Re-purposing Chloroquine for Glioblastoma: Potential Merits and Confounding Variables

Frontiers in Oncology, Journal Year: 2018, Volume and Issue: 8

Published: Aug. 27, 2018

Chloroquine, one of the oldest antimalarials, has been implicated as a therapeutic sensitizer in different types cancers. Reflecting growing attention to anti-neoplastic actions this drug, over thirty trials have initiated within past five years test potential chloroquine an adjuvant treatment for therapy-refractory Glioblastoma is most aggressive human cancers shown better response standard therapy when combined with chloroquine. While there considerable evidence efficacy and safety cancer, mechanisms underlying tumor suppressive drug remain elusive. Up until recently, inhibitory effects on late stage autophagy was thought be major mechanism cancer cells death from However, recent research provided compelling that autophagy-inhibiting activities are dispensable its ability suppress growth. These unexpected findings urge explore role autophagy-independent molecular anti-cancer interesting drug. This review discusses versatile particular focus glioma cells.

Language: Английский

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Salivary Antioxidants and Oxidative Stress in Psoriatic Patients: Can Salivary Total Oxidant Status and Oxidative Status Index Be a Plaque Psoriasis Biomarker?

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 12

Published: Jan. 4, 2020

The aim of our research was to evaluate redox balance parameters and biomarkers oxidative stress (OS) in nonstimulated stimulated saliva as well the blood patients with plaque psoriasis compared healthy controls. study involved 40 generally subjects matched by age gender group patients. We assayed concentration/activity antioxidant enzymes: salivary peroxidase (Px), catalase (CAT), superoxide dismutase (SOD) measured unstimulated (NWS), (SWS), erythrocytes. In plasma NWS SWS, we reduced glutathione (GSH), total potential (TAC), status (TOS), index (OSI), markers modification proteins: advanced glycation end products (AGE), oxidation protein (AOPP), lipid products: malondialdehyde (MDA) hydroperoxide (LOOH). also evaluated rate reactive oxygen species (ROS) production. concentration Px, CAT, SOD significantly higher vs. subjects. SWS psoriatic patients, observed considerably Px erythrocytes psoriasis, GPx CAT that levels AOPP, AGE, MDA, LOOH were NWS, amylase lower control. course imbalances prevalence reactions. Mechanisms synthesis/secretion proteins activity depressed both glands patients; however, they more inhibited parotid gland submandibular gland. TOS OSI value may serve diagnostic psoriasis.

Language: Английский

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The Impact of Oxidative Stress on Pediatrics Syndromes

Antioxidants, Journal Year: 2022, Volume and Issue: 11(10), P. 1983 - 1983

Published: Oct. 5, 2022

Oxidative stress is a condition determined by an imbalance between antioxidant and oxidative factors. can have serious consequences on our organism. Indeed, it causes both necrosis cell apoptosis, determining cellular aging, increased carcinogenesis, vascular stiffening, autoimmune diseases, muscle decay. In the context of pediatric syndromes, could play role in first order. fact, review literature showed that some pathologies, such as fetal alcohol spectrum disorders, related to intake ethanol during pregnancy main etiological factor associated clinical syndrome. On contrary, Williams syndrome, Down Marfan Gaucher ataxia-telangiectasia, autistic disorder, Fanconi’s anemia, primitive immunodeficiencies, increase directly with genetic alterations cause same pathologies. Although further studies are needed better understand relationship knowledge this crucial issue encourages future therapeutic strategies.

Language: Английский

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An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis

Circulation Research, Journal Year: 2023, Volume and Issue: 133(1), P. 25 - 44

Published: June 2, 2023

ERK5 (extracellular signal-regulated kinase 5) is a dual transcription factor containing an N-terminal domain and C-terminal transcriptional activation domain. Many inhibitors have been developed tested to treat cancer inflammatory diseases. However, recent data raised questions about the role of catalytic activity in proliferation inflammation. We aimed investigate how reprograms myeloid cells proinflammatory senescent phenotype, subsequently leading atherosclerosis. A S496A (dephosphorylation mimic) knock (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered repeat-associated 9), atherosclerosis characterized by hypercholesterolemia induction. The plaque phenotyping homozygous KI wild type (WT) mice studied imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic RNA sequencing functional vitro approaches, including senescence, mitochondria reactive oxygen species, inflammation assays, as well metabolic extracellular flux analysis. show that inhibited mice. Furthermore, S496 phosphorylation mediates both senescence-associated secretory phenotype stemness upregulating AHR (aryl hydrocarbon receptor) bone also discovered could induce NRF2 (NFE2-related 2) SUMOylation at novel K518 site inhibit without altering oxidized LDL (low-density lipoprotein)-induced phenotype. Specific (AX15836 XMD8-92) phosphorylation, suggesting involvement anti-inflammatory effects these inhibitors. mechanism which macrophage ERK5-NRF2 axis develops unique phenotype/stemness engender atherogenesis. finding provides molecular explanation resolve paradox senescence proliferative permitting escape senescence-induced cell cycle arrest during formation.

Language: Английский

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Monogenic Disorders of ROS Production and the Primary Anti-Oxidative Defense

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 206 - 206

Published: Feb. 9, 2024

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and cellular anti-oxidant defense mechanisms, plays a critical role in pathogenesis various human diseases. Redox metabolism, comprising network enzymes genes, serves as crucial regulator ROS levels maintains homeostasis. This review provides overview most important genes encoding for proteins involved generation, detoxification, reduced nicotinamide adenine dinucleotide phosphate (NADPH), genetic disorders that lead to dysregulation these vital processes. Insights gained from studies on inherited monogenic metabolic diseases provide valuable basic understanding redox metabolism signaling, they also help unravel underlying pathomechanisms contribute prevalent chronic like cardiovascular disease, neurodegeneration, cancer.

Language: Английский

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Type I IFN–related NETosis in ataxia telangiectasia and Artemis deficiency

Journal of Allergy and Clinical Immunology, Journal Year: 2017, Volume and Issue: 142(1), P. 246 - 257

Published: Nov. 17, 2017

Language: Английский

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Effect of N‐Acetylcysteine on Antioxidant Defense, Oxidative Modification, and Salivary Gland Function in a Rat Model of Insulin Resistance

Oxidative Medicine and Cellular Longevity, Journal Year: 2018, Volume and Issue: 2018(1)

Published: Jan. 1, 2018

Oxidative stress plays a crucial role in the salivary gland dysfunction insulin resistance (IR). It is not surprising that new substances are constantly being sought will protect against harmful effects of IR oral cavity environment. The purpose this study was to evaluate effect N‐acetylcysteine (NAC) on oxidative and secretory function glands rat model resistance. Rats were divided into 4 groups: C—normal diet, C + NAC—normal diet NAC, HFD—high‐fat HFD NAC. We have demonstrated NAC elevated enzymatic (superoxide dismutase, catalase, peroxidase) nonenzymatic antioxidants (reduced glutathione (GSH) total antioxidant capacity (TAS)) parotid rats, while submandibular increased only GSH TAS levels. protects damage stimulated secretion; however, it does increase protein secretion both glands. Summarizing, supplementation prevents decrease saliva secretion, seen rats affected. improves antioxidative rats.

Language: Английский

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The Redox Balance in Erythrocytes, Plasma, and Periosteum of Patients with Titanium Fixation of the Jaw

Frontiers in Physiology, Journal Year: 2017, Volume and Issue: 8

Published: June 7, 2017

Titanium miniplates and screws are commonly used for fixation of fractured or osteotomised jaws. Despite the opinion their biocompatibility, in clinical practice symptoms chronic inflammation around develop some patients, even many years after application screws. The cause these complications is still an open question. Taking into account that oxidative stress one toxic action titanium, we have evaluated antioxidant barrier as well erythrocytes, plasma periosteum covering titanium study group was composed 32 patients aged 20–30 with inserted Antioxidant defence: catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase-1 (SOD1), uric acid (UA), total capacity (TAC), damage products: advanced oxidation protein products (AOPP), glycation end (AGE), dityrosine, kynurenine, N-formylkynurenine, tryptophan, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), oxidant status (TOS), index (OSI) were evaluated. SOD1 activity (↓37%), tryptophan levels (↓34%) showed a significant decrease while AOPP (↑25%), TOS (↑80%) OSI (↑101%) significantly elevated maxillary who underwent bimaxillary osteotomies compared to control group. SOD-1 (↓55%), TAC (↓58.6%), AGE (↓60%) N-formylkynurenine statistically reduced (↑38%), MDA (↑29%), 4-HNE (↑114%), (↑99%) (↑381%) higher mandibular miniplates/screw tissues. There no correlations between antioxidants markers all blood. As exposure Ti6Al4V alloy leads disturbances redox balance surrounding implants maxilla mandible so supplementation should be recommended undergoing treatment dentofacial deformities use implants. results obtained may also indicate need improve quality jaw fixations through increase TiO2 passivation layer thickness new, most highly biodegradable materials production.

Language: Английский

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Exposure to Ti4Al4V Titanium Alloy Leads to Redox Abnormalities, Oxidative Stress, and Oxidative Damage in Patients Treated for Mandible Fractures

Oxidative Medicine and Cellular Longevity, Journal Year: 2018, Volume and Issue: 2018(1)

Published: Jan. 1, 2018

Due to the high biotolerance, favourable mechanical properties, and osseointegration ability, titanium is basic biomaterial used in maxillofacial surgery. The passive layer of dioxide on surface implant effectively provides anticorrosive but it can be damaged, resulting release ions surrounding tissues. aim our work was evaluate influence Ti6Al4V alloy redox balance oxidative damage periosteum miniplates screws as well plasma erythrocytes patients with mandibular fractures. study included 31 previously implanted (aged 21–29) treated for fractures healthy controls. We have demonstrated increased activity/concentration antioxidants both plasma/erythrocytes fixations. However, concentrations products protein lipid modifications were only observed group patients. correlation between modification mandible suggests a relationship increase at implantation site central disorders screws.

Language: Английский

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Eight-Week Consumption of High-Sucrose Diet Has a Pro-Oxidant Effect and Alters the Function of the Salivary Glands of Rats

Nutrients, Journal Year: 2018, Volume and Issue: 10(10), P. 1530 - 1530

Published: Oct. 17, 2018

A high-sucrose diet (HSD) is widely known for its cariogenic effects and promotion of obesity, insulin resistance, type 2 diabetes, cancer. However, the impact HSD on salivary gland function as well level oxidative stress still unknown requires evaluation. Our study first to determine both redox balance injury in parotid submandibular glands rats fed compared control group. We have demonstrated that uric acid concentration activity superoxide dismutase peroxidase varied significantly vs. enhanced damage proteins, lipids, DNA (increase advanced glycation end products, oxidation protein 4-hydroxynonenal, 8-hydroxy-2’-deoxyguanosine) was observed only rats. Moreover, also reduced total content amylase types decreased stimulated flow rate. To sum up, an reduces disturbs glands. are more vulnerable antioxidant disturbances damage.

Language: Английский

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