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American Journal of Translational Research · 2020 · IF 3.375

Three-dimensional-printed titanium alloy porous scaffold combined with trans-cinnamaldehyde for repairing osteonecrosis of the femoral head in a dog model

Runzi Gao,Wenhui Ji,Tianwei Xia,Yanxing Fan,Wei Wei,Le Shi,Jinzhu Liu,Chao Zhang,Lezhen Xue,Jirong Shen

Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic “double line sign” of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, β-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH.

CAS / MDL: 76-03-9
研究领域: 骨科 · 再生医学 · 药理学 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2014 · IF 4.287

Regulation of the migration of endothelial cells by a gradient density of vascular endothelial growth factor

Pian Wu,Ya Fu,Kaiyong Cai

To investigate the effect of the surface gradient density of growth factor on the migration of endothelial cells (ECs), an approach to fabricate a gradient density of vascular endothelial growth factor (VEGF) onto silicon slides has been developed in this study. Our approach involves gradual injection of 3-glycidoxypropyltrimeth oxysilane (GPTMS) and then back filling with 3-triethoxysilylpropyl succinicanhydride (TESPSA) to produce a gradient density of carboxyl groups (–COOH) onto the silicon slides. The –COOH moieties were then activated for the immobilization of VEGF, which leading to a surface gradient density of VEGF. The successful formation of both carboxyl and VEGF gradient densities were confirmed by contact angle measurement, confocal laser scanning microscopy (CLSM) and X-ray photoelectron spectroscopy (XPS), respectively. The treated silicon slide displayed a gradient density of VEGF from 54 to 132   ng/cm 2 with a slope of 7.8   ng/cm 2 /mm. ECs cultured on the surface gradient density of VEGF demonstrated preferential orientation and an enhanced directional migration behavior. Up to 72% of cells migrated towards the region with high surface density of VEGF. However, the gradient density of VEGF had no significant effect on the cell migration rate. The study provides an alternative to explore chemical-directing cells migration, which is essentially important for understanding cell migration/in-growth behavior for angiogenesis involved in implant technology.

CAS / MDL: 92-31-9
研究领域: 生物医学工程 · 细胞生物学 · 组织工程
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NEUROREPORT · 2022 · IF 1.703

Investigation of the effects of high cervical spinal cord electrical stimulation on improving neurological dysfunction and its potential mechanism in rats with traumatic brain injury

Peng-Cheng Zhao,Zhen-Shan Huang,Shao-Nian Xu,Peng-Cheng Deng,Feng Qian,Jian Shi,Yong-Ming Zhang

To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.

CAS / MDL: 110-18-9
研究领域: 神经科学 · 药理学 · 分子生物学
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MACROMOLECULAR BIOSCIENCE · 2024 · IF 4.4

A Novel Food Bore Protein Hydrogel with Silver Ions for Promoting Burn Wound Healing

Xiaowen Fu,Gan Hu,Adil M. Abker,Deog-Hwan Oh,Meihu Ma,Xing Fu

Hydrogels have emerged as a promising option for treating local scald wounds due to their unique physical and chemical properties. This study aims to evaluate the efficacy of ovalbumin/gelatin composite hydrogels in repairing deep II-degree scald wounds using a mouse dorsal skin model. Trauma tissues collected at various time points are analyzed for total protein content, hydroxyproline content, histological features, and expression of relevant markers. The results reveal that the hydrogel accelerates the healing process of scalded wounds, which is 17.27% higher than the control group. The hydrogel treatment also effectively prevents wound enlargement and redness of the edges caused by infection during the initial stage of scalding. The total protein and hydroxyproline content of the treated wounds are significantly elevated. Additionally, the hydrogel up-regulates the expression of VEGF (a crucial angiogenic factor) and down-regulates CD68 (a macrophage marker). In summary, this study provides valuable insights into the potential of multifunctional protein-based hydrogels in wound healing.

CAS / MDL: 4781-83-3
研究领域: 生物医学工程 · 伤口愈合 · 材料科学 · 组织工程
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Scientific Reports · 2020 ·Vol. 10 ·期 1 ·1-9 · IF 3.998

Biomarkers of myocardial injury in rats after cantharidin poisoning: Application for postmortem diagnosis and estimation of postmortem interval

Zhang Youyou,Yu Yalei,Zhang Jie,Guan Chuhuai,Liu Liang,Ren Liang

Postmortem diagnosis of cantharidin-induced myocardial injury and postmortem interval estimation (PMI) are the challenges in forensic science. Cardiac biomarkers play an important role in the prediction and diagnosis of myocardial injury and can be used to determine the PMI. Based on the evidence, we aimed to explore the biomarkers which may be used for the postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation using the study of the proteins expression of TN-T, VEGF and HIF-1α by ELISA. Results of this study suggested that postmortem pathological changes were difficult to identify due to the autolysis of myocardium 72 h after death in cantharidin poisoning group. The plasma levels of TN-T and HIF-1α/TN-T are cardiac biomarkers with higher diagnostic accuracy for postmortem diagnosis of cantharidin-induced myocardial injury, VEGF/HIF-1α promises to be a biomarker for PMI estimation. Further studies are needed to verify these biomarkers, based on population, for being a useful tool in postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation.

CAS / MDL: 56-25-7
研究领域: 法医学 · 病理学 · 毒理学
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Biomaterials Science · 2025 · IF 5.7

A cRGD-modified liposome for targeted delivery of artesunate to inhibit angiogenesis in endometriosis

Jianyu Ma,Zhouzhou Liao,Jinbo Li,Xiao Li,Hongling Guo,Qiyu Zhong,Jianyun Huang,Xintao Shuai,Shuqin Chen

Currently, hormonal therapy for endometriosis faces challenges in achieving a balance between treatment and preserving the chance of pregnancy. Therefore, the development of non-hormonal therapy holds significant clinical importance. Angiogenesis is a hallmark of endometriosis, and anti-angiogenic therapies targeting the hypoxia-inducible factor-1α (HIF-1α) pathway are considered potential approaches for endometriosis. However, angiogenesis is also involved in numerous physiological processes, including pregnancy, and systemic anti-angiogenesis may lead to severe adverse effects. To address this, a cRGD-modified liposome nanodrug (cRGD-LP-ART) is synthesized, which enhances drug efficacy while reducing adverse reactions. Artesunate (ART), a non-hormonal drug used to treat malaria, has shown anti-angiogenic effects beyond its original indications in various benign and malignant diseases. With cRGD modification, cRGD-LP-ART can target ectopic lesions and inhibit local angiogenesis by suppressing the HIF-1α/vascular endothelial growth factor (VEGF) pathway. Furthermore, cRGD-LP-ART exhibits better therapeutic effects than free ART, without affecting ovarian function or causing atrophy of the eutopic endometrium, making it a promising new option for non-hormonal therapy of endometriosis. As a combination of liposomes and a clinically approved drug, cRGD-LP-ART holds great potential and clinical prospects for the treatment of endometriosis.

CAS / MDL: 57-88-5
研究领域: 药理学 · 妇科学 · 纳米医学 · 药物递送系统
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ARCHIVES OF GYNECOLOGY AND OBSTETRICS · 2022 ·Vol. 306 ·期 1 ·115-125 · IF 2.493

Berberine attenuates hyperalgesia in mice with adenomyosis

Zhu Bo,Chen Yumei,Guo Min,zhang Chenhui,Huang Lingxiao,Pan Qiangwei,Lin Tao,Lu Yiyi,Shen Xiaolu,Zhang Hongping

Purpose Adenomyosis is a common gynecological disease, but its pathogenesis and treatment options are not yet completely clear. This study aimed to investigate the analgesic effect of berberine on tamoxifen-induced neonatal mouse adenomyosis and its curative effects on the disease. Methods The mouse adenomyosis model was established in neonatal female mice via oral administration of tamoxifen suspended solution. Adenomyosis mice were given berberine by intraperitoneal injection with the dosage of 5, 10, and 20 mg/kg body weight, respectively, at 17 weeks after birth. The pain sensation of the mice was evaluated by hotplate and tail-flick tests. The mRNA levels of gene expression were detected by RT-qPCR. The protein expression was analyzed by ELISA and Western blot. Results Berberine reduced the uterine weight, suppressed the myometrial infiltration of ectopic endometrium, improved the hotplate and tail-flick latency of the adenomyosis mice. Mechanistically, berberine downregulated the expression of genes related to pain and inflammation, such as TRPV1, COX-2, VEGF and OTR, impaired the inflammatory response at the DRG site, and inhibited the expression of TLR4 in DRG and uterine tissues. Conclusions Berberine attenuates hyperalgesia and exhibits analgesic and therapeutic effects on adenomyosis mice.

CAS / MDL: 2086-83-1
研究领域: 药理学 · 妇科学 · 疼痛研究 · 炎症
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Journal of Materials Chemistry B · 2014 ·Vol. 3 ·期 1 ·119-126 · IF 0

Tri-peptide cationic lipids for gene delivery

Yinan Zhao,Shubiao Zhang,Yuan Zhang,Shaohui Cui,Huiying Chen,Defu Zhi,Yuhong Zhen,Shufen Zhang,Leaf Huang

Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as headgroups, a carbamate group as a linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. Further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.

研究领域: 药学 · 分子生物学 · 癌症研究
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Nano Research · 2021 ·Vol. 15 ·期 2 ·1455-1465 · IF 8.897

Regulation of pathological BBB restoration via nanostructured ROS-responsive glycolipid-like copolymer entrapping siVEGF for glioblastoma targeted therapeutics

Wen Lijuan,Peng Yu,Wang Kai,Huang Zhihua,He Shiying,Xiong Ruiwen,Wu Longping,Zhang Fengtian,Hu Fuqiang

Glioblastoma (GBM) is one of the malignant brain tumors with high mortality and no curative treatments. Abnormally elevated vascular endothelial growth factor (VEGF) in GBM seriously disrupts the blood brain barrier (BBB) with an increased permeability, resulting in poor outcome and prognosis. RNAi interference has shown strong potential to inhibit VEGF expression, thus it is necessary to development an effective and safe gene delivery system possessing the ability to cross the BBB and target GBM cells. This study aims to explore the anti-GBM effect of angiopep-2 (Ap) peptide modified reactive oxygen species (ROS) cleavable thioketal (TK) linked glycolipid-like nanocarrier (CSTKSA) delivering anti-VEGF siRNA (R), termed as Ap-CSTKSA/R complexes. Ap functionalized modification produced an enhanced cellular uptake and a stronger bio-distribution of Ap-CSTKSA/R complexes in U87 MG cells and brain tumor tissues, respectively. Ap-CSTKSA/R complexes exhibited great superiority in GBM growth inhibition and finally translated into the longest survival period mainly via receptor-mediated targeting delivery, VEGF gene silencing accompanied with remarkable angiogenesis inhibition, and suppressed expression of caveolin-1 which is involved in BBB functional regulation in the occurrence and treatment of GBM. The study indicated that Ap functionalization on ROS-responsive glycolipid-like copolymer exhibits a promising and effective gene delivery platform for GBM targeted treatment.

研究领域: 肿瘤学 · 神经科学 · 药学 · 基因治疗
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

In vivo real-time monitoring of the development of hypoxia and angiogenesis in cervical cancer

Dan Chen,Wenjing Wang,Qingxia Zhu,Qinya Wang,Daoyi Quan,Yun Zeng,Ke Li,Yun Zhou,Changhu Liu,Wenhua Zhan,Yonghua Zhan

The growth of solid tumors is inevitably accompanied by hypoxia and angiogenesis. Understanding the true state of tissue hypoxia and angiogenesis during tumor progression will help further comprehend the tumor microenvironment and cancer therapy. Here, we provided a novel strategy for the long-term tracking of tumor hypoxia and angiogenesis in cervical cancer. The hypoxia response elements (HRE)-driven luciferase (LUC) reporter gene transfected cervical cancer cell lines were constructed for hypoxia visualization. The hypoxia response activity of HRE-driven LUC was verified in HeLa cells and then monitored via the HeLa-HRE-LUC tumor-bearing mouse models by bioluminescence imaging (BLI). An oxygen-sensitive nanoparticle was constructed for glycerol monooleate cubic liquid crystal material loaded with Ir(piq) 3 /IR780 and could be used for phosphorescence-fluorescence imaging. The imaging result showed that the nanoparticles labeled the low oxygen region overlapped with the BLI signal region detected by HRE-driven LUC in vivo , which confirmed that the hypoxia visualization platform could genuinely reflect the hypoxia level in vivo . The angiogenesis in vivo was reflected by changes in deoxygenated/oxygenated hemoglobin detected by photoacoustic imaging. Besides these, anticancer drug apigenin down-regulated HIF-1α and VEGF under hypoxia conditions and inhibited the tube formation in vitro . Then, the inhibition effects were verified in the hypoxia and angiogenesis visualization model in vivo . This study confirmed a novel in vivo real-time monitoring of tumor hypoxia and angiogenesis strategy, which can provide useful information for further research on cancer progression and anticancer therapy.

研究领域: 肿瘤学 · 生物医学工程 · 分子生物学 · 癌症治疗
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 43 ·9921-9932 · IF 5.344

PLGA/chitosan–heparin composite microparticles prepared with microfluidics for the construction of hMSC aggregates

Min Ge,Yaqi Sheng,Shuyue Qi,Lei Cao,Yan Zhang,Jun Yang

Incorporating poly(lactic-co-glycolic) acid (PLGA) microparticles into human mesenchymal stem cells (hMSC) aggregates has shown promising application prospects. However, the acidic degradation products and burst release of PLGA microparticles still need to be ameliorated. In this study, the PLGA/chitosan–heparin (P/C–h) composite microparticles were successfully fabricated by integrating the double emulsion and microfluidic technology through the precise manipulation of the emulsion composition and flow rate of the two-phase in a flow-focusing chip. The P/C–h microparticles were highly monodispersed with a diameter of 23.45 ± 0.25 μm and shell–core structure of the PLGA encapsulated C–h complex, which were suitable for the fabrication of hMSC aggregates. When the mass ratio of PLGA to the C–h complex was optimized to 2 : 1, the pH of the leach liquor of P/C–h microparticles remained neutral. Compared with those of PLGA microparticles, the cytotoxicity and the initial burst release (loaded FGF-2 and VEGF) were both significantly reduced in P/C–h microparticles. Furthermore, the survival, stemness, as well as secretion and migration abilities of cells in hMSC aggregates incorporating P/C–h microparticles were also enhanced. In summary, the P/C–h composite microparticles prepared by the droplet microfluidic technique support the optimal biological and functional profile of the hMSC aggregates, which may facilitate the clinical applications of MSC-based therapy.

研究领域: 生物医学工程 · 组织工程 · 干细胞生物学 · 药物递送系统
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BIOMEDICINE & PHARMACOTHERAPY · 2023 · IF 7.5

Fisetin induces the upregulation of AKAP12 mRNA and anti-angiogenesis in a patient-derived organoid xenograft model

Nayun Kim,Junhye Kwon,Ui Sup Shin,Joohee Jung

Colorectal cancer (CRC) is associated with high incidence and mortality rates. Targeted therapies for CRC cause various adverse effects, necessitating the development of novel approaches to control CRC progression. In this milieu, we investigated the anti-CRC effects of fisetin, a natural plant flavonoid. Cytotoxicity was performed in CRC patient-derived organoids (30 T and 33 T). Fisetin-induced tumor growth was evaluated in a CRC patient-derived organoid xenograft (PDOX) model. RNA sequencing, immunohistochemistry, and western blotting were performed subsequently. Fisetin significantly decreased organoid viability in a dose-dependent manner. In the PDOX model, fisetin significantly delayed tumor growth, showing a decrease in Ki-67 expression and the induction of apoptosis. In tumor tissues, four genes were identified as differentially expressed between the control and fisetin-treated groups. Among these, A-kinase anchoring protein 12 ( AKAP12 ) level was significantly increased by fisetin treatment (fold change > 2, p  < 0.05). Notably, fisetin significantly inhibited vascular endothelial growth factor (VEGF) and epithelial cell adhesion molecule (EpCAM) via upregulation of AKAP12. Our results demonstrate the upregulation of AKAP12 mRNA and inhibition of angiogenesis by fisetin as a therapeutic strategy against CRC.

CAS / MDL: 528-48-3
研究领域: 肿瘤学 · 药理学 · 分子生物学
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