Regenerative Biomaterials
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2022
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IF 5.763
Ren Xiuli,Hu Yanan,Chang Linna,Xu Shibo,Mei Xifan,Chen Zhenhua
Bacterial infection and excessive inflammation are still the main obstacles to wound repair. Thus, antibacterial and anti-inflammation nanomaterials are always attracting for infected wound healing. In this work, ultra-uniform (∼20 nm) and colloidally stable Ag nanoparticles (Ag-Hes NPs) with core-shell structure were prepared by using hesperidin as reducing and capping agent. The obtained Ag-Hes NPs present effective antibacterial properties on both Staphylococcus aureus and Escherichia coli. Ag-Hes NPs also got high 1,1-diphenyl-1-picrylhydrazyl scavenging capability of 69%. Under the package of polyvinyl alcohol and sodium alginate, Ag-Hes NPs were encapsulated into electro spun nanofibers to form hydrogel (Ag-Hes@H). This strategy provides a moisture environment which could enrich and release Ag-Hes NPs gradually. Cell experiments and animal wound healing investigation proved that Ag-Hes@H could promote the proliferation and migration of human umbilical vein endothelial cells and accelerate infected wound healing. Meanwhile, Ag-Hes@H significantly reduced the expression of inflammatory cytokines, including IL-6, MMP9 and TNF-α. Immunohistochemistry data further suggested that Ag-Hes@H accelerated wound closure by promoting collagen deposition and skin cell proliferation. The designed antibacterial and anti-inflammatory Ag-Hes@H has great potential for promoting infected wound healing.
研究领域:
材料科学
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纳米技术
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生物医学工程
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Cao Xu,Zhang Ningyi,Chen Hening,Wang Wei,Liang Yijun,Zhang Jiaxin,Liu Ruijia,Li Shuo,Yao Yuhao,Jin Qian,Guo Ziwei,Chen Yue,Gong Yuanyuan,Li Xiaoke,Zao Xiaobin,Ye Yong’an
The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.
研究领域:
药理学
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病毒学
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分子生物学
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网络药理学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2021
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IF 5.34
Jin-hua Fan,Min-min Xu,Li-ming Zhou,Zheng-wei Gui,Lu Huang,Xue-gang Li,Xiao-li Ye
Background and purpose Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear. Method Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets. Results In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes ( CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 , and MMP9 ). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target. Conclusions In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer.
研究领域:
药理学
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肿瘤学
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系统生物学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
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2023
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IF 4
Lingling Song,Jian Xu,Yanqiong Shi,Hemiao Zhao,Min Zhang,Yuefei Wang,Ying Cui,Xin Chai
Febrile seizures (FS) are the most common type of seizures for children. As a commonly used representative cold formula for resuscitation, Zixue Powder (ZP) has shown great efficacy for the treatment of FS in clinic, while its active ingredients and underlying mechanism remain largely unclear. This study aimed to preliminarily elucidate the material basis of ZP and the potential mechanism for the treatment of FS through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and molecular docking. UPLC-Q-TOF-MS was firstly applied to characterize the ingredients in ZP, followed by network pharmacology to explore the potential bioactive ingredients and pathways of ZP against FS. Furthermore, molecular docking technique was employed to verify the binding affinity between the screened active ingredients and targets. As a result, 75 ingredients were identified, containing flavonoids, chromogenic ketones, triterpenes and their saponins, organic acids, etc. Through the current study, we focused on 13 potential active ingredients and 14 key potential anti-FS targets of ZP, such as IL6, STAT3, TNF, and MMP9. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that inflammatory response, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, and neuroactive ligand-receptor interaction were the main anti-FS signaling pathways. Licochalcones A and B, 26-deoxycimicifugoside, and hederagenin were screened as the main potential active ingredients by molecular docking. In conclusion, this study provides an effective in-depth investigation of the chemical composition, potential bioactive components, and possible anti-FS mechanism of ZP, which lays the foundation for pharmacodynamic studies and clinical applications of ZP.
研究领域:
药理学
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分析化学
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神经科学
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中医中药
✓ 已验证
DOI
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
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2022
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IF 4.336
Mengdi Lv,Xiaoting Qian,Shijie Li,Jie Gong,Qun Wang,Yong Qian,Zhi Su,Xuling Xue,Hong-Ke Liu
It is a major challenge to design novel multifunctional metal-based chemotherapeutic agents for anti-tumor and anti-metastasis applications. Two complexes ( OA-Ir and OA-Ru ) were synthesized via CuAAC (copper-catalyzed azide-alkyne cycloaddition) reaction from nontoxic Ir - N 3 or Ru - N 3 species and low toxic alkynyl precursor OA-Alkyne, and exhibited satisfactory anti-tumor and anti-metastasis pharmacological effects . Conjugation of Oleanolic acid (OA) and metal-arene species significantly enhanced the cytotoxicity in A2780 cells compared to the precursors through mitochondrial-induced autophagy pathway. Moreover, the two complexes could inhibit the cell metastasis and invasion through damage of actin dynamics and down-regulation of MMP2/MMP9 proteins. Combination of two precursors improved the lipophilicity and biocompatibility, simultaneously enhanced the cell uptake and the mitochondrial accumulation of metal-arene complexes, which caused mitochondrial membrane potential damage, oxidative phosphorylation , ATP depletion and autophagy. Besides, OA-Ir and OA-Ru displayed excellent activity to disintegrate the 3D multicellular tumor spheroids , showing potential for the treatment of solid tumors. This work provides a new way for developing novel metal-based complexes via CuAAC reaction for simultaneously inhibiting tumor proliferation and metastasis.
研究领域:
化学
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药理学
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癌症研究
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Yan Chen,Ming Zhang,Zhifang Liu,Ning Zhang,Qingpeng Wang
Tumor microenvironment (TME) is a pivotal factor driving the tumor metastasis and leading to the failure of tumor therapy. Here, a series of ursodeoxycholic acid platinum(IV) conjugates with potency in remodeling the TME through suppressing JAK2/STAT3 signaling was developed. A candidate was screened out, which displayed potent antiproliferative and antimetastatic performance both in vitro and in vivo. It displayed superior pharmacokinetic properties compared to cisplatin. Serious DNA injury was induced, and then mitochondria-mediated apoptosis was initiated through the Bcl-2/Bax/Caspase3 pathway. The JAK2/STAT3 and TGF-β1 signaling pathways were remarkably inhibited, and pro-death autophagy was subsequently promoted. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Xudong Yao,Miner Hu,Xinrang Zhai,Junxin Lin,Xiaojun Xia,Wei Wei,Shudong Xia
Elderly patients predispose to cardiovascular implantable electronic devices (CIEDs) pocket infections due to multiple comorbidities. Treating infections with the antibiotics further carry higher risks for complications, and surgical intervention can be costly when device removal and reimplantation are required, both emphasizing the importance of novel preventive strategies to minimize the incidence of pocket infections. To meet the unique needs for elderly, we constructed an CIED surface modified hydrogel which crosslinked polyethylene glycol diacrylate (PEGDA) with hyaluronic acid-nitrobenzene (HN) to form the polymeric structures that mimic the natural environment for promoting “Pocket” surrounding tissue integration and healing. Importantly, we synthesized the new peptidomimetics FK-13 derived by shortening amino acid sequence of LL-37 which is the only human cathelicidin-derived antimicrobial peptide. By incorporating FK-13 with initial PN hydrogel via Schiff base formation, the created PN-FK hydrogel exhibited broad-spectrum antimicrobial activity against bacteria with excellent biocompatibility and mechanical properties in a long-term release manner. In an in vitro setting, PN-FK hydrogel demonstrated the regeneration capacity by expression of Hmox1, Col5 and Col6 associated genes in fibroblasts as well as expression of Gpx1, Cdc20 and MMP9 genes in stem cells to accelerate self-renewal, collagen secretion and reconstitution of matrix components. In the following in vivo model of subcutaneous implantation, CIED-shape titanium mesh with surface modification by PN-FK hydrogel efficiently subsided over-inflammation compared to bare titanium implant, and expedited collagen deposition and angiogenesis in peri -pocket tissues within 2 weeks. These findings underscore the potential of the PN-FK hydrogel as a transformative approach to CIED postoperative management, offering a dual-action solution that combines infection resistance with tissue regeneration capabilities.
研究领域:
生物医学工程
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材料科学
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生物材料
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组织工程
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抗菌技术
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心脏病学
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老年医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）