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A novel saliva-based miRNA profile to diagnose and predict oral cancer

International Journal of Oral Science 2024年第1期16卷 97-109页

作者： Jaikrishna Balakittnen Chameera Ekanayake Weeramange Daniel F.Wallace Pascal H.G.Duijf Alexandre S.Cristino Gunter Hartel Roberto A.Barrero Touraj Taheri Liz Kenny Sarju Vasani Martin Batstone Omar Breik Chamindie Punyadeera Saliva&Liquid Biopsy Translational Laboratory Griffith Institute for Drug DiscoveryGriffith UniversityNathanQLDAustralia Department of medical Laboratory Sciences Faculty of Allied Health SciencesUniversity of JaffnaJaffnaSri Lanka Menzies Health institute Griffith UniversityGold CoastQLDAustralia School of Biomedical Sciences Faculty of HealthQueensland University of TechnologyBrisbaneQLDAustralia Centre for Cancer Biology Clinical and Health SciencesUniversity of South Australia&SA PathologyAdelaideSAAustralia institute of Clinical Medicine Faculty of MedicineUniversity of OsloOsloNorway Department of medical Genetics Oslo University HospitalOsloNorway Griffith institute for Drug Discovery Griffith UniversityNathanQLDAustralia qimr berghofer medical research institute Statistics UnitBrisbaneQLDAustralia School of Public Health The University of QueenslandBrisbaneQLDAustralia School of Nursing Queensland University of TechnologyBrisbaneQLDAustralia eresearch Research InfrastructureAcademic DivisionQueensland University of TechnologyBrisbaneQLDAustralia Department of Anatomical Pathology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Faculty of Medicine The University of QueenslandBrisbaneQLDAustralia Royal brisbane and Women’s Hospital Cancer Care ServicesHerstonQLDAustralia Department of Otolaryngology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Department of Oral and Maxillofacial Surgery Royal Brisbane and Women’s HospitalHerstonQLDAustralia

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

关键词： specificity salivary diagnosis

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Patient-specific monocyte-derived microglia as a screening tool for neurodegenerative diseases

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Neural Regeneration research 2023年第5期18卷 955-958页

作者： Hazel Quek Anthony R.White Mental Health and Neuroscience QIMR Berghofer Medical Research Institute School of Biomedical Science The University of QueenslandBrisbaneQLDAustralia

Microglia, the main driver of neuroinflammation, play a central role in the initiation and exacerbation of various neurodegenerative diseases and are now considered a promising therapeutic target. Previous studies on in vitro human microglia and in vivo rodent models lacked scalability, consistency, or physiological relevance, which deterred successful therapeutic outcomes for the past decade. Here we review human blood monocyte-derived microglia-like cells as a robust and consistent approach to generate a patient-specific microglia-like model that can be used in extensive cohort studies for drug testing. We will highlight the strength and applicability of human blood monocyte-derived microglia-like cells to increase translational outcomes by reviewing the advantages of human blood monocyte-derived microglia-like cells in addressing patient heterogeneity and stratification, the basis of personalized medicine.

关键词： human in vitro microglia models neurodegeneration neuroinflammation patient heterogeneity patient stratification peripheral blood monocyte-derived microglia-like cells therapeutic target transdifferentiation translational outcomes

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Ferroptosis drives immune-mediated neurodegeneration in multiple sclerosis

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Cellular & Molecular Immunology 2023年第1期20卷 112-113页

作者： Anthony R.White Mental Health and Neuroscience QIMR Berghofer Medical Research InstituteHerstonQld4006Australia

One of the leading issues in multiple sclerosis(MS)research is the lack of understanding regarding the triggers of *** demyelination is a major feature in MS,the degeneration of gray matter neurons contributes to major changes in patient function,but the mechanisms driving this neuronal loss are *** exciting research published by Luoqian et al.[1]in the December issue of Cellular and Molecular Immunology,new insights have shown an important contribution of ferroptosis to T-cell-mediated neurodegeneration in the common animal model of MS,‘experimental autoimmune encephalomyelitis’(EAE).Although a relationship between ferroptosis and T-cell activation has been reported in other disorders,this is the first discovery of a link between abnormal iron homeostasis and T-cell infiltration in *** addition,the authors found that unlike other studies on ferroptosis-T-cell interactions[2,3],ferroptotic activation of T cells in EAE,and potentially MS,involved the infiltration and activation of CD4+T cells,rather than CD8+***,in this study,ferroptosis was a key driver of T-cell activation rather than the opposite interaction where CD8+cells drive ferroptosis[3].The research also mapped a key role for Acsl4 in the early stages of ferroptosis-T-cell-mediated ***4 converts free long-chain fatty acids into fatty acyl-CoA esters and has been identified as a central contributor to ferroptotic processes[4].This study has mapped a major new pathway potentially leading to neurodegeneration in MS,and this opens the possibility of new therapeutic approaches to treat MS based on iron targeting as the authors describe in their final experiments.

关键词： neurodegeneration degeneration homeostasis

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Lactate as a regulator of iron homeostasis

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Life Metabolism 2023年第5期2卷 8-11页

作者： Gregory J.Anderson David M.Frazer Iron Metabolism Laboratory QIMR Berghofer Medical Research InstituteBrisbaneQueensland 4006Australia Molecular Nutrition Laboratory QIMR Berghofer Medical Research InstituteBrisbaneQueensland 4006Australia

The key metabolic intermediate lactate can increase expression of the liver-derived peptide hepcidin,the central regulator of body iron homeostasis.A new paper by Liu et *** that lactate achieves this by binding to and activating soluble adenylyl cyclase,thereby increasing cellular cyclic adenosine monophosphate(cAMP)and enhancing signaling through the bone morphogenetic protein(BMP)pathway to modulate hepcidin expression.

关键词： expression thereby homeostasis

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Low back pain and osteoarthritis pain:a perspective of estrogen

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骨研究:英文版 2023年第3期11卷 443-456页

作者： Huiwen Pang Shihui Chen David M.Klyne David Harrich Wenyuan Ding Sidong Yang Felicity Y.Han Australian institute for Bioengineering and Nanotechnology The University of QueenslandSt.LuciaBrisbaneQLD 4072Australia NHMRC Centre of Clinical research Excellence in Spinal Pain Injury and HealthThe University of QueenslandSt.LuciaBrisbaneQLD 4072Australia Department of Cell and Molecular Biology QIMR Berghofer Medical Research InstituteHerstonQLD 4006Australia Department of Spine Surgery The Third Hospital of Hebei Medical University139 Ziqiang RoadShijiazhuang 050051China Hebei Joint International research Center for Spinal Diseases 139 Ziqiang RoadShijiazhuang 050051China

Low back pain(LBP)is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain *** disc(IVD)degeneration and facet joint osteoarthritis(FJOA)are two common causes of LBP,and both occur more frequently in elderly women than in other ***,osteoarthritis(OA)and OA pain,regardless of the joint,are experienced by up to twice as many women as men,and this difference is amplified during *** in estrogen may be an important contributor to these pain *** for estrogen have been found within IVD tissue and nearby joints,highlighting the potential roles of estrogen within and surrounding the IVDs and *** addition,estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression,indicating its potential use as a therapeutic agent for people with LBP and OA *** review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical *** potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.

关键词： agent degeneration pain

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TREM2 marks tumor-associated macrophages

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Signal Transduction and Targeted Therapy 2020年第1期5卷 493-494页

作者： Kyohei Nakamura Mark J.Smyth qimr berghofer medical research institute Herston 4006 QLDAustralia

Immunosuppressive myeloid cells are recognized as a key barrier for cancer *** an integrated technology for single-cell RNA-sequencing and intracellular protein measurements,A recent paper published in Cell provides e... 详细信息

关键词： tumor immunotherapy myeloid

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Myeloid immunosuppression and immune checkpoints in the tumor microenvironment

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Cellular & Molecular Immunology 2020年第1期17卷 1-12页

作者： Kyohei Nakamura Mark J.Smyth Immunology in Cancer and Infection Laboratory QIMR Berghofer Medical Research InstituteHerston 4006 QLDAustralia

Tumor-promoting inflammation and the avoidance of immune destruction are hallmarks of *** innate immune cells,such as neutrophils,monocytes,and macrophages,are critical mediators for sterile and nonsterile inflammation,persistent inflammation,such as that which occurs in cancer,is known to disturb normal *** disturbance leads to the generation of immunosuppressive myeloid cells,such as myeloid-derived suppressor cells(MDSCs)and tumor-associated macrophages(TAMs).Due to their potent suppressive activities against effector lymphocytes and their abundance in the tumor microenvironment,immunosuppressive myeloid cells act as a major barrier to cancer ***,various therapeutic approaches directed toward immunosuppressive myeloid cells are actively being tested in preclinical and clinical *** include antiinflammatory agents,therapeutic blockade of the mobilization and survival of myeloid cells,and immunostimulatory *** recently,immune checkpoint molecules expressed on tumor-infiltrating myeloid cells have emerged as potential therapeutic targets to redirect these cells to eliminate tumor *** this review,we discuss the complex crosstalk between cancer-related inflammation and immunosuppressive myeloid cells and possible therapeutic strategies to harness antitumor immune responses.

关键词： myeloid macrophage innate immunity immune checkpoint inflammation

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Enhanced destabilization of mismatched DNA using gold nanoparticles offers specificity without compromising sensitivity for nucleic acid analyses

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Nano research 2015年第12期8卷 3922-3933页

作者： Abootaleb Sedighi Vicki Whitehall Paul C. H. Li Department of Chemistry Simon Fraser University Burnaby BC VSA 1S6 Canada qimr berghofer medical research institute 300 Herston Rd Brisbane QLD 4006 Australia

这里，我们报导使用金 nanoparticles (AuNPs ) 没有减少它的察觉敏感，提高 DNA 杂交的特性的一个方法。常规紧洗方法利用 high-temperature/low-salt 条件提高 DNA 基于杂交的试金的特性。这个方法为基础配对创造使动摇的环境影响特... 详细信息

这里，我们报导使用金 nanoparticles (AuNPs ) 没有减少它的察觉敏感，提高 DNA 杂交的特性的一个方法。常规紧洗方法利用 high-temperature/low-salt 条件提高 DNA 基于杂交的试金的特性。这个方法为基础配对创造使动摇的环境影响特定并且 nonspecific duplexes。因此，特性在损坏信号紧张或敏感的情况下被完成。然而，在里面求婚洗方法， AuNPs 主要使动摇 nonspecific duplexes，没有妥协的出现特性敏感。这 AuNP 洗技术证明了在在一个像 CD 的 NanoBioArray (CD-NBA ) 薄片甚至在房间温度在 genomic 样品检测单个核苷酸多型性(SNP ) 有效。这个方法与顺序变化也是柔韧的并且与 microarrays 上的复合 DNA 分析兼容。因此， AuNP 洗方法能潜在地为改进 DNA 杂交结果的精确性是有用的。

关键词：检测灵敏度金纳米粒子不稳定核酸分析粒子增强 DNA杂交非特异性单核苷酸多态性

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Optimisation of the DNA dipstick as a rapid extraction method for Schistosoma japonicum in infected mice samples and spiked human clinical samples

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Infectious Diseases of Poverty 2023年第4期12卷 108-108页

作者： Oyime P.Aula Donald P.McManus Malcolm K.Jones Hong You Pengfei Cai Catherine A.Gordon Molecular Parasitology Laboratory QIMR Berghofer Medical Research Institute Brisbane Australia School of Public Health Faculty of Medicine The University of Queensland Brisbane Australia School of Veterinary Science The University of Queensland Brisbane Australia Faculty of Medicine The University of Queensland Brisbane Australia

BackgroundSchistosomiasis remains a public health issue and the need for accurate and affordable diagnostics is crucial in the elimination of the disease. While molecular diagnostics are highly effective, they are expensive, with the main costs been associated with DNA extraction. The DNA dipstick is a rapid, affordable and simple purification method that allows DNA to be extracted from diagnostic samples within 30 s. We aimed to optimise the DNA dipstick method for samples from mice and egg-spiked human ***, blood and faeces were collected from mice exposed to Schistosoma japonicum infection at weekly intervals from Day 0 to Day 42. Urine and faecal samples were also collected from volunteer, uninfected humans and spiked with S. japonicum eggs. All samples were subject to several optimisation procedures and DNA extracted with the DNA dipstick. Amplification of the target DNA was carried out using LAMP and visualised using agarose gel electrophoresis and *** DNA dipstick successfully identified S. japonicum from infected mice and human clinical samples spiked with cracked eggs or genomic DNA from S. japonicum. Amplification was observed from week 4 post infection in infected mice. For human samples, amplification was observed in sieved faecal samples, filtered urine samples heated at 95 ℃ for 30 min, and sera samples heated at 95℃ for 30 *** DNA dipstick combined with LAMP has huge potential in providing cost-effective, simple and accurate detection of schistosomiasis infection in endemic regions. This will allow for rapid treatment, tracking outbreaks—such as occur after typhoons, leading to better health outcomes and contributing to control and eventual elimination of schistosomiasis.

关键词： Schistosomiasis Schistosoma japonicum DNA dipstick Loop-mediated isothermal amplification assay Flocculation

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Health-education to prevent COVID-19 in schoolchildren: a call to action

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Infectious Diseases of Poverty 2020年第4期9卷 142-144页

作者： Darren J.Gray Johanna Kurscheid Mary Lorraine Mationg Gail M.Williams Catherine Gordon Matthew Kelly Kinley Wangdi Donald P.McManus Department of Global Health Research School of Population HealthAustralian National UniversityCanberraAustralia School of Public Health University of QueenslandBrisbaneAustralia Infectious Diseases Division QIMR Berghofer Medical Research InstituteBrisbaneAustralia

Background:There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019(COVID-19).Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults,little is still known about their transmission potential,and with a lot of asymptomatic cases they may be silent transmitters(*** without showing clinical signs of disease),albeit at a lower level than *** relation to this,it is somewhat concerning that in many countries children are cared for,or are often in close contact with,older individuals such as grandparents—the age group most at risk of acquiring serious respiratory complications resulting in *** text:We emphasise that in the absence of a vaccine or an effective therapeutic drug,preventive measures such as good hygiene practices—hand washing,cough etiquette,disinfection of surfaces and social distancing represent the major(in fact only)weapons that we have against ***,we stress that there is a pressing need to develop specific COVID-19 prevention messages for ***:An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this *** such measures in place there would be greater confidence around the opening of schools.

关键词： COVID-19 Children Health education Health promotion Prevention

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