Huimei Chen

Tectorigenin inhibits the in vitro proliferation and enhances miR-338* expression of pulmonary fibroblasts in rats with idiopathic pulmonary fibrosis

UNLABELLED Tectorigenin is one of the main components in rhizomes of Iris tectorum, which is traditionally used to treat disorders such as hepatic cirrhosis caused by fibrosis. Idiopathic pulmonary fibrosis (IPF), one of the most common interstitial lung diseases, is caused by accumulation of fibroblasts in lungs. AIM OF THE STUDY In this work we sought to examine the effects of tectorigenin on pulmonary fibroblasts in the IPF animal model and investigated the molecular mechanism (microRNA regulation) of tectorigenin treatment. MATERIALS AND METHODS A well-known animal disease model of pulmonary fibrosis in rat was established by intratracheally instilling of bleomycin. In vitro cultured pulmonary fibroblasts in bleomycin-treated rats and in controls were treated with or without tectorigenin. Comparative analyses of cell proliferation, apoptosis and cell cycle of pulmonary fibroblasts in bleomycin-treated rats and in controls were performed. Expression of miR-338* and its candidate gene LPA1 related to IPF of tectorigenin-treated pulmonary fibroblasts in bleomycin-treated rats were further investigated. RESULTS Tectorigenin significantly inhibited the proliferation of pulmonary fibroblasts in bleomycin-treated rats but not in controls. However, no altered cell cycle and apoptosis of pulmonary fibroblasts in bleomycin-treated rats and in controls was observed after tectorigenin treatment. Tectorigenin remarkably enhanced miR-338* expression of pulmonary fibroblasts in bleomycin-treated rats and downregulated LPA1 in the protein level. CONCLUSIONS Tectorigenin inhibits the proliferation of pulmonary fibroblasts in vitro and enhances miR-338* expression, which might in turn downregulate LPA1. This indicates a potential inhibitory role of tectorigenin on the pathogenesis of IPF.

A haplotype variation affecting the mitochondrial transportation of hMYH protein could be a risk factor for colorectal cancer in Chinese

BackgroundThe human MutY homolog (hMYH), a DNA glycolsylase involved in the excision repair of oxidative DNA damage, is currently studied in colorectal cancer (CRC). We previously demonstrated a haplotype variant c.53C>T/c.74G>A of hMYH (T/A) increasing the risk for gastric cancer in Chinese. However, most investigations on correlation between hMYH and CRC are conducted in Western countries and the underlying mechanism has been poorly understood.MethodsTo determine whether the haplotype T/A variant of hMYH was related to colorectal carcinogenesis, we performed a case-control study in 138 colorectal cancer (CRC) patients and 343 healthy controls in a Chinese population. Furthermore, the C/G for wild-type, C/A or T/G for single base variant and T/A for haplotype variant hMYH cDNAs with a flag epitope tag were cloned into pcDNA3.1+ vector and transfected into cos-7 cell line. Their subcellular localizations were determined by immunofluorescence assay.ResultsIt was found that the frequency of haplotype variant allele was statistically higher in CRC patients than that in controls (P = 0.02, odds ratio = 5.06, 95% confidence interval = 1.26 – 20.4). Similarly, significant difference of heterozygote frequency was indicated between the two groups (P = 0.019), while no homozygote was found. In addition, immunofluorescence analysis showed that hMYH protein with haplotype T/A variation presented in both nucleus and mitochondria, in contrast to the wild-type protein only converging in mitochondria. However, neither of the single missense mutations alone changed the protein subcelluar localization.ConclusionAlthough preliminarily, these results suggest that: the haplotype variant allele of hMYH leads to a missense protein, which partly affects the protein mitochondrial transportation and results as nuclear localization. This observation might be responsible for the increased susceptibility to cancers, including CRC, in Chinese.

Association of Base Excision Repair Gene Polymorphisms with ESRD Risk in a Chinese Population

The base excision repair (BER) pathway, containing OGG1, MTH1 and MUTYH, is a major protector from oxidative DNA damage in humans, while 8-oxoguanine (8-OHdG), an index of DNA oxidation, is increased in maintenance hemodialysis (HD) patients. Four polymorphisms of BER genes, OGG1 c.977C > G (rs1052133), MTH1 c.247G > A (rs4866), MUTYH c.972G > C (rs3219489), and AluYb8MUTYH (rs10527342), were examined in 337 HD patients and 404 healthy controls. And the 8-OHdG levels in leukocyte DNA were examined in 116 HD patients. The distribution of MUTYH c.972 GG or AluYb8MUTYH differed between the two groups and was associated with a moderately increased risk for end-stage renal disease (ESRD) (P = 0.013 and 0.034, resp.). The average 8-OHdG/106 dG value was significantly higher in patients with the OGG1 c.977G, MUTYH c.972G or AluYb8MUTYH alleles (P < 0.001 via ANOVA). Further analysis showed that combination of MUTYH c.972GG with OGG1 c.977GG or AluYb8MUTYH increased both the risk for ESRD and leukocyte DNA 8-OHdG levels in HD patients. Our study showed that MUTYH c.972GG, AluYb8MUTYH, and combination of OGG1 c.977GG increased the risk for ESRD development in China and suggested that DNA oxidative damage might be involved in such process.

A Clerodane Diterpene with Antibacterial Activity from Ajuga lupulina

The structure of a new diterpene, C30H46O11, with antibacterial activity against Pseudomonas aeruginose and Escherichia coli, isolated from the fresh whole plants of Ajuga lupulina (Labiatae) was established to be 2 beta-hydroxy-2-methylbutanoyl-3 alpha-lupulin (3-deoxy-14,15-dihydro-2-hydroxy-15-methoxycaryoptinol 2-methylbutanoate), by means of X-ray crystallographic analysis. The present study confirms that the two six-membered rings are in ideal chair conformations.

An association between hOGG1 Ser326Cys polymorphism and the risk of bladder cancer in non-smokers: a meta-analysis

BackgroundBladder cancer results from complex interactions between many genetic and environment factors. The polymorphism Ser326Cys in hOGG1 gene has been reported to be associated with bladder cancer in some studies, though the results remain inconclusive. To explore this relationship of hOGG1 polymorphism and the susceptibility for bladder cancer and the impact of smoking exposures, a cumulative meta-analysis was performed in this study.MethodsWe extracted the data from the Pubmed database up to January 9, 2012 using the search phrases “hOGG1, Ser326Cys polymorphism and bladder cancer”. Seven case–control studies were identified, including 2474 patients and 2408 controls. Four of them provided the analysis of smoking effects, with 1372 smokers and 947 non-smokers. The odds ratios (ORs) and associated 95 % confidence intervals (CIs) were calculated using fixed- or random- effects models.ResultsRegarding the overall association between the hOGG1 326Cys allele and bladder cancer risk, the meta-analysis did not reveal a significant effect in the additive model (OR: 1.06, 95 % CI: 0.96-1.26; p = 0.49), the recessive genetic model (OR: 1.05, 95 % CI: 0.65-1.70; p = 0.85) or the dominant genetic model (OR: 1.07, 95 % CI: 0.87-1.32; p = 0.53). Similarly, no significant relationship was observed in the stratified analysis by ethnicity, study design and Hardy-Weinberg equilibrium (all p > 0.05). In the non-smokers, however, hOGG1 326Cys allele significantly increased the risk for bladder cancer and the ORs in the additive model, homozygote contrast and recessive genetic model were 1.59 (p = 0.02), 2.53(p = 0.003) and 2.41(p = 0.0005), respectively. Nevertheless, in the smoker subgroup, similar findings could not be found in all genetic models (all p > 0.05).ConclusionsThe association between the hOGG1 326Cys allele and bladder cancer was significant in non-smoker population, while was non-detectable in common or smoker populations. This meta-analysis suggests that the hOGG1 Ser326Cys polymorphism may be a risk factor for bladder cancer without exposure to smoking. Further functional studies are needed to elucidate the gene polymorphism-bladder cancer relationship and gene-environment interactions.

Base excision repair gene polymorphisms are associated with inflammation in patients undergoing chronic hemodialysis.

Chronic inflammation may increase the risk of mortality for patients undergoing hemodialysis, while enhanced oxidative stress and DNA oxidative damage are involved in the inflammatory response. The purpose of this study was to examine the associations between inflammation and polymorphisms in the base excision repair (BER) system, which protects against oxidative DNA damage, among hemodialysis patients. Data were analyzed from 167 hemodialysis patients and 66 healthy controls. All subjects were evaluated for the expression of inflammatory cytokines (IL-1β and IL-6) and genotyped for two BER genes, including hOGG1 c.977C>G, MUTYH c.972G>C and AluYb8MUTYH. The results showed that the hemodialysis patients had significantly higher levels of IL-1β and IL-6 than the healthy controls. In the healthy controls, no patterns of association were observed between the hOGG1 c.977C>G or MUTYH c.972G>C genotypes and IL-1β or IL-6 levels; however, patients with the MUTYH c.972G/G genotype presented higher levels of IL-1β than those with the C/C genotype. The AluYb8MUTYH genotype was strongly associated with increased IL-1β levels among controls and increased IL-1β and IL-6 levels among hemodialysis patients. Additionally, the synergetic effect of these variations of the BER genes on the levels of IL-1β and IL-6 was investigated. The combinations of the AluYb8MUTYH genotype with the hOGG1 c.977 C>G or MUTYH c.972 G>C genotypes were associated with the IL-1β and IL-6 levels in hemodialysis patients. This is the first report showing an association between BER genetic polymorphisms and the inflammatory state during hemodialysis; this association might be mediated by impaired anti-oxidant defense mechanisms.

Mitochondrial protective effects of Myrica rubra extract against acetaminophen-induced toxicity.

The present study investigates the hepatoprotective activity of Myrica rubra Sieb. et Zucc. extract (MCE) against acetaminophen (AAP)-induced liver damage and elucidates the possible mechanisms behind the hepatoprotection observed. Serum alanine aminotransferase and serum aspartate aminotransferase activities were detected and liver histopathology was observed. Mitochondrial swelling, mitochondrial membrane potential, and voltage-dependent anion channel (VDAC) gene transcription were also investigated. The results showed that 50, 150, and 450 mg/kg MCE could restore AAP-induced changes in mice liver in a dose-dependent manner. The mechanisms behind the hepatoprotective effects of MCE may be related to the mitochondrial protection of liver cells, especially of VDAC, an important protein on the outer membrane of the mitochondria.