Frontiers in Veterinary Science
·
2023
·
IF 3.2
Ahmed Hesham,Marwa Abass,Haanin Abdou,Reham Fahmy,Maha M. Rashad,Abdelnaser A. Abdallah,Wael Mossallem,Ibrahim F. Rehan,Asmaa Elnagar,František Zigo,Silvia Ondrašovičová,Ahmed F. Abouelnaga,Awad Rizk
Introduction The use of ozonized water is gaining importance in medicine due to its effects on hyperglycemia and wound healing mechanisms. Methods This experiment was conducted to assess the impacts of intradermal administration of ozonated water on acute skin wound healing in a diabetic rat model. Sixty-four adult male Wistar rats were randomly divided into two groups: an ozonated water group (O3W) and a control group (CG). Experimental diabetes was chemically induced in the rats by the intraperitoneal administration of 60 mg/kg streptozotocin. One week later, full-thickness skin surgical wounds (1 cm 2 ) were created between the two shoulders of the rats under general anesthesia. The wounds were then daily irrigated with normal saline (CG) or intradermally injected with 1 mL of ozonated water at 10 mg/L O3W. Wound healing was evaluated through macroscopic analysis, measuring wound size, diameter, and percentage of contraction rate before wounding and at 3, 7, 9, 12, 14, 18, 21, 24, and 28 days post-wounding. On days 7, 14, 21, and 28 after induction of the wounds, the body weights and blood glucose levels of rats (8 per group) were measured before the rats were euthanized. Moreover, the morphological structure of the tissue, vascular endothelial and transforming growth factor (VEGF and TGF) affinity and gene expression were examined. Results The O3W group had significantly lower blood glucose levels and wound size and gained body weight. Additionally, epithelial vascularization, stromal edema, TGF, and VEGF gene expression significantly improved in the O3W group. Discussion Therefore, ozonated water has the potential to enhance and promote cutaneous wound healing in diabetic rats.
研究领域:
医学
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药理学
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糖尿病研究
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伤口愈合
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DOI
PubMed
高影响因子
ANALYST
·
2023
·Vol. 148
·期 14
·3295-3305
·
IF 4.2
Yong Huang,Zhengqing Liu,Xiaogang Qin,Jia Liu,Yan Yang,Wei Wei
Highly sensitive protein biomarker detection is critical for the diagnosis of gastric cancer (GC), however the accurate and sensitive detection of low-abundance proteins in early-stage GC is still a challenge. Herein, a surface-enhanced Raman scattering frequency shift assay was performed on a developed microfluidic chip for the detection of GC protein biomarkers carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The chip is made up of three groups of parallel channels and each parallel channel consists of two reaction regions, enabling the simultaneous analysis of multiple biomarkers in multiple samples. The presence of CEA and VEGF in the sample can be captured by the 4-mercaptobenzoic acid (4-MBA)-conjugated antibody functionalized gold nano-sheet (GNS-) substrate, resulting in the Raman frequency shift. As a result, a typical Raman frequency shift of 4-MBA presented a linear relationship with the concentration of CEA and VEGF. The limit of detection (LOD) of the proposed SERS microfluidic chip reaches as low as 0.38 pg mL−1 for CEA and 0.82 pg mL−1 for VEGF. During the detection process, only one step of sample addition is involved, which eliminates the multiple reaction step-induced nonspecific adsorption and significantly increases the convenience and specificity. In addition, serum samples from GC patients and healthy subjects were tested and the results were in good agreement with the current gold-standard method ELISA, suggesting the potential application of the SERS microfluidic chip in clinical settings for early diagnosis and prognosis of GC.
研究领域:
医学
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分析化学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Yating Xie,Wenya Guo,Xi Shen,Weina Yu,Yanping Kuang,Qiuju Chen,Hui Long,Qifeng Lyu,Li Wang
Summary Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS protocol was simulated in mice. The ovulated oocytes, estradiol, progesterone, and luteinizing hormone (LH) levels were analyzed at different hours after trigger. mRNA extraction and real-time PCR, hematoxylin and eosin staining, and immunofluorescence of ovaries were used to explore the involved signaling pathways. The PPOS group had a delayed ovulation at 12.5 h after trigger. Its suppressed LH level reduced the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) on the preovulatory follicles before trigger and significantly decreased the following progesterone synthesis, blood progesterone level, and progesterone receptor (PGR) expression within 4–6 h after trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS-1, VEGF-A, and EDN2 were downregulated, ultimately delaying the ovulation. PPOS suppresses the LH level before trigger and decreases the synthesis of progesterone after trigger, thus delaying the ovulation by downregulating the LHCGR-PGR pathway.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Ophthalmology
·
2019
·
IF 1.189
Li-Fei Wang,Zhong-Yang Yan,Ya-Lin Li,Yan-Hui Wang,Sheng-Juan Zhang,Xin Jia,Lu Lu,Yan-Xia Shang,Xin Wang,Yun-Huan Li,Shan-Yu Li
AIM To explore the effect of Obtusifolin on retinal pigment epithelial cell growth under hypoxia. METHODS In vitro chemical hypoxia model of ARPE-19 cells was established using cobalt chloride (CoCl 2 ). Cell viability was tested by cell counting kit-8 (CCK-8) assay. Western blot and real-time quantitative polymerase chain reaction were applied to detect proteins and mRNAs respectively. Flow cytometry was used to examine the cell cycle. Secretion of vascular endothelial growth factor (VEGF) was tested by using enzyme linked immunosorbent assay (ELISA). RESULTS Under the chemical hypoxia model established by CoCl 2 , hypoxia inducible factor-1α (HIF-1α) mRNA and protein levels was up-regulated. Cell viability was increased and the proportion of S phase was higher. Obtusifolin could reduce cell viability under hypoxic conditions and arrest cells in G1 phase. Obtusifolin reduced the expression of Cyclin D1 and proliferating cell nuclear antigen (PCNA) in the hypoxic environment and increased the expression of p53 and p21. The levels of VEGF, VEGFR2 and eNOS proteins and mRNA were significantly increased under hypoxia while Obtusifolin inhibited the increasing. CONCLUSION Obtusifolin can inhibit cell growth under hypoxic conditions and down-regulate HIF-1/VEGF/eNOS secretions in ARPE-19 cells.
研究领域:
眼科学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2022
·Vol. 13
·期 1
·1-19
·
IF 8.079
Lin Yifeng,Dong Shunni,Ye Xiaohang,Liu Juan,Li Jiaqun,Zhang Yanye,Tu Mixue,Wang Siwen,Ying Yanyun,Chen Ruixue,Wang Feixia,Ni Feida,Chen Jianpeng,Du Binyang,Zhang Dan
Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms.
Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness ( P < 0.001, P < 0.05), decrease fibrous area ( P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate ( P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells. Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract
研究领域:
生殖医学
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干细胞治疗
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组织工程
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再生医学
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DOI
PubMed
高影响因子
Biomedical Materials
·
2026
·Vol. 21
·期 3
·035012
·
IF 3.9
Xuefei Xiang,Yufang Yang,Heyou Gao,ZhiYun Chen,JingYi Xie,QingChuan Hu,Yu Wang
Composite scaffolds composed of porous polyurethane (PU) block copolymer and nano-hydroxyapatite (n-HA) have demonstrated significant potential in bone defect repair. However, the co-effect of osteogenesis and angiogenesis during the process of large bone defect repair is still not yet fully understood. Recent research has found that erythropoietin (EPO) is essential for both osteogenesis and angiogenesis, offering a new research direction for bone regeneration strategies. In this study, a polydopamine (pDA)-modified, EPO-functionalized HA/PU scaffold was fabricated, and its physicochemical properties, release kinetics, and effects on bone repair were systematically investigated. In vitro, a co-culture system of human umbilical vein endothelial cells and rat bone marrow mesenchymal stem cells was used to evaluate the scaffold’s effects on cell proliferation, osteogenic, angiogenic, and HIF-1α/ vascular endothelial growth factor (VEGF) pathway. In vivo, the modified composite scaffold was implanted onto the cranial bone defects of Sprague-Dawley rats to assess its efficacy in promoting bone repair and HIF-1α/VEGF pathway. In vitro, the EPO/pDA/HA/PU group showed more three-dimensional cell morphology with prominent pseudopodia, facilitating cell adhesion, and significantly increased mRNA expression of ALP, Runx2, CD31, CD34, HIF-1α and VEGF. In vivo, the EPO/pDA/HA/PU group exhibited the most significant bone regeneration, with micro- computed tomography analysis confirming a significantly higher the ratio of bone tissue volume to total tissue volume (BV/TV) compared to the blank and HA/PU control groups. These results indicated that the modified composite scaffold enabled sustained release of EPO, which upregulated the expression of HIF-1α and VEGF, thereby enhancing osteogenic and angiogenic capabilities both in vitro and in vivo. Our research demonstrated that loading of EPO onto the HA/PU composite scaffold could effectively promote osteogenesis and angiogenesis. HIF-1α/VEGF signaling plays a crucial role in this process. This discovery provides novel insights and methods for using HIF-1α/VEGF as a regulatory target to advance the clinical translation of large bone defects repair.
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 12.9
Zeguo Chen,Zhongshi Wu,Can Huang,Qiying Wu,Chao Xie,Sicheng Chen,Liang Yi,Haoyong Yuan,Sixi Liu,Abdulraheem Mustapha,Siyao Chen,Wansong Chen,Ting Lu,Zhenjie Tang,Yuhong Liu
Delayed endothelialization and inadequate matrix remodeling remain major obstacles in the development of small-diameter vascular grafts (SDVGs; <6 mm). To address these challenges, we developed an immunomodulatory tissue-engineered vascular graft (iTEVG) by integrating hollow mesoporous silica nanoparticles (HMSNs) with tailored mesopore sizes as delivery carriers for immunoregulatory factors. VEGF was selectively immobilized on the intimal surface, while the adventitia incorporated a sequential release system for VEGF and IL-4. VEGF exhibited rapid release (64.04 ± 4.44% in 7 days), promoting monocyte recruitment and adventitial neovascularization, while IL-4 showed sustained release (65.94 ± 2.06% over 28 days), driving long-term M2 macrophage polarization. In rats, iTEVGs achieved 88% endothelial coverage and smooth muscle cell infiltration within 1 month, full-thickness cellularization with a complete trilaminar structure by 3 months, and maintained mechanical integrity without aneurysm formation up to 6 months. This spatially partitioned platform, built on an acellular vascular scaffold, enables precise spatiotemporal regulation of the immune microenvironment and offers a design paradigm that synergistically promotes endothelialization and vascular matrix remodeling. The “intima-targeted regeneration and adventitia-sequential-release” strategy provides a promising template for SDVG design that may be extended to other complex organ constructs.
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产品关联
DOI
PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
·
2020
·
IF 1.892
Jing Dong,Yuelei Chen,Wenhui Yang,Xi Zhang,Lin Li
Breast cancer is a high incidence disease in humans. Artemisinin is an important extract that is widely used as an antimalarial drug which also serve as effective treatments for cancer. 32 nude mice were injected with 0.2 ml of MDA-MB-231 cell suspension of 2 × 10 7 cells/ml respectively. The nude mice models were randomly divided into four groups of 8 in each group. Each group was given daily gavage, high dose group: 200 mg/kg/0.1 ml, middle dose group 100 mg/kg/0.1 ml, low dose group 50 mg/kg/0.1 ml, control group: 0.1 ml vegetable oil was fed continuously for 21 days. ELISA was used to detect serum vascular endothelial growth the content of factor VEGF and hypoxia-inducible factor HIF-1α were detected. The expression of Notch pathway-related factors in tumor tissue was detected by fluorescence quantitative assay. ELISA results showed that the serum VEGF decreased significantly in the high dose group compared with the control group ( p < .01), while the other dose groups did not have significant ( p > .05). The serum HIF-1α in the high dose group compared with the control group, the decrease in HIF-1α was significant ( p < .05), and the other groups were not significant ( p > .05). The result of fluorescence quantitative section showed that artemisinin could down-regulate the expression of notch signaling related factors notch1, Dll4 and Jagged1, and 200 mg/kg dose group had the most significant effect. It may inhibit the development of tumors by reducing serum angiogenesis-related factors VEGF, HIF-1ɑ and inhibiting the activity of notch1 signaling pathway related factors.
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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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Mingliang Gao,Zhiping Ge,Rui Deng,Beihua Bao,Weifeng Yao,Yudan Cao,Mingqiu Shan,Fangfang Cheng,Hui Yan,Peidong Chen,Li Zhang
Ethnopharmacological relevance Typhae Pollen (TP) is a well-known Traditional Chinese Medicine (TCM) to remove blood stasis . Carbonized Typhae Pollen (CTP), a processed product of TP after being stir-fried, has been widely applied to clinical practice with its capability of hemostasis. However, the underlying mechanism of TP and CTP are still not fully elucidated and discrimination against TP and CTP remains a challenge. Aim of study The aim of this study is to investigate whether TP could remove blood stasis by promoting angiogenesis and the process of carbonizing it could enhance hemostatic effect. Meanwhile, some chemical markers for quality control of CTP had better to be found. Material and methods The changes of constituents between TP and CTP were analyzed by UPLC-QTOF-MS/MS. We investigated pro-angiogenic and hemostatic effects of TP and CTP in two zebrafish models: VRI-induced ISV insufficiency model and Ator-induced cerebral hemorrhage model. Subsequently, quantitative real-time PCR (qRT-PCR) was applied to investigate the mechanism of pharmacological effects. Finally, chemometric method was applied to find chemical markers. Results A total of 19 compounds were identified in qualitative analysis. The loss rate of each compound was calculated and compared. Two compounds (huaicarbon A/B) could only be detected in CTP and the content of flavonoid glycosides in CTP was significantly decreased compared with TP. The average content of the three identified flavonoid aglycones (quercetin, isorhamnetin and kaempferol) was increased about 30 percent in CTP. TP promoted pro-angiogenesis by up-regulating the expression of VEGFA, flt1 and kdr. After heating process, the pro-angiogenic activity was reduced and hemostatic activity was enhanced in CTP. Then qRT-PCR analysis found that CTP could significantly up-regulate the expression of VEGFA and vWF. In the discovery of markers, 6 chemical markers for discrimination of TP and CTP were obtained by chemometric method. Conclusion Our research indicated that the pro-angiogenic activity of TP was involved in VEGF signaling pathway. After processing, hemostatic activity of CTP has been enhanced by up-regulating the expression of VEGFA and vWF. A chemical marker database was established to provide a scientific evidence for quality control, mechanism and the clinical application of TP and CTP.
研究领域:
药理学
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中药学
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生物化学
·
分子生物学
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分析化学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Sheng Ding,Siyu Liu,Shaoyang Kang,Shuwei Wang,Nan Jiang,Yuwei Li,Chunxiao Zhou,Hantao Lou,Chuangnian Zhang,Pingsheng Huang,Wenshuai Liu,Zujian Feng,Weiwei Wang,Deling Kong,Ningbei Yin
Diabetic wound healing poses a major clinical challenge. One of the promising therapy, the flap transplantation surgery exhibited unsatisfactorily low flap survival due to the intertwined pathological barriers: impaired angiogenesis, excessive oxidative stress, and persistent inflammation, leading to poor tissue repair. While the therapeutic platforms based on extracellular vesicles (EVs) emerges as a promising treatment, its efficacy is often limited by the inadequate yield and rapid in vivo clearance. To address this challenge, this study developed a strategy centered on preconditioning human umbilical vein endothelial cells (HUVECs) with high glucose (HG) stress to produce HG-preconditioned extracellular vesicles (hEVs), which significantly improve production, enrich regenerative cargoes (e.g., HIF-1α, VEGF), and enhance homologous cellular internalization. The hEVs derived from HUVECs were encapsulated by microfluidically fabricated gelatin methacryloyl (GelMA) microgels to create GelMA@hEVs. The biodegradable and biocompatible GelMA microgels enabled a sustained hEVs release profile. Therefore, GelMA@hEVs exhibited significant efficacy improvement in promoting endothelial cell proliferation, migration, and tube formation critical for vascularization, mitigating reactive oxygen species, and modulating macrophage polarization toward a pro-reparative phenotype. Mechanistically, these therapeutic effects relied on activating the HIF-1α/VEGF pathway, a core axis for angiogenesis dysregulated in diabetes. In diabetic ischaemic flap models, GelMA@hEVs significantly improved flap survival, restored vascular perfusion, and facilitated tissue regeneration without systemic toxicity. Altogether, this work provides a generalizable strategy for diabetic ischaemic flap repair by combining engineered EVs as bioactive cargo with a microgel scaffold for sustained delivery, offering a promising in situ tissue engineering solution.
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xinyu Liu,Xiaofan Liu,Yuping Zhao,Yang Liu,Huimin Wang,Yi Li,Nan Ma,Hongchen Sun,Fermín E. González,Youliang Zhu,Junfeng Zhou,Yuewei Zhang,Ding Zhou,Xiaowei Xu
Insufficient nutrient and oxygen supply remains a critical barrier to cell survival and tissue regeneration in three-dimensional scaffolds. Here, we developed a self-supplying glucose/oxygen hydrogel (SGO-Gel) that intrinsically provides sustained metabolic support for dental pulp stem cells (DPSCs). The hydrogel was constructed by crosslinking oxidized dextran with phenylboronic acid-grafted carboxymethyl chitosan through dynamic Schiff-base and phenylboronic ester bonds, yielding an injectable, self-healing network capable of releasing glucose upon dextranase degradation. Polydopamine-coated calcium peroxide nanoparticles were incorporated to achieve controlled oxygen release while maintaining structural stability. SGO-Gel exhibited a uniform porous architecture that facilitated nutrient diffusion, as confirmed by molecular dynamics simulations. In vitro , the hydrogel significantly enhanced DPSCs survival under combined glucose starvation and hypoxia, maintaining viability above 70 % after 7 days compared to less than 30 % in control gels. Transcriptomic analysis revealed activation of the MAPK/Erk1/2 pathway and upregulation of VEGF, which was consistent with functional assays showing enhanced endothelial migration and tube formation. In an ectopic transplantation model, SGO-Gel promoted the formation of vascularized pulp-like tissue with abundant collagen deposition and odontoblast differentiation. Overall, SGO-Gel shifts the paradigm from passive scaffolds to metabolically active matrices, offering a promising strategy for dental pulp regeneration and broader tissue engineering applications where ischemia and limited vascularization remain key challenges.
研究领域:
组织工程
·
再生医学
·
干细胞生物学
·
生物材料
·
牙科研究
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产品关联
DOI
高影响因子
Nano Today
·
2021
·
IF 20.722
Xiaoping Zhang,Yuanning Lyu,Yang Liu,Rong Yang,Bo Liu,Jia Li,Ziyang Xu,Qian Zhang,Jianhai Yang,Wenguang Liu
Currently, single therapeutic strategy designed for only boosting anti-inflammatory response or angiogenesis in treating myocardial infarction (MI) has met with limited success due to complicated pathological mechanism. Herein, we propose to create artificial apoptotic cells (AACs) by customizing liposomes with phosphatidylserine (PS) exposing at outlayer, in mimicking the function of apoptotic cells, with an aim to promote M2 polarization of macrophages. The AACs and vascular endothelial growth factor (VEGF) are encapsulated into an extracellular matrix-mimetic injectable hydrogel that recapitulates sulfated glycosaminoglycan. The loaded AACs and VEGF can realize earlier quick and slowly sustainable release, respectively, which is governed by distinct electrostatic interactions. The controlled spatio-temporal delivery of AACs and VEGF achieves on-demand regulation of inflammation immune response and enhanced angiogenesis. In the rat model of MI with intramyocardial administration of this injectable hydrogel bearing AACs and VEGF, the local precise release of AACs inhibits the inflammatory response and reduces the apoptosis of cardiomyocytes . Meanwhile, the sustainable release of VEGF activates the VEGF signaling pathway and thus facilitates revascularization in the targeted infarcted region, eventually contributing to a significant improvement in cardiac function and alleviating pathological remodeling of the left ventricle.
研究领域:
心脏病学
·
组织工程
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生物医学工程
·
免疫学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）