GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2022
·Vol. 261
·期 3
·723-734
·
IF 3.535
Zhou Jin,Ding Yuanyuan,Zhang Yongqiang,Zheng Dehui,Yan Lifeng,Guo Mengxiang,Mao Yani,Yang Lihong
Purpose This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. Methods The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. Results BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo , the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. Conclusion BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo . BMSC-Exos may be promising resources for promoting corneal wound healing.
研究领域:
眼科学
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干细胞生物学
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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
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2023
·Vol. 80
·期 8
·1-19
·
IF 8
Dong Yuechao,Ma Guixing,Hou Xiaoting,Han Yingying,Ding Zhen,Tang Wanze,Chen Litong,Chen Yangshan,Zhou Bo,Rao Feng,Lv Kaosheng,Du Changzheng,Cao Huiling
Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy.
研究领域:
分子生物学
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细胞生物学
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发育生物学
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血管生物学
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治疗学
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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
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Zhao Zhang,Si-Yuan Ma,Xin Yin,Yu-Sang Li,He-Bin Tang
Ethnopharmacological relevance The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. Aim of the study To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. Materials and methods The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. Results FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and β-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. Conclusions FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.
研究领域:
药理学
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中医
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伤口愈合
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微循环
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
·
IF 16.744
Tongchuan Wang,Shuang Liu,Wei Wang,Zhenzhen Shu,Zhaohui Luan,Yu Huang,Qiang Luo,Shiming Yang,Malcolm Xing,Chaoqiang Fan
An anal fistula caused by a perianal abscess is a hollow tubular structure connecting anal canal with skin and often in irregular shapes. The surgical treatment causes damage to the surrounding tissues and results in complications. Current filling plugs in the clinic, derived from the porcine small intestinal submucosa, only seal the opening and cannot fill into the irregular fistula passage due to the poor liquidity, and fails to control the high-frequent infections around fistulas. Injecting gel-like material is a direct and effective way. To this end, we reported injectable microgels from elastic cryogels of biodegradable disulfide-based crosslinking. Microgels with shear-thinning and self-healing remain solid under low strain and fluid under high strain to ensure successful filling and repair the multiple-branched irregular canals. Nano-silver dopped microgels presented antibacterial efficacy . In rabbit models of anal and muscle fistula, the inflammatory cells significantly decreased. CD31 and α-smooth muscle actin (α-SMA) showed the fistula healing was improved considerably. These findings demonstrated that self-healable microgels have enormous potential to repair the abnormal and complicated tubular passages caused by ulcers and fistulas.
研究领域:
生物材料
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组织工程
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外科治疗
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感染性疾病
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
·
IF 8.025
Yongchao Jiang,Haonan Wang,Xiaofeng Wang,Qian Li
Surface modifications are common approaches to promote endothelialization and resist thrombus, therefore obtaining long-term patency of vascular grafts. Herein, we developed a functional coating based on hyaluronic acid (HA), dopamine (DA), and heparin. In the present study, dopamine was firstly grafted to the HA molecules. The DA-grafted HA material was then applied to the surface of fibrous PCL scaffold via oxidation polymerization. Heparin was directly loaded during the coating, instead of grafting. The composite coating enhanced the surface hydrophilicity of PCL scaffold, as well as the mechanical properties. Notably, the coated scaffold could promote EC proliferation and angiogenesis behavior via the upregulation of CD31 gene expression regardless of heparin addition. It also showed more effective inhibition of platelet adhesion and blood clotting in vitro. These results lead us to the conclusion that this functional coating is great potential in treating cardiovascular diseases in terms of promoting endothelialization, reducing thrombus, and maintaining the long-term patency of vascular grafts.
研究领域:
生物材料
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组织工程
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血管移植物
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生物医学工程
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心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2022
·Vol. 65
·期 4
·612-623
·
IF 2.86
Han Ning,Zhang Lihong,Guo Mi,Yu Li
Advanced proliferative diabetic retinopathy (PDR) characterized by aberrant retinal angiogenesis is a leading cause of retinal detachment and blindness. Krüppel-like factor 9 (KLF9), a member of the zinc-finger family of transcription factors, participates in the development of diabetic nephropathy and the promotion of angiogenesis of human umbilical vein endothelial cells. Therefore, we speculate that KLF9 may exert a crucial role in PDR. The current study revealed that KLF9 was highly expressed in the high glucose (HG)-treated human retinal microvascular endothelial cells (HRMECs) and the retinas of oxygen-induced retinopathy (OIR) rats. Knockdown of KLF9 inhibited the proliferation, migratory capability, invasiveness and tube formation of HG-treated HRMECs. Besides, knockdown of KLF9 decreased the expression of yes-associated protein 1 (YAP1) in HG-treated HRMECs. Dual-luciferase reporter assays confirmed that KLF9 transcriptionally upregulated YAP1 expression. Overexpression of YAP1 reversed the KLF9 silencing-induced repression of HRMEC proliferation and tube formation. Further in vivo evidence demonstrated that knockdown of KLF9 reduced the expression of Ki67, CD31 and vascular endothelial growth factor A (VEGFA) in the retinas of OIR rats. Collectively, KLF9 silencing might mitigate the progression of PDR by inhibiting angiogenesis via blocking YAP1 transcription.
研究领域:
糖尿病
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视网膜
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分子生物学
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细胞生物学
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转录因子
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血管生成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2024
·
IF 1.9
Lin Shuai,Cai Hui,Song Xuemei
The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2022
·
IF 0
Liwen Deng,Huidan Lu,Chenxi Tu,Tong Zhou,Wangbei Cao,Changyou Gao
Bacterial infection is a major obstacle to the wound healing process. The hydrogel dressings with a simpler structure and good antibacterial and wound healing performance are appealing for clinical application. Herein, a robust hydrogel was synthesized from acrylamide (AM), acrylic acid (AA) and N , N ′-methylene diacrylamide (MBA) via a redox initiating polymerization. The polymerization conditions were optimized to obtain the hydrogel with minimum unreacted monomers, which were 0.25% and 0.12% for AM and AA, respectively. The hydrogel had good mechanical strength, and could effectively resist damage by external forces and maintain a good macroscopic shape. It showed large water uptake capacity, and could post load a wide range of molecules via hydrogen bonding and electrostatic interaction. Loading of antibiotic doxycycline (DOX) enabled the hydrogel with good antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria in vitro and in vivo . In a rat model of methicillin-resistant Staphylococcus aureus ( MRSA )-infected full-thickness skin defect wound, the DOX-loaded hydrogel showed good therapeutic effect. It could significantly promote the wound closure, increased the collagen coverage area, down-regulate the expressions of pro-inflammatory TNF-α and IL-1β factors, and up-regulate the expressions of anti-inflammatory IL-4 factor and CD31 neovascularization factor.
研究领域:
生物医学工程
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药剂学
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材料科学
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伤口愈合
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抗菌治疗
✓ 已验证
DOI
PubMed
Materials Today Bio
·
2024
·
IF 8.7
Siwen Chen,Yutong Li,Sihang Ren,Yuanyuan Yang,Zhipeng Hou,Siyu Han,Wanhong Zhang,Jing Guo,Jianshe Hu,Xing Zhang,Liqun Yang
Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn 2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.
研究领域:
材料科学
·
生物材料
·
组织工程
·
伤口愈合
✓ 已验证
DOI
高影响因子
Biomed Research International
·
2022
·
IF 3.246
Yan Xu,Mingwei Cheng,Peijun Zhu,Shuo Yang,Chunhua Lai,Shulan Xu
During bone tissue regeneration, neovascularization is critical, and the formation of a blood supply network is crucial for bone growth stimulation and remodeling. Previous studies suggest that bioelectric signals facilitate the process of angiogenesis. Owing to their biomimetic electroactivity, piezoelectric membranes have garnered substantial interest in the field of guided bone regeneration. Nevertheless, the knowledge of their influence due to varying surface potentials on the progression of angiogenesis remains ambiguous. Therefore, we proposed the preparation of an electroactive material, P(VDF-TrFE), and investigated its effects on the activity and angiogenic functions of human umbilical vein endothelial cells (HUVECs). The HUVECs were directly cultured on P(VDF-TrFE) membranes with different surface potentials. Subsequently, cell viability, proliferation, migration, tube formation, and expressions of related factors were assessed through appropriate assays. Our results revealed that the negative surface potential groups exerted differential effects on the modulation of angiogenesis in vitro. The P(VDF-TrFE) membranes with negative surface potential exhibited the greatest effect on cellular behaviors, including proliferation, migration, tube formation, and promotion of angiogenesis by releasing key factors such as VEGF-A and CD31. Overall, these results indicated that the surface potential of piezoelectric P(VDF-TrFE) membranes could exert differential effects on angiogenesis in vitro. We present a novel approach for designing bioactive materials for guided bone regeneration.
研究领域:
生物材料
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组织工程
·
再生医学
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细胞生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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