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Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts

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Bone research 2016年第3期4卷 164-173页

作者： Allahdad Zarei Alireza Morovat Kassim Javaid Cameron P Brown botnar research Centre Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Science University of Oxford Oxford UK Clinical Biochemistry Oxford University Hospitals NHS Trust Oxford UK

The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor （VDR）, we examined their response to different concentrations of 25-hydroxy vitamin D3 [25（OH）D3] （100 or 500 nmol·L^-1） and 1,25-dihydroxy vitamin D3 [1,25（OH）2D3] （0.1 or 0.5 nmol·L^-1） metabolites in cell cultures. Specifically, CD14＋ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand （RANKL） and macrophage colony-stimulating factor （M-CSF）. Tartrate-resistant acid phosphatase （TRAP） histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue （ex vivo） by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR （qRT-PCR） was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25（OH）D3 and 0.1-0.5 nmol·L^-1 of 1,25（OH）2D3, upregulating cytochrome P450 family 27 subfamily B member I （CYP27B1） and cytochrome P450 family 24 subfamily A member I （CYP24A1）. Osteoclast fusion transcripts transmembrane 7 subfamily member 4 （tm7sf4） and nuclear factor of activated T-cell cytoplasmic 1 （nfatcl） where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25（OH）D3 and 1,25（OH）2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25（OH）2D3 on osteoclasts in vitro may therefore provide

关键词： Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts bone

Orthopaedic tissue engineering and stem cells -an unfulfilled promise

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Biomaterials Translational 2021年第2期2卷 89-90页

作者： James T.Triffitt botnar research Centre Nuffield Department of OrthopaedicsRheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK

Despite being over thirty years since there was proof that the hypothetical osteogenic stem cell existed,1 demonstration of any dramatic value for the use of such cells in orthopaedic clinical practice by tissue engineering approaches has not yet been *** is notwithstanding extensive studies concerning the likely nature and potentials of these cells in countless in vitro and in vivo *** part,this is based on the confusion caused by exaggeration of claims by unreliable,or at best naïve,investigators and opportunistic entrepreneurs who have grossly misinterpreted data from many ill-conceived studies.2,3 This pseudo-science has been harmful,especially to the stem cell field,both academically and commercially.

关键词： likely concerning spite

Advancing Smart Biomedical Textiles with Humanoid Robots

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Advanced Fiber Materials 2024年第1期6卷 1-2页

作者： Zekun Liu Pierre‑Alexis Mouthuy Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal SciencesBotnar Research CenterUniversity of OxfordOxford OX37LDUK

Smart implantable biomedical textiles with sensing functions are of increasing interest because they address the shortcoming that conventional medical devices have repair functions but lack of sensing ***,the evaluation of such devices before practical applications is hampered by high cost and/or animal *** bioreactors on humanoid robots open up a new pathway for assessing their performances by closely mimicking both the body biomechanics and the physiological environment.

关键词： Smart cost assessing

Revolutionizing digital healthcare networks with wearable strain sensors using sustainable fibers

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SusMat 2024年第4期4卷 104-151页

作者： Junze Zhang Bingang Xu Kaili Chen Yi Li Gang Li Zekun Liu Nanotechnology center School of Fashion and TextilesThe Hong Kong Polytechnic UniversityKowloonHong KongChina Department of Materials Imperial College LondonLondonUK Department of Materials University of ManchesterManchesterUK National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow UniversitySuzhouChina botnar research center University of OxfordOxfordUK

Wearable strain sensors have attracted research interest owing to their poten-tial within digital healthcare,offering smarter tracking,efficient diagnostics,and lower *** rigid sensors,fiber-based ones compete with their flexibility,durability,adaptability to body structures as well as eco-friendliness to ***,the sustainable fiber-based wearable strain sensors for digital health are reviewed,and material,fabrication,and practical healthcare aspects are *** strain sensors predicated on various sensing modalities,be it resistive,capacitive,piezoelectric,or triboelectric,are explained and analyzed according to their strengths and weaknesses toward fabrication and *** applications in digital healthcare spanning from body area sensing networks,intelligent health management,and medical rehabilitation to mul-tifunctional healthcare systems are also ***,to create a more complete digital health network,wired and wireless methods of data collec-tion and examples of machine learning are elaborated in ***,the prevailing challenges and prospective insights into the advancement of novel fibers,enhancement of sensing precision and wearability,and the establishment of seamlessly integrated systems are critically summarized and *** endeavor not only encapsulates the present landscape but also lays the founda-tion for future breakthroughs in fiber-based wearable strain sensor technology within the domain of digital health.

关键词： advanced fibers digital health flexible electronics strain sensors wearables

Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion

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Bone research 2023年第2期11卷 368-383页

作者： Yu Sheng Li Xiao Wang Bo Hu Qi Sun Mei Wan Andrew Carr Shen Liu Xu Cao Department of Orthopedic Surgery The Johns Hopkins University School of MedicineBaltimoreMD21205USA Nuffield Department of Orthopedics Rheumatology and Musculoskeletal SciencesBotnar Research CentreUniversity of OxfordWindmill RoadOxford OX 37 LDUK

PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of ***,the origin of myofibroblasts in PAF tissues is still *** this study,we found that the concentration of active TGF-β1 and the numbers of macrophages,mesenchymal stromal cells(MSCs),and myofibroblasts in human and mouse adhesion tissues were ***,knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagenⅠandⅢdeposition,***,we found that MSCs differentiated into myofibroblasts to form adhesion *** injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and,subsequently,*** results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous *** improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.

关键词： inhibited injection MSC

Long-term clinical performance of flapless implant surgery compared to the conventional approach with flap elevation:A systematic review and meta-analysis

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World Journal of Clinical Cases 2020年第6期8卷 1087-1103页

作者： He Cai Xing Liang Dong-Yuan Sun Jun-Yu Chen Department of Prosthodontics State Key Laboratory of Oral DiseasesNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041Sichuan ProvinceChina botnar research Centre University of OxfordWindmill RoadOxford OX37LDUnited Kingdom Kennedy Institute of Rheumatology University of OxfordRoosevelt DriveOxford OX37FYUnited Kingdom

BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative *** flapless surgical technique,aided by three-dimensional medical imaging equipment,is regarded as a possible alternative to the conventional approach to alleviate the above *** studies have been performed regarding the role of flapless implant ***,the results are inconsistent and there is no robust synthesis of long-term evidence to better inform surgeons regarding which type of surgical technique is more beneficial to the long-term prognosis of patients in need of implant *** To compare the long-term clinical performance after flapless implant surgery to that after the conventional approach with flap *** PubMed,EMBASE,Cochrane Central Register of Controlled Trials,and grey literature databases were searched from inception to 23 September *** controlled trials (RCTs) and cohort studies comparing the long-term clinical performance after flapless implant surgery to that after the conventional approach over a follow-up of three years or more were ***-analyses were conducted to estimate the odds ratios (ORs) or mean differences (MDs) and their 95 To confidence intervals (CIs) between the long-term implant survival rate,marginal bone loss,and complication rate of the flapless and conventional *** analyses were carried out to account for the possible effects of the guided or free-hand method during flapless *** Ten articles,including four RCTs and six cohort studies,satisfied the eligibility criteria and nine of them were inclded in the *** was no significant difference between the long-term implant survival rate [OR=1.30,95%CI (0.37,4.54),P=0.68],marginal bone loss [MD=0.01,95%CI (-0.42,0.44),P=0.97],and complication rate [OR=1.44,95%CI (0.77,2.68),P=0.25] after flapless implant surgery and the conventional appro

关键词： Flapless implant surgery Dental implantation Minimally invasive surgical procedures Computer-assisted surgery Cone-beam computed tomography Implant survival rate Marginal bone loss Complication rate

Evaluating Performance of Different RNA Secondary Structure Prediction Programs Using Self-cleaving Ribozymes

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 29-41页

作者： Fei Qi Junjie Chen Yue Chen Jianfeng Sun Yiting Lin Zipeng Chen Philipp Kapranov State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Institute of Genomics School of MedicineHuaqiao UniversityXiamen 361021China botnar research Centre University of OxfordOxfordOX37LDUnited Kingdom

Accurate identification of the correct,biologically relevant RNA structures is critical to understanding various aspects of RNA biology since proper folding represents the key to the functionality of all types of RNA molecules and plays pivotal roles in many essential biological ***,a plethora of approaches have been developed to predict,identify,or solve RNA structures based on various computational,molecular,genetic,chemical,or physicochemical *** computational approaches hold distinct advantages over all other strategies in terms of the ease of implementation,time,speed,cost,and throughput,but they strongly underperform in terms of accuracy that significantly limits their broader ***,the advantages of these methods led to a steady development of multiple in silico RNA secondary structure prediction approaches including recent deep learning-based ***,we compared the accuracy of predictions of biologically relevant secondary structures of dozens of self-cleaving ribozyme sequences using seven in silico RNA folding prediction tools with tasks of varying *** found that while many programs performed well in relatively simple tasks,their performance varied significantly in more complex RNA folding ***,in general,a modern deep learning method outperformed the other programs in the complex tasks in predicting the RNA secondary structures,at least based on the specific class of sequences tested,suggesting that it may represent the future of RNA structure prediction algorithms.

关键词： RNA secondary structure RNA secondary structure prediction Ribozyme Deep learning Pseudoknot

Calotropis gigantea Fiber‑Based Sensitivity‑Tunable Strain Sensors with Insensitive Response to Wearable Microclimate Changes

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Advanced Fiber Materials 2023年第4期5卷 1378-1391页

作者： Junze Zhang Jing Liu Zeyu Zhao Weiwei Sun Gaojuan Zhao Jingge Liu Jianchu Xu Yuling Li Zekun Liu Yi Li Gang Li National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow UniversitySuzhou 215123China Jiangsu Advanced Textile Engineering Technology center Nantong 226007China Honghe center for Mountain Futures Kunming Institute of BotanyChinese Academy of SciencesHonghe CountyYunnan 654412China Key Laboratory of Textile Science and Technology Ministry of EducationDonghua UniversityShanghai 201620China Department of Materials University of ManchesterOxford RoadManchester M139PLUK botnar research center University of OxfordOld RoadHeadington OX37LDOxfordUK

Wearable tensile strain sensors have attracted substantial research interest due to their great potential in applications for the real-time detection of human motion and health through the construction of body-sensing *** devices,however,are constantly demonstrated in non-real world scenarios,where changes in body temperature and humidity are ignored,which results in questionable sensing accuracy and reliability in practical *** this work,a fabric-like strain sensor is developed by fabricating graphene-modified Calotropis gigantea yarn and elastic yarn(***)into an independently crossed structure,enabling the sensor with tunable sensitivity by directly altering the sensor *** sensor possesses excellent breathability,allowing water vapor generated by body skin to be discharged into the environment(the water evaporation rate is approximately 2.03 kg m^(-2) h^(-1))and creating a pleasing microenvironment between the sensor and the skin by avoiding the hindering of perspiration *** importantly,the sensor is shown to have a sensing stability towards changes in temperature and humidity,implementing sensing reliability against complex and changeable wearable *** wearing the sensor at various locations of the human body,a full-range body area sensing network for monitoring various body movements and vital signs,such as speaking,coughing,breathing and walking,is successfully *** provides a new route for achieving wearing-comfortable,high-performance and sensing-reliable strain sensors.

关键词： Wearable strain sensor Functionalized Calotropis gigantea fiber Wearable microclimate Graphene coating Tunable sensitivity

Chronic inflammation and achilles tendinopathy

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中华物理医学与康复杂志 2018年第3期40卷 173-173页

作者： Dakin SG Newton J Martinez FO NDORMS Botnar Research Centre University of Oxford Nuffield Orthopaedic Centre Oxford UK. Faculty of Health and Medical Sciences University of Surrey Guildford UK.

BACKGROUND:Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture.;METHODS:We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers.;RESULTS:Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased and expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells.;CONCLUSIONS:Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease.

关键词：免疫力跟腱疾病患者治疗方法