EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Chujun Chen,Zhenming Lin,Wenbin Liu,Qiong Hu,Jie Wang,Xiaoyan Zhuang,Sujuan Guan,Xiaoting Wu,Tingting Hu,Shijian Quan,Xiaobao Jin,Juan Shen
Diabetic wound healing, characterized by chronic inflammation , remains a medical challenge. The failure of prompt conversion from pro-inflammatory M1-like macrophage to pro-healing M2-like macrophage is the main obstacle to diabetic wounds. Emodin , an anthraquinone derivative , has multiple bioactivities, including antibacterial, anticancer, and anti-inflammatory. Recently, emodin has shown potential in promoting wound healing. However, the underlying molecular mechanism remains unclear. In this study, we examined the effects of emodin on wound healing in db/db diabetic mice using a full-thickness excision model. Our results showed that emodin can remarkably accelerate healing by enhancing extracellular matrix (ECM) synthesis and granulation tissue formation. We identified 32 potential targets of emodin by network pharmacology analysis, and our transcriptome analysis highlighted the down-regulation of the NF-κB signaling pathway mediated by emodin. Mechanistically, emodin was shown to inhibit the p65-NF-κB complex and promote the proportion of M2 (anti-inflammatory)-like phenotype macrophages both in vitro and vivo. Then, bone-marrow-derived macrophages were co-cultured with fibroblasts (mouse dermal fibroblasts cells). Treatment of emodin significantly increased the proportion of M2-polarized macrophages and the expression level of TGF-β, a typical ECM formation-related cytokine secreted by the M2 macrophages in the co-cultured supernatant. We further revealed that emodin improved the proliferation of mouse dermal fibroblasts (MDFs) cells and upregulated the expression levels of collagen III, fibronectin and α-SMA in MDFs cells in emodin-treated co-culture systems. 1D11, a neutralizing antibody for all three major TGF-β isoforms, diminished the biological effects of emodin on proliferation and ECM formation in MDFs cells. Taken together, our study suggests emodin may serve as an effective therapeutic agent for diabetic wounds.
研究领域:
药理学
·
免疫学
·
伤口愈合
·
糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TECHNOLOGY AND HEALTH CARE
·
2023
·
IF 1.6
Song Xiaolong,Wang Lei,Liu Min,Pan Renyou,Song Jun,Kong Junhong
BACKGROUND: Hypertension is a well-recognized risk factor for cardiovascular, which is also a critical factor in causing myocardial fibrosis (MF). OBJECTIVE: The study aimed to explore the effect of Atractylenolide II (ATL-II) on MF and oxidative stress in spontaneous hypertension rats (SHR). METHODS: The body weight of rats after injection of ATL-II was quantitatively analyzed. The left ventricular function of SHR was evaluated by Echocardiographic. HE staining, Masson trichrome staining, left ventricular mass index (LVMI) and immunofluorescence was applied to investigate the effects of ATL-II on MF. RT qPCR was used to detect the Collagen I, α-SMA, Fibronectin, and Vimentin mRNA expression levels in myocardial slices. The effect ATL-II on cardiomyocyte apoptosis was detected by TUNEL staining and western blot. An immunohistochemistry assay was conducted to detect α-SMA protein and TGF-β1 protein. The contents of H2O2, GSH-PX, SOD, and MDA were measured by colorimetry. RESULTS: ATL-II could dose-dependently improve the BW of SHRs (P< 0.05) and enhance myocardial function. Moreover, ATL-II effectively reduced cardiomyocyte apoptosis in SHRs. Alternatively, ATL-II could inhibit the Collagen I, α-SMA, Fibronectin, and Vimentin mRNA and protein expression levels in SHRs. ATL-II could ameliorate oxidative stress by improving the activities of SOD and GSH-PX and lowering the contents of H2O2 and MDA in ATL-II-treated SHRs, which reach about 80%. CONCLUSION: ATL-II could exert an inhibiting effect on MF and oxidative stress in SHRs. Hence, ATL-II may hold promise for the treatment of MF and oxidative stress in Spontaneous Hypertension.
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Zhenjiang Zheng,Dingchuan Peng,Mengfei Li,Xuehan Lu,Songlin Gong,Yuan Yuan,Epiphane K. Silli,Jiali Tang,Qiaoyun Zhao,HaoYun Xu,Yufei Lan,Chunlu Tan,Ying Wang
Due to the malignant proliferation and severe tumor fibrosis of pancreatic cancer (PC), the efficacy of chemotherapy has been largely limited. Peptidyl-prolyl cis -trans isomerase NIMA-interacting 1 (Pin1) promotes tumor progression by promoting collagen synthesis and tumor cell proliferation . In this study, we developed nano-liposomes (FU-GEM/Pin1 siRNA@LIP) that act simultaneously on pancreatic tumor cells. FU-GEM/Pin1 siRNA@LIP were designed with suitable particle size and potential, and effectively loaded with Pin1 siRNA and fucoidan (FU) while demonstrating good release stability and biocompatibility . Our study showed that FU-GEM/Pin1 siRNA@LIP effectively inhibited the proliferation of Panc01 and Panc02 tumor cells and significantly enhanced the uptake of these two types of cells in vitro . FU-GEM/Pin1 siRNA@LIP might cause tumor damage, promote apoptosis and reduce collagen formation in vivo . Molecular and histological studies demonstrated that FU-GEM/Pin1 siRNA@LIP regulated the expression of CDH11 and α-SMA, and also reducing collagen synthesis of peripheral matrix. In summary, our experiments highlight that FU-GEM/Pin1 siRNA@LIP is an effective combination delivery system. It can inhibit tumor cell proliferation in vitro , promote tumor cell apoptosis and reduce collagen synthesis in vivo . This system could provide a promising therapeutic option for PC.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2017
·
IF 3.165
Xinyi Zhao,Rui Li,Ying Liu,Xuehong Zhang,Min Zhang,Zhi Zeng,Limin Wu,Xuelin Gao,Tian Lan,Yiqing Wang
Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol , has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl 4 ) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl 4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl 4 , the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl 4 -induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl 4 . Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.
研究领域:
药理学
·
肝病学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2022
·
IF 1.798
Guangquan Hu,Xiaojie Ding,Feng Gao,Jiehua Li
Myocardial infarction (MI) is a severe coronary artery disease resulted from substantial and sustained ischemia. Abnormal upregulation of calcium and integrin binding protein 1 (CIB1) has been found in several cardiovascular diseases. In this study, we established a mouse model of MI by permanent ligation of the left anterior descending coronary artery. CIB1 was upregulated in the heart of MI mice. Notably, CIB1 knockdown by intramuscular injection of lentivirus-mediated short hairpin RNA (shRNA) targeting Cib1 improved cardiac function and attenuated myocardial hypertrophy and infarct area in MI mice. MI-induced upregulation of α-SMA, vimentin, Collagen I, and Collagen III, which resulted in collagen production and myocardial fibrosis, were regressed by CIB1 silencing. In vitro, cardiac fibroblasts (CFs) isolated from mice were subjected to angiotensin II (Ang II) treatment. Inhibition of CIB1 downregulated the expression of α-SMA, vimentin, Collagen I, and Collagen III in Ang II-treated CFs. Moreover, CIB1 knockdown inhibited Ang II-induced phosphorylation of PI3K-p85 and Akt in CFs. The effect of CIB1 knockdown on Ang II-induced cellular injury was comparable to that of LY294002, a specific inhibitor of the PI3K/Akt pathway. We demonstrated that MI-induced cardiac hypertrophy, myocardial fibrosis, and cardiac dysfunction might be attributed to the upregulation of CIB1 in MI mice. Downregulation of CIB1 alleviated myocardial fibrosis and cardiac dysfunction by decreasing the expression of α-SMA, vimentin, Collagen I, and Collagen III via inhibiting the PI3K/Akt pathway. Therefore, CIB1 may be a potential target for MI treatment.
研究领域:
心脏病学
·
分子生物学
·
细胞生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2021
·
IF 5.246
Zhang Yin,Wang Qinge,Xu Yuping,Sun Jing,Ding Yanbo,Wang Li,Chen Bingfang,Sun Kewen,Chen Jianping
Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4890-4906
·
IF 6.6
Jianhao Liu,Xiaoman Xu,Yanying Li,Jingxia Xu,Ruogang Zhao,Siwei Liu,Jingliang Wu,Li Zhang,Bo Zhang
Comprehensively regulating the TME is now regarded as a promising approach for cancer treatment. Herein, a novel “three-in-one” effect is presented for simultaneously killing tumor cells, inhibiting the EMT of CAFs, and improving immune responses. In this study, bortezomib (BTZ) is selected for the treatment of breast cancer; it has multiple pharmacological mechanisms for killing tumor cells through the NF-κB signaling pathway, inhibiting the activity of CAFs by activating caspase-3, and enhancing the function of CD8+ T cells by regulating the expression of immune-stimulating factors. To improve the druggability of BTZ in solid tumors, BTZ-loaded lipid/glycocholic acid mixed micelles (BTZ-LGs) were prepared to verify the “three-in-one” effect in killing tumor cells, inhibiting CAFs, and improving immune responses. In the present work, BTZ-LGs were verified to show enhanced in vitro cytotoxicity in both 4T1 cells and 4T1/NIH3T3 co-cultured cells, as well as a superior in vivo treatment effect in different tumor-bearing mouse models. Additionally, BTZ-LGs could regulate the expression of α-SMA, caspase-3, E-cadherin, and N-cadherin, indicating their good inhibiting ability on both tumor cells and CAFs. More importantly, immunological analysis revealed that BTZ-LGs promoted the expression of the immunostimulatory factor IL-2 in tumor tissues, activated anti-tumor T cells, and overcame tumor-induced CD8+ T cell dysfunction. All these findings suggest that BTZ-LGs can achieve a “three-in-one” effect in terms of killing tumor cells, suppressing CAFs, and improving immune responses. This simple and multi-effective therapeutic strategy offers a promising approach for cancer therapy.
研究领域:
癌症治疗
·
药学
·
免疫学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Min Wu,Yitao Zhao,Meihan Tao,Meimei Fu,Yue Wang,Qi Liu,Zhihui Lu,Jinshan Guo
The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.
研究领域:
生物医学工程
·
组织工程
·
细胞生物能学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Fanjia Dai,Jiaying Zhang,Fengjiao Chen,Xianwu Chen,Celine Jessica Lee,Hongze Liang,Lingling Zhao,Hui Tan
The repair of diabetic wound still encounters huge challenges, such as disordered inflammatory regulation and impaired neovascularization. Here, a pH/ROS/glucose responsive and photothermal hydrogel is developed for diabetic wound healing. The hydrogel is formed through cross-linkage between phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) and oxide dextran (OXD), utilizing Schiff base and phenylboronate ester bonds. Additionally, insulin-like growth factor 1 C domain (IGF-1C) and deferoxamine-loaded polydopamine nanoparticles (D@P) are incorporated into the hydrogel. The hydrogel demonstrates sustained drug release, excellent photo thermal effect, prominent antioxidant, antibacterial and anti-inflammatory activities, desirable mechanical and tissue adhesive properties, enhanced tube formation, and cell migration. Furthermore, the hydrogel combined with mild heat treatment can regulate chronic inflammation by promoting the transformation of macrophages from M1 phenotype to M2 phenotype and enhance angiogenesis by up-regulating the expression levels of angiogenesis-related factors such as hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), CD31, and α-SMA, thus greatly accelerates the wound healing in streptozotocin (STZ)-induced diabetic mice. Therefore, this multi-responsive and multifunctional hydrogel holds potential as a therapeutic strategy for diabetic wounds.
研究领域:
材料科学
·
生物医学工程
·
药学
·
组织工程
·
伤口愈合
✓ 已验证
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）