Redox Status Is Critical for Stemness in Skin Equivalents

The skin is constantly exposed to environmental oxidative stress. Skin equivalent (SE) models are three-dimensional systems in which cell-cell or cell-matrix interactions can be investigated. In this study, the effects of vitamin C or plant extracts with high antioxidant activities were tested. There was no significant difference in the epidermal thickness, but the basal cells became cuboidal when vitamin C or plant extracts were supplemented. Furthermore, immunohistochemical staining showed linear and intense staining ofα6 andβ1 integrin along the basement membrane in vitamin C or plant extract treated models. The p63 and PCNA were also stained. Results showed that the number of p63 and PCNA positive cells was higher in the vitamin C or plant extract treated models than in the control SEs. Although the relationship between oxidative stress and stem cells is not known, our results suggest that redox status affects the stemness and the proliferative potential of epidermal basal cells by modulating microenvironment to epidermal basal stem cells.

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Sequential Analysis of Oxidative Stress Markers and Vitamin C Status in Acute Bacterial Osteomyelitis

Mediators of Inflammation ◽

10.1155/2014/975061 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Rade Grbic ◽

Dijana J Miric ◽

Bojana Kisic ◽

Ljiljana Popovic ◽

Vojkan Nestorovic ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin C ◽

Sequential Analysis ◽

Bone Cells ◽

Redox Status ◽

Oxidative Stress Markers ◽

Total Vitamin ◽

Baseline Serum ◽

Stress Markers ◽

Systemic Oxidative Stress

In bacterial bone infections, excessively formed oxidants may result in local and systemic oxidative stress. Vitamin C is the major extracellular nonenzymatic antioxidant, also implicated in bone cells metabolism and viability. The physiological functions of vitamin C largely depend on its redox status. We sequentially assessed oxidative stress markers, hydroperoxides and malondialdehyde (MDA), total antioxidant activity (AOA), total vitamin C, ascorbic acid (Asc), and oxidized/reduced vitamin C ratio in 137 patients with acute osteomyelitis (OM). Compared to 52 healthy controls, in OM group baseline serum hydroperoxides, MDA and oxidized/reduced vitamin C ratio were higher whilst Asc and AOA were lower (P < 0.05, resp.). On the other side, total vitamin C levels in patients and controls were similar(P > 0.05), thereby suggesting a relative rather than absolute vitamin C deficiency in OM. During the follow-up, oxidative stress markers, AOA, and oxidizedreduced vitamin C ratio were gradually returned to normal, while there was no apparent change of total vitamin C concentrations. Persistently high values of oxidized/reduced vitamin C ratio and serum MDA were found in subacute OM. In conclusion, acute OM was associated with enhanced systemic oxidative stress and the shift of vitamin C redox status towards oxidized forms.

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ERCC1, KRAS mutation, redox status, and oxaliplatin sensitivity in colorectal cancer: “Radical” change in an old model.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14156 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14156-e14156

Author(s):

Armando Orlandi ◽

Mariantonietta Di Salvatore ◽

Michele Basso ◽

Cinzia Bagalà ◽

Antonia Strippoli ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Cell Lines ◽

Pearson Correlation ◽

Redox Status ◽

Mutational Status ◽

Retrospective Clinical Study ◽

Significant Difference ◽

The Impact

e14156 Background: Oxaliplatin (Oxa) is widely used in metastatic colorectal cancer, but currently there are not valid predictors of response to this drug. In our recent retrospective clinical study we have shown a greater efficacy of Oxa in patients with metastatic colorectal cancer with mutated (mt) K-RAS. We hypothesized that the mutational status of K-RAS could influence the expression of ERCC1 and cellular Redox status. Methods: We used four cell lines of colorectal cancer: two K-RAS wild type (wt) (HCT-8, HT-29) and two K-RAS mt (SW620, SW480). We evaluated the sensitivity of these cell lines to Oxa by MTT-test and the ERCC1 levels before and after 24h exposure to Oxa by RT-PCR. We silenced K-RAS in a K-RAS mt cell lines to evaluate the impact on Oxa sensitivity and ERCC1 levels. We also silenced ERCC1 in order to confirm the importance of this protein as a Oxa resistance factor. Cellular oxidative stress was determined by DCFDA. Results: The K-RAS mt cell lines were more sensitive to Oxa (p<0.001). The basal levels of ERCC1 did not show significant differences between K-RAS mt and wt cell line, however, after 24h exposure to Oxa, only the K-RAS wt lines showed the ability to induce ERCC1, with a statistically significant difference (p<0.005). The silencing of K-RAS in K-RAS mt cell lines (SW620s) demonstrated to reduce sensitivity to Oxa associated with the acquisition of the ability to induce ERCC1. The silencing of ERCC1 in K-RAS wt cell lines enhance the sensibility to Oxa. The levels of reactive oxygen species were higher in K-RAS mt cell lines. The Pearson correlation test showed a statistically significant relationship between basal levels of ROS and sensitivity to Oxa ("r" -0,988, p<0.01). The baseline levels of ROS were higher SW620 than the line SW620s. The administration of Oxa in these cell lines resulted in a statistically higher fluorescence index in SW620 versus SW620s (p<0.003). Conclusions: The K-RAS mutated cell lines were more sensitive to Oxa. This feature seems to be secondary to the inability of these cells to induce ERCC1 after exposure to Oxa and to the synergism between K-RAS mutation and Oxa in increasing oxidative stress. K-RAS can thus be a predictor of response to Oxa in colorectal cancer.

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Comparison of Oxidant-Antioxidant Status in Patients with Vitiligo and Healthy Population

Kathmandu University Medical Journal ◽

10.3126/kumj.v12i2.13660 ◽

2015 ◽

Vol 12 (2) ◽

pp. 132-136 ◽

Cited By ~ 7

Author(s):

S Agrawal ◽

A Kumar ◽

TK Dhali ◽

SK Majhi

Keyword(s):

Oxidative Stress ◽

Free Radicals ◽

Vitamin E ◽

Vitamin C ◽

Control Group ◽

Healthy Population ◽

Significant Difference ◽

Destruction Of Melanocytes ◽

And Control

Background Vitiligo is a well-recognized pigmentary disorder of the skin and /or mucous membrane characterized by circumscribed ivory or chalky white macules devoid of identifiable melanocytes. The pathogenesis of vitiligo is complex and still not well understood. According to autocytotoxic hypothesis, oxidative stress has been suggested to be the initial pathogenic event in melanocyte degeneration. The role of free radicals and oxidative damage in the pathophysiology of vitiligo has been documented in recent studies.Objective To evaluate the role of oxidative stress in patients with vitiligo and of healthy controls by measuring levels of the oxidant malondialdehyde (MDA) and antioxidants vitamin C and vitamin E in serum and catalase (CAT) in erythrocytes.Method A total of 80 clinically diagnosed cases of vitiligo and 80 control subjects were included in the study to assess the activity of MDA, vitamin C and vitamin E in serum and CAT in erythrocytes of patients and controls by using the spectrophotometric assay.Result There was statistically significant increase in the levels of MDA in patients with vitiligo compared to the control group (p<0.001). No significant difference was found in the levels of vitamin C (p=0.411) and vitamin E (p=0.771) between the patients with vitiligo and control group. The levels of CAT in the vitiligo patients were found to be significantly lower than those of controls (p<0.001).Conclusion Increased oxidative stress and decreased catalase have been observed in vitiligo patients and the data suggesting that the free radicals may be involved in the destruction of melanocytes or dysregulation of melanogenesis.Kathmandu University Medical Journal Vol.12(2) 2014: 132-136

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Significance of Elevated Blood Metal Ion Levels in Patients with Metal-on-Metal Prostheses: An Evaluation of Oxidative Stress Markers

The Open Orthopaedics Journal ◽

10.2174/1874325001004010221 ◽

2010 ◽

Vol 4 (1) ◽

pp. 221-227 ◽

Cited By ~ 21

Author(s):

Cathy Tkaczyk ◽

Alain Petit ◽

John Antoniou ◽

David J Zukor ◽

Maryam Tabrizian ◽

...

Keyword(s):

Oxidative Stress ◽

Metal Ion ◽

Biological Effects ◽

Redox Status ◽

Heme Oxygenase 1 ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Systemic Oxidative Stress ◽

Metal On Metal ◽

Significant Difference

It is widely known that cobalt and chromium ions can enhance the production of reactive oxygen species, known to be damaging to cells by disturbing their redox status and then generating oxidative stress. The aim of the present study was to determine if increased metal ion levels induce a state of oxidative stress in patients with metal-on-metal (MM) hip arthroplasty. Results indicated that there was no significant difference in the concentration of oxidative stress markers (total antioxidants, peroxides, and nitrated proteins) in the patients with MM bearings compared to patients without prostheses. The activity antioxidant enzymes was stable (catalase and glutathione peroxidase) or slightly decreased (superoxide dismutase and heme oxygenase-1) over time. This work is the first to determine the biological effects of metal ions released from MM hip implants with regards to mid-term systemic oxidative stress and showed that the increased levels of Co and Cr ions are not associated with significant oxidative stress damage in the plasma of patients with these implants.

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Relationship between diet, oxidative stress, and inflammation in ankylosing spondylitis

Archives of Rheumatology ◽

10.46497/archrheumatol.2022.9015 ◽

2021 ◽

Author(s):

Kübra Tel Adıgüzel ◽

Fatma Gül Yurdakul ◽

Nilgün Seremet Kürklü ◽

Evren Yaşar ◽

Hatice Bodur

Keyword(s):

Oxidative Stress ◽

Fatty Acid ◽

Ankylosing Spondylitis ◽

Vitamin C ◽

Antioxidant Status ◽

Total Antioxidant Status ◽

Stress Index ◽

Control Group ◽

Dietary Record ◽

Significant Difference

Objectives: This study aims to investigate the relationship between disease activity, dietary phytochemical index (DPI), and serum total oxidant status (TOS) and total antioxidant status (TAS) in patients with ankylosing spondylitis (AS). Patients and methods: Between August 2020 and January 2021, a total of 37 patients (23 males, 14 females; mean age: 39.3±9.4 years; range, 21 to 61 years) with AS and 36 age-, sex-, and body mass index-matched healthy individuals (24 males, 12 females; mean age: 37.9±8.9 years; range, 20 to 60 years) were included. Serum TAS (μmoLTroloxEq/L) and TOS (μmoL H2O2Eq/L) measurements were performed and the oxidative stress index (OSI) was calculated. Dietary evaluation was made from a one-day dietary record and DPI was calculated. Results: Serum TAS level in AS patients was significantly lower than the healthy group (p=0.003). Serum TOS level was similar in both groups. The OSI of patients was significantly higher than the controls (p=0.035). The mean DPI, polyunsaturated fatty acid, n-3 fatty acid, and vitamin C intake of patients were significantly lower than controls (p=0.042, p=0.033, and p=0.022, respectively). A moderate positive correlation was found between the TAS level and DPI of the control group (r=0.352, p=0.035). According to medications, no significant difference was seen between the groups in terms of patients’ characteristics, DPI, and laboratory tests and there was no correlation between DPI, TAS, TOS, and OSI. Conclusion: Lower DPI and lower n-3 fatty acid and vitamin C intake in patient group demonstrated that patients with AS should pay more attention to their diet to increase serum antioxidant status.

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Effects of Steroid Treatment on Childhood ALL Stem Cells.

Blood ◽

10.1182/blood.v110.11.3462.3462 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3462-3462

Author(s):

Charlotte V. Cox ◽

Paraskevi Diamanti ◽

Pamela R. Kearns ◽

Allison Blair

Keyword(s):

Stem Cells ◽

Annexin V ◽

Absolute Number ◽

Proliferative Potential ◽

Disease Relapse ◽

Childhood All ◽

Cell Counts ◽

Viable Cells ◽

Significant Difference ◽

The Absolute

Abstract Several lines of evidence indicate a central role for stem cells in the pathogenesis of human leukaemias and exemplify the need to develop strategies that target this sub-population of cells. It is proposed that these cells may exhibit different chemo-sensitivity and consequently may be resistant to drug regimens designed to kill the bulk leukaemia population. Inherently resistant leukaemia stem cells may contribute to subsequent disease relapse. Clearly, there is a need to assess the relative efficacy of therapeutic agents on the sub-populations of cells in addition to the bulk leukaemia. We have previously demonstrated that the sub-population of childhood acute lymphoblastic leukaemia (ALL) cells, capable of serially engrafting NOD/SCID mice, have a CD34+/CD19− or CD34+/CD7− phenotype in B cell precursor (BCP) ALL and T-ALL, respectively. In this investigation we have compared the efficacy of a current glucocorticoid therapeutic agent on these putative ALL stem cells with their effects on the bulk leukaemia population. The effect of dexamethasone (dex), a key component of the treatment of childhood ALL, on primary ALL cells from 13 paediatric cases was examined. Unsorted ALL cells were co-cultured with and without dex for 48 hours. Subsequently, cell viability and apoptosis were evaluated by flow cytometry using propidium iodide and annexin V staining, with Flow-Count fluorospheres to directly determine absolute cell counts. Primary cells from 11 patients with BCP ALL were sorted for expression of CD34/CD19 and cells from 2 T-ALL cases were sorted for expression of CD34/CD7. The unsorted cells and the sorted sub-fractions were co-cultured with increasing concentrations of dex (0.05 to 500 μM) to compare the relative chemosensitivity of the bulk and putative leukaemia stem cell populations. The unsorted leukaemia populations were completely refractory to dex with no significant difference in the levels of apoptosis observed or the absolute number of viable cells in the treated samples and in the untreated controls. Interestingly, when the sorted populations were assessed, an increase in the absolute numbers of viable CD34+/CD19− (1.2–9.7 fold, P<0.02) and CD34+/CD7− (2.6–5 fold, P<0.04) leukaemia cells were observed even at the highest steroid dose, compared to the respective untreated sub-fractions. The other leukaemic sub-fractions did not show a significant increase in the number of viable cells following dex exposure. These data show that 10 out of 11 drug treated primary leukaemia cells were resistant to dex. The putative CD34+/CD19− BCP ALL cells and CD34+/CD7− T-ALL cells showed a significantly enhanced proliferative potential when exposed to the drug, suggesting that it is these cells that may be responsible for disease relapse.

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Vitamins E and C Alleviate the Germ Cell Loss and Oxidative Stress in Cryptorchidism When Administered Separately but Not When Combined in Rats

ISRN Pharmacology ◽

10.5402/2012/843569 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Ayobami Oladele Afolabi ◽

Olaolu Opeyemi Olotu ◽

Isiaka Abdullateef Alagbonsi

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Vitamin C ◽

Germ Cell ◽

Cell Count ◽

Cell Loss ◽

Vitamins E And C ◽

Testicular Weight ◽

Significant Difference ◽

And Oxidative Stress

The antioxidant effects of vitamins C and E on cryptorchidism-induced oxidative stress were investigated in male Sprague-Dawley rats. Forty rats (200–250 g) were randomly divided in a blinded fashion into five groups (). Group 1 was sham operated and treated with vehicle (corn-oil, 10 mL/kg). Groups 2, 3, 4, and 5 were rendered unilaterally cryptorchid and treated with vehicle (10 mL/kg), vitamin E solution (75 mg/kg), vitamin C solution (1.25 g/kg), and combination of vitamin E (75 mg/kg) and vitamin C (1.25 g/kg) solutions, respectively. Germ cell count, superoxide dismutase (SOD), total protein (TP), and testicular weight (TW) were lower, but malondialdhyde (MDA) was higher in the cryptorchid rats than the sham-operated rats. When administered separately, vitamins C and E increased germ cell count, SOD, TP, and TW but did not reduce MDA in the cryptorchid rats when compared to the vehicle-treated cryptorchid rats. However, there was no significant difference in these parameters between vehicle-treated and combined vitamins C- and E-treated rats. This suggests that vitamins E and C alleviate the germ cell loss and oxidative stress in cryptorchidism when administered separately but not when combined in rats.

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Peroxiredoxin II Regulates Cancer Stem Cells and Stemness-Associated Properties of Cancers

Cancers ◽

10.3390/cancers10090305 ◽

2018 ◽

Vol 10 (9) ◽

pp. 305 ◽

Cited By ~ 9

Author(s):

Nisansala Chandimali ◽

Dong Jeong ◽

Taeho Kwon

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Redox Status ◽

Cell Phenotype ◽

Therapeutic Effects ◽

Cellular Functions ◽

Unlimited Growth ◽

Current Therapies

Cancer stem cells (CSCs) represent a sub-population of cancer cells with the ability to regulate stemness-associated properties which are specifically responsible for unlimited growth of cancers, generation of diverse cancer cells in differentiated state and resistance to existing chemotherapy and radiotherapy. Even though, current therapies destroy majority of cancer cells, it is believed to leave CSCs without eradicating which may be the conceptualization for chemoresistance and radio-resistance. Reactive oxygen species (ROS) maintain stem cells and regulate the stemness-associated properties of cancers. Beyond the maximum limit, ROS can damage cellular functions of cancers by subjecting them to oxidative stress. Thus, maintenance of ROS level plays an important role in cancers to regulate stemness-associated properties. Peroxiredoxin II (Prx II) is a member of peroxiredoxin antioxidant enzyme family which considers as a regulator of ROS in cellular environments by modulating redox status to maintain CSC phenotype and stemness properties. Prx II has cell type-dependent expression in various types of cancer cells and overexpression or silenced expression of Prx II in cancers is associated with stem cell phenotype and stemness-associated properties via activation or deactivation of various signaling pathways. In this review, we summarized available studies on Prx II expression in cancers and the mechanisms by which Prx II takes parts to regulate CSCs and stemness-associated properties. We further discussed the potential therapeutic effects of altering Prx II expression in cancers for better anticancer strategies by sensitizing cancer cells and stem cells to oxidative stress and inhibiting stemness-associated properties.

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Sublethal Oxidative Stress Induces the Premature Senescence of Human Mesenchymal Stem Cells Derived from Endometrium

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/474931 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 61

Author(s):

Elena Burova ◽

Aleksandra Borodkina ◽

Alla Shatrova ◽

Nikolay Nikolsky

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Proliferative Potential ◽

Premature Senescence ◽

Human Diploid Fibroblasts ◽

Senescent Phenotype ◽

Stressed Cells ◽

The Impact

The specific responses of mesenchymal stem cells to oxidative stress may play a crucial role in regulation of tissue homeostasis as well as regeneration of organs after oxidative injury. The responses of human endometrium-derived mesenchymal stem cells (hMESCs) to oxidative stress remain still unknown. Herein, we examined the impact of H2O2on cell viability, induction of premature senescence, and apoptosis. hMESCs were highly resistant to H2O2compared with human diploid fibroblasts. To test a hypothesis whether hMESCs may undergo oxidative stress-induced premature senescence, cells were briefly exposed to the sublethal H2O2doses. H2O2-treated cells were permanently arrested, lost Ki67 proliferation marker, and exhibited a senescent phenotype including cell hypertrophy and increased SA-β-Gal activity. Additionally, in stressed cells the expression levels of p21Cip1, SOD1, SOD2, and GPX1 were elevated. hMESCs survived under stress were not able to resume proliferation, indicating the irreversible loss of proliferative potential. While the low H2O2doses promoted senescence in hMESCs, the higher H2O2doses induced also apoptosis in a part of the cell population. Of note, senescent hMESCs exhibited high resistance to apoptosis. Thus, we have demonstrated for the first time that hMESCs may enter a state of premature senescence in response to sublethal oxidative stress.

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Evaluation of the antimicrobial activity and compressive strength of a dental cement modified using plant extract mixture

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-020-06455-w ◽

2020 ◽

Vol 31 (12) ◽

Author(s):

Lamia Singer ◽

Gabriele Bierbaum ◽

Katja Kehl ◽

Christoph Bourauel

Keyword(s):

Antimicrobial Activity ◽

Compressive Strength ◽

Plant Extract ◽

Plant Extracts ◽

Micrococcus Luteus ◽

Testing Machine ◽

Alcoholic Extract ◽

Dental Cement ◽

Freeze Dried ◽

Significant Difference

AbstractLiterature lacks sufficient data regarding addition of natural antibacterial agents to glass ionomer cement (GICs). Hence, the aim of the study was to increase the antimicrobial properties of GICs through its modification with mixture of plant extracts to be evaluated along with an 0.5% chlorohexidine-modified GIC (CHX-GIC) with regard to biological and compressive strength properties. Conventional GIC (freeze-dried version) and CHX were used. Alcoholic extract of Salvadora persica, Olea europaea, and Ficus carcia leaves were prepared using a Soxhlet extractor for 12 h. The plant extract mixture (PE) was added in three different proportions to the water used for preparation of the dental cement (Group 1:1 PE, 2:1 PE, and 1:2 PE). Specimens were then prepared and tested against the unmodified GIC (control) and the 0.5% CHX-GIC. Chemical analysis of the extract mixture was performed using Gas chromatography–mass spectrometry. Antimicrobial activity was evaluated using agar diffusion assay against Micrococcus luteus and Streptoccocus mutans. Compressive strength was evaluated according to ISO 9917-1:2007 using a Zwick testing machine at a crosshead speed of 0.5 mm/min. Antimicrobial activity against Streptoccocus mutans was significantly increased for all the extract-modified materials compared to the unmodified cement, and the highest concentration was comparable to the CHX-GIC mixture. The activity against Micrococcus luteus was also significantly increased, but only for the material with the highest extract concentration, and here the CHX-GIC group showed statistically the highest antimicrobial activity. Compressive strength results revealed that there was no statistically significant difference between the different mixtures and the control except for the highest tested concentration that showed the highest mean values. The plant extracts (PEs) enhanced the antimicrobial activity against S. mutans and also against M. luteus in the higher concentration while compressive strength was improved by addition of the PE at higher concentrations.

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