Search

Aims. Few research was reported to explore oxidative stress in individuals with latent autoimmune diabetes in adults (LADA). Therefore, our goal is to study oxidative stress and related factors in LADA patients. Methods. In this study, 250 Chinese inpatients were diagnosed with LADA ( n = 110 ) and type 2 diabetes mellitus ( n = 140 ) and 140 healthy volunteers were recruited. Moreover, individuals with LADA were followed for 6 months to evaluate whether short-term glycemic control during hospitalization can improve oxidative stress. Clinical and laboratory measurements of height, weight, blood pressure, glycosylated hemoglobin (HbA1c), blood lipids, 8-isoprostaglandin F2α (8-iso-PGF2α), and superoxide dismutase (SOD) were performed. Stepwise multiple regression analyses were used to assess factors that related to oxidative stress in individuals with LADA. Results. Compared with patients with type 2 diabetes, individuals with LADA have better oxidative stress and worse oxidative stress than healthy volunteers. After multiple regression analyses, systolic blood pressure, HbA1c, duration of diabetes, and diabetic retinopathy were associated with 8-iso-PGF2α and HbA1c. Diabetic retinopathy and diabetic ketosis were associated with SOD in individuals with LADA. Our results also revealed that, after 6 months of follow-up, oxidative stress was improved to some extent in persons with LADA. Conclusions. Our results show that compared with type 2 diabetes, LADA means less oxidative stress, and compared with healthy volunteers, it means more oxidative stress. Systolic blood pressure, HbA1c, duration of diabetes, diabetic retinopathy, and ketosis were associated with oxidative stress in individuals with LADA. Furthermore, short-term glycemic control can improve oxidative stress to some extent in individuals with LADA.

Two aerobic and obligately acidophilic bacteria, designated 4G-K13T and 4Y35T, were isolated from the forest soil sampled at Dinghushan Biosphere Reserve, Guangdong Province, PR China. These two strains were Gram-stain-negative, non-motile and short rods that multiplied by binary division. Strains 4G-K13T and 4Y35T had the highest 16S rRNA gene sequence similarity of 97.0 and 97.2 % to Silvibacterium bohemicum DSM 103733T and Acidisarcina polymorpha SBC82T, respectively. Phylogenetic trees based on the 16S rRNA gene and whole genome sequences showed consistently that these two strains formed a major clade with members of the genera Acidipila , Acidisarcina , Silvibacterium and Acidobacterium in the family Acidobacteriaceae , but each occupied an unique position. In both the UBCG and the PhyloPhlAn phylogenomic trees, strains 4G-K13T and 4Y35T congruently formed a highly supported subclade with Acidobacterium capsulatum DSM 11244T and Acidobacterium ailaaui DSM 27394T, respectively. The major fatty acids (>5 %) of strain 4G-K13T were iso-C15 : 0, iso-C17 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl), while that of strain 4Y35T were C16 : 0, C18 : 1 ω9c, iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl). Strain 4G-K13T contained phosphatidylethanolamine, four unidentified phospholipids, four glycolipids, two unidentified aminolipids and two unknown lipids, while strain 4Y35T had phosphatidylethanolamine, three unidentified phospholipids, two glycolipids, five unidentified aminolipids and one unknown polar lipid. The DNA G+C contents of 4G-K13T and 4Y35T were 60.5 and 55.8 mol%, respectively. Based on all these phylogenetic, physiological and chemotaxonomic data, we suggest that strains 4G-K13T and 4Y35T represent two novel species of two novel genera in the family Acidobacteriaceae , for which the names Paracidobacterium acidisoli gen. nov., sp. nov. (type strain: 4G-K13T=GDMCC 1.1195T=NBRC 113249T) and Alloacidobacterium dinghuense gen. nov., sp. nov. (type strain: 4Y35T=KACC 21728T=NBRC 114261T) are proposed. We also propose to reclassify Acidobacterium ailaaui and Acidipila dinghuensis as Pseudacidobacterium ailaaui gen. nov., comb. nov. and Silvibacterium dinghuense comb. nov., respectively, based mainly on the results of phylogenomic analysis.

Human oxidation resistance 1 (OXR1) was identified as a protein that decreases genomic mutations in Escherichia coli caused by oxidative DNA damage. However, the mechanism by which OXR1 defends against genome instability has not been elucidated. To clarify how OXR1 maintains genome stability, the effects of OXR1-depletion on genome stability were investigated in OXR1-depleted HeLa cells using gamma-rays (γ-rays). The OXR1-depleted cells had higher levels of superoxide and micronucleus (MN) formation than control cells after irradiation. OXR1-overexpression alleviated the increases in reactive oxygen species (ROS) level and MN formation after irradiation. The increased MN formation in irradiated OXR1-depleted cells was partially attenuated by the ROS inhibitor N-acetyl-L-cysteine, suggesting that OXR1-depeletion increases ROS-dependent genome instability. We also found that OXR1-depletion shortened the duration of γ-ray-induced G2/M arrest. In the presence of the cell cycle checkpoint inhibitor caffeine, the level of MN formed after irradiation was similar between control and OXR1-depleted cells, demonstrating that OXR1-depletion accelerates MN formation through abrogation of G2/M arrest. In OXR1-depleted cells, the level of cyclin D1 protein expression was increased. Here we report that OXR1 prevents genome instability by cell cycle regulation as well as oxidative stress defense.

Cells of bacterial strains G9T and 7MK23T, isolated from forest soil samples collected from the Dinghushan Biosphere Reserve, Guangdong Province, PR China, were Gram-stain-negative, aerobic and rod-shaped. Strain G9T was motile with single polar flagellum and grew at 12–37 °C (optimum, 28 °C), pH 4.5–8.0 (optimum, pH 6.0–7.5) and in the presence of 0–3.5 % NaCl (optimum, 1.5%, w/v); while strain 7MK23T was non-motile and grew at 12–42 °C (optimum, 28–33 °C), pH 2.5–8.5 (optimum, pH 4.5–6.5) and NaCl levels of 0–1.0 % (optimum, 0–0.5 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences revealed that both isolates fell within the cluster of the genus Dyella . The closely related species (with a 16S rRNA gene sequence similarity >98.65%) of strain G9T were Dyella terrae JS14-6T (99.0 %), D . kyungheensis THG-B117T (98.8 %) and D . amyloliquefaciens DHC06T (98.7 %) while that of strain 7MK23T were D . mobilis DHON07T (99.2 %) and D . flava DHOC52T (99.1 %), but the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strains G9T, 7MK23T and the closely related Dyella species listed above were in the ranges of 77.5–83.8 % and 22.0–27.0 %, much lower than the species demarcation lines of 95.5 and 70 %, respectively. Phylogenomic analyses using UBCG and Phylophlan also supported that these two strains represent two novel species of Dyella . The major fatty acids of strain G9T were iso-C15 : 0, iso-C17 : 1 ω9c and iso-C17 : 0 while that of strain 7MK23T were iso-C15 : 0 and anteiso-C15 : 0. Ubiquinone-8 was the only respiratory quinone detected in both strains. The polar lipids of strain G9T consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and several unknown phospholipids, aminophospholipids, aminolipids and lipid while strain 7MK23T contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and several unknown phospholipids and aminophospholipids. The DNA G+C contents of strains G9T and 7MK23T were 64.7 and 63.4 mol%, respectively. On the basis of 16S rRNA gene sequence phylogenetic and phylogenomic analyses as well as phenotypic data obtained, we propose that strains G9T and 7MK23T represent two novel species of the genus Dyella , for which the names Dyella telluris sp. nov. (type strain G9T=KACC 21725T=GDMCC 1.2132T) and Dyella acidiphila sp. nov. (type strain 7MK23T=KCTC 62739T=GDMCC 1.1446T) are proposed.

Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the locomotion of C. elegans, we investigated the dose range that reduces whole-body locomotion or leads to death. Irradiation was performed in the range of 0–6 kGy. In the crawling analysis, motility decreased after irradiation in a dose-dependent manner. Exposure to 6 kGy of radiation affected crawling on agar immediately and caused the complete loss of motility. Both γ-rays and carbon-ion beams significantly reduced crawling motility at 3 kGy. Next, swimming in buffer was measured as a motility index to assess the response over time after irradiation and motility similarly decreased. However, swimming partially recovered 6 h after irradiation with 3 kGy of γ-rays. To examine the possibility of a recovery mechanism, in situ GFP reporter assay of the autophagy-related gene lgg-1 was performed. The fluorescence intensity was stronger in the anterior half of the body 7 h after irradiation with 3 kGy of γ-rays. GFP::LGG-1 induction was observed in the pharynx, neurons along the body, and the intestine. Furthermore, worms were exposed to region-specific radiation with carbon-ion microbeams and the trajectory of crawling was measured by image processing. Motility was lower after anterior-half body irradiation than after posterior-half body irradiation. This further supported that the anterior half of the body is important in the locomotory response to radiation.

To investigate the effect of sodium glucose cotransporter 2 inhibitor (SGLT-2I) on bone turnover markers in overweight and obese patients with type 2 diabetes mellitus. Methods: according to the criteria of selection and exclusion, 42 patients with overweight and obese type 2 diabetes (BMI≥25kg/m2) were selected from October 2019 to May 2020. The patients were randomly divided into experimental group and control group, there were 18 cases in the experimental group and 24 cases in the control group. The experimental group was treated with SGLT-2I, and other oral hypoglycemic agents (or insulin) were added according to the blood glucose situation. The control group received oral hypoglycemic agents (non-SGLT-2I) and/or insulin and/or glucagon-like peptide-1 receptor agonist (GLP-1 RA). Every 28 days of follow-up, medication regimen was adjusted according to blood glucose and adverse reactions of patients. Fasting venous serum of the patients was collected at the beginning and again 24 weeks later and the levels of PINP and β-CTX were detected uniformly. SPSS 21.0 was used to compare the changes of clinical indexes before and after the treatment. Results: 1. In the experimental group, PINP, HbA1c, FPG and BMI decreased (p

Apurinic/apyrimidinic (AP) sites are the most common form of cytotoxic DNA damage. Since AP sites inhibit DNA replication and transcription, repairing them is critical for cell growth. However, the significance of repairing AP sites during early embryonic development has not yet been clearly determined. Here, we focused on APEX1 from the ascidian Ciona intestinalis (CiApex1), a homolog of human AP endonuclease 1 (APEX1), and examined its role in early embryonic development. Recombinant CiApex1 protein complemented the drug sensitivities of an AP endonuclease-deficient Escherichia coli mutant, and exhibited Mg2+-dependent AP endonuclease activity, like human APEX1, in vitro. Next, the effects of abnormal AP site repair on embryonic development were investigated. Treatment with methyl methanesulfonate, which alkylates DNA bases and generates AP sites, induced abnormal embryonic development. This abnormal phenotype was also caused by treatment with methoxyamine, which inhibits AP endonuclease activity. Furthermore, we constructed dominant-negative CiApex1, which inhibits CiApex1 action, and found that its expression impaired embryonic growth. These results suggested that AP site repair is essential for embryonic development and CiApex1 plays an important role in AP site repair during early embryonic development in C. intestinalis.

BACKGROUND Protective effects of reduced beta 2 glycoprotein I (Rb2GPI) against vascular injury of diabetes mellitus have been extensively investigated. However, the effects of Rb2GPI on liver injury in diabetic animals have not been reported. MATERIAL AND METHODS A diabetic rat model of was produced by systemic injection of streptozotocin (STZ). Rats were divided into a normal control group, a model group, and an Rb2GPI treatment group (N=6 in each group). After treatments, blood serum and liver tissue were collected to test the protection of Rb2GPI. AMP-activated protein kinase (AMPK) was detected by immunohistochemistry and Western blotting. RESULTS Our results revealed that Rβ2GPI reduced blood glucose, serum creatinine, and urea nitrogen levels, as well as serum inflammation cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein in the diabetic rats. Importantly, Rβ2GPI prevented liver injury in the diabetic rats as confirmed by hematoxylin-eosin (H&E) staining, alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase. Reactive oxygen species (ROS) were promoted by diabetic modeling and were attenuated by Rβ2GPI administration. Moreover, Rβ2GPI significantly reduced liver catalase, malondialdehyde, and superoxide dismutase levels in the diabetic rats. Rβ2GPI reduced liver glycolipid storage in STZ diabetic rats. Both immunohistochemistry and Western blotting demonstrated that Rβ2GPI promoted AMPK phosphorylation in the diabetic rats. CONCLUSIONS Our data proved that Rβ2GPI prevented liver injury in diabetic rats, likely through activating the AMPK signaling pathway.

Exogenous and endogenous damage to the DNA is inevitable. Several DNA repair pathways including base excision, nucleotide excision, mismatch, homologous and non-homologous recombinations are conserved across all organisms to faithfully maintain the integrity of the genome. The base excision repair (BER) pathway functions to repair single-base DNA lesions and during the process creates the premutagenic apurinic/apyrimidinic (AP) sites. In this review, we discuss the components of the BER pathway in the nematode Caenorhabditis elegans and delineate the different phenotypes caused by the deletion or the knockdown of the respective DNA repair gene, as well as the implications. To date, two DNA glycosylases have been identified in C. elegans, the monofunctional uracil DNA glycosylase-1 (UNG-1) and the bifunctional endonuclease III-1 (NTH-1) with associated AP lyase activity. In addition, the animal possesses two AP endonucleases belonging to the exonuclease-3 and endonuclease IV families and in C. elegans these enzymes are called EXO-3 and APN-1, respectively. In mammalian cells, the DNA polymerase, Pol beta, that is required to reinsert the correct bases for DNA repair synthesis is not found in the genome of C. elegans and the evidence indicates that this role could be substituted by DNA polymerase theta (POLQ), which is known to perform a function in the microhomology-mediated end-joining pathway in human cells. The phenotypes observed by the C. elegans mutant strains of the BER pathway raised many challenging questions including the possibility that the DNA glycosylases may have broader functional roles, as discuss in this review.

Oxidative stress is often initiated by excess reactive oxygen species (ROS) production, resulting in macromolecular damage, which is implicated in many disease states. Glutaredoxin 1 (Grx1) is an antioxidant enzyme that plays an important role in redox signaling and redox homeostasis. In the present study, we generated HeLaS3 cell lines deficient in Grx1 by the CRISPR/CAS9 system to clarify how Grx1 affects the physiological activities of HeLaS3 cells to respond to oxidative stress. First, the survival assay revealed that Grx1-deficient HeLaS3 cells were more sensitive to γ-ray irradiation, heat shock and H2O2 exposure than HeLaS3 wild-type cells. Next, the intracellular redox state was investigated using a fluorescent probe (2′-7′dichlorofluorescin diacetate), and the oxidized state of total proteins and a peroxidase Prx2 were measured by Western blot analysis. Exposure to γ-ray irradiation, heat shock and H2O2 significantly induced more accumulation of intracellular oxidants including ROS and higher levels of oxidized proteins in Grx1-deficient HeLaS3 cells. Furthermore, MitoSox Red staining demonstrated that Grx1 deficiency causes a higher level of oxidants production in mitochondria. Moreover, Grx1-deficient HeLaS3 cells had a higher cytochrome c level and higher apoptosis rate (Annexin-V/FITC and EthD-III staining assay) upon oxidative stress. These results suggested that Grx1 deficiency lead to mitochondrial redox homeostasis disruption and apoptotic cell death upon oxidative stress. In addition, the results of proliferation assay and MitoTracker staining assay (multinuclear cell formation rate) suggested that oxidative stress exposure inhibits cell proliferation maybe by affecting cytoplasmic division in Grx1-deficient HeLaS3 cells.

An enzymatic browning product (EBP) of fresh white salted noodles (FWSNs) was extracted, purified, isolated and identified. The optimum parameters of extraction were as follows: volume fraction of ethanol 70%, solid-liquid ratio 1 : 10 (g: mL, samples: ethanol solution), extraction time 10 days (20 °C). In the purified process, protein (99.86%) and carbohydrates (69.50%) impurities were removed from the crude extract using Sevag method, dialysis method and AB-8 macroporous resin column. The purified EBP was separated using 20% (v: v) methanol solution in a C18 chromatographic column. A monomer of EBP was isolated by high-performance liquid chromatography. Nuclear magnetic resonance and infrared spectroscopy analysis showed that the EBP monomer was 2-hydroxyindole-3-propylamine. This was the first time in the literature that 2-hydroxyindole-3-propylamine was found in the EBP of FWSNs. It would lay a material foundation for investigating the origin of EBPs and the revealing enzymatic browning mechanism of FWSNs.

Nijmegen breakage syndrome (NBS), a condition similar to Ataxia-Telangiectasia (A-T), is a radiation-hypersensitive genetic disorder showing chromosomal instability, radio-resistant DNA synthesis, immunodeficiency, and predisposition to malignances. The product of the responsible gene, NBS1, forms a complex with MRE11 and RAD50 (MRN complex). The MRN complex is necessary for the DNA damage–induced activation of ATM. However, the regulation of MRN complex formation is still unclear. Here, we investigated the regulatory mechanisms of MRN complex formation. We used an immunoprecipitation assay to determine whether levels of the MRN complex were increased by radiation-induced DNA damage and found that the levels of these proteins and their mRNAs did not increase. ATM-dependent phosphorylation of NBS1 contributed to the DNA damage–induced MRN complex formation. However, pre-treatment of cells with an ATM-specific inhibitor did not affect homologous recombination (HR) and non-homologous end-joining (NHEJ) repair. G0 phase cells, decreasing NBS1 and HR activity but not NHEJ, gained HR-related chromatin association of RAD51 by overexpression of NBS1, suggesting that the amount of NBS1 may be important for repressing accidental activation of HR. These evidences suggest that NBS1 is regulated by two kind of mechanisms: complex formation dependent on ATM, and protein degradation mediated by an unknown MG132-resistant pathway. Such regulation of NBS1 may contribute to cellular responses to double-strand breaks., A correction has been published: Journal of Radiation Research, Volume 59, Issue 2, March 2018, Page 243

Three Gram-stain-negative, aerobic, motile and rod-shaped bacterial strains, 7Q-K02T, DHF22T and DHOM02T, were isolated from forest soil sampled at Dinghushan Biosphere Reserve, Guangdong Province, China. Strains 7Q-K02T, DHF22T and DHOM02T grew at 4–37, 4–42 and 12–37 °C, pH 3.0–8.5, 3.5–8.5 and 5.0–8.0, and in the presence of 0–3.0, 0–3.5 and 0–2.5 % (w/v) NaCl; with optima at 28–33, 28 and 28–33 °C, pH 3.5–6.5, 4.0–5.5 and 6.5–7.0, and 0–1.5, 0–1.5 and 0.5–1.5 % (w/v) NaCl, respectively. Strains 7Q-K02T and DHF22T have the highest 16S rRNA gene sequence similarities of 99.0 and 98.0 % to Paraburkholderia sacchari LMG 19450T and 97.7 % between themselves, while strain DHOM02T shares the highest similarity of 98.4 % to ‘Burkholderia rinojensis’ A396T followed by 98.3 % to Burkholderia plantarii ATCC 43733T. In the 16S rRNA gene sequence phylogram, strain 7Q-K02T formed a sister branch with Paraburkholderia sacchari , Paraburkholderia oxyphila and Paraburkholderia paradisi , and strain DHF22T was separated from all other species within the genus Paraburkholderia , while strain DHOM02T formed a separated clade with members of the genus Burkholderia . The DNA G+C contents of strains 7Q-K02T, DHF22T and DHOM02T wwe 64.3, 65.4 and 66.6 %, respectively. Digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) values of strains 7Q-K02T, DHF22T and closely related Paraburkholderia strains were in the ranges of 25.5–43.7 % and 81.5–91.3 %, respectively. While dDDH and ANI values between strain DHOM02T and Burkholderia strains with genome sequence data were in the ranges of 22.4–31.0 % and 78.2–86.1 %, respectively. These three strains have the same major respiratory quinone: ubiquinone-8. Strains 7Q-K02T, DHF22T and DHOM02T have C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) as their major fatty acid compositions. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. On the basis of phenotypic, phylogenetic, genomic analyses and chemotaxonomic data, strains 7Q-K02T and DHF22T represent two novel species of the genus Paraburkholderia , for which the names Paraburkholderia acidiphila sp. nov. (type strain 7Q-K02T=CGMCC 1.15433T=KCTC 62472T=LMG 29209T) and Paraburkholderia acidisoli sp. nov. (type strain DHF22T=GDMCC 1.1448T=LMG 30262T) are proposed, while strain DHOM02T represents a novel species in the genus Burkholderia , for which the name Burkholderia guangdongensis sp. nov. (type strain DHOM02T=KCTC 42625T=LMG 28843T) is proposed. We also propose to transfer Burkholderia ultramafica to the genus Paraburkholderia as Paraburkholderia ultramafica comb. nov. based mainly on the results of phylogenomic analysis.

Apurinic/apyrimidinic (AP) sites are the most common form of cytotoxic DNA damage. Since AP sites inhibit DNA replication and transcription, repairing them is critical for cell growth. However, the significance of repairing AP sites during early embryonic development has not yet been clearly determined. Here, we focused on APEX1 from the ascidian Ciona intestinalis (CiApex1), a homolog of human AP endonuclease 1 (APEX1), and examined its role in early embryonic development. Recombinant CiApex1 protein complemented the drug sensitivities of an AP endonuclease-deficient Escherichia coli mutant, and exhibited Mg

AP endonuclease deficiency causes cell death and embryonic lethality in mammals. However, the physiological roles of AP endonucleases in multicellular organisms remain unclear, especially after embryogenesis. Here, we report novel physiological roles of the AP endonuclease EXO-3 from larval to adult stages in Caenorhabditis elegans, and elucidated the mechanism of the observed phenotypes due to EXO-3 deficiency. The exo-3 mutants exhibited developmental delay, whereas the apn-1 mutants did not. The delay depended on the DNA glycosylase NTH-1 and checkpoint kinase CHK-2. The exo-3 mutants had further developmental delay when treated with AP site-generating agents such as methyl methane sulfonate and sodium bisulfite. The further delay due to sodium bisulfite was dependent on the DNA glycosylase UNG-1. The exo-3 mutants also demonstrated an increase in dut-1 (RNAi)-induced abnormal vulval organogenesis protruding vulva (Pvl), whereas the apn-1 mutants did not. The increase in Pvl was dependent on UNG-1 and CHK-2. Methyl viologen, ndx-1 (RNAi) and ndx-2 (RNAi) enhanced the incidence of Pvl among exo-3 mutants only when combined with dut-1 (RNAi). This further increase in Pvl incidence was independent of NTH-1. These results indicate that EXO-3 prevents developmental delay and Pvl in C. elegans, which are induced via DNA glycosylase-initiated checkpoint activation.

Background DNA damage is generated by various intrinsic and extrinsic sources such as reactive oxygen species (ROS) and environmental mutagens, and causes genomic alterations. DNA damage response (DDR) is activated to induce cell cycle arrest and DNA repair. Oxidation resistance 1 (OXR1) is a protein that defends cells against oxidative stress. We previously reported that OXR1 protein functions in the regulation of G2-phase cell cycle arrest in cells irradiated with gamma-rays, suggesting that OXR1 directly responds to DNA damage. Purpose To clarify the functions of OXR1 against ROS-independent DNA damage, HeLa and OXR1-depleted HeLa cells were treated with heavy-ion beams and the ROS-independent DNA-damaging agent methyl methanesulfonate (MMS). Results First, OXR1-depleted cells exhibited higher sensitivity to MMS and heavy-ion beams than control cells. Next, OXR1 depletion increased micronucleus formation and shortened the duration of G2-phase arrest after treatment with MMS or heavy-ion beams. These results suggest that OXR1 functions in the maintenance of cell survival and genome stability in response to DNA damage. Furthermore, the OXR1 protein level was increased by MMS and heavy-ion beams in HeLa cells. Conclusions Together with our previous study, the present study suggests that OXR1 plays an important role in the response to DNA damage, not only when DNA damage is generated by ROS.

The anticancer drug 5-fluorouracil (5-FU) and its metabolite 5-fluoro-2'-deoxyuridine (FUdR) inhibit thymidylate synthase and induce uracil bases in DNA. FUdR is commonly used for inhibiting fertility when measuring the lifespan of the nematode Caenorhabditis elegans. However, it is not known whether DNA damage induced by FUdR affects lifespan. EXO-3 is an apurinic/apyrimidinic endonuclease in C. elegans, and we reported previously that deletion of the exo-3 gene causes reproductive abnormalities and decreased lifespan. In this study, we found that FUdR extended the lifespan of exo-3 mutants. We measured the lifespan of multiple germline mutants to examine whether this lifespan extension effect was dependent on fertility. In the presence of a fem-1 mutation, which causes a deficiency in sperm production, FUdR did not extend the lifespan of the exo-3 mutant. In glp-1 mutants, which do not develop gonads, the exo-3 mutant was not short-lived, and FUdR did not extend its lifespan. These results suggest that the lifespan extension effect of FUdR depends on fertility and the presence of gonads. fem-3 mutants, which do not produce oocytes, had increased lifespan in the presence of FUdR, independent of the exo-3 mutation. It is possible that the fem-3 mutant was susceptible to the lifespan extension effect of FUdR. From these results, we suggest that FUdR affects the lifespan of C. elegans in two ways: by interfering with fertility, which extends lifespan, and by inducing DNA base damage, which reduces lifespan.

Introduction. Ataxia-telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response and is directly activated by reactive oxygen species (ROSs) in addition to DNA double-stranded breaks. However, the physiological function of the response to ROSs is not understood. Purpose. In the present study, we investigated how ATM responds to ROSs in Caenorhabditis elegans (C. elegans). Materials and Methods. First, we measured sensitivities of larvae to DNA-damaging agents and ROSs. Next, we analyzed the drug sensitivities of fully matured adult worms, which consist of nondividing somatic cells. Dead cell staining with acridine orange was performed to visualize the dead cells. In addition, we performed GFP reporter assays of lgg-1, an autophagy-related gene, to determine the types of cell death. Results. atm-1(tm5027) larvae showed a wide range of sensitivities to both DNA-damaging agents and ROSs. In contrast, fully matured adult worms, which consist of nondividing somatic cells, showed sensitivity to DNA-damaging agent, NaHSO3, but they showed resistance to H2O2. Dead cell staining and GFP reporter assays of lgg-1 suggest that C. elegans ATM-1 induces the cell death with autophagy in intestinal cells in response to H2O2. Conclusion. We revealed that ATM induces cell death in response to H2O2.

Apurinic/apyrimidinic (AP) sites are one of the most frequent DNA lesions. AP sites inhibit transcription and DNA replication, and induce cell death. AP endonucleases are key enzymes in AP site repair. Several types of AP endonucleases have been reported, such as AP endonuclease 2 (APEX2) and ribosomal protein P0 (P0). However, it is not known how the functions and roles differ among AP endonucleases. To clarify the difference of roles among AP endonucleases, we conducted biochemical analysis focused on APEX2 and P0 homologues in Ciona intestinalis. Amino acid sequence analysis suggested that CiAPEX2 and CiP0 are AP endonuclease homologues. Although we could not detect AP endonuclease or 3′-phosphodiesterase activity, these two purified proteins exhibited 3′-5′ exonuclease activity. This 3′-5′ exonuclease activity was sensitive to ethylenediaminetetraacetic acid (EDTA), and the efficiency of this activity was influenced by the 3′-terminus of substrate DNA. Both CiAPEX2 and CiP0 degraded not only a 5′-protruding DNA end, but also nicked DNA, which is generated through AP endonuclease 1 (APEX1) cleavage. These two genes partially complemented the growth rate of AP endonuclease-deficient Escherichia coli treated with hydrogen peroxide. These results indicate that 3′-5′ exonuclease activity is an evolutionarily conserved enzymatic activity of APEX2 and P0 homologues and this enzymatic activity may be important for AP endonucleases. Electronic supplementary material The online version of this article (10.1186/s41021-017-0087-7) contains supplementary material, which is available to authorized users.

Water content has a great influence on the rock mechanics properties. Four kinds of rock samples have been tested in the MTS Electro hydraulic Tri-axial Servo Test System. The result shows that with the increase of water content, the rock uniaxial compressive strength and elastic modulus value are declining. We get the fitting equation between water content and rock mechanical properties with four kind of rocks, provide a new basis for slope stability analysis and landslide prevention and control measures.

Bases on the project of typical natural coarse saline soil area ,Startis from the saline soil salt expansion characteristics of seven cycles of freeze-thaw cycling test and saline soil subgrade model test ,concluses not only the oil can make roadbed fillers for highway and first-class highway directily , but provides experiences for saline land area of natural coarse particles of high highway designs and construction engineering. Meanwhile, this paper also provides reference experiences for the design and construction of high level road engineering at natural coarse saline soil regions.

Apurinic/apyrimidinic (AP) sites are the major DNA damage generated continuously even under normal conditions, and inhibit DNA replication/transcription. AP endonucleases are ubiquitous enzymes required for the repair of AP sites and 3' blocking ends, but their physiological roles in multicellular organisms are not fully understood. In this study, we investigated how an AP endonuclease functions in a multicellular organism (Caenorhabditis elegans (C. elegans)). EXO-3 is one of the AP endonucleases in C. elegans. Using an exo-3 mutant worm, we found that deletion of the exo-3 gene caused shortened lifespan in an ung-1-dependent manner. UNG-1 is a uracil DNA glycosylase in C. elegans, and the present finding suggested that UNG-1 is the major producer of AP sites that affects lifespan, and EXO-3 contributes to longevity by completing the repair of uracil. Next we found that the exo-3 gene was abundantly expressed in the gonads, and AP sites in the gonad were efficiently repaired, suggesting that EXO-3 functioned particularly in the gonad. Deletion of the exo-3 gene resulted in a significant decrease in self-brood size. This was rescued by deficiency of NTH-1, which is a bifunctional DNA glycosylase in C. elegans that recognizes oxidative base damage. This result suggested that the major substrate of EXO-3 in the gonad was 3' blocking end generated by NTH-1, and that EXO-3 played an important role in reproduction. A contribution of EXO-3 to reproduction was also suggested by our finding here that the decrease of self-brood size of the exo-3 mutant became more marked when worms were treated with methyl methanesulfonate (MMS) and sodium bisulfite (NaHSO3). This study demonstrated differential roles of EXO-3 in somatic cells and germ cells.

High serum beta 2 glycoprotein I (β2GPI) is associated with complications of type 2 diabetes mellitus (DM), and especially microvascular disorders. In contrast, reduced β2GPI (Rβ2GPI) can prevent diabetic vascular injury. This study aimed to investigate the protective function of Rβ2GPI in DM vascular disorders, and to assess the under lying mechanisms. High glucose-induced injury in human umbilical vein endothelial cells (HUVECs) was used to model hyperglycemia. Alow concentration of Rβ2GPI (0.5 μM), but not β2GPI, mitigated high glucose-induced cell injury. High glucose decreased miR-21 expression and Akt phosphorylation at 6 h, but facilitated their expression at 48 h. Moreover, high glucose decreased phosphatase and tensin homolog deleted on chromosome ten(PTEN) expression at 6 h, but facilitatedits expression at 48 h. Importantly, by promoting miR-21 expression, Rβ2GPI mitigated high glucose-induced PTEN expression, reduced Akt phosphorylation and nitric oxide synthase activity, and increased cyclooxygenase-2 activity and cell loss. Similar to Rβ2GPI, an miR-21 mimic (1 pM) and PTEN inhibition (1 μM bpV, or PTEN silencing) exerted protective action, while an Akt signaling pathway inhibitor (LY294002, 1 μM) aborted the effect of Rβ2GPI on high glucose-induced cell injury. Finally, Rβ2GPI inhibited high glucose-induced apoptosis via a mitochondria-dependent pathway. These data reveal that Rβ2GPI exerts protective action in high glucose-induced HUVEC injury. The mechanism is related to the miR-21-PTEN-Akt pathway and mitochondria-dependent apoptosis. This study provides in vitro data supporting the therapeutic effect of Rβ2GPI in diabetic vascular injury.

The membranes of single-cell organisms are crucial as the first line of defense. The outer membrane of Gram-negative bacteria is an asymmetric bilayer in which lipopolysaccharides (LPSs) and phospholipids are localized in the outer and inner leaflet, respectively. This asymmetry is important for membrane integrity. In Escherichia coli , the Mla transport pathway maintains this asymmetry by removing phospholipids from the outer leaflet. The MlaD component of this system is a mammalian cell entry (MCE) domain protein, and E. coli has two other MCE domain proteins of unknown function (PqiB and YebT). Here, we show that these two proteins are components of novel transport pathways that contribute to membrane integrity. The pqiAB operon is regulated by SoxS and RpoS. The yebST operon contains pqiAB homologues. Here, we found a third member of the pqi operon, ymbA ( pqiC ). A PqiB-PqiC complex bridges the inner and the outer membrane, and in other bacteria, pqiBC genes are located in operons together with transporter proteins. We show here that simultaneous deletion of pqiABC and yebST operons in an Δ mla background rendered cells more sensitive to SDS-EDTA, and the SDS-EDTA sensitivity of mla mutants was rescued by additional copies of pqiABC . We also found that the yebST operon was induced by a defect in LPS molecules. In conclusion, PqiABC and YebST are novel transport pathways related to the Mla transport pathway and important for membrane integrity. IMPORTANCE Membranes of bacteria are crucial for stress resistance. The composition of the E. coli outer membrane is asymmetric, with asymmetry maintained by the Mla ABC transport pathway. We propose that the stress-inducible pqiABC operon and homologous yebST operon, both of previously unknown function, encode transport pathway proteins related to the Mla transport pathway. Deletion of these operons rendered cells more sensitive to membrane stress, and additional copies of pqiABC suppressed the SDS-EDTA sensitivity of mla mutant strains. We found that yebS′-′lacZ fusion was activated in mutant strains with defective LPS molecules.

Human oxidation resistance 1 (OXR1) functions in protection against oxidative damage and its homologs are highly conserved in eukaryotes examined so far, but its function still remains uncertain. In this study, we identified a homolog (LMD-3) of human OXR1 in the nematode Caenorhabditis elegans (C. elegans). The expressed LMD-3 was able to suppress the mutator phenotypes of E. coli mutMmutY and mutT mutants. Purified LMD-3 did not have enzymatic activity against 8-oxoG, superoxide dismutase (SOD), or catalase activities. Interestingly, the expression of LMD-3 was able to suppress the methyl viologen or menadione sodium bisulfite-induced expression of soxS and sodA genes in E. coli. The sensitivity of the C. elegans lmd-3 mutant to oxidative and heat stress was markedly higher than that of the wild-type strain N2. These results suggest that LMD-3 protects cells against oxidative stress. Furthermore, we found that the lifespan of the C. elegans lmd-3 mutant was significantly reduced compared with that of the N2, which was resulted from the acceleration of aging. We further examined the effects of deletions in other oxidative defense genes on the properties of the lmd-3 mutant. The deletion of sod-2 and sod-3, which are mitochondrial SODs, extended the lifespan of the lmd-3 mutant. These results indicate that, in cooperation with mitochondrial SODs, LMD-3 contributes to the protection against oxidative stress and aging in C. elegans.

To compare the efficacy and safety of adding liraglutide, saxagliptin and vildagliptin to current therapy in Chinese type 2 diabetes subjects with poor glycemic control.A 24-week, randomized, open-label, parallel clinical trial was performed. A total 178 patients completed the trial who had been randomly assigned to add-on once daily liraglutide (1.2 mg/day injected subcutaneously), to saxagliptin (5 mg once daily) or to vildagliptin (50 mg twice daily). Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.Over the 24-week treatment period, greater lowering of mean of HbA1c was achieved with 1.2 mg liraglutide (-1.50%, 95% CI [-1.67, -1.34]) than with saxagliptin (-1.23%, 95% CI [-1.36, -1.11]) and vildagliptin (-1.25%, 95% CI [-1.37, -1.13]). There was no significant between-group difference of percentages of subjects who reached a target HbA1c

Ecological environment material is a sort of material that is developed by human kind out of the active consideration of influences of the material on the ecological environment and is a new concept that was proposed on the precondition of taking full consideration of the correlations between the human kind, the society and the nature. Industrial design is supposed to lay more emphasis on functions of products and requirement of their appearance, to select more suitable materials, design their structure and pattern and establish their combination means. For the time being, study on the environment material has been penetrated into all fields of the industrial design. The environment material is of great advantage in terms of effective usage of resources and energy and reduction on the environmental capacity and it is an important development direction for realizing sustainable development of material industry. Thus, it has become a necessary trend of development of the design industry to conduct green design under the attack of the global tide of environmental protection.

Adipocyte fatty acid-binding protein (A-FABP) has been recognized as an important player in macrophage cholesterol trafficking and inflammation, and may promote the development of atherosclerosis. To further elucidate the role of A-FABP in atherosclerosis in diabetes, we investigated the relationship between serum A-FABP concentrations and peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM).In all, 488 inpatients with T2DM were enrolled in the study (254 men, 234 women; mean (±SD) age 57.3 ± 13.0 years). The severity of peripheral arterial stenosis was assessed by ultrasound examination. Serum A-FABP concentrations were determined by ELISA.Serum A-FABP concentrations were significantly higher in patients with than without PAD (8.0 ± 3.3 vs 6.2 ± 1.6 ng/mL, respectively; P 0.05). Interestingly, there was an obvious gender-related difference in PAD patients with T2DM, with the stenosis rate being higher for female than male T2DM patients in the third A-FABP tertile. Logistic regression analysis revealed that serum A-FABP concentrations were an independent risk factor for PAD in female T2DM patients (odds ratio 1.890, 95% confidence interval 1.041-3.432; P = 0.036), but not in male T2DM patients. Correlation analyses revealed that A-FABP concentrations were correlated with body mass index (BMI), diastolic blood pressure, urinary microalbumin, and serum creatinine in male patients, and with BMI, duration of T2DM, fasting blood glucose, and serum creatinine in female patients.Serum A-FABP concentrations are closely associated with PAD in Chinese women with T2DM. The study findings suggest that A-FABP may be a more specific marker of PAD in diabetic women than men.

Nowadays, under the great background of increasingly fierce competition and more refined social division of labor, there are more advantages for the furniture enterprises to resort to the third party logistics. In order to improve the development level of the third party logistics, furniture enterprises should provide macro guarantee, determine correct logistics ideas, set up professional third party furniture logistics enterprises, and select appropriate third party logistics mode.

Network marketing is developed on the basis of application and development of modern electronic technology and communication technology. Compared with the traditional furniture marketing, it has obvious advantages in several aspects. Furniture enterprises should take a close grasp of this opportunity, enlarge investment in resources of network marketing, make full use of this sort of modernized marketing mode and better serve the business goal of furniture enterprises.

Salt expansion deformation of the saline soil is a common form of the roadbed disease in Saline Soil Area. Salt expansion of saline soil refers to volume expansion by the impact of periodic climate changes in nature. Particle distribution characteristics, compaction characteristics, salt composition and salinity and so on are studied to evaluate the basic engineering properties of saline soil in the location of the project. Seven freeze-thaw cycles test and (no) load single-cooling test are designed to clarify the relation between salt expansion and temperature changes, moisture content, overburden pressure. The results provide design and construction experiences for high-grade highway projects in natural coarse saline soil area.

E. coli YdbK is predicted to be a pyruvate:flavodoxin oxidoreductase (PFOR). However, enzymatic activity and the regulation of gene expression of it are not well understood. In this study, we found that E. coli cells overexpressing the ydbK gene had enhanced PFOR activity, indicating the product of ydbK to be a PFOR. The PFOR was labile to oxygen. The expression of ydbK was induced by superoxide generators such as methyl viologen (MV) in a SoxS-dependent manner after a lag period. We identified a critical element upstream of ydbK gene required for the induction by MV and proved direct binding of SoxS to the element. E. coli ydbK mutant was highly sensitive to MV, which was enhanced by additional inactivation of fpr gene encoding ferredoxin (flavodoxin):NADP(H) reductase (FPR). Aconitase activity, a superoxide sensor, was more extensively decreased by MV in the E. coli ydbK mutant than in wild-type strain. The induction level of soxS gene was higher in E. coli ydbK fpr double mutant than in wild-type strain. These results indicate that YdbK helps to protect cells from oxidative stress. It is possible that YdbK maintains the cellular redox state together with FPR and is involved in the reduction of oxidized proteins including SoxR in the late stages of the oxidative stress response in E. coli.

Modern technological innovation model of furniture enterprises mainly includes imitative innovation model, cooperative innovation model and independent innovation model. Furniture enterprises face a variety of technological innovation uncertainties, with the uncertainty management and risk management technology, innovators are able to recognize the uncertainties of technological innovation to achieve the transformation from the probability of unknown uncertainty to the probability of known uncertainty, as well as the transformation from uncertainty to certainty, this is beneficial to the furniture enterprises to improve the efficiency of technological innovation and the implementation of the innovation strategy.

Reduced β2 glycoprotein I (β2GPI) has been demonstrated to exhibit a beneficial effect in diabetic atherosclerosis and retinal neovascularization. However, the effect of reduced β2GPI on vascular disorders in diabetic mellitus (DM) remains to be elucidated. The present study established a high glucose‑induced injury model using human umbilical cords veins (HUVECs) and evaluated the protective effects of reduced β2GPI against the injury. The data demonstrated that a low concentration of reduced β2GPI (0.5 µM) mitigated high glucose‑induced cell loss, decreased nitric oxide (NO) production and resulted in calcium overloading. Mechanically, reduced β2GPI additionally reversed high glucose‑induced phosphatase and tensin homolog (PTEN) accumulation, decrease of protein kinase B phosphorylation and nitric oxide synthase activity, and increase of cyclooxygenase‑2 activity. It was further confirmed that PTEN inhibitor‑bpV (1 µM) exhibited similar effects to those resulting from reduced β2GPI. Overall, the data revealed that reduced β2GPI exerts protective effects from glucose‑induced injury in HUVECs, potentially via decreasing PTEN levels. The present study suggests reduced β2GPI may act as a novel therapeutic strategy for the treatment of vascular disorders in DM.

The anticancer drug 5-fluorouracil (5-FU) and its metabolite 5-fluoro-2'-deoxyuridine (FUdR) inhibit thymidylate synthase and induce uracil bases in DNA. FUdR is commonly used for inhibiting fertility when measuring the lifespan of the nematode Caenorhabditis elegans. However, it is not known whether DNA damage induced by FUdR affects lifespan. EXO-3 is an apurinic/apyrimidinic endonuclease in C. elegans, and we reported previously that deletion of the exo-3 gene causes reproductive abnormalities and decreased lifespan. In this study, we found that FUdR extended the lifespan of exo-3 mutants. We measured the lifespan of multiple germline mutants to examine whether this lifespan extension effect was dependent on fertility. In the presence of a fem-1 mutation, which causes a deficiency in sperm production, FUdR did not extend the lifespan of the exo-3 mutant. In glp-1 mutants, which do not develop gonads, the exo-3 mutant was not short-lived, and FUdR did not extend its lifespan. These results suggest that the lifespan extension effect of FUdR depends on fertility and the presence of gonads. fem-3 mutants, which do not produce oocytes, had increased lifespan in the presence of FUdR, independent of the exo-3 mutation. It is possible that the fem-3 mutant was susceptible to the lifespan extension effect of FUdR. From these results, we suggest that FUdR affects the lifespan of C. elegans in two ways: by interfering with fertility, which extends lifespan, and by inducing DNA base damage, which reduces lifespan.

Base excision repair (BER), responsible for the removal of altered DNA bases, is accomplished via two pathways that involve different subsets of repair enzymes and result in removal and replacement of one (short-patch BER) or several (long-patch BER) nucleotides. In this study, we constructed single-lesion containing DNA substrates that are predominantly repaired via one of the two pathways and investigated the fidelity of pathway specific repair in human whole cell extracts. We find that a single nucleotide deletion generated during addition of the first nucleotide into the repair gap is the major mutation characteristic for both pathways. This data suggest that for both BER pathways, mutations generated during repair in human whole cell extracts are principally the result of a slippage of DNA polymerase during initiation of repair synthesis.

DNA polymerase beta (Pol beta) is important for the base excision repair (BER) pathway. Overexpression of Pol beta is frequently found in cancer cells and is thought to be associated with tumorigenesis. In this study, we examined BER fidelity in extracts derived from a human lymphoblastoid cell line that over expresses Pol beta compared to normal control cells. Using an in vitro mutagenesis assay, we found an increased rate of frameshift mutations arising during DNA repair in whole-cell extracts derived from the Pol beta-overexpressing cells. We demonstrate that the addition of excess Pol beta to a control cell extract enhances the mutagenic potential of the extract. Furthermore, using cell extracts and purified Pol beta, we demonstrate that the mechanism of frameshift formation involves slippage of Pol beta during the one-nucleotide gap-filling step of BER and that this slippage is fixed by strand-displacement synthesis stimulated by an excess of Pol beta.

In mammalian cells, base excision repair (BER) is the major repair pathway involved in the removal of non-bulky damaged nucleotides. The fidelity of BER is dependent on the polymerization step, where the major BER DNA polymerase (Pol beta) must incorporate the correct Watson-Crick base paired nucleotide into the one nucleotide repair gap. Recent studies have indicated that expression of some Pol beta variants or changes in expression of wild-type Pol beta protein, frequently found in cancer cells, can lead to DNA repair synthesis errors and confers to cells a mutator phenotype.

As a new type of building material, bamboo flooring has been recognized in the market and becomes an ideal material in indoor decoration and refurbishing. The common quality problems of bamboo flooring mainly include the three problems of floor material quality, floor processing quality and decoration and refurbishing quality.

Oxidatively damaged bases in DNA can cause cell death, mutation and/or cancer induction. To overcome such deleterious effects of DNA base oxidation, cells are equipped with base excision repair (BER) initiated by DNA glycosylases. Endonuclease III (Nth), a major DNA glycosylase, mainly excises oxidatively damaged pyrimidines from DNA. The aims of this study were to obtain an overview of the repair mechanism of oxidatively damaged bases and to elucidate the function of BER in maintaining genome stability during embryogenesis and development. In this study, we used the ascidian Ciona intestinalis because at every developmental stage it is possible to observe the phenotype of individuals with DNA damage or mutations. Sequence alignment analysis revealed that the amino acid sequence of Ciona intestinalis Nth homologue (CiNTH) had high homology with those of Escherichia coli, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans and human Nth homologues. It was evident that two domains, the Helix-hairpin-Helix and 4Fe-4S cluster domains that are critical regions for the Nth activity, are well conserved in CiNTH. CiNTH efficiently complemented the sensitivity of E. coli nth nei mutant to H(2)O(2). CiNTH was bifunctional, with DNA glycosylase and AP lyase activities. It removed thymine glycol, 5-formyluracil and 8-oxoguanine paired with G from DNA via a β-elimination reaction. Interestingly, the N-terminal 44 amino acids were essential for the DNA glycosylase activity of CiNTH.

Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable HeLa cell lines overexpressing SOD2, HeLa S3/SOD2 and T-REx HeLa/SOD2, to elucidate the mechanisms underlying the protection against radiation by SOD2. SOD2 overexpression in mitochondria enhanced the survival of HeLa S3 and T-REx HeLa cells following γ-irradiation. The levels of γH2AX significantly decreased in HeLa S3/SOD2 and T-REx HeLa/SOD2 cells compared with those in the control cells. MitoSoxTM Red assays showed that both lines of SOD2-expressing cells showed suppression of the superoxide generation in mitochondria. Furthermore, flow cytometry with a fluorescent probe (2', 7'-dichlorofluorescein) revealed that the cellular levels of ROS increased in HeLa S3 cells during post-irradiation incubation, but the increase was markedly attenuated in HeLa S3/SOD2 cells. DNA microarray analysis revealed that, of 47, 000 probe sets analyzed, 117 and 166 probes showed more than 2-fold changes after 5.5 Gy of γ-irradiation in control and HeLa S3/SOD2 cells, respectively. Pathway analysis revealed different expression profiles in irradiated control cells and irradiated SOD2-overexpressing cells. These results indicate that SOD2 protects HeLa cells against cellular effects of γ-rays through suppressing oxidative stress in irradiated cells caused by ROS generated in the mitochondria and through regulating the expression of genes which play a critical role in protection against ionizing radiation.