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The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang minglu Yan Ryunosuke muro Kazutaka Nakamura masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin m (OSm) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSm receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSm-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

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Engineering nanomedicines for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham m.Abdelgalil Yomna m.Elmorshedy Kadria A.Elkhodairy mahmoud L.Nasr Division of Engineering in medicine and Division of Renal medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TmE)leading to failure of immune response.Numerous therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response.However,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response.Here,we outline the current state of using nanomedicines for boosting ICD of cancer cells.moreover,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TmE via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed.We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses.Endoplasmic reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative approaches.Various challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicines Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response

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Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2024年第11期19卷 2543-2552页

作者： Sam Enayati Karen Chang Anton Lennikov menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen Schepens Eye Research Institute of massachusetts Eye and Ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA Institute of clinical medicine Faculty of MedicineUniversity of OsloOsloNorway Department of medical Biochemistry Oslo University HospitalUniversity of OsloOsloNorway Department of Ophthalmology Drammen HospitalVestre Viken Hospital TrustDrammenNorway Department of Histology and Embryology School of MedicineMarmara UniversityIstanbulTurkiye

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OmR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical

关键词： bipolar cells electrical stimulation neuroprotection photoreceptor degeneration retina retinal explants retinitis pigmentosa transcorneal electrical stimulation waveform

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Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

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World Journal of Diabetes 2024年第3期15卷 455-462页

作者： Ahmed Eldib Shilton Dhaver Karim Kibaa Astrid Atakov-Castillo Tareq Salah marwa Al-Badri Abdelrahman Khater Ryan mcCarragher Omnia Elenani Elena Toschi Osama Hamdy Department of Clinical Behavioral&Outcomes ResearchJoslin Diabetes CenterBostonMA 02215United States Department of medicine Harvard Medical SchoolBostonMA 02115United States

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of medtronic’s 670G HCL in real-world clinical practice.AIm To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.mETHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAm)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAm was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(Pmia fear survey/worry scale decreased significantly by 24.9%(Pm Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The us

关键词： Artificial pancreas Continuous blood glucose monitor Type 1 diabetes Hybrid closed-loop insulin delivery Quality of life

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DLX3(Q178R)mutation delays osteogenic differentiation via H19/miR-29c-3p/KDm5B axis in TDO-iPSCs-derived mSCs

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Genes & Diseases 2024年第4期11卷 49-52页

作者： Liying Dong Na Zhao Dongmei Wang meng Wang Yixin Zhang Liangjie Sun Chong Ding Yixiang Wang Zeyun ma Central Laboratory Peking University School and Hospital of StomatologyBeijing 100081China Department of Oral and maxillofacial Surgery Peking University School and Hospital of StomatologyBeijing 100081China National Engineering Laboratory for Digital and material Technology of Stomatology Peking University School and Hospital of StomatologyBeijing 100081China Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of StomatologyBeijing 100081China The Second Clinical Division Peking University School and Hospital of StomatologyBeijing 100081China Department of VIP Service Peking University School and Hospital of StomatologyBeijing 100081China Department of Restorative Dentistry and Biomaterials Sciences Harvard School of Dental MedicineBostonMA 02115USA Department of Prosthodontics Fudan UniversityShanghai 200001China Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases Shanghai Stomatological HospitalFudan UniversityShanghai 200001China

Tricho-dento-osseous(TDO)syndrome is a rare autosomal dominant disease resulting from distal-less homeobox 3(DLX3)mutation.1,2 Accumulative bone density in alveolar bone is a clinically favorable phenotype for TDO patients.However,the limited number of bone marrow mesenchymal stem cells(BmSCs)in TDO patients restricts their application.

关键词： patients clinically alveolar

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Effect of Jiedu Huayu decoction(解毒化瘀汤) on oral mucosal Axin and β-catenin expression in oral submucosal fibrosis model rats

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Journal of Traditional Chinese medicine 2024年第4期 688-693页

作者： ZHU Xuan LOU An ZHU Keke RUAN mingyu Department of Science and Technology Hunan University of Chinese Medicine Department of prosthodontics Hunan University of Chinese Medicine Affiliated Dental Hospital Department of Stomatology the First Affiliated Hospital of Hunan University of Chinese Medicine school of medicine Hunan University of Chinese Medicine

OBJECTIVE: To investigate the protective effect of the Chinese herbal formula of Jiedu Huayu decoction(解毒化瘀汤, JHD) on oral mucosa of rats with oral submucosal fibrosis(OSF) and its potential mechanism of action. mETHODS: Sprague-Dawley male OSF model rats were constructed by injection of betaine and topical rubbing and were randomly grouped and administered by gavage for 4 weeks. mouth opening and buccal mucosa scores interleukin levels and the expression of Axin and β-catenin proteins or genes were measured before and after drug administration. RESULTS: After treatment with JHD the buccal mucosal lesions of rats were significantly reduced Axin protein and mRNA expression were significantly increased β-catenin protein and m RNA expression were significantly decreased interleukin-1β and interleukin-6 levels were decreased and interleukin-10 levels were increased. CONCLUSION: The mechanism of action of JHD can effectively alleviate the pathological damage of buccal mucosa in OSF rats which may be related to the promotion of Axin expression and inhibition of β-catenin expression.

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Highly Aligned Ternary Nanofiber matrices Loaded with mXene Expedite Regeneration of Volumetric muscle Loss

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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 bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In 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 regeneration.The PCm matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCm matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCm matrices following VmL injury.mechanistic 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 pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These 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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metabolic-associated fatty liver disease and sarcopenia:A double whammy

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World Journal of Hepatology 2024年第2期16卷 152-163页

作者： Aditya Viswanath Sherouk Fouda Cornelius James Fernandez Joseph m Pappachan school of medicine Leicester UniversityLeicester LE17RHUnited Kingdom school of Health and Biomedical Sciences Rmit UniversityMelbourne VICAustralia Department of Endocrinology and metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The prevalence of metabolic-associated fatty liver disease(mAFLD)has increased substantially in recent years because of the global obesity pandemic.mAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between mAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in mAFLD(e.g.,obesity or adiposity)or a consequence of mAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen mAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between mAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

关键词： metabolic-associated fatty liver disease Sarcopenia Sarcopenic obesity Lean metabolic-associated fatty liver disease Cardiovascular disease Liver-muscle axis

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The efficacy of vitamin E in preventing arthrofibrosis after joint replacement

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Animal models and Experimental medicine 2024年第2期7卷 145-155页

作者： Yingfang Fan Jean Yuh Sashank Lekkala mehmet D.Asik Andrew Thomson madeline mcCanne mark A.Randolph Antonia F.Chen Ebru Oral Harris Orthopaedic Laboratory Department of Orthopaedic SurgeryMassachusetts General HospitalBostonMassachusettsUSA Department of Orthopaedic Surgery Harvard Medical SchoolBostonMassachusettsUSA Department of Surgery Harvard Medical SchoolBostonMassachusettsUSA Department of Orthopaedic Surgery Brigham and Women's HospitalBostonMassachusettsUSA

Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2m)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROm)were collected for functional assessment.Results:The ROm and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROm and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.

关键词： arthrofibrosis range of motion total knee arthroplasty vitamin E

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Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

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World Journal of Stem Cells 2024年第5期16卷 560-574页

作者： meng-Hao Lyu Ce Bian Yi-Ping Dou Kang Gao Jun-Ji Xu Pan ma Department of Periodontics School of StomatologyCapital Medical UniversityBeijing 100050China Department of Orthodontics School of StomatologyCapital Medical UniversityBeijing 100050China Department of dental Implantology School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Laboratory of Oral Health Capital Medical UniversityBeijing 100050China

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIm To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BmSCs)following their interaction with macrophages in an inflammatory environment.mETHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BmSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the m2 type through substitution,and these m2 macrophages actively facilitated the osteogenic differentiation of BmSCs.mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BmSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BmSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BmSCs’osteogenic differentiation.

关键词： macrophages Interleukin-10 Bone marrow mesenchymal stem cells Signal transducer and activator of transcription 3 Inflammatory response

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