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Severe neonatal episodic laryngospasm (SNEL) is an ion channel disease characterized by recurrent life-threatening myotonia of respiratory muscle due to mutations in the voltage-gated sodium channel genes. Here we reported a newborn manifested as paroxysmal cyanosis and limb myotonia after birth. The neonate also developed muscle hypertrophy and stunted growth during the follow-up. Whole exome sequencing confirmed c.2395G>A, p. Ala799Thr heterozygous mutation of SCN4A. Carbamazepine was found to be effective on treating the disease. This case expands our understanding of the phenotype resulting from SCN4A mutations. By summarizing the characteristics of reported 16 cases in SNEL, we found they were mainly in the p.G1306E mutation. The common symptoms were upper airway muscle stiffness and feeding difficulties during neonates. When grow up, most patients have different degrees of recurrent attacks of myotonia and progressed muscle hypertrophy. Some of them have athlete-like special faces but all showed myotonic discharge in eletromyogram.
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A case of SNX10 gene mutation in a patient with infantile malignant osteopetrosis (IMO) was admitted to Department of Pediatrics, Third Xiangya Hospital, Central South University. The patient had the symptom of anemia, hepatosplenomegaly and growth retardation. The X-ray examination suggested extensive increase of bone density throughout the body, which was clinically diagnosed as IMO. The homozygous mutation of SNX10 gene c.61C>T was found via gene sequencing. We reviewed the relevant literatures and found that anemia, visual and hearing impairment, hepatosplenomegaly are the main clinical symptoms of IMO, SNX10 gene mutation is a rare cause of IMO, and hematopoietic stem cell transplantation is an effective treatment.
Subject(s)
Child , Humans , Bone Density , Hematopoietic Stem Cell Transplantation , Mutation , Osteopetrosis/genetics , Sorting Nexins/geneticsABSTRACT
OBJECTIVES@#To provide clues for further study of the relationship between miRNAs and Kawasaki disease (KD) development, and to provide molecular markers for ultimately improve the rate of early diagnosis for KD.@*METHODS@#We collected acute, recovery KD children's plasma and normal samples, then used the miRNAs Assay Chip to screen the differentially expressed miRNAs in the plasma from KD children. Subsequently, miR-455-5p, which had identified via miRNAs assay chip, was validated by quantitative real-time PCR via independent cohort.@*RESULTS@#According to the results of miRNAs Assay chip, we identified a miRNAs panel including 5 miRNAs significantly up-regulated and 5 miRNAs remarkably down-regulated in the plasma from KD children compared to the normal control; miR-455-5p in both of acute and recovery KD children's plasma was remarkably lower than that in the normal control (<0.001, =0.013, respectively), and miR-455-5p was also significantly lower than that in the recovery of KD children (=0.007) by independent cohort validation.@*CONCLUSIONS@#There are significantly differentially expressed circulating miRNAs between the KD children and normal control. We identified 10 miRNAs dysregulation in the KD children's plasma compared with the normal group. Circulating miR-455-5p in both of acute and recovery KD children's plasma is remarkably lower than that in the normal control, and miR-455-5p may considered as a marker to show the recovery process of KD children. Plasma specific circulating miRNAs play an important role in the early diagnosis of KD and become the new molecular marker of KD in the future.
Subject(s)
Child , Humans , Biomarkers , MicroRNAs , Genetics , Mucocutaneous Lymph Node Syndrome , Genetics , Oligonucleotide Array Sequence Analysis , Real-Time Polymerase Chain ReactionABSTRACT
Objective:To investigate association between the single nucleotide polymorphisms of endothelial protein C receptor (EPCR) gene and the risk of Kawasaki disease (KD) in a Chinese children.Methods:A total of 103 KD patients including 23 patients with coronary artery lesions (CAL) and 158 controls were recruited.Seven tagging SNPs (rs6088738,rs2069940,rs2069945,rs2069952,rs867186,rs9574,and rs1415774) of EPCR gene were selected for TaqMan allelic discrimination assay.The plasma soluble EPCR (sEPCR) levels of 53 KD and 52 healthy children were detected by ELISA.Results:We found a significant association between rs2069952,rs9574 or rs1415774 and higher probability for the occurrence of KD but not CAL formation.Interestingly,males with these 3 SNPs and rs2069945 SNPs bore a much greater risk of KD than females.The level of plasma sEPCR in children with KD didnot predict the formation of CAL.However,the allele G of rs867186 in EPCR was associated with the increased level of plasma sEPCR in KD patients.Conclusion:The SNPs of EPCR are associated with KD susceptibility in a Chinese Han children.
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Viral myocarditis is a nonspecific myocardial inflammation caused by viral infection,10％ - 20％ of them can develop to dilated cardiomyopathy eventually. Virus infections caused direct myocardial damage as they at-tack. Persistent inflammation and persistent virus infections induced an immune inflammation response and eventually caused indirectly damage,leading to further harm to myocardia. Different forms of cell death including apoptosis,autoph-agy,necrosis and necroptosis were associated with myocarditis. The role and mechanism of different cell death in the development of viral myocarditis will be described.
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Recent studies have found that autophagy was not only involved both in the occurrence and development of viral myocarditis (VMC),but also,it plays a key role in anti-viral infections by degradating the viral components,presenting viral antigens and activating the immune response.Meanwhile,the virus can also escape the protective antiviral activity and maintain their own survival and replication by inducing the autophagy of the host cells,becoming the accelerator of the viral infection.The interaction of the virus and the host cell autophagy in VMC is a complex process.Its detailed pathogenesis has yet to be further explored.
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Kawasaki disease (KD) is an acute febrile systemic vasculitis,and the cause of KD is not well understood.Based on epidemiologic studies and surveys,several features of KD strongly suggest a genetic component to disease pathogenesis.As a result of their involvement in immune response,human leucocyte antigen (HLA) genes have been extensively studied in association with outcomes of autoimmune and infectious diseases.HLA gene polymorphisms have also been reported to be associated with KD.Now,HLA gene polymorphisms related to KD is focused.
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Kawasaki disease (KD) is a systemic vasculitis diseases.It may be involved multisystem.The most serious complication is coronary artery lesions,which is associated with coronary atherosclerosis in adult.Coronary artery disease caused by endothelial cell dysffunction has attracted the attention of many scholars.Now summarize the research progress in recent years as follows:endothelial cell function evaluation methods,KD markers of endothelial cell injury,and the relationship of the endothelial cell dysfunction with KD coronary lesions.
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Kawasaki disease (KD) is a systemic vascular inflammatory lesion in children with acute febrile rash illness. The inci-dence rate in recent years is increasing. The traditional treatment in some patients is ineffective, and KD has high incidence of cardiovas-cular complications. Therefore, the selection of an appropriate therapy for KD is an urgent. With the continuous advance of biomedical and pharmacologically research, many biological agents were developed. The traditional treatment has been gradually replaced by the new biological agents which achieved the desired results. Thus this paper reviewed several common biological agents in the clinical treatment of KD.
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OBJECTIVE@#To investigate the expression of eIF3P170, cdc2, cyclinB1 and cyclinD1 in developing cardiac myocytes, and the correlation between eIF3P170 with cdc2, cyclin D1, and cyclin B1 in mice.@*METHODS@#Mouse cardiac myocytes were obtained at different time points. RT-PCR was employed to detect the expression of eIF3P170, cdc2, cyclin D1 and cyclin B1 mRNA.@*RESULTS@#Expressions of eIF3P170, cdc2, cyclinD1 and cyclinB1 mRNA were higher in the embryonic Day 13, 15, 18 and postnatal Day 1, 2, 3, 5. Expressions at postnatal Day 5 reached the highest (all P values<0.05 vs other time points), and then the expressions of these genes gradually decreased to the weakest at postnatal Day 30 (all P values<0.05 vs other time points). The mRNA expression of eIF3P170 was positively correlated with cdc2, cyclin D1 and cyclin B1 mRNA expression respectively.@*CONCLUSION@#The mRNA expressions of eIF3 P170, cdc2, cyclin D1 and cyclin B1 in the embryo and the early life after birth are high. They reach the maximum at postnatal Day 5, then gradually decreased.
Subject(s)
Animals , Mice , CDC2 Protein Kinase , Metabolism , Cell Cycle , Cyclin B1 , Metabolism , Cyclin D1 , Metabolism , Eukaryotic Initiation Factor-3 , Metabolism , Myocytes, Cardiac , Cell Biology , Metabolism , RNA, MessengerABSTRACT
OBJECTIVE@#To explore the changes of mTOR signal pathway in HeLa cells under different nutritional conditions infected with Coxsackie virus B3 (CVB3).@*METHODS@#The HeLa cells were cultured with two methods: the conventional culture method cultured HeLa cells with medium with 10% fetal bovine serum for 24 h and changed the medium next day, and then infected with CVB3; the serum starvation method cultured HeLa cells with medium without fetal bovine serum for 24 h, and then infected with CVB3. The expression of the coat protein of CVB3, mTOR, p70S6K mRNA was detected with RT-PCR at different time points.@*RESULTS@#The virus group showed the expressions of mTOR and p70S6K mRNA were significantly higher than those in the control group at 12 h and 24 h (P0.05).@*CONCLUSION@#CVB3 can down-regulate the expressions of mTOR and p70S6K mRNA. The mTOR expression in the starvation serum is higher than that in the conventional culture.
Subject(s)
Humans , Cell Culture Techniques , Down-Regulation , Enterovirus B, Human , Virulence , HeLa Cells , RNA, Messenger , Genetics , Metabolism , Signal Transduction , Physiology , TOR Serine-Threonine Kinases , Genetics , MetabolismABSTRACT
ObjectiveTo investigate the effect of different dosage recombinant human erythropoietin(rhEPO),an angiogenesis-like factor,on pulmonary angiogenesis exposed to hyperoxia in newborn rats.MethodsSixty Sprague-Dawley newborn rats were randomly divided into four groups:air group (room air exposure,n =15 ),hyperoxia group ( exposed to 95％ oxygen,n =15 ),hyperoxia + large dosage rhEPO group (received rhEPO 5000 U/kg,intraperitoneally on 1 hour before and 3 days after exposed to hyperoxia,n =15) and hyperoxia + small dosage rhEPO group (received rhEPO 800U/kg,the same time points,n =15 ).The isodose of saline were given intraperitoneally on the same time points in the air group and the hyperoxia group.After 6 d of exposure,the survival rate was compared,CD31 and vascular endothelial growth factor (VEGF) were measured by immunohistochemistry to assess hyperoxia-induced changes in lung morphology.ResultsAfter 6d of exposure,hyperoxia + large dosage rhEPO group prolonged the survival rate in comparison with the hyperoxia group [ 86.7 ％ ( 13/15 ) vs 60.0 ％ ( 9/15 ) ].The expression of lung CD31 [ ( 38.69 ±1.69)％ vs (33.57±4.12)％,P＜0.05] and VEGF (124.4296±7.2823 vs 114.2059 ±-8.345 7,P＜0.05) in newborn rats treated with large dosage of rhEPO was significantly higher than those in hyperoxia group.While there was no significant difference of CD31 [ ( 36.34 ± 1.89 ) ％ ] and VEGF( 115.429 6 ± 6.719 9) in small dosage rhEPO group compared with the hyperoxia group (P＞0.05 ).ConclusionInstead of treatment with small dosage rhEPO (800 U/kg),large dosage rhEPO (5000 U/kg) may have important protective effects on pulmonary angiogenesis in hyperoxia-induced lung injury of newborn rats.
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Mammalian target of rapamycin(mTOR) inhibitors have the anti-tumor ettect,which have been known early.The traditional mTOR inhibitors include rapamycin and its derivatives,which have been applied in clinical use early.Nowadays,some new small molecule inhibitors such as the PI3K/mTOR duel inhibitor,Torinl,one after another are found to play a unique role in the tumor therapy.
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Objective To study the effects of mammalian target of rapamycin(mTOR)transfection on the proliferation of NIH3T3 fibroblasts.Methods The plasmid of pcDNA3-mTOR was transfected into NIH3T3 fibroblasts with electroporation method.The positive cell clones were selected with G418.The stable mRNA and protein expressions of mTOR in the cells were determined by RT-PCR and Western blotting analysis respectively.MTT assay was employed to observe the proliferation of NIH3T3 fibroblasts.Results mTOR mRNA and protein expressions increased obviously in transfected group than that of in control group(P
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Aim To explore the relationship of the single nucleotide polymorphisms of multidrug resistance gene 1 and brain derived neurotrophic factor(BDNF) gene to childhood drug resistance epilepsy.Methods Two single nucleotide polymorphisms,T-129C polymorphism in multidrug resistance gene 1 and C270T polymorphism in BDNF gene,were conducted with PCR-restriction fragment length polymorphism analysis.The distribution of genotypes and allele frequencies of two single nucleotide polymorphisms in childhood drug resistance epilepsy were compared to those in drug respond epilepsy and controls.Results The distribution of TT genotype and T allele frequencies of multidrug resistance gene 1 in drug resistance epilepsy differed significantly from those in drug respond epilepsy and controls(P0.05).Conclusions The findings suggested that the T-129C polymorphism of multidrug resistance gene 1 maybe associated with childhood drug resistance epilepsy and played some role in the etiology of drug resistance epilepsy,but C270T polymorphism of BDNF gene was not confirmed to relate to childhood drug resistance epilepsy.