JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Fanxing Xu,Jingxian Wu,Yumei Hu,Chun Chu,Wenjun Liu,Xiang Li,Wen Zheng,Weishuo Yang,Boyan Zhao,Jiangxue Guo,Zhenzhong Wang,Ying Jia,Wei Xiao
Ethnopharmacological relevance Tongsaimai (TSM) is a traditional Chinese medicine that has several therapeutic qualities, including anti-inflammatory, anti-oxidative, and anti-vasculitis effects. However, its impacts and underlying mechanisms on wound healing remain unclear. Aim of the study The aim of our study was to evaluate TSM for its pro-healing effect and the relevant mechanisms using both experimental validation and network pharmacology analysis. Materials and methods The components of TSM were detected by high-performance liquid chromatography combined with diode array detector (HPLC-DAD). Skin wounds with a diameter of 4 mm were created on the backs of mice, after which, topical treatments of 2.5–10% TSM were applied onto the lesions once daily for either 2 or 7 days. Then, the wound tissues were collected to determine the impacts of TSM on collagen deposition, epithelial cell proliferation , oxidative stress, inflammation, and angiogenesis. Moreover, the effects of TSM (0.5–2 mg/mL) on the cell viability of HUVECs and HaCaT cells were evaluated. Results A total of 11 components in TSM were identified by HPLC-DAD. TSM was found to enhance the rate of wound contraction and increase epithelial thickness and collagen deposition during the healing process. In addition, TSM increased SOD activity and downregulated MDA and IL-1β levels in the wound tissues. Immunofluorescence analysis further indicated an increased expression of Ki67, CD31, and VEGF in wound tissues following TSM administration. Results of the network pharmacology analysis revealed that multiple pathways including VEGF, PI3K/Akt, and MAPK pathways were involved in the pharmacological actions of TSM on wound healing. Accordantly, in vitro experiments revealed that TSM promoted the proliferation of HUVECs and HaCaT cells while activating the PI3K/Akt pathway. Conclusions Our results suggest that TSM may serve as a therapeutic medication to improve wound healing by employing multiple regulatory mechanisms that affect proliferation, angiogenesis, collagen deposition, oxidative stress, and inflammation.
研究领域:
药理学
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民族药理学
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传统中药
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伤口愈合
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Qiteng Ding,Chuanbo Ding,Xinglong Liu,Yinan Zheng,Yingchun Zhao,Shuai Zhang,Shuwen Sun,Zanwen Peng,Wencong Liu
In this study, a new wound dressing was developed to speed up the healing process of diabetic wounds. First of all, taxifolin liposome (TL) was manufactured in this study. Then, taxifolin (TAX) and TL were mixed with polyvinyl alcohol (PVA) and chitosan (CS) by electrostatic spinning to prepare nanocomposite membranes. Finally, the mechanism of nanocomposite membranes to accelerate diabetic wound healing was investigated. The diameter of TL-loaded polyvinyl alcohol/chitosan nanocomposite membranes (PVA/CS/TL) was 429.43 ± 78.07 nm. The results of in vitro experiments demonstrated that the PVA/CS/TL had better water absorption, water vapor transmission rate (WVTR), porosity, hydrophilicity, mechanical properties, slow-release, antioxidant capacity, and antibacterial properties. The results of in vivo experiments demonstrated that the wound healing rate of mice treated with PVA/CS/TL for eighteen days was 98.39 ± 0.34 %. Histopathological staining, immunohistochemical staining, and western blot experiments also demonstrated that PVA/CS/TL could promote wound healing in diabetic mice by inhibiting the activation of inhibitor kappa B alpha (IκBα)/nuclear factor-kappa B (NF-κB) signaling pathway and related pro-inflammatory factors to increase the expression of CD31 and VEGF in skin tissues. These results suggested that PVA/CS/TL could be a potential candidate for wound dressing to promote chronic skin wound healing.
研究领域:
材料科学
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药学
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生物医学工程
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糖尿病研究
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Photodiagnosis and Photodynamic Therapy
·
2020
·
IF 2.894
Tongtong Zhang,Jianwei Bao,Mengmeng Zhang,Yuanyuan Ge,Jianming Wei,Yu Li,Weixia Wang,Miao Li,Yiguang Jin
Lung cancer is a severe disease with high mortality. Chemotherapy is one major treatment for lung cancer. However, systemic chemotherapeutics usually distribute throughout the body without specific lung distribution so that serious side effects are unavoidable. Photodynamic therapy (PDT) is occasionally used for lung cancer treatment but photosensitizers are also systemically administered and the bronchoscopic intervention under anesthesia may hurt lung tissues. Here, we combined inhaled chemotherapeutics and photosensitizers for chemo-photodynamic therapy (CPDT) of primary lung cancer of rats with external laser light irradiation. Gefitinib PLGA nanoparticles (GNPs) were prepared. The anti-cancer effects of GNPs and/or a common photosensitizer 5-aminolevulinic acid (5-ALA) were explored on A549 cells (adenocarcinomic human alveolar basal epithelial cells) and primary lung cancer rats after intratracheal administration. External light irradiation was applied due to its higher safety compared to internal light irradiation that may result in injuries after a laser optic fiber was intubated into the lung. The remarkable synergistic effect of CPDT was confirmed although the single therapies were also effective, where the high anti-lung cancer effects were shown and some typical lung cancer markers, including CD31, VEGF, NF-κB p65 and Bcl-2, significantly decreased. Moreover, the treatments attenuated inflammation with the downregulation of TNF-α. The combination of pulmonary drug delivery and chemo-photodynamic therapy is a promising strategy for treatment of lung cancer.
研究领域:
肿瘤学
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药学
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生物医学工程
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Pan Yongting,Mai Li,He Wenkai,Yang Xuqi,Wu Enting,Zhao Jiayuan,Liu Bailiang,Li Mingyan
Introduction: Peripheral artery disease (PAD) is an increasingly common disease, causing significant complications for patients. Trimetazidine (TMZ) not only improves clinical symptoms in PAD patients but also facilitates angiogenesis in ischemic hind limbs. Our aim was to find the function of TMZ in promoting angiogenesis and tissue perfusion in ischemic rat skeletal muscle.Methods: The rats underwent femoral artery ligation (FAL) and then treated with TMZ and saline. Hematoxylin-eosin and Masson’s trichrome stain in the ischemic gastrocnemius muscle to analyze muscle morphology and atrophy. To identify angiogenesis and the tissue perfusion, CD31 immunohistochemical staining and laser speckle contrast imaging was conducted. Additionally, hind limb motor ability was measured. Finally, qRT-PCR and Western blotting were used to statistically analyze the expression levels of HIF-1α and VEGF.Results: Our study demonstrated significant enhancement in angiogenesis and tissue perfusion after FAL when treated with TMZ compared to the saline group. Histologically, it mitigates ischemia-induced muscle atrophy and inflammation, as well as reduces fibrosis progression in the TMZ group. Additionally, hind limb motor ability improved in rats treated with TMZ during motor experiments.Discussion: It suggests that TMZ can promote angiogenesis and improve tissue perfusion in ischemic skeletal muscle of rats by activating the HIF-1α/VEGF signaling pathway. Additionally, it leads to significant improvement in ischemia-induced motor limitations in the hind limbs of rats.
研究领域:
药理学
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心血管疾病
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肌肉骨骼系统
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分子生物学
✓ 已验证
DOI
高影响因子
Advanced Materials Interfaces
·
2023
·
IF 5.4
Weixing Wang,Yifeng Yu,Hao Zhang,Zhiwei Wang,Honglian Dai,Aixi Yu
To solve the problem of tendon adhesion after an operation, an anti-adhesion membrane is designed, which can inhibit the exogenous healing of tendons and promote endogenous healing. Here, poly[3(S)-methyl-morpholine-2,5-dione- co -lactic acid] P(MMD- co -LA) containing alanine units is obtained by melt ring-opening polymerization (ROP). It can effectively reduce the production of acidic degradation products that cause aseptic inflammation. Then a kind of oriented P(MMD- co -LA)/deferoxamine (DFO) anti-adhesion membrane with good mechanical properties, cell adhesion properties, and induced macrophage polarization properties is constructed by electrospinning. In vitro and in vivo studies have shown that oriented fibrous membranes can down-regulate the expression of inflammatory cytokines. In addition, the fibrous membrane can up-regulate the expression of angiogenesis-related genes, namely HIF1-α, SDF-1α, and VEGF, by releasing DFO in situ, thus promoting the revascularization of tendon defects and providing nutritional support for endogenous tendon healing. This method provides a new barrier strategy to reduce tendon adhesion through anti-inflammation combined with vascularization to inhibit exogenous tendon healing while promoting tendon endogenous healing. The results provide essential insights into the corresponding regulation of the tendon healing microenvironment.
研究领域:
生物医学工程
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组织工程
·
材料科学
·
再生医学
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Chuanxin Zhong,Shan He,Yuhong Huang,Jianfeng Yan,Junqin Wang,Wentao Liu,Ju Fang,Fuzeng Ren
Clustered regularly interspaced short palindromic repeat activation (CRISPRa) technology has emerged as a precise genome editing tool for activating endogenous transgene expression. While it holds promise for precise cell modification, its translation into tissue engineering has been hampered by biosafety concerns and suboptimal delivery methods. To address these challenges, we have developed a CRISPRa non-viral gene delivery platform by immobilizing non-viral CRISPRa complexes into a biocompatible hydrogel/nanofiber (Gel/NF) composite scaffold. The Gel/NF scaffold facilitates the controlled and sustained release of CRISPRa complexes and also promotes cell recruitment to the scaffold for efficient and localized transfection. As a proof of concept, we employed this CRISPRa delivery platform to activate the vascular endothelial growth factor (VEGF) gene in a rat model with full-thickness skin defects. Our results demonstrate sustained upregulation of VEGF expression even at 21 days post-implantation, resulting in enhanced angiogenesis and improved skin regeneration. These findings underscore the potential of the Gel/NF scaffold-based CRISPRa delivery platform as an efficient and durable strategy for gene activation, offering promising prospects for tissue regeneration. Statement of significance Translation of clustered regularly interspaced short palindromic repeat activation (CRISPRa) therapy to tissue engineering is limited by biosafety concerns and unsatisfactory delivery strategy. To solve this issue, we have developed a CRISPRa non-viral gene delivery platform by immobilizing non-viral CRISPRa complexes into a biocompatible hydrogel/nanofiber (Gel/NF) composite scaffold. This scaffold enables controlled and sustained release of CRISPRa and can induce cell recruitment for localized transfection. As a proof of concept, we activated vascular endothelial growth factor (VEGF) in a rat model with full-thickness skin defects, leading to sustained upregulation of VEGF expression, enhanced angiogenesis and improved skin regeneration in vivo . These findings demonstrate the potential of this platform for gene activation, thereby offering promising prospects for tissue regeneration.
研究领域:
生物技术
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组织工程
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基因治疗
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2023
·
IF 3.9
Yan Nan,Wang Zhengdong,Li Zhou,Zheng Yang,Chang Nan,Xu Kangjie,Wang Qian,Duan Xiaoxu
This study aimed to examine the immuntoxic effects of arsenic in the nervous system. Our results showed that arsenic increased corticocerebral and hippocampal weights ( p < 0.05). Morris water maze tests revealed that arsenic significantly increased the time spent in latency to platform on the fourth day in 50 mg/L arsenic exposure and the fifth day in 25 and 50 mg/L arsenic exposure, as well as reduced the path length in target quadrant, time spent in target quadrant, and crossing times of the platform ( p < 0.05). Hematoxylin–eosin staining showed that the vacuolated degeneration and pyknosis was found in the cerebral cortex and hippocampus of arsenic-treated mice. The mRNA levels of corticocerebral and hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were decreased in the 50 mg/L arsenic-treated group ( p < 0.05). In addition, immunofluorescence staining showed that 25 and 50 mg/L arsenic all increased the expression of CD11b and glial fibrillary acidic protein (GFAP) in the cerebral cortex and hippocampus ( p < 0.05). Arsenic markedly raised antigen-presenting molecule MHCII and CD40 mRNA levels in the cerebral cortex and hippocampus and upregulated the cell chemokine receptor 5 (CCR5) and CCR7 mRNA levels in the cerebral cortex at the 50 mg/L arsenic group, and increased the CCR7 mRNA levels in the hippocampus at the 25 and 50 mg/L arsenic groups ( p < 0.05). Arsenic activated the nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome, and enhanced its upstream promoter NF-κB protein level and downstream regulators IL-18 mRNA levels. Collectively, these results provide new evidences for the neuro-immune toxicity of arsenic. Graphical abstract
研究领域:
神经毒理学
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免疫毒理学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
An Shao,Lulu Jin,Yanni Ge,Ziqiang Ye,Mingyu Xu,Yifan Zhou,Yingyu Li,Linyan Wang,Pinglong Xu,Kai Jin,Zhengwei Mao,Juan Ye
Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated “eat me” signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.
研究领域:
眼科学
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纳米技术
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免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Kuo Zhang,Hui Zhang,Yong-Hong Gao,Jia-Qi Wang,Yuan Li,Hui Cao,Ying Hu,Lei Wang
The overexpression of growth factors and receptors on neovascular endothelial cells (ECs) and their binding may promote the abnormal growth of new blood vessels, leading to corneal neovascularization (CNV). Normally, monoclonal antibodies may bind and block only one growth factor or receptor, such as bevacizumab binding and blocking vascular endothelial growth factor (VEGF). Herein, we develop a monotargeting peptidic network antibody (pepnetibody) that blocks multiple receptors on the membrane of ECs through forming a fibrous network and ultimately achieves high-efficient treatment of CNV. The pepnetibody could bind to integrin αvβ3 in particulate formulation and in situ fibrillogenesis on ECs, mimicking the process of fibronectin fibrillogenesis on the cell membrane. The in situ formed peptidic network could firmly block integrin and cover other angiogenesis-related receptors, such as VEGF receptor-2 and neuropilin-1, exhibiting competitive efficacy of antiangiogenesis compared with traditional monoclonal antibody bevacizumab with 97.7 times lower dose.
研究领域:
药理学
·
分子生物学
·
眼科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Hao Chang,He Zhang,Mi Hu,Jia-yan Chen,Bo-chao Li,Ke-feng Ren,M.Cristina L. Martins,Mário A. Barbosa,Jian Ji
Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly( l -lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.
研究领域:
生物材料
·
组织工程
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jintao Zhong,Wenhua Li,Hetong Li,Jin Zhang,Zuoxu Hou,Xiao Wang,Enhui Zhou,Ke Lu,Weida Zhuang,Hongxun Sang
The periosteum, a highly specialized thin tissue, is instrumental in contributing to as much as 70% of early bone formation. Recognizing the periosteum's vital physiological roles, the fabrication of a biomimetic periosteum has risen as an auspicious strategy for addressing extensive bone defects. In the study, we obtained such biomimetic periosteum by utilizing periosteum-derived stem cells (PDSCs) spheroids. These spheroids are induced to spontaneously generate a bioactive membrane on a delicate 3D-printed polycaprolactone (PCL) substrate. This process yields a biomimetic periosteum rich in the resources needed for bone repair. The in vitro evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The release kinetics confirmed a sustained delivery of BMP-2 and VEGF, which promoted enhanced osteogenesis and angiogenesis in vitro , respectively. The in vivo results further highlighted robust bone regeneration from critical cranial defects upon the application of this biomimetic periosteum. The biomimetic periosteum, easily harvested and potent in bioactivity, presents substantial clinical potential, particularly for the treatment of critical-sized bone defects. Statement of Significance PDSC theoretically demonstrates substantial potential in membrane construction, a value we've harnessed in this pioneering application. By employing cell spheroids, we've successfully integrated a substantial number of cells into the membrane framework. PDSC spheroids exhibit the remarkable ability to self-assemble into functional membranes, endowing them with robust biological capabilities that enhance their performance in biological systems. The in vitro evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The in vivo bone repair facilitated by this membrane is notably effective, characterized by superior bone quality and accelerated formation rates. This process mirrors the natural intramembrane ossification, offering a promising approach to bone integration and regeneration.
研究领域:
组织工程
·
再生医学
·
骨生物学
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干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 22
·2201155
·
IF 17.521
Xiaocheng Wang,Yunru Yu,Chaoyu Yang,Luoran Shang,Yuanjin Zhao,Xian Shen
Biological scaffolds hold promising perspectives for random skin flap regeneration, while the practical application is greatly limited by their insufficient vascularization ability and the lack of responsiveness during the dynamical healing process. Herein, a novel MXene-incorporated hollow fibrous (MX-HF) scaffold with dynamically responsive channels is presented for promoting vascularization and skin flap regeneration by using a microfluidic-assisted 3D printing strategy. Benefiting from the photothermal conversion capacity of the MXene nanosheets and temperature-responsive ability of poly(NIPAM) hydrogels in the MX-HF scaffolds, they display a near-infrared (NIR)-responsive shrinkage/swelling behavior, which facilitates the cell penetration into the scaffold channels from the surrounding environment. Moreover, by incorporating vascular endothelial growth factor (VEGF) into the hydrogel matrix for controllable delivery, the MX-HF scaffolds can achieve promoted proliferation, migration, and proangiogenic effects of endothelial cells under NIR irradiation. It is further demonstrated in vivo that the NIR-responsive VEGF@MX-HF scaffolds can effectively improve skin flap survival by promoting angiogenesis, decreasing inflammation, and attenuating apoptosis in skin flaps. Thus, it is believed that such responsive MX-HF scaffolds are promising candidates for clinical random skin flap regeneration as well as other diverse tissue engineering applications.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
材料科学
·
生物材料
✓ 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）