Embryonic neurogenesis is the process of generating neurons,the functional units of the brain.Because of its sensitivity to adverse intrauterine environment such as infection,dysregulation of this process has emerged ...Embryonic neurogenesis is the process of generating neurons,the functional units of the brain.Because of its sensitivity to adverse intrauterine environment such as infection,dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders(ASD).Adult neurogenesis,although is restricted to a few neurogenic niches,plays pivotal roles in brain plasticity and repair.Increasing evidence suggests that impairments in adult neurogenesis are involved in major neurodegenerative disorders such as Alzheimer's disease.A hallmark feature of these brain disorders is neuroinflammation,which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment.In this review paper,we present evidence from both experimental and human studies to show a complex picture of relationship between these two events,and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neurodevelopmental and neurological disorders.展开更多
Background:Oxygen therapy provided to support the lungs of premature newborns often leads to damages to the retina called retinopathy of prematurity(ROP)and long-term visual impairments.Current treatments for ROP are ...Background:Oxygen therapy provided to support the lungs of premature newborns often leads to damages to the retina called retinopathy of prematurity(ROP)and long-term visual impairments.Current treatments for ROP are invasive and aim at preventing further progression of the damages to the retina,but do not repair these damages.Our goal is to investigate the therapeutic effect of sildenafil on retinal structure in a rat model of ROP.Methods:Sprague-Dawley rats were exposed to hyperoxia(i.e.,80%oxygen)interrupted by three 0.5-hour periods of normoxia(i.e.,21%oxygen)(hyperoxic animals)per day or room air only(i.e.,21%oxygen)(control animals)from post-natal day 4(P4)to 14(P14).Pups were then housed in room air.Sildenafil(50 mg/kg)or vehicle was given per os twice daily after oxygen exposure(from P15 to P21).At P30,retinas were extracted,and sectioned.For retinal histology,eyes were stained with toluidine blue to measure the thicknesses of the different retinal layers.Immunohistochemistry was also performed to count the number of retinal ganglion cells and bipolar cells in the inner retina,as well as the number of astrocytes and microglia within the different retinal layers.Results:Hyperoxia caused a reduction in thickness of the outer plexiform layer(OPL)and a decrease in the number of bipolar cells in some parts of the retina,compared to control animals(P<0.05);in addition,the number of microglia cells was significantly increased in the rats exposed to hyperoxia,compared to controls(P<0.05).Sildenafil improved OPL thickness in ROP animals,but did not change the number of bipolar cells.In hyperoxic rats treated with sildenafil,the number of microglia were similar to control rats.The number of retinal ganglion cells and astrocytes did not differ significantly between the groups.Conclusions:Treatment with sildenafil following oxygen exposure provided some recovery of the structure of the retina.This beneficial effect may be modulated by a decrease of inflammation within the retina.展开更多
The intestinal tract is colonized soon after birth with a variety of ingested environmental and maternal microflora. This process is influenced by many factors including mode of delivery, diet, environment, and the us...The intestinal tract is colonized soon after birth with a variety of ingested environmental and maternal microflora. This process is influenced by many factors including mode of delivery, diet, environment, and the use of antibiotics. Normal intestinal microflora provides protection against infection, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. In addition, enteral feeding and colonization with the normal commensal flora are necessary for the maintenance of intestinal barrier function and play a vital role in the regulation of intestinal barrier function. Intestinal commensal microorganisms also provide signals that foster normal immune system development and influence the ensuing immune responses. There is increasingly recognition that alterations of the microbial gut flora and associated changes in intestinal barrier function may be related to certain diseases of the gastrointestinal tract. This review summarizes recent advances in understanding the complex ecosystem of intestinal microbiota and its role in regulating intestinal barrier function and a few common pediatric diseases. Disruption in the establishment of a stable normal gut microflora may contribute to the pathogenesis of diseases including inflammatory bowel disease, nosocomial infection, and neonatal necrotizing enterocolitis.展开更多
Myelin regeneration is indispensably important for patients suffering from several central nervous system(CNS) disorders such as multiple sclerosis(MS) and spinal cord injury(SCI), because it is not only essential for...Myelin regeneration is indispensably important for patients suffering from several central nervous system(CNS) disorders such as multiple sclerosis(MS) and spinal cord injury(SCI), because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1(LINGO-1) monoclonal antibodies to treat MS patients in clinical trials.展开更多
Aplasia Cutis Congenita (ACC) is a rare condition characterized by absence of skin layers, usually on the scalp, but can also affect the foot. ACC can occur as an isolated condition or in the presence of the other con...Aplasia Cutis Congenita (ACC) is a rare condition characterized by absence of skin layers, usually on the scalp, but can also affect the foot. ACC can occur as an isolated condition or in the presence of the other congenital anomalies. Here we describe a case of a 1-day-old baby boy with an isolated ACC of the left foot, with no family or siblings positive disease history. The patient was managed by both conservatively and surgically until the defect has formed scar tissue 5 months later.展开更多
Importance:Congenital chylothorax is a rare condition with pulmonary and multiorgan system effects,for which there are no standardized treatment recommendations.Collective review of known cases offers some conclusions...Importance:Congenital chylothorax is a rare condition with pulmonary and multiorgan system effects,for which there are no standardized treatment recommendations.Collective review of known cases offers some conclusions and suggestions for treatment.Objective:The aim of this study was to present a case series of 5 patients who were treated in the neonatal intensive care unit with chylothorax.Methods:We describe 5 infants who were diagnosed prenatally with hydrops fetalis and postnatally had clinically significant congenital chylothorax.Results:Treatment guidelines specific to congenital forms of chylothorax have not yet been developed,although there are consistent trends across our cases.Four of the 5 infants in this study have survived to date.Chylothorax was treated with chest tube placement and chylous fluid drainage,scrupulous attention to fluid balance,mechanical ventilation,and nutritional management and,in 3 cases,with octreotide infusions.Some of the infants also required treatment for immunodeficiency and altered coagulation pathways.None of the infants underwent surgical thoracic duct ligation.Interpretation:Aided by the advantage of prenatal diagnosis,many cases of congenital chylothorax can be successfully treated by a combination of nutritional and medical management as well as careful attention to fluid and electrolyte balance and avoidance of infection,thereby avoiding the need for surgical ligation of the thoracic duct.展开更多
Background To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. Methods We used bloodspots from 2010 ...Background To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. Methods We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. Results We obtained five mutations (G199D, A299V, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang popula-tions (0.0045 vs. 0.0064, respectively,P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous vari-ants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB;F341L was also not previously reported in exome sequencing project. Conclusions The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1B LPCAT1,CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.展开更多
Background: Rare mutations in surfactant-associatedgenes contribute to neonatal respiratory distress syndrome.The frequency of mutations in these genes in the Chinesepopulation is unknown.Methods: We obtained blood sp...Background: Rare mutations in surfactant-associatedgenes contribute to neonatal respiratory distress syndrome.The frequency of mutations in these genes in the Chinesepopulation is unknown.Methods: We obtained blood spots from the GuangxiNeonatal Screening Center in Nanning, China thatincluded Han (n=443) and Zhuang (n=313) ethnic groups.We resequenced all exons of the surfactant proteins-B(SFTPB), -C (SFTPC), and the ATP-binding cassettemember A3 (ABCA3) genes and compared the frequenciesof 5 common and all rare variants.Results: We found minor differences in thefrequencies of the common variants in the Han andZhuang cohorts. We did not find any rare mutations inSFTPB or SFTPC, but we found three ABCA3 mutationsin the Han [minor allele frequency (MAF)=0.003] and 7 inthe Zhuang (MAF=0.011) cohorts (P=0.10). The ABCA3mutations were unique to each cohort;five were novel.The collapsed carrier rate of rare ABCA3 mutations inthe Han and Zhuang populations combined was 1.3%,which is signifi cantly lower than that in the United States(P<0.001).Conclusions: The population-based frequency ofmutations in ABCA3 in south China newborns is signifi cantlylower than that in United States. The contribution of theserare ABCA3 mutations to disease burden in the south Chinapopulation is still unknown.展开更多
Dear Editor,As one of the most abundant modifications on mRNA in mammal,A^6-methyladenosine(m6A)has been demonstrated to play important roles in various biological processes including nuclear RNA export,mRNA splicing,...Dear Editor,As one of the most abundant modifications on mRNA in mammal,A^6-methyladenosine(m6A)has been demonstrated to play important roles in various biological processes including nuclear RNA export,mRNA splicing,miRNA processing,mRNA degradation and translation(Shi et al.,2019).Importantly,different m6A reader proteins have been shown to play central roles in these processes.展开更多
基金supported by grants from NIH(R01NS080844)(LWF)Michael J.Fox foundation(YP)+1 种基金Intramural Research Support Program(YP)the Department of Pediatrics,University of Mississippi Medical Center
文摘Embryonic neurogenesis is the process of generating neurons,the functional units of the brain.Because of its sensitivity to adverse intrauterine environment such as infection,dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders(ASD).Adult neurogenesis,although is restricted to a few neurogenic niches,plays pivotal roles in brain plasticity and repair.Increasing evidence suggests that impairments in adult neurogenesis are involved in major neurodegenerative disorders such as Alzheimer's disease.A hallmark feature of these brain disorders is neuroinflammation,which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment.In this review paper,we present evidence from both experimental and human studies to show a complex picture of relationship between these two events,and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neurodevelopmental and neurological disorders.
文摘Background:Oxygen therapy provided to support the lungs of premature newborns often leads to damages to the retina called retinopathy of prematurity(ROP)and long-term visual impairments.Current treatments for ROP are invasive and aim at preventing further progression of the damages to the retina,but do not repair these damages.Our goal is to investigate the therapeutic effect of sildenafil on retinal structure in a rat model of ROP.Methods:Sprague-Dawley rats were exposed to hyperoxia(i.e.,80%oxygen)interrupted by three 0.5-hour periods of normoxia(i.e.,21%oxygen)(hyperoxic animals)per day or room air only(i.e.,21%oxygen)(control animals)from post-natal day 4(P4)to 14(P14).Pups were then housed in room air.Sildenafil(50 mg/kg)or vehicle was given per os twice daily after oxygen exposure(from P15 to P21).At P30,retinas were extracted,and sectioned.For retinal histology,eyes were stained with toluidine blue to measure the thicknesses of the different retinal layers.Immunohistochemistry was also performed to count the number of retinal ganglion cells and bipolar cells in the inner retina,as well as the number of astrocytes and microglia within the different retinal layers.Results:Hyperoxia caused a reduction in thickness of the outer plexiform layer(OPL)and a decrease in the number of bipolar cells in some parts of the retina,compared to control animals(P<0.05);in addition,the number of microglia cells was significantly increased in the rats exposed to hyperoxia,compared to controls(P<0.05).Sildenafil improved OPL thickness in ROP animals,but did not change the number of bipolar cells.In hyperoxic rats treated with sildenafil,the number of microglia were similar to control rats.The number of retinal ganglion cells and astrocytes did not differ significantly between the groups.Conclusions:Treatment with sildenafil following oxygen exposure provided some recovery of the structure of the retina.This beneficial effect may be modulated by a decrease of inflammation within the retina.
基金Supported by In part by Zhejiang Provincial Natural Science Foundation,No.LY12H04005 and LY13H040011
文摘The intestinal tract is colonized soon after birth with a variety of ingested environmental and maternal microflora. This process is influenced by many factors including mode of delivery, diet, environment, and the use of antibiotics. Normal intestinal microflora provides protection against infection, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. In addition, enteral feeding and colonization with the normal commensal flora are necessary for the maintenance of intestinal barrier function and play a vital role in the regulation of intestinal barrier function. Intestinal commensal microorganisms also provide signals that foster normal immune system development and influence the ensuing immune responses. There is increasingly recognition that alterations of the microbial gut flora and associated changes in intestinal barrier function may be related to certain diseases of the gastrointestinal tract. This review summarizes recent advances in understanding the complex ecosystem of intestinal microbiota and its role in regulating intestinal barrier function and a few common pediatric diseases. Disruption in the establishment of a stable normal gut microflora may contribute to the pathogenesis of diseases including inflammatory bowel disease, nosocomial infection, and neonatal necrotizing enterocolitis.
基金supported by grants from NIH(R01NS080844)Michel J.Fox foundation,Intramural Research Support Programby funds from the Department of Pediatrics,University of Mississippi Medical Center
文摘Myelin regeneration is indispensably important for patients suffering from several central nervous system(CNS) disorders such as multiple sclerosis(MS) and spinal cord injury(SCI), because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1(LINGO-1) monoclonal antibodies to treat MS patients in clinical trials.
文摘Aplasia Cutis Congenita (ACC) is a rare condition characterized by absence of skin layers, usually on the scalp, but can also affect the foot. ACC can occur as an isolated condition or in the presence of the other congenital anomalies. Here we describe a case of a 1-day-old baby boy with an isolated ACC of the left foot, with no family or siblings positive disease history. The patient was managed by both conservatively and surgically until the defect has formed scar tissue 5 months later.
文摘Importance:Congenital chylothorax is a rare condition with pulmonary and multiorgan system effects,for which there are no standardized treatment recommendations.Collective review of known cases offers some conclusions and suggestions for treatment.Objective:The aim of this study was to present a case series of 5 patients who were treated in the neonatal intensive care unit with chylothorax.Methods:We describe 5 infants who were diagnosed prenatally with hydrops fetalis and postnatally had clinically significant congenital chylothorax.Results:Treatment guidelines specific to congenital forms of chylothorax have not yet been developed,although there are consistent trends across our cases.Four of the 5 infants in this study have survived to date.Chylothorax was treated with chest tube placement and chylous fluid drainage,scrupulous attention to fluid balance,mechanical ventilation,and nutritional management and,in 3 cases,with octreotide infusions.Some of the infants also required treatment for immunodeficiency and altered coagulation pathways.None of the infants underwent surgical thoracic duct ligation.Interpretation:Aided by the advantage of prenatal diagnosis,many cases of congenital chylothorax can be successfully treated by a combination of nutritional and medical management as well as careful attention to fluid and electrolyte balance and avoidance of infection,thereby avoiding the need for surgical ligation of the thoracic duct.
基金the National Natural Science Foundation of China 81260094National Institutes of Health R01 HL065174+3 种基金R01 HL082747K12 HL089968K08 HL105891Foundation of Health Department of Guangxi Zhuang Autonomous Region 2012059.
文摘Background To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. Methods We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. Results We obtained five mutations (G199D, A299V, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang popula-tions (0.0045 vs. 0.0064, respectively,P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous vari-ants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB;F341L was also not previously reported in exome sequencing project. Conclusions The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1B LPCAT1,CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.
基金supported by the National Natural Science Foundation of China 81260094(Chen YJ)National Institutes of Health R01 HL065174(Cole FS,Hamvas A),R01 HL082747(Cole FS,Hamvas A),K12 HL089968(Wambach JA,Cole FS),K08 HL105891(Wambach JA)Foundation of Health Department of Guangxi Zhuang Autonomous Region 2012059(Chen YJ).
文摘Background: Rare mutations in surfactant-associatedgenes contribute to neonatal respiratory distress syndrome.The frequency of mutations in these genes in the Chinesepopulation is unknown.Methods: We obtained blood spots from the GuangxiNeonatal Screening Center in Nanning, China thatincluded Han (n=443) and Zhuang (n=313) ethnic groups.We resequenced all exons of the surfactant proteins-B(SFTPB), -C (SFTPC), and the ATP-binding cassettemember A3 (ABCA3) genes and compared the frequenciesof 5 common and all rare variants.Results: We found minor differences in thefrequencies of the common variants in the Han andZhuang cohorts. We did not find any rare mutations inSFTPB or SFTPC, but we found three ABCA3 mutationsin the Han [minor allele frequency (MAF)=0.003] and 7 inthe Zhuang (MAF=0.011) cohorts (P=0.10). The ABCA3mutations were unique to each cohort;five were novel.The collapsed carrier rate of rare ABCA3 mutations inthe Han and Zhuang populations combined was 1.3%,which is signifi cantly lower than that in the United States(P<0.001).Conclusions: The population-based frequency ofmutations in ABCA3 in south China newborns is signifi cantlylower than that in United States. The contribution of theserare ABCA3 mutations to disease burden in the south Chinapopulation is still unknown.
文摘Dear Editor,As one of the most abundant modifications on mRNA in mammal,A^6-methyladenosine(m6A)has been demonstrated to play important roles in various biological processes including nuclear RNA export,mRNA splicing,miRNA processing,mRNA degradation and translation(Shi et al.,2019).Importantly,different m6A reader proteins have been shown to play central roles in these processes.
