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Article: Human Adipose-Derived Mesenchymal Stem Cells-Derived Exosomal microRNA-19b Promotes the Healing of Skin Wounds Through Modulation of the CCL1/TGF-β Signaling Axis.

Cao, Guoxiu / Chen, Bei / Zhang, Xian / Chen, Hongyun

Clinical, cosmetic and investigational dermatology

2020 Volume 13, Page(s) 957–971

Abstract: Introduction: Human adipose-derived mesenchymal stem cells (ADMSCs) with their secretory factors are able to induce collagen synthesis and fibroblast migration in the wound healing process. This study is launched to figure out the effect of human ADMSCs- ...

Abstract	Introduction: Human adipose-derived mesenchymal stem cells (ADMSCs) with their secretory factors are able to induce collagen synthesis and fibroblast migration in the wound healing process. This study is launched to figure out the effect of human ADMSCs-derived exosomes on skin wound healing. Methods: ADMSCs were extracted and ADMSCs-derived exosomes were identified. Skin damage models were established by treating HaCaT cells and human skin fibroblasts with H Results: H Conclusion: Our study indicates that exosomal miR-19b derived from ADMSCs regulates the TGF-β pathway by targeting CCL1, thereby promoting the healing of skin wounds.
Language	English
Publishing date	2020-12-15
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2494852-4
ISSN	1178-7015
ISSN	1178-7015
DOI	10.2147/CCID.S274370
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Article ; Online: Novel Indole-Chalcone Derivative-Ligated Platinum(IV) Prodrugs Attenuate Cisplatin Resistance in Lung Cancer through ROS/ER Stress and Mitochondrial Dysfunction.

Liu, Zhikun / Wang, Meng / Huang, Rizhen / Hu, Tianhui / Jing, Yi / Huang, Xiaochao / Hu, Weiwei / Cao, Guoxiu / Wang, Hengshan

Journal of medicinal chemistry

2023 Volume 66, Issue 7, Page(s) 4868–4887

Abstract: Developing multifunctional platinum(IV) prodrugs via integrating bioactive pharmacophores into one entity is an attractive strategy to ameliorate the defects of platinum(II) drugs. Herein, a series of indole-chalcone derivative-ligated platinum(IV) ... ...

Abstract	Developing multifunctional platinum(IV) prodrugs via integrating bioactive pharmacophores into one entity is an attractive strategy to ameliorate the defects of platinum(II) drugs. Herein, a series of indole-chalcone derivative-ligated platinum(IV) complexes were synthesized and evaluated for their anticancer activities. Among them, optimal complex
MeSH term(s)	Humans ; Cisplatin/pharmacology ; Cisplatin/therapeutic use ; Platinum/pharmacology ; Platinum/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/metabolism ; Prodrugs/pharmacology ; Prodrugs/therapeutic use ; Prodrugs/metabolism ; Reactive Oxygen Species/metabolism ; Chalcones/pharmacology ; Chalcones/therapeutic use ; Cell Line, Tumor ; Lung Neoplasms/metabolism ; Apoptosis ; Mitochondria
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Platinum (49DFR088MY) ; Antineoplastic Agents ; Prodrugs ; Reactive Oxygen Species ; Chalcones
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c02036
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Article ; Online: Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis.

Wang, Meng / Cao, Guoxiu / Zhou, Junjie / Cai, Jinyuan / Ma, Xianjie / Liu, Zhikun / Huang, Xiaochao / Wang, Hengshan

Journal of medicinal chemistry

2023 Volume 66, Issue 19, Page(s) 13587–13606

Abstract: Developing multitarget platinum(IV) prodrugs is an important strategy to attenuate cisplatin (CDDP) resistance in tandem with reduced toxicity. Herein, six novel ligustrazine-derived chalcones-modified platinum(IV) complexes were synthesized and ... ...

Abstract	Developing multitarget platinum(IV) prodrugs is an important strategy to attenuate cisplatin (CDDP) resistance in tandem with reduced toxicity. Herein, six novel ligustrazine-derived chalcones-modified platinum(IV) complexes were synthesized and evaluated for their anti-proliferative activities. Among them,
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c00922
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Article ; Online: Regulation of Mammalian UDP-Glucuronosyltransferases.

Wang, Hong / Cao, Guoxiu / Wang, Guangji / Hao, Haiping

Current drug metabolism

2018 Volume 19, Issue 6, Page(s) 490–501

Abstract: Background: UDP-glucuronosyltransferases (UGTs) are a class of important phase II drug metabolizing enzymes (DMEs), playing essential roles in the homeostasis of endobiotics as well as the dispositional behavior of exogenous compounds. The expression ... ...

Abstract	Background: UDP-glucuronosyltransferases (UGTs) are a class of important phase II drug metabolizing enzymes (DMEs), playing essential roles in the homeostasis of endobiotics as well as the dispositional behavior of exogenous compounds. The expression and enzyme activity of UGTs are regulated by multiple dimensions of mechanisms and can be influenced by diverse factors. Thus, the intensive research of its regulatory network is pivotal for better understanding about the physiological, pathological, and therapeutic significance of UGTs. Despite the lag to the research in cytochrome P450s, extensive efforts have been made to advance the understanding of the regulatory network of UGTs in recent years. Method: This review presents a comprehensive summary and intensive discussion about the recent advancement on the regulatory network of UGTs. Results: UGTs can be regulated at the epigenetic level via DNA methylation and histone modification. Various nuclear receptors can influence the mRNA levels of UGTs in a ligand dependent manner. Some general transcriptional factors such as AP-1, NF-κB, and p53, and some tissue specific transcriptional factors including HFN1α and HNF4α can also regulate UGTs at the transcriptional level. Multiple miRNAs have been found to be involved in the regulation of UGTs at post-transcriptional level. UGT proteins can be directly regulated via various post-translational modifications, protein-protein interactions, and protein-chemicals interactions, leading to the alternation of enzyme activities. Conclusion: In addition to the well-defined genetic polymorphism that induce individual variation of UGTs, this review reinforces the importance of other mechanisms that are critical for the regulation of UGTs.
MeSH term(s)	Animals ; Glucuronosyltransferase/metabolism ; Humans ; Signal Transduction
Chemical Substances	Glucuronosyltransferase (EC 2.4.1.17)
Language	English
Publishing date	2018-03-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2064815-7
ISSN	1875-5453 ; 1389-2002
ISSN (online)	1875-5453
ISSN	1389-2002
DOI	10.2174/1389200219666180307122945
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Article ; Online: Novel Platinum(IV) complexes intervene oxaliplatin resistance in colon cancer via inducing ferroptosis and apoptosis.

Liu, Zhikun / Cai, Jinyuan / Jiang, Guiyang / Wang, Meng / Wu, Chuang / Su, Kangning / Hu, Weiwei / Huang, Yaxian / Yu, Chunhao / Huang, Xiaochao / Cao, Guoxiu / Wang, Hengshan

European journal of medicinal chemistry

2023 Volume 263, Page(s) 115968

Abstract: Platinum-based chemotherapeutics are widely used for cancer treatment but are frequently limited because of dosage-dependent side effects and drug resistance. To attenuate these drawbacks, a series of novel platinum(IV) prodrugs (15a-18c) were ... ...

Abstract	Platinum-based chemotherapeutics are widely used for cancer treatment but are frequently limited because of dosage-dependent side effects and drug resistance. To attenuate these drawbacks, a series of novel platinum(IV) prodrugs (15a-18c) were synthesized and evaluated for anti-cancer activity. Among them, 17a demonstrated superior anti-proliferative activity compared with oxaliplatin (OXA) in the cisplatin-resistant lung cancer cell line A549/CDDP and OXA-resistant colon cancer cell line HCT-116/OXA but showed a lower cytotoxic effect toward human normal cell lines HUVEC and L02. Mechanistic investigations suggested that 17a efficiently enhanced intracellular platinum accumulation, induced DNA damage, disturbed the homeostasis of intracellular reactive oxygen molecules and mitochondrial membrane potential, and thereby activated the mitochondrion-dependent apoptosis pathway. Moreover, 17a significantly induced ferroptosis in HCT-116/OXA via triggering the accumulation of lipid peroxides, disrupting iron homeostasis, and inhibiting solute carrier family 7 member 11 and glutathione peroxidase 4 axial pathway transduction by inhibiting the expression of the phosphorylated signal transducer and activator of transcription 3 and nuclear factor erythroid 2-related factor 2. Moreover, 17a exerted remarkable in vivo antitumor efficacy in the HCT-116/OXA xenograft models but showed attenuated toxicity. These results indicated that these novel platinum(IV) complexes provided an alternative strategy to develop novel platinum-based antineoplastic agents for cancer treatment.
MeSH term(s)	Humans ; Oxaliplatin/pharmacology ; Platinum/pharmacology ; Ferroptosis ; Drug Resistance, Neoplasm ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cisplatin/pharmacology ; Apoptosis ; Colonic Neoplasms/drug therapy ; Cell Line, Tumor
Chemical Substances	Oxaliplatin (04ZR38536J) ; Platinum (49DFR088MY) ; Antineoplastic Agents ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2023-11-19
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2023.115968
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Article: Intestinal mucosal metabolites-guided detection of trace-level ginkgo biloba extract metabolome

Cao, Guoxiu / Wang, Nian / He, Dandan / Wang, Xinmiao / Tian, Yang / Wan, Ning / Yan, Wenchao / Ye, Hui / Hao, Haiping

Journal of chromatography. 2019 Dec. 20, v. 1608

2019

Abstract: The characterization of metabolome for poorly absorptive natural medicines is challenging. Previous identification strategy often relies on nontargeted scanning biological samples from animals administered with natural medicines in a data-dependent ... ...

Abstract	The characterization of metabolome for poorly absorptive natural medicines is challenging. Previous identification strategy often relies on nontargeted scanning biological samples from animals administered with natural medicines in a data-dependent acquisition (DDA) mode by LC–MS/MS. Substances that displayed significant increases following drug administration are thus assigned as potential metabolites. The accurate m/z of precursors and the corresponding MS/MS fragment ions are used to match with herbal ingredients and to infer possible metabolic reactions. Nevertheless, the low concentration of these metabolites within complex biological matrices has often hampered the detection. Herein we developed a strategy termed intestinal mucosal metabolome-guided detection (IMMD) to tackle this challenge using ginkgo biloba (GBE) as an example. The rationale is that poorly absorptive natural products are usually concentrated and extensively metabolized by enterocytes before they enter the blood stream and distribute to other organs. Therefore, we firstly identified the metabolites from intestinal mucosa of GBE-treated rats, and then used the identified intestinal mucosal GBE metabolome as targeted repository for MRM analysis. The presences of these metabolites were subsequently examined in rat plasma, liver and brain. The resultant GBE metabolome showed significantly improved coverage with 39, 45 and 6 metabolites identified in plasma, liver and brain compared to 22, 16 and 0 metabolites from the corresponding regions via the DDA-based strategy. In addition, we integrated the previously reported nontargeted diagnostic ion network analysis to facilitate the characterization of GBE components, and a chemicalome-metabolome matching approach (CMMA) to assist the identity assignment of GBE metabolome with IMMD. Combinatorially, we establish a multi-faceted platform to streamline the workflow of metabolome characterization for herbal medicines of low bioavailability. The metabolome information is expected to shed light on the elucidation of metabolic pathways for natural products, and the underlying mechanisms of their biological efficacies.
Keywords	Ginkgo biloba ; bioavailability ; biochemical pathways ; blood flow ; blood plasma ; brain ; enterocytes ; herbal medicines ; ingredients ; ions ; liquid chromatography ; liver ; metabolites ; metabolome ; rats ; tandem mass spectrometry
Language	English
Dates of publication	2019-1220
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	218139-3
ISSN	0021-9673 ; 0378-4355 ; 0376-737X
ISSN	0021-9673 ; 0378-4355 ; 0376-737X
DOI	10.1016/j.chroma.2019.460417
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Intestinal mucosal metabolites-guided detection of trace-level ginkgo biloba extract metabolome.

Cao, Guoxiu / Wang, Nian / He, Dandan / Wang, Xinmiao / Tian, Yang / Wan, Ning / Yan, Wenchao / Ye, Hui / Hao, Haiping

Journal of chromatography. A

2019 Volume 1608, Page(s) 460417

Abstract	The characterization of metabolome for poorly absorptive natural medicines is challenging. Previous identification strategy often relies on nontargeted scanning biological samples from animals administered with natural medicines in a data-dependent acquisition (DDA) mode by LC-MS/MS. Substances that displayed significant increases following drug administration are thus assigned as potential metabolites. The accurate m/z of precursors and the corresponding MS/MS fragment ions are used to match with herbal ingredients and to infer possible metabolic reactions. Nevertheless, the low concentration of these metabolites within complex biological matrices has often hampered the detection. Herein we developed a strategy termed intestinal mucosal metabolome-guided detection (IMMD) to tackle this challenge using ginkgo biloba (GBE) as an example. The rationale is that poorly absorptive natural products are usually concentrated and extensively metabolized by enterocytes before they enter the blood stream and distribute to other organs. Therefore, we firstly identified the metabolites from intestinal mucosa of GBE-treated rats, and then used the identified intestinal mucosal GBE metabolome as targeted repository for MRM analysis. The presences of these metabolites were subsequently examined in rat plasma, liver and brain. The resultant GBE metabolome showed significantly improved coverage with 39, 45 and 6 metabolites identified in plasma, liver and brain compared to 22, 16 and 0 metabolites from the corresponding regions via the DDA-based strategy. In addition, we integrated the previously reported nontargeted diagnostic ion network analysis to facilitate the characterization of GBE components, and a chemicalome-metabolome matching approach (CMMA) to assist the identity assignment of GBE metabolome with IMMD. Combinatorially, we establish a multi-faceted platform to streamline the workflow of metabolome characterization for herbal medicines of low bioavailability. The metabolome information is expected to shed light on the elucidation of metabolic pathways for natural products, and the underlying mechanisms of their biological efficacies.
MeSH term(s)	Animals ; Chromatography, Liquid/methods ; Drugs, Chinese Herbal/analysis ; Drugs, Chinese Herbal/metabolism ; Ginkgo biloba/chemistry ; Intestinal Mucosa/chemistry ; Intestinal Mucosa/metabolism ; Male ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Plant Extracts/analysis ; Plant Extracts/metabolism ; Plants, Medicinal/metabolism ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry/methods
Chemical Substances	Drugs, Chinese Herbal ; Plant Extracts ; Ginkgo biloba extract (19FUJ2C58T)
Language	English
Publishing date	2019-08-05
Publishing country	Netherlands
Document type	Evaluation Study ; Journal Article
ZDB-ID	1171488-8
ISSN	1873-3778 ; 0021-9673
ISSN (online)	1873-3778
ISSN	0021-9673
DOI	10.1016/j.chroma.2019.460417
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Article ; Online: Characterization of isochlorogenic acid A metabolites in rats using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

Wang, Jing / Cao, Guoxiu / Wang, Hong / Ye, Hui / Zhong, Yunxi / Wang, Guangji / Hao, Haiping

Biomedical chromatography : BMC

2017 Volume 31, Issue 8

Abstract: Isochlorogenic acid A is widely present in fruits, vegetables and herbal medicines, and is characterized by anti-inflammatory, hepatoprotective and antiviral properties. However, little is known about its metabolic fate and pharmacokinetic properties. ... ...

Abstract	Isochlorogenic acid A is widely present in fruits, vegetables and herbal medicines, and is characterized by anti-inflammatory, hepatoprotective and antiviral properties. However, little is known about its metabolic fate and pharmacokinetic properties. This study is thus designed to investigate the metabolic fate of isochlorogenic acid A. An analytical method based on high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) was established to characterize the metabolites of isochlorogenic acid A in the plasma, urine and feces of rats. A total of 32 metabolites were identified. The metabolic pathways mainly include hydrolyzation, dehydroxylation, hydrogenation and conjugation with methyl, glucuronic acid, glycine, sulfate, glutathione and cysteine. Moreover, the pharmacokinetic profiles of all the circulating metabolites were investigated. M11 resulting from hydrolyzation, dehydroxylation and hydrogenation was the dominant circulating metabolite after the intragastric administration of isochlorogenic acid A. The results obtained will be useful for further study of elucidating potential bioactive metabolites which can provide better explanation of the pharmacological and/or toxicological effects of this compound.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/blood ; Anti-Inflammatory Agents/metabolism ; Anti-Inflammatory Agents/pharmacokinetics ; Anti-Inflammatory Agents/urine ; Antiviral Agents/blood ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/urine ; Chlorogenic Acid/analogs & derivatives ; Chlorogenic Acid/blood ; Chlorogenic Acid/metabolism ; Chlorogenic Acid/pharmacokinetics ; Chlorogenic Acid/urine ; Chromatography, High Pressure Liquid/methods ; Feces/chemistry ; Male ; Mass Spectrometry/methods ; Metabolic Networks and Pathways ; Plants, Medicinal/metabolism ; Protective Agents/metabolism ; Protective Agents/pharmacokinetics ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Anti-Inflammatory Agents ; Antiviral Agents ; Protective Agents ; isochlorogenic acid (178AQM8R56) ; Chlorogenic Acid (318ADP12RI)
Language	English
Publishing date	2017-08
Publishing country	England
Document type	Journal Article
ZDB-ID	632848-9
ISSN	1099-0801 ; 0269-3879
ISSN (online)	1099-0801
ISSN	0269-3879
DOI	10.1002/bmc.3927
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Article ; Online: A simple boronic acid-based fluorescent probe for selective detection of hydrogen peroxide in solutions and living cells.

Han, Jialing / Chu, Chengyu / Cao, Guoxiu / Mao, Wuxiang / Wang, Sen / Zhao, Zhou / Gao, Mingqi / Ye, Hui / Xu, Xiaowei

Bioorganic chemistry

2018 Volume 81, Page(s) 362–366

Abstract: An approach of high sensitivity and selectivity for hydrogen peroxide ( ... ...

Abstract	An approach of high sensitivity and selectivity for hydrogen peroxide (H
MeSH term(s)	4-Chloro-7-nitrobenzofurazan/analogs & derivatives ; 4-Chloro-7-nitrobenzofurazan/radiation effects ; A549 Cells ; Boronic Acids/chemistry ; Boronic Acids/radiation effects ; Fluorescent Dyes/chemistry ; Fluorescent Dyes/radiation effects ; Humans ; Hydrogen Peroxide/analysis ; Light ; Limit of Detection ; Microscopy, Confocal/methods
Chemical Substances	Boronic Acids ; Fluorescent Dyes ; Hydrogen Peroxide (BBX060AN9V) ; 4-Chloro-7-nitrobenzofurazan (EQF2794IRE)
Language	English
Publishing date	2018-09-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120080-x
ISSN	1090-2120 ; 0045-2068
ISSN (online)	1090-2120
ISSN	0045-2068
DOI	10.1016/j.bioorg.2018.08.036
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Article ; Online: Nontargeted diagnostic ion network analysis (NINA): A software to streamline the analytical workflow for untargeted characterization of natural medicines.

Ye, Hui / Zhu, Lin / Sun, Di / Luo, Xiaozhuo / Lu, Gaoyuan / Wang, Hong / Wang, Jing / Cao, Guoxiu / Xiao, Wei / Wang, Zhenzhong / Wang, Guangji / Hao, Haiping

Journal of pharmaceutical and biomedical analysis

2016 Volume 131, Page(s) 40–47

Abstract: The characterization of herbal prescriptions serves as a foundation for quality control and regulation of herbal medicines. Previously, the characterization of herbal chemicals from natural medicines often relied on the analysis of signature fragment ... ...

Abstract	The characterization of herbal prescriptions serves as a foundation for quality control and regulation of herbal medicines. Previously, the characterization of herbal chemicals from natural medicines often relied on the analysis of signature fragment ions from the acquired tandem mass spectrometry (MS/MS) spectra with prior knowledge of the herbal species present in the herbal prescriptions of interest. Nevertheless, such an approach is often limited to target components, and it risks missing the critical components that we have no prior knowledge of. We previously reported a "diagnostic ion-guided network bridging" strategy. It is a generally applicable and robust approach to analyze unknown substances from complex mixtures in an untargeted manner. In this study, we have developed a standalone software named "Nontargeted Diagnostic Ion Network Analysis (NINA)" with a graphical user interface based on a strategy for post-acquisition data analysis. NINA allows one to rapidly determine the nontargeted diagnostic ions (NIs) by summarizing all of the fragment ions shared by the precursors from the acquired MS/MS spectra. A NI-guided network using bridging components that possess two or more NIs can then be established via NINA. With such a network, we could sequentially identify the structures of all the NIs once a single compound has been identified de novo. The structures of NIs can then be used as "priori" knowledge to narrow the candidates containing the sub-structure of the corresponding NI from the database hits. Subsequently, we applied the NINA software to the characterization of a model herbal prescription, Re-Du-Ning injection, and rapidly identified 56 herbal chemicals from the prescription using an ultra-performance liquid chromatography quadrupole time-of-flight system in the negative mode with no knowledge of the herbal species or herbal chemicals in the mixture. Therefore, we believe the applications of NINA will greatly facilitate the characterization of complex mixtures, such as natural medicines, especially when no advance information is available. In addition to herbal medicines, the NINA-based workflow will also benefit many other fields, such as environmental analysis, nutritional science, and forensic analysis.
MeSH term(s)	Biological Products/analysis ; Drugs, Chinese Herbal/analysis ; Software/standards ; Tandem Mass Spectrometry/methods ; Tandem Mass Spectrometry/standards
Chemical Substances	Biological Products ; Drugs, Chinese Herbal
Language	English
Publishing date	2016-11-30
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.2016.08.007
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