Nano Research
·
2024
·
IF 9.5
Wang Peng,Wang Qianjin,Wu Dengxian,Zhang Yunyang,Kang Shixiong,Wang Xucai,Gu Jiayu,Wu Hao,Xu Zhihong,Jiang Qing
Bone tissue engineering provides a promising strategy for the treatment of bone defects. Nonetheless, the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive properties. Here, we proposed to endow nano-scaffold (NS) constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles (IONPs) and icaritin (ICA). Four types of nano-scaffolds (NS, ICA@NS, NS-IONPs and ICA@NS-IONPs) were prepared. The incorporation of ICA and IONPs minimally impact their surface morphological and chemical properties. IONPs enhanced the mechanical properties of NS scaffolds, including hardness, tensile strength, and elastic modulus. In vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase (ALP) activity level, expressions of osteogenesis-related genes and proteins as well as mineralized nodule formation. Mechanistic investigations revealed that MEK/ERK (MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK)) signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@NS-IONPs. Furthermore, the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone regeneration. Therefore, IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Bolin Tang,Xiaojun Shen,Yaru Yang,Zhi Xu,Jie Yi,Yongbo Yao,Miao Cao,Yalin Zhang,Hongqin Xia
Cellular responses can be regulated and manipulated through combining stimuli-responsive biomaterial with external stimulus. In this present, the magneto-responsive CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were designed to understand cell behaviors of preosteoblasts, as well as get insight into the underlying mechanism of osteogenic differentiation under static magnetic field (SMF). CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings with differential magnetic property (low, medium and high magnetization) were prepared by incorporation of different mass fraction of CoFe 2 O 4 nanoparticles (6%, 13 %, 20 %) into P(VDF-TrFE) matrix. Cell experiments indicated that all nanocomposite coatings with the assistance of SMF could promote the cell attachment, proliferation and osteogenic differentiation of MC3T3-E1 cells. Among different nanocomposite coatings, low magnetization coating (6%) showed a higher ALP activity and gene expression of Runx2, Col-I, OCN. Molecular biology assays demonstrated that the combination of nanocomposite coatings and SMF could significantly up-regulate the expression level of α2β1 integrin and p-ERK. Whereas, the addition of inhibitor U0126 down-regulated sharply the expression level of p-ERK, which indicated that cellular osteogenic differentiation of MC3T3-E1 cells was governed through α2β1 integrin-mediated MEK/ERK signaling pathways during CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were combined with SMF. This work provided a promising strategy to enhance cellular osteogenic differentiation through a remote-control manner, which exhibited great potential in the application of bone tissue repair and regeneration.
研究领域:
生物材料
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组织工程
·
细胞生物学
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磁性材料
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Kaijia Zhang,Jian Dong,Jun Lu,Lan Li,Huan Liang,Jing Jin,Peng Wang,Xiaolian Sun,Qing Jiang
Bone fracture is a huge medical and sociological problem. Among various therapeutic drugs, icaritin (ICA), as a novel natural osteoinductive agent, has attracted considerable attention due to its remarkable osteogenic effect, but it still has some drawbacks such as poor bone targeting and a rapid plasma clearance rate. Recently, iron oxide nanoparticles (IONPs) show increasingly potential as drug delivery vehicles to overcome these limitations. In this study, porous hollow iron oxide nanoparticles (PHNPs) were synthesized via thermal decomposition and controllable oxidation methods and ICA was incorporated during the hydrophilic phase transfer process. The preosteoblastic MC3T3-E1 cell line was used to evaluate their osteogenic effect, and the results demonstrated that ICA-incorporated PHNPs displayed superior biocompatibility and pronounced alkaline phosphatase activity and expression of osteogenic-related genes and proteins in a synergistic manner. Mechanistic investigations demonstrated that the MEK/ERK/p90RSK signaling pathway might provide a potential explanation for ICA-incorporated PHNP-mediated osteogenic differentiation. Furthermore, hyaluronic acid–cholesterol (HA–CHOL) was used to establish nanoclusters (ICA-PHNP-NCs) for in vivo bone regeneration assessment using a murine femur fracture as a model. The results showed that ICA-PHNP-NCs efficiently accumulated at the fracture site in the presence of a static magnetic field and accelerated fracture repair rapidly and effectively. For the first time, the dual application of osteogenic agents transport and ICA delivery using the ICA-PHNP-NC formulation was achieved against bone fracture, providing a new treatment strategy for diseases related to fractures.
研究领域:
纳米技术
·
药学
·
骨科
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Fangguo Liang,Yusheng Yang,Yuyong Chen,Jiajun Xie,Shencai Liu,Zilin Tan,Liangjie Tian,Zhiqiang Yu,Zhanjun Shi,Peigen Xie,Hong Ding,Qinfeng Yang
In recent years, electroconductive hydrogels (ECHs) have shown great potential in promoting nerve regeneration and motor function recovery following diabetic peripheral nerve injury (PNI), attributed to their similar electrical and mechanical characteristics to innate nervous tissue. It is well-established that PNI causes motor deficits and pain, especially in diabetics. Current evidence suggests that ropivacaine (ROP) encapsulated in poly lactic-co-glycolic acid (PLGA) microspheres (MSs) yield a sustained analgesic effect. In this study, an ECH electroconductive network loaded with MS/ROP (ECH-MS/ROP) was designed as a promising therapeutic approach for diabetic PNI to exert lasting analgesia and functional recovery. This dual delivery system allowed ROP's slow and sequential release, achieving sustained analgesia as demonstrated by our in vivo experiments. Meanwhile, this system was designed like a lamellar dressing, with desirable adhesive and self-curling properties, convenient for treating injured nerve tissues via automatically wrapping tube-like structures, facilitating the process of implantation. Our in vitro assays verified that ECH-MS/ROP was able to enhance the adhesion and motility of Schwann cells. Besides, both in vitro and in vivo studies substantiated that ECH-MS/ROP stimulated myelinated axon regeneration through the MEK/ERK signaling pathway, thereby improving muscular denervation atrophy and facilitating functional recovery. Therefore, this study suggests that the ECH-MS/ROP dressing provides a promising strategy for treating diabetic PNI to facilitate nerve regeneration, functional recovery and pain relief.
研究领域:
生物医学工程
·
神经科学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2018
·
IF 3.382
T.H. Wang,S.Y. Wang,X.D. Wang,H.Q. Jiang,Y.Q. Yang,Y. Wang,J.L. Cheng,C.T. Zhang,W.W. Liang,H.L. Feng
Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro , as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
研究领域:
神经科学
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药理学
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分子生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 17
·期 2
·2373-2383
·
IF 1.692
Yan Li,Chunxia Liu,Ke Tang,Yan Chen,Kang Tian,Zhiqiang Feng,Jindong Chen
Activation of kinase-associated signaling pathways is one of the leading causes of various malignant phenotypes in breast tumors. Strategies of drug discovery and development have investigated approaches to target the inhibition of protein kinase signaling. In the current study, the anti‑tumor activities of a novel multi‑kinase inhibitor, T03 were evaluated in breast cancer. T03 inhibited Taxol‑resistant breast cancer cell proliferation and induced cell cycle arrest and apoptosis in vitro and in vivo. The current results demonstrated that T03 downregulated c‑Raf, platelet‑derived growth factor receptor‑β and other kinases, thus inhibited Raf/mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase and Akt/mechanistic target of rapamycin survival pathways in MCF‑7 and MCF‑7/Taxol xenograft tumors. At a dose of 100 mg/kg, T03 inhibited tumor growth by 62.90 and 59.98% in tumor weight in MX‑1 and MX‑1/T xenograft models, respectively and by 62.60 and 60.22% in MCF‑7 and MCF‑7/T tumors, respectively. These data indicate that the novel multi‑kinase inhibitor, T03, may present as a potential compound to develop novel treatments against breast cancer and Taxol‑resistant breast tumors.
研究领域:
肿瘤学
·
药理学
·
癌症研究
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Jianan Qiao,Shuhui Liu,Yanfeng Huang,Xiang Zhu,Chenyang Xue,Yan Wang,Hui Xiong,Jing Yao
Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond. The BEZ and SEL blocked PI3K/AKT/mTOR and RAF/MEK/ERK respectively to remodel glycolysis and non-canonical glutamine metabolism. ZnPc mediated photodynamic therapy (PDT) could enhance drug release through ROS generation, further facilitating KRAS downstream dual-blockade to create treatment-promoting drug delivery-therapeutic positive feedback. Benefiting from this broad metabolic modulation cascade, the metabolic symbiosis between normoxic and hypoxic tumor cells was also cut off simultaneously and effective tumor vascular normalization effects could be achieved. As a result, PDT was dramatically promoted through glycolysis-non-canonical glutamine dual-metabolism regulation, achieving complete elimination of tumors in vivo . Above all, this study achieved effective multidimensional metabolic modulation based on integrated smart nanodrug delivery, helping overcome the therapeutic challenges posed by KRAS mutations of PDAC.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
代谢调控
·
光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-25
·
IF 10.6
Zhou Shiqi,Xiao Cairong,Fan Lei,Yang Jinghong,Ge Ruihan,Cai Min,Yuan Kaiting,Li Changhao,Crawford Ross William,Xiao Yin,Yu Peng,Deng Chunlin,Ning Chengyun,Zhou Lei,Wang Yan
The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.
研究领域:
骨科
·
生物材料
·
组织工程
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Wen Shuai,Huan Xiao,Panpan Yang,Yiwen Zhang,Faqian Bu,Yongya Wu,Qiu Sun,Guan Wang,Liang Ouyang
The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified 36c with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit 18. In preclinical studies, 36c showed powerful ERK1/2 inhibitory activities (ERK1/2 IC50 = 0.11/0.08 nM) and potent antitumor efficacy both in vitro and in vivo against triple-negative breast cancer and colorectal cancer models harboring BRAF and RAS mutations. 36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.
研究领域:
肿瘤学
·
药理学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Jin-Feng Teng,Da-Lian Qin,Qi-Bing Mei,Wen-Qiao Qiu,Rong Pan,Rui Xiong,Ya Zhao,Betty Yuen-Kwan Law,Vincent Kam-Wai Wong,Yong Tang,Chong-Lin Yu,Feng Zhang,Jian-Ming Wu,An-Guo Wu
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Our previous studies have proven that Trillium tschonoskii Maxim. (TTM), a traditional Chinese medicine , possesses potent anti-tumor effect. However, the detailed components and molecular mechanism of TTM in anti-NSCLC are still unknown. In the present experiment, polyphyllin VI (PPVI) was successfully isolated from TTM with guidance of the anti-proliferative effect in A549 cells, and the cell death of PPVI treated A549 and H1299 cells was closely linked with the increased intracellular ROS levels. In addition, PPVI induced apoptosis by promoting the protein expression of Bax/Bcl2, caspase-3 and caspase-9, and activated autophagy by improving LC3 II conversion and GFP-LC3 puncta formation in A549 and H1299 cells. The mechanism study found that the activity of mTOR which regulates cell growth, proliferation and autophagy was significantly suppressed by PPVI. Accordingly, the PI3K/AKT and MEK/ERK pathways positively regulating mTOR were inhibited, and AMPK negatively regulating mTOR was activated. In addition, the downstream of mTOR, ULK1 at Ser 757 which downregulates autophagy was inhibited by PPVI. The apoptotic cell death induced by PPVI was confirmed, and it was significantly suppressed by the overexpression of AKT, ERK and mTOR, and the induced autophagic cell death which was depended on the Atg7 was decreased by the inhibitors, such as LY294002 (LY), Bafilomycin A1 (Baf), Compound C (CC) and SBI-0206965 (SBI). Furthermore, the mTOR signaling pathway was regulated by the increased ROS as the initial signal in A549 and H1299 cells. Finally, the anti-tumor growth activity of PPVI in vivo was validated in A549 bearing athymic nude mice . Taken together, our data have firstly demonstrated that PPVI is the main component in TTM that exerts the anti-proliferative effect by inducing apoptotic and autophagic cell death in NSCLC via the ROS-triggered mTOR signaling pathway, and PPVI may be a promising candidate for the treatment of NSCLC in future.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
·
2024
·Vol. 29
·期 1
·67
·
IF 1.6
Li Yang,Zhuanyun Du,Yuhang Peng,Wenyao Zhang,Wenli Feng,Ying Yuan
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
研究领域:
肿瘤学
·
药理学
·
血液学
·
癌症治疗
·
药物重定位
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Yian Luo,Lei Fan,Can Liu,Huiquan Wen,Shihuan Wang,Pengfei Guan,Dafu Chen,Chengyun Ning,Lei Zhou,Guoxin Tan
Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury (SCI) by bridging cavity spaces. However, there are limited reports of injectable, electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI. Hence, a natural extracellular matrix (ECM) biopolymer (chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole, which imparted electroconductive properties, is developed for traumatic SCI repair. The resulting hydrogels showed mechanical (~928 Pa) and conductive properties (4.49 mS/cm) similar to natural spinal cord tissues. Moreover, the hydrogels exhibited shear-thinning and self-healing abilities, which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI. In vitro, electroconductive ECM hydrogels promoted neuronal differentiation, enhanced axon outgrowth, and inhibited astrocyte differentiation. The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo (n = 6), and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways, thereby achieving significant locomotor function restoration in rats with spinal cord injury (p < 0.001, compared to SCI group). Overall, the injectable self-healing electroconductive ECM-based hydrogels developed in this study are ideal biomaterials for treatment of traumatic SCI.
研究领域:
生物材料
·
神经科学
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）