ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Jin Cui,Gongzheng Wang,Li Xian Yip,Mengzhen Dong,Mengyao Mu,Liya Tian,Yuan Gao,Qing Fan,Qiang Zhu,Xinya Zhao,Xueli Xu,David Tai Leong,Xiao Sun
Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin-manganese interaction by nanoplatinum growth, a novel ferritin-platinum-manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree-dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram-based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase-like activity can catalyze the generation of O 2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF-1α, blocking the TGF-β1/Smad signaling pathway. In addition, metformin shows synergy with HIF-1α reduction in blocking the TGF-β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real-time anti-fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti-fibrotic therapy with real-time monitoring.
研究领域:
医学影像
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纳米技术
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药理学
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分子生物学
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治疗学
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
·
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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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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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
MATERIALS & DESIGN
·
2024
·
IF 7.6
Pei Gong,Lulu Ren,Xinghui Gao,Jie Long,Weidong Tian,Min He
Local oxidative stress induced by surgical trauma has been recognized as one of pathogenesis for postsurgical adhesion tissue formation. Herein, tannic acid (TA) based metal-phenolic networks (MPNs) was assembled via chelating with Fe 3+ , and acted as a novel bio-filler for nanofibrous polycaprolactone (PCL) barrier membrane to endow it with reactive oxygen species (ROS) scavenging capacity. By chelating with Fe 3+ , the release of TA could last for more than 20 days, rendering the membrane with continuous ROS scavenging capacity. The modified membrane could effectively inhibit fibroblasts adhesion and proliferation, as well as immune cells recruitment, infiltration, and expression of pro-inflammatory cytokines. Consequently, a complete prevention of peritoneal adhesion formation was obtained in a rat model of sidewall defect-cecum abrasion, far better than commercial Poly lactic acid (PLA) membrane. Systematic biological mechanism investigations revealed that the enhanced anti-adhesion function was mainly ascribed to its robust ROS scavenging capacity, through which the PI3K-Akt signaling pathway was blocked, leading to repress of downstream NF-κB-TGFβ1-SMAD signaling pathway, finally inhibiting the bioactivity of fibroblasts and immune cells. This work provided a new strategy for the design of advanced barrier membrane, demonstrated its efficacy and mechanism on preventing postoperative adhesion, holding great promise for future clinical application.
研究领域:
生物医学工程
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材料科学
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外科手术
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药理学
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产品关联
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
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2021
·Vol. 43
·期 1
·133-145
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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
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2024
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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
·
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
ADVANCED MATERIALS
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2024
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IF 27.4
Chenchen Li,Xiyang Tan,Dashi Deng,Chenfan Kong,Lida Feng,Weijing Wang,Kaida Lin,Yuqing Li,Qifang Lei,Lisha Liu,Tao Tao,Ruile Pan,Guangzhi Li,Song Wu
Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1β and Wnt-β catenin-TGFβ-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.
研究领域:
生殖医学
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药理学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICON
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2021
·
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
·
2023
·
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
ESC Heart Failure
·
2023
·
IF 3.8
Yu Li,Qian He,Chao-Yong He,Chao Cai,Zhen Chen,Jing-Zhu Duan
Aims Diabetic cardiomyopathy (DC) is one of serious complications of diabetic patients. This study investigated the biological function of activating transcription factor 4 (ATF4) in DC. Methods and results Streptozotocin-treated mice and high glucose (HG)-exposed HL-1 cells were used as the in vivo and in vitro models of DC. Myocardial infarction (MI) was induced by left coronary artery ligation in mice. Cardiac functional parameters were detected by echocardiography. Target molecule expression was determined by real time quantitative PCR and western blotting. Cardiac fibrosis was observed by haematoxylin and eosin and Masson's staining. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling. Activities of superoxide dismutase, glutathione peroxidase, and levels of malonic dialdehyde and reactive oxygen species were used to assess oxidative stress damage. Molecular mechanisms were evaluated by chromatin immunoprecipitation, dual luciferase assay, and co-immunoprecipitation. ATF4 was up-regulated in the DC and MI mice ( P < 0.01). Down-regulation of ATF4 improved cardiac function as evidenced by changes in cardiac functional parameters ( P < 0.01), inhibited myocardial collagen I ( P < 0.001) and collagen III ( P < 0.001) expression, apoptosis ( P < 0.001), and oxidative stress ( P < 0.001) in diabetic mice. Collagen I ( P < 0.01) and collagen III ( P < 0.01) expression was increased in MI mice, which was reversed by ATF4 silencing ( P < 0.05). ATF4 depletion enhanced viability ( P < 0.01), repressed apoptosis ( P < 0.001), oxidative damage ( P < 0.001), and collagen I ( P < 0.001), and collagen III ( P < 0.001) expression of HG-stimulated HL-1 cells. ATF4 transcriptionally activated Smad ubiquitin regulatory factor 2 (Smurf2, P < 0.001) to promote ubiquitination and degradation of homeodomain interacting protein kinase-2 ( P < 0.001) and subsequently caused inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway ( P < 0.001). The inhibitory effects of ATF4 silencing on HG-induced apoptosis ( P < 0.01), oxidative injury ( P < 0.01), collagen I ( P < 0.001), and collagen III ( P < 0.001) expression were reversed by Smurf2 overexpression. Conclusions ATF4 facilitates diabetic cardiac fibrosis and oxidative stress by promoting Smurf2-mediated ubiquitination and degradation of homeodomain interacting protein kinase-2 and then inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway, suggesting ATF4 as a treatment target for DC.
研究领域:
分子生物学
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心脏病学
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糖尿病
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病理生理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hewei Wei,Ting Zhao,Xinglong Liu,Qiteng Ding,Shuai Zhang,Jiali Yang,Ning Wang,Lifeng Zhang,Guodong Chai,Guofeng Xia,Anning Li,Chuanbo Ding,Wencong Liu
To solve the difficulty of natural healing in patients with severe bone defects, and the challenges of insufficient autologous bone graft material and large incisions in conventional surgery, we were designed an intelligent co-regulated hydrogel system with NIR response. The goal is to be able to prevent inflammation and bacterial adhesion, thereby promoting repair and development of the bone defect area. The hydrogel system consisted of hyaluronic acid, carboxymethyl chitosan and Pht-loaded PDA-encapsulated ZIF-8 NPs (Pht@ZIF-8@PDA) by Schiff base reaction. Compared to high-temperature photothermal therapy (PTT), which destroyed surrounding healthy cells, the present study was based on a new strategy of mild photothermal therapy (42.5 ± 1.2 °C) and leaded to a better promotion of osteogenesis. NIR activated the photothermal properties of PDA in scaffolds, intelligently released Pht and Zn 2+ , inhibited Escherichia coli and Staphylococcus aureus (inhibition rate ≥ 96 %), and promoted bone regeneration in the rat model. Meanwhile, it could promote bone regeneration by upregulating osteogenic factors and stimulating the expression of proteins related to BMP/SMAD signaling pathway. The research highlights the potential applications of synergistically modulated hydrogels, which opens up a new application path for this material in bone tissue engineering, regenerative medicine, and other related fields.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
材料科学
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药学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）