Marker Of Oxidative DNA Damage Research Articles

LBSUN85 Acipimox Normalizes The Cardiac Phenotype Induced By Electronic Cigarettes

Abstract Electronic nicotine delivery systems or electronic cigarettes (e-cigarettes) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both among smokers and people who have never smoked. Nicotine can induce lipolysis in adipose tissue, leading to increased serum free fatty acids (FFAs). Increased levels of FFAs are one of the key elements in generating a pro-inflammatory response and lead to ectopic lipid accumulation, lipotoxicity, mitochondrial dysfunction, and DNA damage. Our laboratory has shown that e-cigarettes induce cardiac dysfunction associated with oxidative stress and inflammatory phenotype. We investigated the effects of acipimox, an antihyperlipidemic drug that blocks lipolysis, on e-cigarettes-induced cardiac dysfunction and its associated inflammatory signals and oxidative stress. C57BL/6J wild type mice on high fat diet were exposed to saline, e-cigarette with nicotine (2.4%), e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction was decreased in mice exposed to e-cigarette (2.4%) compared with saline and acipimox. Therefore, acipimox normalized the e-cigarette-induced cardiac dysfunction. Transcriptomic evaluation with Gene Set Enrichment Analysis revealed that e-cigarette treated mice had genes enriched in the G2/M DNA damage checkpoint pathways. These transcriptomic changes were normalized by acipimox. Mice exposed to e-cigarettes had increased circulating levels of M-CSF, IL-6, and FFAs, which were decreased by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1, a marker of oxidative stress. Additionally, treatment with e-cigarette (2.4%) increased the apurinic/apyrimidinic sites. This marker of oxidative DNA damage was normalized by acipimox. Understanding the consequences of e-cigarette use on the cardiovascular system is directly relevant to developing policies related to e-cigarette use. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Modulation of biomarkers associated with risk of cancer in humans by olive oil intake: A systematic review

This systematic review summarized the role of olive oil intake in modulation of cancer risk biomarkers in healthy adults. A total of four randomized clinical trials with crossover design were included with intervention periods ranging from three to eight weeks, none of them at high risk of bias. meta-analysis was not performed because the studies were heterogeneous. Results showed that continuous olive oil intake was associated with the reduction of oxidized DNA bases, IL-8, TNF-α, and 8-OH deoxyguanosine, but did not affect ethene-DNA adducts. In summary, this study showed a potential role of olive oil intake by healthy individuals for prevention and repair of cancer-related DNA damage, through lower levels of markers of oxidative DNA damage and inflammation. High levels of these molecules are present and linked with tumor initiation and other carcinogenesis-related events. Therefore, olive oil is a promising agent for cancer risk reduction. To make this association robust, more intervention studies are needed, especially high-quality randomized controlled trials evaluating similar biomarkers over longer periods of time.

Markers of cytotoxicity and oxidative DNA damage in Diabesity: A new age illness.

The oral mucous membrane is particularly sensitive to certain types of systemic disorders such as anemia, vitamin deficiencies, infectious diseases, hormonal disturbances and can be objectively reproduced through definite measurements using cytomorphometry. The objective of the study is to evaluate the quantitative and qualitative changes in cytological buccal smears of obese individuals with type II diabetes (Group 1 = 20), obese individuals without type II diabetes (Group 2 = 20), individuals with type II diabetes without obesity (Group 3 = 20) by comparing with controls (individuals without obesity and without type II diabetes) (Group 4 = 20). Buccal mucosal cells were scraped from study participants and were subjected to morphometric analysis (Magnus Pro software). Clinical history, hemoglobin A1c, heights and weights of participants were measured and consequently, their body mass index was calculated. Quantitative parameters (nuclear area, cytoplasmic area, nucleo-cytoplasmic ratio) and qualitative parameters (micronuclei [MN], nuclear budding, nuclear disintegration, apoptosis, necrosis) were assessed among the groups. The data were statistically interpreted using SPSS software version 20.0. There is an increase in nuclear diameter and nuclear: cytoplasmic ratio of Groups 1 and 3 relative to Group 2. The qualitative assessment revealed MN and nuclear disintegration in Group 1 and 3 individuals. In addition, other qualitative changes such as nuclear budding and apoptotic bodies were evident in patients with type II diabetes. The aforementioned qualitative and quantitative parameters facilitate early diagnosis and identification of individuals at risk of developing new age systemic illnesses such as diabetes and obesity.

Oxidative Stress and DNA Damage Markers in Colorectal Cancer.

Oxidative stress (OS) and inflammation are known to play an important role in chronic diseases, including cancer, and specifically colorectal cancer (CRC). The main objective of this study was to explore the diagnostic potential of OS markers in patients with CRC, which may translate into an early diagnosis of the disease. To do this, we compared results with those in a group of healthy controls and assessed whether there were significant differences. In addition, we explored possible correlations with the presence of tumors and tumor stage, with anemia and with inflammatory markers used in clinical practice. The study included 80 patients with CRC and 60 healthy controls. The following OS markers were analyzed: catalase (CAT), reduced glutathione (GSH) and oxidized glutathione (GSSG) in serum; and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and F2-isoprotanes in urine (F2-IsoPs). Tumor markers (CEA and CA 19.9), anemia markers (hemoglobin, hematocrit and medium corpuscular volume) and inflammatory markers (leukocytes, neutrophils, N/L index, platelets, fibrinogen, C-reactive protein, CRP and IL-6) were also determined. Comparison of means between patients and controls revealed highly significant differences for all OS markers, with an increase in the prooxidant markers GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and a decrease in the antioxidant markers CAT and GSH. Tumor and inflammatory markers (except CRP) correlated positively with GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and negatively with CAT and GSH. In view of the results obtained, OS markers may constitute a useful tool for the early diagnosis of CRC patients.

Development of l-Dopa-containing diketopiperazines as blood-brain barrier shuttle

In our overall goal to develop anti-Parkinson drugs, we designed novel diketopiperazines (DKP1-6) aiming to both reach the blood-brain barrier and counteract the oxidative stress related to Parkinson's Disease (PD).The anti-Parkinson properties of DKP 1–6 were evaluated using neurotoxin-treated PC12 cells, as in vitro model of PD, while their cytotoxicity and genotoxicity potentials were investigated in newborn rat cerebral cortex (RCC) and primary human whole blood (PHWB) cell cultures. The response against free radicals was evaluated by the total antioxidant capacity (TAC) assay. Comet assay was used to detect DNA damage while the content of 8-hydroxyl-2′-deoxyguanosine (8-OH-dG) was determined as a marker of oxidative DNA damage. PAMPA-BBB and Caco-2 assays were employed to evaluate the capability of DKP1-6 to cross the membranes. Stability studies were conducted in simulated gastric and intestinal fluids and human plasma.Results showed that DKP5-6 attenuate the MPP + -induced cell death on a nanomolar scale, but a remarkable effect was observed for DKP6 on Nrf2 activation that leads to the expression of genes involved in oxidative stress response thus increasing glutathione biosynthesis and ROS buffering. DKP5-6 resulted in no toxicity for RCC neurons and PHWB cells exposed to 10–500 nM concentrations during 24 h as determined by MTT and LDH assays and TAC levels were not altered in both cultured cell types. No significant difference in the induction of DNA damage was observed for DKP5-6. Both DKPs resulted stable in simulated gastric fluids (t1/2 > 22h). In simulated intestinal fluids, DKP5 underwent immediate hydrolysis while DKP6 showed a half-life higher than 3 h. In human plasma, DKP6 resulted quite stable. DKP6 displayed both high BBB and Caco-2 permeability confirming that the DKP scaffold represents a useful tool to improve the crossing of drugs through the biological membranes.

Molineria recurvata Ameliorates Streptozotocin-Induced Diabetic Nephropathy through Antioxidant and Anti-Inflammatory Pathways

Molineria recurvata (MR) has been traditionally used to manage diabetes mellitus in India. However, the molecular mechanism of MR on the diabetic-induced nephropathy has not been clearly investigated. Thus, this study investigates the protective effects of the MR extract on nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was instigated by a single intraperitoneal injection of STZ (45 mg/kg) in male Sprague-Dawley rats. Once the diabetes was successfully induced, the MR extract (200 mg/kg/day) or metformin (200 mg/kg/day) was orally administered for 14 days. Renal function, morphology changes and levels of inflammatory cytokines were measured. Blood glucose concentrations were considerably reduced in STZ-induced diabetic rats following treatment with the MR extract. The administration of the MR extract substantially restored the abnormal quantity of the oxidative DNA damage marker 8-hydroxy-2′-deoxy-guanosine (8-OHdG), malondialdehyde, glutathione, oxidized glutathione, superoxide dismutase, catalase, interleukin (IL)-1β, IL-6, IL-10, and transforming growth factor-β (TGF-β). The urinary excretion of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), selenium binding protein 1 (SBP1), and pyruvate kinase M2 (PKM2) was significantly reduced in diabetes rats after administration of the MR extracts. In the kidneys of STZ-induced diabetic rats, the MR extracts markedly downregulated the expression of fibronectin, collagen-1, and α-smooth muscle actin (α-SMA). In particular, the MR extracts markedly increased the level of SIRT1 and SIRT3 and reduced claudin-1 in the kidney. These results suggest that the MR extracts exhibits therapeutic activity in contrast to renal injury in STZ-induced diabetic rats through repressing inflammation and oxidative stress.

Non-Invasive Skin Imaging Assessment of Human Stress During Head-Down Bed Rest Using a Portable Handheld Two-Photon Microscope.

Spaceflight presents a series of physiological and pathological challenges to astronauts resulting from ionizing radiation, microgravity, isolation, and other spaceflight hazards. These risks cause a series of aging-related diseases associated with increased oxidative stress and mitochondria dysfunction. The skin contains many autofluorescent substances, such as nicotinamide adenine dinucleotide phosphate (NAD(P)H), keratin, melanin, elastin, and collagen, which reflect physiological and pathological changes in vivo. In this study, we used a portable handheld two-photon microscope to conduct high-resolution in vivo skin imaging on volunteers during 15 days of head-down bed rest. The two-photon microscope, equipped with a flexible handheld scanning head, was used to measure two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) images of the left forearm, left front chest, and forehead of volunteers. Changes in TPEF, SHG, and the extended SHG-to-AF(TPEF) aging index of the dermis (SAAID) were measured. It was found that TPEF intensity increased during bed rest and was restored to normal levels after recovery. Meanwhile, SHG increased slightly during bed rest, and the skin aging index increased. Moreover, we found the skin TPEF signals of the left forearm were significantly negatively associated with the oxidative stress marker malondialdehyde (MDA) and DNA damage marker 8-hydroxy-2′-desoxyguanosine (8-OHdG) values of subjects during head-down bed rest. Meanwhile, the SHG signals were also significantly negatively correlated with MDA and 8-OHDG. A significant negative correlation between the extended SAAID of the left chest and serum antioxidant superoxide dismutase (SOD) levels was also found. These results demonstrate that skin autofluorescence signals can reflect changes in human oxidant status. This study provides evidence for in-orbit monitoring of changes in human stress using a portable handheld two-photon microscope for skin imaging.

HIV Promotes Neurocognitive Impairment by Damaging the Hippocampal Microvessels.

Current evidence suggests that mild cerebrovascular changes could induce neurodegeneration and contribute to HIV-associated neurocognitive disease (HAND) in HIV patients. We investigated both the quantitative and qualitative impact of HIV infection on brain microvessels, especially on hippocampal microvessels, which are crucial for optimal O2 supply, and thus for maintaining memory and cognitive abilities. The results obtained using cultured human brain microvascular endothelial cells (HBMEC) were reproduced using a suitable mouse model and autopsied human HIV hippocampus. In HBMEC, we found significantly higher oxidative stress-dependent apoptotic cell loss following 5h of treatment of GST-Tat (1µg/ml) compared to GST (1µg/ml) control. We noticed complete recovery of HBMEC cells after 24h of GST-Tat treatment, due to temporal degradation or inactivation of GST-Tat. Interestingly, we found a sustained increase in mitochondrial oxidative DNA damage marker 8-OHdG, as well as an increase in hypoxia-inducible factor hypoxia-inducible factor-1α (HIF-1α). In our mouse studies, upon short-term injection of GST-Tat, we found the loss of small microvessels (mostly capillaries) and vascular endothelial growth factor (VEGF), but not large microvessels (arterioles and venules) in the hippocampus. In addition to capillary loss, in the post-mortem HIV-infected human hippocampus, we observed large microvessels with increased wall cells and perivascular tissue degeneration. Together, our data show a crucial role of Tat in inducing HIF-1α-dependent inhibition of mitochondrial transcriptional factor A (TFAM) and dilated perivascular space. Thus, our results further define the underlying molecular mechanism promoting mild cerebrovascular disease, neuropathy, and HAND pathogenesis in HIV patients.

The Evaluation of Thiol/Disulfide Homeostasis and Oxidative DNA Damage in Patients with Obsessive Compulsive Disorder.

ObjectiveIn this study, we aimed to examine thiol/disulfide homeostasis and oxidative DNA damage in patients with OCD and compare them with healthy controls.MethodsThirty-five patients previously diagnosed with OCD in Van Yuzuncu Yil University Department of Psychiatry and thirty-three healthy volunteers were included in the study. The severity of the symptoms was measured using the Yale-Brown Obsessive-Compulsive Scale. Five μL of blood samples were taken from the patient and control groups. The samples were stored at appropriate conditions until use. Leukocyte DNA was isolated and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and deoxyguanosine were detected to assess the oxidative DNA damage. The level of oxidative DNA damage was expressed as 8-OHdG/106dG. Total thiol/native thiol levels were measured for thiol/disulfide homeostasis. The level of disulfide was determined by subtracting the native thiol value from the total thiol value and the result was divided by two. Results were given as percentages.ResultsThe total and native thiol levels in patients with OCD were significantly lower, and the disulfide levels were significantly higher in patients with OCD than healthy control subjects. In addition, 8-OHdG, an indicator of DNA damage, was significantly lower in the control group compared to the patient group.ConclusionIncreased levels of disulfide/native thiol and disulfide/total thiol in patients with OCD show that levels of oxidative stress were elevated and therefore, higher 8-OHdG levels in patients with OCD is a marker of oxidative DNA damage.

OGG1 in Lung-More than Base Excision Repair.

As the organ executing gas exchange and directly facing the external environment, the lungs are challenged continuously by various stimuli, causing the disequilibration of redox homeostasis and leading to pulmonary diseases. The breakdown of oxidants/antioxidants system happens when the overproduction of free radicals results in an excess over the limitation of cleaning capability, which could lead to the oxidative modification of macromolecules including nucleic acids. The most common type of oxidative base, 8-oxoG, is considered the marker of DNA oxidative damage. The appearance of 8-oxoG could lead to base mismatch and its accumulation might end up as tumorigenesis. The base 8-oxoG was corrected by base excision repair initiated by 8-oxoguanine DNA glycosylase-1 (OGG1), which recognizes 8-oxoG from the genome and excises it from the DNA double strand, generating an AP site for further processing. Aside from its function in DNA damage repairment, it has been reported that OGG1 takes part in the regulation of gene expression, derived from its DNA binding characteristic, and showed impacts on inflammation. Researchers believe that OGG1 could be the potential therapy target for relative disease. This review intends to make an overall summary of the mechanism through which OGG1 regulates gene expression and the role of OGG1 in pulmonary diseases.

Protective effect of Tulbaghia violacea extract on cardiac damage: deep circulatory arrest rat model

Objectives: Total circulatory arrest (TCA) technique is a method used in cardiac surgery accompanied by cardiopulmonary bypass (CPB). It has been shown that Tulbaghia violacea extract increases antioxidant capacity, regulates blood pressure, decreases lipid peroxide, and reduces atherosclerosis. In this experimental study, we aimed to investigate the effect of T. violacea extract administration on serum oxidative stress parameters (Total antioxidant status [TAS], total oxidant status [TOS] and oxidative stress index [OSI] and deoxyribonucleic acid [DNA] damage level with 8-Hydroxy-2-Deoxyguanosine [8-OHdG]) and histopathological changes in the heart and other organs in rats with deep circulatory arrest model. Methods: In this study, 48 Wistar Albino adult rats, 24 female and 24 male, obtained from Harran University Experimental Animals Research Center were used. The average weight of female rats was 250-300 g, and the average weight of male rats was 450-500 g. These rats were randomly divided into four groups. 6 male and 6 female rats were used in each group (Group 1 = Sham, Group 2 = Injury, Group 3 = Treatment and Injury, Group 4 = Treatment). Results: As a result of this experimental study, the changes in the biochemical 8-OHdG, TOS, OSI and TAS levels of the groups were found to be statistically significant (p < 0.001). In the subgroup analyzes of the data, 8-OHdG level, which is an oxidative DNA damage marker in Group 2 was higher than the Group 1, Group 3 and Group 4 and there was a statistically significant difference (p < 0.001, p = 0.027 and p < 0.001; respectively). The TOS level of the injury group was higher than Group 1, Group 3 and Group 4 and there was a statistically significant difference (p < 0.001, p = 0.003 and p < 0.001; respectively). Conclusions: As a result of our study, we revealed that T. violacea extract has a protective effect on organ and tissue damage in the TCA model.

Oxidative stress of glyphosate, AMPA and metabolites of pyrethroids and chlorpyrifos pesticides among primary school children in Cyprus

BackgroundExposure to various pesticides, such as pyrethroids and chlorpyrifos, has been previously associated with adverse effects on children's health. Scientific evidence on the human toxicity of glyphosate (GLY) and its primary metabolite, aminomethylphosphonic acid (AMPA) is limited, particularly for children. This study aimed to i) assess the exposure determinants of the studied pesticides measured in children in Cyprus, and ii) determine the association between the urinary pesticides and the biomarkers of DNA and lipid oxidative damage. MethodsA children's health study was set up in Cyprus (ORGANIKO study) by aligning it with the methodology and tools used in the European Human Biomonitoring Initiative (HBM4EU). Urinary GLY and AMPA, pyrethroid metabolites and the chlorpyrifos metabolite TCPy were measured in 177 children aged 10–11 years old, using mass spectrometry. Oxidative stress was assessed with 8-iso-prostaglandin F2a (8-iso-PGF2α) as a marker of lipid damage and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a DNA oxidative damage marker, both measured with immunoassays. Questionnaires about demographic characteristics, pesticide usage, and dietary habits were filled out by the parents. Μultivariable regression models examined associations between pesticides and biomarkers of effect using two creatinine adjustments (cr1: adding it as covariate and cr2: biomarkers of exposure and effect were creatinine-adjusted). ResultsParental educational level was a significant predictor of urinary pyrethroids but not for GLY/AMPA. Median [interquartile range, IQR] values for GLY and AMPA were <LOQ [<LOQ, 0.19] μg/L and 0.18 [0.10, 0.29] μg/L, respectively, while a moderate correlation was shown between GLY and AMPA (r = 0.45). 8-OHdG was positively associated with AMPA (beta = 0.17; 95% CI: 0.02, 0.31, p = 0.03 cr2, and beta = 0.12; 95% CI: 0.0,0.24, p = 0.06, cr1), albeit not with GLY (p > 0.05). Similar significant associations with 8-OHdG were shown for a pyrethroid metabolite (3-PBA) and the chlorpyrifos metabolite (TCPy). No associations were observed between the aforementioned pesticides and 8-iso-PGF2α (p > 0.05). ConclusionsThis is the first children's health dataset demonstrating the association between AMPA and DNA oxidative damage, globally. More data is needed to replicate the observed trends in other children's populations around the globe.

Neuroprotective effects of carvacrol against cadmium-induced neurotoxicity in rats: role of oxidative stress, inflammation and apoptosis.

Cadmium (Cd), is a heavy metal reported to be associated with oxidative stress and inflammation. In this paper, we investigated the possible protective effects of carvacrol against Cd-induced neurotoxicity in rats. Adult male Sprague Dawley rats were treated orally with Cd (25mg/kg body weight) and with carvacrol (25 and 50mg/kg body weight) for 7 days. Carvacrol decreased the levels of malondialdehyde (MDA), glial fibrillary acidic protein (GFAP) and monoamine oxidase (MAO), and significantly increased the levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in brain tissue. Additionally, carvacrol alleviated the in levels of inflammation and apoptosis related proteins involving p38 mitogen-activated protein kinase (p38 MAPK), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), B-cell lymphoma-3 (Bcl-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), prostaglandin E2 (PGE2), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), cysteine aspartate specific protease-3 (caspase-3) and Bcl-2 associated X protein (Bax) in the Cd-induced neurotoxicity. Carvacrol also decreased the mRNA expression of matrix metalloproteinases (MMP9 and MMP13), as well as 8-hydroxy-2'-deoxyguanosine (8 - OHdG) level, a marker of oxidative DNA damage. Collectively, our findings indicated that carvacrol has a beneficial effect in ameliorating the Cd-induced neurotoxicity in the brain of rats.

Placental lesions and differential expression of pro-and anti-angiogenic growth mediators and oxidative DNA damage marker in placentae of Ghanaian suboptimal and optimal health status pregnant women who later developed preeclampsia.

BackgroundAngiogenic growth mediators (AGMs) and oxidative stress (OS) both play essential roles in normal placental vascular development and as such, placental alterations in these factors contribute to pre-eclampsia (PE). Suboptimal health status (SHS), an intermediate between health and disease, has been associated with imbalanced AGMs and OS biomarkers. Thus, SHS pregnant women may be at increased risk of developing PE and may present abnormal placental alteration and expression of AGMs and OS compared to optimal health status (OHS) pregnant women. We examined the histopathological morphology, immunohistochemical expression of AGMs antibodies and oxidative DNA damage marker in the placentae of SHS and OHS pregnant women who developed early-onset PE (EO-PE) and late-onset (LO-PE) compared to normotensive pregnancy (NTN-P).MethodsThis nested case-control study recruited 593 singleton normotensive pregnant women at baseline (10–20 weeks gestation) from the Ghanaian Suboptimal Health Status Cohort Study (GHOACS) undertaken at the Komfo Anokye Teaching Hospital, Ghana. Socio-demographic, clinical and obstetrics data were collected, and a validated SHS questionnaire-25 (SHSQ-25) was used in classifying participants into SHS (n = 297) and OHS (n = 296). Participants were followed until the time of PE diagnosis and delivery (32–42 weeks gestation). Blood samples were collected at the two-time points and were assayed for AGMs; soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PIGF), vascular endothelial growth factor-A (VEGF-A), and soluble endoglin (sEng), and OS biomarkers; 8-hydroxydeoxyguanosine (8-OHdG), 8-epiprostaglandinF2-alpha (8- epi-PGF2α) and total antioxidant capacity (TAC) using ELISA. Placental samples were collected for histopathological and immunohistochemical analysis.ResultsOf the 593 pregnant women, 498 comprising 248 SHS and 250 OHS women returned for delivery and were included in the final analysis. Of the 248 SHS women, 56, 97 and 95 developed EO-PE, LO-PE and NTN-P, respectively, whereas 14, 30 and 206 of the 250 OHS mothers developed EO-PE, LO-PE and NTN-P, respectively. At baseline, SHS_NTN pregnant women had a significant imbalance in AGMs and OS biomarkers compared to OHS_NTN pregnant women (p<0.0001). At the time of PE diagnosis, SHS_NTN-P women who developed EO-PE, LO-PE, and NTN-P had lower serum levels of P1GF, VEGF-A and TAC and correspondingly higher levels of sEng, sFlt-1, 8-epiPGF2α, and 8-OHdG than OHS-NTN-P women who developed EO-PE and LO-PE, NTN-P (p<0.0001). A reduced placental size, increased foetal/placental weight ratio, and a significantly higher proportion of fibrinoid necrosis, infarction, villous fibrin, syncytial knots, calcification, chorangiosis, tunica media/vascular wall hypertrophy and chorioamnionitis was associated with the SHS group who developed PE (EO-PE>LO-PE) more than OHS groups who developed PE (EO-PE>LO-PE) when all were compared to NTN-P (p<0.0001). The intensity of antibody expression of PIGF and VEGF-A were significantly reduced, whereas Flt-1, Eng and 8-OHdG were significantly increased in placentae from SHS-pregnant women who developed EO-PE>LO-PE more than OHS- pregnant women who developed EO-PE>LO-PE when all were compared to NTN-P (p<0.0001).ConclusionIncreased lesions, oxidative DNA damage, and imbalanced expression between pro-and anti-AGMs are associated more with SHS-embodied PE placentae rather than OHS-embodied PE subtypes, thus potentially allowing differential evaluation of PE.

Cadmium Body Burden and Inflammatory Arthritis: A Pilot Study in Patients from Lower Silesia, Poland.

The purpose of this study was to determine the relationship between cadmium exposure and the likelihood of developing or exacerbating symptoms of inflammatory arthritis (IA). The study included 51 IA patients and 46 control subjects. Demographic and lifestyle data were collected. Haematological and biochemical parameters and blood cadmium levels (Cd-B) were determined. Cd-B correlated positively with age, smoking, living in a high-traffic area, and serum levels of inflammatory markers and negatively with mean corpuscular haemoglobin concentration (MCHC). The binary logistic regression model implied that high Cd-B (≥0.65 μg/L) is linked with an increased risk of IA in the studied population (odds ratio: 4.4). High levels of DNA oxidative damage marker (8-hydroxy-2’-deoxyguanosine) (≥7.66 ng/mL) and cyclooxygenase-2 (≥22.9 ng/mL) and frequent consumption of offal was also associated with increased risk of IA. High Cd-B was related to increased risk of disease symptoms onset in the group of IA patients, decreased the level of interleukin 10, and positively correlated with the disease activity. Increased Cd-B is associated with intensified inflammatory processes and decreased haemoglobin levels; in IA patients with decreased anti-inflammatory interleukin 10. These changes partly explain why cadmium exposure and a high cadmium body burden may raise the risk of IA and of disease symptoms exacerbation.

Metabolomic and transcriptomic responses of mouse testis to the dextran sulfate sodium induced colitis

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis, are widespread in developed countries and gradually increasing in developing countries. Evidences showed that man with CD has a decrease of serum testosterone, but how IBD take effects on testicular testosterone synthesis is not well elucidated. To investigate the effects of IBD on testis, we analyzed testicular metabolome and transcriptome data of the dextran sulfate sodium (DSS) induced IBD mice. As a result, metabolomic data showed that DSS indeed induced androgen decrease in mouse testis. Correspondingly, androgen synthesis associated genes, especially Lhcgr, were down-regulated in DSS testis. From the metabolomic data, we found vitamin intake associated metabolites vitamin B2 and pyridoxamine were significantly decreased, whereas fatty acid metabolism associated molecules N-lauroylglycine and N-decanoylglycine were increased in DSS testis. In addition, we found 8-hydroxy-deoxyguanosine, a DNA oxidative damage marker, and 8-oxoguanine, a molecule responsible for DNA damage repair, were also changed in DSS testis. Simultaneously, our data also showed that DSS up-regulated the expression of meiosis initiation associated gene Stra8 and oxygen transport associated genes in testis. In summary, these results depicted the complex effects of colitis on testis. These metabolites and transcripts changed in DSS testis could be used as potential targets for IBD treatment or symptom relieve.

Enhanced oxidative stress and presence of ventricular aneurysm for risk prediction in cardiac sarcoidosis

ObjectiveSudden cardiac death (SCD) is the major cause of death in cardiac sarcoidosis (CS). We aimed to identify the prognostic markers for sustained ventricular tachycardia (sVT) and SCD in patients...

Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes.

PurposeTo explore whether oxidative stress and premature senescence occur in the anterior segment of acute primary angle-closure (APAC) eyes after increased intraocular pressure.MethodsThe eye samples of 21 APAC patients, 22 age-related cataract patients, and 10 healthy donors were included. Aqueous humor (AqH), iris, and anterior lens capsule samples were collected. The levels of oxidative stress markers and senescence-associated secretory phenotype (SASP)–related cytokines in AqH were estimated using relevant reagent kits and multiplex bead immunoassay technique. The intensity of relevant markers in anterior segment tissues was examined by immunofluorescence- and senescence-associated β-galactosidase (SA-β-gal) staining.ResultsOxidative stress marker levels elevated significantly in the AqH of APAC eyes. Reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine levels were positively correlated with preoperative peak intraocular pressure and age, whereas reduced glutathione/oxidized glutathione (GSH/GSSH) ratio was negatively correlated with both parameters. The levels of several SASP-related cytokines were markedly increased. ROS and malondialdehyde levels were positively correlated with the levels of some SASP-related cytokines, whereas superoxide dismutase level and GSH/GSSH ratio showed an opposite trend. The number of cells positive for oxidative mitochondrial DNA damage and apoptosis-related markers increased in the iris and anterior lens capsule of the APAC group. Senescence-associated markers (p16, p21, and p53) and SA-β-gal activity were increased in the iris of the APAC group.ConclusionsOxidative stress and premature senescence occurred in the anterior segment of APAC patients, suggesting that they may be involved in the development of pathological changes in the anterior segment of APAC eyes.

Effects of electroconvulsive therapy on nitrosative stress and oxidative DNA damage parameters in patients with a depressive episode

Background Few studies have investigated the relationship between electroconvulsive therapy (ECT) and markers of nitrosative stress and oxidative DNA damage. Objective The aim of this study is to examine changes in nitrosative stress and oxidative DNA damage in patients with a depressive episode treated with ECT. Methods The current study included 48 patients with a depressive episode treated with ECT and 30 healthy control participants. First, the serum nitrosative stress markers of nitric oxide (NO•), nitric oxide synthase (NOS), and peroxynitrite (ONOO-) and the oxidative DNA damage marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) were compared between the study and control groups. These parameters were also compared pre- and post-treatment for the study group. Results NO•, NOS, and ONOO- levels were significantly higher in patients with depressive disorder (DD) than in the control group. NO• and NOS levels significantly decreased in the ECT group after treatment while 8-OHdG levels significantly increased. Conclusions The study findings suggest that ECT may have reduced nitrosative stress levels while increasing oxidative DNA damage. More research is now needed to better understand the issue. KEY POINTS Nitrosative stress levels can increase in patients with depressive disorder. Electroconvulsive therapy may reduce nitrosative stress while increasıng oxidative DNA damage. These results suggest that nitrosative stress plays an important role in the mechanism of action of electroconvulsive therapy.

Potential Mechanisms of Methylglyoxal-Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis.

Methylglyoxal (MGO) is a reactive carbonyl species that can cause cellular damage and is closely related to kidney disease, especially diabetic nephropathy. The toxic effect of MGO (0.5, 1, and 2 mM) on human embryonic kidney (HEK293) cells and its underlying mechanisms were explored in this study. Cell viability, apoptosis and the signaling pathways were measured with MTT, fluorescent staining and western blot experiments, the results showed that MGO could induce oxidative stress and cell inflammation, the level of reactive oxygen species (ROS) increased, and p38MAPK, JNK and NF-κB signaling pathways were activated. Meanwhile, MGO also induced DNA damage. The expression of DNA oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) increased, the expression of double-strand break marker γH2AX increased significantly, and ATM/Chk2/p53 DNA damage response signaling pathway was activated. Furthermore, the expression of the receptor for advanced glycation end products (RAGE) also increased. Finally, mitochondrial membrane potential (MMP) decreased, fluorescence intensity of Hoechst33258 increased, and the protein expression ratio of Bax/Bcl-2 increased significantly after the treatment of MGO. These results demonstrated that MGO might induce HEK293 cells damage by regulating oxidative stress, inflammation, DNA damage, and cell apoptosis, which revealed the specific mechanisms of MGO-induced damage to HEK293 cells.