Odontology
·
2023
·
IF 2.5
Cui Zhao,Xu Yunhe,Wu Peng,Lu Ying,Tao Yongxin,Zhou Chuibing,Cui Ruting,Li Jingying,Han Rongpeng
Periodontal tissue regeneration engineering based on human periodontal ligament stem cells (hPDLSCs) provides a broad prospect for the treatment of periodontal disease. N-Acetyltransferase 10 (NAT10)-catalyzed non-histone acetylation is widely involved in physiological or pathophysiological processes. However, its function in hPDLSCs is still missing. hPDLSCs were isolated, purified, and cultured from extracted teeth. Surface markers were detected by flow cytometry. Osteogenic, adipogenic, and chondrogenic differentiation potential was detected by alizarin red staining (ARS), oil red O staining, and Alcian blue staining. Alkaline phosphatase (ALP) activity was assessed by ALP assay. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of key molecules, such as NAT10, Vascular endothelial growth factor A (VEGFA), PI3K/AKT pathway, as well as bone markers (RUNX2, OCN, OPN). RNA-Binding Protein Immunoprecipitation PCR (RIP-PCR) was used to detect the N4-acetylcytidine (ac4C) mRNA level. Genes related to VEGFA were identified by bioinformatics analysis. NAT10 was highly expressed in the osteogenic differentiation process with enhanced ALP activity and osteogenic capability, and elevated expression of osteogenesis-related markers. The ac4C level and expression of VEGFA were obviously regulated by NAT10 and overexpression of VEGFA also had similar effects to NAT10. The phosphorylation level of PI3K and AKT was also elevated by overexpression of VEGFA. VEGFA could reverse the effects of NAT10 in hPDLSCs. NAT10 enhances the osteogenic development of hPDLSCs via regulation of the VEGFA-mediated PI3K/AKT signaling pathway by ac4C alteration.
研究领域:
干细胞生物学
·
分子生物学
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再生医学
·
牙科科学
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DOI
PubMed
高影响因子
PLoS One
·
2026
·Vol. 21
·期 5
·e0350087
·
IF 2.8
Yan Duan,Weixin Wang,Yuanyuan Jin,Ming Jiang,Bolin Wang,Jianle Chen,Yun Jiang
Research objectives
Full-thickness skin defects present substantial challenges to the healing process, arising from the loss of the dermal layer, inadequate vascular supply, and insufficient growth factor availability. Although previous studies have established that growth factors and platelet-rich plasma (PRP) individually promote tissue repair, the synergistic benefits of their combined application for achieving superior therapeutic outcomes remain unclear. Here, we introduce a novel composite biomaterial: a hydrogel integrating nanoparticles loaded with basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) genes (bFGF/VEGFA NPs) with PRP (termed bFGF/VEGFA@PRP hydrogel), engineered to enable the synergistic delivery of growth factors and bioactive components.
Methods
In this study, we hypothesized that the bFGF/VEGFA@PRP hydrogel can promote wound healing. This hypothesis was tested through various experimental perspectives and methods including material characterization, wound healing rate, wound blood flow signal intensity, skin attachment, cell proliferation, apoptosis, collagen deposition, and growth factor levels.
Results
In a rat cutaneous wound model, this hydrogel accelerated wound closure, enhanced local blood perfusion, and increased the density of skin appendages and collagen fibers. Mechanistic investigations revealed upregulated expression of angiogenic factors bFGF, VEGFA, and platelet and endothelial cell adhesion molecule 1 (CD31), the anti-apoptotic protein BCL2, the cell proliferation marker Ki67, and type III collagen (COL III) in the treated group.
Conclusions
Collectively, these results demonstrate that the bFGF/VEGFA@PRP hydrogel promotes wound healing through the synergistic enhancement of growth factor expression, angiogenesis, and COL III deposition. The combination of gene therapy with PRP treatment was found to be more effective than either modality alone. This study establishes a promising therapeutic strategy for managing complex full-thickness skin injuries.
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DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Xiaofeng Liu,Bowen Fan,Shuai Huang,Maolin Wang,Hongbo Teng,Xu Wang,Mengqi Shi,Tianshi Li,Yan Zhao,Liyan Wang
Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia–reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.
研究领域:
药理学
·
心血管疾病
·
药物设计与合成
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Huanchen Yao,Dayang Wang,Jiashuo Ye,Hailin Cong,Bing Yu
Ethnopharmacological relevance Lung cancer is a common respiratory cancer worldwide, which seriously threatens people's lives. The current treatment of lung cancer is not satisfactory. Traditional Chinese medicine records that Hedyotis diffusa Willd (HDW) has effects that include clearing heat and detoxifying, promoting diuresis and dehumidification, relieving pain and resolving masses, and exhibiting anti-cancer properties. It has shown extraordinary therapeutic value in the clinical practice of traditional Chinese medicine. It is commonly used to treat various tumors, inflammation, and other diseases. Aim of the study The purpose of this experiment is to isolate the components with anti-lung cancer effects from HDW and to explore its anti-lung cancer effect and mechanism through network pharmacology and in vitro cell experiments in order to find more effective and less side effects—anticancer drugs. Materials and methods We used ethanol to extract HDW preliminarily and then used ethyl acetate, n-butanol, petroleum ether, and water to extract it, obtaining the ethyl acetate fraction with the highest inhibition rate on lung cancer H1299 cells. The silica gel column purification, TOF, and nuclear magnetic resonance analysis yielded the Fisetin, which has an inhibitory effect on H1299 cells. The mechanism and application of Fisetin in inhibiting lung cancer were explored by network pharmacology and in vitro cell experiments. Results Using network pharmacology to explore the mechanism of Fisetin inhibiting lung cancer, 115 Fisetin targets, and 26,857 lung cancer targets were obtained, and 90 GO functions and 19 KEGG pathways were obtained (P < 0.01). Molecular docking results demonstrated that target protein-drug binding was stable. Afterward, the toxicity of Fisetin to H1299 cells was verified by in vitro cell experiments. MTT, live-dead staining, and confocal microscopy all showed that Fisetin had a good inhibitory effect on H1299 cells and had good cell compatibility. Through Western blot analysis, Fisetin can reduce the protein content of PI3K, MTOR, HIF1A and VEGFA. And it can reduce the mRNA expression levels of HIF1A and VEGFA. Moreover, Fisetin can also increase the expression of tumor suppressor molecule PTEN protein and mRNA in H1299 cells. Conclusions Fisetin and HDW can successfully stop lung cancer H1299 cells from growing. The mechanism of Fisetin may be related to the inhibition of PI3K/MTOR/HIF1A/VEGFA signaling pathway.
研究领域:
药理学
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肿瘤学
·
生物信息学
·
细胞生物学
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药物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2023
·Vol. 51
·期 5
·1-16
·
IF 5.4
Sheng Huan,Sumin Sun,Shilian Song,Jin Dai,Guining Zhu,Yanling Zhong,Yihao Ji,Shizhong Zheng,Guoping Yin
Liver fibrosis is an early pathological feature of hepatic diseases. Hepatic stellate cell (HSC) activation and disordered proliferation are associated with liver fibrosis. The present study identified significant differences in the expression levels of microRNA (miRNA/miR)‑29b‑3p in clinical samples and multiple miRNA databases. Subsequently, the specific antifibrotic mechanism of miR‑29b‑3p was further elucidated. Reverse transcription‑quantitative PCR, western blot, ELISA and immunofluorescence were used to detect the expression levels of target genes and proteins. Oil red O, Nile red and trypan blue staining were used to evaluate HSC activation and cell viability. A luciferase assay was used to detect the relationship between miR‑29b‑3p and VEGFA. Adhesion, wound healing, apoptosis double staining and JC‑1 assays were used to detect the effects of VEGFR1 and VEGFR2 knockdown on HSCs. Immunoprecipitation and fluorescence colocalization were used to identify interactions between the proteins. Furthermore, a rat fibrosis model was constructed to investigate the effects of dihydroartemisinin (DHA) and miR‑29b‑3p in vivo and in vitro. The results indicated that miR‑29b‑3p both inhibited the activation of HSCs and limited the proliferation of activated HSCs via lipid droplet recovery and VEGF pathway regulation. VEGFA was identified as a direct target of miR‑29b‑3p, and knockdown of VEGFA induced cell apoptosis and autophagy. Notably, VEGFR1 and VEGFR2 knockdown both promoted apoptosis; however, VEGFR1 knockdown inhibited autophagy, whereas VEGFR2 knockdown induced autophagy. Furthermore, it was revealed that VEGFR2 regulated autophagy by mediating the PI3K/AKT/mTOR/ULK1 pathway. VEGFR2 knockdown also led to ubiquitination of heat shock protein 60, ultimately inducing mitochondrial apoptosis. Finally, DHA was identified as a natural agonist of miR‑29‑3p that effectively prevented liver fibrosis in vivo and in vitro. Overall, the present study determined the molecular mechanism by which DHA inhibited HSC activation and prevented liver fibrosis.
研究领域:
分子生物学
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药理学
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肝病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2019
·Vol. 47
·期 1
·85-94
·
IF 2.336
Ning Han,Haitao Xu,Na Yu,Yazhen Wu,Li Yu
Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA-203-3p (miR-203-3p) was found to be down-regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR-203a-3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR-203a-3p agomir by intravitreal injection. The results showed that the level of miR-203a-3p was decreased in OIR rats, and forced over-expression of miR-203a-3p inhibited OIR-induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR-induced up-regulation of VEGFA, HIF-α, PCNA, and MMPs in the retina was also counteracted by miR-203a-3p. Additionally, high glucose (HG)-induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up-regulation of miR-203a-3p. Dual-luciferase reporter assay showed that miR-203a-3p could specifically bind to the 3′UTR of VEGFA and HIF-1α. Over-expression of VEGFA or HIF-1α restored the tube formation activity of HRMECs suppressed by miR-203a-3p. In conclusion, our findings demonstrate that up-regulation of miR-203a-3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF-1α.
研究领域:
分子生物学
·
眼科学
·
糖尿病研究
·
微小RNA
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2023
·Vol. 29
·期 1
·1-21
·
IF 5.7
Bai Tao,Li Mingxing,Liu Yuanfeng,Qiao Zhentao,Zhang Xusheng,Wang Yafeng,Wang Zhiwei
Background Diabetes-related limb ischemia is a challenge for lower extremity amputation. Aurora Kinase A (AURKA) is an essential serine/threonine kinase for mitosis, while its role in limb ischemia remains unclear. Method Human microvascular endothelial cells (HMEC-1) were cultured in high glucose (HG, 25 mmol/L d -glucose) and no additional growth factors (ND) medium to mimic diabetes and low growth factors deprivation as in vitro model. Diabetic C57BL/6 mice were induced by streptozotocin (STZ) administration. After seven days, ischemia was surgically performed by left unilateral femoral artery ligation on diabetic mice. The vector of adenovirus was utilized to overexpress AURKA in vitro and in vivo. Results In our study, HG and ND-mediated downregulation of AURKA impaired the cell cycle progression, proliferation, migration, and tube formation ability of HMEC-1, which were rescued by overexpressed AURKA. Increased expression of vascular endothelial growth factor A (VEGFA) induced by overexpressed AURKA were likely regulatory molecules that coordinate these events. Mice with AURKA overexpression exhibited improved angiogenesis in response to VEGF in Matrigel plug assay, with increased capillary density and hemoglobin content. In diabetic limb ischemia mice, AURKA overexpression rescued blood perfusion and motor deficits, accompanied by the recovery of gastrocnemius muscles observed by H&E staining and positive Desmin staining. Moreover, AURKA overexpression rescued diabetes-related impairment of angiogenesis, arteriogenesis, and functional recovery in the ischemic limb. Signal pathway results revealed that VEGFR2/PI3K/AKT pathway might be involved in AURKA triggered angiogenesis procedure. In addition, AURKA overexpression impeded oxidative stress and subsequent following lipid peroxidation both in vitro and in vivo, indicating another protective mechanism of AURKA function in diabetic limb ischemia. The changes in lipid peroxidation biomarkers (lipid ROS, GPX4, SLC7A11, ALOX5, and ASLC4) in in vitro and in vivo were suggestive of the possible involvement of ferroptosis and interaction between AUKRA and ferroptosis in diabetic limb ischemia, which need further investigation. Conclusions These results implicated a potent role of AURKA in diabetes-related impairment of ischemia-mediated angiogenesis and implied a potential therapeutic target for ischemic diseases of diabetes.
研究领域:
分子生物学
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细胞生物学
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糖尿病研究
·
血管生物学
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产品关联
DOI
PubMed
高影响因子
STEM CELLS AND DEVELOPMENT
·
2024
·
IF 2.5
Yaping Xu,Xiangli Zhang,Zhikun Fu,Yan Dong,Yuexin Yu,Yingtian Liu,Ziyu Liu,Jinfu Chen,Yao Yao,Yan Chen,Jer Ping Ooi,Bakiah Shaharuddin,Bin Yang,Jun Jie Tan,zhikun Guo
Heart failure is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced heart failure (HF) rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (N=5). These cells that primarily expressed SCA-1, NANOG, mesenchymal markers CD90, CD105 and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 ×105 cells/heart) were injected into the pericardial cavity of the doxorubicin (DOX)-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted RFP-tagged hPFCs co-expressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFCs treatment (P<0.0001 versus untreated). The elevated inflammatory cytokine IL-6, IL-10, and TNF-α in the DOX-treated hearts were found to have significantly reduced (P<0.001 versus untreated), while the regional pro-angiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFCs-treated group after 4 weeks (P<0.05 versus untreated). hPFCs possess stem cell characteristics and can improve cardiac functions of DOX-induced heart failure rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional pro-angiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.
研究领域:
心脏病学
·
干细胞生物学
·
再生医学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 7
·870
·
IF 4.9
Zikang Xing,Xuewen Li,Zhen Ning Tony He,Xin Fang,Heng Liang,Chunxiang Kuang,Aiying Li,Qing Yang
Glioma is characterized by strong immunosuppression and excessive angiogenesis. Based on existing reports, it can be speculated that the resistance to anti-angiogenic drug vascular endothelial growth factor A (VEGFA) antibody correlates to the induction of novel immune checkpoint indoleamine 2,3-dioxygenase 1 (IDO1), while IDO1 has also been suggested to be related to tumor angiogenesis. Herein, we aim to clarify the potential role of IDO1 in glioma angiogenesis and the mechanism behind it. Bioinformatic analyses showed that the expressions of IDO1 and angiogenesis markers VEGFA and CD34 were positively correlated and increased with pathological grade in glioma. IDO1-overexpression-derived-tryptophan depletion activated the general control nonderepressible 2 (GCN2) pathway and upregulated VEGFA in glioma cells. The tube formation ability of angiogenesis model cells could be inhibited by IDO1 inhibitors and influenced by the activity and expression of IDO1 in condition medium. A significant increase in serum VEGFA concentration and tumor CD34 expression was observed in IDO1-overexpressing GL261 subcutaneous glioma-bearing mice. IDO1 inhibitor RY103 showed positive anti-tumor efficacy, including the anti-angiogenesis effect and upregulation of natural killer cells in GL261 glioma-bearing mice. As expected, the combination of RY103 and anti-angiogenesis agent sunitinib was proved to be a better therapeutic strategy than either monotherapy.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
神经科学
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产品关联
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
·
生殖生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Chen Jiaqi,Yin Min,Yang Chenguang,Wang Kun,Ma Lili,Yu Haiyang,Huang Yue,Liu Feng,Tang Zhaohui
Introduction: The prognosis of advanced renal carcinoma is not ideal, necessitating the exploration of novel treatment strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) possess the dual capability of CA4 (targeting blood vessels to induce tumor necrosis) and BLZ945 (inducing M2 macrophage apoptosis), thereby inhibiting tumor growth.Methods: Here, the therapeutic effects and underlying mechanism was explored by CCK-8 cytotoxicity experiment, transwell cell invasion and migration experiment, H&E, western blot analysis, immunohistochemistry, flow cytometry, and other techniques.Results: These results demonstrated that CB-NPs could inhibit the growth of Renca cells and subcutaneous tumors in mice, with an impressive tumor inhibition rate of 88.0%. Results suggested that CB-NPs can induce necrosis in renal carcinoma cells and tissues, downregulate VEGFA expression, promote renal carcinoma cell apoptosis, and reduce the polarization of M2 macrophages.Discussion: These findings offer innovative perspectives for the treatment of advanced renal carcinoma.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT EYE RESEARCH
·
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
·
药剂学
·
细胞生物学
·
炎症
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）