CHEMISTRY & BIODIVERSITY
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2025
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IF 2.5
Zebin Huang,Wanying Zhang,Qi Shu,Xiao-Chun Guo,Xi Zheng,YuJing Lu
Inflammation is an important predisposing factor for many chronic diseases. The dietary flavonoid silibinin has excellent anti-inflammatory properties in cells, but its low bioavailability in the blood compromises its therapeutic potential. This study aims to investigate the potential of dibenzoylmethane (DBM) to synergistically enhance the anti-inflammatory benefits of silibinin (SB). The synergistic effects of DBM and SB in combination were evaluated in LPS-induced RAW264.7 cells and TPA-induced mice. In addition, a network pharmacology approach and molecular docking were used to explore the key targets and signaling pathways of DBM and SB in combination. The results showed that DBM and SB synergistically inhibited the production of NO, ROS, IL-1β, and TNF-α in a 1:1 concentration ratio. These two compounds may exert their synergistic effects by modulating the NF-κB and HIF-1 signaling pathways, among others. Molecular docking revealed that both compounds exhibited high binding affinities to iNOS and COX-2. Compared with single compound use, the two compounds in combination significantly reduced ear edema and inflammatory cell infiltration, and inhibited the protein expression of iNOS and COX-2 in TPA-induced mice. This research provides a rationale for the combination of DBM and SB as an effective anti-inflammatory agent.
研究领域:
药理学
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免疫学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2017
·Vol. 5
·期 11
·2251-2267
·
IF 4.21
Jie Wu,Kunxi Zhang,Xi Yu,Jianxun Ding,Lei Cui,Jingbo Yin
The key barrier to the clinical application of tissue engineering scaffolds is the limitation of rapid and sufficient vascularization. Adipose-derived stem cells (ASCs), especially multicellular aggregates, exhibited a promising angiogenic activity. Herein, we designed a series of poly(L-glutamic acid) (PLGA)-based hydrogels with tunable hydration to control the in situ formation of multicellular spheroids. Oligo(ethylene glycol)s (OEGs) were employed to regulate the hydration of hydrogels. The hydrogel cross-linked with ethylene glycol (OEG1) supported the most excellent adhesion and proliferation of human ASCs in vitro. However, as the hydration of hydrogels strengthened, the adherent ASCs were gradually replaced with multicellular spheroids. Moreover, the in situ formation of spheroids was more effective in upregulating hypoxia-adaptive signals (e.g., hypoxia-inducible factor-1α, HIF-1α) and enhancing the secretion of angiogenic factors (e.g., vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2)) compared to adherent cells in OEG1 hydrogels. The hydrogel cross-linked with oligo(ethylene glycol)400 (OEG9) carrying spheroids induced a high angiogenic response of host tissue in vivo, resulting in an improved system vascularization, compared to adherent cells in the OEG1 hydrogel. These features indicated that the PLGA-based hydrogels were expected to be applied toward bone and fat tissue regeneration.
研究领域:
组织工程
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生物材料
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再生医学
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细胞生物学
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血管生成
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
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IF 5.4
Beibei Zhang,Mengnan Zeng,Ru Wang,Qimei Tie,Ruyi Fan,Xuyuan Zhang,Xiaoke Zheng,Weisheng Feng
Ethnopharmacological relevance The Chinese herbal Plantaginis Herba (PL) is one of the most widely used plants for both medicinal and dietary purposes. Plantaginis Herba is the main medicine used in a traditional Chinese prescription called Cheqiancao decoction, and it is known for its liver and kidney protective properties. Aim of the study : The aim of the present study was to explore the interventions and mechanisms of PL in ADR nephropathy by performing an integrated analysis of in vitro and in vivo experiments. Materials and methods The ingredients of PL were analysed by Ultra High Performance Liquid Chromatography (UPLC). The biochemical indicators of renal injury in the serum and urine were detected by a Micronumerase assay and ELISA. The renal histopathology and ultrastructure were analysed by H&E staining, Masson’s trichrome staining and transmission electron microscopy (TEM), respectively. By identifying the targets of PL and ADR nephropathy, a network of PL–constituents–targets–ADR nephropathy was constructed, and a KEGG signaling pathway enrichment analysis was performed to complete the network pharmacology. A transcriptomic analysis was performed on a sequencing platform (Illumina). Results Plantaginis Herba significantly decreased the levels of BUN, Scr, ALB, MAU and KIM-1. Plantaginis Herba inhibited renal histopathological injury and alleviate foot process fusion and podocyte basement membrane thickening. In addition, the results of the transcriptomic analysis and network pharmacology analysis indicated that the HIF-1, TGF-β, and PI3K/AKT signaling pathways; apoptosis; and ECM–receptor interactions might be pivotal pathways for the effect of the PL intervention on ADR nephropathy. Moreover, the validation results revealed that PL could effectively attenuate collagen fibre deposition and inhibit oxidative stress. Plantaginis Herba could regulate the expression levels of pivotal proteins in the β-catenin/TGF-β1, HIF-1, and PI3K signaling pathways in renal tissues. Plantaginis Herba could reduce the level of apoptosis and the percentage of decrease in the mitochondrial membrane potential (MMP) in primary renal cells from rats with ADR nephropathy, and regulate key proteins involved in mitochondrial apoptosis. Furthermore, Luteolin from PL had good affinity for HIF-1α, and the ability of Luteolin to ameliorate in ameliorating ADR-induced MPC-5 cell injury was attenuated by overexpressing HIF-1α. Conclusions Plantaginis Herba alleviates ADR-induced nephropathy by regulating mitochondrial apoptosis via the HIF-1α signaling pathway. Luteolin may be one of the active ingredients responsible for these effects, and these findings provide an innovative strategy for the intervention and treatment of ADR nephropathy.
研究领域:
民族药理学
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药理学
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转录组学
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网络药理学
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肾病学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Yongsheng Zheng,Dong Yang,Botao Gao,Shuai Huang,Yubo Tang,Qingde Wa,Yong Dong,Shan Yu,Jun Huang,Sheng Huang
Chronic diabetic wounds are a severe complication of diabetes, often leading to high treatment costs and high amputation rates. Numerous studies have revealed that nitric oxide (NO) therapy is a promising option because it favours wound revascularization. Here, base-paired injectable adhesive hydrogels (CAT) were prepared using adenine- and thymine-modified chitosan (CSA and CST). By further introducing S-nitrosoglutathione (GSNO) and binary L-arginine (bArg), we obtained a NO sustained-release hydrogel (CAT/bArg/GSON) that was more suitable for the treatment of chronic wounds. The results showed that the expression of HIF-1α and VEGF was upregulated in the CAT/bArg/GSON group, and improved blood vessel regeneration was observed, indicating an important role of NO. In addition, the research findings revealed that following treatment with the CAT/bArg/GSON hydrogel, the viability of Staphylococcus aureus and Escherichia coli decreased to 14 ± 2% and 6 ± 1%, respectively. Moreover, the wound microenvironment was improved, as evidenced by a 60 ± 1% clearance of DPPH. In particular, histological examination and immunohistochemical staining results showed that wounds treated with CAT/bArg/GSNO exhibited denser neovascularization, faster epithelial tissue regeneration, and thicker collagen deposition. Overall, this study proposes an effective strategy to prepare injectable hydrogel dressings with dual NO donors. The functionality of CAT/bArg/GSON has been thoroughly demonstrated in research on chronic wound vascular regeneration, indicating that CAT/bArg/GSON could be a potential option for promoting chronic wound healing. Statement of significance This article prepares a chitosan hydrogel utilizing the principle of complementary base pairing, which offers several advantages, including good adhesion, biocompatibility, and flow properties, making it a good material for wound dressings. Loaded GSNO and bArg can steadily release NO and L-arginine through the degradation of the gel. Then, the released L-arginine not only possesses antioxidant properties but can also continue to generate a small amount of NO under the action of NOS. This design achieves a sustained and stable supply of NO at the wound site, maximizing the angiogenesis-promoting and antibacterial effects of NO. More neovascularization and abundant collagen were observed in the regenerated tissues. This study provides an effective repair hydrogel material for diabetic wound.
研究领域:
生物医学工程
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材料科学
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药剂学
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伤口愈合
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组织工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
·
IF 4.8
Zhuojun Yu,Yi Li,Liping Bai,Yanbo Zheng,Xiujun Liu,Yongsu Zhen
Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.
研究领域:
免疫学
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药理学
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炎症
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2024
·
IF 18
Lili Sun,Haoyi Niu,Yuqiong Wu,Shiyan Dong,Xuefeng Li,Betty Y.S. Kim,Changsheng Liu,Yifan Ma,Wen Jiang,Yuan Yuan
Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.
研究领域:
组织工程
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骨再生
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生物材料
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骨科
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yan Chen,Ming Zhang,Yanqin He,Suying Li,Shuaiqi Feng,Zhifang Liu,Ning Zhang,Meifeng Liu,Qingpeng Wang
Epithelial–mesenchymal transition (EMT) is a critical process for cancer progression, which is crucial in inhibiting the immunity in tumors and further boosting tumor metastasis. The suppression of EMT represents a promising strategy for inhibiting metastatic tumors. Herein, a series of new canadine platinum(IV) conjugates with potent antiproliferative and antimetastatic activities were developed, which activated by suppressing EMT and provoking immune response in tumors besides causing DNA injury. The complexes could covalently conjugate to DNA and induce mitochondria-mediated apoptosis via Bcl-2/Bax/caspase3 signaling. The EMT process was remarkably inhibited by suppressing the Wnt/β-catenin pathway, reversing the inflammatory tumor microenvironment, and inhibiting the HIF-1α pathway, which further resulted in the inhibited angiogenesis in tumors. Moreover, the antitumor immunity was elevated by blocking immune checkpoints PD-L1 and CD47 accompanied by the improvement of CD3+ and CD8+ T lymphocytes and the macrophage polarization from M2- toward M1-type simultaneously in tumors.
研究领域:
癌症生物学
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药理学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Yingying Zhang,Yun Pan,Xiangyu Bai,Wen Sun,Xingfan Zhou,Qing Dong,Hui Wang,Yuanbao Zhang,Wenlin Bai,Wenping Zhang
Epidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team’s previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.
研究领域:
毒理学
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细胞生物学
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代谢组学
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环境健康
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2024
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IF 7.2
Xiuhong Huang,Liqin Zheng,Pengfei Li,Ziling Lin,Shaohong Huang,Changren Zhou
Bone defects have been a tough clinical challenge. The natural trabecular tissue reflects a balance between the minimal metabolic cost of maintenance and maximal network stability, with mitochondria being the energy suppliers for osteogenesis. Herein, a 3D printed trabecular bone-templated scaffold composed of polylactide (PLA) modified with europium (III)-organic ligands (polydopamine and chitooligosaccharide, PDA/COS@Eu) was fabricated (denoted as Tra-PLA/PDA/COS@Eu) to augment bone repair by facilitating mitochondrial function. First, the trabecular bone templated-scaffold provides superior mechanical performance and permeability in contrast to a computer aided designed (CAD) scaffold under a same volume fraction. Tra-PLA/PDA/COS@Eu scaffold up regulated PI3K/AKT/S6K/HIF-1α pathway and significantly promoted BMSCs proliferation and osteogenic differentiation. In addition, Tra-PLA/PDA/COS@Eu scaffold provided anti-inflammatory environment by promoting macrophages M2 polarization through COS, and significantly stimulated BMSCs osteogenesis with enhanced mitochondrial function and biosynthesis. Remarkably, Eu ions are the key ingredient in enhancing mitochondrial function and biosynthesis in BMSCs. Further studies showed that the above-mentioned facilitations in a rabbit bone defect model were found to be more significant with trabecular bone-templated scaffolds, as opposed to CAD scaffolds. In summary, this novel trabecular bone-templated scaffold targeting mitochondrial function has the potential to become an effective method in the treatment of large bone defects.
研究领域:
生物材料
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组织工程
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生物医学工程
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再生医学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2024
·
IF 1.8
Ping Huang,Ting Xiang,Qiong Wang,Lintao Han,Sili Zheng,Dongning Zhang,Fang Huang,Bailu Duan,Jingjing Li,Huamao Li,Tao Huang
Xixin–Ganjiang herb pair (XGHP) is a classic combination for warming the lungs to dissolve phlegm and is often used to treat a variety of chronic lung diseases; it can treat the syndrome of cold phlegm obstruction of lungs. First, ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to examine the composition of XGHP, and network pharmacology was used to predict its potential core targets and signaling pathways in the current study. Second, a rat model of chronic obstructive pulmonary disease (COPD) was established for assessing the anti-COPD activity of XGHP, and metabolomics was used to explore the biomarkers and metabolic pathways. Finally, the sample was validated using molecular docking and Western blotting. The integration of metabolomics and network pharmacology results identified 11 targets, 3 biomarkers, 3 pathways, and 2 metabolic pathways. Western blotting showed that XGHP effectively regulated the expression of core proteins via multiple signaling pathways (downregulation of toll-like receptor 4 [ TLR4 ] and upregulation of serine/threonine-protein kinase 1 [ p-AKT1 ] and nitric oxide synthase 3 [ NOS3 ]). Molecular docking results showed that the 10 potentially active components of XGHP have good affinity with tumor necrosis factor-alpha ( TNF-α ), interleukin-6 ( IL-6 ), matrix metalloproteinase 9 ( MMP-9 ), TLR4 , p-AKT1 , and NOS3 . Our findings suggest that XGHP may regulate glucolipid metabolism, improve energy supply, and inhibit inflammatory responses ( TNF-α , IL-6 , and MMP-9 ) via the PI3K-Akt signaling pathway and HIF-1 signaling pathway in the management of COPD.
研究领域:
药理学
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代谢组学
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网络药理学
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慢性阻塞性肺疾病
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中药学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Wang Weili,Zheng Huizhen,Jiang Jun,Li Zhi,Jiang Dongpeng,Shi Xiangru,Wang Hui,Jiang Jie,Xie Qianqian,Gao Meng,Chu Jianhong,Cai Xiaoming,Xia Tian,Li Ruibin
While hypoxia promotes carcinogenesis, tumour aggressiveness, metastasis, and resistance to oncological treatments, the impacts of hyperoxia on tumours are rarely explored because providing a long-lasting oxygen supply in vivo is a major challenge. Herein, we construct micro oxygen factories, namely, photosynthesis microcapsules (PMCs), by encapsulation of acquired cyanobacteria and upconversion nanoparticles in alginate microcapsules. This system enables a long-lasting oxygen supply through the conversion of external radiation into red-wavelength emissions for photosynthesis in cyanobacteria. PMC treatment suppresses the NF-kB pathway, HIF-1α production and cancer cell proliferation. Hyperoxic microenvironment created by an in vivo PMC implant inhibits hepatocarcinoma growth and metastasis and has synergistic effects together with anti-PD-1 in breast cancer. The engineering oxygen factories offer potential for tumour biology studies in hyperoxic microenvironments and inspire the exploration of oncological treatments.
研究领域:
生物医学工程
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肿瘤学
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纳米技术
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Shue Jin,Renli Yang,Chenyu Chu,Chen Hu,Qin Zou,Yubao Li,Yi Zuo,Yi Man,Jidong Li
The fate of biomaterials is orchestrated by biocompatibility and bioregulation characteristics, reported to be closely related to topographical structures. For the purpose to investigate the topography of fibrous membranes on the guided bone regeneration performance, we successfully fabricated poly (lactate- co -glycolate)/fish collagen/nano-hydroxyapatite (PFCH) fibrous membranes with random, aligned and latticed topography by electrospinning. The physical, chemical and biological properties of the three topographical PFCH membranes were systematically investigated by in vitro and in vivo experiments. The subcutaneous implantation of C57BL6 mice showed an acceptable mild foreign body reaction of all three topological membranes. Interestingly, the latticed PFCH membrane exhibited superior abilities to recruit macrophage/monocyte and induce angiogenesis . We further investigated the osteogenesis of the three topographical PFCH membranes via the critical-size calvarial bone defect model of rats and mice and the results suggested that latticed PFCH membrane manifested promising performance to promote angiogenesis through upregulation of the HIF-1α signaling pathway ; thereby enhancing bone regeneration. Our research illustrated that the topological structure of fibrous membranes, as one of the characteristics of biomaterials, could regulate its biological functions, and the fibrous structure of latticed topography could serve as a favorable surface design of biomaterials for bone regeneration. Statement of significance In material-mediated regeneration medicine, the interaction between the biomaterial and the host is key to successful tissue regeneration . The micro-and nano-structure becomes one of the most critical physical clues for designing biomaterials. In this study, we fabricated three topological electrospun membranes (Random, Aligned and Latticed) to understand how topological structural clues mediate bone tissue regeneration. Interestingly, we found that the Latticed topographical PFCH membrane promotes macrophage recruitment, angiogenesis, and osteogenesis in vivo , indicating the fibrous structure of latticed topography could serve as a favorable surface design of biomaterials for bone regeneration.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
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