scholarly journals Erythropoietin, Forkhead Proteins, and Oxidative Injury: Biomarkers and Biology

2009 ◽  
Vol 9 ◽  
pp. 1072-1104 ◽  
Author(s):  
Kenneth Maiese ◽  
Jinling Hou ◽  
Zhao Zhong Chong ◽  
Yan Chen Shang
Keyword(s):  
Oxidative Stress ◽  
Cell Biology ◽  
Cellular Proliferation ◽  
Clinical Care ◽  
Disease Onset ◽  
Cell Development ◽  
The Body ◽  
Treatment Regimens ◽  
Cellular Pathways ◽  
Novel Therapeutic Strategies

Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO), and members of the mammalian forkhead transcription factors of the O class (FoxOs), may offer the greatest promise for new treatment regimens, since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. Yet, EPO and FoxOs may sometimes have unexpected and undesirable effects that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as the complex role that EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

scholarly journals A Fork in the Path: Developing Therapeutic Inroads with FoxO Proteins

2009 ◽  
Vol 2 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Kenneth Maiese ◽  
Jinling Hou ◽  
Zhao Zhong Chong ◽  
Yan Chen Shang
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cellular Proliferation ◽  
Cell Injury ◽  
Clinical Care ◽  
Immune Surveillance ◽  
The Body ◽  
Wnt Proteins ◽  
Promote Cell Survival ◽  
Novel Therapeutic Strategies

Advances in clinical care for disorders involving any system of the body necessitates novel therapeutic strategies that can focus upon the modulation of cellular proliferation, metabolism, inflammation and longevity. In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. Furthermore, these transcription factors are closely integrated with several novel signal transduction pathways, such as erythropoietin and Wnt proteins, that may influence the ability of FoxOs to act as a “double-edge sword” to sometimes promote cell survival, but at other times lead to cell injury. Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer.

scholarly journals Identify and Assess Drug Interactions with Atorvastatin in Inpatient Care

2021 ◽  
pp. 297-306
Author(s):  
Ibrahim Dighriri ◽  
Abdulrahman Hommadi ◽  
Hatim Zaeri ◽  
Rahaf Aldajany ◽  
Rahaf Alotaibi ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Health Care Professionals ◽  
Clinical Care ◽  
Density Lipoprotein ◽  
The Body ◽  
Heart Attacks ◽  
Treatment Regimens ◽  
Long Acting ◽  
Coa Reductase ◽  
Clinical Interactions

Background: Atorvastatin is a recent HMG-COA reductase inhibitor used to treat primary hypercholesterolemia, homozygous familial hypercholesterolemia, and mixed dyslipidemias. It is also taken to prevent heart disease, including strokes and heart attacks. In addition, Atorvastatin is used to lower bad cholesterol low-density lipoproteins (LDL) levels, increase good cholesterol high-density lipoprotein (HDL) levels, and lower triglycerides. It works by reducing the amount of cholesterol produced in the body, hence reducing the amount of cholesterol that may build up on the walls of arteries. Atorvastatin is long-acting, has few adverse effects, and is low in price. Nevertheless, it interacts with a wide variety of medications. These interactions may be lead to adverse drug reactions. Objective: The study aims to identify and asset atorvastatin interactions with other medicines at King Abdulaziz Hospital. Also, to prevent atorvastatin interactions in the future. Methods: The retrospective study investigated 280 electronic prescriptions inside the inpatient clinic at King Abdulaziz Hospital in Saudi Arabia between January and April 2021 to identify and asset interactions among atorvastatin and different medications. Results: Most atorvastatin interactions are category C (44.64%) and category B (41.43%). Atorvastatin had the most common interactions with esomeprazole (16.07%), clopidogrel (14.64%), and sitagliptin (12.14%). Atorvastatin had clinical interactions with medications metabolized by the cytochrome P450 3A4 )CYP3A4(. Use of atorvastatin with cyclosporine or clarithromycin increased the risk for atorvastatin toxicities such as myopathy and rhabdomyolysis. In addition, Atorvastatin decreases clopidogrel's antiplatelet effect and increases the risk of skeletal muscle toxicity of daptomycin. Conclusion: The majority of atorvastatin interactions may be avoided by adhering to best practices in clinical care and clinical pharmacology, such as avoiding complicated treatment regimens, utilizing a single pharmacy for all prescriptions, and recognizing patient risk factors. Health care professionals should use drug-drug interaction checkers such as Medscape and Micromedex, as well as a book such as the Handbook of Drug Interactions.

Iron Metabolism in the Human Body and Setting its Hygienic Limits for Drinking Water. Review. Part 2

2020 ◽  
Vol 99 (5) ◽  
pp. 504-508
Author(s):  
Natalija A. Egorova ◽  
N. V. Kanatnikova
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Iron Overload ◽  
Iron Metabolism ◽  
Subcutaneous Tissue ◽  
Allergic Diseases ◽  
The Body ◽  
Urogenital System ◽  
High Iron Content ◽  
Labile Iron Pool

Iron is an assential element for the growth, division, differentiation and functioning of any cell in the body. Iron is virtually important for human and danger at the same time, because with excessive accumulation it causes oxidative stress with formation of highly active oxygen radicals and reactive form of nitrogen that can destroy cell membranes, proteins, nucleic acids, reduce cell viability, with, according to modern concepts, can contribute to the development of many diseases (cardiovascular, rheumatic, gastrointestinal, neurodegenerative, oncological, metabolic and others), and also accelerate the aging process. Part 1 of this review discussed the issues of iron metabolism in human, including its regulation at the cellular and systemic levels, the intake, transport, use, accumulation and export of iron in cells, the role of the labile iron pool in the cytoplasm of cells and plasma non-transferrin bound iron. Data are provided on the causes, frequency and significance of iron overload in the formation of free radicals and the development of oxidative stress. Part 2 of the review provides information on diseases associated with iron overload as well as information on ferroptosis - a new type of iron-dependent regulated cell death. Attention is paid to the works of domestic authors, where it was found that prolonged use of drinking water with a high iron content is unfavorable for the population and leads to an increase in the overall incidence, the development of the diseases of the blood, skin and subcutaneous tissue, musculoskeletal system, digestive system, urogenital system, and allergic diseases. Separate publications are cited on the possibility of a negative effect of iron at concentrations in water of 0.3 mg/l and lower. The material of the review emphasizes the preventive significance of caution attitude to regulating iron in the water in the Russian Federation, where 1/3 of the population uses iron-containing water for drinking, and substantiate the feasibility of establishing a hygienic limit for iron in water not higher than 0.3 mg/l.

Assessment of indicators of nervous and emotional stress in medical center personnel depending on the characteristics of their professional activity

2020 ◽  
Vol 60 (10) ◽  
pp. 650-657
Author(s):  
Irina V. Fedotova ◽  
Tatyana N. Vasilyeva ◽  
Tatyana V. Blinova ◽  
Irina A. Umnyagina ◽  
Yuliya V. Lyapina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Emotional Stress ◽  
Functional State ◽  
Working Conditions ◽  
Medical Staff ◽  
Medical Center ◽  
The Body ◽  
Office Workers ◽  
Glutathione System ◽  
Medical Centers

Introduction. Digital technologies are actively used in the work of specialists of medical centers of various profiles, which causes the impact on employees of a number of professional factors that determine the characteristics of their work. The aim of the study is to evaluate the influence of professional factors on the functional state of the employees' body and the glutathione system as an objective indicator of stress based on the analysis of the subjective perception of the medical center employees of the specifics of working with personal computers and psychophysiological testing. Materials and methods. The study involved 109 specialists of medical centers (25 ophthalmologists, 31 representatives of the secondary medical staff - nurses and paramedics, 53 office employees). The anonymous survey concerned the assessment of working conditions and their impact on the functional state of the body of the respondents. Performance and stress tolerance indicators were evaluated using three standard questionnaires. The study of 66 subjects' levels of glutathione in the blood: total, reduced, oxidized and the ratio of reduced and oxidized - was used to analyze the relationship of the neuro-emotional nature of labor with the reaction of oxidative stress. Statistical processing of the obtained data was carried out using traditional methods of variation statistics and calculating the value of the odds ratio (OR) with a 95% confidence interval (CI). Results. The survey revealed a significant proportion of people in all groups of respondents who constantly use computer technology in their work. Describing the quality of the processed information, doctors more than representatives of other groups note its complexity, importance, negative emotional color, a high degree of responsibility and tension. Doctors more often than average medical staff and office workers associate the manifestation of fatigue with an uncomfortable state of the visual organ, nervous system, and musculoskeletal system. The subjects showed reduced performance and stress tolerance with the most pronounced negative trends in the group of doctors. Changes in the glutathione system were detected, indicating the presence of oxidative stress in 40% of ophthalmologists and office workers, and in half of nurses. Conclusions. The work of specialists of medical centers of various profiles in accordance with their assessment is characterized by high nervous and emotional stress, due to the need to process a significant amount of complex and important professionally significant information. Subjectively noted by respondents the influence of working conditions on the functional state of the body is confirmed by indicators of the glutathione system, which can be used as indicators of nervous and emotional stress.

Gender differences in biochemical measurement reflecting the state of free-radical oxidation and antioxidant protection among workers in metallurgical production

2019 ◽  
Vol 1 (10) ◽  
pp. 877-881
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Gender Differences ◽  
Free Radical ◽  
Biochemical Parameters ◽  
Free Radical Oxidation ◽  
The Body ◽  
Antioxidant Protection ◽  
Radical Oxidation ◽  
Metallurgical Production ◽  
Production Factors

Introduction. To date, age and sex differences have been established for many biochemical parameters. Gender differences in indicators for systems such as antioxidant, thiol-disulfide, oxidative stress and inflammation systems are absent or under study.The aim of the study was to identify gender differences in biochemical parameters reflecting the functioning of antioxidant systems of the body and free radical oxidation in workers of metallurgical production, in contact with harmful production factors.Materials and methods. The blood of men and women working at the metallurgical enterprise of the Nizhny Novgorod region (n=80) under the influence of a complex of physical and chemical production factors was studied. Total oxidative stress, total antioxidant capacity of serum, glutathione levels were studied by photometric biochemical methods. Levels of C-reactive protein and 8-hydroxy–2-deoxyguanosine were studied by ELISA.Results. The average amount of peroxides in the serum of women exceeded 1.6 times this figure in men. In the group of men, the content of 8-Ondg was higher by 26% (p=0.012), the level of GS-by 12% (p=0.019), the activity of SOD — by 1.5–2 times (p=0.0001), the level of CRP — by 2 times (p=0.008) compared to similar indicators in women.Conclusions. Studies of gender differences in workers under the influence of harmful production factors will allow more effective approach to the etiology, treatment and prognosis of production-related diseases. Indicators of oxidative stress and antioxidant protection can be indicators of the health of workers under the influence of harmful industrial factors and be important in the prevention of diseases associated with oxidative stress.

Sam Domains in Multiple Diseases

2020 ◽  
Vol 27 (3) ◽  
pp. 450-476 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Disease Onset ◽  
Protein Domain ◽  
Sam Domain ◽  
Different Types ◽  
Protein Functions ◽  
Helical Protein ◽  
The Many ◽  
Novel Therapeutic Strategies ◽  
Novel Drug ◽  
Pathological Event

Background: The sterile alpha motif (Sam) domain is a small helical protein module, able to undergo homo- and hetero-oligomerization, as well as polymerization, thus forming different types of protein architectures. A few Sam domains are involved in pathological processes and consequently, they represent valuable targets for the development of new potential therapeutic routes. This study intends to collect state-of-the-art knowledge on the different modes by which Sam domains can favor disease onset and progression. Methods: This review was build up by searching throughout the literature, for: a) the structural properties of Sam domains, b) interactions mediated by a Sam module, c) presence of a Sam domain in proteins relevant for a specific disease. Results: Sam domains appear crucial in many diseases including cancer, renal disorders, cataracts. Often pathologies are linked to mutations directly positioned in the Sam domains that alter their stability and/or affect interactions that are crucial for proper protein functions. In only a few diseases, the Sam motif plays a kind of "side role" and cooperates to the pathological event by enhancing the action of a different protein domain. Conclusion: Considering the many roles of the Sam domain into a significant variety of diseases, more efforts and novel drug discovery campaigns need to be engaged to find out small molecules and/or peptides targeting Sam domains. Such compounds may represent the pillars on which to build novel therapeutic strategies to cure different pathologies.

Evaluation of Salivary Antioxidants and Oxidative Stress Markers in Male Smokers

2019 ◽  
Vol 22 (7) ◽  
pp. 496-501
Author(s):  
Fatemeh Ahmadi-Motamayel ◽  
Parisa Falsafi ◽  
Hamidreza Abolsamadi ◽  
Mohammad T. Goodarzi ◽  
Jalal Poorolajal
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Free Radicals ◽  
Antioxidant Capacity ◽  
Cigarette Smoke ◽  
Total Antioxidant Capacity ◽  
The Body ◽  
Total Antioxidant ◽  
The Mean ◽  
And Oxidative Stress

Background: Cigarette smoke free radicals can cause cellular damage and different diseases. All the body fluids have antioxidants which protect against free radicals. Objective: The aim of this study was to evaluate salivary total antioxidant capacity and peroxidase, uric acid and malondialdehyde levels in smokers and a nonsmoking control group. Methods: Unstimulated saliva was collected from 510 males. A total of 259 subjects were current smokers and 251 were non-smokers. The levels of salivary total antioxidant capacity, uric acid, peroxidase and malondialdehyde were measured using standard procedures. Data were analyzed with t test and ANOVA. Results: The smokers were younger and dental hygiene index was higher than healthy nonsmoking controls. The mean total antioxidant capacity in smokers and nonsmokers was 0.13±0.07 and 0.21±011, respectively (P=0.001). Smokers had significantly lower peroxidase and uric acid levels than healthy controls. In addition, the mean malondialdehyde levels in the smokers and nonsmokers were 4.55 ±2.61 and 2.79 ±2.21, respectively (P=0.001). Conclusion: Cigarette smoke produces free radical and oxidative stress, causing many side effects. Salivary antioxidant levels decreased and malondialdehyde levels increased in smokers, indicating the high oxidative stress among smokers compared to nonsmokers. Cigarette smoke had deleterious effects on main salivary antioxidants levels.

scholarly journals Hypoglycemic and antioxidative activities of ethanol seed extract of Hunteria umbellate (Hallier F.) on streptozotocin-induced diabetic rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olubanke O. Ogunlana ◽  
Babatunde O. Adetuyi ◽  
Miracle Rotimi ◽  
lohor Esalomi ◽  
Alaba Adeyemi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Seed Extract ◽  
The Body ◽  
High Concentration ◽  
Group 5

Abstract Background Diabetes, a global cause of mortality in developing countries is a chronic disorder affecting the metabolism of macromolecules and has been attributed to the defective production and action of insulin characterized by persistent hyperglycemic properties. This global disorder harms organs of the body such as the liver, kidney and spleen. Medicinal plants such as Hunteria umbellate have been shown to possess hypoglycemic, antioxidative and anti-diabetic properties owing to the high concentration of active phytochemical constituents like flavonoids and alkaloids. The present study seeks to evaluate the hypoglycemic activities of ethanolic seed extract of Hunteria umbellate on streptozotocin-induced diabetes rats. Methods Thirty (30) female experimental rats were randomly divided into five groups with six rats per group and were administered streptozotocin (STZ) and Hunteria umbellate as follows. Group 1 served as control and was given only distilled water, group 2 rats were administered 60 mg/kg STZ; Group 3 was administered 60 mg/kg STZ and 100 mg/kg metformin; group 4 rats were administered 60 mg/kg STZ and 800 mg/kg Hunteria umbellate, group 5 rats 60 mg/kg STZ and 400 mg/kg Hunteria umbellate. The fasting blood glucose level of each rat was measured before sacrifice. Rats were then sacrificed 24 h after the last dose of treatment. Results The results showed that Hunteria umbellate significantly reversed STZ-induced increase in fasting blood glucose and increase in body and organs weight of rats. Hunteria umbellate significantly reversed STZ-induced decrease in antioxidant enzyme in liver, kidney and spleen of rats. Hunteria umbellate significantly reversed STZ-induced increase in oxidative stress markers in liver, kidney and spleen of rats. Conclusion Collectively, our results provide convincing information that inhibition of oxidative stress and regulation of blood glucose level are major mechanisms through which Hunteria umbellate protects against streptozotocin-induced diabketes rats.

scholarly journals Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 557
Author(s):  
Stephanie D. Burr ◽  
James A. Stewart
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Hydrogen Peroxide ◽  
Cardiac Fibroblasts ◽  
The Body ◽  
Signaling Cascade ◽  
Diabetic Mice ◽  
Pkc Ζ ◽  
Type 2 Diabetic

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accumulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. Previously, our lab has identified a small GTPase, Rap1a, that possibly overlaps the AGE/RAGE signaling cascade to affect the downstream outcomes. Rap1a acts as a molecular switch connecting extracellular signals to intracellular responses. Therefore, we hypothesized that Rap1a crosses the AGE/RAGE cascade to alter the expression of AGE/RAGE associated signaling proteins in cardiac fibroblasts in type 2 diabetic mice. To delineate this cascade, we used genetically different cardiac fibroblasts from non-diabetic, diabetic, non-diabetic RAGE knockout, diabetic RAGE knockout, and Rap1a knockout mice and treated them with pharmacological modifiers (exogenous AGEs, EPAC, Rap1a siRNA, and pseudosubstrate PKC-ζ). We examined changes in expression of proteins implicated as markers for myofibroblasts (α-SMA) and inflammation/oxidative stress (NF-κB and SOD-1). In addition, oxidative stress was also assessed by measuring hydrogen peroxide concentration. Our results indicated that Rap1a connects to the AGE/RAGE cascade to promote and maintain α-SMA expression in cardiac fibroblasts. Moreover, Rap1a, in conjunction with activation of the AGE/RAGE cascade, increased NF-κB expression as well as hydrogen peroxide concentration, indicating a possible oxidative stress response. Additionally, knocking down Rap1a expression resulted in an increase in SOD-1 expression suggesting that Rap1a can affect oxidative stress markers independently of the AGE/RAGE signaling cascade. These results demonstrated that Rap1a contributes to the myofibroblast population within the heart via AGE/RAGE signaling as well as promotes possible oxidative stress. This study offers a new potential therapeutic target that could possibly reduce the risk for developing diabetic cardiovascular complications attributed to AGE/RAGE signaling.

scholarly journals Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuang Li ◽  
Wenjuan Sun ◽  
Kai Zhang ◽  
Jiawei Zhu ◽  
Xueting Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Antioxidant Systems ◽  
Tunel Staining ◽  
White Pulp ◽  
Sibling Pairs ◽  
Se Deficiency ◽  
Spleen Index

Abstract Background The immune system is one aspect of health that is affected by dietary selenium (Se) levels and selenoprotein expression. Spleen is an important immune organ of the body, which is directly involved in cellular immunity. However, there are limited reports on Se levels and spleen health. Therefore, this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis. Methods Twenty-four pure line castrated male Yorkshire pigs (45 days old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into two equal groups and fed Se-deficient diet (0.007 mg Se/kg) or Se-adequate diet (0.3 mg Se/kg) for 16 weeks. At the end of the trial, blood and spleen were collected to assay for erythroid parameters, the osmotic fragility of erythrocytes, the spleen index, histology, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining, Se concentrations, the selenogenome, redox status, and signaling related inflammation and apoptosis. Results Dietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes (P < 0.05). The spleen index did not change, but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased, the red pulp increased, and splenocyte apoptosis occurred in the Se deficient group. Se deficiency decreased the Se concentration and selenoprotein expression in the spleen (P < 0.05), blocked the glutathione and thioredoxin antioxidant systems, and led to redox imbalance. Se deficiency activated the NF-κB and HIF-1α transcription factors, thus increasing pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α), decreasing anti-inflammatory cytokines (IL-10, IL-13, and TGF-β) and increasing expression of the downstream genes COX-2 and iNOS (P < 0.05), which in turn induced inflammation. In addition, Se-deficiency induced apoptosis through the mitochondrial pathway, upregulated apoptotic genes (Caspase3, Caspase8, and Bak), and downregulated antiapoptotic genes (Bcl-2) (P < 0.05) at the mRNA level, thus verifying the results of TUNEL staining. Conclusions These results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins, oxidative stress, inflammation and apoptosis.

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