李涛
阜外华中心血管病医院 检验科
Lipopolysaccharide (LPS) can induce vascular endothelial injury. Circular RNAs (circRNAs) have been verified to regulate different cellular processes in various diseases. This study intended to explore the potential role and mechanism of circ_0057583 in brain microvascular endothelial cell injury. Human brain microvascular endothelial cells (hBMECs) were exposed to different doses of LPS to induce cell damage. The levels of circ_0057583, microRNA-204-5p (miR-204-5p) and nuclear receptor 4A1 (NR4A1) were detected by quantitative real-time PCR or Western blot assays. Cell viability, apoptosis, inflammation and angiogenesis were assessed by Counting Kit-8 (CCK-8), flow cytometry, enzyme linked immunosorbent assay (ELISA) and tube formation assays. The targeting relationship between miR-204-5p and circ_0057583 or NR4A1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. LPS treatment elevated the expression of circ_0057583 and NR4A1, but decreased the expression of miR-204-5p in LPS-induced hBMECs. Downregulation of circ_0057583 abated LPS-induced hBMEC injury by inducing cell proliferation and angiogenesis, as well as inhibiting cell apoptosis, autophagy and inflammation. Circ_0057583 aggravated LPS-evoked hBMEC injury by regulating miR-204-5p. Also, miR-204-5p suppressed LPS-evoked hBMEC damage via targeting NR4A1. Moreover, circ_0057583 sponged miR-204-5p to up-regulate NR4A1 level. Depletion of circ_0057583 alleviated LPS-triggered brain microvascular endothelial endothelial cell injury through modulating miR-204-5p/NR4A1 axis.
Metabolic brain disease 2022
OBJECTIVE:To carry out genetic testing and prenatal diagnosis for 90 families affected with spinal muscular atrophy (SMA), and discuss the necessity for carrier screening.METHODS:All families were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis. Combined MLPA and allele-specific PCR (AS-PCR) was used for prenatal diagnosis of the pregnant women.RESULTS:Among the 90 couples, 84 (93%) had a negative family history, 85 (94%) had given birth to an affected child before. Eighty-five husbands and 88 wives carried heterozygous deletion of exon 7 of the SMN1 gene. Two wives had homozygous deletion of exon 7 of the SMN1 gene and were affected. Prenatal diagnosis showed that 19 fetuses were SMA patients, 48 fetuses were carriers, and 23 fetuses were normal. Of note, eighteen affected fetuses were conceived by couples without a family history, which accounted for 20% of all pregnancies and 95% of all affected fetuses.CONCLUSION:To screen SMA carriers using MLPA and carry out prenatal diagnosis using combined MLPA and AS-PCR can ensure accurate diagnosis, which has a significant value for the prevention of SMA affected births.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2020
At present, there are no effective methods for the treatment of hemophilia B, and it has high mortality and disability. Therefore, it is very important for the carriers to carry out genetic counseling and make prenatal diagnosis. In this study, we made gene and prenatal diagnoses in a family with a novel F9 gene mutation, and report a novel F9 gene mutation.All exon sequences and flanking sequences of F9 gene were analyzed by Sanger sequencing in the proband; and then according to the F9 gene mutation in the proband, the F9 gene sequencing was performed on the family members. Based on the above results, the pathogenic mutation in F9 gene was finally identified, which was used for prenatal diagnosis.Sanger sequencing revealed c.1232G>C [p.Ser411Thr] mutation in F9 gene in the proband. c.1232G>C heterozygous mutation was also found in the proband's mother and grandmother, but male family members without hemophilia B had no this mutation. The analyses of amniotic fluid samples indicated positive sex-determining region on Y chromosome (SRY), and no c.1232G>C [p.Ser411Thr] mutation in F9 gene.We identified a pathogenic mutation in F9 gene in the family, made a prenatal diagnosis for the female carrier and reported a novel F9 gene mutation.
Medicine 2019
OBJECTIVE:To carry out genetic testing for a family affected with distal hereditary motor neuronopathy V (dHMN V).METHODS:Potential mutations of the GARS and BSCL2 genes were analyzed with PCR and Sanger sequencing. Suspected mutation was verified among unaffected members of the family and 100 healthy controls. Prenatal diagnosis was provided based on the above results.RESULTS:Sequencing analysis has identified a heterozygous c.269C>T (p.S90L) mutation in the BSCL2 gene, which resulted in replacement of Serine (TCG) to Leucine (TTG). The same mutation was found in all other 3 patients from the pedigree but not among unaffected members or the 100 healthy controls. By prenatal diagnosis, the fetus did not carry the above mutation.CONCLUSION:Pathogenic mutation of BSCL2 gene probably underlies the dHMN V in this pedigree, which enabled prenatal diagnosis for the proband.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2019
