Traumatic brain injury(TBI) is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventual...Traumatic brain injury(TBI) is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. Micro RNAs control a range of physiological and pathological functions such as development, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific micro RNAs in serum/plasma(mi R-425-p,-21,-93,-191 and-499) and cerebro-spinal fluid(CSF)(mi R-328,-362-3 p,-451,-486 a) as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific micro RNAs as biomarkers and therapeutic targets for moderate and mild TBI(e.g., mi R-21, mi R-23 b). Micro RNA profiling was altered by voluntary exercise. Differences in basal micro RNA expression in the brain of adult and aged animals and alterations in response to TBI(e.g., mi R-21) have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in micro RNA profiles in different age groups(children, adults, and elderly).展开更多
Increasing evidence has revealed that micro RNAs play a pivotal role in the post transcriptional regulation of gene expression in response to pathogens in plants. However, there is little information available about t...Increasing evidence has revealed that micro RNAs play a pivotal role in the post transcriptional regulation of gene expression in response to pathogens in plants. However, there is little information available about the expression patterns of mi RNAs and their targets in Chinese cabbage(Brassica rapa ssp. pekinensis) under Plasmodiophora brassicae stress. In the present study, using deep sequencing and degradome analysis, a genome-wide identification of mi RNAs and their targets during P. brassicae stress was performed. A total of 221 known and 93 potentially novel mi RNAs were successfully identified from two root libraries of one control(635-10CK) and P. brassicae-treated Chinese cabbage samples(635-10T). Of these, 14 known and 10 potentially novel mi RNAs were found to be differentially expressed after P. brassicae treatment. Degradome analysis revealed that the 223 target genes of the 75 mi RNAs could be potentially cleaved. KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway analysis suggested that the putative target genes of the mi RNAs were predominately involved in selenocompound metabolism and plant hormone signal transduction. Then the expression of 12 mi RNAs was validated by quantitative real-time PCR(q RT-PCR). These results provide insights into the mi RNA-mediated regulatory networks underlying the stress response to the plant pathogen P. brassicae.展开更多
Introduction In 2008 over 1.2 million new cases along with 608 700 estimated CRC-associated deaths have occurred.In China,where it is now the third most common malignancy and the fifth leading cause of cancer-related ...Introduction In 2008 over 1.2 million new cases along with 608 700 estimated CRC-associated deaths have occurred.In China,where it is now the third most common malignancy and the fifth leading cause of cancer-related death,the incidence of CRC is still increasing even with the improvements in the standard of living and changes in lifestyle.Despite improvements in展开更多
Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome...Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome(Met S)show decreased vitality.A growing number of micro RNAs(mi RNAs)are recognized as key modulators of senescence,but their role in regulating senescence in MSC in Mets is unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet(n=6 each).Next-generation mi RNA sequencing(mi RNA-seq)was performed to identify mi RNAs up-or down-regulated in Met S-MSC compare to Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We found the 7 upregulated mi RNAs,including mi R-27b,and 3 downregulated mi RNAs in Met S-MSCs,which regulate 35 SA genes,particularly MAPK signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions Met S modulate MSC expression of SA-mi RNAs that may play the role in modulating their senescence,and the p16 pathway in Met S-MSCs senescence is the primary pathway.展开更多
In recent decades,the potential health hazards of microwave exposure have been attracting increasing attention.Our previous studies have demonstrated that microwave exposure impaired learning and memory in experimenta...In recent decades,the potential health hazards of microwave exposure have been attracting increasing attention.Our previous studies have demonstrated that microwave exposure impaired learning and memory in experimental animal models[1,2].展开更多
The prevalence of diabetes has been increasing in the U.S.,with diabetes as a significant concern for patients’physical and financial health.Diabetic retinopathy is the leading cause of visual loss in working-age of ...The prevalence of diabetes has been increasing in the U.S.,with diabetes as a significant concern for patients’physical and financial health.Diabetic retinopathy is the leading cause of visual loss in working-age of adults and is characterized by retinal neurodegeneration and microvascular abnormalities in the eye.Hyperglycemia is one significant risk factor for diabetic retinopathy and can result in increased inflammatory responses展开更多
Micro RNAs(mi RNAs) are dynamically regulated during neurodevelopment,yet few reports have examined their role in spina bifida.In this study,we used an established fetal rat model of spina bifida induced by intragastr...Micro RNAs(mi RNAs) are dynamically regulated during neurodevelopment,yet few reports have examined their role in spina bifida.In this study,we used an established fetal rat model of spina bifida induced by intragastrically administering olive oil-containing all-trans retinoic acid to dams on day 10 of pregnancy.Dams that received intragastric administration of all-trans retinoic acid-free olive oil served as controls.The mi RNA expression profile in the amniotic fluid of rats at 20 days of pregnancy was analyzed using an mi RNA microarray assay.Compared with that in control fetuses,the expression of mi RNA-9,mi RNA-124 a,and mi RNA-138 was significantly decreased(> 2-fold),whereas the expression of mi RNA-134 was significantly increased(> 4-fold) in the amniotic fluid of rats with fetuses modeling spina bifida.These results were validated using real-time quantitative reverse-transcription polymerase chain reaction.Hierarchical clustering analysis of the microarray data showed that these differentially expressed mi RNAs could distinguish fetuses modeling spina bifida from control fetuses.Our bioinformatics analysis suggested that these differentially expressed mi RNAs were associated with many cytological pathways,including a nervous system development signaling pathway.These findings indicate that further studies are warranted examining the role of mi RNAs through their regulation of a variety of cell functional pathways in the pathogenesis of spina bifida.Such studies may provide novel targets for the early diagnosis and treatment of spina bifida.展开更多
Valproic acid(VPA)has been a first-choice drug for clinical treatment of epilepsy and manic disorder.For decades,its pharmacological action was believed to act on inhibition of gamma-aminobutyric acid(GABA)transaminas...Valproic acid(VPA)has been a first-choice drug for clinical treatment of epilepsy and manic disorder.For decades,its pharmacological action was believed to act on inhibition of gamma-aminobutyric acid(GABA)transaminase,in turn,increasing GABA in inhibitory synapses.However,in recent years,VPA has been investigated on other therapeutic actions.Those investigations demonstrate that VPA shows neuroprotective effects by promoting neurogenesis,neuronal differentiation。展开更多
Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent...Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.展开更多
Micro RNAs(mi RNAs) are known to regulate post-transcriptional gene expression.They are involved in carcinogenesis and tumor progression.The aim of this study was to explore the micro RNA-m RNA regulatory network in e...Micro RNAs(mi RNAs) are known to regulate post-transcriptional gene expression.They are involved in carcinogenesis and tumor progression.The aim of this study was to explore the micro RNA-m RNA regulatory network in esophageal squamous cell carcinoma(ESCC) using comprehensive computational approaches.In this study we have selected a total of 11 mi RNAs from one previously reported study in ESCC.The m RNA targets of these mi RNAs were predicted using various algorithms.The expression profiles of these m RNA targets were identified on DNA microarray experiment dataset across ESCC tissue samples.Based on the mi RNA-m RNA regulatory relationships,the network was inferred.A total of 23 mi RNA-m RNA regulatory interactions,with 11 mi RNAs and 13 m RNA targets,were inferred in ESCC.The mi RNA-m RNA regulatory network with increased confidence provides insights into the progression of ESCC and may serve as a biomarker for prognosis or the aggressiveness of ESCC.However,the results should be examined with further experimental validation.展开更多
Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the devel...Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing world.Currently used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often underestimated.Although a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical implementation.This editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area.展开更多
Micro RNAs(mi RNAs) have attracted significant attention in biomedical research and clinical diagnosis.However, due to their inherent characteristics of low abundance and the high complexity of corresponding biologica...Micro RNAs(mi RNAs) have attracted significant attention in biomedical research and clinical diagnosis.However, due to their inherent characteristics of low abundance and the high complexity of corresponding biological matrices, simultaneous detection of multiple mi RNAs at low abundance is still a challenge.In this work, a method coupling exponential amplification reaction(EXPAR) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) is developed for label-free and simultaneous detection of multiple mi RNAs. The assay can be performed under isothermal conditions in a single reaction tube, and finished in less than 30 min. It exhibits good quantification ability and with attomolar-level sensitivity for mi RNAs detection. It also shows high specificity to distinguish mi RNAs at single-nucleotide resolution. We used the method to detect the mi RNA-21, let-7a, mi RNA-100, and mi RNA-125b in samples of spiked human serum and breast cancer cells(i.e., MCF-7, MDA-MB-231 and SK-BR-3). The quantification results were well consistent with the standard real-time fluorescence EXPAR.Consequently, the label-free mass-spectrometric platform could be a potential tool for mi RNAs analysis in complex biological samples, and may be used for clinical diagnosis.展开更多
With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE)...With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)<sub>n−1</sub> DNA] * DNA and [(MPTE)<sub>n−1</sub> DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).展开更多
Prostate cancer(PCa)is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality.It emerges through the acquisition of genetic and epigenetic alterations.Epigenetic modifica...Prostate cancer(PCa)is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality.It emerges through the acquisition of genetic and epigenetic alterations.Epigenetic modifications include DNA methylation,histone modifications and micro RNA deregulation.These generate heritable transformations in the expression of genes but do not change the DNA sequence.Alterations in DNA methylation(hypo and hypermethylation)are the most characterized in PCa.They lead to genomic instability and inadequate gene expression.Major and minor-specific modifications in chromatin recasting are involved in PCa,with signs suggesting a dysfunction of enzymes modified by histones.Micro RNA deregulation also contributes to the initiation of PCa,including involvement in androgen receptor signalization and apoptosis.The influence of inflammation on prostate tumor carcinogenesis is currently much better known.Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation,promoting prostate inflammatory atrophy and eventually leading to PCa.Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa.The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis,treatment decisions,evaluation of prognosis and posttreatment surveillance.展开更多
Atrial fibrillation(AF)is the most frequent arrhythmogenic syndrome in humans.With an estimate incidence of1%-2%in the general population,AF raises up to almost10%-12%in 80+years.Thus,AF represents nowadays a highly p...Atrial fibrillation(AF)is the most frequent arrhythmogenic syndrome in humans.With an estimate incidence of1%-2%in the general population,AF raises up to almost10%-12%in 80+years.Thus,AF represents nowadays a highly prevalent medical problem generating a large economic burden.At the electrophysiological level,distinct mechanisms have been elucidated.Yet,despite its prevalence,the genetic and molecular culprits of this pandemic cardiac electrophysiological abnormality have remained largely obscure.Molecular genetics of AF familiar cases have demonstrated that single nucleotide mutations in distinct genes encoding for ion channels underlie the onset of AF,albeit such alterations only explain a minor subset of patients with AF.In recent years,analyses by means of genome-wide association studies have unraveled a more complex picture of the etiology of AF,pointing out to distinct cardiac-enriched transcription factors,as well as to other regulatory genes.Furthermore a new layer of regulatory mechanisms have emerged,i.e.,post-transcriptional regulation mediated by non-coding RNA,which have been demonstrated to exert pivotal roles in cardiac electrophysiology.In this manuscript,we aim to provide a comprehensive review of the genetic regulatory networks that if impaired exert electrophysiological abnormalities that contribute to the onset,and subsequently,on self-perpetuation of AF.展开更多
文摘Traumatic brain injury(TBI) is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. Micro RNAs control a range of physiological and pathological functions such as development, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific micro RNAs in serum/plasma(mi R-425-p,-21,-93,-191 and-499) and cerebro-spinal fluid(CSF)(mi R-328,-362-3 p,-451,-486 a) as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific micro RNAs as biomarkers and therapeutic targets for moderate and mild TBI(e.g., mi R-21, mi R-23 b). Micro RNA profiling was altered by voluntary exercise. Differences in basal micro RNA expression in the brain of adult and aged animals and alterations in response to TBI(e.g., mi R-21) have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in micro RNA profiles in different age groups(children, adults, and elderly).
基金supported by the Excellent Young Scientist Foundation of Henan Academy of Agricultural Sciences(2016YQ11)the National Key Technology R&D Program(2012BAD02B01-3)+1 种基金the Specialized Scientific Research Fund of Henan Academy of Agricultural Sciences(20157805)the Excellent Technology Innovation Team of Henan Province
文摘Increasing evidence has revealed that micro RNAs play a pivotal role in the post transcriptional regulation of gene expression in response to pathogens in plants. However, there is little information available about the expression patterns of mi RNAs and their targets in Chinese cabbage(Brassica rapa ssp. pekinensis) under Plasmodiophora brassicae stress. In the present study, using deep sequencing and degradome analysis, a genome-wide identification of mi RNAs and their targets during P. brassicae stress was performed. A total of 221 known and 93 potentially novel mi RNAs were successfully identified from two root libraries of one control(635-10CK) and P. brassicae-treated Chinese cabbage samples(635-10T). Of these, 14 known and 10 potentially novel mi RNAs were found to be differentially expressed after P. brassicae treatment. Degradome analysis revealed that the 223 target genes of the 75 mi RNAs could be potentially cleaved. KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway analysis suggested that the putative target genes of the mi RNAs were predominately involved in selenocompound metabolism and plant hormone signal transduction. Then the expression of 12 mi RNAs was validated by quantitative real-time PCR(q RT-PCR). These results provide insights into the mi RNA-mediated regulatory networks underlying the stress response to the plant pathogen P. brassicae.
文摘Introduction In 2008 over 1.2 million new cases along with 608 700 estimated CRC-associated deaths have occurred.In China,where it is now the third most common malignancy and the fifth leading cause of cancer-related death,the incidence of CRC is still increasing even with the improvements in the standard of living and changes in lifestyle.Despite improvements in
基金Guangdong Provincial Center for clinical engineering of blood purification(507204531040)
文摘Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome(Met S)show decreased vitality.A growing number of micro RNAs(mi RNAs)are recognized as key modulators of senescence,but their role in regulating senescence in MSC in Mets is unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet(n=6 each).Next-generation mi RNA sequencing(mi RNA-seq)was performed to identify mi RNAs up-or down-regulated in Met S-MSC compare to Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We found the 7 upregulated mi RNAs,including mi R-27b,and 3 downregulated mi RNAs in Met S-MSCs,which regulate 35 SA genes,particularly MAPK signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions Met S modulate MSC expression of SA-mi RNAs that may play the role in modulating their senescence,and the p16 pathway in Met S-MSCs senescence is the primary pathway.
基金supported by National Science Foundation of China[No.81172620]。
文摘In recent decades,the potential health hazards of microwave exposure have been attracting increasing attention.Our previous studies have demonstrated that microwave exposure impaired learning and memory in experimental animal models[1,2].
基金supported by R01EY022045 (JJS)P30EY04068 (PI: Hazlett)an Unrestricted Grant to the Department of Ophthalmology from Research to Prevent Blindness (Kresge Eye Institute)
文摘The prevalence of diabetes has been increasing in the U.S.,with diabetes as a significant concern for patients’physical and financial health.Diabetic retinopathy is the leading cause of visual loss in working-age of adults and is characterized by retinal neurodegeneration and microvascular abnormalities in the eye.Hyperglycemia is one significant risk factor for diabetic retinopathy and can result in increased inflammatory responses
文摘Micro RNAs(mi RNAs) are dynamically regulated during neurodevelopment,yet few reports have examined their role in spina bifida.In this study,we used an established fetal rat model of spina bifida induced by intragastrically administering olive oil-containing all-trans retinoic acid to dams on day 10 of pregnancy.Dams that received intragastric administration of all-trans retinoic acid-free olive oil served as controls.The mi RNA expression profile in the amniotic fluid of rats at 20 days of pregnancy was analyzed using an mi RNA microarray assay.Compared with that in control fetuses,the expression of mi RNA-9,mi RNA-124 a,and mi RNA-138 was significantly decreased(> 2-fold),whereas the expression of mi RNA-134 was significantly increased(> 4-fold) in the amniotic fluid of rats with fetuses modeling spina bifida.These results were validated using real-time quantitative reverse-transcription polymerase chain reaction.Hierarchical clustering analysis of the microarray data showed that these differentially expressed mi RNAs could distinguish fetuses modeling spina bifida from control fetuses.Our bioinformatics analysis suggested that these differentially expressed mi RNAs were associated with many cytological pathways,including a nervous system development signaling pathway.These findings indicate that further studies are warranted examining the role of mi RNAs through their regulation of a variety of cell functional pathways in the pathogenesis of spina bifida.Such studies may provide novel targets for the early diagnosis and treatment of spina bifida.
基金supported by the Agency for Science and Technology(A*STAR)intramural funding for the Integrative Neuroscience Programme,Singapore Institute for Clinical Sciences
文摘Valproic acid(VPA)has been a first-choice drug for clinical treatment of epilepsy and manic disorder.For decades,its pharmacological action was believed to act on inhibition of gamma-aminobutyric acid(GABA)transaminase,in turn,increasing GABA in inhibitory synapses.However,in recent years,VPA has been investigated on other therapeutic actions.Those investigations demonstrate that VPA shows neuroprotective effects by promoting neurogenesis,neuronal differentiation。
基金Supported by The Deutsche Forschungsgemeinschaft,Nos.FE785/2-2 and FE785/4-1the Bundesministerium für Bildung und Entwicklung,No.031A331
文摘Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.
基金supported by grants from Natural Science Foundation of Hubei Province,China(No.2010CDB09204)Youth Dawn Plan of Science and Technology in Wuhan,China(No.201150431137)
文摘Micro RNAs(mi RNAs) are known to regulate post-transcriptional gene expression.They are involved in carcinogenesis and tumor progression.The aim of this study was to explore the micro RNA-m RNA regulatory network in esophageal squamous cell carcinoma(ESCC) using comprehensive computational approaches.In this study we have selected a total of 11 mi RNAs from one previously reported study in ESCC.The m RNA targets of these mi RNAs were predicted using various algorithms.The expression profiles of these m RNA targets were identified on DNA microarray experiment dataset across ESCC tissue samples.Based on the mi RNA-m RNA regulatory relationships,the network was inferred.A total of 23 mi RNA-m RNA regulatory interactions,with 11 mi RNAs and 13 m RNA targets,were inferred in ESCC.The mi RNA-m RNA regulatory network with increased confidence provides insights into the progression of ESCC and may serve as a biomarker for prognosis or the aggressiveness of ESCC.However,the results should be examined with further experimental validation.
文摘Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing world.Currently used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often underestimated.Although a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical implementation.This editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area.
基金supported by the National Natural Science Foundation of China (NSFC, Nos. 22022401, 22074022 and 21934001)the Ministry of Science and Technology of China (Nos. 2020YFF0426500, 2020YFF0304502)。
文摘Micro RNAs(mi RNAs) have attracted significant attention in biomedical research and clinical diagnosis.However, due to their inherent characteristics of low abundance and the high complexity of corresponding biological matrices, simultaneous detection of multiple mi RNAs at low abundance is still a challenge.In this work, a method coupling exponential amplification reaction(EXPAR) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) is developed for label-free and simultaneous detection of multiple mi RNAs. The assay can be performed under isothermal conditions in a single reaction tube, and finished in less than 30 min. It exhibits good quantification ability and with attomolar-level sensitivity for mi RNAs detection. It also shows high specificity to distinguish mi RNAs at single-nucleotide resolution. We used the method to detect the mi RNA-21, let-7a, mi RNA-100, and mi RNA-125b in samples of spiked human serum and breast cancer cells(i.e., MCF-7, MDA-MB-231 and SK-BR-3). The quantification results were well consistent with the standard real-time fluorescence EXPAR.Consequently, the label-free mass-spectrometric platform could be a potential tool for mi RNAs analysis in complex biological samples, and may be used for clinical diagnosis.
文摘With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)<sub>n−1</sub> DNA] * DNA and [(MPTE)<sub>n−1</sub> DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).
文摘Prostate cancer(PCa)is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality.It emerges through the acquisition of genetic and epigenetic alterations.Epigenetic modifications include DNA methylation,histone modifications and micro RNA deregulation.These generate heritable transformations in the expression of genes but do not change the DNA sequence.Alterations in DNA methylation(hypo and hypermethylation)are the most characterized in PCa.They lead to genomic instability and inadequate gene expression.Major and minor-specific modifications in chromatin recasting are involved in PCa,with signs suggesting a dysfunction of enzymes modified by histones.Micro RNA deregulation also contributes to the initiation of PCa,including involvement in androgen receptor signalization and apoptosis.The influence of inflammation on prostate tumor carcinogenesis is currently much better known.Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation,promoting prostate inflammatory atrophy and eventually leading to PCa.Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa.The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis,treatment decisions,evaluation of prognosis and posttreatment surveillance.
基金Supported by A CNIC translational grant(CNIC2006/08)to Franco Dthe University of Jaén on translational biomedicine to Franco D(UJA2013/01)
文摘Atrial fibrillation(AF)is the most frequent arrhythmogenic syndrome in humans.With an estimate incidence of1%-2%in the general population,AF raises up to almost10%-12%in 80+years.Thus,AF represents nowadays a highly prevalent medical problem generating a large economic burden.At the electrophysiological level,distinct mechanisms have been elucidated.Yet,despite its prevalence,the genetic and molecular culprits of this pandemic cardiac electrophysiological abnormality have remained largely obscure.Molecular genetics of AF familiar cases have demonstrated that single nucleotide mutations in distinct genes encoding for ion channels underlie the onset of AF,albeit such alterations only explain a minor subset of patients with AF.In recent years,analyses by means of genome-wide association studies have unraveled a more complex picture of the etiology of AF,pointing out to distinct cardiac-enriched transcription factors,as well as to other regulatory genes.Furthermore a new layer of regulatory mechanisms have emerged,i.e.,post-transcriptional regulation mediated by non-coding RNA,which have been demonstrated to exert pivotal roles in cardiac electrophysiology.In this manuscript,we aim to provide a comprehensive review of the genetic regulatory networks that if impaired exert electrophysiological abnormalities that contribute to the onset,and subsequently,on self-perpetuation of AF.
