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Microarray analysis of signalling interactions between inflammation and angiogenesis in subchondral bone in temporomandibular joint osteoarthritis

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Biomaterials Translational 2024年第2期5卷 175-184页

作者： Qin W. Gao J. Yan J. Han X. Lu W. Ma Z. Niu L. Jiao K. Department of Stomatology Tangdu Hospital and State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration School of Stomatology The Fourth Military Medical University Shaanxi Province Xi’an China State Key laboratory of Oral and Maxillofacial Reconstruction and Regeneration and National Clinical Research Centre for Oral Diseases Shaanxi Key Laboratory of Stomatology School of Stomatology The Fourth Military Medical University Shaanxi Province Xi’an China

Inflammation and angiogenesis, the major pathological changes of osteoarthritis (OA), are closely associated with joint pain; however, pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated. Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint. Microarray-based transcriptome analysis, besides quantitative real-time polymerase chain reaction, was performed to identify differentially expressed genes (DEGs). Overall, 182 DEGs (fold change ≥ 2, P < 0.05) were identified between the control and unilateral anterior crossbite groups: 168 were upregulated and 14 were downregulated. On subjecting significant DEGs to enrichment analyses, inflammation and angiogenesis were identified as the most affected. Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling. Furthermore, angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling. Protein– protein interaction analysis revealed a close interaction between inflammation-and angiogenesis-related DEGs, suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Pi3kcd), cathelicidin antimicrobial peptide (Camp), C-X-C motif chemokine receptor 4 (Cxcr4), and MYB proto-oncogene transcription factor (Myb) play a central role in their interaction. To summarize, our findings reveal that in subchondral bone of osteoarthritic joints, signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain; moreover, our data highlight potential t

关键词： angiogenesis inflammation osteoarthritic pain osteoarthritis subchondral bone temporomandibular joint (TMJ)

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New aspects of a small GTPase RAB35 in brain development and function

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Neural Regeneration Research 2025年第7期20卷 1971-1980页

作者： Ikuko Maejima Ken Sato laboratory of Molecular Traffic Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or *** processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS *** of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative ***,it is important to understand the physiological and pathological roles of RAB proteins in brain ***35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell ***35 is also involved in neurite outgrowth and turnover of synaptic *** generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and *** mice exhibited defects in anxiety-related behaviors and spatial ***,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal *** contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex *** studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's *** this review,we provide an overview of the current understanding of subcellular functions of *** also provide insights into the phys

关键词： endocytosis endosomes hippocampal development neurodegenerative diseases RAB35

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Fasn involved in the nephrotoxicity induced by polystyrene nanoplastics and the intervention of melatonin through intestinal microbiota-mediated lipid metabolism disorder

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Nano Research 2024年第8期17卷 7365-7375页

作者： Huiwen Kang Danyang Huang Jiaru Jing Wei Zhang Lei Zhang Jingyu Wang Ziyan Liu Lin Han Ziyan Wang Lefeng Zhang Ai Gao Department of Occupational Health and Environmental Health School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China

Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still *** this study,in vivo(60μg/day,42 days)and in vitro(0.4μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,*** study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal ***-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in ***,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn *** conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.

关键词： nanoplastics nephrotoxicity lipid metabolism fatty acid synthase(Fasn) melatonin

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A nonenzymatic electrochemical sensor for the detection of hydrogen peroxide in vitro and in vivo fibrosis models

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Chinese Chemical Letters 2024年第3期35卷 394-398页

作者： Hongyao Liu Yan Yu Taixiong Xue Cailing Gan Yuting Xie Doudou Wang Peilin Li Zhiyong Qian Tinghong Ye Department of Gastroenterology and Hepatology Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer and Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Fibrosis occurs due to the excessive deposition of extracellular matrix caused by cell *** various types of tissue injury,the dysregulation of the internal response can eventually lead to the destruction of organ structure and *** is increasing evidence that oxidative stress,which is characterized by excessive production of hydrogen peroxide(H_(2)O_(2)),is an important cause of ***,we synthesized a biosensitive and efficient electrochemical H_(2)O_(2)sensor based on PtNi nanoparticle-doped N-reduced graphene oxide(PtNi-N-rGO)to detect H_(2)O_(2)released from transforming growth factorβ1(TGFβ1)-induced *** addition,the sensor could easily detect changes in H_(2)O_(2)in the lung and bronchoalveolar lavage fluid(BALF)of mice with pulmonary ***,the sensor could also detect H_(2)O_(2)in activated hepatic stellate cells and the liver of carbon tetrachloride(CCl_(4))-induced liver ***,the alterations in H_(2)O_(2)detected by the sensor were consistent with nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)protein expression and the staining results of pathological *** together,these results highlight the use of H_(2)O_(2)sensors for the rapid detection of fibrosis and facilitate the rapid evaluation of antifibrotic drug candidates.

关键词： Fibrosis H_(2)O_(2) Electrochemical sensor NOX4 Nintedanib

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Targeting synaptic pathology in Alzheimer’s disease

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Zoological Research 2024年第4期45卷 875-876页

作者： Jing Cao Yun-Wu Zhang Fujian Provincial Key laboratory of Neurodegenerative Disease and Aging Research Institute of NeuroscienceSchool of MedicineXiamen UniversityXiamenFujian 361102China

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by memory and cognitive *** two primary pathological hallmarks of AD include the accumulation ofβ-amyloid(Aβ)plaques and formation of neurofibrillary tangles(NFTs)composed predominantly of hyperphosphorylated tau protein(Zhang et al.,2023).Moreover,synaptic dysfunction is considered another crucial factor in AD pathogenesis and is closely associated with cognitive ***,synaptic damage,loss,and dysfunction manifest earlier than the pathological features of Aβplaques and NFTs(Knopman et al.,2021).Therefore,understanding the mechanisms underlying synaptic dysfunction in AD is vital for providing insights into disease mechanisms and developing novel therapeutic strategies.

关键词： Alzheimer Aβ tau

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Bioengineered skin organoids:from development to applications

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Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-Tian Zhu Hao Li Jing-Zhi Luo Yu Yang Yang An Xi Wang Kai Wang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina Department of Plastic Surgery Peking University Third HospitalBeijing 100191China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China State Key laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key laboratory of Metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin *** as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical *** inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic *** review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with ***,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic *** review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage Tissue engineering Disease modelling Regenerative medicine

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Spatial transcriptomics:recent developments and insights in respiratory research

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Military Medical Research 2024年第3期11卷 430-448页

作者： Wen-Jia Wang Liu-Xi Chu Li-Yong He Ming-Jing Zhang Kai-Tong Dang Chen Gao Qin-Yu Ge Zhou-Guang Wang Xiang-Wei Zhao State Key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035ZhejiangChina Orthopaedic Bioengineering Research Group Division of Surgery and Interventional ScienceUniversity College LondonLondon HA74LPUK

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this *** bulk RNA sequencing and single-cell RNA sequencing(scRNA-seq)have provided insights into cell types and heterogeneity in the respiratory system,the relevant specific spatial localization and cellular interactions have not been clearly *** transcriptomics(ST)has filled this gap and has been widely used in respiratory *** review focuses on the latest iterative technology of ST in recent years,summarizing how ST can be applied to the physiological and pathological processes of the respiratory system,with emphasis on the ***,the current challenges and potential development directions are proposed,including high-throughput full-length transcriptome,integration of multi-omics,temporal and spatial omics,bioinformatics analysis,*** viewpoints are expected to advance the study of systematic mechanisms,including respiratory studies.

关键词： Spatial transcriptomics Lung Tumor Spatial multi-omics

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Intratumoural microbiota:a new frontier in cancer development and therapy

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Signal Transduction and Targeted Therapy 2024年第2期9卷 597-620页

作者： Yaqi Cao Hui Xia Xueyun Tan Chunwei Shi Yanling Ma Daquan Meng Mengmeng Zhou Zhilei Lv Sufei Wang Yang Jin Department of Respiratory and Critical Care Medicine Hubei Province Clinical Research Center for Major Respiratory DiseasesKey Laboratory of Respiratory Diseases of National Health CommissionState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy MOE Key Laboratory of Biological Targeted TherapyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Hubei Province Key laboratory of Biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Pathogen Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Human microorganisms,including bacteria,fungi,and viruses,play key roles in several physiological and pathological *** studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms,which have been confirmed to be closely related to *** concept of intratumoural microbiota was subsequently *** could colonise tumour tissues through mucosal destruction,adjacent tissue migration,and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour *** studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations,affecting epigenetic modifications,promoting inflammation response,avoiding immune destruction,regulating metabolism,and activating invasion and *** more comprehensive and profound insights about intratumoral microbiota are continuously emerging,new methods for the early diagnosis and prognostic assessment of cancer patients have been under *** addition,interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy,especially immunotherapy,although there are some inevitable ***,we aim to provide an extensive review of the concept,development history,potential sources,heterogeneity,and carcinogenic mechanisms of intratumoural microorganisms,explore the potential role of microorganisms in tumour prognosis,and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.

关键词： tumour invasion metabolism

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Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration Research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor Carlos Spuch José Antonio Lamas Lucas C.González-Matías Federico Mallo Biomedical Research Centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience Research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical Research Centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and ***-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain ***-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural *** glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous *** brain insult,microglia are the first cells to respond,followed by reactive *** activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the ***,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many *** processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control *** glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry *** review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkins

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

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Transcription factor Foxp1 is essential for the induction of choroidal neovascularization

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Eye and Vision 2024年第3期10卷 1-12页

作者： Meifang Yan Junjian Li Li Yan Xue Li Jie-Guang Chen School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical UniversityState Key Laboratory of OptometryOphthalmology and Vision Scienceand Zhejiang Provincial Key Laboratory of Optometry and Ophthalmology270 Xueyuan RoadWenzhouZhejiang325027People’s Republic of China Joint Shantou International Eye Center(JSIEC)of Shantou University and the Chinese University of Hong Kong ShantouGuangdong515000People’s Republic of China

Background The exudative form of age-related macular degeneration(AMD)is characterized by abnormal blood vessel growth,which is stimulated by vascular endothelial growth factor(VEGF)released from retinal pigment epithelium(RPE).The angiogenic behaviors of vascular endothelial cells in vitro depend on forkhead box protein P1(Foxp1),a transcription repressor widely expressed in human and murine tissues during *** this study,we aimed to determine whether loss of Foxp1 affects laser-induced choroidal neovascularization(CNV)in *** Eye-selective deletion of Foxp1 was obtained by crossing Foxp1flox/flox with Six3-Cre *** photocoagulation was delivered to six-to eight-week-old mice to induce *** expression of Foxp1 and Cre was determined by immunofluorescence in cryostat sections of the *** fluorescein angiography(FFA),optical coherence tomography(OCT),and B4 isolectin staining were applied to analyze the leakage,bulge height,and area of CNV lesions,***-choroid tissues were isolated for the determination of VEGF and pigment epithelium derived factor(PEDF)by Western *** Foxp1 was expressed in retinal ganglion cells,RPE,and the choroidal endothelial *** photocoagulation increased the number of Foxp1+-endothelial cells and induced ***3-Cre reduced Foxp1 expression in RPE but not the endothelium,leading to a lower level of VEGF in the ***1 knockout inhibited pathological angiogenesis and vascular leakage of the laser-induced CNV *** Foxp1 regulates the expression of VEGF in the RPE,and inhibition of Foxp1 could potentially be a novel strategy for the prevention and therapy of neovascularization related to AMD.

关键词： Foxp1 Choroidal neovascularization Angiogenesis Laser photocoagulation Age-related macular degeneration

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