Aim To compare the cytotoxicity of geni-poside (GS)and its metabolite genipin (GP)on hu-man hepatocelluar HepG2 cells and explore the sub-stance and mechanism of hepatotoxicity induced by Fructus Gardeniae.Methods The cytotoxic effect of GS and GP was analyzed by MTT method;the antioxi-dant enzyme activities of manganese superoxide dis-mutase (Mn-SOD),catalase (CAT)and levels of glu-tathione (GSH)were detected by respective kits;the change of intracellular reactive oxygen species (ROS ) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA)staining method;multiparameter cytotox-icity analysis (cell loss,nuclear size and morphologi-cal changes,DNA content,cell membrane permeabili-ty,mitochondrial membrane potential changes,cyto-chrome C release ) were measured simultaneously by high content screening (HCS)assays.Results No cytotoxicity was found in GS (20~1 000 μmol·L-1 ) groups (P>0.05 ),but GP was found to exert obvi-ous cytotoxic effect,and 50μmol·L-1 GP could obvi-ously inhibit HepG2 cell proliferation (P<0.05 ),and the IC50 value was (450.00 ±26.15)μmol·L-1;GS showed no obvious effects on Mn-SOD, CAT, GSH ,ROS (P >0. 0 5 ),GP could significantly decrease the activity of Mn-SOD,CAT and the level of GSH,and obviously increase the content of ROS (P<0.05 or P <0.01 );treatment with 50,500,1 000μmol·L-1 GP resulted in loss of mitochondrial mem-brane potential,cytochrome C release and increased cell permeability (P<0.05 or P<0.01),500,1 000μmol· L-1 GP could also show abvious nuclear con-densation,increased total nuclear intensity and cell loss (P<0.0 1 ).Opposed with GP,GS had no signif-icant effect on the cytotoxic parameters (P>0.05 ). Conclusion GP is the direct substance of hepatotox-icity induced by Fructus Gardeniae,and the mecha-nism might be associated with oxidative stress,mito-chondria injury and apoptosis.

OBJECTIVE: To explore the genetic characteristics of a child with Focal segmental glomerulosclerosis and neurodevelopmental syndrome (FSGSNEDS). METHODS: A child with FSGSNEDS who had visited Shengli Oilfield Central Hospital on September 15, 2019 was selected as the study subject. Clinical data of the child was collected, and trio-whole exome sequencing (trio-WES), Sanger sequencing, chromosomal karyotyping analysis, and copy number variation sequencing (CNV-seq) were used to analyze the child and his parents. RESULTS: The child, a 3-year-old boy, had manifested developmental delay, nephrotic syndrome, and epilepsy. Trio-WES and Sanger sequencing showed that he has carried a heterozygous c.1375C＞T (p.Q459*) variant of the TRIM8 gene, for which both his parents were of the wild type. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. No abnormality was found in the chromosomal karyotyping and CNV-seq results of the child and his parents. CONCLUSION The child was diagnosed with FSGSNEDS, for which the c.1375C＞T variant of the TRIM8 gene may be accountable.
Male ; Humans ; Child ; Child, Preschool ; DNA Copy Number Variations ; Glomerulosclerosis, Focal Segmental/genetics* ; Genomics ; Heterozygote ; Karyotyping ; Carrier Proteins ; Nerve Tissue Proteins