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Engineered Regeneration 2024年第2期5卷 255-268页

作者： Hadi Hajiali Jane McLaren Cristina Gonzalez-García Salah Abdelrazig Dong-Hyun Kim Matthew J.Dalby Manuel Salmerón-Sánchez Felicity R.A.J.Rose School of Pharmacy Nottingham Biodiscovery InstituteUniversity of NottinghamNottinghamUK Healthcare Technologies Institute School of Chemical EngineeringUniversity of BirminghamBirminghamUK Centre for the Cellular Microenvironment University of GlasgowGlasgowUK Centre for Analytical Bioscience Advanced Materials&Healthcare Technologies DivisionSchool of PharmacyUniversity of NottinghamNottinghamUK Marine Microbiomics Program in BiologyDivision of Science and MathematicsNew York University Abu Dhabi(NYUAD)P.O.Box 129188Abu DhabiUnited Arab Emirates

Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe ***,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor *** study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone *** study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive *** into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways *** gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC *** adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic *** study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone *** adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.

关键词： Adenosine release Osteogenic signalling pathways Human mesenchymal stromal cells Bone regeneration

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Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury

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Neural Regeneration Research 2022年第6期17卷 1240-1247页

作者： Kamilla Faritovna Idrisova Alina Kazymovna Zeinalova Galina Andreevna Masgutova Alexey Andreevich Bogov Jr. Cinzia Allegrucci Valeriia Yurievna Syromiatnikova Ilnur Ildusovich Salafutdinov Ekaterna Evgenievna Garanina Dina Ivanovna Andreeva Adilet Abdullaatovich Kadyrov Albert Anatolevich Rizvanov Ruslan Faridovich Masgutov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia Republican Clinical Hospital KazanRussia biodiscovery Institute School of Veterinary Medicine and ScienceUniversity of NottinghamNottinghamUK Department of Traumatology and Orthopedics Kazan State Medical AcademyKazanRussia

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe *** often leads to poor motor function and permanent *** approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve *** drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix *** growth factor plays its own specific angiotrophic or neurotrophic ***,growth factors are widely studied as accelerators of nerve *** noteworthy is synergy between various growth factors,that is essential for both angiogenesis and *** growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic *** the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous *** together,their neurotrophic and angiogenic properties have positive effect on the regeneration *** this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.

关键词： fibroblast growth factor 2 growth factors nerve growth factor peripheral nerve injury peripheral nervous system vascular endothelial growth factor

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GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： William R.Swindell Krzysztof Bojanowski Mark S.Kindy Raymond M.W.Chau Dorothy Ko Heritage College of Osteopathic Medicine Ohio UniversityAthensOHUSA sunny biodiscovery IncSanta PaulaCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAMC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALS)is currently an incurable disease without highly effective pharmacological *** peptide drug GM604(GM6 or Alirinetide)was developed as a candidate ALS therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment(6,24 and 48 h).Results:We identified 2867 protein-coding genes with expression significantly altered by GM6(FDR<0.10).Early(6 h)responses included up-regulation of Notch and hedgehog signaling components,with increased expression of developmental genes mediating neurogenesis and axon *** GM6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mRNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes(STAT3,HOXD11,HES7,GLI1).We identified 77 ALS-associated genes with expression significantly altered by GM6 treatment(FDR<0.10),which were known to function in neurogenesis,axon guidance and the intrinsic apoptosis ***:Our findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECM modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： Alzheimer’s disease Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s disease Neurodegenerative disease Notch,Parkinson’s disease RNA-seq Transcriptome

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Making Modified Cyclic Peptides Using Enzymes

Making Modified Cyclic Peptides Using Enzymes

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第十届全国化学生物学学术会议

作者： Marcel Jaspars Marine biodiscovery Centre University of Aberdeen

＜正＞Cyanobactins are a group of post-translationally modified ribosomal peptides of which the patellamides are the most complex examples. These modified cyclic peptides contain heterocycles and have epimerised stereocentres. The patellamides were originally obtained from the seasquirt Lissoclinum patella, but were later shown to be produced by its cyanobacterial symbiont Prochloron sp. The patellamide

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Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1

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Acta Pharmaceutica Sinica B 2019年第5期9卷 997-1007页

作者： Alexander J.Trevarton Yan Zhou Dehua Yang Gordon W.Rewcastle Jack U.Flanagan Antony Braithwaite Peter R.Shepherd Cristin G.Print Ming-Wei Wang Annette Lasham Department of Molecular Medicine and Pathology University of AucklandAucklandNew Zealand The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai201203China Auckland Cancer Society Research Centre AucklandNew Zealand Maurice Wilkins Centre for Molecular biodiscovery University of AucklandAucklandNew Zealand Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand Maurice Wilkins Centre for Molecular biodiscovery University of OtagoDunedinNew Zealand School of Pharmacy Fudan UniversityShanghai201203China

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the E2 F1 promoter by YB-1. The second approach is a novel application of the Alpha Screen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.

关键词： Cancer YB-1 Luciferase Alpha Screen Transcription factor Single-stranded DNA

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Targeting growth hormone function: strategies and therapeutic applications

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Signal Transduction and Targeted Therapy 2019年第1期4卷 614-624页

作者： Man Lu Jack U.Flanagan Ries J.Langley Michael P.Hay Jo K.Perry Liggins Institute University of AucklandAucklandNew Zealand Auckland Cancer Society Research Centre School of Medical SciencesUniversity of AucklandAucklandNew Zealand Maurice Wilkins Centre for Molecular biodiscovery AucklandNew Zealand Department of Molecular Medicine and Pathology School of Medical SciencesUniversity of AucklandAucklandNew Zealand

Human growth hormone(GH)is a classical pituitary endocrine hormone that is essential for normal postnatal growth and has pleiotropic effects across multiple physiological *** is also expressed in extrapituitary tissues and has localized autocrine/paracrine effects at these *** adults,hypersecretion of GH causes acromegaly,and strategies that block the release of GH or that inhibit GH receptor(GHR)activation are the primary forms of medical therapy for this *** of GH has also been linked to cancer and the microvascular complications that are associated with ***,studies to investigate the therapeutic potential of GHR antagonism in these diseases have been limited,most likely due to difficulty in accessing therapeutic tools to study the pharmacology of the receptor in *** review will discuss current and emerging strategies for antagonizing GH function and the potential disease indications.

关键词： therapeutic pituitary diseases

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Lithography and Fabrication of Frictional Tiers on Poly(Dimethylsiloxane) Using Atomic Force Microscopy

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Journal of Surface Engineered Materials and Advanced Technology 2012年第3期2卷 233-237页

作者： Gregory S. Watson Jolanta A. Watson School of Pharmacy and Molecular Sciences and Centre for biodiscovery and Molecular Development of Therapeutics James Cook University Townsville Australia.

This study investigates controlled micro/nano manipulation of polydimethylsiloxane (PDMS) using Atomic Force Microscopy (AFM). Lithographic results revealed stick-slip phenomena along the slow scan direction. Varying the normal loading force, scan size, scan number and contact conditions allowed the control of certain lithographic outcomes e.g., channel spacing. The PDMS surface experienced significant in-plane deformation in response to the tip-induced lateral force. This displacement increased with increasing loading force, creating greater spacing between channels in the slow scan direction. Simultaneous generation of a lateral displacement in the fast scan direction caused a decrease in channel length with increasing loading force due to an increase in static friction with normal force, resulting in a greater surface relaxation, and shorter track length of dynamic friction. By controlling both the loading force and the number of scans over an area, frictional tiers were produced.

关键词： Stick-Slip PDMS Manipulation Friction Polymer AFM

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BET inhibition prevents aberrant RUNX1 and ERG transcription in STAG2 mutant leukaemia cells

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Journal of Molecular Cell Biology 2020年第5期12卷 397-399页

作者： Jisha Antony Gregory Gimenez Terry Taylor Umaima Khatoon Robert Day Ian MMorison Julia AHorsfield Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9016New Zealand Maurice Wilkins Centre for Molecular biodiscovery The University of AucklandPrivate Bag 92019AucklandNew Zealand Southern Community Laboratories Dunedin 9016New Zealand Department of Biochemistry University of OtagoDunedin 9054New Zealand

Cohesin is a multiprotein complex that not only is essential for cell division but also has key roles in genome organization that underpin its gene regulatory *** mutations of genes encoding cohesin subunits occur in myeloid malignancies at 10%–12%(Kon et al.,2013),and the frequency of cohesin mutation in Down syndrome-associated megakaryoblastic leukaemia is even higher(~50%)(Yoshida et al.,2013).Cohesin insufficiency reinforces stem cell programmes and impairs differentiation in haematopoietic stem cells(Mazumdar et al.,2015;Mullenders et al.,2015;Viny et al.,2015).The STAG2 subunit of cohesin is the most frequently mutated in myeloid malignancies(Kon et al.,2013).In contrast to other cohesin subunits,complete loss of STAG2 is tolerated due to partial compensation by ***2 and STAG1 have redundant roles in cell division(Benedetti et al.,2017;van der Lelij et al.,2017).However,cohesin-STAG1 and cohesin-STAG2 have non-redundant roles in facilitating 3D genome organization to delineate tissue-specific gene expression(Kojic et al.,2018).

关键词： function. redundant

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The complexities of proanthocyanidin biosynthesis and its regulation in plants

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Plant Communications 2023年第2期4卷 12-27页

作者： Keji Yu Yushuang Song Jinxing Lin Richard A.Dixon National Engineering Research Center of Tree Breeding and Ecological Restoration Beijing Forestry UniversityBeijing 100083China College of Biological Sciences and Biotechnology Beijing Forestry UniversityBeijing 100083China biodiscovery Institute and Department of Biological Sciences University of North TexasDentonTX 76203USA Beijing Advanced Innovation Center for Tree Breeding by Molecular Design Beijing Forestry UniversityBeijing 100083China

Proanthocyanidins(PAs)are natural flavan-3-ol polymers that contribute protection to plants under biotic and abiotic stress,benefits to human health,and bitterness and astringency to food *** are also potential targets for carbon sequestration for climate *** recent years,from model species to commercial crops,research has moved closer to elucidating the flux control and channeling,subunit biosynthesis and polymerization,transport mechanisms,and regulatory networks involved in plant PA *** review extends the conventional understanding with recent findings that provide new insights to address lingering questions and focus strategies for manipulating PA traits in plants.

关键词： condensed tannin proanthocyanidin carbocation chemistry metabolic channeling non-enzymatic polymerization

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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

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