Andrographolide induce human embryonic stem cell apoptosis by oxidative stress response

Huarong Huang,Huanhuan Cao,Chun Xing,Yunfen Hua,Ming Zhang,Lifang Jin 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2

Backgrounds: The anti-inflammatory effect of andrographolide is widely accepted; however, its exact role in reproductive toxicity requires further elucidation. The embryonic stem cell test (EST) is a promising system for detecting the reproductive toxicity of drugs in vitro. In this study, we applied a prediction model to our EST data after classifying andrographolide according to published criteria. The possible mechanism of andrographolide reproductive toxicity was also studied. Methods: Reproductive toxicity of andrographolide was evaluated in vitro EST model and in vivo mouse model. Human embryonic stem cells (ESCs) were cultured with different concentrations of andrographolide with or without N-acetyl-L-cysteine (NAC). Cell viability was assessed with MTT assay, and reactive oxygen species (ROS) level was measured with DCFH-DA assay. Gene and protein expression levels were measured with qRT-PCR and western-blot, respectively. Results: Results showed that andrographolide exhibited strong reproductive toxicity according to the prediction model of the EST and mouse studies. An increase in ROS levels, damage to mitochondrial membrane potential, and induction of caspase-3 were observed in the andrographolide-treated human ESCs. Scavenging of andrographolide-induced ROS by NAC blocked these activities. Western blot and qRT-PCR analysis revealed that the nuclear factor erythroid-2-related factor 2 (Nrf2) protein and its target antioxidant genes were up-regulated after andrographolide treatment at certain concentrations. Furthermore, NAC treatment significantly increased the activity of the Nrf2 signaling pathway. Conclusion: We demonstrated that andrographolide is a drug with strong reproductive toxicity, which resulted from ROS-mediated oxidative stress. In addition, the Nrf2 pathway appears to be involved in the NAC protection of human ESCs against andrographolide-induced cell apoptosis.

An Effective Krill Herd Algorithm for Numerical Optimization

Songwei Huang,Lifang He,Xu Si,Yuanyuan Zhang,Pengyu Hao 보안공학연구지원센터 2016 International Journal of Hybrid Information Techno Vol.9 No.7

The krill herd (KH) algorithm is a novel swarm intelligent algorithm which is inspired the herding behavior of the krill swarms. The various test results in the relevant literature show that the KH algorithm has better performance than the other swarm intelligent algorithm for optimization problem. In order to further improve the performance of the KH algorithm, an improved KH is proposed in this paper. The algorithm is performed on ten test functions and the results are compared with the basic KH algorithm, PSO, DE and GA algorithm. The experimental results indicate that the improved algorithm is a good method for numerical optimization problem.

Inhibition of quorum sensing, biofilm, and spoilage potential in Shewanella baltica by green tea polyphenols

Junli Zhu,Xuzheng Huang,Fang Zhang,Lifang Feng,Jianrong Li 한국미생물학회 2015 The journal of microbiology Vol.53 No.12

We investigated the quorum sensing (QS) system of Shewanella baltica and the anti-QS related activities of green tea polyphenols (TP) against spoilage bacteria in refrigerated large yellow croaker. Autoinducer-2 (AI-2) and the diketopiperazines (DKPs) cyclo-(L-Pro-L-Leu) and cyclo-(L-Pro-L-Phe) were detected in the culture extract of S. baltica XH2, however, no N-acylhomoserine lactones (AHLs) activity was observed. Green TP at sub-inhibitory concentrations interfered with AI-2 and DKPs activities of S. baltica without inhibiting cell growth and promoted degradation of AI-2. The green TP treatment inhibited biofilm development, exopolysaccharide production and swimming motility of S. baltica in a concentration- dependent manner. In addition, green TP decreased extracellular protease activities and trimethylamine production in S. baltica. A transcriptional analysis showed that green TP repressed the luxS and torA genes in S. baltica, which agreed with the observed reductions in QS activity and the spoilage phenotype. Epigallocatechin gallate (EGCG)-enriched in green TP significantly inhibited AI-2 activity of S.baltica. These findings strongly suggest that green TP could be developed as a new QS inhibitor for seafood preservation to enhance shelf life.

Complete genome sequence of the sesame pathogen Ralstonia solanacearum strain SEPPX 05

Xinshen Li,Xiaomei Huang,Gongyou Chen,Lifang Zou,Lingen Wei,Juling Hua 한국유전학회 2018 Genes & Genomics Vol.40 No.6

Ralstonia solanacearum is a soil-borne phytopathogen associated with bacterial wilt disease of sesame. R. solanacearum is the predominant agent causing damping-off from tropical to temperate regions. Because bacterial wilt has decreased the sesame industry yield, we sequenced the SEPPX05 genome using PacBio and Illumina HiSeq 2500 systems and revealed that R. solanacearum strain SEPPX05 carries a bipartite genome consisting of a 3,930,849 bp chromosome and a 2,066,085 bp megaplasmid with 66.84% G+C content that harbors 5,427 coding sequences. Based on the whole genome, phylogenetic analysis showed that strain SEPPX05 is grouped with two phylotype I strains (EP1 and GMI1000). Pan-genomic analysis shows that R. solanacearum is a complex species with high biological diversity and was able to colonize various environments during evolution. Despite deletions, insertions, and inversions, most genes of strain SEPPX05 have relatively high levels of synteny compared with strain GMI1000. We identified 104 genes involved in virulence-related factors in the SEPPX05 genome and eight absent genes encoding T3Es of GMI1000. Comparing SEPPX05 with other species, we found highly conserved secretion systems central to modulating interactions of host bacteria. These data may provide important clues for understanding underlying pathogenic mechanisms of R. solanacearum and help in the control of sesame bacterial wilt.

Fe3+-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma

Youmei Xiao,Zhanxue Xu,Yuan Cheng,Rufan Huang,Yuan Xie,Hsiang‑i Tsai,Hualian Zha,Lifang Xi,Kai Wang,Xiaoli Cheng,Yanfeng Gao,Changhua Zhang,Fang Cheng,Hongbo Chen 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC.

Flavonoids in Resina Draconis protect against pulmonary fibrosis via the TGF‑β1/NOTCH1 pathway

Liteng Yang,Xin Liu,Ning Zhang,Gaohui Wu,Lifang Chen,Jingyi Xu,Xi Ren,Xiaoming Jiang,Zhijing Huang 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.2

Background It is known that flavonoids in Resina Draconis (FRD) have anti-inflammatory and analgesic effects, but the function and mechanisms of FRD against pulmonary fibrosis remain unknown. Objective The study aimed to study the effect and mechanism of FRD on pulmonary fibrosis. Methods Pulmonary fibroblasts were isolated and identified. After treatment with transforming growth factor (TGF)-β1 and FRD-containing serum, expressions of TGF-β1, Jagged1, Notch1, alpha-smooth muscle actin, and collagen I were examined using real-time quantitative PCR and Western blot. Besides, the related proteins were verified in rats with bleomycin-induced pulmonary fibrosis. Results We successfully isolated and identified pulmonary fibroblasts and proved that FRD-containing serum inhibits proliferation and downregulates Notch1 expression in TGF-β1-induced fibroblasts. Moreover, our results indicate that FRD might alleviate pulmonary fibrosis via the Jagged1/Notch1 signaling pathways in vivo. Conclusion Flavonoids in Resina Draconis might play a key role in pulmonary fibrosis via critical pathways, especially the TGF-β1 and NOTCH1 signaling pathways.

Regulatory Role of SFN Gene in Hepatocellular Carcinoma and Its Mechanism

Ying Hui,Hao Zeng,Yi Feng,Wenzhou Qin,Peisheng Chen,Lifang Huang,Wenfu Zhong,Liwen Lin,Hui Lv,Xue Qin 한국생물공학회 2021 Biotechnology and Bioprocess Engineering Vol.26 No.3

Purpose: This study aims to explore the differential expression of SFN gene and its regulatory role in different hepatocarcinoma cells, and the impact on hepatocarcinoma. Materials and Methods: High and low SFN expression cells were screened by qRT-PCR and western blotting methods. SFN over expression and interference vectors were constructed. Cell viability was detected by CCK8 kit, cell cycle and apoptosis were detected by flow cytometry. Cell invasion and migration were detected. CCNB1 and CDK1 expression levels were detected by qRT-PCR and Western blotting methods. Results: The high SFN expression BEL7402 cells and the low SFN expression Hep3B cells were screened from Hep3B, HepG2, and BEL7402 cells. The activity of Hep3B cells overexpression vector SFNpcDNA3.1(+) decreased and apoptosis increased, the ratio of G0/G1 decreased and the ratio of S phase increased. The activity of BEL7402 cells transfected with SFN siRNA decreased and apoptosis increased, the ratio of G0/G1 decreased and the ratio of G2/M increased. Interference and overexpression vectors have little effect on the invasion and migration of the two cells. The expression of CDK1 in Hep3B cells decreased significantly, the expression of CDK1 and CCNB1 in BEL7402 cells increased significantly. Conclusions: The differentially expressed SFN gene can regulate the growth of the two hepatocarcinoma cells, high expression of SFN gene can inhibit their growth. The mechanism may be achieved by regulating CCNB1 and CDK1 expression.

Antioxidant and Antigenotoxic Activities of Ethanol Extracts from Rhus chinensis Mill Leaves

Zhenyu Qiu,Mingli Tang,Guanjun Deng,Hao Yang,Xuan Zhang,Shengwei Huang,Lifang Wu 한국식품과학회 2014 Food Science and Biotechnology Vol.23 No.4

Ethanol extracts were obtained from Rhuschinensis Mill (RCM) leaves and used for antioxidant andantigenotoxic activity assays. IC50 values in DPPH assayswere 15.96, 18.83, 20.43, 27.93, 37.43, 46.21, and 141.84μg/mL for TPP, IPE, LLE, Vc, CE, BHT, and Trolox. Similar results were obtained using ABTS and FRAPassays. In vivo testing showed strong antioxidant activitiesthat were positively correlated with polyphenol contents. Leaf tissue contained abundant polyphenols, and more than10 phenolic compounds were detected in extracts. Quantitative results showed that quercetin-3-rhamnoside(26.4±0.76 mg/g of extract) was the most abundantingredient, followed by hyperoside (15.2±0.42 mg/g ofextract), quercetin (1.5±0.07mg/g of extract), and kaempferol(0.48±0.05 mg/g of extract). This study increases theknowledge for possible uses of forest by-products as asubstitute for gallnuts.

Case-control Study of Single Nucleotide Polymorphisms of PSCA and MUC1 Genes with Gastric Cancer in a Chinese

Li, Fang,Zhong, Mei-Zuo,Li, Jian-Huang,Liu, Wei,Li, Bin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Aims: A case-control study of 300 gastric cancer patients and 300 controls was conducted to investigate whether the polymorphisms rs2294008 in PSCA and rs2070803 in MUC1 might be associated with risk of gastric cancer in a Chinese population. Methods: Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform. Results: The data showed that the rs2294008 TT genotype increased gastric cancer risk to an adjusted odds ratio (OR) of 2.26 (95%CI 1.25-4.07), TC to 1.72 (95%CI 1.23-2.42) and TC/TT to 1.81 (95% CI 1.31-2.50), while the rs2070803 GA genotype was associated with a decrease in risk to an adjusted OR of 0.42 (95% CI 0.28-0.62) and rs2070803 GA / AA to 0.46 (95% CI 0.32-0.67). Further stratification analysis revealed that rs2294008 in PSCA consistently increased risk of both intestinal and diffuse-type gastric cancers. The effect of rs2070803 in MUC1 was noteworthily also consistent with both subtypes. Conclusions: Our study suggested rs2294008 in the PSCA gene to be associated with increased risk of gastric cancer and rs2070803 in MUC1 to play a protective role in a Chinese population.