Abstract	Metal implants can heavily attenuate X-rays in computed tomography (CT) scans, leading to severe artifacts in reconstructed images, which significantly jeopardize image quality and negatively impact subsequent diagnoses and treatment planning. With the rapid development of deep learning in the field of medical imaging, several network models have been proposed for metal artifact reduction (MAR) in CT. Despite the encouraging results achieved by these methods, there is still much room to further improve performance. In this paper, a novel Dual-domain Adaptive-scaling Non-local network (DAN-Net) for MAR. We correct the corrupted sinogram using adaptive scaling first to preserve more tissue and bone details as a more informative input. Then, an end-to-end dual-domain network is adopted to successively process the sinogram and its corresponding reconstructed image generated by the analytical reconstruction layer. In addition, to better suppress the existing artifacts and restrain the potential secondary artifacts caused by inaccurate results of the sinogram-domain network, a novel residual sinogram learning strategy and nonlocal module are leveraged in the proposed network model. In the experiments, the proposed DAN-Net demonstrates performance competitive with several state-of-the-art MAR methods in both qualitative and quantitative aspects. Comment: 29 pages, 11 figures
Keywords	Physics - Medical Physics ; Computer Science - Computer Vision and Pattern Recognition
Subject code	006
Publishing date	2021-02-16
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: DAN-SNR

Huang, Liwei / Ma, Yutao / Liu, Yanbo / He, Keqing

A Deep Attentive Network for Social-Aware Next Point-of-Interest Recommendation

2020

Abstract: ... POI recommendation called DAN-SNR. In particular, the DAN-SNR makes use of the self-attention ... multi-head self-attention, the DAN-SNR can model long-range dependencies between any two historical ... location-based social networks, namely Gowalla and Brightkite. Experimental results indicate that the DAN ...

Abstract	Next (or successive) point-of-interest (POI) recommendation has attracted increasing attention in recent years. Most of the previous studies attempted to incorporate the spatiotemporal information and sequential patterns of user check-ins into recommendation models to predict the target user's next move. However, none of these approaches utilized the social influence of each user's friends. In this study, we discuss a new topic of next POI recommendation and present a deep attentive network for social-aware next POI recommendation called DAN-SNR. In particular, the DAN-SNR makes use of the self-attention mechanism instead of the architecture of recurrent neural networks to model sequential influence and social influence in a unified manner. Moreover, we design and implement two parallel channels to capture short-term user preference and long-term user preference as well as social influence, respectively. By leveraging multi-head self-attention, the DAN-SNR can model long-range dependencies between any two historical check-ins efficiently and weigh their contributions to the next destination adaptively. Also, we carried out a comprehensive evaluation using large-scale real-world datasets collected from two popular location-based social networks, namely Gowalla and Brightkite. Experimental results indicate that the DAN-SNR outperforms seven competitive baseline approaches regarding recommendation performance and is of high efficiency among six neural-network- and attention-based methods. Comment: 25 pages, 7 figures, and 6 tables
Keywords	Computer Science - Social and Information Networks ; Computer Science - Information Retrieval ; H.3.3
Subject code	006
Publishing date	2020-04-25
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A newly-discovered tea population variety processed Bai Mu Dan white tea: Flavor characteristics and chemical basis.

Lin, Yanping / Huang, Yibiao / Zhou, Su / Li, Xiaolan / Tao, Yike / Pan, Yani / Feng, Xinyu / Guo, Haowei / Chen, Ping / Chu, Qiang

Food chemistry

2024 Volume 446, Page(s) 138851

Abstract: The quality of white tea (WT) is impacted by selected tea cultivars. To explore the organoleptic quality of a recently-discovered WT ("Caicha", CC), HS-SPME/GC-MS and UPLC were employed to identify volatile and non-volatile compounds in tea samples. ... ...

Abstract	The quality of white tea (WT) is impacted by selected tea cultivars. To explore the organoleptic quality of a recently-discovered WT ("Caicha", CC), HS-SPME/GC-MS and UPLC were employed to identify volatile and non-volatile compounds in tea samples. Multiple statistical methods demonstrated the distinctions between CC and four mainstream WT varieties from main producing areas. CC exhibited abundant volatile alcohol, terpenoids, ketone, aldehyde and ester, as well as non-volatile lignans and coumarins, phenolic acids and low-molecular carbohydrates. These substances combinedly contributed to the flavor attributes of CC, characterized by an intense herbal/citrus-like cleanness and flower/fruit-like sweetness, scarce in existing commercial WT varieties. Sensory evaluation corroborated these findings. In conclusion, we have processed a new tea variety (CC) with WT manufacturing technology, and discovered the unique cleanness and sweetness of it. This study enriches the raw material database for WT production and blending, and boosts the development of more premium WT varieties.
MeSH term(s)	Tea/chemistry ; Camellia sinensis/chemistry ; Volatile Organic Compounds/analysis ; Gas Chromatography-Mass Spectrometry/methods ; Lignans
Chemical Substances	Tea ; Volatile Organic Compounds ; Lignans
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	243123-3
ISSN	1873-7072 ; 0308-8146
ISSN (online)	1873-7072
ISSN	0308-8146
DOI	10.1016/j.foodchem.2024.138851
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Article ; Online: Dan-Deng-Tong-Nao softgel capsule promotes angiogenesis of cerebral microvasculature to protect cerebral ischemia reperfusion injury via activating HIF-1α-VEGFA-Notch1 signaling pathway.

Wang, Lei / Li, Jiacheng / Wang, Yang / Ge, Chaowen / Huang, Qi / Li, Lili / Wang, Ning / Chen, Yuang / Zhou, Xian / Chang, Dennis / Li, Dan / Hou, Jincai

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 118, Page(s) 154966

Abstract: Background: A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC ...

Abstract	Background: A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized. Objective: To explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels. Methods: Chemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro. Results: Seven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNCCSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo. Conclusions: DDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-NOTCH1 signal transduction pathway.
MeSH term(s)	Rats ; Animals ; Endothelial Cells ; Vascular Endothelial Growth Factor A/metabolism ; Angiostatins/metabolism ; Angiostatins/pharmacology ; Angiostatins/therapeutic use ; Brain-Derived Neurotrophic Factor/metabolism ; Endostatins/metabolism ; Endostatins/pharmacology ; Endostatins/therapeutic use ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Infarction, Middle Cerebral Artery/drug therapy ; Infarction, Middle Cerebral Artery/metabolism ; Reperfusion Injury/drug therapy ; Reperfusion Injury/metabolism ; Microvessels/metabolism ; Receptor, Notch1/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A ; Angiostatins (86090-08-6) ; Brain-Derived Neurotrophic Factor ; Endostatins ; Reactive Oxygen Species ; Notch1 protein, rat ; Receptor, Notch1
Language	English
Publishing date	2023-07-13
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.154966
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Article ; Online: Dan-Deng-Tong-Nao Softgel Capsule Promotes Angiogenesis of Cerebral Microvasculature to Protect Cerebral Ischemia Reperfusion Injury via Activating HIF-1a-VEGFA-Notch1 Signaling Pathway

Wang, Lei / Li, Jiacheng / Wang, Yang / Ge, Chaowen / Huang, Qi / Li, Lili / Wang, Ning / Chen, Yuang / Zhou, Xian / Chang, Dennis / Li, Dan / Hou, Jincai

Phytomedicine. 2023 July 13, p.154966-

2023 , Page(s) 154966–

Abstract: A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used ...

Abstract	A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized. To explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels. Chemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro. Seven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNC-CSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo. DDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-Notch1 signal transduction pathway.
Keywords	angiogenesis ; apoptosis ; blood serum ; brain ; cell viability ; cortex ; cytotoxicity ; fluorescent antibody technique ; infarction ; ischemia ; mitochondria ; models ; neurons ; pharmacology ; protein synthesis ; reperfusion injury ; signal transduction ; stroke ; transmission electron microscopy ; vascular endothelial growth factor receptor-2 ; DDTNC ; Network pharmacology ; HIF-1α-VEGFA-Notch1 ; CIRI ; Dll4 ; UPLC
Language	English
Dates of publication	2023-0713
Publishing place	Elsevier GmbH
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.154966
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Babao Dan alleviates gut immune and microbiota disorders while impacting the TLR4/MyD88/NF-кB pathway to attenuate 5-Fluorouracil-induced intestinal injury.

Huang, Bin / Gui, Mengxuan / An, Honglin / Shen, Jiayu / Ye, Feimin / Ni, Zhuona / Zhan, Hanzhang / Che, Li / Lai, Zhicheng / Zeng, Jiahan / Peng, Jun / Lin, Jiumao

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 166, Page(s) 115387

Abstract: ... prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects ...

Abstract	Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.
MeSH term(s)	Animals ; Mice ; NF-kappa B ; Myeloid Differentiation Factor 88 ; Toll-Like Receptor 4 ; RNA, Ribosomal, 16S ; Microbiota ; Adaptor Proteins, Signal Transducing
Chemical Substances	NF-kappa B ; Myeloid Differentiation Factor 88 ; Toll-Like Receptor 4 ; babao dan ; RNA, Ribosomal, 16S ; Adaptor Proteins, Signal Transducing
Language	English
Publishing date	2023-08-27
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115387
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Article ; Online: Chemical components characterization and in vivo metabolites profiling of Lingbao Huxin Dan by gas chromatography-mass spectrometry and ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry.

Huang, Fan / Wang, Ziying / Wang, Lulu / Liu, Ruxia / Ma, Chi / Che, Yanzhong / He, Yiwen / Ye, Ji

Journal of separation science

2023 Volume 47, Issue 1, Page(s) e2300233

Abstract: Lingbao Huxin Dan (LBHX) is an effective prescription for treating various cardiovascular diseases ...

Abstract	Lingbao Huxin Dan (LBHX) is an effective prescription for treating various cardiovascular diseases. However, its systematic chemical composition analysis and important marker components remain unclear, which hinders the development of standards or guidelines for quality evaluation. Herein, a high-resolution and efficient method was established to comprehensively investigate the chemical ingredients and metabolites of LBHX by using gas chromatography-tandem mass spectrometry and ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. AutoDock Vina was applied to conduct visual screening for identifying potential active compounds targeting two important sick sinus syndrome-associated proteins. As a result, 53 volatile compounds, as well as 191 non-volatile chemical components, including bufadienolides, diterpenoids, bile acids, phenolic acids, and triterpenoid saponins, were unambiguously characterized or tentatively identified. Fifty prototypes and 62 metabolites were identified in the plasma of rats, whilst metabolism reactions included phase I reactions (hydrolysis, oxidation, and hydroxylation) and phase II reactions (glucuronidation and methylation). Eleven compounds with good binding affinity have been observed by docking with key proteins. It is the first systematic study on the pharmacodynamic material basis of LBHX and the result consolidates the foundation for further study regarding the mechanism in treating cardiovascular diseases.
MeSH term(s)	Rats ; Animals ; Chromatography, High Pressure Liquid/methods ; Rats, Sprague-Dawley ; Gas Chromatography-Mass Spectrometry ; Tandem Mass Spectrometry/methods ; Cardiovascular Diseases ; Drugs, Chinese Herbal/analysis
Chemical Substances	huxin ; Drugs, Chinese Herbal
Language	English
Publishing date	2023-11-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2047990-6
ISSN	1615-9314 ; 1615-9306
ISSN (online)	1615-9314
ISSN	1615-9306
DOI	10.1002/jssc.202300233
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: DAN-Net: Dual-domain adaptive-scaling non-local network for CT metal artifact reduction.

Wang, Tao / Xia, Wenjun / Huang, Yongqiang / Sun, Huaiqiang / Liu, Yan / Chen, Hu / Zhou, Jiliu / Zhang, Yi

Physics in medicine and biology

2021 Volume 66, Issue 15

Abstract: ... performance. In this paper, a novel dual-domain adaptive-scaling non-local network (DAN-Net) is proposed ... in the proposed network model. Experiments demonstrate the performance of the proposed DAN-Net is competitive ...

Abstract	Metallic implants can heavily attenuate x-rays in computed tomography (CT) scans, leading to severe artifacts in reconstructed images, which significantly jeopardize image quality and negatively impact subsequent diagnoses and treatment planning. With the rapid development of deep learning in the field of medical imaging, several network models have been proposed for metal artifact reduction (MAR) in CT. Despite the encouraging results achieved by these methods, there is still much room to further improve performance. In this paper, a novel dual-domain adaptive-scaling non-local network (DAN-Net) is proposed for MAR. We correct the corrupted sinogram using adaptive scaling first to preserve more tissue and bone details. Then, an end-to-end dual-domain network is adopted to successively process the sinogram and its corresponding reconstructed image is generated by the analytical reconstruction layer. In addition, to better suppress the existing artifacts and restrain the potential secondary artifacts caused by inaccurate results of the sinogram-domain network, a novel residual sinogram learning strategy and non-local module are leveraged in the proposed network model. Experiments demonstrate the performance of the proposed DAN-Net is competitive with several state-of-the-art MAR methods in both qualitative and quantitative aspects.
MeSH term(s)	Algorithms ; Artifacts ; Image Processing, Computer-Assisted ; Metals ; Phantoms, Imaging ; Tomography, X-Ray Computed
Chemical Substances	Metals
Language	English
Publishing date	2021-07-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/1361-6560/ac1156
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Article ; Online: Quantification and discovery of quality control chemical markers for Ba-Bao-Dan by UPLC-MS/MS combined with chemometrics.

Cheng, Zaixing / Zhuo, Shi / Guo, Shuang / Liu, Jian / Zhang, Xiaoqin / Lin, Jiumao / Huang, Mingqing

Journal of pharmaceutical and biomedical analysis

2021 Volume 204, Page(s) 114273

Abstract: Ba-Bao-Dan (BBD) is a well-known Traditional Chinese medicine (TCM) prescription in China. It was ...

Abstract	Ba-Bao-Dan (BBD) is a well-known Traditional Chinese medicine (TCM) prescription in China. It was first formulated in approximately 1555 AD. As one of the National Protected TCM, it is widely used to treat jaundice, viral hepatitis, cholecystitis, acute urinary tract infection, cancer, and other diseases. It is a healthcare medicine that is used to prevent many diseases in China. In other Asian countries and in European and American countries, BBD is used as a drug to protect the liver. However, a systematic quality study on BBD chemical markers has not been carried out. This study aimed to establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method for the quantitative determination of 43 compounds in BBD. Furthermore, the method was used to further find chemical markers for quality control through the combination with chemometrics. The modified chromatographic conditions were achieved on Waters Cortecs C
MeSH term(s)	Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Quality Control ; Tandem Mass Spectrometry
Chemical Substances	Drugs, Chinese Herbal
Language	English
Publishing date	2021-07-21
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2021.114273
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Article ; Online: A multiomics and network pharmacological study reveals the neuroprotective efficacy of Fu-Fang-Dan-Zhi tablets against glutamate-induced oxidative cell death.

Gu, Yu / Huang, Pengli / Cheng, Taofang / Yang, Jian / Wu, Gaosong / Sun, Yuting / Liu, Aijun / Li, Houkai / Zhao, Jing / Ye, Ji

Computers in biology and medicine

2022 Volume 148, Page(s) 105873

Abstract: ... still insufficient. The Fu-Fang-Dan-Zhi tablet (FFDZT) is a proprietary Chinese medicine clinically ...

Abstract	Neuroprotective therapy after ischemic stroke remains a significant need, but current measures are still insufficient. The Fu-Fang-Dan-Zhi tablet (FFDZT) is a proprietary Chinese medicine clinically employed to treat ischemic stroke in the recovery period. This work aims to systematically investigate the neuroprotective mechanism of FFDZT. A systems strategy that integrated metabolomics, transcriptomics, network pharmacology, and in vivo and in vitro experiments was used. First, middle cerebral artery occlusion (MCAO) model rats were treated with FFDZT. FFDZT treatment significantly reduced the infarct volume in the brains of middle cerebral artery occlusion (MCAO) model rats. Then, samples of serum and brain tissue were taken for metabolomics and transcriptomics studies, respectively; gene expression profiles of MCF7 cells treated with FFDZT and its 4 active compounds (senkyunolide I, formononetin, drilodefensin, and tanshinone IIA) were produced for CMAP analysis. Computational analysis of metabolomics and transcriptomics results suggested that FFDZT regulated glutamate and oxidative stress-related metabolites (2-hydroxybutanoic acid and 2-hydroxyglutaric acid), glutamate receptors (NMDAR, KA, and AMPA), glutamate involved pathways (glutamatergic synapse pathway; d-glutamine and d-glutamate metabolism; alanine, aspartate and glutamate metabolism), as well as the reactive oxygen species metabolic process. CMAP analysis indicated that two active ingredients of FFDZT (tanshinone ⅡA and senkyunolide I) could act as glutamate receptor antagonists. Next, putative therapeutic targets of FFDZT's active ingredients identified in the brain were collected from multiple resources and filtered by statistical criteria and tissue expression information. Network pharmacological analysis revealed extensive interactions between FFDZT's putative targets, anti-IS drug targets, and glutamate-related enzymes, while the resulting PPI network exhibited modular topology. The targets in two of the modules were significantly enriched in the glutamatergic synapse pathway. The interactions between FFDZT's ingredients and important targets were verified by molecular docking. Finally, in vitro experiments validated the effects of FFDZT and its ingredients in suppressing glutamate-induced PC12 cell injury and reducing the generation of reactive oxygen species. All of our findings indicated that FFDZT's efficacy for treating ischemic stroke could be due to its neuroprotection against glutamate-induced oxidative cell death.
MeSH term(s)	Animals ; Cell Death ; Drugs, Chinese Herbal ; Glutamic Acid ; Infarction, Middle Cerebral Artery ; Ischemic Stroke ; Molecular Docking Simulation ; Neuroprotection ; Oxidative Stress ; Rats ; Reactive Oxygen Species ; Tablets
Chemical Substances	Drugs, Chinese Herbal ; Reactive Oxygen Species ; Tablets ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2022-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2022.105873
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In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito