Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual los... more Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of Aβ to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the uni...
Alcohol-related liver disease (ARLD) refers to a spectrum of hepatic damage triggered by excessiv... more Alcohol-related liver disease (ARLD) refers to a spectrum of hepatic damage triggered by excessive alcohol intake, resulting in inflamed and swollen livers, ultimately, liver cirrhosis. Alcoholic liver disease (ALD) is a similar term denoting liver disorders encompassing steatosis, cirrhosis, and hepatocellular carcinoma. Recent evidence has suggested a vital role for epigenetic factors, which modulate gene expression in the absence of changes in DNA sequence, in the onset and progression of liver disorders, to foster hepatic fibrogenesis and cirrhosis. Mounting findings have delineated that alcohol consumption extensively modulates liver epigenetics, thus, prompting the etiology of ARLD and ALD. Alcohol-induced epigenetic modifications (AIEM) in the liver encompass histone modification, microRNA-induced genetic modulation, DNA methylation, and alcohol-evoked cell signaling that alters gene expression. Herein, we aim at summarizing key findings to decipher AIEM and its role in the onset and development of ARLD and ALD from the perspectives of both cellular and animal models of alcohol exposure. Furthermore, we will share our viewpoints on epigenetics-based therapeutic options in the management of ARLD and ALD.
Atherosclerosis refers to a unique form of chronic proinflammatory anomaly of the vasculature, pr... more Atherosclerosis refers to a unique form of chronic proinflammatory anomaly of the vasculature, presented as rupture-prone or occlusive lesions in arteries. In advanced stages, atherosclerosis leads to the onset and development of multiple cardiovascular diseases with lethal consequences. Inflammatory cytokines in atherosclerotic lesions contribute to the exacerbation of atherosclerosis. Pharmacotherapies targeting dyslipidemia, hypercholesterolemia, and neutralizing inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have displayed proven promises although contradictory results. Moreover, adjuvants such as melatonin, a pluripotent agent with proven anti-inflammatory, anti-oxidative and neuroprotective properties, also display potentials in alleviating cytokine secretion in macrophages through mitophagy activation. Here, we share our perspectives on this concept and present melatonin-based therapeutics as a means to modulate mitophagy in macrophages and, thereby, ameliorate atherosclerosis.
Viral infections persist globally, among all ages, gender, and ethnicity. Of particular importanc... more Viral infections persist globally, among all ages, gender, and ethnicity. Of particular importance is COVID-19, associated with asymptomatic to severe symptoms, including complications/mortality. Cardiovascular disease (CVD) involves heart and blood vessel disorders including coronary heart disease, cerebrovascular disease, peripheral artery disease, thrombosis, and more. CVD associated with severe COVID-19 includes heart failure, coronary artery disease, cardiomyopathy, hypertension, and cerebrovascular disease/stroke. Data were acquired from PubMed, Google Scholar, Centers for Disease Prevention and Control, and Lexi-Comp using the search terms “COVID-19 and cardiovascular pathology;” “COVID-19 induced CVD;” “Viral infection induced CVD;” and “Viral infection induced heart damage.” COVID-19-induced CVD mechanisms include direct viral entry, inflammation, cytokine storm, hypoxia, interferon-mediated immune response, plaque destabilization, stress, and drug-induced causes. Other viral pathologies causing CVD include atherosclerosis, inflammation, cytokine storm, and plaque destabilization. Individual parameters, such as old age, males, and higher body mass index (BMI), are more likely to experience viral-associated complications, possibly explained by patient risk factors or comorbidities. Populations at higher risk include older males with an elevated BMI. Viral mechanisms associated with CVD are similar but differ in disease severity, potentially explained by diverse cytokine profiles where COVID-19 activates different types at higher quantities.
Given the unprecedented global pandemic of obesity, a better understanding of the etiology of adi... more Given the unprecedented global pandemic of obesity, a better understanding of the etiology of adiposity will be necessary to ensure effective management of obesity and related complications. Among the various potential factors contributing to obesity, endoplasmic reticulum (ER) stress refers to a state of excessive protein unfolding or misfolding that is commonly found in metabolic diseases including diabetes mellitus, insulin resistance (IR), and non-alcoholic fatty liver disease, although its role in obesogenesis remains controversial. ER stress is thought to drive adiposity by dampening energy expenditure, making ER stress a likely therapeutic target for the management of obesity. We summarize the role of ER stress and the ER stress response in the onset and development of obesity, and discuss the underlying mechanisms involved with a view to identifying novel therapeutic strategies for obesity prevention and management.
Heart failure (HF) refers to a progressive pathological condition when cardiac muscles fail to pu... more Heart failure (HF) refers to a progressive pathological condition when cardiac muscles fail to pump adequate blood supply (cardiac output) to meet the metabolic demand of the body. Among various cellular and molecular mechanisms identified for the onset and progression of HF, autophagy dysregulation is increasingly getting recognized. Autophagy is a natural cellular process that is observed in almost all eukaryotic cells. Autophagy removes damaged/long-lived organelles, protein aggregates, and unwanted cellular compomemts via forming autophagosomes then fusing with lysosomes. Although mild-to-moderate induction of autophagy is deemed cytoprotective and adaptive, excessive or unchecked induction of autophagy can be detrimental and maladaptive. Both adaptive and maladaptive autophagy play a vital role in the pathophysiology of HF. In the current review, we provide an overview of autophagy regulation in HF and possible strategies targeting autophagy for the management of HF.
Iron deficiency and iron overload are the most prevalent and opposite forms of dysregulated iron ... more Iron deficiency and iron overload are the most prevalent and opposite forms of dysregulated iron metabolism that affect approximately 30 percent of the world population, in particularly, elderly and patients with chronic diseases. Both iron deficiency and overload are frequently observed in a wide range of cardiovascular diseases, contributing to the onset and progression of these diseases. One of the devastating seqeulae for iron overload is the induction of ferroptosis, a newly defined form of regulated cell death which heavily impacts cardiac function through ferroptotic cell death in cardiomyocytes. In this review, we will aim to evaluate iron deficiency and iron overload in cardiovascular diseases. We will summarize current therapeutic strategies to tackle iron deficiency and iron overload, major pitfalls of current studies, and future perspectives.
Stroke constitutes the second leading cause of death and a major cause of disability worldwide. S... more Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as an essential cellular process to maintain cellular homeostasis and organismal survival. However, unchecked or excessive induction of autophagy has been perceived to be detrimental and its contribution to neuronal cell death remains largely unknown. In this review, we will summarize the role of autophagy in IS, and discuss potential strategies, particularly, employment of natural compounds for IS treatment through manipulation of autophagy.
Background: Stroke is one of the leading causes of death worldwide and has different characterist... more Background: Stroke is one of the leading causes of death worldwide and has different characteristics. Different physiopathological mechanisms characterize the different subtypes of ischemic stroke. In this study, we investigated the correlation between serum levels of autophagy-5 protein, Apo-lipoprotein B-48, and oxidative stress markers in patients with ischemic stroke. Methods and results: We enrolled 100 participants, including 50 ischemic stroke (IS) patients as the case group and 50 healthy individuals as the control group. Then, we conducted a case-control study at Imam Reza Hospital from March 2019 to April 2020. We quantified the serum levels of ATG5, Apo B-48, and oxidative stress markers in both groups. And we evaluated the incremental diagnostic value of these factors by receiver operating characteristic analysis (ROC) in both groups. The mean serum levels of ATG5, Apo B-48, and oxidative stress markers were higher in the case group than in the control group, with a p–va...
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual los... more Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of Aβ to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the uni...
Alcohol-related liver disease (ARLD) refers to a spectrum of hepatic damage triggered by excessiv... more Alcohol-related liver disease (ARLD) refers to a spectrum of hepatic damage triggered by excessive alcohol intake, resulting in inflamed and swollen livers, ultimately, liver cirrhosis. Alcoholic liver disease (ALD) is a similar term denoting liver disorders encompassing steatosis, cirrhosis, and hepatocellular carcinoma. Recent evidence has suggested a vital role for epigenetic factors, which modulate gene expression in the absence of changes in DNA sequence, in the onset and progression of liver disorders, to foster hepatic fibrogenesis and cirrhosis. Mounting findings have delineated that alcohol consumption extensively modulates liver epigenetics, thus, prompting the etiology of ARLD and ALD. Alcohol-induced epigenetic modifications (AIEM) in the liver encompass histone modification, microRNA-induced genetic modulation, DNA methylation, and alcohol-evoked cell signaling that alters gene expression. Herein, we aim at summarizing key findings to decipher AIEM and its role in the onset and development of ARLD and ALD from the perspectives of both cellular and animal models of alcohol exposure. Furthermore, we will share our viewpoints on epigenetics-based therapeutic options in the management of ARLD and ALD.
Atherosclerosis refers to a unique form of chronic proinflammatory anomaly of the vasculature, pr... more Atherosclerosis refers to a unique form of chronic proinflammatory anomaly of the vasculature, presented as rupture-prone or occlusive lesions in arteries. In advanced stages, atherosclerosis leads to the onset and development of multiple cardiovascular diseases with lethal consequences. Inflammatory cytokines in atherosclerotic lesions contribute to the exacerbation of atherosclerosis. Pharmacotherapies targeting dyslipidemia, hypercholesterolemia, and neutralizing inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have displayed proven promises although contradictory results. Moreover, adjuvants such as melatonin, a pluripotent agent with proven anti-inflammatory, anti-oxidative and neuroprotective properties, also display potentials in alleviating cytokine secretion in macrophages through mitophagy activation. Here, we share our perspectives on this concept and present melatonin-based therapeutics as a means to modulate mitophagy in macrophages and, thereby, ameliorate atherosclerosis.
Viral infections persist globally, among all ages, gender, and ethnicity. Of particular importanc... more Viral infections persist globally, among all ages, gender, and ethnicity. Of particular importance is COVID-19, associated with asymptomatic to severe symptoms, including complications/mortality. Cardiovascular disease (CVD) involves heart and blood vessel disorders including coronary heart disease, cerebrovascular disease, peripheral artery disease, thrombosis, and more. CVD associated with severe COVID-19 includes heart failure, coronary artery disease, cardiomyopathy, hypertension, and cerebrovascular disease/stroke. Data were acquired from PubMed, Google Scholar, Centers for Disease Prevention and Control, and Lexi-Comp using the search terms “COVID-19 and cardiovascular pathology;” “COVID-19 induced CVD;” “Viral infection induced CVD;” and “Viral infection induced heart damage.” COVID-19-induced CVD mechanisms include direct viral entry, inflammation, cytokine storm, hypoxia, interferon-mediated immune response, plaque destabilization, stress, and drug-induced causes. Other viral pathologies causing CVD include atherosclerosis, inflammation, cytokine storm, and plaque destabilization. Individual parameters, such as old age, males, and higher body mass index (BMI), are more likely to experience viral-associated complications, possibly explained by patient risk factors or comorbidities. Populations at higher risk include older males with an elevated BMI. Viral mechanisms associated with CVD are similar but differ in disease severity, potentially explained by diverse cytokine profiles where COVID-19 activates different types at higher quantities.
Given the unprecedented global pandemic of obesity, a better understanding of the etiology of adi... more Given the unprecedented global pandemic of obesity, a better understanding of the etiology of adiposity will be necessary to ensure effective management of obesity and related complications. Among the various potential factors contributing to obesity, endoplasmic reticulum (ER) stress refers to a state of excessive protein unfolding or misfolding that is commonly found in metabolic diseases including diabetes mellitus, insulin resistance (IR), and non-alcoholic fatty liver disease, although its role in obesogenesis remains controversial. ER stress is thought to drive adiposity by dampening energy expenditure, making ER stress a likely therapeutic target for the management of obesity. We summarize the role of ER stress and the ER stress response in the onset and development of obesity, and discuss the underlying mechanisms involved with a view to identifying novel therapeutic strategies for obesity prevention and management.
Heart failure (HF) refers to a progressive pathological condition when cardiac muscles fail to pu... more Heart failure (HF) refers to a progressive pathological condition when cardiac muscles fail to pump adequate blood supply (cardiac output) to meet the metabolic demand of the body. Among various cellular and molecular mechanisms identified for the onset and progression of HF, autophagy dysregulation is increasingly getting recognized. Autophagy is a natural cellular process that is observed in almost all eukaryotic cells. Autophagy removes damaged/long-lived organelles, protein aggregates, and unwanted cellular compomemts via forming autophagosomes then fusing with lysosomes. Although mild-to-moderate induction of autophagy is deemed cytoprotective and adaptive, excessive or unchecked induction of autophagy can be detrimental and maladaptive. Both adaptive and maladaptive autophagy play a vital role in the pathophysiology of HF. In the current review, we provide an overview of autophagy regulation in HF and possible strategies targeting autophagy for the management of HF.
Iron deficiency and iron overload are the most prevalent and opposite forms of dysregulated iron ... more Iron deficiency and iron overload are the most prevalent and opposite forms of dysregulated iron metabolism that affect approximately 30 percent of the world population, in particularly, elderly and patients with chronic diseases. Both iron deficiency and overload are frequently observed in a wide range of cardiovascular diseases, contributing to the onset and progression of these diseases. One of the devastating seqeulae for iron overload is the induction of ferroptosis, a newly defined form of regulated cell death which heavily impacts cardiac function through ferroptotic cell death in cardiomyocytes. In this review, we will aim to evaluate iron deficiency and iron overload in cardiovascular diseases. We will summarize current therapeutic strategies to tackle iron deficiency and iron overload, major pitfalls of current studies, and future perspectives.
Stroke constitutes the second leading cause of death and a major cause of disability worldwide. S... more Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as an essential cellular process to maintain cellular homeostasis and organismal survival. However, unchecked or excessive induction of autophagy has been perceived to be detrimental and its contribution to neuronal cell death remains largely unknown. In this review, we will summarize the role of autophagy in IS, and discuss potential strategies, particularly, employment of natural compounds for IS treatment through manipulation of autophagy.
Background: Stroke is one of the leading causes of death worldwide and has different characterist... more Background: Stroke is one of the leading causes of death worldwide and has different characteristics. Different physiopathological mechanisms characterize the different subtypes of ischemic stroke. In this study, we investigated the correlation between serum levels of autophagy-5 protein, Apo-lipoprotein B-48, and oxidative stress markers in patients with ischemic stroke. Methods and results: We enrolled 100 participants, including 50 ischemic stroke (IS) patients as the case group and 50 healthy individuals as the control group. Then, we conducted a case-control study at Imam Reza Hospital from March 2019 to April 2020. We quantified the serum levels of ATG5, Apo B-48, and oxidative stress markers in both groups. And we evaluated the incremental diagnostic value of these factors by receiver operating characteristic analysis (ROC) in both groups. The mean serum levels of ATG5, Apo B-48, and oxidative stress markers were higher in the case group than in the control group, with a p–va...
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Papers by Amir Ajoolabady