1.The synergism and mechanism of action of rClone30-hDR5 in combination with TRAIL on HCC.
Tian SUN ; Zeshan NIU ; Xueying LIU ; Guiyou TIAN ; Yin BAI ; Fuliang BAI ; Jiechao YIN ; Dan YU ; Yunzhou WU ; Deshan LI ; Qingzhong YU ; Siming LI ; Guiping REN
Acta Pharmaceutica Sinica 2014;49(7):985-92
To investigate the cell-killing effect and its possible mechanism of rClone30-hDR5 in combination with TRAIL on human hepatic carcinoma (HCC) cell line, first of all, recombinant plasmid pee12.4-hDR5 was introduced into HepG2 cells by liposome transfection. After five rounds of screening by flow cytometry, HepG2 cells expressing high levels of DR5 on cell surface were isolated. The cytotoxicity of TRAIL to selected cells was higher than that of TRAIL to HepG2 cells by MTT method (P < 0.01). The result suggested that the cloned hDR5 gene had biological activity. MTT assay showed that, rClone30- hDR5 in combination with TRAIL more efficiently inhibited the tumor growth of HepG2 cells compared to rClone30-hDR5 or TRAIL in vitro. The results of Annexin V-FITC/PI staining and Quantitative Real-time PCR indicated that rClone30-hDR5 in combination with TRAIL significantly increased the mRNA levels of caspase 3 and caspase 8, and induced the apoptosis of tumor cells. HepG2 cells were infected with rClone30-hDR5 or rClone30 at MOI of 1. The expression of hDR5 on tumor surface increased significantly by rClone30-hDR5 compared to that by rClone30, which contributed to the sensitivity to TRAIL. In conclusion, rClone30-hDR5 in combination with TRAIL has potential application value in cancer treatment.
2.Antitumor efficacy of the recombinant Newcastle disease virus rNDV-IL15 on melanoma models.
Zeshan NIU ; Fuliang BAI ; Tian SUN ; Hui TIAN ; Jiechao YIN ; Hongwei CAO ; Dan YU ; Guiyou TIAN ; Yunzhou WU ; Deshan LI ; Guiping REN
Acta Pharmaceutica Sinica 2014;49(3):310-5
In order to enhance the antitumor efficacy of recombinant Newcastle disease virus, rNDV-IL15 was rescued in this study. Recombinant plasmid prNDV-IL15 was constructed, and BHK21 cells were transfected with the recombinant plasmid. Finally, the recombinant Newcastle disease virus rNDV-IL15 was successfully rescued. The growth curves of these two recombinant viruses were determined. Murine melanoma B16F10 cells were infected with rNDV-IL15 at MOI of 0.1, and the expression level of IL15 in the supernatant was detected by ELISA. The antitumor efficacy of rNDV-IL15 and rNDV was compared in vitro and in vivo. Results showed that prNDV-IL15 was constructed and recombinant virus rNDV-IL15 was successfully rescued. The growth curve of rNDV-IL15 showed that the growth of rNDV-IL15 had not been changed after insertion of IL15 gene. Results showed that there was high level of IL15 expression in the supernatant of rNDV-IL5-infected B16F10 cells (1 044.3 +/- 27.7 ng x mL(-1)). rNDV-IL15 and rNDV significantly inhibited the growth of B16F10 cells in vitro in a time-dependent manner. However, there was no significant difference between them. In animal experiments, rNDV-IL15 efficiently suppressed tumor growth in vivo when compared with rNDV, and the difference was statistically significant. The results suggested that rNDV-IL15 is a more effective antitumor agent.
3.Application value of the Status Epilepticus in Pediatric Severity Score and PEDSS in assessing the short-term prognosis of children with status epilepticus
Jiechao NIU ; Yu ZHANG ; Jiandong WANG ; Haiying LI ; Mengjiao ZHANG ; Huiqiong LIU ; Peisheng JIA ; Erhu WEI ; Huaili WANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(1):54-58
Objective:To validate and compare the value of the Status Epilepticus in Pediatric Severity Score (STEPSS) versus PEDSS in assessing the short-term prognosis of children with status epilepticus (SE).Methods:Clinical data of 152 children with SE hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were retrospectively analyzed.According to the STEPSS and PEDSS scores, children with SE were scored and their prognosis was predicted.Receiver operating characteristic (ROC) curves of the 2 scales in assessing the short-term prognosis of SE in children were plotted, and the area under the curve (AUC), optimal cut-off, sensitivity and specificity were calculated, thus validating and comparing the value of the STEPSS versus PEDSS in assessing the short-term prognosis of children with SE.Results:Of the 152 children with SE, 90 were male and 62 were female, with the age of (5.8±3.9) years (1 month to 15 years). There were 112 cases with good prognosis and 40 cases with poor prognosis, involving 13 deaths.The AUC of STEPSS and PEDSS scores in predicting the death in children with SE were 0.908(95% CI: 0.848-0.967) and 0.887(95% CI: 0.831-0.942), respectively, both with the optimal cut-off value of 4.The sensitivity of STEPSS and PEDSS scores in predicting the death in children with SE were 0.740 and 0.846, respectively, and the specificity were 0.745 and 0.835, respectively.There was no significant difference in predicting the death in children with SE between the 2 scales ( P>0.05). In predicting adverse outcomes, the AUC of the STEPSS and PEDSS scores were 0.869(95% CI: 0.800-0.937) and 0.926(95% CI: 0.873-0.979), respectively, both with the optimal cut-off value of 3.The sensitivity of STEPSS and PEDSS scores in predicting adverse outcomes in children with SE were 0.827 and 0.900, respectively, and the specificity were 0.732 and 0.866, respectively.There was significant difference in predicting the adverse outcomes in children with SE between the 2 scales ( P<0.05). Conclusions:Compared with the STEPSS, the PEDSS has a higher application in predicting the short-term treatment outcome of children with SE, which can be used as a routine method to assess the prognosis of children with SE.
4.Analysis of ADAR gene variants in a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria in conjunct with developmental delay
Yu ZHANG ; Zheng CHEN ; Jiandong WANG ; Guangshuai WEI ; Jiechao NIU ; Yao WANG ; Huaili WANG
Chinese Journal of Medical Genetics 2024;41(5):591-595
Objective:To explore the clinical characteristics and genetic etiology for a Chinese pedigree affected with Dyschromatosis symmetrica hereditaria (DSH) in conjunct with developmental delay.Methods:A child who had presented at the First Affiliated Hospital of Zhengzhou University on May 28 2021 for abnormal skin pigmentation of the extremities and growth retardation for over 2 years was selected as the study subject. Clinical data of the child and his pedigree (11 individuals from three generations) was collected. The child was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing.Results:The child, a two-year-and-seven-month-old male, had hyper- and hypopigmentation on his hands, feet and face, in addition with delayed development. All members of his pedigree had typical presentation of DSH. A heterozygous c. 2657G>A variant was found in exon 8 of the ADAR gene in the child, his mother, and elder sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PM1+ PM2_Supporting+ PP1+ PP3). Conclusion:The c. 2657G>A variant of the ADAR gene probably underlay the DSH in this pedigree.
5.Advances in the use of Anakinra in febrile infection-related epilepsy syndrome
Jiechao NIU ; Yu ZHANG ; Erhu WEI ; Huaili WANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(8):637-640
Febrile infection-related epilepsy syndrome (FIRES) is primarily characterized by frequent focal epileptic seizures followed by generalized seizures and status epilepticus.Multiple anti-seizure drugs are ineffective in its treatment, and there′s a high mortality rate during the acute phase.Survivors often suffer from drug-resistant epilepsy and neurological dysfunctions.Anakinra is an interleukin-1 receptor antagonist.Recent studies have shown that it has potential therapeutic effects on FIRES.This article analyzes the mechanism, efficacy, safety, and future challenges of Anakinra in the treatment of FIRES, aiming to provide a basis for its application in FIRES.