Purpose: In age-restricted youth sport, the over-selection of athletes born in the first quarter of the year and under-selection of athletes born in the last quarter of the year has been called the relative age effe...Purpose: In age-restricted youth sport, the over-selection of athletes born in the first quarter of the year and under-selection of athletes born in the last quarter of the year has been called the relative age effect (RAE). Its existence in youth sports like soccer is well established. Why it occurs has not been identified, however, one thought is that older players, generally taller and heavier, are thought to improve the team's chances of winning. To test this assumption, birth dates and match outcome were correlated to see if teams with the oldest mean age had a systematic advantage against teams with younger mean ages. Methods: Player birth dates and team records (n = 5943 players on 371 teams; both genders; U11-U16) were obtained from the North Carolina Youth Soccer Association for the highest level of statewide youth competition. Results: The presence of an RAE was demonstrated with significant oversampling from players born in the I st vs. the 4th quarter (overall: 29.6% vs. 20.9% respectively, p 〈 0.0001). Mean team age was regressed on match outcomes (winning %, points/match, points/goal, and goals for, against, and goal difference), but there was no evidence of any systematic influence of mean team age and match outcomes, except possibly in U11 males. Conclusion: Selecting players based on physical maturity (and subsequently, on age) does not appear to have any systematic influence on match outcome or season record in youth soccer suggesting that the selection process should be focused on player ability and not on physical maturation.展开更多
e-related macular degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests fr...e-related macular degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer's-linked amyloid beta (Aβ) group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer's disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for latestage AMD.展开更多
Objective The paper aims to evaluate the risk factors for age‐related macular degeneration (AMD) in elderly Chinese population in Shenyang,a northeast city of China.Methods A case‐control study was conducted to in...Objective The paper aims to evaluate the risk factors for age‐related macular degeneration (AMD) in elderly Chinese population in Shenyang,a northeast city of China.Methods A case‐control study was conducted to investigate the risk factors for the prevalence of AMD.Ninety three AMD patients diagnosed by a complete ophthalmic examination were recruited as cases from the outpatient departments of two eye hospitals in Shenyang,while 108 normal subjects of similar age and sex were recruited as controls.A questionnaire was administered among both cases and controls.Results AMD patients aged 60 years and older accounted for 75.3%.There were significantly higher educational levels,shorter smoking history,less sunlight exposure and cataract,and higher proportion of antioxidants intake in controls than in AMD patients.The frequency of intake of fruits,legumes,fish and shrimps was significantly higher in controls than in AMD patients.In a binary logistic regression analysis,smoking and cataract were the risk factors for AMD (OR:4.44,95% CI:2.27‐8.69;OR:4.47,95% CI:2.26‐8.85 respectively).The high educational background was a protective factor for AMD (OR:0.761,95% CI:0.51‐0.98).Conclusion A low educational background,smoking and cataract are associated with a higher prevalence of AMD.展开更多
AIM:To identify the pathological role of amyloid beta(Aβ) deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells(RPE) layer and the associated structural and functi...AIM:To identify the pathological role of amyloid beta(Aβ) deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells(RPE) layer and the associated structural and functional changes in Alzheimer's disease transgenic mice.METHODS:RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic(NTG) mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin(H&E) staining and transmission electron microscopy(TEM) examination,whereas the expression of amyloid precursor protein(APP),Aβ,Zonula occludens-1(ZO-1) and Ionized calcium binding adaptor molecule-1(IBA-1) were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS:In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch's membrane(Br M) complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION:The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.展开更多
Age-related macular degeneration(AMD)is a kind of progressive eye disease that seriously damages vision,and it is one of the important causes of blindness.In recent years,a large number of studies have found that ther...Age-related macular degeneration(AMD)is a kind of progressive eye disease that seriously damages vision,and it is one of the important causes of blindness.In recent years,a large number of studies have found that there is a significant correlation between genetic factors and the occurrence and development of AMD.The study of gene polymorphism provides new ideas and directions for clinical diagnosis and treatment.In this paper,we will make a brief review of the research progress related to complement factor H(CFH),serine protease(HtrA1),age-related macular degeneration susceptibility factor 2(ARMS2)and vascular endothelial growth factor(VEGF)gene single nucleotide polymorphisms(SNP).展开更多
Subretinal hemorrhage is a vision threatening complication of exudative age related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV). Timely removal or displacement of subretinal hemorrhage from th...Subretinal hemorrhage is a vision threatening complication of exudative age related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV). Timely removal or displacement of subretinal hemorrhage from the central macula, ideally within 7 to 10 days after onset, is critical to allowing potential recovery of vision. Surgical techniques with the use of a bubble to displace the subretinal hemorrhage can now be performed with tissue plasminogen activator to lyze the blood and with or without vitrectomy.展开更多
AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age...AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).展开更多
A number of studies have shown that oxidative stress can be harmful for the retina. The real causal circumstances that lead to degenerative diseases like age related macular degeneration remain obscure. Whether light ...A number of studies have shown that oxidative stress can be harmful for the retina. The real causal circumstances that lead to degenerative diseases like age related macular degeneration remain obscure. Whether light induced radical stress is a direct interaction of light with photoreceptors or a secondary mechanism within the pigment epithelium or choroid is in discussion. Among the molecular mechanisms involved are production of reactive oxygen species(ROS), secondary lipid peroxidation, protein oxidation and DNA-damage. The initial trigger to write this review was first a recent finding of our group that the photoreceptor outer segments produce great amounts of ROS and second the detection of ectopic enzymes of the respiratory chainlocalized there- in addition to the hitherto known ROS sources like the visual pigments with their intermediates and the photoreceptor mitochondria harbouring the respiratory chain.展开更多
Background:Age-related macular degeneration(AMD)is the most suspected cause of vision loss in the elderly.Given the considerable evidence,oxidative stress is thought to be a primary contributing factor to AMD.Retinal ...Background:Age-related macular degeneration(AMD)is the most suspected cause of vision loss in the elderly.Given the considerable evidence,oxidative stress is thought to be a primary contributing factor to AMD.Retinal pigment epithelium(RPE)could be detrimentally compromised by oxidative stress along which blebs called retinal microparticles(RMPs)start to shed.In continue these particles would be taken by retina,causing RPE senescence,dysfunction and ultimately cell death.Along with the intracellular damages,accumulative deposit of microparticles in subretinal region can cause most known histological hallmark of dry AMD namely drusen.Based on our preliminary study,of 20 present miRNAs,Let-7f is the most abundant microRNAs in RMPs.As the accused substrate of RMPs through which retina function is compromised has yet to be well understood,we aimed to investigate pathophysiological role of let-7f and specific signaling triggered in RPE dysfunction.In brief,the principal objective is to further understand how RMPs implicate in RPE dysfunction.Methods:By oxidative stress inducing,RMPs were isolated from cultured ARPE-19 cells.We considered the effect of RMPs on ARPE-19 cells viability using MTT assay.In addition,to see whether RMPs effect could be ascribed to let-7f,ARPE-19 cells were transfected by carrier containing miRNA Let-7f.These transfected cells were then subjected senescence(β-galactosidase)and cell cycle assay to explore the molecular events responsible for Let-7f induced RPE cell dysfunction.Results:Regarding result we found that RMPs adversely affected RPE cell growth and resulted in significant decrease(≥30%)in cell viability.Let-7f-treated cells also revealed considerable increases of the senescence-associatedβ-galactosidase activity.Alongside RMPs impact,let-7f treatment group also showed similar result in cell growth.Conclusions:To the best of our knowledge,RPE cells uptake microparticles derived from oxidative-injured retinal cells,deteriorating integrity of vision compartments.Not only these finding would suggest that RMP’s impression likely corresponds to the miRNA let-7f,but introduce Let-7f as a mediator exacerbating the oxidative damages to RPE cells.This undesirable interplay is followed probably by dry AMD.Taken together,it seems by finding involved downstream pathways under RMPs pathogenesis,we can inhibit AMD disease in the early stage as well.In this line,we plan to investigate consecutive effect of RMP-associated miRNA inhibition in oxidative damage of retinal pigment epithelium.展开更多
This study was carried out to investigate if on-farm cut vs. grazed pastures differed in soil fertility and species density in the temperate Himalayan highlands. Soil fertility and species relative density were measur...This study was carried out to investigate if on-farm cut vs. grazed pastures differed in soil fertility and species density in the temperate Himalayan highlands. Soil fertility and species relative density were measured from 30 cut and 30 grazed dairy pastures. In both types of pasture, soil pH, available phosphorus(P) and exchangeable potassium(K) were negatively correlated with pasture age and slope. In cut pasture, cocksfoot(Dactylis glomerata) and pasture age were positively correlated,whereas in grazed pasture, they were negatively correlated. In grazed pasture, unsown species and pasture age were positively correlated. Soil available P was significantly greater in cut pastures whereas soil exchangeable K was significantly greater in grazed pastures. In terms of species density, cut pasture had greater densities of cocksfoot and Italian ryegrass(Lolium multiflorum), whereas grazed pasture showed greater densities of white clover, sedge and local grass. Our study suggests that, if there are no improvements in the current method of pasture management, the cut pastures in the future are likely to have a simple pasture mixture constituting only cocksfoot and white clover(Trifolium repens).Whereas in grazed pasture, the pasture mixture is likely to be comprised of white clover and unsown species such as sedge, local grass and broadleaf weeds.展开更多
BACKGROUND: With the given diversity and abundance of several targets of miRNAs, they functionally appear to interact with several elements of the multiple cellular networks to maintain physiologic homeostasis. They ...BACKGROUND: With the given diversity and abundance of several targets of miRNAs, they functionally appear to interact with several elements of the multiple cellular networks to maintain physiologic homeostasis. They can function as tumor suppressors or oncogenes, whose under or overexpression has both diagnostic and prognostic significance in various cancers while being implicated as prospective regulators of age-related disorders (ARD) as well. Establishing a concatenate between ARD and cancers by looking into the insights of the shared miRNAs may have a practical relevance. METHODS: In the present work, we performed network analysis of miRNA-disease association and miRNA-target gene interaction to prioritize miRNAs that play significant roles in the manifestation of cancer as well as ARD. Also, we developed a repository that stores miRNAs common to both ARD and cancers along with their target genes. RESULTS: We have comprehensively curated all miRNAs that we found to be shared in both the diseases in the human genome and established a database, miRACA (Database for microRNAs Associated with Cancers and ARD) that currently houses information of 1648 miRNAs that are significantly associated with 38 variants supported with pertinent data. It has been made available online at http://genomeinformatics.dtu.ac.in/miraca/for easy retrieval and utilization of data by the scientific community. CONCLUSION: To the best of our knowledge, our database is the first attempt at compilation of such data. We believe this work may serve as a significant resource and facilitate the analysis of miRNA regulatory mechanisms shared between cancers and ARD to apprehend disease etiology.展开更多
Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been...Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been several studies demonstrating strong associations between AMD and sites of heritable genetic variation at multiple loci,including a highly significant association at 10q26.The 10q26 risk region contains two genes,HTRA1 and ARMS2,both of which have been separately implicated as causative for the disease,as well as dozens of sites of non-coding variation.To date,no studies have successfully pinpointed which of these variant sites are functional in AMD,nor definitively identified which genes in the region are targets of such regulatory variation.In order to efficiently decipher which sites are functional in AMD phenotypes,we describe a general framework for combinatorial assembly of large‘synthetic haplotypes’along with delivery to relevant disease cell types for downstream functional analysis.We demonstrate the successful and highly efficient assembly of a first-draft 119kb wild-type‘assemblon’covering the HTRA1/ARMS2 risk region.We further propose the parallelized assembly of a library of combinatorial variant synthetic haplotypes covering the region,delivery and analysis of which will identify functional sites and their effects,leading to an improved understanding of AMD development.We anticipate that the methodology proposed here is highly generalizable towards the difficult problem of identifying truly functional variants from those discovered via GWAS or other genetic association studies.展开更多
Background:Total hip arthroplasty (THA) is one of the most effective treatments for phase Ⅲ and Ⅳ hip arthrosis.Lower limb length balancing is one of the determining factors of a successful surgery,particularly i...Background:Total hip arthroplasty (THA) is one of the most effective treatments for phase Ⅲ and Ⅳ hip arthrosis.Lower limb length balancing is one of the determining factors of a successful surgery,particularly in patients with developmental dysplasia of the hip (DDH).The purpose of this study was to evaluate the postoperative change in intra-pelvic obliquity (intra-PO) angle in the coronal plane and its effects on leg length discrepancy (LLD) within 2 years.Methods:A total of 78 patients (70 females,8 males) were enrolled in this study.All patients were suffering from DDH with varying degrees of LLD.Pelvic plain radiographs were collected before and after the operation.The intra-PO angles were measured 0,0.5,1 and 2 years after THA.At the same time,postoperative LLD was measured with blocking test.Results:PO changed significantly in the first year after THA surgery (0 year vs.0.5 year,P 〈 0.01;0.5 year vs.1 year,P 〈 0.01),and the changing value of intra-PO angle (△PO) slowed down substantially during the first 2 years after THA (0.5 year vs.0.5-1 year,P 〈 0.01;0.5-1 year vs.1-2 years,P 〈 0.01).With the change in intra-PO angle,LLD also got narrow within the 1st year (0 year vs.0.5 year,P 〈 0.01;0.5 year vs.1 year,P 〈 0.01).Elderly patients had a smaller intra-PO angle reduction (Group A vs.Group B,P =0.01;Group B vs.Group C,P〈 0.01).Conclusions:Intra-PO angle and LLD gap narrowed with time after THA surgery.In particular,elderly patients had smaller change in intra-PO angle.展开更多
文摘Purpose: In age-restricted youth sport, the over-selection of athletes born in the first quarter of the year and under-selection of athletes born in the last quarter of the year has been called the relative age effect (RAE). Its existence in youth sports like soccer is well established. Why it occurs has not been identified, however, one thought is that older players, generally taller and heavier, are thought to improve the team's chances of winning. To test this assumption, birth dates and match outcome were correlated to see if teams with the oldest mean age had a systematic advantage against teams with younger mean ages. Methods: Player birth dates and team records (n = 5943 players on 371 teams; both genders; U11-U16) were obtained from the North Carolina Youth Soccer Association for the highest level of statewide youth competition. Results: The presence of an RAE was demonstrated with significant oversampling from players born in the I st vs. the 4th quarter (overall: 29.6% vs. 20.9% respectively, p 〈 0.0001). Mean team age was regressed on match outcomes (winning %, points/match, points/goal, and goals for, against, and goal difference), but there was no evidence of any systematic influence of mean team age and match outcomes, except possibly in U11 males. Conclusion: Selecting players based on physical maturity (and subsequently, on age) does not appear to have any systematic influence on match outcome or season record in youth soccer suggesting that the selection process should be focused on player ability and not on physical maturation.
基金funded by the National Centre for the Replacement Refinement&Reduction of Animals in Research(NC3R:Grant#NC/L001152/1)the Macular Society,UK,National Eye Research Centrethe Gift of Sight Appeal
文摘e-related macular degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer's-linked amyloid beta (Aβ) group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer's disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for latestage AMD.
基金supported by a grant from the Nutritional Science Foundation of the Chinese Nutrition Society (No. 07016), China
文摘Objective The paper aims to evaluate the risk factors for age‐related macular degeneration (AMD) in elderly Chinese population in Shenyang,a northeast city of China.Methods A case‐control study was conducted to investigate the risk factors for the prevalence of AMD.Ninety three AMD patients diagnosed by a complete ophthalmic examination were recruited as cases from the outpatient departments of two eye hospitals in Shenyang,while 108 normal subjects of similar age and sex were recruited as controls.A questionnaire was administered among both cases and controls.Results AMD patients aged 60 years and older accounted for 75.3%.There were significantly higher educational levels,shorter smoking history,less sunlight exposure and cataract,and higher proportion of antioxidants intake in controls than in AMD patients.The frequency of intake of fruits,legumes,fish and shrimps was significantly higher in controls than in AMD patients.In a binary logistic regression analysis,smoking and cataract were the risk factors for AMD (OR:4.44,95% CI:2.27‐8.69;OR:4.47,95% CI:2.26‐8.85 respectively).The high educational background was a protective factor for AMD (OR:0.761,95% CI:0.51‐0.98).Conclusion A low educational background,smoking and cataract are associated with a higher prevalence of AMD.
基金Supported by the National Natural Science Foundation of China(No.81430009No.81400424)the Science and Technology Research and Development Project of Shaanxi Province(No.2014K11-03-07-04)
文摘AIM:To identify the pathological role of amyloid beta(Aβ) deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells(RPE) layer and the associated structural and functional changes in Alzheimer's disease transgenic mice.METHODS:RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic(NTG) mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin(H&E) staining and transmission electron microscopy(TEM) examination,whereas the expression of amyloid precursor protein(APP),Aβ,Zonula occludens-1(ZO-1) and Ionized calcium binding adaptor molecule-1(IBA-1) were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS:In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch's membrane(Br M) complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION:The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.
基金Qinghai science and technology department (2017-ZJ-756)
文摘Age-related macular degeneration(AMD)is a kind of progressive eye disease that seriously damages vision,and it is one of the important causes of blindness.In recent years,a large number of studies have found that there is a significant correlation between genetic factors and the occurrence and development of AMD.The study of gene polymorphism provides new ideas and directions for clinical diagnosis and treatment.In this paper,we will make a brief review of the research progress related to complement factor H(CFH),serine protease(HtrA1),age-related macular degeneration susceptibility factor 2(ARMS2)and vascular endothelial growth factor(VEGF)gene single nucleotide polymorphisms(SNP).
文摘Subretinal hemorrhage is a vision threatening complication of exudative age related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV). Timely removal or displacement of subretinal hemorrhage from the central macula, ideally within 7 to 10 days after onset, is critical to allowing potential recovery of vision. Surgical techniques with the use of a bubble to displace the subretinal hemorrhage can now be performed with tissue plasminogen activator to lyze the blood and with or without vitrectomy.
文摘AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).
文摘A number of studies have shown that oxidative stress can be harmful for the retina. The real causal circumstances that lead to degenerative diseases like age related macular degeneration remain obscure. Whether light induced radical stress is a direct interaction of light with photoreceptors or a secondary mechanism within the pigment epithelium or choroid is in discussion. Among the molecular mechanisms involved are production of reactive oxygen species(ROS), secondary lipid peroxidation, protein oxidation and DNA-damage. The initial trigger to write this review was first a recent finding of our group that the photoreceptor outer segments produce great amounts of ROS and second the detection of ectopic enzymes of the respiratory chainlocalized there- in addition to the hitherto known ROS sources like the visual pigments with their intermediates and the photoreceptor mitochondria harbouring the respiratory chain.
文摘Background:Age-related macular degeneration(AMD)is the most suspected cause of vision loss in the elderly.Given the considerable evidence,oxidative stress is thought to be a primary contributing factor to AMD.Retinal pigment epithelium(RPE)could be detrimentally compromised by oxidative stress along which blebs called retinal microparticles(RMPs)start to shed.In continue these particles would be taken by retina,causing RPE senescence,dysfunction and ultimately cell death.Along with the intracellular damages,accumulative deposit of microparticles in subretinal region can cause most known histological hallmark of dry AMD namely drusen.Based on our preliminary study,of 20 present miRNAs,Let-7f is the most abundant microRNAs in RMPs.As the accused substrate of RMPs through which retina function is compromised has yet to be well understood,we aimed to investigate pathophysiological role of let-7f and specific signaling triggered in RPE dysfunction.In brief,the principal objective is to further understand how RMPs implicate in RPE dysfunction.Methods:By oxidative stress inducing,RMPs were isolated from cultured ARPE-19 cells.We considered the effect of RMPs on ARPE-19 cells viability using MTT assay.In addition,to see whether RMPs effect could be ascribed to let-7f,ARPE-19 cells were transfected by carrier containing miRNA Let-7f.These transfected cells were then subjected senescence(β-galactosidase)and cell cycle assay to explore the molecular events responsible for Let-7f induced RPE cell dysfunction.Results:Regarding result we found that RMPs adversely affected RPE cell growth and resulted in significant decrease(≥30%)in cell viability.Let-7f-treated cells also revealed considerable increases of the senescence-associatedβ-galactosidase activity.Alongside RMPs impact,let-7f treatment group also showed similar result in cell growth.Conclusions:To the best of our knowledge,RPE cells uptake microparticles derived from oxidative-injured retinal cells,deteriorating integrity of vision compartments.Not only these finding would suggest that RMP’s impression likely corresponds to the miRNA let-7f,but introduce Let-7f as a mediator exacerbating the oxidative damages to RPE cells.This undesirable interplay is followed probably by dry AMD.Taken together,it seems by finding involved downstream pathways under RMPs pathogenesis,we can inhibit AMD disease in the early stage as well.In this line,we plan to investigate consecutive effect of RMP-associated miRNA inhibition in oxidative damage of retinal pigment epithelium.
文摘This study was carried out to investigate if on-farm cut vs. grazed pastures differed in soil fertility and species density in the temperate Himalayan highlands. Soil fertility and species relative density were measured from 30 cut and 30 grazed dairy pastures. In both types of pasture, soil pH, available phosphorus(P) and exchangeable potassium(K) were negatively correlated with pasture age and slope. In cut pasture, cocksfoot(Dactylis glomerata) and pasture age were positively correlated,whereas in grazed pasture, they were negatively correlated. In grazed pasture, unsown species and pasture age were positively correlated. Soil available P was significantly greater in cut pastures whereas soil exchangeable K was significantly greater in grazed pastures. In terms of species density, cut pasture had greater densities of cocksfoot and Italian ryegrass(Lolium multiflorum), whereas grazed pasture showed greater densities of white clover, sedge and local grass. Our study suggests that, if there are no improvements in the current method of pasture management, the cut pastures in the future are likely to have a simple pasture mixture constituting only cocksfoot and white clover(Trifolium repens).Whereas in grazed pasture, the pasture mixture is likely to be comprised of white clover and unsown species such as sedge, local grass and broadleaf weeds.
文摘BACKGROUND: With the given diversity and abundance of several targets of miRNAs, they functionally appear to interact with several elements of the multiple cellular networks to maintain physiologic homeostasis. They can function as tumor suppressors or oncogenes, whose under or overexpression has both diagnostic and prognostic significance in various cancers while being implicated as prospective regulators of age-related disorders (ARD) as well. Establishing a concatenate between ARD and cancers by looking into the insights of the shared miRNAs may have a practical relevance. METHODS: In the present work, we performed network analysis of miRNA-disease association and miRNA-target gene interaction to prioritize miRNAs that play significant roles in the manifestation of cancer as well as ARD. Also, we developed a repository that stores miRNAs common to both ARD and cancers along with their target genes. RESULTS: We have comprehensively curated all miRNAs that we found to be shared in both the diseases in the human genome and established a database, miRACA (Database for microRNAs Associated with Cancers and ARD) that currently houses information of 1648 miRNAs that are significantly associated with 38 variants supported with pertinent data. It has been made available online at http://genomeinformatics.dtu.ac.in/miraca/for easy retrieval and utilization of data by the scientific community. CONCLUSION: To the best of our knowledge, our database is the first attempt at compilation of such data. We believe this work may serve as a significant resource and facilitate the analysis of miRNA regulatory mechanisms shared between cancers and ARD to apprehend disease etiology.
基金supported in part by National Institutes of Health grants 1RM1HG009491,HG008135,EY025090,and CA217642。
文摘Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been several studies demonstrating strong associations between AMD and sites of heritable genetic variation at multiple loci,including a highly significant association at 10q26.The 10q26 risk region contains two genes,HTRA1 and ARMS2,both of which have been separately implicated as causative for the disease,as well as dozens of sites of non-coding variation.To date,no studies have successfully pinpointed which of these variant sites are functional in AMD,nor definitively identified which genes in the region are targets of such regulatory variation.In order to efficiently decipher which sites are functional in AMD phenotypes,we describe a general framework for combinatorial assembly of large‘synthetic haplotypes’along with delivery to relevant disease cell types for downstream functional analysis.We demonstrate the successful and highly efficient assembly of a first-draft 119kb wild-type‘assemblon’covering the HTRA1/ARMS2 risk region.We further propose the parallelized assembly of a library of combinatorial variant synthetic haplotypes covering the region,delivery and analysis of which will identify functional sites and their effects,leading to an improved understanding of AMD development.We anticipate that the methodology proposed here is highly generalizable towards the difficult problem of identifying truly functional variants from those discovered via GWAS or other genetic association studies.
文摘Background:Total hip arthroplasty (THA) is one of the most effective treatments for phase Ⅲ and Ⅳ hip arthrosis.Lower limb length balancing is one of the determining factors of a successful surgery,particularly in patients with developmental dysplasia of the hip (DDH).The purpose of this study was to evaluate the postoperative change in intra-pelvic obliquity (intra-PO) angle in the coronal plane and its effects on leg length discrepancy (LLD) within 2 years.Methods:A total of 78 patients (70 females,8 males) were enrolled in this study.All patients were suffering from DDH with varying degrees of LLD.Pelvic plain radiographs were collected before and after the operation.The intra-PO angles were measured 0,0.5,1 and 2 years after THA.At the same time,postoperative LLD was measured with blocking test.Results:PO changed significantly in the first year after THA surgery (0 year vs.0.5 year,P 〈 0.01;0.5 year vs.1 year,P 〈 0.01),and the changing value of intra-PO angle (△PO) slowed down substantially during the first 2 years after THA (0.5 year vs.0.5-1 year,P 〈 0.01;0.5-1 year vs.1-2 years,P 〈 0.01).With the change in intra-PO angle,LLD also got narrow within the 1st year (0 year vs.0.5 year,P 〈 0.01;0.5 year vs.1 year,P 〈 0.01).Elderly patients had a smaller intra-PO angle reduction (Group A vs.Group B,P =0.01;Group B vs.Group C,P〈 0.01).Conclusions:Intra-PO angle and LLD gap narrowed with time after THA surgery.In particular,elderly patients had smaller change in intra-PO angle.