1,551 results match your criteria dysfunctional oxidative

Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(iii) dithiocarbamates.

Chem Sci 2020 Sep 18;11(38):10465-10482. Epub 2020 Sep 18.

Department of Chemistry, University of Kentucky Lexington KY 40506 USA

Metabolic reprogramming is a key cancer hallmark that has led to the therapeutic targeting of glycolysis. However, agents that target dysfunctional mitochondrial respiration for targeted therapy remains underexplored. We report the synthesis and characterization of ten (10) novel, highly potent organometallic gold(iii) complexes supported by dithiocarbamate ligands as selective inhibitors of mitochondrial respiration. Read More

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September 2020

Physiologically Relevant Concentrations of Dolutegravir, Emtricitabine, and Efavirenz Induce Distinct Metabolic Alterations in HeLa Epithelial and BV2 Microglial Cells.

Front Immunol 2021 20;12:639378. Epub 2021 May 20.

Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States.

Microglia, the resident brain phagocytes, likely play a key role in human immunodeficiency virus (HIV) infection of the central nervous system (CNS) and subsequent neuropathogenesis; however, the nature of the infection-induced changes that yield damaging CNS effects and the stimuli that provoke microglial activation remains elusive, especially in the current era of using antiretroviral (ARV) drugs for ARV therapy (ART). Altered microglial metabolism can modulate cellular functionality and pathogenicity in neurological disease. While HIV infection itself alters brain energy metabolism, the effect of ARV drugs, particularly those currently used in treatment, on metabolism is understudied. Read More

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Flunixin Meglumine Reduces Milk Isoprostane Concentrations in Holstein Dairy Cattle Suffering from Acute Coliform Mastitis.

Antioxidants (Basel) 2021 May 24;10(6). Epub 2021 May 24.

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

Dysfunctional inflammation contributes significantly to the pathogenesis of coliform mastitis and the classical pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is the target of medical intervention using the non-steroidal anti-inflammatory drug (NSAID) flunixin meglumine (FM). Inhibition of COX-2 by FM can decrease concentrations of pro-inflammatory fatty acid-based mediators called eicosanoids, providing antipyretic and analgesic effects in dairy cows suffering from coliform mastitis. However, approximately 50% of naturally occurring coliform mastitis with systemic involvement results in death of the animal, even with NSAID treatment. Read More

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Mitophagy and Oxidative Stress: The Role of Aging.

Antioxidants (Basel) 2021 May 17;10(5). Epub 2021 May 17.

Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. Read More

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Hidrox and Endometriosis: Biochemical Evaluation of Oxidative Stress and Pain.

Antioxidants (Basel) 2021 May 4;10(5). Epub 2021 May 4.

Department of Biomedical, Dental and Morphological and Functional Imaging University of Messina, Via Consolare Valeria, 98125 Messina, Italy.

Endometriosis is a gynecological and painful condition affecting women of reproductive age. It is characterized by dysfunctional endometrium-like implants outside of the uterine cavity. The purpose of this study was to evaluate the effects of Hidrox, an aqueous extract of olive pulp containing hydroxytyrosol, on endometriotic lesions associated with pro-oxidative alterations and pain-like behaviors. Read More

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Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila.

Aging Cell 2021 Jun 1:e13379. Epub 2021 Jun 1.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.

Increased levels of dysfunctional mitochondria within skeletal muscle are correlated with numerous age-related physiopathological conditions. Improving our understanding of the links between mitochondrial function and muscle proteostasis, and the role played by individual genes and regulatory networks, is essential to develop treatments for these conditions. One potential player is the mitochondrial outer membrane protein Fis1, a crucial fission factor heavily involved in mitochondrial dynamics in yeast but with an unknown role in higher-order organisms. Read More

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Oxidative Modifications of RNA and Its Potential Roles in Biosystem.

Front Mol Biosci 2021 12;8:685331. Epub 2021 May 12.

Biochemistry and Biophysics Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Elevated level of oxidized RNA was detected in vulnerable neurons in Alzheimer patients. Subsequently, several diseases and pathological conditions were reported to be associated with RNA oxidation. In addition to several oxidized derivatives, cross-linking and unique strand breaks are generated by RNA oxidation. Read More

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[Stress and pathophysiological mechanisms for the development of psychosomatic disease].

Psychiatriki 2021 May 28. Epub 2021 May 28.

Hellenic Psychiatric Association.

According to the biopsychosocial model, disease is the dysfunctional resultant of various fields of human function (biological, psychological, behavioral, socioeconomic). This article deals with the psycho-biological field of Psychosomatic research, namely, the effect of stress on the body. The human organism, in the prospect of evolution, has developed biological mechanisms for maintaining its homeostasis (ομοιόσταση), in its interchange with the stressor stimuli. Read More

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NEIL3 prevents senescence in hepatocellular carcinoma by repairing oxidative lesions at telomeres during mitosis.

Cancer Res 2021 May 27. Epub 2021 May 27.

Department of Oncology-Pathology, Karolinska Institute

Hepatocellular carcinoma (HCC) patients suffer from few treatment options and poor survival rates. Here we report that endonuclease VIII-like protein 3 (NEIL3) is overexpressed in HCC and correlates with poor survival. All six HCC cell lines investigated were dependent on NEIL3 catalytic activity for survival and prevention of senescence, while NEIL3 was dispensable for non-transformed cells. Read More

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Adhesion-mediated mechanosignaling forces mitohormesis.

Cell Metab 2021 May 17. Epub 2021 May 17.

Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences and Department of Radiation Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and The Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Mitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of aging. However, the physical characteristics of the extracellular matrix are also altered in cancerous and aging tissues. Read More

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Immunomodulatory nanosystems for treating inflammatory diseases.

Biomaterials 2021 Jul 10;274:120875. Epub 2021 May 10.

Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India. Electronic address:

Inflammatory disease (ID) is an umbrella term encompassing all illnesses involving chronic inflammation as the central manifestation of pathogenesis. These include, inflammatory bowel diseases, hepatitis, pulmonary disorders, atherosclerosis, myocardial infarction, pancreatitis, arthritis, periodontitis, psoriasis. The IDs create a severe burden on healthcare and significantly impact the global socio-economic balance. Read More

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Oleuropein Protects Against Cerebral Ischemia Injury in Rats: Molecular Docking, Biochemical and Histological Findings.

Neurochem Res 2021 May 18. Epub 2021 May 18.

Laboratory of Organic Chemistry LR17ES08 (Natural Substances Team), Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia.

This study was designed to evaluate the underlying protective mechanisms of oleuropein involved in alleviating brain damage in a rat model of ischemic stroke. Male Wistar rats were divided into four groups; Control, stroke (MCAO), MCAO + clopidogrel (Clop) and MCAO + oleuropein (Ole). Results showed that the MCAO group evidenced significant brain edema (+ 9%) as well as increases of plasma cardiac markers such as lactate deshydrogenase (LDH), creatine kinase (CK-MB), fibrinogen and Trop-T by 11 %, 43%, 168 and 590%, respectively, as compared to the control group. Read More

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Cdk5 regulatory subunit-associated protein 1 knockout mice show hearing loss phenotypically similar to age-related hearing loss.

Mol Brain 2021 May 17;14(1):82. Epub 2021 May 17.

Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1- Honjo, Chuo-ku, Kumamoto, 8608556, Japan.

Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Read More

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PINK1 Activation Attenuates Impaired Neuronal-Like Differentiation and Synaptogenesis and Mitochondrial Dysfunction in Alzheimer's Disease Trans-Mitochondrial Cybrid Cells.

J Alzheimers Dis 2021 May 14. Epub 2021 May 14.

Department of Surgery and Therapeutics, Columbia University New York, NY, USA.

Background: Mitochondrial dysfunction, bioenergetic deficit, and extensive oxidative stress underlie neuronal perturbation during the early stage of Alzheimer's disease (AD). Previously, we demonstrated that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with AD pathology in AD-affected human brains and AD mice.

Objective: In the present study, we highlight the essential role of PINK1 in AD-relevant mitochondrial perturbation and neuronal malfunction. Read More

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Abnormal levels of apolipoprotein A-I in chronic thromboembolic pulmonary hypertension.

Pulm Circ 2021 Apr-Jun;11(2):20458940211010371. Epub 2021 Apr 22.

Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA.

Recent studies have shown low high-density lipoprotein cholesterol (HDL-C) and dysregulated lipid metabolism in chronic thromboembolic pulmonary hypertension (CTEPH). Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-C and mediates most of its functions. We hypothesize that ApoA-1 and its oxidative state might be more sensitive biomarkers in CTEPH. Read More

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Anabolic-androgenic steroids impair mitochondrial function and redox status in the heart and liver of mice.

Steroids 2021 May 11;172:108861. Epub 2021 May 11.

Laboratory of Neurotrauma and Biomarkers, PPG-Ciências Biológicas Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil. Electronic address:

Supraphysiological doses of anabolic-androgenic steroids (AAS) may cause long-term functional abnormalities, particularly in the heart and liver, which may only represent the later-stage of the cumulative damage caused by dysfunctional organelles. We investigated whether mid-term supraphysiological doses of Testosterone and Nandrolone impair mitochondrial Ca and membrane potential (ΔΨm) dynamics, and redox machinery in the heart and liver of mice. CF1 albino mice were treated daily with 15 mg/kg of Nandrolone (ND) or Testosterone (T), or oil (vehicle) for 19 days. Read More

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Iron Toxicity and Chelation Therapy in Hematopoietic Stem Cell Transplant.

Transplant Cell Ther 2021 May 11;27(5):371-379. Epub 2020 Dec 11.

Iron Research Program, Lindsley Kimball Research Institute, New York Blood Center, New York, New York; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York. Electronic address:

Many patients with hematologic malignancies receive RBC transfusion support, which often causes systemic and tissue iron toxicity. Because of their compromised bone marrow function, hematopoietic stem cell transplant (HSCT) recipients are especially vulnerable to excess iron levels. Iron toxicity may compromise transplant engraftment and eventually promote relapse by mediating oxidative and genotoxic stress in hematopoietic stem cells (HSCs) and further impairing the already dysfunctional bone marrow microenvironment in HSCT recipients. Read More

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Ablation of dynamin-related protein 1 promotes diabetes-induced synaptic injury in the hippocampus.

Cell Death Dis 2021 May 5;12(5):445. Epub 2021 May 5.

Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam, 52727, Republic of Korea.

Dynamin-related protein 1 (Drp1)-mediated mitochondrial dysfunction is associated with synaptic injury in the diabetic brain. However, the dysfunctional mitochondria by Drp1 deletion in the diabetic brain are poorly understood. Here, we investigated the effects of neuron-specific Drp1 deletion on synaptic damage and mitophagy in the hippocampus of a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Read More

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Pathophysiology of Mitochondrial Dysfunction in Human Spermatozoa: Focus on Energetic Metabolism, Oxidative Stress and Apoptosis.

Antioxidants (Basel) 2021 Apr 28;10(5). Epub 2021 Apr 28.

Andrology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

The dogma of mitochondria as the major source of energy in supporting sperm motility should be critically reconsidered in the light of several experimental data pointing to a major role of glycolysis in mammalian spermatozoa. In this light, the reported positive correlation between the mitochondrial membrane potential (ΔΨm) and motility of ejaculated spermatozoa cannot be explained convincingly by an impaired mitochondrial ATP generation only. Evidence has been produced suggesting that, in human sperm, dysfunctional mitochondria represent the main site of generation of reactive oxygen species (ROS). Read More

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The Role of Oxidative Stress Markers in Predicting Acute Thrombotic Occlusion of Haemodialysis Vascular Access and Progressive Stenotic Dysfunction Demanding Angioplasty.

Antioxidants (Basel) 2021 Apr 8;10(4). Epub 2021 Apr 8.

Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina, Chapel Hill, NC 27599, USA.

Haemodialysis vascular access (VA) dysfunction is a major cause of morbidity in haemodialysis (HD) patients. Primary venous outflow occlusion and restenosis after percutaneous transluminal angioplasty (PTA) are two major obstacles for the long-term use of dialysis VA. It remains unclear whether oxidative stress markers can be used as predictors for thrombotic occlusion of VA and progressive stenosis dysfunction demanding PTA. Read More

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Abnormalities of mitochondrial dynamics and bioenergetics in neuronal cells from CDKL5 deficiency disorder.

Neurobiol Dis 2021 Jul 24;155:105370. Epub 2021 Apr 24.

Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Discipline of Child & Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. Electronic address:

CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental disorder caused by pathogenic variants in the Cyclin-dependent kinase-like 5 (CDKL5) gene, resulting in dysfunctional CDKL5 protein. It predominantly affects females and causes seizures in the first few months of life, ultimately resulting in severe intellectual disability. In the absence of targeted therapies, treatment is currently only symptomatic. Read More

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Shear-Regulated Extracellular Microenvironments and Endothelial Cell Surface Integrin Receptors Intertwine in Atherosclerosis.

Fan-E Mo

Front Cell Dev Biol 2021 6;9:640781. Epub 2021 Apr 6.

Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Mechanical forces imposed by blood flow shear stress directly modulate endothelial gene expression and functional phenotype. The production of extracellular matrix proteins and corresponding cell-surface integrin receptors in arterial endothelial cells is intricately regulated by blood flow patterns. Laminar blood flow promotes mature and atheroresistant endothelial phenotype, while disturbed flow induces dysfunctional and atheroprone endothelial responses. Read More

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Proline metabolism and transport in retinal health and disease.

Amino Acids 2021 Apr 19. Epub 2021 Apr 19.

Department of Ophthalmology, University of Washington, Seattle, WA, 98109, USA.

The retina is one of the most energy-demanding tissues in the human body. Photoreceptors in the outer retina rely on nutrient support from the neighboring retinal pigment epithelium (RPE), a monolayer of epithelial cells that separate the retina and choroidal blood supply. RPE dysfunction or cell death can result in photoreceptor degeneration, leading to blindness in retinal degenerative diseases including some inherited retinal degenerations and age-related macular degeneration (AMD). Read More

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Myeloperoxidase Targets Apolipoprotein A-I for Site-Specific Tyrosine Chlorination in Atherosclerotic Lesions and Generates Dysfunctional High-Density Lipoprotein.

Chem Res Toxicol 2021 Apr 16. Epub 2021 Apr 16.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Jiangxi Key Laboratory of Green Chemistry, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear. Read More

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The Kidney-Heart Connection in Obesity.

Nephron 2021 Apr 13:1-5. Epub 2021 Apr 13.

Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.

There is a strong relationship between the kidney and the heart, where if one of these organs fails, so does the other, in the so-called cardiorenal syndrome (CRS). Besides, there are also interactions with the rest of the body leading to a metabolic state that establishes a feedback loop that is perpetuated. The CRS is characterized by hemodynamic changes, activation of neuro-humoral systems, natriuretic peptides, and changes in mineral metabolism. Read More

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Fatty acid synthase inhibition ameliorates diabetes induced liver injury in rodent experimental model.

Eur J Pharmacol 2021 Jun 9;901:174078. Epub 2021 Apr 9.

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India. Electronic address:

The abnormal dietary life style leads to hyperlipidemia and insulin resistance with ectopic lipid accumulation and elevated levels of hepatic glucose development which are the underlying pathological characteristics of fatty liver diseases. The pharmacological inhibition of fatty acid synthase of de novo lipogenesis may regulate the dysfunctional lipid biotransformation and reverse the pathological state of diabetic liver injury. The three pharmacological interventions (PTS; Pterostilbene, ARB; Arbutin, PUR; Purpurin) were administered to manage the condition of diabetic liver injury against the high fat diet (HFD) + Streptozotocin (STZ) 30 mg/kg b. Read More

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A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden.

Eur J Endocrinol 2021 May 4;184(6):823-835. Epub 2021 May 4.

Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.

Background: The response of advanced adrenocortical carcinoma (ACC) to current chemotherapies is unsatisfactory and a limited rate of response to immunotherapy was observed in clinical trials. High tumour mutational burden (TMB) and the presence of a specific DNA signature are characteristic features of tumours with mutations in the gene MUTYH encoding the mutY DNA glycosylase. Both have been shown to potentially predict the response to immunotherapy. Read More

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Kv1.3 voltage-gated potassium channels link cellular respiration to proliferation through a non-conducting mechanism.

Cell Death Dis 2021 Apr 7;12(4):372. Epub 2021 Apr 7.

School of Medicine, University of Leeds, Leeds, LS2 9JT, UK.

Cellular energy metabolism is fundamental for all biological functions. Cellular proliferation requires extensive metabolic reprogramming and has a high energy demand. The Kv1. Read More

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Detection of Rare Germline Variants in the Genomes of Patients with B-Cell Neoplasms.

Cancers (Basel) 2021 Mar 16;13(6). Epub 2021 Mar 16.

Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.

There is growing evidence indicating the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of likely disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment for two genes in rare dysfunctional variants, both of which participate in the regulation of oxidative stress pathways ( and ). Read More

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Abundance of Microvascular Endothelial Cells Is Associated with Response to Chemotherapy and Prognosis in Colorectal Cancer.

Cancers (Basel) 2021 Mar 23;13(6). Epub 2021 Mar 23.

Roswell Park Comprehensive Cancer Center, Department of Surgical Oncology, Buffalo, NY 14263, USA.

The generation of pathologic, immature, and dysfunctional vessels by angiogenesis is a mechanism of metastasis that has been a therapeutic target for colorectal cancer (CRC). In this study, we investigated the clinical relevance of intra-tumoral microvascular endothelial (mvE) cells in CRC using the xCell algorithm on transcriptome. A total of 1244 CRC patients in discovery and validation cohorts were analyzed. Read More

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