JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
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IF 10.6
Hou Yu,Zhu Lin,Ye Xiaofeng,Ke Qiaoying,Zhang Qibin,Xie Xiaowei,Piao Ji-gang,Wei Yinghui
Background Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. Results In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang ( L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. Conclusion In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation. Graphical Abstract
研究领域:
药学
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生物医学工程
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肾病学
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微生物学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
·
IF 5.4
Huilin Huang,Xue Song,Jiangjiang Zhang,Yan Fan,Ming Kong,Li Zhang,Hu Hou
Scaffolds with multiphasic structures are considered to be superior for guided tissue regeneration. Two types of tilapia skin collagen gradient membranes (stepped gradient and linear gradient) with multiphasic structures were prepared by controlling the collagen concentrations and the freezing rates. The results revealed that collagen gradient membranes were more capable of guiding tissue regeneration compared to homogeneous membranes. These two gradient membranes featured a dense outer layer and a loose inner layer, with good mechanical properties as indicated by tensile strengths of more than 250 Kpa and porosities exceeding 85%. Additionally, these membranes also showed good hydrophilicity and water absorption, with an inner layer contact angle of less than 91° and a water absorption factor greater than 40 times. Furthermore, the multiphasic scaffolds were proved to be biocompatible by the acute toxicity assay, the intradermal irritation test and so on. Gradient membranes could effectively promote the adhesion and proliferation of fibroblasts and osteoblasts, through elevating the TGF-β/Smad signaling pathway by TGF-β and Smads, and activating the Wnt/β-catenin signaling pathway by LRP5 and β-catenin, similar to homogenous membranes. Therefore, collagen gradient membranes from tilapia skin show important application value in guiding tissue regeneration.
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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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2021
·Vol. 43
·期 1
·133-145
·
IF 6.15
Shen Dai-fei,Cheng He,Cai Bo-zhi,Cai Wen-feng,Wang Bin,Zhu Qing,Wu Yue-bin,Liu Man,Chen Run-ji,Gao Fen-fei,Zhang Yan-mei,Niu Yong-dong,Shi Gang-gang
N -n-Butyl haloperidol iodide (F 2 ) is a novel compound that has antiproliferative and antifibrogenic activities. In this study we investigated the therapeutic potential of F 2 against liver fibrosis in mice and the underlying mechanisms. Two widely used mouse models of fibrosis was established in mice by injection of either carbon tetrachloride (CCl 4 ) or thioacetamide (TAA). The mice received F 2 (0.75, 1.5 or 3 mg·kg −1 ·d −1 , ip) for 4 weeks of fibrosis induction. We showed that F 2 administration dose-dependently ameliorated CCl 4 - or TAA-induced liver fibrosis, evidenced by significant decreases in collagen deposition and c-Jun, TGF-β receptor II (TGFBR2), α-smooth muscle actin (α-SMA), and collagen I expression in the liver. In transforming growth factor beta 1 (TGF-β1)-stimulated LX-2 cells (a human hepatic stellate cell line) and primary mouse hepatic stellate cells, treatment with F 2 (0.1, 1, 10 μM) concentration-dependently inhibited the expression of α-SMA, and collagen I. In LX-2 cells, F 2 inhibited TGF-β/Smad signaling through reducing the levels of TGFBR2; pretreatment with LY2109761 (TGF-β signaling inhibitor) or SP600125 (c-Jun signaling inhibitor) markedly inhibited TGF-β1-induced induction of α-SMA and collagen I. Knockdown of c-Jun decreased TGF-β signaling genes, including TGFBR2 levels. We revealed that c-Jun was bound to the TGFBR2 promoter, whereas F 2 suppressed the binding of c-Jun to the TGFBR2 promoter to restrain TGF-β signaling and inhibit α-SMA and collagen I upregulation. In conclusion, the therapeutic benefit of F 2 against liver fibrosis results from inhibition of c-Jun expression to reduce TGFBR2 and concomitant reduction of the responsiveness of hepatic stellate cells to TGF-β1. F 2 may thus be a potentially new effective pharmacotherapy for human liver fibrosis.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Feng Sa,Liu Linyan,Cheng Yuelin,Zhou Mengmeng,Zhu Haoqiang,Zhao Xinyan,Chen Ziyu,Kan Shunli,Fu Xuanhao,Hu Wei,Zhu Rusen
Objective: The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury.Methods: A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation.Results: The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus.Conclusion: Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2021
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IF 0
Shuguang Wang,Kun Shi,Jiawei Lu,Weilian Sun,Qinghui Han,Lingbin Che,Dong Zhang
As a common complication of spine surgery, postoperative epidural fibrosis is an important cause of failed back surgery syndrome (FBSS), yet there is no effective clinical intervention to tackle it. Herein, for the first time, we develop a strategy of combining a gelatin methacryloyl (GelMA) hydrogel matrix with poly(lactic-co-glycolic acid) (PLGA) microsphere-encapsulated resveratrol (RSV), which aims to synergistically promote the inhibition effect on epidural fibrosis. The resultant RSV@PLGA-GelMA (8% w/v) hydrogels possess optimal mechanical properties and prompt the matrix sustainably and stably to release RSV for several weeks. It is further shown that the hybrid hydrogels without the drug exhibit good biosafety without distinct cytotoxicity, while RSV@PLGA-GelMA could prevent fibroblast proliferation and migration. Further rat laminectomy model indicates that the RSV@PLGA-GelMA hydrogels reduce epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overexpression and deposition via a TGF-β/Smad signaling pathway. Consequently, we believe that such a creative structural combination will be a promising strategy for preventing postoperative epidural fibrosis of spine surgery.
研究领域:
生物医学工程
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药学
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神经外科
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产品关联
DOI
PubMed
TOXICON
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2021
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IF 3.033
Xiong Zhang,Chen Feng,Yimao Li,Chenlin Su,Shuxin Zhao,Shengdi Su,Feng Yu,Ji LI
Aristolactam I (AL-I) is the main active ingredient in the Aristolochia plant species, which have been associated with severe nephrotoxicity. In order to investigate the mechanism of AL-I induced renal epithelial-mesenchymal transition (EMT), we established an AL-I induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Biochemical analysis experiment including Morphological examination, 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis were performed. The results showed that AL-I accumulates in the cytosol causing cytotoxicity and inhibition of proliferation in a concentration- and time-dependent manner. Morphological examination showed that with the increasing concentration of AL-I, the tendency of HK-2 cells transform form epithelial cell to fibroblast cells was stronger. In the Western blot analysis, the expression of α-Smooth muscle actin (α-SMA) and Transforming Growth Factor β1 (TGF-β1) were significantly up-regulated, the expression of E-cadherin was significantly down-regulated after administrating. The ratio of the expression of P-Smad2/3 and Smad2/3 was significantly up-regulated, suggested that TGF-β/Smad-dependent signaling pathway was activated in this process. With presence of TGF-β receptor inhibitor (LY364947), we found that the expressions of three EMT related proteins (E-cadherin, α-SMA and TGF-β1) were obviously reversed. In conclusion, we acknowledge that AL-I can induce renal EMT process in HK-2 cell, which is triggered by the activation of TGF-β/Smad-dependent signaling pathway.
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2023
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IF 8.4
Susu Huang,Yuelin Fang,Boguang Yang,Prabhleen Kaur,Yanqing Wang,Jicheng Zhang,Qiaoying Hu,Xiaoye Yang,Yabin Zhang,Guangxi Zhai,Lei Ye
Postoperative adhesions are one of the most common complications post intraperitoneal surgery. Even after the adhesiolysis, the recurrence of adhesions is as high as 85%. Although zwitterionic-based materials have been reported for the application, unlike the conventional zwitterionic hydrogel, a series of poly (sulfobetaine methacrylate) grafted dextran derivatives (Dex-g-PSBMA) were synthesized by atom transfer radical polymerization (ATRP) reaction, making it fined controllable copolymer by its living polymerization property. Intriguingly, the Dex-g-PSBMA copolymer can self-assemble into a physical hydrogel under physiological conditions. When injected at the site of the lesions, it can immediately cover the wound area, and as the ion concentration increases, the chemical bonds dissociate and the hydrogel may degrade completely. In the abdominal wall-cecum injury adhesion model in rats, Dex-g-PSBMA hydrogel showed excellent anti-adhesion ability, effectively preventing postoperative abdominal wall-cecum adhesion. The mechanism exploration revealed that Dex-g-PSBMA hydrogel can take an effect on the TGF-β/Smad signaling pathway, which can inhibit the Smad3 and activate the Smad7 pathway, thereby reducing the probability of tissue fibrosis, reducing fibrin deposition, and resisting fibroblast adhesions. In conclusion, these findings demonstrated that this Dex-g-PSBMA physical hydrogel is a promising candidate for completely preventing post-surgical adhesions.
研究领域:
生物医学工程
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材料科学
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外科研究
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药剂学
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产品关联
DOI
高影响因子
Advanced Fiber Materials
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2025
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IF 21.3
Li Chao,Li Wentao,Deng Ronghui,Huang Lingan,Song Yifan,Wei Xianjie,Xu Bingbing,Cui Guoqing,Chen Zehao,Yu Jiakuo
Excessive interface friction and advanced glycation end products (AGEs) disrupt collagen ordered deposition, promoting scar formation in tendinopathies. Inspired by tendon sheath anatomy, we developed a bionic bilayer nano-membrane via electrospinning and photocrosslinking to initiate the directional and orderly regeneration process of tendon tissue. The lubricating layer (PP), containing phosphatidylserine (PS), reduces frictional stress, while the regenerative layer (GM/GV), composed of gelatin methacrylate (GM) and vanillin-modified gelatin (GV), scavenges ROS and mitigates AGEs-induced collagen disorder deposition. This parallel bilayer structure guides tendon cell alignment and promotes ordered collagen deposition. Additionally, vanillin suppresses the AGEs/TGF-β/Smad pathway, reducing scar formation and tissue adhesion. In vitro/in vivo tests showed a fivefold decrease in coefficient of friction (COF) and a tenfold increase in Achilles tendon function index (AFI) compared to the PCL and normal groups, respectively. The PP@GM/GV membrane, regulated by mechano-biochemical coupling factors, offers a promising strategy for tendinopathy repair, and holds significant potential for clinical translation in guiding functional tendon regeneration and improving patient outcomes. Graphical
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料
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骨科
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Qiuhui Hu,Yongzhao Su,Siying Ma,Peiying Wei,Chengbin He,Di Yang,Yue Qian,Youqing Shen,Xiaoxuan Zhou,Zhuxian Zhou,Hongjie Hu
Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvβ3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-β (TGF-β)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.
研究领域:
纳米技术
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生物医学工程
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药理学
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医学影像
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肝病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2022
·Vol. 27
·期 5
·160
·
IF 3.115
Yuzhu Cao,Keqin Lu,Yawen Xia,Yufei Wang,Aiyun Wang,Yang Zhao
Background: The interactions between platelets and tumor cells are well-known to play important roles in the progression of malignant tumors. Danshensu, a main water-soluble component of Salvia miltiorrhiza, can resist platelet aggregation and exert significant anti-tumor effects on various types of tumors. However, whether Danshensu could inhibit the progression of malignant tumors by suppressing the activities of platelets had not been reported. Methods: The effects of Danshensu on the platelet activity and epithelial-mesenchymal transformation (EMT)-like invasive phenotype of SW620 colon cancer cells were assessed by stimulating with the supernatants from co-cultured platelets and SW620 cells with direct contact (SCP). The expression and secretion of proteins were determined by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin and eosin (H&E) staining was performed to analyzed the histopathology of tumor tissues and immunohistochemical staining was conducted to examine the protein expression in tumors. Results: Co-incubation of SW620 cells with platelets directly or SCP both generated long spindle-shaped invasive phenotype. Pretreatment of platelets with Danshensu (25 μM) inhibited the morphological changes of SW620 cells induced by SCP, which was associated with the inhibitory effects of Danshensu on platelet secretion. Danshensu diminished the secretion of a list of biological factors in SCP, including interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) that are all involved in tumor cell EMT and chemoresistance. Moreover, Danshensu up-regulated the expression of E-cadherin but down-regulated the levels of N-cadherin and Vimentin, resulting in the repression of SW620 cell migration. It was also shown that Danshensu enhanced the sensitivity of SW620 cells to oxaliplatin by suppressing the expression of MDR1. Furthermore, Danshensu could not only reduced the growth of subcutaneous tumors and liver metastasis that induced by SCP, but also down-regulated the expression of MDR1 in vivo. Mechanistic studies revealed that Danshensu suppressed the activation of the TGF-β/Smad signaling pathway. Conclusions: Danshensu attenuated EMT-like characteristics and chemoresistance by inhibiting secretion capability of platelets and activation of the TGF-β/Smad signaling pathway, suggesting that it may be optimized to be a therapeutic agent for fighting against colon cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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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）