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Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

Nano-Micro Letters 2024年第4期16卷 269-292页

作者： Moon Sung Kang Yeuni Yu Rowoon Park Hye Jin Heo Seok Hyun Lee Suck Won Hong Yun Hak Kim Dong‑Wook Han Department of Cogno‑Mechatronics Engineering College of Nanoscience and NanotechnologyPusan National UniversityBusan 46241Republic of Korea Medical research institute School of MedicinePusan National UniversityYangsan 50612Republic of Korea Department of Anatomy School of MedicinePusan National UniversityYangsan 50612Republic of Korea Engineering research Center for Color‑Modulated Extra‑Sensory Perception Technology Pusan National UniversityBusan 46241Republic of Korea Department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612Republic of Korea Periodontal Disease Signaling Network research Center and Dental and Life Science institute School of DentistryPusan National UniversityYangsan 50612Republic of Korea BIO‑IT Fusion Technology research institute Pusan National UniversityBusan 46241Republic of Korea Present Address:Osstem Implant Inc. Seoul 07789Republic of Korea

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient *** overcome these limitations,tissue-engineered scaffolds have emerged as a promising *** this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue *** PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and *** vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 ***,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML *** insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT ***,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast *** findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

关键词： Ti_(3)C_(2)T_(x)MXene nanoparticle Ternary nanofibrous matrices Myogenesis Regeneration of volumetric muscle loss Next generation sequencing

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Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

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Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai State Key Laboratory of oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China Department of Implant dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China State Key Laboratory of oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan 430079China

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells Bone development Epigenetics Ptip Glycolysis

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Streptococcus mutans activates the AIM2, NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages

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International Journal of oral Science 2018年第3期10卷 190-196页

作者： Yuri Song Hee Sam Na Eunjoo Park Mi Hee Park Hyun Ah Lee Jin Chung Department of oral Microbiology School of Dentistry Pusan National University institute of Translational Dental Sciences Pusan National University

Streptococcus mutans(S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin(IL)-1β, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1β secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma(AIM2), NLR family pyrin domain-containing 3(NLRP3) and NLR family CARD domain-containing 4(NLRC4)inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate(ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection.

关键词： NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages THP Streptococcus mutans activates the AIM2 AIM

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Ptip维持骨骼干细胞静息态及潜能影响骨形成的表观机制（英文）

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Science Bulletin 2024年第13期 2099-2113页

作者：梁建飞王菁隋秉东童弈博柴纪华周秦郑晨曦王浩孔亮张好建白轶 State Key Laboratory of oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Taikang Center for Life and Medical Sciences Wuhan University Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research College of Stomatology Xi'an Jiaotong University Department of Implant dentistry College of Stomatology Xi'an Jiaotong University State Key Laboratory of oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences State Key Laboratory of oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Oral and Maxillofacial Surgery School of Stomatology The Fourth Military Medical University Department of Hematology Zhongnan Hospital Wuhan University Frontier Science Center for Immunology and Metabolism Medical Research Institute Wuhan University Taikang Center for Life and Medical Sciences Wuhan University

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells（SSCs） in skeletogenesis governed by a key regulator, Ptip（also known as Paxip1, Pax interaction with transcription-activation domain protein-1）. Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen（Col2）+progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1（Pgk1） by repressing histone H3 lysine 27acetylation（H3K27ac） at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.

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The effect of dimiristoylphosphatidylethanol on the rotational mobility of n-(9-Anthroyloxy) stearic acid in neuronal and model membranes

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Journal of Biophysical Chemistry 2010年第3期1卷 133-140页

作者： Young-Sik Park No-Soo Park Jun-Bong Seo Soo-Kyoung Bae You-Kwang kim Ki-Soo Seong Young-Jun Kim Ju-Won Park Joung-Moung Shin Young-Chan Jeon In-Kyo Chung Moon-Kyoung Bae Hye-Ock Jang Il Yun school of dentistry and research institute for oral biotechnology pusan national university

The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of ethanol. We studied di?myristoyl?phosphatidylethanol (DMPEt)’s effects on specific locations of n-(9-anthroyloxy) palmitic acid or stearic acid (n-AS) within phos?pholipids of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV) and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from SPMV. DMPEt increased rotational mobility (increased disordering) of hydrocarbon interior, but it decreased mobility (increased ordering) of membrane interface, in native and model membranes. The degree of rotational mobility in accordance with the carbon atom numbers of phospholipids comprising neuronal membranes was in the order at the 16, 12, 9, 6 and 2 position of aliphatic chain present in phospholipids. The sensitivity of increasing or decreasing effect of rotational mobility of hydrocarbon interior or surface region by DMPEt differed depending on the neuronal and model membranes in the descending order of SPMV, SPMVPL and SPMVTL.

关键词： Ethanol Phosphatidylethanol Fluorescence Quenching Technique Rotational Mobility Hydrocarbon Interior Membranes lnterface

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TGF-β2 downregulates osteogenesis under inflammatory conditions in dental follicle stem cells

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International Journal of oral Science 2018年第4期10卷 232-243页

作者： Soyoun Um Joo-Hee Lee Byoung-Moo Seo Biotooth Engineering Lab Dental Research InstituteDental Regenerative BiotechnologyDepartment of Dental ScienceSchool of DentistrySeoul National University Biotooth Engineering Lab Department of Oral and Maxillofacial Surgery and Craniomaxillofacial Life ScienceDental Research InstituteSchool of DentistrySeoul ational University

Bone formation is important for the reconstruction of bone-related structures in areas that have been damaged by *** conditions such as those that occur in patients with rheumatoid arthritis, cystic fibrosis, and periodontitis have been shown to inhibit osteoblastic differentiation. This study focussed on dental follicle stem cells(DFSCs), which are found in developing tooth germ and participate in the reconstruction of alveolar bone and periodontal tissue in periodontal disease. After bacterial infection of inflamed dental tissue, the destruction of bone was observed. Currently, little is known about the relationship between the inflammatory environment and bone formation. Osteogenic differentiation of inflamed DFSCs resulted in decreased alkaline phosphatase(ALP) activity and alizarin red S staining compared to normal DFSCs. Additionally, in vivo transplantation of inflamed and normal DFSCs demonstrated severe impairment of osteogenesis by inflamed DFSCs. Protein profile analysis via liquid chromatography coupled with tandem mass spectrometry was performed to analyse the differences in protein expression in inflamed and normal tissue. Comparison of inflamed and normal DFSCs showed significant changes in the level of expression of transforming growth factor(TGF)-β2. Porphyromonas gingivalis(P.g.)-derived lipopolysaccharide(LPS) was used to create in vitro inflammatory conditions similar to periodontitis. The osteogenic differentiation of LPS-treated DFSCs was suppressed, and the cells displayed low levels of TGF-β1 and high levels of TGF-β2. DFSCs treated with TGF-β2 inhibitors showed significant increases in alizarin red S staining and ALP activity. TGF-β1 expression was also increased after inhibition of TGF-β2. By examining inflamed DFSCs and LPS-triggered DFSCs, these studies showed both clinically and experimentally that the increase in TGF-β2 levels that occurs under inflammatory conditions inhibits bone formation.

关键词： TGF downregulates osteogenesis under inflammatory conditions in dental follicle stem cells

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The extract of the immature fruit of Poncirus trifoliata induces apoptosis in colorectal cancer cells via mitochondrial autophagy

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Food Science and Human Wellness 2020年第3期9卷 237-244页

作者： Sun-Young Kim Ho-Keun Yi Bong-Sik Yun Dae-Yeol Lee Pyung Han Hwang Hae-Ryong Park Min Sun Kim research institute of Clinical Medicine of Jeonbuk national university Biomedical Research Institute of Jeonbuk National University HospitalJeonju54907South Korea Department of oral Biochemistry Institute of Oral BioscienceSchool of DentistryJeonbuk National UniversityJeonju54907South Korea Division of biotechnology and Advanced institute of Environment and Bioscience Jeonbuk National UniversityIksan-si54596South Korea Department of Pediatrics Jeonbuk National University Medical SchoolJeonju54907South Korea Department of Food Science and biotechnology Kyungnam UniversityChangwon-si51767South Korea

The immature fruits of Poncirus trifoliate are used as a medicine for the treatment of gastrointestinal disorders,inflammation,and allergies in East ***,their effect on colon cancer cells remains *** investigated the effect of the immature fruit of *** extract on colorectal *** extract of the immature fruit of *** inhibited the proliferation of CT-26 cells compared with untreated cells and it induced autophagy and apoptosis through the protein kinase B/mammalian target of rapamycin and 5'-AMP-activated protein kinase *** number of autophagic vacuoles and autophage markers increased in response to the *** later time-points,apoptosis increased dose/*** CT-26 cells pre-treated a pan-caspase inhibitor prior to *** immature fruit extract treatment,we did not find any change in pro-caspase 3 and pro-PARP ***,in cells pre-treated autphage inhibitor,SQSTM1/p62 and LC3AB,pro-caspase 3 and pro-PARP levels did not *** results indicate the molecular mechanisms that the extract of the immature fruit of *** induces apoptosis in colorectal carcinoma cells by inducing mitochondrial *** this study,we provided a draft for further investigate the use of MEPT for colorectal cancer inhibition.

关键词： Anticancer Autophagy Apoptosis Mitochondria Poncirus trifoliata

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Long-term observation of the mineral trioxide aggregate extrusion into the periapical lesion:a case series

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International Journal of oral Science 2013年第1期5卷 54-57页

作者： Seok-Woo Chang Tae-Seok Oh WooCheol Lee Gary Shun-Pan Cheung Hyeon-Cheol Kim Department of Conservative dentistry School of DentistryKyung Hee University Department of Conservative dentistry The Institute of Oral Health ScienceSamsung Medical CenterSungkyunkwan University School of Medicine Department of Conservative dentistry School of DentistryDental Research InstituteSeoul National University Area of Endodontics Faculty of Dentistrythe University of Hong Kong Department of Conservative dentistry School of DentistryPusan National UniversityDental Research Institute

One-step apexification using mineral trioxide aggregate(MTA) has been reported as an alternative treatment modality with more benefits than the use of long-term calcium hydroxide for teeth with open ***,orthograde placement of MTA is a challenging procedure in terms of length *** case series describes the sequence of events following apical extrusion of MTA into the periapical area during a one-step apexification procedure for maxillary central incisor with an infected immature *** long-term observation revealed complete resolution of the periapical radiolucent lesion around the extruded *** cases revealed that direct contact with MTA had no negative effects on healing of the periapical ***,intentional MTA overfilling into the periapical lesion is not to be recommended.

关键词： extrusion immature apex mineral trioxide aggregate one-step apexification open apex periapical healing

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Growth effects of botulinum toxin type A injected unilaterally into the masseter muscle of developing rats

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Journal of Zhejiang university-Science B(Biomedicine & biotechnology) 2015年第1期16卷 46-51页

作者： Chanyoung PARK Kitae PARK Jiyeon KIM Department of Pediatric dentistry Institute of Oral Health Science Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 135-710 Korea Department of Pediatric dentistry School of Dentistry Dental Research Institute Pusan National UniversityYangsan 626-870 Korea

Objective： To evaluate the effects of botulinum toxin type A （BTX-A） on mandible skeletal development by inducing muscle hypofunction. Methods： Four-week-old Sprague-Dawley rats （n=60） were divided into three groups： Group 1 animals served as controls and were injected with saline; Group 2 animals were injected unilaterally with BTX-A （the contralateral side was injected with saline）; and Group 3 animals were injected bilaterally with BTX-A. In Group 2, the saline-injected side was designated the control side （Group 2-1）, whereas the BTX-A-injected side was designated the experimental side （Group 2-2）. After four weeks, the animals were sacrificed, dry skulls were prepared, and mandibles were measured. Results： In the unilateral group, the experimental side （Group 2-2） had reduced di- mensions for all mandible measurements compared with the control side （Group 2-1）, suggesting a local effect of BTX-A on mandible growth, likely due to muscle reduction. Conclusions： Localized BTX-A injection induced a change in craniofacial growth, and the skeletal effect was unilateral despite both sides of the mandible functioning as one unit.

关键词： Botulinum toxin Craniofacial growth Mandible

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Design of drug-like hepsin inhibitors against prostate cancer and kidney stones

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1309-1320页

作者： Vincent Blay Mu-Chun Li Sunita P.Ho Mashall L.Stoller Hsing-Pang Hsieh Douglas R.Houston Division of Biomaterials and Bioengineering School of DentistryUniversity of California San FranciscoSan FranciscoCA 94143USA Department of Urology School of MedicineUniversity of California San FranciscoSan FranciscoCA 94143USA institute of biotechnology and Pharmaceutical research National Health Research InstitutesZhunanTaiwan 350China university of Edinburgh Institute of Quantitative BiologyBiochemistry and BiotechnologyEdinburghScotlandEH93BFUK

Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate *** is involved in the release and polymerization of uromodulin in the urine,which plays a role in kidney stone *** this work,we design new potential hepsin inhibitors for high activity,improved specificity towards hepsin,and promising ADMET *** ligands were developed in silico through a novel hierarchical *** pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA(human hepatocyte growth factor activator).We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization *** ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental *** computational pipeline proposed is remarkably costefficient and can be easily adapted for designing inhibitors against new drug targets.

关键词： Virtual screening Docking Library Hepsin Tamm-Horsfall protein Biomineralization

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