Nadezda Apostolova

Nadezda Apostolova
University of Valencia | UV · Department of Pharmacology

PhD

About

110
Publications
72,503
Reads
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12,970
Citations
Citations since 2017
37 Research Items
8241 Citations
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Introduction
Nadezda Apostolova currently works at the Department of Pharmacology, University of Valencia. Nadezda does research in Cell Biology, Molecular Biology and Hepatology. Her current project is 'Implication of the anti-HIV therapy in the progression of chronic liver diseases .'

Publications

Publications (110)
Article
Significance: Type 2 diabetes, which is related to oxidative stress and mitochondrial dysfunction, is one of the most prevalent diseases in the world. In the last decade, alterations in autophagy have been shown to play a fundamental role in the development and control of type 2 diabetes. Furthermore, mitophagy has been recognised as a key player i...
Article
Full-text available
Lonp1 is a mitochondrial protease that degrades oxidized and damaged proteins, assists protein folding, and contributes to the maintenance of mitochondrial DNA. A higher expression of LonP1 has been associated with higher tumour aggressiveness. Besides the full-length isoform (ISO1), we identified two other isoforms of Lonp1 in humans, resulting fr...
Article
Full-text available
Gold-ceria nanoparticles (Au/CeO2) are known to have antioxidant properties. However, whether these nanoparticles can provide benefits in type 2 diabetes mellitus (T2D) remains unknown. This work aimed to study the effects of Au/CeO2 nanoparticles at different rates of gold purity (10, 4.4, 1.79 and 0.82) on leukocyte–endothelium interactions and i...
Article
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Editorial on the Research Topic Novel pharmacological approaches targeting mitochondrial dysfunction in diseases Because mitochondria play a crucial role in cellular homeostasis and energy balance, mitochondrial dysfunction is critically implicated in the pathobiology of various human diseases/conditions. Redox imbalance, abnormal mitochondrial bio...
Article
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The Ohrid-Prespa lake system is the oldest and most diverse permanent lake system in Europe, dating from the Pliocene era and aged at over 4Ma. Its smaller component is Lake Macro Prespa (thereafter called Prespa), shared by North Macedonia, Albania, and Greece. Lake Prespa’s depth was reported as 14 m mean and 48 m maximum before its major water l...
Article
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Type 2 diabetes is a chronic metabolic disease that affects mitochondrial function. In this context, the rescue mechanisms of mitochondrial health, such as mitophagy and mitochondrial biogenesis, are of crucial importance. The gold standard for the treatment of type 2 diabetes is metformin, which has a beneficial impact on the mitochondrial metabol...
Article
Full-text available
As the main extracellular matrix-producing cells, activated hepatic stellate cells (HSC) are fundamental mediators of liver fibrosis (LF), and understanding their activation/inactivation mechanisms is paramount to the search for novel therapeutics. The antiretroviral drug Rilpivirine (RPV) has demonstrated a hepatoprotective effect in several anima...
Article
Full-text available
The activity of sirtuin 1 (SIRT1), a class III histone deacetylase with a critical role in several biological functions, decreases with age and its deficiency is associated with many inflammatory and age-related diseases. It also regulates the chronic immune activation and viral latency during an HIV infection. The life-span and particularly the he...
Article
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Drug-induced liver injury (DILI) constitutes a clinical challenge due to the incomplete characterization of the mechanisms involved and potential risk factors. Efavirenz, an anti-HIV drug, induces deleterious actions in hepatocytes that could underlie induction of the NLRP3 inflammasome, an important regulator of inflammatory responses during liver...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Liver fibrosis (LF) occurs as a result of persistent liver injury and can be defined as a pathologic, chronic, wound‐healing process in which functional parenchyma is progressively replaced by fibrotic tissue. As a phenomenon involved in the majority of chronic liver diseases, and therefore prevalent, it exerts a significant impact on public health...
Article
Full-text available
Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency compli...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Type 2 diabetes is closely related to oxidative stress and cardiovascular diseases. In this study, we hypothesized that polymorphonuclear (PMN) leukocytes-endothelium interactions and autophagy are associated. We evaluated PMN-endothelial interactions, ROS production and autophagy parameters in 47 type 2 diabetic patients and 57 control subjects. P...
Article
Full-text available
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral...
Article
Full-text available
Type 2 diabetes (T2D) is one of the main current threats to human health. Both T2D and its numerous clinical complications are related to mitochondrial dysfunction and oxidative stress. Over the past decade, great progress has been made in extending our knowledge about the signaling events regulated by mitochondria. However, the links among mitocho...
Article
The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced i...
Article
Full-text available
Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor tha...
Article
Objective Liver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regene...
Article
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Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stre...
Article
Full-text available
Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stre...
Article
Self-assembled cationic micelles are an attractive platform for binding biologically-relevant polyanions such as heparin. This has potential applications in coagulation control, where a synthetic heparin rescue agent could be a useful replacement for protamine, which is in current clinical use. However, micelles can have low stability in human seru...
Article
Efavirenz (EFV), a first generation non-nucleoside analogue reverse transcriptase inhibitor widely employed in combination antiretroviral therapy regimens over the last 20 years, has been associated with a wide range of neuropsychiatric effects and has also been linked with HIV-associated neurocognitive disorder (HAND). EFV has been reported to alt...
Article
Full-text available
Significance: Type 2 diabetes mellitus and hyperglycaemia can lead to the development of comorbidities such as atherosclerosis and microvascular/macrovascular complications. Both type 2 diabetes and its complications are related to mitochondrial dysfunction and oxidative stress. Type 2 diabetes is also a chronic inflammatory condition that leads t...
Article
Full-text available
Since mitochondrial dysfunction is associated with NLRP3 activation in type 2 diabetes (T2D), which can eventually lead to an impaired immune response, we set out to determine if glycaemic control modulates the effects of T2D on the NLRP3 inflammasome. We have studied leukocytes from 61 diabetic patients (25 with HbA1c≤7% and 36 with HbA1c≥8%) and...
Article
Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tendency to aggregate in water. Bio...
Article
Full-text available
Background and purpose: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and...
Article
Background and purpose: Mitochondria-associated membranes (MAMs) are specific ER-domains that enable direct interaction with mitochondria and mediate metabolic flow and Ca(2+) transfer. A growing list of proteins have been identified as MAMs components, but how they are recruited and function during complex cell stress situations is still not unde...
Article
The HIV infection remains an important health problem worldwide. However, due to the efficacy of combined antiretroviral therapy (cART), it has ceased to be a mortal condition, becoming a chronic disease instead. Efavirenz, the most prescribed non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), has been a key component of cART since it...
Article
: There is a long-lasting controversy surrounding an association between Abacavir (ABC) and an increased risk of cardiovascular (CV) disease in HIV-positive subjects. While differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independe...
Conference Paper
Background and aim: Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. Chronic liver diseases are more prevalent in HIV patients than in the general population, mostly due to the infection itself but also to chronic antiretroviral treatment. Activation of hepatic stellate cells (HSCs) is a key process in the pr...
Poster
Full-text available
What is Studenchishte? • The very last wetland of a previously extensive riparian fringe located on the shore of ancient Lake Ohrid, a UNESCO World Heritage Site. • Mixture of natural and semi-natural habitats including fens and wet meadows that currently occupy about 50ha • In constant relationship with ancient Lake Ohrid • Important biodiversity...
Article
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Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was...
Article
Heat preconditioning is a rapid cellular adaptive mechanism shared by many cells/ organs / organisms that results in synthesis and accumulation of heat shock proteins (HSPs), which are responsible for increased tolerance and survival of animals during and after heat stress (HS). HSPs function as molecular chaperones by restoring cellular homeostasi...
Article
Proper function of the endoplasmic reticulum and mitochondria is essential for cellular homeostasis and the regulation of metabolic pathways. Perturbation of their function has been linked to pathophysiological states, including metabolic and liver diseases. Fatty liver diseases are a major health problem whose prevalence is dramatically increasing...
Article
Full-text available
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
Background: NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hepatotoxicity also involves mitochondrial interference, we hypothesized that it would be exacerbated in the context of ART. Methods: We e...
Article
Full-text available
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
Ceria nanoparticles with rhodamine B groups covalently attached on their surface (RhB-CeNPs) were successfully prepared to simultaneously exhibit antioxidant activity and the ability to detect oxidant species. In order to use them for biomedical purposes, the nanoparticles were internalized in two human cell lines (HeLa and Hep3B), confirmed by con...
Article
The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other...
Article
The NNRTI efavirenz is among the most widely employed antiretroviral drugs. Although it is considered safe, efavirenz has been linked with several adverse effects including neurological manifestations, which appear in the majority of the patients on efavirenz-containing regimens. The molecular mechanisms responsible for these manifestations are not...
Article
The relevance of heat preconditioning resides in its ability to protect cells from different kinds of injury by induction of heat shock proteins, a process in which the intensity of heat stress (HS) and duration of subsequent recovery are vital. This study evaluates the effects of moderate HS (45min/43°C) and time-dependent changes during recovery...
Chapter
The implication of autophagy, a highly conserved and regulated process of intracellular degradation in human pathophysiology, has been highlighted over the last few years. Abundant and growing evidence points to a major role of this phenomenon in virtually all fields of hepatology, inevitably linking it to the development of many liver diseases. Th...
Article
Significance: Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics particularly involving mitochondria-targeted antioxidants have attracted increa...
Article
The anti-HIV drug efavirenz alters mitochondrial function in cultured neurons and glial cells. Nitric oxide is a mediator of mitochondrial dysfunction associated with HIV CNS-symptoms. We show that Efavirenz promotes inducible nitric oxide synthase (iNOS)-expression in cultured glial cells and generated NO undermines their mitochondrial function, a...
Article
Full-text available
Background and purpose: The non-nucleoside analogue reverse transcriptase inhibitor efavirenz is associated with hepatic toxicity and metabolic disturbances. Although the mechanisms involved are not clear, recent evidence has pinpointed a specific mitochondrial action of efavirenz accompanied by the induction of an endoplasmic reticulum (ER) stres...
Article
Objectives Growing evidence associates the non-nucleoside reverse transcriptase inhibitor efavirenz with several adverse events. Newer antiretrovirals, such as the integrase inhibitor raltegravir, the non-nucleoside reverse transcriptase inhibitor rilpivirine and the protease inhibitor darunavir, claim to have a better toxicological profile than ef...
Article
Oxidative and endoplasmic reticulum (ER) stress are related to type 2 diabetes (T2D), but the influence of glycaemic control on these parameters and its relationship with leukocyte-endothelial interactions is not known. In our study population consisting of 164 diabetic patients, 102 with glycated haemoglobin (HbA1c) <7% and 62 with HbA1c >7%) and...
Article
Endothelial dysfunction involving dysfunctional mitochondria precedes the development of cardiovascular diseases. This impairment results from an increase in reactive oxygen species, which leads to oxidative stress and a reduced bioavailability of nitric oxide. It has been demonstrated that oxidative stress and alterations in glucose and lipid home...
Article
Background: Neurological pathogenesis is associated with mitochondrial dysfunction and differences in neuronal/glial handling of oxygen and glucose. The main side effects attributed to efavirenz involve the CNS, but the underlying mechanisms are unclear. Methods: Human cell lines and rat primary cultures of neurons and astrocytes were treated wi...
Article
There is abundant evidence to suggest that mitochondrial dysfunction is a main cause of insulin resistance and related cardiometabolic comorbidities. On the other hand, insulin resistance is one of the main characteristics of type 2 diabetes, obesity, and metabolic syndrome. Lipid and glucose metabolism require mitochondria to generate energy, and...
Data
Full-text available
Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful an...
Article
Full-text available
A defective induction of epithelial autophagy may have a role in the pathogenesis of inflammatory bowel diseases. This process is regulated mainly by extracellular factors such as nutrients and growth factors and is highly induced by diverse situations of stress. We hypothesized that epithelial autophagy is regulated by the immune response that in...
Article
ER-stress is associated with a growing number of liver diseases, including drug-induced hepatotoxicity. The non-nucleoside analogue reverse transcriptase inhibitor Efavirenz, a cornerstone of the multidrug strategy employed to treat HIV1 infection, has been related to the development of various adverse events, including metabolic disturbances and h...
Article
Full-text available
Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scop...
Article
Ceria-supported gold nanoparticles are prepared exhibiting peroxidase activity and acting as radical traps. Au/CeO(2) shows a remarkable biocompatibility as demonstrated by measuring cellular viability, proliferation, and lack of apoptosis for two human cell lines (Hep3B and HeLa). The antioxidant activity of Au/CeO(2) against reactive oxygen speci...
Article
Hepatic toxicity and metabolic disorders are major adverse effects elicited during the pharmacological treatment of the human immunodeficiency virus (HIV) infection. Efavirenz (EFV), the most widely used non-nucleoside reverse transcriptase inhibitor (NNRTI), has been associated with these events, with recent studies implicating it in stress respon...
Article
Full-text available
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GTN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GTN tolerance (in rat and human vessels) produced a decrease in mitochondrial O(2) consumption. Co-incubation wi...
Article
Thirty years after the discovery of HIV infection, there are numerous antiretroviral drugs that control the disease when administered in a potent combination referred to as Highly Active Antiretroviral Therapy (HAART). This therapy reduces the viral load and improves immune system reconstitution, leading to a significant reduction of HIV-related mo...
Article
Mitochondria are crucial, multifunctional organelles which actively regulate cellular homeostasis. Their complex and diverse role includes maintenance of the cellular energetic balance through hosting several catabolic pathways which result in the process of oxidative phosphorylation, as well as enabling various fundamental anabolic processes and c...