scholarly journals The Role of Nrf2 in Cardiovascular Function and Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Sandro Satta ◽  
Ayman M. Mahmoud ◽  
Fiona L. Wilkinson ◽  
M. Yvonne Alexander ◽  
Stephen J. White
Keyword(s):  
Cardiovascular Disease ◽  
Free Radicals ◽  
Cell Function ◽  
Treatment Strategies ◽  
Antioxidant Response ◽  
Cellular Damage ◽  
Current Status ◽  
Intercellular Signaling ◽  
Dynamic Regulation ◽  
The Impact

Free radicals, reactive oxygen/nitrogen species (ROS/RNS), hydrogen sulphide, and hydrogen peroxide play an important role in both intracellular and intercellular signaling; however, their production and quenching need to be closely regulated to prevent cellular damage. An imbalance, due to exogenous sources of free radicals and chronic upregulation of endogenous production, contributes to many pathological conditions including cardiovascular disease and also more general processes involved in aging. Nuclear factor erythroid 2-like 2 (NFE2L2; commonly known as Nrf2) is a transcription factor that plays a major role in the dynamic regulation of a network of antioxidant and cytoprotective genes, through binding to and activating expression of promoters containing the antioxidant response element (ARE). Nrf2 activity is regulated by many mechanisms, suggesting that tight control is necessary for normal cell function and both hypoactivation and hyperactivation of Nrf2 are indicated in playing a role in different aspects of cardiovascular disease. Targeted activation of Nrf2 or downstream genes may prove to be a useful avenue in developing therapeutics to reduce the impact of cardiovascular disease. We will review the current status of Nrf2 and related signaling in cardiovascular disease and its relevance to current and potential treatment strategies.

scholarly journals Prevalence of comorbidity in Chinese patients with COVID-19: systematic review and meta-analysis of risk factors

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingxuan Yin ◽  
Yuanjun Li ◽  
Ying Ying ◽  
Zhijun Luo
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Cerebrovascular Disease ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Chinese Patients ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Underlying Diseases ◽  
The Impact

Abstract Background Coronavirus disease 2019 (COVID-19) is an infectious disease characterized by cough, fever, and fatigue and 20% of cases will develop into severe conditions resulting from acute lung injury with the manifestation of the acute respiratory distress syndrome (ARDS) that accounts for more than 50% of mortality. Currently, it has been reported that some comorbidities are linked with an increased rate of severity and mortality among COVID-19 patients. To assess the role of comorbidity in COVID-19 progression, we performed a systematic review with a meta-analysis on the relationship of COVID-19 severity with 8 different underlying diseases. Methods PubMed, Web of Science, and CNKI were searched for articles investigating the prevalence of comorbidities in severe and non-severe COVID-19 patients. A total of 41 studies comprising 12,526 patients were included. Results Prevalence of some commodities was lower than that in general population such as hypertension (19% vs 23.2%), diabetes (9% vs 10.9%), chronic kidney disease (CKD) (2% vs 9.5%), chronic liver diseases (CLD) (3% vs 24.8%) and chronic obstructive pulmonary disease (COPD) (3% vs 8.6%), while some others including cancer (1% vs 0.6%), cardiovascular disease (6% vs 1.8%) and cerebrovascular disease (2% vs 0.9%) exhibited greater percentage in COVID-19. Cerebrovascular disease (OR = 3.70, 95%CI 2.51–5.45) was found to be the strongest risk factor in disease exacerbation, followed by CKD (OR = 3.60, 95%CI 2.18–5.94), COPD (OR = 3.14, 95% CI 2.35–4.19), cardiovascular disease (OR = 2.76, 95% CI 2.18–3.49), malignancy (OR = 2.63, 95% CI 1.75–3.95), diabetes (OR = 2.49, 95% CI 2.10–2.96) and hypertension (OR = 2.13, 95% CI 1.81–2.51). We found no correlation between CLD and increased disease severity (OR = 1.32, 95% CI 0.96–1.82). Conclusion The impact of all eight underlying diseases on COVID-19 deterioration seemed to be higher in patients outside Hubei. Based on different comorbidities, COVID-19 patients tend to be at risk of developing poor outcomes to a varying degree. Thus, tailored infection prevention and monitoring and treatment strategies targeting these high-risk subgroups might improve prognosis during the COVID-19 pandemic.

scholarly journals Glia-Neuron Interactions in the Retina Can Be Studied in Cocultures of Müller Cells and Retinal Ganglion Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
D. M. Skytt ◽  
A. K. Toft-Kehler ◽  
C. T. Brændstrup ◽  
S. Cejvanovic ◽  
I. S. Gurubaran ◽  
...  
Keyword(s):  
Cell Function ◽  
Ganglion Cells ◽  
Glutamate Uptake ◽  
Treatment Strategies ◽  
Müller Cells ◽  
Müller Cell ◽  
Retinal Ganglion ◽  
Muller Cells ◽  
Muller Cell ◽  
The Impact

Glia-neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing energy sources. The aim was to explore the impact of Müller cells on RGC survival. To investigate the Müller cell/RGC interactions we developed a coculture model, in which primary Müller cells were grown in inserts on top of pure primary RGC cultures. The impact of starvation and mitochondrial inhibition on the Müller cell ability to protect RGCs was studied. Moreover, the ability of Müller cells to remove glutamate from the extracellular space was investigated. RGC survival was evaluated by cell viability assays and glutamate uptake was assessed by kinetic uptake assays. We demonstrated a significantly increased RGC survival in presence of untreated and prestarved Müller cells. Additionally, prestarved Müller cells significantly increased RGC survival after mitochondrial inhibition. Finally, we revealed a significantly increased ability to take up glutamate in starved Müller cells. Overall, our study confirms essential roles of Müller cells in RGC survival. We suggest that targeting Müller cell function could have potential for future treatment strategies to prevent blinding neurodegenerative retinal diseases.

scholarly journals DNA Base Excision Repair: The Achilles' Heel of Tumour Cells and their Microenvironment?

2017 ◽  
Vol 23 (32) ◽  
pp. 4758-4772 ◽  
Author(s):  
Mattia Poletto ◽  
Arnaud J. Legrand ◽  
Grigory L. Dianov
Keyword(s):  
Dna Repair ◽  
Base Excision Repair ◽  
Synthetic Lethality ◽  
Excision Repair ◽  
Treatment Strategies ◽  
Current Status ◽  
Repair System ◽  
Dna Base ◽  
Base Excision ◽  
The Impact

Our current understanding of cancer suggests that every tumour has individual features. Approaches to cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system that is responsible for maintaining genome integrity. The BER pathway prevents the occurrence of disease, including cancer, by constantly repairing DNA base lesions and DNA single strand breaks caused by endogenous and exogenous mutagens. BER is an important DNA repair system for cancer cell survival, as it can affect both chemoand radio-resistance of tumours. Variations in BER capacity are likely responsible for a number of cases of sporadic cancer and may also modulate cancer sensitivity and resistance to therapeutic treatments. For these reasons, it is broadly accepted that targeting BER enzymes might be a promising approach to personalised anti-cancer therapy. However, recent advances in both treatment strategies and the comprehension of cancer development call for a better understanding of the consequences of BER inhibition. Indeed, the impact on both the tumour microenvironment and healthy tissues is still unclear. This review will summarise the current status of the approaches exploiting BER targeting, describing the most promising small molecule inhibitors and synthetic lethality strategies, as well as potential limitations of these approaches.

scholarly journals Coffee Extends Yeast Chronological Lifespan through Antioxidant Properties

2020 ◽  
Vol 21 (24) ◽  
pp. 9510
Author(s):  
Jadwiga Czachor ◽  
Michał Miłek ◽  
Sabina Galiniak ◽  
Karolina Stępień ◽  
Małgorzata Dżugan ◽  
...  
Keyword(s):  
Free Radicals ◽  
High Performance ◽  
Cell Function ◽  
Budding Yeast ◽  
Antioxidant Properties ◽  
Strand Break ◽  
Yeast Cells ◽  
Chromatography Method ◽  
Chronological Lifespan ◽  
The Impact

Aging is a multifactorial process accompanied by loss of cell function. Science has been looking for factors responsible for aging for many years. However, despite identifying a number of possible causes, the definite reason for aging has been elusive so far. One of the factors contributing to aging is oxygen free radicals. In this context, beneficial effects of coffee on various organisms, including humans, were investigated, although the results are far from unequivocal. In our research, we used the budding yeast—something of a workhorse in many studies, including the studies of aging. So far, the impact of coffee on the aging of cells in the budding yeast experimental setup has little known about it. Here, we provide strong evidence that coffee compounds, particularly flavonoids, are responsible for scavenging free radicals and longevity in yeast lacking Sod1, Sod2 and Rad52 proteins. In this paper, we compared Arabica and Robusta coffee types. We present an analysis of the concentration of caffeine and flavonoids measured by the High-Performance Liquid Chromatography method. We show that Robusta has a much greater antioxidant capacity than Arabica. We also conclude that coffee infusions significantly extend the chronological lifespan of the Saccharomyces cerevisiae yeast cells by protecting cells against reactive oxygen species, double DNA-strand break and decrease in metabolic activity.

scholarly journals Oxidative Free Radicals and Other Species: Selective Messengers with a Reactive Capacity for Unselective Tissue Damage

Chemosensors ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 89
Author(s):  
Pankaj Vadgama
Keyword(s):  
Cardiovascular Disease ◽  
Free Radicals ◽  
Tissue Damage ◽  
Antioxidant Status ◽  
Molecular Assembly ◽  
Current Status ◽  
Target Species ◽  
Molecular Reactivity ◽  
Reactive Capacity ◽  
Damage Processes

Oxygen and nitrogen free radicals (RONS) form an exceptionally reactive molecular assembly within eukaryote cells. This perspective article gives a combined overview of different facets of research covering molecular reactivity, resultant tissue damage and final tissue outcomes as they relate to major disease. There is an emphasis on cardiovascular disease, as the damage processes are best liked to the pathology. The overriding importance of inflammation in driving damage across all tissues is highlighted. Brief coverage is also provided of measurement approaches, respectively for antioxidant status, using potentiometry, and voltammetry for selected target species. Whilst damage due to RONS is a common focus, the fundamental importance of RONS to biological signalling is also covered here as an indispensable basis for life. The article thus provides a global overview of this topic for anyone wishing to understand the current status across multiple fronts.

IDENTIFICATION AND ASSESSMENT OF RISK FACTORS ROLE IN MYOCARDIAL INFARCTION DEVELOPMENT

2019 ◽  
Vol 72 (5) ◽  
pp. 779-783
Author(s):  
Victor A. Ognev ◽  
Anna A. Podpriadova ◽  
Anna V. Lisova
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Control Group ◽  
Biological Factors ◽  
Prevention And Treatment ◽  
High Level ◽  
Social Importance ◽  
The Impact

Introduction:The high level of morbidity and mortality from cardiovascular disease is largely due toinsufficient influence on the main risk factors that contribute to the development of myocardial infarction.Therefore, a detailed study and assessment of risk factors is among the most important problems of medical and social importance. The aim: To study and evaluate the impact of biological, social and hygienic, social and economic, psychological, natural and climatic risk factors on the development of myocardial infarction. Materials and methods: A sociological survey was conducted in 500 people aged 34 to 85. They were divided into two groups. The main group consisted of 310 patients with myocardial infarction. The control group consisted of 190 practically healthy people, identical by age, gender and other parameters, without diseases of the cardiovascular system. Results: It was defined that 30 factors have a significant impact on the development of myocardial infarction.Data analysis revealed that the leading risk factors for myocardial infarction were biological and socio-hygienic. The main biological factors were: hypertension and hypercholesterolemia. The man socio-hygienic factor was smoking. Conclusions: Identification of risk factors provides new opportunities for the development of more effective approaches for the prevention and treatment of myocardial infarction.

Clinical Pharmacokinetic Studies in Pregnant Women and the Relevance of Pharmacometric Tools

2019 ◽  
Vol 25 (5) ◽  
pp. 483-495 ◽  
Author(s):  
André Dallmann ◽  
Paola Mian ◽  
Johannes Van den Anker ◽  
Karel Allegaert
Keyword(s):  
Pregnant Women ◽  
Clinical Pharmacokinetic ◽  
Individual Variability ◽  
Current Status ◽  
Pharmacokinetic Studies ◽  
Full Potential ◽  
Pbpk Models ◽  
Pregnancy And Postpartum ◽  
Population Pk ◽  
The Impact

Background: In clinical pharmacokinetic (PK) studies, pregnant women are significantly underrepresented because of ethical and legal reasons which lead to a paucity of information on potential PK changes in this population. As a consequence, pharmacometric tools became instrumental to explore and quantify the impact of PK changes during pregnancy. Methods: We explore and discuss the typical characteristics of population PK and physiologically based pharmacokinetic (PBPK) models with a specific focus on pregnancy and postpartum. Results: Population PK models enable the analysis of dense, sparse or unbalanced data to explore covariates in order to (partly) explain inter-individual variability (including pregnancy) and to individualize dosing. For population PK models, we subsequently used an illustrative approach with ketorolac data to highlight the relevance of enantiomer specific modeling for racemic drugs during pregnancy, while data on antibiotic prophylaxis (cefazolin) during surgery illustrate the specific characteristics of the fetal compartments in the presence of timeconcentration profiles. For PBPK models, an overview on the current status of reports and papers during pregnancy is followed by a PBPK cefuroxime model to illustrate the added benefit of PBPK in evaluating dosing regimens in pregnant women. Conclusions: Pharmacometric tools became very instrumental to improve perinatal pharmacology. However, to reach their full potential, multidisciplinary collaboration and structured efforts are needed to generate more information from already available datasets, to share data and models, and to stimulate cross talk between clinicians and pharmacometricians to generate specific observations (pathophysiology during pregnancy, breastfeeding) needed to further develop the field.

Treatment Strategies Against Diabetic Foot Ulcer: Success so far and Road Ahead

2020 ◽  
Vol 16 ◽  
Author(s):  
Ankit Awasthi ◽  
Sachin Kumar Singh ◽  
Bimlesh Kumar ◽  
Monica Gulati ◽  
Rajesh Kumar ◽  
...  
Keyword(s):  
Lower Limb ◽  
Diabetic Foot ◽  
Treatment Strategies ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Arterial Disease ◽  
Current Status ◽  
Limb Amputation ◽  
Bibliographic Databases ◽  
Inflammatory Phase

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It isassociated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. Basically, there are four stages of wound healing namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Traditionally the dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer from many years. Introduction: In this review the global prevalence as well as etiopathogenesis related to diabetic foot ulcer has been discussed. Potential role of various synthetic and herbal drugs as well as their conventional dosage form for the effective management of diabetes foot ulcer has been highlighted. Methods: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of various approaches that are used for the treatment of diabetic foot ulcer. Results: About 142 papers including both, research and review articles, were included in this review in order to produce a comprehensive as well as readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action. Conclusion: DFU has become one of the most common complications in patients having more than ten years of diabetes. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as judicious selection of drug as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemics or, they have been repositioned. Moreover, in clinical practice, much focus has been given towards dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that a combination therapy of herbal and synthetic drug with multiple treatment pathway could be able to overcome the disease.

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

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