Association Between Polymorphisms of DNA Repair Gene XRCC1 and DNA Damage in Asbestos-Exposed Workers

Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. Methods DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. Results The basal comet scores （3.95±2.95） were significantly higher in asbestos-exposed workers than in control workers （0.10±0.28）. After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98±19.53 in asbestos-exposed workers and 18.32±12.04 in controls. The residual DNA damage （RD） was significantly greater （P〈0.01） in asbestos-exposed workers （35.62%） than in controls （27.75%）. XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 （polymorphisms in codon 399） and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gin/Gin, Gln/Arg, and Arg/Arg were 40.26±18.94, 38.03±28.22, and 32.01±11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes （25.58±11.08, 37.08±14.74, and 29.38±10.15）. There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gin/Gin by Student＇s t-test （P〈0.05 or 0.01）. The comet scores were higher in asbestosis workers with Gin/Gin than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. Conclusions Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DNA repair gene XRCC 1 codon 399 may be responsible for the inter-individual susceptibility in DNA damage and repair capacities.

Fermented soy whey induced changes on intestinal microbiota and metabolic influence in mice

Soy whey(SW)is generated as process waste while preparing soy protein isolates(SPI),and causing severe environmental pollution.Therefore,its value-added utilization is of prime importance for transforming and upgrading traditional industry.This study aims to utilize SW as a substrate for the growth of probiotics and produce a SW based synbiotics.By a series of trials,the effect of the dietary supplementation with this fermented SW(FSW)was analyzed on ICR mice's body weight,metabolites,and intestinal microbiota in 4 weeks.The results showed that,when SW was concentrated 15 times,the count of viable Lactobacillus casei reached 3.4×10^(9) CFU/mL by liquid fermentation method,which was the highest viable cell count among all test strains.In this FSW,the protein,amino acid,total dietary fibre,soluble dietary fibre,and oligosaccharide were 2.10%,1.63%,0.52%,0.51% and 0.79%,respectively.Compared to two control group,the total yields of the short chain fatty acids(SCFAs)were significantly improved(75%-125% at average),while the SCFAs structure was also significantly changed(especially acetic acid and butyrate)in the faeces of mice fed FSW.Meanwhile,FSW dietary addition was associated with the diversity and richness of the intestinal microbiota.Obviously,with mice's body weight loss,Firmicutes/Bacteroides ratio reduced accordingly(<1.21),and the abundance of Akkermansia muciniphila was significantly increased(the maximum amount was about 0.013%).In summary,our results indicated that the dietary supplementation of FSW affected mice's intestinal microbiota and metabolism and improved their health profile.

PM_(2.5) obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B

Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well understood.Methods: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.Conclusion: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.

Three new ursane-type triterpenoids from Rosmarinus officinalis and their biological activities

Three new ursane-type triterpenoids,3-oxours-12-en-20,28-olide(1),3β-hydroxyurs-12-en-20,28-olide(2)and 3β-hydroxyurs-11,13(18)-dien-20,28-olide(3),were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis.Their structures were elucidated by a combination of extensive 1D-and 2D-NMR experiments,MS data and comparisons with literature reports.Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages,but no antibacterial activity was found at a concentration of 128μg·mL^(-1).

Parallel screening and cheminformatics modeling of flavonoid activated aptasensors

A parallel screening of 27 different flavonoids and chalcones was conducted using 6 artificial naringenin-activated riboswitches(M1,M2,M3,O,L and H).A quantitative structure-property relationship approach was applied to understand the physicochemical properties of the flavonoid structures resulting in specificity differences relied on the fluorescence intensity of a green fluorescent protein reporter.Robust models of riboswitches M1,M2 and O that had good predictive power were constructed with descriptors selected for their high correlation.Increased electronegativity and hydrophilicity of the flavonoids structures were identified as two properties that increased binding affinity to RNA riboswitches.Hydroxyl groups at the C-3′and C-4’positions of the flavonoid molecule were strictly required for ligand-activation with riboswitches M1 and M2.Riboswitches O and L preferred multi-hydroxylated flavones as ligands.Substitutions on the A ring of the flavonoid molecule were not important in the molecular recognition process.O-glycosylated derivatives were not recognized by any of the riboswitches,presumably due to steric hindrances.Despite the challenges of detecting RNA conformational change after ligand binding,the resulting models elucidate important physicochemical features in the ligands for conformational structural studies of artificial aptamer complexes and for design of ligands having higher binding specificity.

Mitochondrial dysfunction and cellularmetabolic deficiency in Alzheimer's disease

Alzheimer＇s disease （AD） is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β （Aβ） deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways ofAβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

Magnetic Resonance Imaging of Alzheimer's Disease:from Diagnosis to Therapeutic Evaluation

Alzheimer＇s disease（AD）is a devastating late-life dementia that produces progressive loss of memory and mental faculties in elderly people.It is important to identify the earliest evidence of AD and to monitor the development of this disease for us to make positive response to its management.Magnetic resonance imaging（MRI）is powerful to image the tissue or organ without damnification.MRI can be employed to diagnose the early AD development and monitor the key biomarker development in AD.MRI may be helpful not only in diagnosing early AD,but also in evaluating its development.This article reviews the progress of MRI on the diagnosis and detection of AD,and makes comments on its therapeutic application.