摘要:
Doxorubicin (DOX) is a potent and currently available antitumor therapeutic agent; however, its clinical application is limited by the occurrence of cardiotoxicity. Preliminary evidence indicates that hydrogen sulfide (H2S) may exert protective effects against DOX cardiotoxicity. Therefore, the aim of the present study was to investigate whether calreticulin (CRT) is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. DOX was observed to markedly induce injuries, including cytotoxicity and apoptosis, and also enhance the expression level of CRT. Notably, pretreatment of H9c2 cells with sodium hydrosulfide (a donor of H2S) significantly attenuated the decreased cell viability, the increased apoptosis rate and the increased expression level of CRT in H9c2 cells. In addition, pretreatment of H9c2 cells with N-acetyl-L-cysteine, a scavenger of reactive oxygen species (ROS) prior to exposure to DOX, markedly decreased the expression of CRT. These results indicate that exogenous H2S attenuates DOX-induced cardiotoxicity by inhibiting CRT expression in H9c2 cardiac cells.
摘要:
Rhodococcus opacus strain PD630 (R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super ability of carbon source biosynthesis and catabolism. The comparative transcriptome analysis from three culture conditions revealed the landscape of gene-altered expressions responsible for lipid accumulation. The LD proteomes further identified the proteins that mediate lipid synthesis, storage and other biological functions. Integrating these three omics uncovered 177 proteins that may be involved in lipid metabolism and LD dynamics. A LD structure-like protein LPD06283 was further verified to affect the LD morphology. Our omics studies provide not only a first integrated omics study of prokaryotic LD organelle, but also a systematic platform for facilitating further prokaryotic LD research and biofuel development.
期刊:
MOLECULAR MEDICINE REPORTS,2014年10(3):1619-1625 ISSN:1791-2997
通讯作者:
Hu, Sihai
作者机构:
[Deng, Suhong; Hu, Sihai; Zhang, Lusi; Zhang, Yukuai; Xie, Meihua; Ying, Shangyun; He, Jun; Yu, Minjun] Univ South China, Pathogen Biol Inst, Coll Basic Med, Hengyang 421001, Hunan, Peoples R China.;[He, Jun] Univ South China, Dept Clin Lab, Nanhua Affiliated Hosp, Hengyang 421001, Hunan, Peoples R China.;[Hu, Sihai] Univ South China, Pathogen Biol Inst, Coll Basic Med, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Hu, Sihai] U;Univ South China, Pathogen Biol Inst, Coll Basic Med, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Neisseria surface protein A;recombinant protein;vaccine candidate;protection;Neisseria meningitides serogroup B
摘要:
Neisseria meningitidis is the pathogen of epidemic encephalomyelitis and is responsible for permanent damage to the brain and nervous system. In the present study, the prokaryotic expression vector pGEX-6p-1/neisseria surface protein A (NspA) was constructed and the immune protective effect was investigated with the purified recombinant rNspA. Female BALB/c mice were immunized by intraperitoneal inoculation of rNspA, glutathione S-transferase (GST) or phosphate-buffered saline (PBS). The protection experiment in mice demonstrated that the protection rate of the rNspA group was 85% against the N. meningitidis strain MC58, and a serum bactericidal assay in vitro revealed that the serum bactericidal titer of the rNspA group reached 1:64 following three immunizations. The levels of specific immunoglobulin (Ig) A (SIgA), IgG, IgG1, IgG2a, IgG2b and IgG3 of mice in the rNspA group peaked at week six and were higher than those in the mice in the GST and PBS groups. The levels of stimulation index, interleukin-4 and interferon-gamma in the culture supernatant of the spleen lymphocytes of the rNspA group increased in a time-dependent manner and were higher than those of the mice in the GST and PBS groups over the same period. The results suggested that rNspA may induce increased specific humoral and cellular immune responses, and that it is effectively protective against N. meningitidis serogroup B in mice. The present study offered novel evidence that may lead to the development of a novel effective N. meningitidis serogroup B vaccine.
作者机构:
[Yu, M. J.; Tang, S. Y.; Liu, A. Y.; Liu, Y.; Liu, L. Z.; Wan, Y. P.; Zhang, Y.] Univ South China, Pathogen Biol Inst, Hengyang 421001, Peoples R China.;[Li, L.] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
通讯机构:
[Tang, S. Y.] U;Univ South China, Pathogen Biol Inst, Hengyang 421001, Peoples R China.
关键词:
human papillomavirus type16 (HPV16);E2;Daxx;interaction
摘要:
The aim of the study was to explore the interactions of human papilloma virus 16 (HPV16) E2 protein and Daxx. The localization or co-localization of PML and E2 with Daxx in Caski cells was observed by indirect immunofluorescence. The interaction of E2 and Daxx was analyzed by co-immunoprecipitation, Western-blot and yeast-two hybrid assays. In Caski cells the fluorescence of Daxx and PML was mainly distributed in the cytoplasm or nucleus, respectively, and in the align image their signals did not overlap. However, when the red signal of HPV16 E2 and the green signal of Daxx in the cytoplasm of Caski cells were merged, the yellow signal appeared. The yeast co-transformed with pGBKT7/Daxx and pGADT7/E2 or pGADT7/E2 TAD can grow on SD/-Trp-Leu-His and SD/-Trp-Leu-His-Ade plates. So Daxx is not colocated with PML but with HPV16 E2 mainly in the cytoplasm of Caski cells. On the base of the results one can propose that HPV16 E2, in particularly its transcription-activity domain (TAD), interacts with Daxx.
摘要:
Objective. Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease, yet effective therapeutic approaches are lacking. This study aimed to determine the effects of application of berberine gelatin in the treatment of minor RAS (MiRAS). Methods. A randomized, double-blind, placebo-controlled, clinical trial was performed. The gelatin containing berberine (5 mg/g) or vehicle only was applied 4 times per day for 5 days. Clinical evaluation included pain level, size, erythema, and exudation of certain ulcers on days 1, 2, 4, and 6. Results. A total of 84 subjects fulfilled the study without obvious side effects. Berberine gelatin treatment reduced the ulcer pain score compared with placebo gelatin (P < 0.05). Ulcer size was significantly reduced (P < 0.05) and lower erythema (P < 0.05) and exudation (P < 0.05) levels were associated with berberine treatment. Conclusions. Berberine gelatin may be a safe and effective treatment for MiRAS. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:212-217)
期刊:
Molecular and Cellular Biology,2013年33(6):1104-1113 ISSN:0270-7306
通讯作者:
Jiang, Zhi-Sheng
作者机构:
[Jiang, Zhi-Sheng] Univ South China, Inst Cardiovasc Dis, Hengyang City, Hunan, Peoples R China.;Univ South China, Key Lab Arteriosclerol Hunan Prov, Hengyang City, Hunan, Peoples R China.
通讯机构:
[Jiang, Zhi-Sheng] U;Univ South China, Inst Cardiovasc Dis, Hengyang City, Hunan, Peoples R China.
作者机构:
[Yang, Shou-Kang; Zhang, Hao; Lu, Kun; Jiang, Xiao-Wen; Sun, Guo-Liang] First Peoples Hosp Chenzhou, Dept Stomatol, Chenzhou, Hunan, Peoples R China.;[Jiang, Xiao-Wen] Univ S China, Inst Translat Med, Chenzhou, Hunan, Peoples R China.;[Zhang, Yi] First Peoples Hosp Chenzhou, Dept Neurol, Chenzhou, Hunan, Peoples R China.;[Jiang, Xiao-Wen] First Peoples Hosp Chenzhou, Dept Stomatol, 102 Luojiajing Rd, Chenzhou City 423000, Hunan, Peoples R China.
通讯机构:
[Jiang, Xiao-Wen] F;First Peoples Hosp Chenzhou, Dept Stomatol, 102 Luojiajing Rd, Chenzhou City 423000, Hunan, Peoples R China.
摘要:
Objective. The aim of this study was to investigate the effectiveness of triamcinolone acetonide (TA) and salvianolic acid B (SA-B) intralesional combined injection in the treatment of oral submucous fibrosis (OSF). Material and Methods. A randomized clinical trial was performed. TA, SA-B, and TA combined with SA-B were consecutively applied intralesionally weekly for 20 weeks. Mouth opening and burning sensation improvement as determined by a 100-mm visual analog scale were evaluated at weeks 10, 20, and 44. Results. Forty-two subjects fulfilled the study without obvious adverse reactions. The net gain in mouth opening was 2.00 +/- 1.21 mm in the TA group, 3.48 +/- 2.23 mm in the SA-B group, and 5.50 +/- 1.80 mm in the TA + SA-B group at week 44. The burning sensation improved by 3.05 +/- 0.76 in the TA group, 4.96 +/- 0.97 in the SA-B group, and 6.11 +/- 0.93 in the TA + SA-B group by the end of the study. Conclusions. TA + SA-B intralesional injections improved mouth open and burning sensation in these OSF patients. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:339-344)
摘要:
Angiogenic stimulation is a promising new strategy for treating patients with arteriosclerotic coronary artery disease. This strategy aims to ameliorate cardiac function by improving myocardial perfusion and lowering the risk of myocardial infarction. However, angiogenesis may contribute to the growth of atherosclerotic lesions. Atherogenesis is also a potential side effect of angiogenic therapy. Early clinical trials were performed using fibroblast growth factor 2 (FGF2) protein, which enhances the formation of new collateral vessels to reduce ischaemic symptoms. Conversely, angiogenic stimulation by FGF2 is a dilemma because it could cause negative angiogenic effects, such as atherosclerosis. Thus far, clinical trials in patients with recombinant FGF2 protein therapy have not yet yielded undisputable beneficial effects. Future trials should determine whether an improvement can be obtained in patients with coronary artery disease using a combination of FGF2 and other growth factors or a combination of the FGF2 gene and stem cell therapy. This review summarises the multiple roles of FGF2 in the progression of atherosclerosis, its effect on pro-angiogenesis and improvement of cardiac function in coronary artery disease, and the potentially unfavourable effect of angiogenesis on the prevention and treatment of atherogenesis.
作者机构:
[Zhang, Jifeng; Chen, Y. Eugene] Univ Michigan, Med Ctr, Dept Internal Med, Cardiovasc Ctr, Ann Arbor, MI 48109 USA.;[Zhang, Yuan; Sun, Tingwan; Fu, Mingui] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.;[Huang, Shengping; Guo, Fang; Fu, Mingui] Univ Missouri, Dept Basic Med Sci, Kansas City, MO 64108 USA.;[Huang, Shengping; Guo, Fang; Fu, Mingui] Univ Missouri, Shock Trauma Res Ctr, Sch Med, Kansas City, MO 64108 USA.;[Guo, Fang] Univ South China, Sch Med, Inst Cardiovasc Dis, Hengyang City 421001, Hunan, Peoples R China.
通讯机构:
[Chen, Y. Eugene] U;Univ Michigan, Med Ctr, Dept Internal Med, Cardiovasc Ctr, MSRB 3 7301E,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
摘要:
The molecular mechanism to regulate energy balance is not completely understood. Here we observed that Egr-1 expression in white adipose tissue (WAT) was highly correlated with dietary-induced obesity and insulin resistance both in mice and humans. Egr-1 null mice were protected from diet-induced obesity and obesity-associated pathologies such as fatty liver, insulin resistance, hyperlipidemia and hyperinsulinemia. This phenotype can be largely explained by the increase of energy expenditure in Egr-1 null mice. Characterization of these mice revealed that the expression of FOXC2 and its target genes were significantly elevated in white adipose tissues, leading to WAT energy expenditure instead of energy storage. Altogether, these studies suggest an important role for Egr-1, which, by repressing FOXC2 expression, promotes energy storage in WAT and favored the development of obesity under high energy intake.
通讯机构:
[Zhang, Yan] U;Univ South China, Inst Pathogen Biol, Hengyang 421001, Peoples R China.
关键词:
Helicobacter pylori;VacA;THP-1 cells;proinflammatory cytokines;apoptosis;nuclear factor kappa B (NF-κB);Helicobacter pylori;VacA;cellules THP-1;cytokines proinflammatoires;apoptose;facteur nucléaire kappa B
摘要:
Vacuolating cytotoxin (VacA) is an important virulence factor in the pathogenesis of Helicobacter pylori-related diseases. The aim of this study was to investigate the function of the amino-terminal 476 residue fragment (p52) of VacA and the possible molecular mechanisms responsible for its induction of proinflammatory cytokines secretion and apoptosis. Human acute monocytic leukemia cell line THP-1 was used as an in vitro model to study proinflammatory cytokines secretion and apoptosis induced by transfection of a recombinant plasmid encoding the amino-terminal 476 residue fragment (p52) of VacA. The results showed that VacA p52 overexpression induced the production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1_), nitric oxide, and reactive oxygen species in THP-1 cells in a time-dependent manner. VacA p52 overexpression also promoted THP-1 cells apoptosis. In addition, VacA p52 triggered the activation of nuclear factor kappa B (NF-κB), indicating a possible mechanism for its induction of proinflammatory cytokines secretion and cell apoptosis. Our study demonstrated that the induction of cytokines secretion and apoptosis by VacA p52 in THP-1 cells could be mediated through activation of nuclear factor kappa B. Key words: Helicobacter pylori, VacA, THP-1 cells, proinflammatory cytokines, apoptosis, nuclear factor kappa B (NF-kB).
通讯机构:
[Xiao, Jianhua] U;Univ S China, Inst Pathogen Biol, Hengyang 421001, Hunan, Peoples R China.
关键词:
Schistosoma japonicum;eggshell protein gene;hammerhead ribozyme;in vitro cleavage;anti-reproduction
摘要:
Schistosoma japonicum (S. japonicum) is an extremely harmful pathogen, which infects humans and causes severe public health problems. To date, no effective therapeutic drugs for this pathogen are available. In this study, we designed and constructed three hammerhead ribozymes targeting the eggshell protein gene of S. japonicum (SjESG). The cleavage activities of these three ribozymes were determined using cleavage experiments. The in vitro cleavage results showed that among the three synthesized ribozymes (Rz1, Rz2 and Rz3), Rz1 and Rz3 cleaved their target RNAs effectively. However, Rz2 did not cleave its target RNA detectably. The putative therapeutic roles of these three ribozymes to inhibit the reproduction of S. japonicum in mice were studied in vivo. Compared with the negative controls, Rz1 and Rz3 treatments resulted in increased levels of IFN-γ but decreased levels of IL-4 in mice. Rz2 affected levels of IFN-γ and IL-4 to degrees similar with those caused by the vector controls. In addition, Rz1 and Rz3 reduced the amounts of adult worms and eggs in the livers of mice more extensively than Rz2 and the vector controls. Altogether, these results suggest a correlation between the in vitro cleavage abilities of Rz1 and Rz3 and their roles in reproduction inhibition of S. japonicum.
摘要:
Isolation rearing induces profound behavioral and neurochemical abnormalities in rodents. However there have been many controversies with its anxiogenic-like effects using models like elevated-plus maze. In the current study we aimed to address this by using one novelty-based anxiety paradigm that has been largely overlooked in previous isolation rearing studies. We found that eight-week isolation rearing produced potent anxiogenic-like effects in novelty-induced hypophagia test in mice. We also demonstrated PSD-95 levels were elevated in the hippocampus and amygdala and reduced in the frontal cortex after social isolation. This study provides further behavioral and neurochemical evidence to support that isolation rearing can produce anxiogenic-like effects in rodents. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
摘要:
In the present study, immunomodulatory responses of a DNA vaccine constructed by fusing Treponema pallidum (Tp) glycerophosphodiester phosphodiesterase (Gpd) to interleukin-2 (IL-2) and using chitosan (CS) nanoparticles as vectors were investigated. New Zealand white rabbits were immunized by intramuscular inoculation of control DNAs, Tp Gpd DNA vaccine, or Gpd-IL-2 fusion DNA vaccine, which were vectored by CS nanoparticles. Levels of the anti-Gpd antibodies and levels of IL-2 and interferon-gamma in rabbits were increased upon inoculation of Gpd-IL-2 fusion DNA vaccine, when compared with the inoculation with Gpd DNA vaccine, with CS vectoring increasing the effects. The Gpd-IL-2 fusion DNA vaccine efficiently enhanced the antigen-specific lymphocyte proliferative response. When the rabbits were challenged intradermally with 10(5) Tp (Nichols) spirochetes, the Gpd-IL-2 fusion DNA vaccine conferred better protection than the Gpd DNA vaccine (P < 0.05), as characterized by lower detectable amounts of dark field positive lesions (17.5%), lower ulcerative lesion scores (15%), and faster recovery. Individuals treated with the Tp Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles had the lowest amounts of dark field positive lesions (10%) and ulcerations (5%) observed and the fastest recovery (42 days). These results indicate that the Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles can efficiently induce Th1-dominant immune responses, improve protective efficacy against Tp spirochete infection, and effectively attenuate development of syphilitic lesions.
作者机构:
[Dai, Yongming] Third People Hosp, Clin Lab, Kunshan City 215300, Jiangsu, Peoples R China.;[He, Fei] Shanghai Ctr Bioinformat Technol SCBIT, Shanghai 200235, Peoples R China.;Univ S China, Canc Res Inst, Sch Med, Hengyang City 421001, Hunan, Peoples R China.;[Wu, Yimou] Univ S China, Pathogen Biol Inst, Hengyang 421001, Peoples R China.
通讯机构:
[Runliang Gan] C;[Yimou Wu] P;Cancer Research Institute, University of South China, People’s Republic of China<&wdkj&>Cancer Research Institute, University of South China, School of Medicine, Hengyang City, People’s Republic of China<&wdkj&>Pathogenic Biology Institute, University of South China, People’s Republic of China<&wdkj&>Pathogenic Biology Institute, University of South China, Hengyang, China
关键词:
Epstein-Barr virus (EBV);Lymphocyte transformation;Lymphoblastoid cell line (LCL);Gene expression;Gene chip
摘要:
Epstain-Barr virus (EBV) can transform human B lymphocytes making them immortalized and inducing tumorigenic ability in vitro, but the molecular mechanisms remain unclear. The aim of the present study is to detect and analyze differentially expressed genes in two types of host cells, normal human lymphocytes and coupled EBV-transformed lymphoblasts in vitro using gene chips, and to screen the key regulatory genes of lymphocyte transformation induced by EB virus. Fresh peripheral blood samples from seven healthy donors were collected. EBV was used to transform lymphocytes in vitro. Total RNA was extracted from 7 cases of the normal lymphocytes and transformed lymphoblasts respectively, marked with dihydroxyfluorane after reverse transcription, then hybridized with 4 × 44 K Agilent human whole genome microarray. LIMMA, String, Cytoscape and other softwares were used to screen and analyze differentially expressed genes. Real-time PCR was applied to verify the result of gene expression microarrays. There were 1745 differentially expressed genes that had been screened, including 917 up-regulated genes and 828 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 38 genes may be key controlled genes related to EBV-transformed lymphocytes, including 22 up-regulated genes(PLK1, E2F1, AURKB, CDK2, PLCG2, CD80, PIK3R3, CDC20, CDC6, AURKA, CENPA, BUB1B, NUP37, MAD2L1, BIRC5, CDC25A, CCNB1, RPA3, HJURP, KIF2C, CDK1, CDCA8) and 16 down-regulated genes(FYN, CD3D, CD4, CD3G, ZAP70, FOS, HCK, CD247, PRKCQ, ITK, LCP2, CXCL1, CD8A, ITGB5, VAV3, CXCR4), which primarily control biological processes such as cell cycle, mitosis, cytokine-cytokine pathway, immunity response and so on. Human lymphocyte transformation induced by EB virus is a complicated process, involving multiple-genes and –pathways in virus-host interactions. Global gene expression profile analysis showed that EBV may transform human B lymphocytes by promoting cell cycle and mitosis, inhibiting cell apoptosis, hindering host immune function and secretion of cytokines.
摘要:
Zbtb7, a member of the POK protein family, is involved in tumorigenesis and cellular differentiation by acting as a crucial transcription factor, but its role in cell cycle modulation remains uncharacterized. In the present study, CDK2 and E2F4, two cell cycle regulators, are shown to be downregulated at the mRNA and protein levels by Zbtb7 in HepG2 and QGY7703 cells. Moreover, we demonstrate that the activities of CDK2 and E2F4 promoters were suppressed by the modulation of Zbtb7 levels and that Zbtb7 represses promoter activities through a mechanism involving direct binding of Zbtb7 to the promoters. Furthermore, it was identified that the site at -259 to -252 within the CDK2 promoter is responsible for Zbtb7-induced repression of the promoter activity. It was found that siRNA-induced knockdown of Zbtb7 resulted in the suppression of cell cycle progression in HepG2 and QGY7703 cells. Collectively, these data indicate that CDK2 and E2F4 are the downstream targets of Zbtb7, and Zbtb7 may be a cell cycle modulator by regulating the expression of cell cycle-associated genes in liver cancer cells.