ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Wenjing Zai,Wei Chen,Zimei Wu,Xin Jin,Jiajun Fan,Xuyao Zhang,Jingyun Luan,Shijie Tang,Xiaobin Mei,Qiang Hao,Hongrui Liu,Dianwen Ju
Nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease, and there is currently no available treatment strategy. Interleukin-22 (IL-22) has been recognized as a promising agent for alleviating NAFLD, but the efficacy of IL-22 is far from satisfactory because safe dose of IL-22 elicited limited improvement, whereas higher concentration might induce serious side effects and off-target toxicities. Thus, targeted and sustained expression of IL-22 in the liver is necessary. To meet the challenge, we elaborately developed a novel polymetformin carrier by conjugating biguanide to chitosan, termed chitosan–metformin (CM), which could exert advanced gene delivery efficiency and possess intrinsic therapeutic efficacy from metformin for NAFLD. CM accompanied with penetratin and DSPE-PEG2000 could self-assemble to form stable nanocomplexes with IL-22 gene via electrostatic interaction. This nanoparticle (CDPIA) exerted desirable particle size at ∼100 nm, fine morphology, and efficient cellular internalization. Furthermore, CDPIA also demonstrated a unique superiority in endosomal escape capacity and satisfactory biocompatibility as well as predominant liver accumulation. Most importantly, CDPIA distinctly alleviated hepatic steatosis, restored insulin sensitivity, and improved metabolic syndrome in high-fat-diet-fed mice model. This liver-targeted delivery of IL-22 activated STAT3/Erk1/2 and Nrf2/SOD1 signaling transductions as well as modulated lipid-metabolism-related gene expression. These findings altogether demonstrated that the polymetformin and penetratin-based hybrid nanoparticles could be exploited as a novel safe and efficient strategy for the improvement of NAFLD.
研究领域:
药学
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分子生物学
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生物技术
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肝病学
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代谢性疾病
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 16
·2657-2666
·
IF 5.047
Maowen Chen,Yan Hu,Yanhua Hou,Menghuan Li,Maohua Chen,Caiyun Mu,Bailong Tao,Wei Zhu,Zhong Luo,Kaiyong Cai
Autophagy is associated with the proliferation and differentiation of mesenchymal stem cells (MSCs). In this study, we investigated the biological impact of silica-based nanobiomateiral-induced autophagy on the differentiation of MSCs, in which the nanoparticulate cues include solid silica nanoparticles (SSN), mesoporous silica nanoparticles (MSN) and biodegradable mesoporous silica nanoparticles (DMSN). The treatment with SSN significantly up-regulated the LC3-II expression via ERK1/2 and AKT/mTOR signaling pathways compared to DMSN and MSN, leading to a higher autophagic activity in MSCs. The enhanced protein adsorption of DMSN and MSN could prevent the direct interaction between cells and nanoparticles, which consequently reduces the autophagic stimulation of MSCs. It should be noted that MSCs exhibited increased differentiation potential when the autophagic activity was enhanced by the treatment with different nanoparticles. In comparison, no difference in the cell differentiation potential was found when an autophagy inhibitor (chloroquine, CQ) was incorporated in all groups. The study may contribute to the development of silica-based nanobiomaterials in the future.
研究领域:
纳米生物技术
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干细胞生物学
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材料科学
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细胞与分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Jiale Chen,Zhixiang Mu,Dongfan Chen,Chen Huang,Ting Jin,Lin Li,Youyun Zeng,Qiang Zhou,Yanmei Zhang,Hongli Mao,Hui Deng,Xinkun Shen,Hong Yang,Xiaojun Cai
Smart hydrogel dressings capable of simultaneously highly effective antimicrobial, anti-inflammatory, and promoting re-epithelialization and angiogenesis are urgently needed for the management of diabetic wounds. Herein, a H 2 S-releasing multifunctional hydrogel was developed by utilizing the dynamic Schiff base reaction between carboxymethyl chitosan (CMC) and polyhexamethylene guanidine (PHMG)-modified aldehyde F108 (PFC). Diallyl trisulfide (DATS) was encapsulated into the PFC nanoparticles. Apart from possessing the essential properties necessary for an idealized hydrogel dressing, such as excellent injectability, tissue adhesion, self-healing, and stimulus–response degradation, the [email protected] &CMC also utilized the synergistic effect of the PHMG and DATS to provide an efficient antimicrobial effect; the H 2 S was slowly released from the DATS under the action of GSH and exerted excellent anti-inflammatory effects, by inhibiting the expression of p-ERK and p-STAT3 in activated macrophages, and promoting macrophage polarization to the M2 phenotype. Strikingly, following the completion of the efficient antimicrobial and anti-inflammatory effects, the continuously generated H 2 S further significantly accelerated the proliferation, migration, and vascularization of endothelial cells by extending the activation of the p-p38 and p-ERK1/2. Owing to superior performances, [email protected] &CMC significantly promoted the healing of diabetic wounds induced by streptozotocin with good biocompatibility. This study demonstrates that [email protected] &CMC is a versatile hydrogel dressing with great potential for the management of diabetic wounds.
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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糖尿病管理
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产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Qingfeng Guo,Shenyu Shen,Xinyang Wang,Lei Shi,Yuwei Ren,Dandan Li,Zhenhua Yin,Juanjuan Zhang,Baocheng Yang,Xuewei Wang,Gang Ding,Lin Chen
The chemical engineering of natural extracts has emerged as an effective strategy for the production of diverse libraries of chemicals, making it integral to drug discovery. A chemical engineering strategy based on the epoxidation and ring-opening reactions was used to prepare diversity-enhanced extracts of Chaetomium madrasense 375. Eleven unnatural cytochalasan derivatives ( 1–11 ) with unique functional groups, such as amine and isoxazole, were isolated and characterized from these chemically engineered extracts of C. madrasense 375. The identification of these new structures was accomplished through comprehensive spectroscopic analysis, supplemented by synthetic considerations. Notably, compounds 5 and 13 – 16 displayed potent phytotoxic effects on Arabidopsis thaliana , while compounds 1 , 2 , 5 , 10 , and 12 demonstrated inhibitory activities on LPS-induced NO production in RAW264.7 cells. Among them, compound 1 was found to be able to inhibit the upregulated expression of the inducible nitric oxide synthase (iNOS) protein induced by LPS, while also decreasing the production of pro-inflammatory cytokines (IL-6) and influencing the phosphorylation of p38, ERK1/2, and JNK at 100 μM. Our findings demonstrate that the chemical engineering of natural product extracts can be an efficient technique for the generation of novel bioactive molecules.
研究领域:
药理学
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化学工程
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天然产物化学
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免疫学
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植物科学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2015
·Vol. 9
·期 6
·2072-2080
·
IF 1.269
Yang Li,Jiefang Wang,Guangming Chen,Shuiwang Feng,Panpan Wang,Xiaofeng Zhu,Ronghua Zhang
The aim of the present study was to investigate the effects of quercetin on the mitogen-activated protein kinase (MAPK) signaling pathway in the osteogenic differentiation of rat mesenchymal stem cells (MSCs). A 3-(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and an alkaline phosphatase (ALP) assay were used to determine the effects of quercetin (concentrations of 0.1, 1 and 10 µmol/l) on the proliferation and differentiation of MSCs and the expression of ALP, respectively. In addition, through the introduction of inhibitors of p38 MAPK, extracellular signal‑regulated kinase (ERK)1/2 and c‑Jun NH2‑terminal kinase (JNK), the effects of quercetin on the proteins, ALP, collagen type I (COL I) and bone γ‑carboxyglutamate protein (BGP), which are indicators of osteogenic differentiation, were investigated. Immunoblotting was performed to determine the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, while fluorescent quantitative polymerase chain reaction was used to determine the mRNA expression levels of transforming growth factor (TGF)‑β1, bone morphogenetic protein (BMP)‑2 and core binding factor (CBF)α1. At all the concentrations tested, the concentrations of 10, 1 and 0.1 µmol/l quercetin were shown to promote the differentiation of MSCs and the expression of ALP, in which the concentration of 10 µmol/l was optimal. When compared with the control group, the phosphorylation levels of p38 MAPK, ERK1/2 and JNK, the protein expression levels of ALP, COL I and BGP, and the mNRA expression levels of TGF‑β1, BMP‑2 and Cbfα1 were increased in the quercetin‑treated group. However, with the introduction of inhibitors, the levels of phosphorylated p38 MAPK, ERK1/2 and JNK, and the protein expression levels of ALP, COL I and BGP decreased. Furthermore, the mRNA expression levels of TGF‑β1, BMP‑2 and CBFα1 decreased in the quercetin + SP600125 (inhibitor of JNK) and quercetin + PD98059 (inhibitor of ERK1/2) groups. Therefore, quercetin was demonstrated to promote the osteogenic differentiation of MSCs by activating the MAPK signaling pathway. The ERK1/2 and JNK signaling pathways regulate the expression of TGF‑β1, BMP‑2 and CBFα1. Thus, activation of the ERK1/2 and JNK signaling pathways may play a leading role in the quercetin‑promoted osteogenic proliferation and differentiation of MSCs.
研究领域:
药理学
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干细胞生物学
·
细胞信号转导
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Xionghua Sun,Mei Zhu,Wei Xia,Xihan Xu,Jian Zhang,Xiaogang Jiang
Eupatorium lindleyanum DC . has been used as a functional food in China for a long time. However, the antifibrotic activity of total sesquiterpenoids from Eupatorium lindleyanum DC . (TS-EL) is still unknown. In this study, we discovered that TS-EL reduced the increase in α-smooth muscle actin (α-SMA), type I collagen and fibronectin content, the formation of cell filaments and collagen gel contraction in transforming growth factor-β1-stimulated human lung fibroblasts. Intriguingly, TS-EL did not change the phosphorylation of Smad2/3 and Erk1/2. TS-EL decreased the levels of serum response factor (SRF), a critical transcription factor of α-SMA, and SRF knockdown alleviated the transition of lung myofibroblasts. Furthermore, TS-EL significantly attenuated bleomycin (BLM)-induced lung pathology and collagen deposition and reduced the levels of two profibrotic markers, total lung hydroxyproline and α-SMA. TS-EL also decreased the levels of SRF protein expression in BLM-induced mice. These results suggested that TS-EL attenuates pulmonary fibrosis by inhibiting myofibroblast transition via the downregulation of SRF.
研究领域:
药理学
·
肺科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Suqiu Dong,Chunmei Zhang,Yunjue Wang,Shuping Liu,Junhua Yang,Lixia Li,Yuxin Ma,Jing Liu
Rutin (Rut) is a flavonoid with pharmacological activities such as anti-inflammatory and antioxidant. Acrylamide (ACR) is a toxic substance widely found in human life that can induce neurotoxicity. Some studies have confirmed that neurotoxicity caused by ACR induces myelin damage, which in turn causes neurological dysfunction. Therefore, we established a rutin intervention model to investigate the protective effect of Rut on ACR-induced sciatic nerve injury in rats and its mechanism. The results showed that superoxide dismutase (SOD) activity and glutathione (GSH) content increased and lactate dehydrogenase (LDH) activity decreased in the middle and high dose groups of Rut compared with the ACR group, and the expression of Myelin basic protein (MBP), Extracellular-regulated kinase 1/2(ERK1/2), Phosphorylated extracellular regulated kinase 1/2 (P-ERK1/2), and Nuclear factor E−2-associated factor (Nrf2) was promoted in the Rut-protected group, which suggests that Rutin has a protective effect on ACR-induced sciatic nerve injury and that the mechanism of Rutin's protective effect is related to activation of the ERK1/2 pathway and alleviation of oxidative stress injury.
研究领域:
药理学
·
神经科学
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毒理学
·
分子生物学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Yiyuan Duan,Shan Yu,Peifang Xu,Xuemei Wang,Xue Feng,Zhengwei Mao,Changyou Gao
Capture of endothelial progenitor cells (EPCs) in situ has been considered as a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and implant devices. In this study, a CD133 + EPC capture surface was fabricated by grafting CD133 antibody (a more specific EPC surface marker than CD34) and Arg-Glu-Asp-Val (REDV) peptideon the methacrylate-grafted hyaluronic acid (MA-HA) and heparin-hybridized (MA-HA&Heparin) resisting layer. Vascular endothelial growth factor (VEGF) was further conjugated to the immobilized heparin. This engineered surface showed good hemocompatibility and significantly higher ability of capturing CD133 + EPCs from human peripheral blood mononuclear cells (PBMCs) and obviously upregulated the expression of endothelial cell (EC) marker genes of EPCs such as VEGF receptor 2 (VEGFR2), CD31 , VE-cadherin, and von Willebrand factor (vWF), facilitating the differentiation of EPCs into ECs. The dramatically enhanced EPC proliferation on this surface was dependent on the integrin-VEGFR synergistic signaling, as ERK1/2 phosphorylation was only significantly enhanced on the REDV and VEGF co-immobilized surface. This study highlights a new surface coating strategy for blood-contact materials based on the specific EPC capturing and rapid endothelialization. Statement of Significance Capture of endothelial progenitor cells (EPCs) in situ is a promising strategy for the rapid endothelialization and long-term patency of artificial blood vessels and scaffolds. More specific capture of EPCs by targeting CD133 rather than CD34 can better reduce the risk of inflammation and restenosis. On the other hand, an appropriate microenvironment for EPC proliferation is equally important for endothelialization, which is rarely considered by the existing EPC capture strategies. In this study, the capture ratio of EPCs was significantly increased by simultaneously grafting CD133 antibody and VEGF on a MA-HA and heparin-hybridized antifouling layer. Further, proliferation of EPCs after capture was significantly promoted by grafting VEGF and REDV peptide through the integrin–VEGFR synergistic signaling. This study highlights a new strategy for the surface coating of blood-contact materials based on specific EPC capture and rapid endothelialization.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Tanjun Deng,Wenli Lu,Xiaoxian Zhao,Haoyu Wang,Yumeng Zheng,Ao Zheng,Zhengyu Shen
Chronic wounds with bacterial infection present formidable clinical challenges. In this study, a versatile hydrogel dressing with antibacterial and angiogenic activity composite of silk fibroin (SF), chondroitin sulfate (CS), and graphene oxide quantum dots (GOQDs) is fabricated. GOQDs@SF/CS (GSC) hydrogel is rapidly formed through the enzyme catalytic action of horseradish peroxidase. With the incorporation of GOQDs both gelation speed and mechanical properties have been enhanced, and the photothermal characteristics of GOQDs in GSC hydrogel enabling bacterial killing through photothermal treatment (PTT) at ~51 °C. In vitro studies show that the GSC hydrogels demonstrate excellent antibacterial performance and induces type H vessel differentiation of endothelial cells via the activated ERK1/2 signaling pathway and upregulated SLIT3 expression. While in vivo results show that the hydrogel significantly promotes type H vessels formation, which related to the collagen deposition, epithelialization and, ultimately accelerating the regeneration of infected skin defects. Collectively, this multifunctional GSC hydrogel, with dual action of antibacterial efficacy and angiogenesis promotion, emerges as an innovative skin dressing with potential for advancing in infected wound healing.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
·
组织工程
·
纳米技术
·
生物材料
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2016
·Vol. 3
·期 5
·299-307
·
IF 0
Sun Hong-Ji,Wang Yan,Hao Tong,Wang Chang-Yong,Wang Qi-Yu,Jiang Xiao-Xia
Glutathione (GSH) depletion has been an important contributor to the dysfunction of dopamine neurons. Polyamidoamine-GSH (PAMAM-GSH) was synthesized and the delivery effect of GSH into PC12 cells was tested. MTT assessment for cytotoxicity and reactive oxygen species (ROS) as well as nitrite oxide (NO) and intracelluar superoxide dismutase (SOD) detection for antioxidative ability were performed. Furthermore, the antiapoptotic ability was analysed by assessing caspase-3, JNK1/2 and Erk1/2 expression. Our data indicated that PAMAM-GSH is an effective agent to replenish GSH into PC12 cells. PAMAM-GSH developed its antioxidative and protective ability for 1-methyl-4-phenylpyridinium (MPP)-induced PC12 cells by reducing the intracellular levels of ROS and SOD activity as well as decreasing the release of NO. Meanwhile, PAMAM-GSH could inhibit caspase-3 activation and might show its antiapoptotic ability to MPP-induced PC12 cells through JNK2/Erk1/2 pathway. In summary, these studies suggest that PAMAM-GSH conjugate has an intrinsic ability to penetrate PC12 cells and deliver GSH into these cells which may provide a new strategy for clinical applications in the treatment of Parkinson’s disease.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
疾病模型
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产品关联
DOI
PubMed
Scientific Reports
·
2017
·
IF 4.259
Yuhong Liu,Jiali Liang,Jiazhen Wu,Hanbin Chen,Zhenbiao Zhang,Hongmei Yang,Liping Chen,Haiming Chen,Ziren Su,Yucui Li
Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.
研究领域:
药理学
·
胃肠病学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 16
·8593-8604
·
IF 6.317
Yanfang Yu,Yuhuan Chen,Xuping Shi,Chuan Ye,Junwen Wang,Jinzhi Huang,Bing Zhang,Zeyuan Deng
This study investigated the hepatoprotective effects of various mulberry (Morus alba L.) leaf extracts (MLEs), including mulberry ethanol extract (MEE), aqueous extract (MAE) and a combination extract (MCE) against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in rats. It aimed to explore the possible molecular mechanism of the liver-protecting function of mulberry leaves and provide a reference for choosing the appropriate extraction method. The results showed that the three extracts contained different amounts of phenolic compounds, 1-deoxynojirimycin (DNJ) and polysaccharides. MLEs markedly improved the pathological status of rat liver tissue, decreased the levels of AST, ALT, TNF-α, IL-1β, IL-6 and MDA, while increased the levels of GSH, SOD and CAT in the D-GalN/LPS-treated rats at the same time. MEE, with the highest amount of total phenolics, exhibited the highest antioxidant activity corresponding to the protein expression level of Nrf2 and HO-1. MCE significantly suppressed the expression of apoptosis-related dot-like protein (ASC) and Caspase-1 and inhibited the phosphorylation of p38 MAPK and ERK1/2, thereby showing high anti-inflammatory activity. These results indicated that the active components from mulberry leaves protected rats against acute liver injury, attributed to a reduction in both oxidative stress and inflammatory response. The protective effect may be implicated in regulating the Nrf2, NLRP3 and MAPK signaling pathways.
研究领域:
药理学
·
肝病学
·
生物化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）