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International journal of Oral Science 2015年第2期7卷 95-102页

作者： jing Yang Ling Ye Tian-Qian Hui Dong-Mei Yang Ding-Ming Huang Xue-Dong Zhou jeremy j Mao Cheng-Lin Wang State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan University Center for Craniofacial Regeneration(CCR) Columbia University Medical Center

Both bone morphogenetic protein 2（BMP2） and the wingless-type MMTV integration site（WNT）/p-catenin signalling pathway play important roles in odontoblast differentiation and ***-talk between BMP2 and WNT/p-catenin in osteoblast differentiation and bone formation has been ***,the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely ***,we demonstrate that BMP2 promotes the differentiation of human dental pulp cells（HDPCs） by activating WNT/p-catenin signalling,which is further mediated by p38mitogen-activated protein kinase（MAPK） in ***2 stimulation upregulated the expression of p-catenin in HDPCs,which was abolished by SB203580 but not by Noggin or ***,BMP2 enhanced cell differentiation,which was not fully inhibited by Noggin or ***,SB203580 partially blocked BMP2-induced p-catenin expression and cell *** together,these data suggest a possible mechanism by which the elevation of p-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway,which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.

关键词： dental catenin morphogenetic stimulation canonical inhibited blocked repair activating mitogen

A dahlia flower extract has antidiabetic properties by improving insulin function in the brain

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Life Metabolism 2023年第4期2卷 39-50页

作者： Dominik Pretz Philip M.Heyward jeremy Krebs joel Gruchot Charles Barter Pat Silcock Nerida Downes Mohammed Zubair Rizwan Alisa Boucsein julia Bender Elaine j.Burgess Geke Aline Boer Pramuk Keerthisinghe Nigel B.Perry Alexander Tups Centre for Neuroendocrinology School of Biomedical SciencesUniversity of OtagoDunedin 9054New Zealand Department of Physiology School of Biomedical SciencesUniversity of OtagoDunedin 9054New Zealand Maurice Wilkins Centre for Molecular Biodiscovery University of AucklandAuckland 1010New Zealand Department of Medicine University of OtagoWellingtonWellington South 6242New Zealand Centre for Endocrine Diabetes and Obesity Research Wellington Regional HospitalNewtownWellington 6021New Zealand Product Development Research Centre University of OtagoDunedin 9054New Zealand Department of Chemistry The New Zealand Institute for Plant and Food ResearchUniversity of OtagoDunedin 9054New Zealand

Butein,a rare chalcone found in the toxic plant Toxicodendron vernicifluum,has been shown to regulate glucose homeostasis via inhibition of the nuclear factor kappa-B kinase subunit beta(IKKβ)/nuclear factor kappa B(NF-κB)pathway in the ***,we investigated whether the nonpoisonous plant Dahlia pinnata could be a source of butein as a potential treatment for type 2 diabetes(T2D).In mice fed a high-fat diet(HFD)to induce glucose intolerance,an oral *** petal extract improved glucose tolerance at doses of 3.3 mg/kg body weight and 10 mg/kg body ***,this effect was not mediated by butein alone but by butein combined with the closely related flavonoids,sulfuretin and/or ***,the extract improved systemic insulin *** of phosphatidylinositol 3-kinase to block insulin signaling in the brain abrogated the glucoregulatory effect of the orally administered *** extract reinstated central insulin signaling and normalized astrogliosis in the hypothalamus of HFD-fed *** NF-κB reporter zebrafish to determine IKKβ/NF-κB activity,a potent anti-inflammatory action of the extract was found.A randomized controlled crossover clinical trial on participants with predia-betes or T2D confirmed the safety and efficacy of the extract in *** conclusion,we identified an extract from the flower petals of *** as a novel treatment option for T2D,potentially targeting the central regulation of glucose homeostasis as a root cause of the disease.

关键词： inflammation hypothalamus signal transduction neuroendocrine arcuate nucleus

Cementomimetics——constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides

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International journal of Oral Science 2012年第2期4卷 69-77页

作者： Mustafa Gungormus Ersin E Oren jeremy A Horst Hanson Fong Marketa Hnilova Martha j Somerman Malcolm L Snead Ram Samudrala Candan Tamerler Mehmet Sarikaya Genetically Engineered Materials Science and Engineering Center and Department of Materials Science and EngineeringUniversity of WashingtonSeattleUSA Departmentof Orofacial Sciences University of California at San FranciscoSan FranciscoUSA Laboratory of Oral Connective Tissue Biology National Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institutes of HealthBethesdaUSA Center for Craniofacial Molecular Biology Ostrow School of Dentistry of the University of Southern CaliforniaLos AngelesUSA Department of Microbiology University of WashingtonSeattleUSA

Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides （HABPs） previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 （ADP5） was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.

关键词： amelogenin amelogenin-derived peptides bioinformatics biomineralization cementomimetics cementum demineral-ization remineralization

A Within-Host Model of Dengue Infection with a Non-Constant Monocyte Production Rate

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Applied Mathematics 2016年第18期7卷 2382-2393页

作者： jeremy j. Thibodeaux Michael Hennessey Department of Mathematical Sciences Loyola University New Orleans New Orleans LA USA Department of Mathematical Sciences Rensselaer Polytechnic Institute Troy NY USA

In this paper we modify previous models to develop a new model of within-host dengue infection without the assumption that monocyte production is constant. We show that this new model exhibits behavior not seen in previous models. We then proceed by obtaining an expression for the net reproductive rate of the virus and thus establish a stability result. We also perform a sensitivity analysis to test various treatment strategies and find that two strategies might be fruitful. One is the reduction of the infection rate of monocytes by viruses and the other, more effective, theoretical approach is to reduce the number of new viruses per infected monocyte.

关键词： Dengue Within-Host Model Net Reproductive Rate Treatment Scenarios

The world of james Bond

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The world of James Bond

Universal soldier： Pseudomonas aeruginosa -- an opportunistic generalist

作者： jeremy Black.

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Frontiers in Biology 2013年第4期8卷 387-394页

作者： jeremy GROSS Ian j. PASSMORE jade C. S. CHUNG Olena RZHEPISHEVSKA Madeleine RAMSTEDT Martin WELCH Department of Biochemistry University of Cambridge Cambridge CB2 1QW UK Department of Chemistry Umed University Umed 901 87 Sweden

The opportunistic pathogen Pseudomonas aeruginosa commonly causes chronic and ultimately deadly lung infections in individuals with the genetic disease cystic fibrosis （CF）. P. aeruginosa is metabolically diverse; it displays a remarkable ability to adapt to and successfully occupy almost any niche, including the ecologically complex CF lung. These P. aeruginosa lung infections are a fascinating example of microbial evolution within a ＂natural＂ ecosystem. Initially, P. aeruginosa shares the lung niche with a plethora of other microorganisms and is vulnerable to antibiotic challenges. Over time, adaptive evolution leads to certain commonly-observed phenotypic changes within the P. aeruginosa population, some of which render it resistant to antibiotics and apparently help it to out-compete the other species that co-habit the airways. Improving genomics techniques continue to elucidate the evolutionary mechanisms of P. aeruginosa within the CF lung and will hopefully identify new vulnerabilities in this robust and versatile pathogen.

关键词： Pseudomonas aeruginosa cystic fibrosis evolution adaptive radiation antibiotic resistance quorum sensing

Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2329-2344页

作者： junhui Hu Ping Tan Moe Ishihara Nicholas ABayley Shiruyeh Schokrpur jeremy GReynoso Yangjun Zhang Raymond jLim Camelia Dumitras Lu Yang Steven MDubinett Parmjit Sjat jacques Van Snick jiaoti Huang Arnold IChin Robert MPrins Thomas GGraeber Hua Xu Lily Wu Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Urology West China HospitalChengduChina Department of Hematology and Oncology University of California San DiegoSan DiegoCA92103USA Department of Neurosurgery David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Biological Repositories Department of UrologyZhongnan Hospital of Wuhan UniversityWuhanChina Department of Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA jonsson Comprehensive Cancer Center David Geffen School of Medicine at UCLAUniversity of California Los AngelesLos AngelesCA90095USA MRC Prion Unit at UCL Institute of Prion Diseases33 Cleveland StreetLondonW1W 7FFUK Ludwig Institute for Cancer Research Ltd BrusselsBelgium Department of Pathology Duke UniversityDurhamNCUSA Department of Urology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center WuhanChina

Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under *** study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic *** VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)*** tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic *** tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic *** poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+***(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular *** deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical *** work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

关键词： VHL metastasis motility

Site-directed deuteration of dronedarone preserves cytochrome P4502j2 activity and mitigates its cardiac adverse effects in canine arrhythmic hearts

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3905-3923页

作者： Aneesh V.Karkhanis Gopalakrishnan Venkatesan Ryuichi Kambayashi jacqueline Wen Hui Leow Marcus Qingrui Han Hiroko Izumi-Nakaseko Ai Goto jeremy Kah Sheng Pang Boon Seng Soh Pipin Kojodjojo Atsushi Sugiyama Eric Chun Yong Chan Department of Pharmacy Faculty of ScienceNational University of SingaporeSingapore 117543Singapore Department of Pharmacology Faculty of MedicineToho UniversityTokyo 143-8540Japan Institute of Molecular and Cell Biology Agency for ScienceTechnology and ResearchSingapore 138673Singapore Department of Biological Sciences Faculty of ScienceNational University of SingaporeSingapore 117558Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore

Cytochrome P4502j2(CYP2j2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adverse effects(AEs)with poorly understood *** previously demonstrated that dronedarone inactivates CYP2j2 potently and irreversibly,disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET *** this study,we investigated if mitigation of CYP2j2 inhibition prevents dronedarone-induced cardiac *** first synthesized a deuterated analogue of dronedarone(termed poyendarone)and demonstrated that it neither inactivates CYP2j2,disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in *** patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by ***,we show that dronedarone treatment or CYP2j2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2j2 activity exacerbates beat-to-beat(BTB)variability reflective of proarrhythmic *** contrast,poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2j2 ***,poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF,while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic *** findings prove that deuteration of dronedarone prevents CYP2j2 inactivation and mitigates dronedarone-induced cardiac AEs.

关键词： Arachidonic acid Atrial fibrillation CYP2j2 Drug-induced proarrhythmia Epoxyeicosatrienoic acids Mechanism-based inactivation Dronedarone

P2X7 receptor signaling during adult hippocampal neurogenesis

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Neural Regeneration Research 2019年第10期14卷 1684-1694页

作者： Hannah C. Leeson Tailoi Chan-Ling Michael D. Lovelace jeremy C. Brownlie Ben j. Gu Michael W. Weible II Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQueenslandAustralia Griffith Institute for Drug Discovery Griffith UniversityBrisbaneQueenslandAustralia Discipline of Anatomy and Histology School of Medical ScienceThe University of SydneySydneyNew South WalesAustralia Bosch Institute The University of SydneySydneyNew South WalesAustralia Applied Neurosciences Program Peter Duncan Neurosciences Research UnitSt. Vincent’s Centre for Applied Medical ResearchSydneyNew South WalesAustralia Faculty of Medicine St. Vincent’s Clinical SchoolUniversity of New South Wales SydneySydneyNew South WalesAustralia School of Environment and Science Griffith UniversityBrisbaneQueenslandAustralia Florey Institute of Neuroscience and Mental Health University of MelbourneMelbourneVictoriaAustralia

Neurogenesis is a persistent and essential feature of the adult mammalian *** neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new *** of hippocampal neurogenesis is complex and multifaceted,and numerous signaling pathways converge to modulate cell proliferation,apoptosis,and clearance of cellular debris,as well as synaptic integration of newborn immature *** expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored.P2X7 receptors are exceptionally versatile:in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation.P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication,and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form,which induce apoptotic cell death through cytosolic ion ***,as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis,as well as during some disease *** how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative *** review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus,and neural stem and progenitor cells.

关键词： P2X7 P2X7R adult neurogenesis neural stem cells neural progenitor cells hippocampus SGZ calcium signaling purinergic signaling

Tooth regeneration: a revolution in stomatology and evolution in regenerative medicine

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International journal of Oral Science 2011年第3期3卷 107-116页

作者： Sibel Yildirim Susan Y. Fu Keith Kim Hong Zhou Chang Hun Lee Ang Li Sahng Gyoon Kim Shuang Wang jeremy j. Mao Tissue Engineering and Regenerative Medicine Laboratory （TERML） Center for Craniofacial Regeneration Columbia University Medical Center New York NY 10032 USA Department of Basic Science Xi＇an Jiaotong University School of Stomatology Xi＇ an 710049 China

A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth？ If not, what are the therapeutically viable sources of stem cells for tooth regeneration？ Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration？ How can regenerated teeth be economically competitive with dental implants？ Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide？ This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration： repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.

关键词： stem cells bioactive cues biomaterials cell homing dental pulp tooth regeneration growth factors scaffold dental implants pulp regeneration