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Coordination-driven self-assembly of metallo-nanodrugs for local inflammation alleviation

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Nano research 2023年第12期16卷 13259-13266页

作者： Lijuan Tang Zhenghan Di Jingfang Zhang Feiying Yin Lele Li Li Zheng Guangxi Key Laboratory of regenerative medicine Guangxi Engineering Center in Biomedical Material for Tissue and Organ RegenerationCollaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development nd Application Co-Constructed by the Province and MinistryThe First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Pharmaceutical College Guangxi Medical UniversityNanning 530021China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable *** this study,we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug *** resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability,allowing for the combination of magnetic resonance imaging and anti-inflammatory *** the case of osteoarthritis(OA),the metallo-nanodrugs remarkably alleviate synovial inflammation,preventing cartilage destruction and extracellular matrix *** addition,it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse *** work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.

关键词： drug delivery coordination-driven assembly nanomedicine anti-inflammation therapy

Neuroinflammation and comorbidities are frequently ignored factors in CNS pathology

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Neural regeneration research 2015年第9期10卷 1349-1355页

作者： Raluca Elena Sandu Ana Maria Buga Adriana Uzoni Eugen Bogdan Petcu Aurel Popa-Wagner Center of Clinical and Experimental research University of Medicine and Pharmacy Craiova Department of Psychiatry University of Medicine Rostock Biochemistry Department University of Medicine and Pharmacy "Victor Babes" Timisoara Griffith University School of medicine Regenerative Medicine Centre

Virtually all drug interventions that have been successful pre-clinically in experimental stroke have failed to prove their efficacy in a dinical setting. This could be partly explained by the complexity and heterogeneity of human diseases as well as the associated co-morbidities which may render neuroprotective drugs less efficacious in dinical practice. One aspect of crucial importance in the physiopathology of stroke which is not completely understood is neuroinflammation. At the pres- ent time, it is becoming evident that subtle, but continuous neuroinflammation can provide the ground for disorders such as cerebral small vessel disease. Moreover, advanced aging and a number of highly prevalent risk factors such as obesity, hypertension, diabetes and atherosclerosis could act as ＂silent contributors＂ promoting a chronic proinflammatory state. This could aggravate the out- come of various pathological entities and can contribute to a number of subsequent post-stroke complications such as dementia, depression and neurodegeneration creating a pathological vicious cycle. Moreover, recent data suggests that the inflammatory process might be dosely linked with multiple neurodegenerative pathways related to depression. In addition, pro-inflammatory cyto- kines could play a central role in the pathophysiology of both depression and dementia.

关键词： aging stroke neuroinflammation comorbidities depression dementia

Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis

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research 2023年第4期2023卷 163-180页

作者： Jinhong Cai Lian-feng Liu Zainen Qin Shuhan Liu Yonglin Wang Zhengrong Chen Yi Yao Li Zheng Jinmin Zhao Ming Gao Collaborative Innovation centre of regenerative medicine and medical Bioresource Development and Application Co-constructed by the Province and Ministry The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ regeneration Guangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of Ultrasound Guangxi Medical University Cancer HospitalNanning530021China Department of Orthopedics The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Life Sciences Institute Guangxi Medical UniversityNanning530021China.

Osteoarthritis(OA)is always characterized as excessive reactive oxygen species(ROS)inside articular *** natural metalloenzymes with metal ions as the active centers,stable metal organic framework(MOF)formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory ***,a series of novel copper-morin-based MOF(CuMHs)with different molar ratios of Cu^(2+)and MH were employed to serve as ROS scavengers for OA *** a result,CuMHs exhibited enhanced dispersion in aqueous solution,improved biocompatibility,and efficient ROS-scavenging ability compared to *** the basis of H_(2)O_(2)-stimulated chondrocytes,intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu_(6)MH(Cu^(2+)and MH molar ratio of 6:1).Meanwhile,Cu_(6)MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6,MMP13,and MMP3,and up-regulating cartilage specific gene expression as ***,Cu_(6)MH could repair mitochondrial function by increasing mitochondrial membrane potential,reducing the accumulation of calcium ions,as well as promoting ATP content *** OA joint model,intra-articular(IA)injected Cu_(6)MH suppressed the progression of *** endowed that Cu_(6)MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

关键词： Osteoarthritis prevention inflammation

The gene expression patterns of BMPR2,EP300,TGFβ2,and TNFAIP3 in B-Lymphoma cells

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Cancer Biology & medicine 2014年第3期11卷 202-207页

作者： Dong-Mei He Hong Wu Xiu-Li Wu Li Ding Ling Xu Yang-Qiu Li Institute of Hematology Medical College Key Laboratory for regenerative medicine of Ministry of Education Jinan University

Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor, type II(BMPR2), E1 A binding protein p300(EP300), transforming growth factor-β2(TGFβ2), and tumor necrosis factor, and alpha-induced protein 3(TNFAIP3) gene expression patterns in B-cell malignancies were studied. Methods: The relative expression levels of BMPR2, EP300, TGFβ2, and TNFAIP3 mRNA in B-lymphoma cell lines, myeloid cell lines, as well as in cells from healthy volunteers, were determined by real-time quantitative reverse transcriptpolymerase chain reaction(qRT-PCR) with SYBR Green Dye. Glyceraldehyde-3-phosphate dehydrogenase(GAPDH) was used as reference. results: The expression level of TGFβ2 mRNA in B-lymphoma cell lines was significantly higher than those in the cells from the healthy control(Pression level of TNFAIP3 mRNA in B-malignant cells was significantly lower than that of the healthy control(Pression levels of BMPR2 and EP300 mRNA showed no significant difference between B-malignant cell lines and the healthy group(P>0.05). In B-lymphoma cell lines, correlation analyses revealed that the expression of BMPR2 and TNFAIP3(r=0.882, P=0.04) had significant positive relation. The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in cell lines from myeloid leukemia were significantly lower than those in the cells from the healthy control(Pression levels of TGFβ2 mRNA showed no significant difference between myeloid leukemia cell lines and the healthy control or B-malignant cell lines(P>0.05). The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in B-lymphoma cells were significantly higher than those of the myeloid leukemia cells(Prent expression patterns of BMPR2, EP300, TGFβ2, and TNFAIP3 genes in B-lymphoma cells exist.

关键词： Bone morphogenetic protein receptor type II(BMPR2) E1A binding protein p300(EP300) transforming growth factor-β2(TGFβ2) tumor necrosis factor and alpha-induced protein 3(TNFAIP3) B-lymphoma cells myeloid leukemia cells quantitative reverse transcription polymerase chain reaction(qRT-PCR)

Immunoprophylactic potential of filarial glutathione-s-transferase in lymphatic filariaisis

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Asian Pacific Journal of Tropical medicine 2011年第3期4卷 185-191页

作者： Madhusmita Bal Mandal N Achary KG Das MK Kar SK Division of Immunology Regional Medical Research Centre(Indian Council of Medical Research) ChandrasekharpurBhubaneswar-751023India

Objective:To elucidates the immunoprophylactic potential of glutathion-s-transferase(GST) from cattle filarial parasite Setaria digitata(***) against lymphatic ***: GST was purified through affinity chromatography(SdGST) and chacterized by SDS-PAGE and Nano-LC MS/MS *** isotypes to SdGST were measured by *** dependant cellular cytotoxicity(ADCC) was performed in vitro using sera from immunized animals and immune individuals.T-cell proliferation and cytokine response to SdGST in different groups of filariasis were *** potential of SdGST was evaluate in animal ***:SdGST exhibited 30-fold enhancement of enzyme activity over crude parasitic *** was found to be 26 kDa by *** LC-MS/MS analysis followed by blast search showed 100%homology with Dirqfilaria immitis(***) and only 43%with Homo sapiens(***).Immunoblotting analysis showed putatively immune individuals carry significant level of antibodies to SdGST as compared with *** sera and sera endemic normal could neutralize the enzymatic activity of SdGST and inducing in vitro cytotoxicity of *** blood mononuclear cells(PBMC) from endemic normals upon stimulation with SdGST showed a mixed type of Th1/Th2 *** immunization clear microfilariae from circulation in *** implanted ***:The heterologous GST could be potentially developed as a vaccine candidate against lymphatic filarial parasite.

关键词： Glutathione-s-transferase Setaria digitata Lymphatic filariasis

Advances in regenerative therapies for spinal cord injury:a biomaterials approach

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Neural regeneration research 2015年第5期10卷 726-742页

作者： Magdalini Tsintou Kyriakos Dalamagkas Alexander Marcus Seifalian UCL centre for Nanotechnology & regenerative medicine Division of Surgery and Interventional ScienceUniversity College of London Royal Free London NHS Foundation Trust Hospital

Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mech- anism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing re- search interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaf- fold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerativel neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction.

关键词： tissue engineering neuroregeneration repair central nervous system biomaterial regenerative medicine nanotechnology spinal cord injury

3D chromatin architecture and epigenetic regulation in cancer stem cells

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Protein & Cell 2021年第6期12卷 440-454页

作者： Yuliang Feng Xingguo Liu Siim Pauklin Botnar research centre Nuffield Department of OrthopaedicsRheumatology and Musculoskeletal Sciences Old RoadUniversity of OxfordOxford OX37LDUK Guangzhou regenerative medicine and Health Guangdong Laboratory CAS Key Laboratory of Regenerative BiologyJoint School of Life SciencesHefei Institute of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Guangdong Provincial Key Laboratory of Stem Cell and regenerative medicine Institute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China

Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer *** this process,a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early *** characteristics allow these cancer stem cells(CSCs)to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer *** development and progression are demarcated by transcriptional *** this article,we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation,with an emphasis on 3D chromatin *** the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin *** suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.

关键词： chromatin architecture 3D chromatin topology epigenetics tumorigenesis cancer stem cells pluripotent stem cells

Epigenome-Metabolome-Epigenome signaling cascade in cell biological processes

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Journal of Genetics and Genomics 2022年第4期49卷 279-286页

作者： Linpeng Li Keshi Chen Yi Wu Ge Xiang Xingguo Liu CAS Key Laboratory of regenerative Biology Joint School of Life SciencesGuangzhou Medical UniversityGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Bioland Laboratory(Guangzhou regenerative medicine and Health Guangdong Laboratory) Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesGuangzhouGuangdong 510530China c centre for regenerative medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many ***,the mechanisms of multilevel regulation of cell fate determination remain ***,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell *** this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic *** E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.

关键词： Cell biological processes Chromatin Epigenome Metabolome Signaling cascade

Role of integrin b1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel

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regenerative Biomaterials 2024年第5期3卷 59-73页

作者： Yuanjun Huang Miao Sun Zhenhui Lu Qiuling Zhong Manli Tan Qingjun Wei Li Zheng Guangxi Engineering Center in Biomedical Materials for Tissue and Organ regeneration The First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Collaborative Innovation centre of regenerative medicine and medical Bioresource Development and Application Co-Constructed by the Province and Ministry First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Department of Trauma Orthopedic and Hand Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Guangxi Key Laboratory of regenerative medicine The First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Life Science Institute Guangxi Medical UniversityNanning 530021China

Cartilage defects may lead to severe degenerative joint *** engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage ***,the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully ***,we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced *** showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-b signaling pathway,and integrin-b1(ITGB1),a receptor of collagen,was highly expressed in bone marrow mesenchymal stem cells(BMSCs).Further analysis showed genes such as COL2A1 and Tenascin C(TNC)that interacted with ITGB1 were significantly enriched in extracellular matrix(ECM)structural constituents in the chondrogenic induction *** of ITGB1 led to the downregulation of cartilage-specific genes(SOX9,ACAN,COL2A1),SMAD2 and TNC,as well as the downregulation of phosphorylation of SMAD2/*** of TNC also resulted in the decrease of cartilage markers,ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite ***,in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage *** summary,we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen *** can activate TGF-SMAD2/3 signaling,followed by impacting TNC expression,which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance *** may provide concernful support for cartilage tissue engineering and biomaterials development.

关键词： collagen hydrogel chondrogenic induction integrin b1 tenascin C TGF-SMAD2/3 signaling