Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address t...Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded(n = 7) and non-infraoccluded(n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432(2.3%) genes were differentially expressed between the two groups(false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez;tissues that are central to the ankylotic process.We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.展开更多
Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-compu...Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (pCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major micro- structural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (~FE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis.展开更多
An association between Candida and oral cancer has long been discussed in the literature and in particular Candida albicans has been proposed to play a significant role in the development of oral cancer. Although this...An association between Candida and oral cancer has long been discussed in the literature and in particular Candida albicans has been proposed to play a significant role in the development of oral cancer. Although this organism is a common member of the oral mucosa and can cause a variety of oral mucosal lesions, the exact mechanisms by which C. albicans potentially causes the development of malignant disease still require much research. We have undertaken an extensive literature search to understand pathogenicity of C. albicans, including its virulence factors, its interactions with the host immune, how a dysregulation of the immune response can result in malignancy, and how a potential C. albicans specific cytokine response may be involved in oral carcinogenesis. We present here a candid assessment of the role of Candida in oral carcinogenesis and a hypothetical model about how this may occur. Finally, we present potential future research which is necessary to elucidate this role.展开更多
BACKGROUND Aortic dissection(AD)is a life-threatening condition with a high mortality rate without immediate medical attention.Early diagnosis and appropriate treatment are critical in treating patients with AD.In the...BACKGROUND Aortic dissection(AD)is a life-threatening condition with a high mortality rate without immediate medical attention.Early diagnosis and appropriate treatment are critical in treating patients with AD.In the emergency department,patients with AD commonly present with classic symptoms of unanticipated severe chest or back pain.However,it is worth noting that atypical symptoms of AD are easily misdiagnosed.CASE SUMMARY A 51-year-old woman was first diagnosed with scapulohumeral periarthritis due to left shoulder pain.After careful examination of her previous medical history and contrast-enhanced computed tomography angiography,the patient was diagnosed with a new type A AD after chronic type B dissection in the ascending aorta.The patient was successfully treated with surgical replacement of the dissected aortic arch and remains in good health.CONCLUSION New retrograde type A AD after chronic type B dissection is relatively rare.It is worth noting that a physician who has a patient with suspected AD should be vigilant.Both patient medical history and imaging tests are crucial for a more precise diagnosis.展开更多
Dental implants are the most common therapeutic approach for resolving tooth loss and damage.Despite technical advances in treatment,implant failure rates can be as high as 23%with the major cause of peri-implantitis:...Dental implants are the most common therapeutic approach for resolving tooth loss and damage.Despite technical advances in treatment,implant failure rates can be as high as 23%with the major cause of peri-implantitis:a multi-species bacterial infection.With an annual growth rate in implant placements of 8.78%per annum,implant failure caused by bacterial infection is a significant oral and general health issue.The rise in antibiotic resistance in oral bacteria further adds pressure to implant failure;thus,there is a need for adjunctive therapy to improve implant outcomes.Due to the broad spectrum of activity and a low risk of inducing bacterial resistance,peptide antibiotics are emerging as a promising implant coating material to reduce/prevent peri-implantitis and improve dental implant success rates.In this review,we summarised the current strategies of coating antimicrobial peptides(AMPs)onto dental implant material surfaces with multi-functional properties to enhance osteoblast growth and prevent bacterial infections.This review compared the recent reported literature on dental implant coating with AMPs,which will provide an overview of the current dental implant coating strategies using AMPs and insights for future clinical applications.展开更多
Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through ...Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism membranes.Our earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of bacteria.It is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential leakage.Thus,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of MSI-78(4–20)and pardaxin(1–22).Molecular modeling results suggest that aggregation of the N-lipidated AMPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental peptide.Our experimental and computationalfindings provide insights into how N-terminal lipidation of AMPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.展开更多
基金supported by a grant from the Australian Society of Orthodontists Foundation for Research and Education(ASOFRE).
文摘Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded(n = 7) and non-infraoccluded(n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432(2.3%) genes were differentially expressed between the two groups(false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez;tissues that are central to the ankylotic process.We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.
基金This work was partially supported by grants from National Institutes of Health(AR051376,AR058004)
文摘Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (pCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major micro- structural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (~FE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis.
文摘An association between Candida and oral cancer has long been discussed in the literature and in particular Candida albicans has been proposed to play a significant role in the development of oral cancer. Although this organism is a common member of the oral mucosa and can cause a variety of oral mucosal lesions, the exact mechanisms by which C. albicans potentially causes the development of malignant disease still require much research. We have undertaken an extensive literature search to understand pathogenicity of C. albicans, including its virulence factors, its interactions with the host immune, how a dysregulation of the immune response can result in malignancy, and how a potential C. albicans specific cytokine response may be involved in oral carcinogenesis. We present here a candid assessment of the role of Candida in oral carcinogenesis and a hypothetical model about how this may occur. Finally, we present potential future research which is necessary to elucidate this role.
文摘BACKGROUND Aortic dissection(AD)is a life-threatening condition with a high mortality rate without immediate medical attention.Early diagnosis and appropriate treatment are critical in treating patients with AD.In the emergency department,patients with AD commonly present with classic symptoms of unanticipated severe chest or back pain.However,it is worth noting that atypical symptoms of AD are easily misdiagnosed.CASE SUMMARY A 51-year-old woman was first diagnosed with scapulohumeral periarthritis due to left shoulder pain.After careful examination of her previous medical history and contrast-enhanced computed tomography angiography,the patient was diagnosed with a new type A AD after chronic type B dissection in the ascending aorta.The patient was successfully treated with surgical replacement of the dissected aortic arch and remains in good health.CONCLUSION New retrograde type A AD after chronic type B dissection is relatively rare.It is worth noting that a physician who has a patient with suspected AD should be vigilant.Both patient medical history and imaging tests are crucial for a more precise diagnosis.
基金National Health and Medical Research Council(NHMRC)of AustraliaNHMRC,Grant/Award Numbers:APP1142472,APP1158841,APP1185426+5 种基金ARC,Grant/Award Numbers:DP210102781,DP160101312,LE200100163Cancer Council Victoria,Grant/Award Number:APP1163284Australian Dental ResearchNHMRC Investigator,Grant/Award Number:APP2018256Shandong Provincial Hospital Affiliated to Shandong First Medical University,Grant/Award Number:2020FY027Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2021QH333。
文摘Dental implants are the most common therapeutic approach for resolving tooth loss and damage.Despite technical advances in treatment,implant failure rates can be as high as 23%with the major cause of peri-implantitis:a multi-species bacterial infection.With an annual growth rate in implant placements of 8.78%per annum,implant failure caused by bacterial infection is a significant oral and general health issue.The rise in antibiotic resistance in oral bacteria further adds pressure to implant failure;thus,there is a need for adjunctive therapy to improve implant outcomes.Due to the broad spectrum of activity and a low risk of inducing bacterial resistance,peptide antibiotics are emerging as a promising implant coating material to reduce/prevent peri-implantitis and improve dental implant success rates.In this review,we summarised the current strategies of coating antimicrobial peptides(AMPs)onto dental implant material surfaces with multi-functional properties to enhance osteoblast growth and prevent bacterial infections.This review compared the recent reported literature on dental implant coating with AMPs,which will provide an overview of the current dental implant coating strategies using AMPs and insights for future clinical applications.
基金The National Health and Medical Research Council,Grant/Award Numbers:APP2018256,APP1142472,APP1158841,APP1185426Australian Research Council,Grant/Award Numbers:FT210100271,DP210102781,DP160101312,LE200100163+5 种基金Cancer Council Victoria funding,Grant/Award Number:APP1163284Australia-China Science and Research Fund-Joint Research Centre on Personal Health Technologies,Grant/Award Number:ACSRF65777Australian Dental Research Foundation GrantPawsey Supercomputing CentreNational Computational InfrastructureAustralian National Fabrication Facility,Grant/Award Number:VictorianNode。
文摘Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism membranes.Our earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of bacteria.It is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential leakage.Thus,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of MSI-78(4–20)and pardaxin(1–22).Molecular modeling results suggest that aggregation of the N-lipidated AMPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental peptide.Our experimental and computationalfindings provide insights into how N-terminal lipidation of AMPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.