Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Guo, Qi,Shen, Zhiyang,Yu, Hongxia,Lu, Gaofeng,Yu, Yong,Liu, Xia,Zheng, Pengyuan The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

Carnosic acid protects against acetaminophen-induced hepatotoxicity by potentiating Nrf2-mediated antioxidant capacity in mice

Qi Guo,Zhiyang Shen,Hongxia Yu,Gaofeng Lu,Yong Yu,Xia Liu,Pengyuan Zheng 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.1

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-a, IL-1b, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkBa and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

DnaJ of Streptococcus suis Type 2 Contributes to Cell Adhesion and Thermotolerance

Zhang, Xiaoyan,Jiang, Xiaowu,Yang, Ling,Fang, Lihua,Shen, Hongxia,Lu, Xingmeng,Fang, Weihuan The Korean Society for Microbiology and Biotechnol 2015 Journal of microbiology and biotechnology Vol.25 No.6

To examine if the molecular chaperone DnaK operon proteins of Streptococcus suis type 2 (SS2) are involved in adhesion to host cells, the abundance values of these proteins from the surface of two SS2 strains of different adhesion capability were compared. Their roles in growth and adhesion to human laryngeal epithelial cell line HEp-2 cells were investigated on SS2 strain HA9801 and its mutants with DnaK operon genes partially knocked-out (PKO mutant) under heat stress. The major difference was that DnaJ was more abundant in strain HA9801 than in strain JX0811. Pretreatment of the bacteria with hyperimmune sera to DnaJ, but not with those to other proteins, could significantly reduce SS2 adhesion to HEp-2 cells. PKO of dnaJ g ene resulted in decreased SS2 growth at 37℃ and 42℃, and reduced its adhesion to HEp-2 cells. The wild-type strain stressed at 42℃ had increased expression of DnaJ on its surface and elevated adhesion to HEp-2 cells, which was also inhibitable by DnaJ specific antiserum. These results indicate that the DnaJ of S. suis type 2 is important not only for thermotolerance but also for adhesion to host cells. Because DnaJ expression is increased upon temperature upshift with increased exposure on the bacterial surface, the febrile conditions of the cases with systemic infections might help facilitate bacterial adhesion to host cells. DnaJ could be one of the potential candidates as a subunit vaccine because of its good immunogenicity.

A serine/threonine phosphatase 1 of Streptococcus suis type 2 is an important virulence factor

Lihua Fang,Jingjing Zhou,Pengcheng Fan,Yunkai Yang,Hongxia Shen,Weihuan Fang 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.4

Streptococcus suis is regarded as one of the major pathogens of pigs, and Streptococcus suis type 2 (SS2) is considered a zoonotic bacterium based on its ability to cause meningitis and streptococcal toxic shock-like syndrome in humans. Many bacterial species contain genes encoding serine/threonine protein phosphatases (STPs) responsible for dephosphorylation of their substrates in a single reaction step. This study investigated the role of stp1 in the pathogenesis of SS2. An isogenic stp1 mutant (stp1) was constructed from SS2 strain ZJ081101. The stp1 mutant exhibited a significant increase in adhesion to HEp-2 and bEnd.3 cells as well as increased survival in RAW264.7 cells, as compared to the parent strain. Increased survival in macrophage cells might be related to resistance to reactive oxygen species since the stp1 mutant was more resistant than its parent strain to paraquat-induced oxidative stress. However, compared to parent strain virulence, deletion of stp1 significantly attenuated virulence of SS2 in mice, as shown by the nearly double lethal dose 50 value and the lower bacterial load in organs and blood in the murine model. We conclude that Stp1 has an essential role in SS2 virulence.

Evaluation of 관-Amyloid Peptides Fibrillation Induced by Nanomaterials Based on Molecular Dynamics and Surface Plasmon Resonance.

Hou, Yafei,Li, Pengfei,Zhou, Hongjian,Zhu, Xiaoli,Chen, Haifeng,Lee, Jaebeom,Koh, Kwangnak,Shen, Zhongming,Chen, Hongxia American Scientific Publishers 2015 Journal of Nanoscience and Nanotechnology Vol.15 No.2

<P>This report investigated the effect of carbon nanomaterials, single-wall carbon nanotube (SWCNT) and graphene oxide, on fibrillation of 관-amyloid 40 (A관40) based on surface plasmon resonance (SPR) and molecular dynamics (MD). MD simulations are carried out in order to reveal the molecular mechanisms of the interaction between nanomaterials and A관40. The strong interaction between A관40 and nanomaterials is related to Van der Waals forces and the Coulomb force, inducing delicate manipulation of the main bonding energy for fibrillation of A관40. The interaction energy between the A관 peptide and graphene is higher than that of SWCNT. Experimental results show both carbon nanomaterials enhance the appearance of a critical nucleus for nucleation of peptide fibrils. Graphene is more beneficial to assist the nucleation process than SWCNT. Combination of SPR and molecular dynamics could be a high-throughput method to screen protein fibrillation.</P>

Family History of Cancer and Head and Neck Cancer Risk in a Chinese Population

Huang, Yu-Hui Jenny,Lee, Yuan-Chin Amy,Li, Qian,Chen, Chien-Jen,Hsu, Wan-Lun,Lou, Pen-Jen,Zhu, Cairong,Pan, Jian,Shen, Hongbing,Ma, Hongxia,Cai, Lin,He, Baochang,Wang, Yu,Zhou, Xiaoyan,Ji, Qinghai,Zho Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Background: The aim of this study was to investigate whether family history of cancer is associated with head and neck cancer risk in a Chinese population. Materials and Methods: This case-control study included 921 cases and 806 controls. Recruitment was from December 2010 to January 2015 in eight centers in East Asia. Controls were matched to cases with reference to sex, 5-year age group, ethnicity, and residence area at each of the centers. Results: We observed an increased risk of head and neck cancer due to first degree family history of head and neck cancer, but after adjustment for tobacco smoking, alcohol drinking and betel quid chewing the association was no longer apparent. The adjusted OR were 1.10 (95% CI=0.80-1.50) for family history of tobacco-related cancer and 0.96 (95%CI=0.75-1.24) for family history of any cancer with adjustment for tobacco, betel quid and alcohol habits. The ORs for having a first-degree relative with HNC were higher in all tobacco/alcohol subgroups. Conclusions: We did not observe a strong association between family history of head and neck cancer and head and neck cancer risk after taking into account lifestyle factors. Our study suggests that an increased risk due to family history of head and neck cancer may be due to shared risk factors. Further studies may be needed to assess the lifestyle factors of the relatives.

Genetic variations in DROSHA and DICER and survival of advanced non-small cell lung cancer: a two-stage study in Chinese population

Shuangshuang Wu,Yun Pan,Songyu Cao,Jiali Xu,Yan Liang,Yan Wang,Lei Chen,Yunyan Wei,Chongqi Sun,Weihong Zhao,Zhibin Hu,Hongxia Ma,Hongbing Shen,Jianqing Wu 한국유전학회 2015 Genes & Genomics Vol.37 No.7

MicroRNAs (miRNA) are a class of small, noncoding RNA molecules involved in carcinogenesis. Genetic variations in miRNA processing genes may affect the biogenesis of miRNAs, and consequently affect miRNAs regulation and development and progression of human cancer. Therefore, we hypothesized that polymorphisms in two main miRNA biosynthesis genes (DROSHA and DICER) may modulate the survival of advanced non-small cell lung cancer (NSCLC) patients in China. We selected 36 common tagging SNPs in DROSHA and DICER and evaluated the associations of these SNPs with survival of advanced NSCLC patients by a two-stage study in Chinese Han population (discovery cohort: 303 patients; replication cohort: 340 patients). Thirty-six SNPs were detected in the discovery cohort and 12 promising SNPs were validated in the replication cohort. The results showed that DROSHA rs3805525 was marginally associated with the survival of NSCLC patients in the replication cohort (dominant model: HR 0.69, 95 % CI 0.46–1.03, P = 0.071), which was in the same direction as that in the discovery cohort. When combing all patients into one group, three SNPs (rs3805525, rs17410035 and rs7719497) in DROSHA showed significantly associations with NSCLC survival (additive model: HR 0.82, 95 % CI 0.68–0.99 for rs3805525; HR 0.79, 95 % CI 0.62–1.00 for rs17410035; HR 0.76, 95 % CI 0.62–0.93 for rs7719497). Additionally, the combined analysis of those three SNPs showed a significant locus-dosage effect between number of favorable alleles and death risk of NSCLC (Trend P = 0.002). Genetic variations in DROSHA might be associated with the survival of advanced NSCLC patients in Chinese population.