Publications by authors named "Mohammad Amrollahi-Sharifabadi"

6 Publications

  • Page 1 of 1

TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: reversal by monoclonal TNFα antibodies.

Cardiovasc Res 2021 Jan 23. Epub 2021 Jan 23.

Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Switzerland.

Aims: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular (CV) complications, but the molecular mechanism of action is unknown.We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA.

Methods And Results: Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two TNFα transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time- and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNFα plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly upregulated leading to increased vascular oxLDL uptake and NFκB-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNFα treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNFα treatment restored LOX-1 and ARG2 serum levels in RA patients.

Conclusions: Increased TNFα levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NFκB/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNFα treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL and Arg2 levels.
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http://dx.doi.org/10.1093/cvr/cvab005DOI Listing
January 2021

Cardiomyocyte-Specific JunD Overexpression Increases Infarct Size following Ischemia/Reperfusion Cardiac Injury by Downregulating Sirt3.

Thromb Haemost 2020 Jan 13;120(1):168-180. Epub 2019 Dec 13.

Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland.

Ischemia/reperfusion (I/R) injury in acute myocardial infarction activates several deleterious molecular mechanisms. The transcription factor JunD regulates pathways involved in oxidative stress as well as in cellular proliferation, differentiation, and death. The present study investigated the potential role of JunD as a modulator of myocardial injury pathways in a mouse model of cardiac I/R injury. Infarct size, systemic and local inflammation, and production of reactive oxygen species, as well as cytosolic and mitochondrial apoptotic pathways were investigated in adult males after myocardial I/R. In wild-type (WT) mice, 30 minutes after ischemia and up to 24 hours following reperfusion, cardiac messenger ribonucleic acid expression was reduced while increased. Cardiac-specific JunD overexpressing mice ( ) displayed larger infarcts compared with WT. However, postischemic inflammatory or oxidative responses did not differ. JunD overexpression reduced Sirt3 transcription by binding to its promoter, thus leading to mitochondrial dysfunction, myocardial cell death, and increased infarct size. On the other hand, JunD silencing reduced, while Sirt3 silencing increased infarct size. In human myocardial autopsy specimens, JunD-positive areas within the infarcted left ventricle staining corresponded to undetectable Sirt3 areas in consecutive sections of the same heart. Cardiac-specific JunD overexpression increases myocardial infarct size following I/R. These effects are mediated via Sirt3 transcriptional repression, mitochondrial swelling, and increased apoptosis, suggesting that JunD is a key regulator of myocardial I/R injury. The present data set the stage for further investigation of the potential role of Sirt3 activation as a novel target for the treatment of acute myocardial infarction.
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http://dx.doi.org/10.1055/s-0039-3400299DOI Listing
January 2020

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application.

Int J Nanomedicine 2018 22;13:4757-4769. Epub 2018 Aug 22.

NanoRegMed ltd, Nanotechnology and Regenerative Medicine Commercialization Centre, The London Bioscience Innovation Centre, London, UK.

Background: Graphene is considered as a wonder material; it is the strongest material on the planet, super-elastic, and conductive. Its application in biomedicine is huge, with a multibillion-dollar industry, and will revolutionize the diagnostic and treatment of diseases. However, its safety and potential toxicity is the main challenge.

Methods: This study assessed the potential toxicity of graphene oxide nanoplatelets (GONs) in an in vivo animal model using systemic, hematological, biochemical, and histopathological examinations. Normal saline (control group) or GONs (3-6 layers, lateral dimension=5-10 μm, and thickness=0.8-2 nm) at dose rate of 50, 150, or 500 mg/kg were intraperitoneally injected into adult male Wistar rats (n=5) every 48 hours during 1 week to receive each animal a total of four doses. The animals were allowed 2 weeks to recover after the last dosing. Then, animals were killed and the blood was collected for hematological and biochemical analysis. The organs including the liver, kidney, spleen, lung, intestine, brain, and heart were harvested for histopathological evaluations.

Results: The results showed GONs prevented body weight gain in animals after 21 days, treated at 500 mg/kg, but not in the animals treated at 150 or 50 mg/kg GONs. The biochemical analysis showed a significant increase in total bilirubin, with a significant decrease in triglycerides and high-density lipoprotein in animals treated at 500 mg/kg. Nonetheless, other hematological and biochemical parameters remained statistically insignificant in all GONs treated animals. The most common histopathological findings in the visceral organs were granulomatous reaction with giant cell formation and accumulation of GONs in capsular regions. Also, small foci of neuronal degeneration and necrosis were the most outstanding findings in the brain, including the cerebellum.

Conclusion: In conclusion, this study shows that GONs without functionalization are toxic. The future study is a comparison of the functionalized with non-functionalized GONs.
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http://dx.doi.org/10.2147/IJN.S168731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110298PMC
October 2018

Permanent Ocular Injury Following Paintball Pellet Hit: A Medicolegal Case.

J Forensic Sci 2016 Jan 26;61(1):277-9. Epub 2015 Jul 26.

Legal Medicine Research Center, Legal Medicine Organization, Bahar Cross, Taleghani Avenue, Tehran, 1114795113, Iran.

Paintball is a ubiquitous recreation, with severe and occasionally irreversible injuries. In this study, a rare medicolegal case of paintball-related closed globe blunt ocular injury was described. An 18-year-old boy who was hit in his right eye by a paintball pellet presented with severe eye pain and blurred vision. Ophthalmologic examinations showed lid edema, conjunctival hyperemia, conjunctival laceration, subconjunctival hemorrhage, corneal edema, anterior vitreous hemorrhage, congested sclera, commotio retinae, vitreous hemorrhage, retinal hemorrhage, macular edema, and macular hole. After maximum medical improvement, the patient who sustained incurable maculopathy and decreased visual acuity was referred to the legal medicine center for appraisal of the impairment. AMA Guides was used to assess the impairment of the functional vision. Despite his monocular visual defect, the patient was rated in the range of mild vision loss namely AMA class 1 with 22 percentage visual system impairment.
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http://dx.doi.org/10.1111/1556-4029.12917DOI Listing
January 2016

Comments on "Fatal colchicine intoxication".

Saudi J Anaesth 2015 Apr-Jun;9(2):220

Department of Internal Medicine, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.

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http://dx.doi.org/10.4103/1658-354X.152894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374235PMC
April 2015

Fatal colchicine poisoning by accidental ingestion of Colchicum persicum: a case report.

Am J Forensic Med Pathol 2013 Dec;34(4):295-8

From the *Forensic Laboratory and †Autopsy Hall, Legal Medicine Center of Yazd, Legal Medicine Organization of Iran, Yazd City, Yazd Province; ‡Province Health Center, Hormozgan University of Medical Sciences, Bandar-Abbas City, Hormozgan Province; §Medical Committee Office; and ∥Medical Committee Office, Legal Medicine Center of Yazd, Legal Medicine Organization of Iran, Yazd City, Yazd Province, Islamic Republic of Iran.

Colchicine poisoning can occur not only by taking dosage form but also by ingesting a plant containing colchicine. A 39-year-old man presented to the emergency room with nausea, vomiting, and diarrhea 9 hours after ingestion of wild garlic. Symptoms attributed to food poisoning, and he received supportive cares and discharged. However, he was admitted to the hospital because of severe gastrointestinal presentations 4 hours later. He received treatments based on the diagnosis of acute gastroenteritis. The patient was in a fair condition during 30 hours of hospitalization until he suddenly developed respiratory distress and unfortunately died with cardiopulmonary arrest. The deceased body referred to our legal medicine center for determining cause of death and investigating possible medical staff malpractices. Postmortem examination, autopsy, macropathology and micropathology study, and postmortem toxicological analysis were performed. All results were submitted to the medical committee office for decision. The unknown cause of death was disclosed after determination of colchicine in the plant and botanical identification as Colchicum persicum. The committee determined the most probable cause of death as acute cardiopulmonary complications induced by colchicine poisoning and the manner of death as accidental. The medical staff was acquitted of the malpractice.
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http://dx.doi.org/10.1097/PAF.0000000000000059DOI Listing
December 2013