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Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to inhibit glioma growth

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Regenerative Biomaterials 2024年第5期3卷 121-134页

作者： Yifu Wang Hongfeng Wu zhu Chen Jun Cao xiangdong zhu Xingdong Zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064P.R.China College of Biomedical Engineering Sichuan UniversityChengdu 610064P.R.China Medical School Kunming University of Science and TechnologyKunming 650500P.R.China Institute of tissue engineering and stem cells Nanchong Central HospitalNorth Sichuan Medical CollegeNanchong 637000P.R.China

Despite a growing body of studies demonstrating the specific antitumor effect of nano-hydroxyapatite(n-HA),the underlying mechanism remained *** reticulum(ER)and mitochondria are two key players in intracellular Ca^(2+)homeostasis and both require Ca^(2+)to ***,the ER–mitochondria interplay coordinates the maintenance of cellular Ca^(2+)homeostasis to prevent any negative consequences from excess of Ca^(2+),hence there needs in-depth study of n-HA effect on *** this study,we fabricated needle-like n-HA to investigate the anti-tumor effectiveness as well as the underlying mechanisms from cellular and molecular *** from in vitro experiments indicated that the growth and invasion of glioma cells were obviously reduced with the aid of *** is interesting to note that the expression of ER stress biomarkers(GRP78,p-IRE1,p-PERK,PERK,and ATF6)were all upregulated after n-HA treatment,along with the activation of the pro-apoptotic transcription factor CHOP,showing that ER stress produced by n-HA triggered cell ***,the increased expression level of intracellular reactive oxygen species and the mitochondrial membrane depolarization,as well as the downstream cell apoptotic signaling activation,further demonstrated the pro-apoptotic roles of n-HA induced Ca^(2+)overload through inducing mitochondria *** in vivo data provided additional evidence that n-HA caused ER stress and mitochondria damage in cells and effectively restrain the growth of glioma ***,the work showed that n-HA co-activated intracellular ER stress and mitochondria damage are critical triggers for cancer cells apoptosis,offering fresh perspectives on ER-mitochondria targeted anti-tumor therapy.

关键词： nano-hydroxyapatite endoplasmic reticulum stress glioma apoptosis protein mitochondria damage

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Humic acid and metal ions accelerating the dechlorination of 4-chlorobiphenyl by nanoscale zero-valent iron

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Journal of Environmental Sciences 2011年第8期23卷 1286-1292页

作者： Yu Wang Dongmei Zhou Yujun Wang xiangdong zhu Shengyang Jin State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil Science Chinese Academy of Sciences Nanjing 210008 China. Graduate University of Chinese Academy of Sciences Beijing 100049 China

Transformation of polychlorinated biphenyls （PCBs） by zero-valent iron represents one of the latest innovative technologies for environmental remediation. The dechlorination of 4-chlorobiphenyl （4-C1BP） by nanoscale zero-valent iron （NZVI） in the presence of humic acid or metal ions was investigated. The results showed that the dechlorination of 4-C1BP by NZVI increased with decreased solution pH. When the initial pH value was 4.0, 5.5, 6.8, and 9.0, the *** efficiencies of 4-CIBP after 48 hr were 53.8%, 47.8%, 35.7%, and 35.6%, respectively. The presence of humic acid inhibited the reduction of 4-CIBP in the first 4 hi＇, and then significantly accelerated the dechlorination by reaching 86.3% in 48 hr. Divalent metal ions, Co2＋, Cu2＋, and Ni2＋, were reduced and formed bimetals with NZVI, thereby enhanced the dechlorination of 4-CIBP. The dechlorination percentages of 4-CIBP in the presence of 0.1 mmol/L Co2~, Cuz~ and Niz~ were 66.1%, 66.0% and 64.6% in 48 hr, and then increased to 67.9%, 71.3% and 73.5%, after 96 hr respectively. The dechlorination kinetics of 4-C1BP by the NZVI in all cases followed pseudo-first order model. The results provide a basis for better understanding of the dechlorination mechanisms of PCBs in real environment.

关键词： 4-chlorobiphenyl nanoscale zero-valent iron humic acid metal ions dechlorination

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Exploration of the key functional proteins from an efficient cellulolytic microbial consortium using dilution-to-extinction approach

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Journal of Environmental Sciences 2016年第5期28卷 199-207页

作者： Qinghua Zhang Hanguang Li xiangdong zhu Fenju Lai Zhijun Zhai Yuanxiu Wang College of Bioscience and engineering Jiangxi engineering Laboratory for the development and Utilization of Agricultural Microbial ResourcesJiangxi Agricultural University Nanehan9 330045 China

In the present study, the cellulose binding proteins（CBPs） secreted by a putative cellulolytic microbial consortium were isolated and purified by affinity digestion. The purified CBPs were subsequently separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis（SDS-PAGE）. Using mass spectrometric analyses, eight CBPs were identified and annotated to be similar to known proteins secreted by Clostridium clariflavum DSM 19732 and Paenibacillus sp. W-61. In addition, in combination with dilution-to-extinction approach and zymogram analysis technique, CBPs 6（97 k Da） and 12（52 k Da） were confirmed to be the key functional proteins that influence cellulolytic activities. Moreover, structural domain analyses and enzymatic activity detection indicated that CBPs 6 and 12 contained glycoside hydrolase families（GH） 9 and 48 catalytic modules, which both revealed endoglucandase and xylanase activities. It was suggested that the coexistence of GH9 and GH48 catalytic domains present in these two proteins could synergistically promote the efficient degradation of cellulose.

关键词： Microbial consortium Cellulolytic Cellulose binding protein Dilution-to-extinction approach

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Urgently reveal longly hidden toxicant in a familiar fabrication process of biomass-derived environment carbon material

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Journal of Environmental Sciences 2021年第2期33卷 250-256页

作者： Chao Jia Jiewen Luo Jiajun Fan James H.Clark Shicheng Zhang xiangdong zhu Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention(LAP3) Department of Environmental Science and EngineeringFudan UniversityShanghai 200433China Green Chemistry Centre of Excellence Department of ChemistryUniversity of YorkYork YO105DDUnited Kingdom Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China Shanghai Technical Service Platform for Pollution Control and Resource Utilization of Organic Wastes Shanghai200438China

Biomass-derived N-doped carbon(BNC)is an important environmental material and widely used in the fields of water purification and soil ***,the toxicant in the commonly used synthesis process of BNC materials have been largely ***,we firstly report the presence of a highly toxic by-product(KCN)in the activation process of BNC materials consequential of the carbothermal reduction *** this carbothermal reduction reaction also regulates the N-doping and pore development of BNC materials,the KCN content directly relates with the properties of BNC material ***,a high KCN content(-611 mg)can occur in the production process of per g BNC material with high specific surface area(-3600 m^2/g).Because the application performance of BNC material is determined by the surface area and available N doping,therefore,production of a BNC material with high performance entails high ***,this study proves a completely new risk recognition on a familiar synthesis process of biomass-based ***,strict protective device should be taken in fabrication process of biomass-derived carbon material.

关键词： Biomass Biomass based N-doped carbon Carbothermal reduction reaction Pore Toxic by-product

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The morphology of hydroxyapatite nanoparticles regulates clathrinmediated endocytosis in melanoma cells and resultant anti-tumor efficiency

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Nano Research 2022年第7期15卷 6256-6265页

作者： Hongfeng Wu Yuchen Hua Jinjie Wu Qin Zeng Xiao Yang xiangdong zhu Xingdong Zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials&Institute of Regulatory Science for Medical Devices&NMPA Research Base of Regulatory Science for Medical Devices Sichuan UniversityChengdu 610064China Research Center for Materials Genome Engineering Sichuan UniversityChengdu 610064China

Clathrin-mediated endocytosis plays a critical role for hydroxyapatite nanoparticles(HANPs)to enter tumor cells,induce mitochondrial apoptosis,and inhibit tumor *** study was aimed to investigate how the morphology of HANPs impacts the endocytosis of the particles in melanoma cells,and their anti-tumor effect by using in vitro cell experiments and in vivo tumor animal *** shapes of HANPs,including granular HANPs(G-HANPs),rod-like HANPs(R-HANPs),and needle-like HANPs(N-HANPs),were successfully prepared by wet chemical *** the three HANPs could be internalized into A375 melanoma cells as indicated by cellular transmission electron microscopy *** these HANPs,only G-HANPs induced morphological change of mitochondria and loss of mitochondrial membrane potential(Δψm),and exhibited the greatest intracellular internalization efficiency in the tumor ***,the results of immunofluorescence staining and western blotting indicated that the level of adaptin-2(AP2)protein was up-regulated by all the HANPs,and highest in G-HANPs treated A375 ***,in the tumor-bearing mouse model,we found that tumor growth was delayed by all the three HANPs,of which,G-HANPs delayed tumor growth most efficiently and presented a highest expression level of AP2 protein in tumor ***,this study suggested that the morphology of HANPs regulated their endocytosis efficiency and their effect to inhibit tumor *** work facilitates to direct the rational design of nano-materials for tumor therapy.

关键词： hydroxyapatite nanoparticles adaptin-2 protein morphology endocytosis anti-tumor effect

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Whisker of biphasic calcium phosphate ceramics: Osteoimmunomodulatory behaviors

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Nano Research 2022年第10期15卷 9169-9182页

作者： Jinjie Wu Cong Feng Menglu Wang Hongfeng Wu xiangdong zhu Xiangfeng Li Xuening Chen Xingdong Zhang National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengdu 610064China

Immune systems play a critical role in the regulation of bone formation and homeostasis,which arouses a growing interest in the development of biomaterials that can modulate both immune response and *** this study,biphasic calcium phosphate(BCP)ceramics were modified with different whiskered surface,and their effects on macrophage polarization and functional status were *** results showed that compared to BCP-W ceramics with long and solid whiskers,BCPHW ceramics with short and hollow whiskers surface were conducive to protein adsorption and macrophage ***,BCP-HW ceramics down-regulated the expression of M1 macrophage markers(Il1β,Tnfα,and iNos),promoted the expression of M2 macrophage markers(Il10 and Arg)and growth factors(Tgfβ1 and Bmp2),which might be attributed to the differential integrin expression regulated by different whisker *** conditioned medium derived from the supernatant of macrophage/whiskered ceramic co-culture was further used to culture MC3T3-E1 pre-osteoblasts to evaluate the effects of whiskered ceramic-mediated macrophage secretion on osteogenesis in *** with BCP-W ones,the secretion pattern induced by BCP-HW ceramics could promote the expression of bone markers in pre-osteoblasts,which might due to the activation of intracellular signaling cascades like BMP/Smad and TGF-β/Smad signaling pathways.A murine intramuscular implantation model suggested that after implantation for 1,2,and 3 weeks,BCP-HW ceramics drove the switch of macrophages to ARG+wound-healing M2 phenotype,while BCP-W ceramics increased the proportion of iNOS+M1 inflammatory *** 2 months,only BCP-HW could induce ectopic bone *** together,these results indicated that BCP ceramics with hollow whiskers were capable of creating a proper inflammatory microenvironment to induce bone *** whiskered BCP ceramics with good osteo-immunomodulatory capacity hold promise in serving as bone gra

关键词： whisker macrophage polariztion osteoinduction biphasic calcium phosphate surface structure

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Functionalize d 3D-printe d porous titanium scaffold induces in situ vascularized bone regeneration by orchestrating bone microenvironment

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Journal of Materials Science & Technology 2023年第22期153卷 92-105页

作者： Bo Yuan Pin Liu Rui Zhao Xiao Yang Zhanwen Xiao Kai Zhang xiangdong zhu Xingdong Zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China College of Biomedical Engineering Sichuan UniversityChengdu 610064China

Titanium(Ti)and its alloys have been extensively explored for treating load-bearing bone ***-ever,high-stress shielding,weak osteogenic activity,and insufficient vascularization remain key chal-lenges for the long-term clinical outcomes of Ti-based ***,inspired by structural and func-tional cues of bone regeneration,a silicon-doped nano-hydroxyapatite(nSiHA)/titanium dioxide(TiO_(2))composite coating with a hierarchical micro/nano-network structure is constructed on the surface of a 3D-printed porous Ti scaffold via a combined strategy of acid-alkali(AA)treatment and electrochemi-cal deposition technique,which not only endows the scaffold with excellent osteoinduction ability but can also effectively immobilize and release vascular endothelial growth factor(VEGF).The results of the in vitro cell experiments show that the functionalized Ti scaffold significantly promotes osteogenesis in bone marrow mesenchymal stem cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs)by activating the extracellular signal-regulated protein kinase(ERK)and HIF-1αsignaling *** being implanted into a rat femoral condyle defect model,the functionalized Ti scaffold can induce in situ vascularized bone regeneration by orchestrating the two coupled processes of angio-genesis and *** findings indicate that the functionalized Ti scaffold has great potential in bone tissue regeneration and is a promising candidate for load-bearing bone defect repair.

关键词： Porous titanium 3D-printing Hierarchical micro/nano-structure Bone microenvironment Vascularization Bone regeneration

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Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response

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Neural Regeneration Research 2014年第23期9卷 2074-2080页

作者： Feng Zhou Liang Wang Panpan Liu Weiwei Hu xiangdong zhu Hong Shen Yuanyuan Yao Department of Neurosurgery Second Affiliated Hospital School of Medicine Zhejiang University Medical College Ningbo University Department of Anesthesiology Second Affiliated Hospital School of Medicine Zhejiang University

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.

关键词： nerve regeneration brain injury puerarin cerebral ischemia reperfusion injury rats inflammatory reaction Toll-like receptor-4 nuclear factor kappa B myeloid differentiation factor 88 tumor necrosis factor-α middle cerebral artery occlusion neural regeneration

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Promoting proliferation and differentiation of BMSCs by green tea polyphenols functionalized porous calcium phosphate

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Regenerative Biomaterials 2018年第1期5卷 35-41页

作者： Kang Zhou Xiuli Ren Mengen Zhao Xifan Mei Peng Zhang Zhenhua Chen xiangdong zhu Jinzhou Medical University Jinzhou 121001People’s Republic of China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064People’s Republic of China

In this article,we proposed a facile protocol to functionalize porous calcium phosphate ceramics(PCPC)using dietary tea polyphenols(TP).TP molecules was attracted and anchored by Ca2t ions from the surface of *** TP molecules modulated the nucleation and crystallization of calcium phosphate nanorods assemblies on the surface of *** results prove that these calcium phosphate nanorods assemblies accompanies functional groups of TP make PCPC/TP effectively promote proliferation and differentiation of bone mesenchymal stem cells(BMSCs).We inferred that these calcium phosphate nanorods assemblies might change the surface microenvironment of PCPC,which is critical to promote the proliferation and differentiation of *** with naked PCPC,PCPC/TP obviously increased BMP2,ErK/MAPK and JNK/MAPK level and mineralization capacity of cells(ALP level).

关键词： green tea polyphenols porous ceramics BMSCs osteoinduction

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Osteoporotic bone recovery by a bamboo-structured bioceramic with controlled release of hydroxyapatite nanoparticles

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Bioactive Materials 2022年第11期7卷 379-393页

作者： Rui Zhao Tieliang Shang Bo Yuan xiangdong zhu Xingdong Zhang Xiao Yang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu610064China

While most bone defects can be repaired spontaneously,the healing process can be complicated due to insuf-ficient bone regeneration when osteoporosis *** materials that intrinsically stimulate bone for-mation without inclusion of exogenous cells or growth factors represent a highly desirable alternative to current grafting strategies for the management of osteoporotic ***,we developed a series of hydroxyapatite bioceramics composed of a microwhiskered scaffold(wHA)reinforced with multiple layers of releasable hy-droxyapatite nanoparticles(nHA).These novel bioceramics(nwHA)are tunable to optimize the loading amount of nHA for osteoporotic bone *** utility of nwHA bioceramics for the proliferation or differentiation of osteoporotic osteoblasts in vitro is demonstrated.A much more compelling response is seen when bioceramics are implanted in critical-sized femur defects in osteoporotic rats,as nwHA bioceramics promote significantly higher bone regeneration and delay adjacent bone ***,the nwHA bioceramics loaded with a mod-erate amount of nHA can induce new bone formation with a higher degree of ossification and *** types of osteogenesis inside the nwHA bioceramic pores were discovered for the first time,depending on the direction of growth of the new *** current study recommends that these tailored hybrid micro/nano-structured bioceramics represent promising candidates for osteoporotic bone repair.

关键词： Nano hydroxyapatite Bioceramics Osteogenesis Bone regeneration Osteoporosis

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