Papers by aida zarfeshani
Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus... more Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE), present in up to 80% of patients and leading to a diminished quality of life. We have developed a model of lupus-like cognitive impairment which is initiated when anti-DNA, anti-N-methyl D-aspartate receptor (NMDAR) cross-reactive antibodies, which are present in 30% of SLE patients, penetrate the hippocampus. This leads to immediate, self-limited excitotoxic death of CA1 pyramidal neurons followed by a significant loss of dendritic arborization in the remaining CA1 neurons and impaired spatial memory. Both microglia and C1q are required for dendritic loss. Here we show that this pattern of hippocampal injury creates a maladaptive equilibrium that is sustained for at least one year. It requires HMGB1 secretion by neurons to bind RAGE, a receptor for HMGB1 expressed on microglia, and leads to decreased expression of microglial LAIR-1, an inhibitory receptor for C1q. The angioten...
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Clinical Epigenetics, 2014
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The FASEB Journal
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Journal of clinical medicine, Jan 16, 2015
Health issues associated with excessive caloric intake and sedentary lifestyle are driving a mode... more Health issues associated with excessive caloric intake and sedentary lifestyle are driving a modern "epidemic" of liver disease. Initially presenting in the clinic as an excessive accumulation of fat within hepatocyte cells (steatosis), the progression to more severe non-alcoholic steatohepatitis (NASH) in which liver damage and inflammation are overt features, is becoming increasingly common. Often developing as a sequela of obesity, non-alcoholic fatty liver disease (NAFLD) arises in almost one-third of people initially carrying excess hepatic fat and is likely the result of the liver's limited capacity to cope with the modern-day levels of dietary fatty acids circulating in the blood. While routine imaging can readily assess the presence and level of "extra-hepatic fat", a proper diagnosis of disease progression to NASH is currently only possible by liver biopsy. A general reluctance to undergo such screening means that the prevalence of NASH is likely to ...
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Current Rheumatology Reports, 2021
A Correction to this paper has been published: https://doi.org/10.1007/s11926-021-01021-x
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The obesity prevalence is increasing worldwide, resulting in more bariatric surgeries interventio... more The obesity prevalence is increasing worldwide, resulting in more bariatric surgeries interventions being performed. However, the success of surgical approaches in treating obesity and its co-morbidities varies between types of surgery and is not readily explained by baseline clinical features. Better understanding is needed of the metabolic shifts, and their underpinning mechanisms, which result from different types of surgery.
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The severity of diabetes mellitus often manifested by a progressive inflammatory biomarkers. Redu... more The severity of diabetes mellitus often manifested by a progressive inflammatory biomarkers. Reducing the rate of the inflammation progression is one of the many measures to reduce complication of the disease. Many established evidences have suggested the beneficial effect of probiotic consumption on the progression of inflammatory bowel syndrome (IBS). In the present study, possible benefit of probiotics on inflammatory progression of diabeties mellitus (DM) is investigated. The present study employed two different approaches to induce hyperglycemia in adult Sprague-Dawley rats. The initial approach using high fructose diet (HFD), (21% w/v), was unable to induce satisfactorily hyperglycemia in the animal. Chemical induction using streptozotocin (STZ), ( 50 mg/ kg body weight) induced hyperglycemia in all animals injected. Rats in both batches were divided into groups. A non-diabetic group (ND), a non-treated group with a standard diet (NT) and two diabetic groups which were treated...
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Current Rheumatology Reports
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The Journal of Rheumatology
In this 2020 Dunlop-Dottridge Lecture, the authors discuss cognitive impairment (CI), one of the ... more In this 2020 Dunlop-Dottridge Lecture, the authors discuss cognitive impairment (CI), one of the most prevalent neuropsychiatric syndromes in systemic lupus erythematosus (SLE). Patients often report CI as the most bothersome disease-related manifestation, with a great effect on their quality of life. Nevertheless, studies focusing on CI remain scarce and no effective targeted therapy has been identified. We herein present murine models of CI in SLE with insights into the pathogenesis of this condition as well as the role of the renin angiotensin system in microglial activation. We will discuss the role of neuroimaging as a useful objective assessment tool, describing our experience in previous and ongoing clinical trials of CI in patients with SLE.
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Advanced biomedical research, 2018
Anterior knee pain is a major problem in total knee arthroplasty (TKA). It is accepted that anter... more Anterior knee pain is a major problem in total knee arthroplasty (TKA). It is accepted that anterior knee pain (AKP) often contributes to a patellofemoral etiology; however, its etiology or treatment is not understood completely. Disabling pain receptors by electrocautery could theoretically lead to anterior knee area denervation. The present study aimed to evaluate the pain post-patellar denervation (PD) with electrocautery in TKA. Clinical results for 92 patients who underwent TKA (58 women, 34 men; mean age 67.5 years) were analyzed. In addition to removal of all osteophytes, PD by electrocautery was performed on patella of treatment group ( = 46) and debridement alone including removing of all osteophytes was performed on the control group ( = 46). Knee Society System (KSS) score, patella score (PS), and visual analog scale (VAS) were used to determine pre- and post-operative AKP. The follow-up duration was 10 months. No revision or reoperations were performed. There were no pat...
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NPJ biofilms and microbiomes, 2017
E. coli releases a 33 amino acid peptide melanocortin-like peptide of E. coli (MECO-1) that is id... more E. coli releases a 33 amino acid peptide melanocortin-like peptide of E. coli (MECO-1) that is identical to the C-terminus of the E. coli elongation factor-G (EF-G) and has interesting similarities to two prominent mammalian melanocortin hormones, alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH). Note that MECO-1 lacks HFRW, the common pharmacophore of the known mammalian melanocortin peptides. MECO-1 and the two hormones were equally effective in severely blunting release of cytokines (HMGB1 and TNF) from macrophage-like cells in response to (i) endotoxin (lipopolysaccharide) or (ii) pro-inflammatory cytokine HMGB-1. The in vitro anti-inflammatoty effects of MECO-1 and of alpha-MSH were abrogated by (i) antibody against melanocortin-1 receptor (MC1R) and by (ii) agouti, an endogenous inverse agonist of MC1R. In vivo MECO-1 was even more potent than alpha-MSH in rescuing mice from death due to (i) lethal doses of LPS endotoxin or (ii) cecal ligation an...
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NPJ biofilms and microbiomes, 2017
E. coli releases a 33 amino acid peptide melanocortin-like peptide of E. coli (MECO-1) that is id... more E. coli releases a 33 amino acid peptide melanocortin-like peptide of E. coli (MECO-1) that is identical to the C-terminus of the E. coli elongation factor-G (EF-G) and has interesting similarities to two prominent mammalian melanocortin hormones, alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH). Note that MECO-1 lacks HFRW, the common pharmacophore of the known mammalian melanocortin peptides. MECO-1 and the two hormones were equally effective in severely blunting release of cytokines (HMGB1 and TNF) from macrophage-like cells in response to (i) endotoxin (lipopolysaccharide) or (ii) pro-inflammatory cytokine HMGB-1. The in vitro anti-inflammatoty effects of MECO-1 and of alpha-MSH were abrogated by (i) antibody against melanocortin-1 receptor (MC1R) and by (ii) agouti, an endogenous inverse agonist of MC1R. In vivo MECO-1 was even more potent than alpha-MSH in rescuing mice from death due to (i) lethal doses of LPS endotoxin or (ii) cecal ligation an...
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Health issues associated with excessive caloric intake and sedentary lifestyle are driving a mode... more Health issues associated with excessive caloric intake and sedentary lifestyle are driving a modern " epidemic " of liver disease. Initially presenting in the clinic as an excessive accumulation of fat within hepatocyte cells (steatosis), the progression to more severe non-alcoholic steatohepatitis (NASH) in which liver damage and inflammation are overt features, is becoming increasingly common. Often developing as a sequela of obesity, non-alcoholic fatty liver disease (NAFLD) arises in almost one-third of people initially carrying excess hepatic fat and is likely the result of the liver's limited capacity to cope with the modern-day levels of dietary fatty acids circulating in the blood. While routine imaging can readily assess the presence and level of " extra-hepatic fat " , a proper diagnosis of disease progression to NASH is currently only possible by liver biopsy. A general reluctance to undergo such screening means that the prevalence of NASH is likely to be under reported and, thus, risk assessment for future metabolic syndrome (MetS) markedly compromised. The seemingly inevitable progression to overt insulin resistance that characterizes MetS may in part be the consequence of the body's attempt to cope with NAFLD by driving systemic insulin sensitivity and, thus, fatty acid breakdown. The potential significance of miRNAs in both physiological homeostasis and pathogenesis is increasingly appreciated and in the liver may contribute specifically to the regulation of lipid pathways and NAFLD progression. As such, they may have utility as molecular indicators for the accurate profiling of both initial risk and disease progression from simple steatosis to NASH, and further to fibrosis/cirrhosis. OPEN ACCESS
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Accumulating data clearly claimed that Punica granatum L. (pomegranate) has several health benefi... more Accumulating data clearly claimed that Punica granatum L. (pomegranate) has several health benefits. Pomegranates can help prevent or treat various disease risk factors including high blood pressure, high cholesterol, oxidative stress, hyperglycemia, and inflammatory activities. It is demonstrated that certain components of pomegranate such as polyphenols have potential antioxidant, anti‑inflammatory, and anticarcinogenic effects. The antioxidant potential of pomegranate juice is more than that of red wine and green tea, which is induced through ellagitannins and hydrosable tannins. Pomegranate juice can reduce macrophage oxidative stress, free radicals, and lipid peroxidation. Moreover, pomegranate fruit extract prevents cell growth and induces apoptosis, which can lead to its anticarcinogenic effects. In addition, promoter inhibition of some inflammatory markers and their production are blocked via ellagitannins. In this article, we highlight different studies on the therapeutic effects of pomegranate and their suggested mechanisms of actions.
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Background: Elevated plasma levels of the branched-chain amino acid (BCAA) leucine are associated... more Background: Elevated plasma levels of the branched-chain amino acid (BCAA) leucine are associated with obesity
and insulin resistance (IR), and thus the propensity for type 2 diabetes mellitus development. However, other clinical
studies suggest the contradictory view that leucine may in fact offer a degree of protection against metabolic syndrome.
Aiming to resolve this apparent paradox, we assessed the effect of leucine supplementation on the metabolism
of human hepatic HepG2 cells.
Results: We demonstrate that pathophysiological leucine appears to be antagonistic to insulin, promotes glucose
uptake (and not glycogen synthesis), but results in hepatic cell triglyceride (TG) accumulation. Further, we provide
evidence that myostatin (MSTN) regulation of AMP-activated protein kinase (AMPK) is a key pathway in the metabolic
effects elicited by excess leucine. Finally, we report associated changes in miRNA expression (some species previously
linked to metabolic disease etiology), suggesting that epigenetic processes may contribute to these effects.
Conclusions: Collectively, our observations suggest leucine may be both ‘friend’ and ‘foe’ in the context of metabolic
syndrome, promoting glucose sequestration and driving lipid accumulation in liver cells. These observations provide
insight into the clinical consequences of excess plasma leucine, particularly for hyperglycemia, IR and nonalcoholic fatty
liver disease (NAFLD).
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It has been demonstrated that probiotic supplementation has positive effects in several murine mo... more It has been demonstrated that probiotic supplementation has positive effects in several murine models of disease through influences on host immune responses. This study examined the effect of Lactobacillus casei strain Shirota (L. casei Shirota) on the blood glucose, C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-4 (IL-4), and body weight among STZ-induced diabetic rats. Diabetes mellitus was induced by streptozotocin (STZ, 50 mg/kg BW) in male Sprague–Dawley rats. Streptozotocin caused a significant increase in the blood glucose levels, CRP, and IL-6. L. casei Shirota supplementation lowered the CRP and IL-6 levels but had no significant effect on the blood glucose levels, body weight, or IL-4. Inflammation was determined histologically. The presence of the innate immune cells was not detectable in the liver of L. casei Shirota-treated hyperglycemic rats. The probiotic L. casei Shirota significantly lowered blood levels of pro-inflammatory cytokines (IL-6, CRP) and neutrophils in diabetic rats, showing a lower risk of diabetes mellitus and its complications.
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Papers by aida zarfeshani
and insulin resistance (IR), and thus the propensity for type 2 diabetes mellitus development. However, other clinical
studies suggest the contradictory view that leucine may in fact offer a degree of protection against metabolic syndrome.
Aiming to resolve this apparent paradox, we assessed the effect of leucine supplementation on the metabolism
of human hepatic HepG2 cells.
Results: We demonstrate that pathophysiological leucine appears to be antagonistic to insulin, promotes glucose
uptake (and not glycogen synthesis), but results in hepatic cell triglyceride (TG) accumulation. Further, we provide
evidence that myostatin (MSTN) regulation of AMP-activated protein kinase (AMPK) is a key pathway in the metabolic
effects elicited by excess leucine. Finally, we report associated changes in miRNA expression (some species previously
linked to metabolic disease etiology), suggesting that epigenetic processes may contribute to these effects.
Conclusions: Collectively, our observations suggest leucine may be both ‘friend’ and ‘foe’ in the context of metabolic
syndrome, promoting glucose sequestration and driving lipid accumulation in liver cells. These observations provide
insight into the clinical consequences of excess plasma leucine, particularly for hyperglycemia, IR and nonalcoholic fatty
liver disease (NAFLD).
and insulin resistance (IR), and thus the propensity for type 2 diabetes mellitus development. However, other clinical
studies suggest the contradictory view that leucine may in fact offer a degree of protection against metabolic syndrome.
Aiming to resolve this apparent paradox, we assessed the effect of leucine supplementation on the metabolism
of human hepatic HepG2 cells.
Results: We demonstrate that pathophysiological leucine appears to be antagonistic to insulin, promotes glucose
uptake (and not glycogen synthesis), but results in hepatic cell triglyceride (TG) accumulation. Further, we provide
evidence that myostatin (MSTN) regulation of AMP-activated protein kinase (AMPK) is a key pathway in the metabolic
effects elicited by excess leucine. Finally, we report associated changes in miRNA expression (some species previously
linked to metabolic disease etiology), suggesting that epigenetic processes may contribute to these effects.
Conclusions: Collectively, our observations suggest leucine may be both ‘friend’ and ‘foe’ in the context of metabolic
syndrome, promoting glucose sequestration and driving lipid accumulation in liver cells. These observations provide
insight into the clinical consequences of excess plasma leucine, particularly for hyperglycemia, IR and nonalcoholic fatty
liver disease (NAFLD).