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.

OBJECTIVETo detect potential mutation of the WAS gene in a Chinese family affected with Wiskott-Aldrich syndrome.

METHODSPeripheral blood samples were collected from the proband and his family members. All exons and flanking regions of the WAS gene were subjected to PCR amplification - Sanger sequencing as well as restriction endonuclease analysis. Plasma level of B-cell activating factor (BAFF) was also determined for all family members.

RESULTSA hemizygous mutation (c.257G>A) of the WAS gene was identified in all patients from the family, for which the patient's mother was heterozygous. The same mutation was not found among healthy members of the family. Compared with unaffected members, all patients had a higher level of BAFF.

CONCLUSIONThe c.257G>A mutation of the WAS gene probably underlies the Wiskott-Aldrich syndrome in this family.

B-Cell Activating Factor ; blood ; Child, Preschool ; Heterozygote ; Humans ; Male ; Mutation ; Wiskott-Aldrich Syndrome ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics

Objective: To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients). Methods: The family members' medical history, general physical examination and hip joint X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA were extracted from these samples. The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method. Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands. The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing. Results: The family consisted of 5 generations and 38 members. Pedigree analysis was consistent with autosomal dominant inheritance. There were 17 patients in the family, and their clinical manifestations showed abnormal walking posture in childhood, pain in hip and knee joints, and typical pathological changes of epiphyseal dysplasia on X-ray. Cartilage oligomeric matrix protein (COMP) gene c.1153G>A (p.Asp385Asn) missense heterozygous mutation was screened in proband, which was genotypically and phenotypically segregated in the pedigree. Conclusion A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family. Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.

OBJECTIVE: To explore the clinical and genetic features of a patient suspected with Juvenile Parkinson's syndrome (JP). METHODS: Clinical features of the patient were analyzed. Genomic DNA of the patient and his parents was extracted from peripheral blood samples and sequenced by exome capture sequencing. The nature and impact of detected mutations were predicted and validated. RESULTS: The patient displayed typical features including resting tremor, bradykinesia, rigidity, but with excellent response to low dose levodopa. DNA sequencing showed that she has carried compound heterozygous mutations of the Parkin gene, namely c.1381dupC and c.619-1G>C, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis predicted that both mutations are pathogenic. CONCLUSION The patient has JP caused by mutations of the Parkin gene. Exome capture sequencing is an accurate and efficient method for genetic diagnosis of such disease.
Adolescent ; Base Sequence ; Female ; Humans ; Mutation ; Parkinson Disease ; Ubiquitin-Protein Ligases ; Whole Exome Sequencing

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