Objective: To study the effect of genistein(Gen) on expression of monocyte chemotactic protein-1 ( MCP-1) mRNA and MCP-1 induced by oxidized low density lipoprotein (ox-LDL) in human umbilical venous smooth mulscle cells (hUVSMC). Methods: Gen at different doses (1.0?10-5、3.0?10-5、9.0?10-5mol/L) were used to observe the effect on expression of MCP-1 mRNA and MCP-1 induced by ox-LDL in hUVSMC cultures and compared with the effect of 17b-estradiol(17b-E). RT-PCR and ELISA were used to measure expression of MCP-1 mRNA and MCP-1 respectively. Results: Gen significantly inhibited the expression of MCP-1 mRNA and MCP-1 in cell culture supernant . There was no significant difference in the inhibitory effect between high concentration of Gen and physiological level of 17b-E . Conclusion: Gen can down-regulate hUVSMC expression of MCP-1 mRNA and MCP-1. It suggests that this may be the important antiatherogenic mechanism of Gen.

OBJECTIVE: To study the effect of hesperidin and rutin on oxidative modification of high density lipoprotein (HDL) in vitro. METHODS: HDL was isolated from healthy human plasma by sequential ultracentrifugation, and was oxidized by copper ions. The inhibitory effects of hesperidin and rutin on HDL oxidative modification were valued by the formation of malondialdehyde (MDA). RESULTS: Hesperidin and rutin significantly inhibited copper-induced oxidation of HDL in a dose-dependent manner. CONCLUSION: Both hesperidin and rutin can prevent HDL from copper-induced oxidative modification in vitro. This result suggests that they might have antiatherogenic effect.

Objective To evaluate the antioxidant effect of hesperidin and its effect on transcription of monocyte chemoattractant protein 1 (MCP 1) in rabbits with dietary atherosclerotic lesions. Methods (1) Low density lipoprotein (LDL) was isolated from healthy human plasma by sequential ultra centrifugation and oxidized by copper. The contents of malondialdehyde (MDA) were measured at different dosages of the drug and at different reaction time. (2) Atherosclerotic model of rabbits was established by feeding rabbits with high lipid diet and immune injury. A total of 18 rabbits were divided randomly into three groups: control group, model group, and hesperidin group ( n =6 in each group). Rabbits in the control group were fed with common diet, those in the model group with high lipid diet, and those in the hesperidin group with high lipid diet plus hesperidin. After 10 experimental weeks, blood samples were collected from the marginal ear veins for the detection of the contents of MDA and nitric oxide (NO). The rabbits were sacrificed for the isolation of the thoracic aorta. MCP 1 mRNA transcription in the thoracic aorta was detected by RT PCR. Results Hesperidin could significantly inhibit MDA production in a dose dependent manner in vitro ( P

Prospective research have shown that whole exome sequencing (WES) may be considered when a diagnosis cannot be obtained using routine prenatal methods, e. g., chromosomal karyotyping and copy number variation sequencing, for fetuses with significant structural anomalies. WES can increase the diagnostic rate of genetic disorders in such fetuses by 8%~10%. Prenatal WES has been gaining wide acceptance. However, due to the limitations of fetal phenotypic evaluation and complexity of ethical issues in prenatal diagnosis, to justify and standardize the application of prenatal WES and maximize its clinical utility has become an urgent need. In view of this, a consensus has been formed by referring to the latest guidelines, expert consensus and authoritative literature. This consensus has put forward suggestions on the suitable objects of prenatal WES, pre-test consultation, sampling and laboratory testing, results report, post-test consultation, pregnancy outcome follow-up, multidisciplinary consultation of difficult cases, preservation of prenatal WES samples and data information.

Objective To detect variants of ARSA gene in a child featuring late infantile metachromatic leukodystrophy (MLD).Methods PCR and Sanger sequencing was carried out for the patient and her parents.Results The patient had typical features of MLD including ARSA deficiency,regression of walking ability,and demyelination.Compound heterozygous variants of the ARSA gene,namely c.960G＞A and c.244C＞T,were detected in the patient,for which her mother and father were respectively heterozygous carriers.ARSA c.960G＞A was known to be pathogenic,while ARSA c.244C＞T was a novel variant.The same variants were not detected among 50 healthy controls.Conclusion The compound heterozygous variants c.960G＞A and c.244C＞T of the ARSA gene probably underlie the MLD in this patient.

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.
Child ; Humans ; Male ; Pregnancy ; Histone Acetyltransferases ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Female ; Fetus ; Finland ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Nephrotic Syndrome ; congenital ; diagnosis ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To carry out prenatal diagnosis for a fetus with ultrasonographic abnormality. METHODS: Chromosomal karyotyping and array comparative genomic hybridization (array-CGH) analysis were applied for the diagnosis. Peripheral blood samples were also taken from the parents for chromosome karyotyping analysis. RESULTS: The fetal karyotype showed additional material of unknown-origin attached to Yq. Array CGH analysis confirmed that the material was derived from 3q22.1q29. The father was found to carry a balanced translocation 46, X, t(Y;3)(q12;q23) (which was diagnosed as 46,XY,Y≥18 elsewhere), whilst the mother was found to be normal. CONCLUSION 3q partial trisomy may present as malformation of multiple systems. Combination of chromosome karyotyping and array-CGH can provide reliable diagnosis for fetuses with abnormalities by ultrasonography.
Chromosomes, Human, Pair 3 ; genetics ; Comparative Genomic Hybridization ; Female ; Fetus ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; Trisomy

OBJECTIVE: To explore the genetic basis for a pedigree affected with Bartter's syndrome (BS). METHODS: Panel-based next-generation sequencing (NGS) was carried out to detect mutation in BS-related genes SLC12A1, KCNJ1, BSND and CLCNKB. Sanger sequencing of MAGED2 gene and chromosomal microarray analysis (CMA) were also performed on the patient. Suspected mutation was validated in her family members. RESULTS: No pathogenic mutation was detected by NGS, while a 0.152 Mb microdeletion at Xp11.21 (54 834 585-54 986 301) was found in the male fetus, which removed the entire coding region of the MAGED2 gene. His mother was a heterozygous carrier of the deletion. His father and sister did not carry the same deletion. CONCLUSION The loss of the MAGED2 gene may underlie the BS in this pedigree.
Adaptor Proteins, Signal Transducing ; genetics ; Antigens, Neoplasm ; genetics ; Bartter Syndrome ; genetics ; Female ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Sequence Deletion

OBJECTIVE: To analyze the clinical features and genetic mutations in a patient with mucolipidosis type II α/β by using next generation sequencing. METHODS: Clinical data of the patient was collected. Genomic DNA of the patient and her parents was extracted by a standard method. The patient was subjected to targeted sequencing using an Ion Ampliseq panel, which included genes related to mucolipidosis and mucopolysaccharidosis. Suspected mutations were verified by Sanger sequencing. RESULTS: Compound heterozygous mutations, namely c.1284+1G>T and c.1090C>T (p.Arg364*), were detected in the patient, which were respectively inherited from her mother and father. No other disease-causing mutation was detected in the patient. GNPTAB c.1090C>T was known to be pathogenic, while GNPTAB c.1284+1G>T is a novel mutation. The same mutations were not detected among 50 healthy controls. CONCLUSION The compound heterozygous mutations c.1284+1G>T and c.1090C>T (p.Arg364*) of GNPTAB gene probably account for the mucolipidosis type II α/β in the patient. NGS has a great value for the molecular diagnosis and typing of mucolipidosis.
Female ; High-Throughput Nucleotide Sequencing ; Humans ; Mucolipidoses ; genetics ; Mutation ; Transferases (Other Substituted Phosphate Groups) ; genetics