BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Yang Ding,Shengyun Wan,Long Ma,Kaikai Wei,Kun Ye
Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 10 9 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis . PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O 2 ) for 24 h. The percentage of pro-inflammatory CD86 + macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.
研究领域:
心脏病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cutaneous and Ocular Toxicology
·
2025
·
IF 1.3
Fuqin He,Yongjun Liu,Ruiying Yu,Tianli Zhang,Fang Guo,Xiayu Wu,Yi Fan,Xuedong Zhu,Qianyi Zhou,Dan Shu
Objective Wound repair remains a significant challenge in the field of regenerative medicine. Notably, while numerous studies have investigated the effects of isolated nicotine or chlorogenic acid, the systematic evaluation of tobacco ethanol extract (TEE) on cutaneous wound healing has remained uncharted territory. Therefore, this study aims to systematically explore TEE’s multifaceted effect on wound healing.Methods The hepatorenal toxicity of 5% TEE was evaluated in 6-7-week-old ICR mice. Subsequently, full-thickness 6 mm wounds were created, and images were captured on days 0, 3, 6, 9, and 12. Tissues were collected for H&E staining, Masson trichrome staining, and immunohistochemistry to assess wound healing.Results The TEE we prepared showed little hepatorenal toxicity (p > 0.05). By day 12, the wound closure rate in the TEE group reached 95.26%, significantly higher than that in the vehicle group (89.20%, p < 0.05). Histopathological analysis demonstrated that TEE reduced neutrophil infiltration in the wound tissues, accelerated granulation tissue formation, and increased collagen content by 20.99% compared to the vehicle group (p < 0.05). Immunohistochemical staining revealed that on day 6, the positive areas of IL-6 and TNF-α in the TEE group were 5.91% and 4.87% lower than those in the vehicle group (p < 0.05), respectively. On day 9, CD31 expression in the TEE group (8.58%) was significantly higher than that in the vehicle group (5.54%) (p < 0.05).Conclusion This study reveals that TEE accelerates wound healing, providing new insights into effective topical therapies for skin wounds while highlighting the potential for tobacco waste valorization.
研究领域:
再生医学
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药理学
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皮肤生物学
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炎症生物学
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血管生物学
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天然产物药学
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创伤修复
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTEGRATIVE CANCER THERAPIES
·
2019
·
IF 2.634
Decai Tang,Shuo Zhang,Xiaoxia Shi,Jiafei Wu,Gang Yin,Xiying Tan,Fuyan Liu,Xingdong Wu,Xiangyu Du
Normalizing the disordered tumor vasculature, rather than blocking it, is a novel method for anticancer therapy. Astragali polysaccharide (APS) and curcumin were reported to be active against carcinomas. However, the effect and mechanism of the combination of APS and curcumin on vascular normalization in hepatocellular carcinoma (HCC) was not clear. In the present study, effects of combined APS and curcumin on tumor vascular normalization were evaluated in HepG2 tumor-bearing mice. Photoacoustic tomography (PAT) was performed to observe the morphological structure of tumor vessels in vivo. The microstructure of the tumor vessels was also analyzed through scanning electron microscopy. Additionally, the expression of CD31 and NG2 was analyzed by immunohistochemical staining. Tumor vessels of HepG2 tumor-bearing mice treated with the combination were sparse with uniform growth, morphology rules, and complete vascular walls, which had fewer branches and sprouts. ECs of tumor vessels were arranged regularly and were tightly connected, tending toward normalization. The expression of CD31 was reduced while NG2 was increased significantly by the combination of APS and curcumin. The results indicated that APS and curcumin in combination showed a better effect on inhibiting tumor growth in an orthotopic nude-mouse model of HCC. More important, the combination induced normalization of tumor vascular better than APS or curcumin administration alone, improving the morphological structure of tumor vessels and promoting maturation of tumor vessels. The results of the present study provided a reasonable possibility for combination therapy of APS and curcumin in the treatment of HCC via tumor vascular normalization.
研究领域:
肿瘤学
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药理学
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分子生物学
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成像技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
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IF 3.457
Jian Yin,Ge Gong,Chao Sun,Zhaoyang Yin,Chao Zhu,Bin Wang,Qin Hu,Yuerong Zhu,Xinhui Liu
Angiogenesis plays a key role in the repair of large segmental bone defects with tissue-engineered bones. However, there is no effective method of promoting angiogenesis in tissue-engineered bone. Both angiopoietin 2 (Ang2) and autophagy have been shown to be involved in angiogenesis, but their roles in angiogenesis of tissue-engineered bone remains unknown. In this in vivo study, a radius bone defect was created in New Zealand white rabbits, which were then treated by implantation of a hydroxyapatite/collagen scaffold followed by injection of different concentrations of Ang2. Expression of the autophagic modulators microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and SQSTM1/P62 were measured via western blotting, while the angiogenic modulators VEGF and CD31 were detected by western blotting and immunohistochemistry, respectively. X-ray imaging combined with general observation was used to evaluate bone defect healing. Expression of LC3 -I/LC3-II, Beclin-1, VEGF, and CD31 in the callus area increased and SQSTM1/p62 decreased in a dose-dependent manner with increasing Ang2 concentration. In the group treated with a high concentration of Ang2, the new callus grew well, accompanied by remarkable angiogenesis, leading to good repair of the bone defects. However, in the low concentration of Ang2 group, in spite of the existence of angiogenesis and new bone formation, the bone defects were not repaired. Furthermore, angiogenesis and osteogenesis were both obstructed in the control group. In conclusion, our study demonstrated that a high concentration of Ang2 promoted angiogenesis in tissue-engineered bone and improved repair of bone defects by inducing autophagy.
研究领域:
生物医学工程
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组织工程
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骨科
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2023
·
IF 3.3
He Dongjie,Song Yanli,Xiao Huidongzi,Shi Shaoqi,Song Hongyan,Cui Tianwei,Ni Tingting,Wang Jing,Ren Xingxing,Wei Aiwu
Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.
研究领域:
药理学
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生殖生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2023
·Vol. 18
·期 1
·1-15
·
IF 2.6
Sun Kai,Xue Yuman,Zhang Xin,Li Xiaodong,Zhao Jun,Xu Xilin,Zhang Xiaofeng,Yang Fubiao
Background The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I (TsI), on SIONFH remain unknown. Here, we evaluated the effects of TsI on SIONFH, particularly focusing on its effects on angiogenesis, in in vivo and in vitro research. Methods SIONFH was induced in Sprague–Dawley rats by an intramuscular injection of methylprednisolone (40 mg/kg) in combination with an intraperitoneal injection of lipopolysaccharide (20 μg/kg). Morphological alterations of the femoral head were observed by dual-energy X-ray absorptiometry and HE staining. Western blot, qRT-PCR, and immunohistochemical/immunofluorescence staining were used to determine gene expression. Results TsI (10 mg/kg) alleviated bone loss and rescued the expression of angiogenesis-related molecules (CD31, VWF, VEGF, and VEGFR2) in the femoral heads of SIONFH rats. Notably, TsI rescued the down-regulated expression of SRY-box transcription factor 11 (SOX11) in CD31 + endothelial cells in the femoral heads of SIONFH rats. In vitro studies showed that TsI preserved the dexamethasone-harmed angiogenic property (migration and tube formation) of human umbilical vein cells (EA.hy926), suppressed dexamethasone-induced cell apoptosis, reduced pro-apoptotic proteins (cytosolic cytochrome C, Bax, and caspase 3/9) and increased anti-apoptotic protein Bcl-2, whereas silencing of SOX11 reversed these beneficial effects. Conclusions This study demonstrates that TsI alleviates SIONFH and promotes angiogenesis by regulating SOX11 expression. Our work would provide new evidence for the application of TsI to treat SIONFH. Graphical Abstract
研究领域:
药理学
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骨科
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-11
·
IF 4.6
Li Hongwei,Chen Xin,Ren Kang,Wu Lihao,Chen Gong,Xu Ling
Diabetes may leave patients more prone to skin problems, and minor skin conditions can more easily turn into serious damage to the extracellular matrix, which further impairs the skin's mechanical properties and delays wound healing. Therefore, the aim of the work is to develop extracellular matrix substitution to remodel the mechanical properties of diabetic cutaneous wound and thus accelerate diabetic wound healing. A green fabrication approach was used to prepare radiation crosslinked bilayer collagen scaffold from collagen dispersion. The morphological, mechanical and swelling characteristics of radiation crosslinked bilayer collagen scaffold were assessed to be suitable for cutaneous wound remodeling . The feasibility of radiation crosslinked bilayer collagen scaffold was performed on full-skin defect of streptozotocin-induced diabetic rats. The tissue specimens were harvested after 7, 14, and 21 days. Histopathological analysis showed that radiation crosslinked bilayer collagen scaffold has beneficial effects on inducing skin regeneration and remodeling in diabetic rats. In addition, immunohistochemical staining further revealed that the radiation crosslinked bilayer collagen scaffold could not only significantly accelerate the diabetic wound healing, but also promote angiogenesis factor (CD31) production. Vascularization was observed as early as day 7. The work expands the therapeutic ideas for cutaneous wound healing in diabetes.
研究领域:
生物材料
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组织工程
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糖尿病研究
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伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
CURRENT EYE RESEARCH
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2022
·
IF 2.555
Xiaotian Liu,Shanjun Wu,Yan Gong,Lili Yang
Purpose To compare the therapeutic effects of different forms of nintedanib ophthalmic preparations on neovascularization corneal alkali burns in rats.Methods Forty rat models of left eye corneal alkali burns were constructed, and the five groups (N = 8) were treated with normal saline, dexamethasone ointment (dexamethasone), 0.2% nintedanib aqueous solution and nintedanib nano thermoreversible hydrogel (NNTH). A slit lamp microscope was used to observe the area of neovascularization. The levels of the inflammatory factors were detected by ELISA. HE staining was performed on the rat corneas. Vascular endothelial growth factor (VEGFA) was detected by immunohistochemistry, and the expression of corneal VEGFA and CD31 was detected by western blotting. An MTT assay was performed to detect the cytotoxicity of nintedanib on human corneal epithelial cells (HCECs) and human umbilical vein vascular endothelial cells (HUVECs). Cell migration was detected by a cell scratch assay, and the proportion of apoptotic cells was detected by Annexin/PI double staining. Immunofluorescence and western blotting were performed to detect the protein expression of VEGFA and CD31.Results NNTH had a stronger inhibitory effect on corneal neovascularization (CNV) in alkali-burned rats while reducing the level of inflammatory factors. NNTH had a longer drug duration of release than nanoformulations in vitro. Nintedanib at low concentrations (<8 μM) had no significant cytotoxicity to HCECs but significantly induced apoptosis and inhibited the expression of VEGFA and CD31 and the migration of HUVECs.Conclusions Nanomorphic thermoreversible hydrogel is superior among the nintedanib ophthalmic preparations, showing better inhibition of CNV in alkali-burned eyeballs and it blocked the migration and proangiogenic ability of HUVECs.
研究领域:
眼科学
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药剂学
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细胞生物学
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炎症
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·
IF 3.9
Jingrong Yu,Zhengkun Gao,Qingyue Han,Zi Wang,Wenjie Zhang,Jie Zhao,Shan Qiao,Xinxin Zou,Fengjie Huang
At present, wound dressings in clinical applications are primarily used for superficial skin wounds.However these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address this issue, t this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis.The CSDG hydrogel exhibites acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Both in vitro and in vivo results showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.
研究领域:
生物医学工程
·
材料科学
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伤口愈合
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yudie Wang,Hang Gao,Xin Wang,Dawei Li,Wen Zhang,Xuan Meng,Lijie Wang,Tao Zhu,Peijie Dong,Yao Chen,Xin Meng
A series of intricate and dynamic physiological healing processes are involved in the healing of skin wounds. Herein, a multifunctional hydrogel is firstly designed and constructed by L -arginine-grafted O -carboxymethyl chitosan (CMCA), catechol-modified oxidized hyaluronic acid (DOHA), and dopamine nanoparticles (pDA-NPs). pDA-NPs were loaded in hydrogel for inherently powerful antimicrobial properties and could be as a cross-linking agent to construct hydrogels. Raffinose (Raf) was further incorporated to obtain CMCA-DOHA-pDA2@Raf hydrogel for its function of modulating epidermal differentiation. The hydrogel has good physicochemical properties and could promote cell proliferation and migration, which shows superior hemostatic capabilities in animal models of hemorrhage. The hydrogel significantly promoted wound healing on rat skin defect models by upregulating VEGF and CD31 and decreasing IL-6 and TNF-α, stimulating neovascularization and collagen deposition in epithelial structures. This multifunctional hydrogel implies the potential to be a dynamic wound dressing.
研究领域:
生物材料
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伤口愈合
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纳米技术
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组织工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhiwan Chen,Mengfei Yuan,Haojing Li,Lihua Li,Binghong Luo,Lu Lu,Qi Xiang,Shan Ding
The inflammation of chronic wounds plays a key hindering role in the wound healing process. Slowing down the inflammatory response is significant for the repair of chronic wounds. Studies have revealed that succinate can inactivate gastrin D (GSDMD) and prevent cell pyroptosis. Chitosan has anti-inflammatory properties and is commonly used as wound healing material. Therefore, we used succinic anhydride to modify chitosan and found that N-succinylated chitosan (NSC) was more effective in inhibiting inflammation. The results showed that the stimulation of TNF-α and high glucose induces overexpression of capase-1 and TNF-α in human umbilical vein endothelial cells (HUVEC), and down-expression of CD31. However, the expression of capase-1 and TNF-α decreased, while the expression of CD31, VEGF and IL-10 was up-regulated significantly in dysfunctional HUVEC cells after treated by NSC. Moreover, NSC can speed wound healing, histological examination results showed that wounds treated with NSC exhibited faster epithelial tissue regeneration and thicker collagen deposition. Overall, this study results suggested that NSC has the function of restoring the physiological functions of dysfunctional HUVEC cells induced by high glucose and TNF-α, and can accelerate wound healing, indicating that NSC has good potential to be applied in inflammatory chronic wounds such as diabetic foot.
研究领域:
药理学
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伤口愈合
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炎症
·
细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Materials
·
2024
·
IF 6.8
Duan Yi,Lin Jiangtao,Yue Jiang,Li Yuanyuan,Liao Jinghan,Sun Ying,Wang Quan,Duan Yourong,Li Zhaojun
Atherosclerosis remains a major cause of morbidity and mortality worldwide. Intraplaque neovascularization critically promotes atherosclerotic progression and instability. Vascular endothelial growth factor A (VEGFA) stimulates aberrant microvessel growth in plaques by inducing endothelial cell proliferation and migration. Pigment epithelium-derived factor (PEDF) potently inhibits VEGFA-dependent neovascularization. This study introduces a thermosensitive hydrogel (PFSgel) developed from poloxamer 407 (F127) and sodium alginate (SA) to deliver PEDF locally to atherosclerotic lesions. The PFSgel demonstrated a suitable liquid-solid transition at body temperature (37°C), then forming a stable 3D network structure after SA gelling with the Ca 2+ in the physiological environment which contributed to the character of controlled release. Rheological analysis confirmed its phase transition temperature of 28.7°C and notable self-healing properties, making it ideal for dynamic vascular environments. In vitro experiments showed that PFSgel could suppress VEGFA-induced endothelial cells’ proliferation and migration through modulation of CD31 and MMP-2/MMP-9 signaling. Notably, in vivo degradation test validated the controlled release pattern of PFSgel. In Apoe-deficient atherosclerotic mice, ultrasound-guided PFSgel injection onto the abdominal aorta enabled gradual in situ release of encapsulated PEDF. This effectively reduced plaque burden, neovascularization, and luminal stenosis, even with exogenous VEGFA administration. Histological analyses confirmed reduced lipid deposition, plaque area, and neovascularization within plaques. Overall, this novel in situ -forming PEDF delivery platform enables targeted suppression of pathological neovascularization via CD31 and MMP-2/MMP-9 pathways, representing a promising approach to stabilize high-risk plaques by intervening against VEGFA-dependent neovascularization.
研究领域:
心血管疾病
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）