Materials Today Bio
·
2024
·
IF 8.7
Yuliang Sun,Wenlong Zhang,Yilin Lu,Yanan He,Badrul Yahaya,Yanli Liu,Juntang Lin
In tumor treatment, the deposition of nanoenzymes in normal tissues and cause potential side effects are unavoidable. Here, we designed an intelligent biomimetic nanoenzymes carrier platform (MSC intelligent ) that endows the carrier platform with “wisdom” by introducing Affibody-Notch(core)-VP64-GAL4/UAS-HSV-TK artificial signal pathways to mesenchymal stem cells (MSCs). This intelligent nanoenzymes carrier platform is distinguished from the traditional targeting tumor microenvironment or enhancing affinity with tumor, which endue MSC intelligent with tumor signal recognition capacity, so that MSC intelligent can autonomously distinguish tumor from normal tissue cells and feedback edited instructions. In this study, MSC intelligent can convert tumor signals into HSV-TK instructions through artificial signal pathway after recognizing Her2 (+) tumor. Subsequently, the synthesized HSV-TK can rupture MSC intelligent under the mediation of ganciclovir, and release the preloaded Cu/Fe nanocrystal clusters to kill the tumor accurately. Meanwhile, MSC intelligent without recognizing tumors will not initiate the HSV-TK instructions, thus being unresponsive to GCV and blocking the release of nanoenzymes in normal tissues. Consequently, MSC intelligent is the first intelligent biomimetic nanoenzymes carrier platform, which represents a new biomimetic nanoenzymes targeting mode.
研究领域:
癌症生物学
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纳米技术
·
分子生物学
·
干细胞研究
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2021
·Vol. 100
·期 2
·
IF 2.273
Haijing Wang,Zhuolei Feng,Xue Han,Yue Xing,Xiaomei Zhang
The endothelial-mesenchymal transition (EndMT) participates in the progression of diabetic retinopathy (DR), but cell-intrinsic factors modulating this process remain elusive. In this study, we explored the role of lysophosphatidic acid (LPA) – producing enzyme, acylglycerol kinase (AGK), in the EndMT of human retinal microvascular endothelial cells (HRECs) under high-glucose (HG) conditions. We found that AGK was significantly elevated in HG-treated cells. In addition, AGK knockdown reversed the HG-induced EndMT in HRECs, which was evidenced by the increased endothelial markers (CD31 and VE-cadherin) and decreased mesenchymal markers (FSP1 and α-SMA). Furthermore, downregulation of AGK inhibited the HG-induced activation of transforming growth factor β (TGF-β)/Notch pathways, whereas exogenous TGF-β1 (10 ng/mL) impeded the inhibitory effects of AGK knockdown on HG-induced EndMT in HRECs. Additionally, the silencing of AGK abolished the HG-induced upregulation of LPA and its receptor, LPA receptor 1 (LPAR1), and overexpression of LPAR1 further rescued the AGK knockdown-mediated inhibition of the EndMT process. In conclusion, we demonstrate that downregulation of AGK suppresses HG-induced EndMT in HRECs through regulating the LPAR1/TGF-β/Notch signaling pathway, indicating that AGK might be a potential therapeutic target for the treatment of DR.
研究领域:
分子生物学
·
细胞生物学
·
糖尿病研究
·
眼科学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Ruijing Li,Zhao Fang,Cheng Wang,Xinlin Zhu,Xiaolong Fu,Jiajun Fu,Wuwei Yan,Yong Yang
Solid-state polymer electrolytes (SPEs) with outstanding flexibility and self-healing capacity are appealing for utilization in reliable and wearable electronic devices. Herein, a highly stretchable (extensibility > 1500% and stress > 490 kPa), non-flammable and notch-insensitive intrinsic self-healing SPE based on six-armed poly(N,N,N-trimethyl-N-((2-(dimethylamino)ethyl methacrylate)-7-propyl)-ammonium dual bis(trifluoromethanesulfonyl) imides), imidazole-based ionic liquid (EMIM–TFSI) and LiTFSI is fabricated. The multi-armed structure in combination with the multiple charged center endow the six-armed dicationic polymeric ionic liquid (DPIL-6) with significantly strengthened ionic attractions and Van der Waals' force among the polymer segments, thus conferring the DPIL-6 derived SPE (DPIL-6-SPE) with prominent self-healing ability (recovery time < 2 h, 25 ℃). Moreover, DPIL-6-SPE presents a superior adhesion strength (weight loading > 200 g) towards lithium electrode, signifying excellent interfacial compatibility. Compared with the counterpart of monocationic polymeric ionic liquid derived SPE (MPIL-6-SPE), the multiple cationic center in DPIL-6-SPE facilitates the dissociation of lithium salt and liberates more Li + from trapping with TFSI - , thereby resulting in a superior ionic conductivity (over 10 -5 S cm −1 at room temperature) and lithium ion transference number (0.46). The as-assembled LiFePO 4 /DPIL-6-SPE/Li battery can deliver a high discharge capacity of 152.6 mAh g −1 at 0.1C, and its capacity retention rate reaches 94% after 50 cycles with a coulombic efficiency of 96%. In particular, the mechanical properties and conductivity of DPIL-6-SPE can fully recover after repeated damage, conferring the derived soft-pack battery stable powering capacity upon multi-angle bending and folding. The design of multi-armed and multiple charged PILs provides new avenues for developing flexible electronic devices with self-healing capacity.
研究领域:
材料科学
·
能源科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Shaochen Pang,Yue Gao,Fengbang Wang,Yuanyuan Wang,Mengxi Cao,Wenjuan Zhang,Yong Liang,Maoyong Song,Guibin Jiang
Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo . We revealed that AgNP treatment at the concentration of 2 μg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.
研究领域:
纳米技术
·
伤口愈合
·
斑马鱼生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Shaojun Liang,Shengxian Liang,Hui Zhou,Nuoya Yin,Francesco Faiola
2′,2′,4,4′-tetrabromo diphenyl ether (BDE-47), one of the most abundant congeners of commercial pentaBDE utilized as flame retardants , has been phased out of production due to its potential neural toxicity and endocrine disrupting activities, and yet still present in the environment. Several alternatives to BDE-47, including tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), tetrachlorobisphenol A (TCBPA) and decabromodiphenyl ether (BDE-209), are presently employed without restrictions and their potential toxic effects on human neural development are still unclear. In this study, we utilized a human neural stem cell (hNSC)-based system to evaluate the potential developmental neurotoxic effects of the above-mentioned five chemicals, at environment and human exposure relevant concentrations. We found that those compounds slightly altered the expression of hNSC identity markers ( SOX2 , SOX3 and NES ), without impairing cell viability or proliferation, in part by either modulating glycogen synthase kinase 3 beta (GSK3β) signaling (TBBPS, TCBPA and BDE-47), and slightly disturbing the NOTCH pathway (TBBPA, TBBPS and TCBPA). Moreover, the five chemicals seemed to alter hNSC differentiation by perturbing triiodothyronine (T3) cellular signaling. Thus, our findings suggest that the five compounds, especially TBBPS, TCBPA, and BDE-47, may affect hNSC self-renewal and differentiation abilities and potentially elicit neural developmental toxicity.
研究领域:
神经科学
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毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Yingqi Chen,Zuocheng Qiu,Xueling Hu,Tiehua Wang,Guoqing Li,Ziling Tang,Chongzhou Fang,Weibei Sheng,Jin Zhao,Fei Yu,Jian Weng,Anjaneyulu Udduttula,Geetha Manivasagam,Hui Zeng
In clinical settings, regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods, restricted bone growth medications, and a scarcity of commercial bone grafts. To treat this life-threatening issue, improved biofunctional grafts capable of properly healing critical-sized bone defects are required. In this study, we effectively created anti-fracture hydrogel systems using spongy-like metal-organic (magnesium-phosphate) coordinated chitosan-modified injectable hydrogels (CPMg) loaded with a bioinspired neobavaisoflavone (NBF) component. The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphate-buffered saline. They also demonstrated prolonged and stable release profiles of Mg 2+ and NBF. Importantly, CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells. To better understand the underlying mechanism of Mg 2+ and NBF component, as well as their synergistic effect on osteogenesis, we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways. Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins (Runx2, OCN, OPN, BMPS and ALP). In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects. Based on these findings, we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
研究领域:
生物材料
·
组织工程
·
骨科
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Shisuo Jing,Huayuan Chen,Ergang Liu,Meng Zhang,Feng Zeng,Huan Shen,Yuefei Fang,Bahtiyor Muhitdinov,Yongzhuo Huang
Inflammatory bowel disease (IBD) is a chronic, life quality-reducing disease with no cures available yet. To develop an effective medication suitable for long-term use is an urgent but unmet need. Quercetin (QT) is a natural dietary flavonoid with good safety and multifaceted pharmacological activities against inflammation. However, orally administrated quercetin yields unproductive outcomes for IBD treatment because of its poor solubility and extensive metabolism in the gastrointestinal tract . In this work, a colon-targeted QT delivery system (termed COS-CaP-QT) was developed, of which the pectin (PEC)/Ca 2+ microspheres were prepared and then crosslinked by oligochitosan (COS). The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon. The mechanism study showed that QT triggered the Notch pathway to regulate the proliferation of T helper 2 (Th2) cells and group 3 innate lymphoid cells (ILC3s) and the inflammatory microenvironment was remodeled. The in vivo therapeutic results revealed that COS-CaP-QT could relieve the colitis symptoms and maintain the colon length and intestinal barrier integrity.
研究领域:
药剂学
·
药理学
·
胃肠病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Zhongyuan Zhang,Wenshu Xu,Zhenhua Zhang,Xiaoxue Chen,Hui Jin,Ningning Jiang,Hui Xu
This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.
研究领域:
药理学
·
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 108
·期 1
·30-38
·
IF 3.221
Rui Ma,Zhen-Gang Ma,Jin-Lai Gao,Yu Tai,Lan-Jun Li,Hai-Bin Zhu,Li Li,De-Li Dong,Zhi-Jie Sun
Niclosamide is an antihelminthic drug. Recent studies show that niclosamide exerts antitumor activity through inhibiting multiple signals including Wnt/β-catenin, mTORC1, signal transducer and activator of transcription 3, NF-κB, notch signals; however, the insolubility and poor bioavailability limits its potential clinic use, the aim of the present work is to synthesize an injectable pegylated niclosamide (polyethylene glycol-modified niclosamide) and investigate its antitumor activity in vitro and in vivo. The pegylated niclosamide (mPEG5000-Nic) was synthesized and the chemical structure was identified by Fourier transform infrared spectra and 1 H nuclear magnetic resonance spectra. The antitumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. The water solubility of niclosamide in mPEG5000-Nic was significantly increased. Niclosamide could be released from mPEG5000-Nic nanoparticles in PBS solution. mPEG5000-Nic inhibited the cell viability of CT26 and HCT116 cells in vitro. No animal death was observed in mice with intraperitoneal injection of mPEG5000-Nic (equivalent to 1000 mg/kg niclosamide) within 24 hr, indicating that mPEG5000-Nic was less toxic. In nude mouse, xenograft model of CT26 colon carcinoma, intraperitoneal injection of mPEG5000-Nic (equivalent to niclosamide 50 mg/kg) inhibited tumor growth but had no effect on animal body weight and heart, liver, kidney, and lung weight in vivo. Meanwhile, in the same model, intraperitoneal injection of the positive clinic drug 5-fluorouracil not only inhibited the tumor growth, but also reduced the animal body weight. Our study demonstrates that pegylated niclosamide is novel niclosamide delivery system with clinical perspective for cancer therapy.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
npj Science of Food
·
2023
·Vol. 7
·期 1
·1-13
·
IF 6.4
Xu Enbo,Niu Ruihao,Lao Jihui,Zhang Shengliang,Li Jie,Zhu Yiyuan,Shi Huimin,Zhu Qingqing,Chen Yijian,Jiang Yuyan,Wang Wenjun,Yin Jun,Chen Qihe,Huang Xiao,Chen Jun,Liu Donghong
Tissue-like cultured meats of some livestock have successfully been established by different approaches. However, the production of a structure similar to fish fillets is still challenging. Here, we develop tissue-like cultured fish fillets by assembly of large yellow croaker muscle fibers and adipocytes with 3D-printed gel. Inhibition of Tgf-β and Notch signals significantly promoted myogenic differentiation of piscine satellite cells (PSCs). The mixture of fish gelatin and sodium alginate combined with a p53 inhibitor and a Yap activator supported PSC viability and proliferation. Based on the texture of fish muscle tissue, a 3D scaffold was constructed by gelatin-based gel mixed with PSCs. After proliferation and differentiation, the muscle scaffold was filled with cultured piscine adipocytes. Finally, tissue-like fish fillets with 20 × 12 × 4 mm were formed, consisting of 5.67 × 10 7 muscles and 4.02 × 10 7 adipocytes. The biomanufacture of tissue-like cultured fish fillet here could be a promising technology to customize meat production with high fidelity.
研究领域:
生物技术
·
食品科学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Caiping Yan,Pengrui Zhang,Qiwei Qin,Ke Jiang,Yue Luo,Chao Xiang,Jiangtao He,Lu Chen,Dianming Jiang,Wenguo Cui,Yuling Li
The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨生物学
·
血管生物学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Xu Zhang,Zhang Yuan,Jianshuang Wu,Ye He,Guifang Lu,Dan Zhang,Yan Zhao,Rongqian Wu,Yi Lv,Kaiyong Cai,Shuixiang He
Traditional drug-based treatments for inflammatory bowel disease (IBD) have significant limitations due to their potential off-target systemic side-effects. Currently, there is a lack of understanding on how to effectively address excessive oxidative stress, dysregulated immune homeostasis, and microbiota dysbiosis within the IBD microenvironment. Herein, we introduce a nanotherapeutic approach, named LBL-CO@MPDA, for IBD treatment. LBL-CO@MPDA is an orally administered formulation that supplies carbon monoxide (CO) for therapeutic purposes. To create the LBL-CO@MPDA nanocomposite, we developed a layer by layer (LBL) self-assembly strategy where we coated chitosan/alginate polyelectrolytes onto the surface of CO prodrug-loaded mesoporous polydopamine nanoparticles (CO@MPDA). Benefiting from the negatively charged surface of the LBL coating, it allows for targeted accumulation of LBL-CO@MPDA specifically onto the positively charged inflamed colon lesions through electrostatic interactions. Furthermore, in the oxidative microenvironment of the inflamed colon, the nanotherapeutic system releases CO in a responsive manner. Interestingly, CO@MPDA ameliorates inflammatory conditions by MPDA-mediated ROS-scavenging and CO-mediated immunomodulation. CO-supplying activates heme oxygenase-1, leading to macrophage M2 polarization via the Notch/Hes1/Stat3 signaling pathway, while suppressing the inflammatory response by down-regulating the p38 MAPK and NF-κB (p50/p65) signaling pathways. In the mice model of dextran sulfate sodium (DSS)-induced IBD, LBL-CO@MPDA effectively reverses the pro-inflammatory microenvironment and restores gut barrier functions through multiple mechanisms, including scavenging oxidative stress, restoring immune homeostasis, and modulating the gut microbiota. Collectively, our findings highlight the promising potential of this innovative nanotherapeutic strategy for the targeted treatment of IBD.
研究领域:
药学
·
纳米技术
·
免疫学
·
胃肠病学
·
生物医学工程
✓ 已验证
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）