Humans ; Telomere ; metabolism ; Telomere-Binding Proteins ; metabolism

Objective To explore the protective mechanism of tea polyphenols (TPs) ion oxidative stress damage of the rat articular cartilage tissue caused by brick-tea fluorosis. Methods One hundred and twenty wistar male rats were randomly divided into 6 groups according to body mass: fluoride group with drinking water containing 100.00 mg/L F-, fluoride plus TPs group treated with 100.00 mg/L F- and 10.0 g/L TPs, fluoride plus aluminum group fed with 100.00 mg/L F- and 200.00 mg/L Al3+, fluoride plus aluminium and TPs group treated with 100.00 mg/L F-,200.O0 mg/L Al3+ and 10.0 g/L TPs;brick-tea group treated with drinking water containing 100.00 mg/L F-,215.00 mg/L Al3+ and 9.2 g/L TPs, which was steeped by the brick-tea;control group treated with tap water. The animals were bred for three months and then sacrificed. The level of SOD,T-AOC and MDA in blood serum were detected,also the level of NO and cytokine IL-1β and IL-6, the expression of iNOS mRNA and protein in articular cartilage were respectively analyzed by RT-PCR and immunohistochemistry. Results Blood serum SOD level in the fluoride plus aluminum and TPs group[(664.009 ± 29.589)kU/L] was higher compared with that in the fluoride group[(625.328 ± 27.199)kU/L], fluoride plus aluminum group[(652.282±13.926)kU/L], although no statistically significant differences was found(P > 0.05) ;blood serum T-AOC level of the fluoride plus TPs, fluoride plus aluminum and TPs group, brick tea group[(10.874 ± 0.721), (11.871 ± 0.941), (10.380 ± 2.747)kU/L] was higher compared with fluoride group, fluoride plus aluminum group [(8.849 ± 1.887), (8.210 ± 1.740)kU/L], the differences all being statistically significant(P < 0.05) ;blood serum MDA level in the fluoride plus aluminum and TPs group[(3.235 ± 0.446)μmol/L] had significances compared with fluoride group, fluoride plus aluminum group [(3.889 ± 0.387), (4.580 ± 0.474)μmol/L, all P < 0.05)];blood serum NO level in fluoride plus Tps group, fluoride plus aluminum and TPs group, brick-tea group[(23.278 ± 2.386), (20.643 ± 2.623), (24.367 ± 6.072) μmol/L] had tatistical differences compared with fluoride group, fluoride plus aluminum group[(32.962 ± 8.268), (34.909 ± 6.288)μmol/L, all P < 0.05];blood serum IL-1β level of fluoride group, fluoride plus aluminum, fluoride plus Tps, fluoride plus aluminum and TPs group and brick-tea group [(4.728 ± 0.297), (4.412 ± 0.229), (4.432 ± 0.285), (4.516 ± 0.351), (4.614 ±0.2270)n/L] did not have inter-group differences (F = 2.314,P > 0.05);the blood serum IL-6 level of fluoride plus aluminum and TPs group, brick-tea group[(7.231 ± 0.596), (7.325 ± 0.290)ng/L] had statistical differences compared with fluoride plus aluminum[(8.256 ± 0.635)ng/L, P < 0.05]. The iNOS mRNA correspondent expression content of fluoride plus Tps group, fluoride plus aluminum and TPs group, brick-tea group(0.482 ± 0.021,0.447±0.021,0.491 ± 0.022) had statistical differences compared with fluoride group, fluoride plus aluminum group (0.562 ± 0.025,0.591 ± 0.020, all P < 0.05). Cells with positive iNOS protein expression of control group were mainly distributed at the surface layer of joint, while the cells of experiment groups were distributed both at the surface layer and the intermediate layer. Conclusions Tea polyphenols could alleviate oxidative stress damage on the articular cartilage, exerting protection against brick-tea fluorosis on rats through cleaning up free radicals, elevating total anti-oxidation capability, diminishing the generation of lipid peroxide.

Objective To discover the mutation of ADAR gene in a pedigree with dyschromatosis symmetrical hereditaria(DSH). Methods We investigated this family and collected blood samples of the individuals in this family. Mutation screening was carried out by PCR and direct sequencing. The allele specific primer was designed for the mutation point, and allele-specific PCR was carried out on the patients, normal family members and 40 normal individuals. Results A single nucleotide deletion (c.1642 delC) was identified in exon3 of ADAR gene in the patients of this family. This mutation was not detected in the normal family members and in any of the control individuals. Conclusion This single nucleotide deletion was responsible for the disease in the family.

OBJECTIVETo investigate the effect of different pH on rectum permeability of chlorogenic acid and geniposide.

METHODFour kinds of Reduning suppositories of different pH were separated and put into the rectum to study the suppositories in vitro and the content of chlorogenic acid and geniposide samples was determined by HPLC to calculate the permeation in 24 hours.

RESULTWith increase of pH within 2.5-7.4, the steady state flux of chlorogenic acid was increased, but the steady state flux of geniposidesamples was steady.

CONCLUSIONAdjusted the pH can increase the rectum permeability of active ingredients in Reduning auppositories.

Animals ; Chlorogenic Acid ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacokinetics ; Hydrogen-Ion Concentration ; Iridoids ; pharmacokinetics ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley ; Rectum ; metabolism ; Suppositories ; pharmacokinetics

Immune and tissue cells usually express pattern-recognition receptors (PRRs) to detect viruses and other microorganisms, thereby inducing signal cascade amplification and host innate immune responses. Since PRRs have strain-specific substrates and mechanisms of recognition, the identification of PRRs and mechanisms of PRRs-mediated responses is highly challenging. Besides, the research on RLRs-mediated immune responses has become more popular in cellular immunology recently. Accumulating evidence shows that post-translation modifications, such as ubiquitination, deubiquitination and ISGylation, play an important role in regulating host innate immune responses. In parallel, these approaches may be used by viruses to evade PRRs-mediated responses or to actively subvert these pathways for their own benefit. It was identified that STING (also called MITA/MPYS/ERIS) plays an important role in RIG-Ⅰ-like receptor(RLR) signaling as a type Ⅰ IFN stimulator, providing a special method for the research on complex host antiviral innate immune responses.

ObjectiveTo investigate the protective effect of all-trans retinoic acid (ATRA) on injury of human immortalized hepatocytes (HHL-5 cells ) induced by sodium arsenite and possible mechanisms.Methods After cultured for 48 h,HHL-5 cells were divided into four groups:normal group,ATRA group,sodium arsenite group and ATRA + sodium arsenite group.HHL-5 cell viability was tested by using cell proliferation experiment (WST).Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px) activity,malondialdehyde(MDA) content,and aspartate aminottransferase (AST) activity in each group were determined by biochemical method.The microstructure of HHL-5 cells in each group was observed under transmission electron microscopy.ResultsHHL-5 cell viability(0.57 ± 0.02) of sodium arsenite group was compared with that of normal group(0.70 ± 0.01 ),the difference was statistically significant(P ＜ 0.05).Levels of SOD,GSH-Px,MDA and AST[ (153.84 ± 2.35),(0.08 ±0.02)U/mg Prot,(4.15 ± 0.50)nmol/mg Prot,(265.43 ± 4.62) × 103 U/L] of sodium arsenite group were compared with that of normal group[(237.41 ± 18.30),(0.93 ± 0.02)U/mg Prot,(2.26 ± 0.40)nmol/mg Prot,(177 ± 9.85) ×103 U/L],and the difference was statistically significant (all P ＜ 0.05).HHL-5 cell viability (0.65 ± 0.04) of ATRA + sodium arsenite group was compared with that of sodium arsenite group, and the difference was statistically significant (P ＜ 0.05).Levels of SOD,GSH-Px,MDA and AST[ (286.85 ± 3.39),(0.56 ± 0.09)U/mg Prot,(3.36 ± 0.37)nmol/mg Prot, (220.02 ± 1.07) × 103 U/L] of ATRA+ sodium arsenite group were compared with that of sodium arsenite group,the difference was statistically significant(all P ＜ 0.05).Compared with normal group and ATRA group,the surface microvilli of HHL-5 cells of sodium arsenite group decreased,double-membrane structure was unclear,vacuolar degeneration was seen in the cytoplasm,and glycogen was aggregated.The damage level of ATRA + sodium arsenite group was decreased.ConclusionsATRA plays a protective role through increasing intracellular antioxidant enzyme activity of HHL-5 cells,removal or reduction of oxygen free radicals produced by sodium arsenite.

Objective To observe the influences of different doses of sodium arsenite on mRNA transcription of keratinizing related and nuclear factor E2-related factor 2(Nrf2) genes in HaCaT cells.Methods Cell proliferation was evaluated by Cell Counting Kit-8(CCK-8) assay after the HaCaT cells were exposed to 0.00,3.13,6.25,12.50,25.00,50.00,75.00,100.00 μ mol/L sodium arsenite for 48 h,respectively.Based on the previous results of cell proliferation,0.00(control),6.25,12.50,and 25.00 μmol/L of sodium arsenite were selected to treat HaCaT cells for 48 h,respectively.The mRNA expression of keratin 1,keratin 10,involucrin,loricrin and Nrf2 were detected by real-time fluorescent quantitative PCR.ResultsCompared with the control group (100.05％),HaCaT cell proliferation rates(83.06％,51.04％,39.52％,24.51％,16.99％ and 9.04％) were significantly lower in 6.25,12.50,25.00,50.00,75.00 and 100.00 μ mol/L of sodium arsenite groups and the 50％ inhibiting concentration was 12.38 μmol/L.Compared with the control group( 1.06 ± 0.28,1.00 ± 0.12,1.00 ± 0.08),the mRNA expression of keratin 1,involucrin and loricrin (0.08 ± 0.04,0.13 ± 0.12,0.05 ± 0.03;0.47 ± 0.11,0.21 ± 0.09,0.10 ± 0.15; 0.50 ± 0.27,0.31 ± 0.10,0.57 ± 0.23) were significantly decreased(all P ＜ 0.05) in HaCaT cells treated with 6.25,12.50,25.00 μmol/L sodium arsenite,respectively.But keratin 10 mRNA expression showed a rise trend and the 6.25 μmoL/L sodium arsenite group (1.83 ± 0.45) was significantly higher than that of the control( 1.07 ± 0.14,P ＜ 0.05 ).The Nrf2 mRNA expressions of HaCaT cells in 12.50,25.00 μmol/L sodium arsenite groups(0.13 ± 0.07,0.69 ± 0.33) were significantly lower than that of the control ( 1.00 ± 0.09,all P ＜ 0.05 ).ConclusionsThe cellular proliferation and keratinization are decreased when HaCaT cells are exposed to sodium arsenite,which may be regulated by lowering Nrf2 mRNA transcription.

Objective To provide a basis for preventive strategies to national drinking-water-borne endemic arsenicosis through mastering the implementing progress of preventive measures and observing the dynamic changes.Methods Surveillances were carried out according to the provisions and requirements of The Surveillance Project for National Drinking-Water-Borne Endemic Arsenicosis(Trial).Total of 11 provinces(autonomous regions) and Xinjiang Production and Construction Corps were selected as the surveillance provinces (autonomous regions).Endemic arsenicosis villages with exposed population over 100 persons were chosen as monitoring villages in each province,81 villages in 2010 and 89 villages in 2011 were selected.Potential endemic arsenicosis villages with exposed population over 100 persons were included; 26 villages in 2010 and 19 villages in 2011 were selected.The operation of water-improving projects was investigated,the arsenic content in water from resident house was tested in potential endemic arsenicosis villages and the prevalence of endemic arsenicosis based on the residents who lived in monitoring villages was surveyed:Results ①Total of 225 water-improving projects in 45 counties were monitored,1349 villages were covered and 72.66 million persons were benefited in 2010.Total of 233 waterimproving projects in 48 counties were monitored,1576 villages were covered and 84.61 million persons were benefited in 2011.②)Total of 107 villages with high level of water arsenic were investigated and 81 villages had improved the water quality in these villages in 2010.The water-improving projects running normally reached 90.12％(73/81),intermittent operation rate was 9.88％ (8/81) and without abandoned projects.The projects with qualified water reached 86.42％ (70/81).Total of 108 villages with high level of water arsenic were investigated and 89 villages with water improved in 2011.Normally operated projects reached 86.52％ (77/89),intermittent operation rate was 11.24％ (10/89)and abandoned projects was 2.25％ (2/89).The projects with qualified water arsenic level reached 82.02％(73/89).In addition,26 villages without water-improvement were investigated in 2010,and the families with high level of water arsenic reached 66.01％(371/562).Total of 19 villages were surveyed in 2011,and the families with high level of arsenic reached 54.99％(204/371).③Total of 23 964 persons were examined in villages with improved water in 2010,the detection rate of patients with endemic arsenicosis was 4.43％ (1061/23 964),3964 persons were examined in the villages without water-improvement and the detection rate was 5.98％(237/3964),two new cases were diagnosed.Total of 25 225 persons were examined in villages with waterimproved,the detection rate was 4.68％(1181/25 225),3145 persons were examined in the villages without waterimprovement,and the detection rate was 2.26％(71/3145) in 2011,none new case was detected.Conclusions It is not optimistic about the operating status and quality of water-improving projects.The prevalence in water-improved villages remains higher than that in water-unimproved villages.The long-term mechanism of surveillance should be established and perfected as soon as possible,and the management and maintenance of water-improving projects also should be strengthened.

Objective To observe the expressions of inducible nitric oxide synthase(iNOS) in the progress of rat subchronic fluorosis,and analyse the mechanism of nitric oxide(NO) free radical injnry in bone.Methods Male wistar rats were divided randomly by body weight into two groups.i.e.sodium fluoride group and control group.Sodium fluoride group was given drinking water with 150 mg/L sodium fluoride,and control group was given tap water only.The animals were bred for 24 weeks.Every four weeks some rats were killed.The contents of serum and bone fluoride were examined and analyzed.The levels of serum NO were determined by Griess Reagent.The expressions of iNOS mRNA and protein were analyzed by RT-PCR and immunohistochemistry.Results The serum NO contents significantly increased(t=9.36,P＜0.01) in NaF-treated rats after 8 weeks[(19.94±3.04)nmol/L],but significantly decreased(t=10.47,4.46,P＜0.01) after 20 weeks[(11.55±3.54)nmol/L]and 24 weeks[(20.83±2.49)nmol/L],compared with control group[(9.11±1.21,31.13±3.93,33.10±7.37)nmol/L].The expression of iNOS mRNA significantly increased(t=13.09,4.82,14.23,4.64,7.82,5.29,P＜0.01)in rats treated with sodium fluoride[(1.87±0.11),(1.87±0.78),(1.90±0.29),(1.93±0.67),(1.88±0.38),(1.84±0.03)],compared with control group[(0.41±0.25),(0.30±0.17),(0.18±0.06),(0.63±0.15),(0.66±0.04),(0.65±0.55)],and these proteins mainly appeared in hyperplasie zone and hypertrophic zone cells of epiphyseal plate,cartilages,articular cartilage cells,osteoblasts and ligament cells.Conclusions High dose fluoride might persistentlv induce the expressions of iNOS and catalyze synthesis of NO,then regulates osteoblast and osteoclast activitv and finally influences bone turnover.

Objective To observe the expressions of matrix metal proteinases-13(MMP-13) mRNA and tissue inhibitor of metal protease- 1 (TIMP- 1) mRNA and analyse the molecular mechanism of bone matrix degradation in the progress of rat subchronic fluorosis. Methods Male Wistar rats were randomly divided into two groups according to body weight, i.e. sodium floride group and control group. Rats in the sodium fluoride group were given drinking water containing 150 mg/L F-, and the animals in the control group were given tap water. The animals were bred for 24 weeks. Every 4 weeks some rats were killed. The change of obsteoclst was observed by transmission electron microscope. The expression levels of MMP-13 mRNA and TIMP-I mRNA were analyzed by RT-PCR. Results The number of lysesome and the synthesis of lysosoma enzyme in osteeclast were decreased. The expression of MMP-13 mRNA was significantly increased(t=2.29,2.41,3.07,2.52, 3.15,2.22, P<0.05) in rats treated with sodium fluoride (1.87±0.67,1.87±0.75,1.90±0.73,1.93±0.86,1.88±0.61,1.84±0.53), compared with control group(1.24±0.39, 1.19±0.27,1.07±0.22, I. 15 ~ 0.17, 1.17±0.18, 1.20±0.62). The expression of TIMP-1 mRNA was significantly increased (t=2.69,2.19,2.68,2.46,2.43,2.96, P<0.05) in rats treated with sodium fluoride(1.89±0.77,1.70±0.85,1.61±0.82,1.81±0.84,1.70±0.74, 2.06±0.96), compared with control group (1.07±0.39,0.87±0.49,0.71±0.48,0.99±0.43,0.95±0.46,0.89±0.57). Conclusion High dose fluoride might persistently induce the expressions of MMP-13 mRNA and TIMP-1 mRNA and may be involved in bone turnover.