CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Guanqun Peng,Jia Hu,Jinnan Guo,Jiahui Dong,Yuanyuan Zhao,Tong Ye,Fengjun Xiao,Zhiyun Meng,Hui Gan,Ruolan Gu,Peng Han,Wenzhong Sun,Guifang Dou,Yunbo Sun,Shuchen Liu
The management of combined radiation-wound injury (CRWI) is a major clinical challenge owing to the delayed and prolonged wound-healing process. Moreover, the mechanisms underlying the healing of CRWI are complex, and chronic wounds can increase vulnerability to multidrug-resistant bacterial infections, vascular disease, and other adverse conditions. Although exosomes from iPSC-derived mesenchymal stem cells (iMSCs) can promote injury repair, the feasibility of encapsulating them within polysaccharide-based hydrogels to treat CRWI remains to be explored. Here, iMSC-derived exosomes were encapsulated within an injectable hydrogel (HACC/OSA) consisting of quaternized chitosan (HACC) and oxidized sodium alginate (OSA). The HACC/OSA hydrogel exhibited good self-healing properties, excellent injectability, and good biocompatibility. In mouse models of CRWI, the HACC/OSA hydrogel could form a protective barrier covering the wound. Due to the presence of quaternary ammonium salts, the hydrogel could provide long-term antimicrobial protection to the wound, which was favorable for wound healing. In addition, the hydrogel could also promote CRWI repair by stabilizing exosome release. The exosome-loaded hydrogel (HACC/OSA@Exos) significantly inhibited bacterial growth and promoted the repair of CRWI, as indicated by enhanced wound healing efficiency, rapid re-epithelialization, favorable collagen deposition, and abundant angiogenesis at the wound site. Together, the in vivo and in vitro results indicated that the exosome-loaded polysaccharide-based hydrogel (HACC/OSA@Exos) can promote the healing of CRWI and potentially serve as a valuable clinical agent for CRWI management.
研究领域:
生物材料
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组织工程
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伤口愈合
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生物医学工程
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干细胞生物学
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产品关联
DOI
高影响因子
Bioactive Materials
·
2024
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IF 18
Yu-hong Wang,Ting-ting Liu,Yan-ping Guo,Shuo-ji Zhu,Zi-ming Liao,Jia-mei Song,Xi-ming Zhu,Jia-liang Liang,Moussa Ide Nasser,Nan-bo Liu,De-hua Chang,Ping Zhu,Bin Yao
The preclinical evaluation of drug-induced cardiotoxicity is critical for developing novel drug, helping to avoid drug wastage and post-marketing withdrawal. Although human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and the engineered heart organoid have been used for drug screening and mimicking disease models, they are always limited by the immaturity and lack of functionality of the cardiomyocytes. In this study, we constructed a Cardiomyocytes-on-a-Chip (CoC) that combines micro-grooves (MGs) and circulating mechanical stimulation to recapitulate the well-organized structure and stable beating of myocardial tissue. The phenotypic changes and maturation of CMs cultured on the CoC have been verified and can be used for the evaluation of cardiotoxicity and cardioprotective drug responses. Taken together, these results highlight the ability of our myocardial microarray platform to accurately reflect clinical behaviour, underscoring its potential as a powerful pre-clinical tool for assessing drug response and toxicity.
研究领域:
生物医学工程
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药理学
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干细胞研究
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药物开发
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
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IF 6.8
Jiabao Lu,Jianchao Li,Peiyi Yin,Nana Huang,Rong Sun
BAP improved glycolipid metabolism, insulin resistance, and hepatic steatosis in MAFLD mice. • Human iPSC-derived liver organoids were used to model MAFLD and evaluate BAP. • Network pharmacology and multi-model validation revealed the mechanism of BAP. Ethnopharmacological relevance Bupleuri Radix (Chaihu) and Aurantii Fructus Immaturus (Zhishi) is a classic herb pair from Si-Ni-San. In traditional Chinese medicine theory, they regulate liver-spleen qi movement through a “one ascending, one descending” dynamic, and are used for syndromes of liver depression and spleen deficiency with phlegm-stasis intermingling. This syndrome pattern closely mirrors the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the mechanisms underlying the anti-MAFLD effect of this herb pair remain unclear. Aim of the study To determine the effects and molecular mechanisms of the Bupleuri Radix- Aurantii Fructus Immaturus pair (BAP) in alleviating MAFLD. Materials and methods The quality of the BAP preparation used in this study was partially assessed by high-performance liquid chromatography (HPLC). Potential mechanisms were predicted via network pharmacology and functional enrichment analysis, and experimentally explored using high-fat high-sucrose diet mice, FFA-induced AML12 hepatocytes and human induced pluripotent stem cell (iPSC)-derived liver organoids. The PI3K/Akt-GSK3β/FoxO1 signaling pathway was further examined by LY294002 rescue assay. Results BAP ameliorated MAFLD-related hepatic phenotypes both in vivo and in vitro. Four representative quality control markers, namely synephrine, naringin, saikosaponin A, and saikosaponin D, were identified using validated reference standard methods. Network pharmacological analysis predicted that AKT1, GSK3B, and FOXO1 might be central targets, and the PI3K-Akt signalling pathway was identified as a potential pathway associated with the anti-MAFLD effects of BAP. GO and KEGG enrichment analyses revealed that the overlapping targets were significantly enriched in insulin signalling, lipid metabolism, and FoxO signalling pathways. In vivo, BAP treatment significantly reduced body weight gain, improved serum lipid profiles and liver function, alleviated insulin resistance, and attenuated hepatic steatosis and inflammation in HFSW-fed mice. Energy metabolism monitoring indicated that BAP markedly enhanced oxygen consumption and carbon dioxide production throughout the 24-hour light-dark cycle. In human iPSC-derived liver organoids, BAP reduced FFA-induced hepatocyte injury, lipid accumulation, and oxidative stress, and partially normalized the aberrant expression of genes involved in lipogenesis (SREBF1, FASN, SCD1), fatty acid oxidation (PPARA, CPT1A), and gluconeogenesis (G6PC). Western blot analysis demonstrated that BAP significantly upregulated PI3K expression and the phosphorylation levels of Akt (Ser473), GSK-3β (Ser9), and FoxO1 (Ser256), while downregulating p-GS (Ser641) in mouse livers, liver organoids, and AML12 cells. Moreover, co-treatment with the PI3K inhibitor LY294002 partially counteracted the beneficial effects of BAP on these proteins and counteracted the improvements in glycolipid metabolism, suggesting that the anti-MAFLD effects of BAP are associated with modulation of the PI3K/Akt pathway. Conclusions With BAP as the research subject, this study conducts cross-validation across a multi-model system including whole-animal models, hepatocytes and human liver organoids, and suggests that BAP ameliorates glucolipid metabolic disorders and slows MAFLD progression, effects that are closely associated with modulation of the PI3K/Akt-GSK3β/FoxO1 signaling pathway. These findings provide novel compatibility insights and experimental evidence for traditional Chinese medicine-based intervention of MAFLD. Download: Download high-res image (291KB) Download: Download full-size image
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DOI
PubMed
高影响因子
Journal of Translational Medicine
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2023
·Vol. 21
·期 1
·1-22
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IF 7.4
Liu Qian,Liu Jun,Guo Minmei,Sung Tzu-Cheng,Wang Ting,Yu Tao,Tian Zeyu,Fan Guoping,Wu Wencan,Higuchi Akon
Background Retinal degeneration (RD) is a group of disorders on irreversible vision loss. Multiple types of stem cells were used in clinical trials for RD treatment. However, it remains unknown what kinds of stem cells are most effective for the treatment. Therefore, we investigated the subretinal transplantation of several types of stem cells, human adipose-derived stem cells (hADSCs), amniotic fluid stem cells (hAFSCs), bone marrow stem cells (hBMSCs), dental pulp stem cells (hDPSCs), induced pluripotent stem cell (hiPSC), and hiPSC-derived retinal pigment epithelium (RPE) cells for protection effects, paracrine effects and treatment efficiency in an RD disease model rats.Methods The generation and characterization of these stem cells and hiPSC-derived RPE cells were performed before transplantation. The stem cells or hiPSC-derived RPE cell suspension labelled with CellTracker Green to detect transplanted cells were delivered into the subretinal space of 3-week-old RCS rats. The control group received subretinal PBS injection or non-injection. A series of detections including fundus photography, optomotor response (OMR) evaluations, light–dark box testing, electroretinography (ERG), and hematoxylin and eosin (HE) staining of retinal sections were conducted after subretinal injection of the cells.Results Each stem cell, hiPSC-derived RPE cell or PBS (blank experiment) was successfully transplanted into at least six RCS rats subretinally. Compared with the control rats, RCS rats subjected to subretinal transplantation of any stem cells except hiPSCs showed higher ERG waves (p < 0.05) and quantitative OMR (qOMR) index values (hADSCs: 1.166, hAFSCs: 1.249, hBMSCs: 1.098, hDPSCs: 1.238, hiPSCs: 1.208, hiPSC-RPE cells: 1.294, non-injection: 1.03, PBS: 1.06), which indicated better visual function, at 4 weeks post-injection. However, only rats that received hiPSC-derived RPE cells maintained their visual function at 8 weeks post-injection (p < 0.05). The outer nuclear layer thickness observed in histological sections after HE staining showed the same pattern as the ERG and qOMR results.Conclusion sCompared to hiPSC-derived RPE cells, adult and fetal stem cells yielded improvements in visual function for up to 4 weeks post-injection; this outcome was mainly based on the paracrine effects of several types of growth factors secreted by the stem cells. Patients with RD will benefit from the stem cell therapy.
研究领域:
眼科学
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干细胞研究
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神经科学
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再生医学
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产品关联
DOI
PubMed
高影响因子
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