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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Teaching pharmacology to medical students in an integrated problem-based learning curriculum:an Australian perspective

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Acta Pharmacologica Sinica 2004年第9期 93-101页

作者： Owen L WOODMAN,Agnes E DODDS,Albert G FRAUMAN,Mosepele MOSEPELE Department of Pharmacology faculty Education Unit Clinical Pharmacology and Therapeutics Unit faculty Education Unit faculty of medicine dentistry and health sciences faculty of medicine dentistry and health sciences Department of medicine The University of Melbourne Australia faculty of medicine dentistry and health sciences

The world-wide move away from the didactic teaching of single disciples to integrated Problem-based Learning (PBL) curricula in medical education has posed challenges for the basic sciences. In this paper we identify two major challenges. The first challenge is the need to describe a core disciplinary curriculum that can be articulated and mapped onto the new structure. We illustrate how the British Pharmacological Society (BPS)

关键词： Teaching pharmacology to medical students in an integrated problem-based learning curriculum

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Dental pulp stem cells stimulate neuronal differentiation of PC12 cells

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Neural Regeneration Research 2021年第9期16卷 1821-1828页

作者： Nessma Sultan Laila E.Amin Ahmed R.Zaher Mohammed E.Grawish Ben A.Scheven School of dentistry Oral BiologyCollege of Medical and Dental SciencesUniversity of BirminghamBirminghamUK Department of oral Biology Faculty of DentistryMansoura UniversityEgypt faculty of dentistry Horus UniversityNew DamiettaEgypt Department of oral Biology Faculty of Oral and Dental MedicineDelta University for Science and TechnologyMansouraEgypt

Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, an

关键词： brain-derived neurotrophic factor conditioned medium dental pulp stem cell glial cell line-derived nerve growth factor neurite outgrowth neurotrophic factor neurotrophin-3 phaeochromocytoma PC12 cell

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oral manifestations in patients with diabetes mellitus

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World Journal of Diabetes 2019年第9期10卷 485-489页

作者： Bita Rohani Department of oral medicine Faculty of Dentistry Aja University of Medical Sciences

The purpose of this article was to increase the knowledge about oral manifestations and complications associated with diabetes *** overview was performed on Google,especially in recent reliable papers in relation to diabetes mellitus and its oral manifestations(keywords were“diabetes mellitus”,“oral manifestations”,and“oral complications”).Data were collected and the results were *** mellitus is one of the most common chronic disorders characterized by *** disease can have many complications in various regions of the body,including the oral *** important oral manifestations and complications related to diabetes include xerostomia,dental caries,gingivitis,periodontal disease,increased tendency to oral infections,burning mouth,taste disturbance,and poor wound *** complications in diabetic patients are considered major complications and can affect patients’quality of *** is evidence that chronic oral complications in these patients have negative effects on blood glucose control,so prevention and management of the oral complications are important.

关键词： Diabetes mellitus oral complications oral manifestations Periodontal disease Xerostomia

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Characterization of the salivary microbiome in healthy Thai children

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Asian Pacific Journal of Tropical medicine 2019年第4期12卷 163-169页

作者： Izumi Mashima Citra F.Theodorea Boonyanit Thaweboon Sroisiri Thaweboon Tippanart Vichayanrat Frank A.Scannapieco Futoshi Nakazawa Department of Microbiology School of Pharmacy Aichi Gakuin University Department of oral Biology Faculty of Dentistry Universitas Indonesia Department of oral Microbiology Faculty of Dentistry Mahidol University Department of Community dentistry Faculty of Dentistry Mihidol University Department of oral Biology School of Dental Medicine University at Buffalo the State University of New York Department of Microbiology School of Dentistry Health Sciences University of Hokkaido

Objective: To investigate the composition of the salivary microbiome of 50 healthy Thai children. Methods: A total 76 provinces in Thailand are grouped into 5 geographical clusters based on unique economics, foods and lifestyles. Geographical locations and the results of an oral assessment were also considered. Genomic DNA was extracted from stimulated saliva samples. Subsequently, amplicon libraries were prepared by 16 S Metagenomic Sequencing Library Preparation. The amplicons were sequenced using an Illumina Miseq platform followed by bioinformatics and statistical ***: The correlation between oral hygiene status and caries history varied from r^2=0.887 to r^2=0.999 in the geographical groups, suggesting oral hygiene status a strong association between caries history. Twenty taxonomic groups were found in all subjects and constituted 93.6%-96.5% of the microbiome. Of these, genus Veillonella and Prevotella showed significant differences in their proportions between the geographical groups(Poral hygiene status, which was also related to higher dental caries ***: The differences in the salivary microbiome as related to geographic regions suggest that environmental factors, which may include dietary habits, could influence the predominant bacteria found in the mouth of Thai children, especially the genus Veillonella and Prevotella. The ratio of Veillonella parvula, Rothia aeria and Rothia dentocariosa may be indicators of worse oral hygiene status and future caries in this population.

关键词： Saliva Microbiome Thai Children Region Simplified oral hygiene index

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Effect of roselle calyx extract on in vitro viability and biofilm formation ability of oral pathogenic bacteria

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Asian Pacific Journal of Tropical medicine 2016年第2期9卷 115-120页

作者： Herastuti Sulistyani Mari Fujita Hiroshi Miyakawa Futoshi Nakazawa Department of oral Microbiology School of Dentistry Health Sciences University of Hokkaido

Objective: To investigate the effect of the roselle calyx extract(RCE)(Hibiscus sabdariffa L.) on the in vitro viability and biofilm formation ability of oral pathogenic bacteria. Methods:RCE was prepared by soaking roselle calyx powder with ethyl alcohol for 24 h at room temperature. After centrifugation, the extract was lyophilized. Then, the extract was dissolved in phosphate-buffered saline, the p H was adjusted, and the extract was aseptically filtered. We used Streptococcus mutans, Streptococcus sanguinis, Lactobacillus casei, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia in this study. The antibacterial activity of the RCE was determined by treating the cells of these bacteria with the extract for 10 or 20 min at room temperature. The minimum inhibitory concentration(MIC) and minimum bactericidal concentration was determined using the micro dilution method, and the effect of the RCE on the ability to form biofilm was determined using a polystyrene micro plate assay. In addition, we used the WST-1 assay to determine the cytotoxicity of the RCE on HGF, Ca9-22 and KB cells. Results: The RCE had antibacterial activity against oral bacteria used in this study. In particular, most significant antibacterial activity was observed against Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. The MIC and minimum bactericidal concentration were 7.2 mg/m L–28.8 mg/m L and 14.4 to >57.6 mg/m L. The RCE had an inhibitory effect on biofilm formation at the MIC and sub-MIC levels. In addition, the RCE had low cytotoxic effects on HGF, Ca9-22 and KB cells. Conclusions: Thus, our results indicate that the RCE may be used for preventing oral diseases.

关键词： oral bacteria oral biofilm oral cells Roselle calyx extract

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Orexins and male reproduction

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Asian pacific Journal of Reproduction 2019年第5期8卷 233-238页

作者： Pallav Sengupta Sulagna Dutta Maiza Tusimin Ivan Rolland Karkada Department of Physiology Faculty of Medicine and Biomedical SciencesMAHSA UniversityMalaysia Department of oral Biology and Biomedical sciences Faculty of DentistryMAHSA UniversityMalaysia faculty of medicine and health sciences Universiti Putra MalaysiaMalaysia

Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system,i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functionsvia modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.

关键词： Obesity Orexin Testis Steroidogenesis Spermatogenesis

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Tricking the tumour microenvironment into becoming our best rational drug design factory:reversal of immune suppression

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 615-623页

作者： Martin L.Ashdown faculty of medicine Dentistry and Health SciencesUniversity of MelbourneMelbourne 3011Australia

The immune cellular components of the tumour microenvironment are a diverse group of cells that paradoxically are now appreciated to have a coordinated opposing duality of either promoting or retarding tumour *** this seemingly dynamic interaction for therapeutic benefit is a hotbed of much *** findings in tumour immunology(both preclinical and clinical)build on more than a century of insights and provide a way forward to improving patient outcomes,long term survival and the predictability of“cures”.This opinion piece attempts to summarise some of these historical and contemporary insights with a view to describing eminently testable therapeutic solutions.

关键词： Tumour microenvironments immune suppression regulatory T cells immune modulation reversal plasticity spatio-temporal

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Helicobacter pylori in human health and disease:Mechanisms for local gastric and systemic effects

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World Journal of Gastroenterology 2018年第28期24卷 3071-3089页

作者： Denisse Bravo Anilei Hoare Cristopher Soto Manuel A Valenzuela Andrew FG Quest oral Microbiology Laboratory Pathology and Oral Medicine DepartmentFaculty of DentistryUniversidad de Chile Advanced Center for Chronic Diseases Institute for Health-Related Research and InnovationFaculty of Health SciencesUniversidad Central de Chile Advanced Center for Chronic Diseases Center for Studies on ExerciseMetabolism and CancerBiomedical Science InstituteFaculty of MedicineUniversidad de Chile

Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.

关键词： Helicobacter pylori Co-evolution Extragastric diseases Inflammation Microbiome

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Enhancing metabolic activity and differentiation potential in adipose mesenchymal stem cells via high-resolution surface-acoustic-wave contactless patterning

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Microsystems & Nanoengineering 2022年第4期8卷 111-124页

作者： Karina Martinez Villegas Reza Rasouli Maryam Tabrizian Departmentof Biological and Biomedical Engineering McGill UniversityMontrealQCCanada faculty of Dental medicine and oral health sciences McGill UniversityMontrealQcCanada

Acoustofluidics has shown great potential for label-free bioparticle patterning with excellent *** patterning enables the induction of cell–cell interactions,which play fundamental roles in organogenesis and tissue *** of the current challenges in tissue engineering is not only the control of the spatial arrangement of cells but also the preservation of cell patterns over *** this work,we developed a standing surface acoustic wave-based platform and demonstrated its capability for the well-controlled and rapid cell patterning of adipose-derived mesenchymal stem cells in a high-density homogenous collagen *** biocompatible hydrogel is easily UV crosslinked and can be retrieved within 3 *** waves successfully guided the cells toward pressure nodal lines,creating a contactless alignment of cells in90%)48 h after acoustic ***,45.53%and 30.85%increases in metabolic activity were observed in growth and differentiation media,respectively,on Day *** Day 14,a 32.03%change in metabolic activity was observed using growth media,and no significant difference was observed using differentiation *** alkaline phosphatase activity showed an increase of 80.89%and 24.90%on Days 7 and 14,respectively,for the acoustically patterned cells in the *** results confirm the preservation of cellular viability and improved cellular functionality using the proposed high-resolution acoustic patterning technique and introduce unique opportunities for the application of stem cell regenerative patches for the emerging field of tissue engineering.

关键词： potential resolution wave

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