201 results match your criteria Genetic and Inflammatory Mechanisms in Stroke


Multiplexed mRNA analysis of brain-derived extracellular vesicles upon experimental stroke in mice reveals increased mRNA content with potential relevance to inflammation and recovery processes.

Cell Mol Life Sci 2022 May 31;79(6):329. Epub 2022 May 31.

Neurology Department, Experimental Research in Stroke and Inflammation (ERSI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that represent newly discovered means for cell-to-cell communication as well as promising disease biomarkers and therapeutic tools. Apart from proteins, lipids, and metabolites, EVs can deliver genetic information such as mRNA, eliciting a response in the recipient cells. In the present study, we have analyzed the mRNA content of brain-derived EVs (BDEVs) isolated 72 h after experimental stroke in mice and compared them to controls (shams) using nCounter Nanostring panels, with or without prior RNA isolation. Read More

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Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk.

Arthritis Rheumatol 2022 May 18. Epub 2022 May 18.

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Objectives: To assess the causality of the associations of rheumatoid arthritis (RA) with coronary artery disease (CAD) and stroke using Mendelian randomization approach.

Methods: Independent single nucleotide polymorphisms strongly associated with RA (n=70) were selected as instrumental variables from a genome-wide association meta-analysis including 14,361 RA cases and 43,923 controls of European ancestry. Summary-level data for CAD, all stroke, any ischemic stroke and its subtypes, intracerebral hemorrhage, and subarachnoid hemorrhage were obtained from meta-analyses of genetic studies, international genetic consortia, the UK Biobank, and the FinnGen consortium. Read More

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Targeting the CCL2-CCR2 axis for atheroprotection.

Eur Heart J 2022 May;43(19):1799-1808

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, D-81377 Munich, Germany.

Decades of research have established atherosclerosis as an inflammatory disease. Only recently though, clinical trials provided proof-of-concept evidence for the efficacy of anti-inflammatory strategies with respect to cardiovascular events, thus offering a new paradigm for lowering residual vascular risk. Efforts to target the inflammasome-interleukin-1β-interleukin-6 pathway have been highly successful, but inter-individual variations in drug response, a lack of reduction in all-cause mortality, and a higher rate of infections also highlight the need for a second generation of anti-inflammatory agents targeting atherosclerosis-specific immune mechanisms while minimizing systemic side effects. Read More

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Novel Multifaceted Roles for RNF213 Protein.

Int J Mol Sci 2022 Apr 19;23(9). Epub 2022 Apr 19.

Laboratory of Neurobiology, Neurology IX Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

Ring Finger Protein 213 (RNF213), also known as Mysterin, is the major susceptibility factor for Moyamoya Arteriopathy (MA), a progressive cerebrovascular disorder that often leads to brain stroke in adults and children. Although several rare RNF213 polymorphisms have been reported, no major susceptibility variant has been identified to date in Caucasian patients, thus frustrating the attempts to identify putative therapeutic targets for MA treatment. For these reasons, the investigation of novel biochemical functions, substrates and unknown partners of RNF213 will help to unravel the pathogenic mechanisms of MA and will facilitate variant interpretations in a diagnostic context in the future. Read More

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Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin Against Brain Ischemia in Rats.

Curr Pharm Des 2022 05 6. Epub 2022 May 6.

Center for Genetic Engineering and Biotechnology, Havana, Cuba.

Background: Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options.

Objective: This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes on the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis.

Methods: Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Read More

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Genetically predicted frailty index and risk of stroke and Alzheimer's disease.

Eur J Neurol 2022 Jul 5;29(7):1913-1921. Epub 2022 Apr 5.

Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background And Purpose: Previous studies have reported the association between frailty and stroke or Alzheimer's disease (AD). However, the causality remains unclear. The aim of the present study was to evaluate whether genetically predicted frailty is associated with the risk of stroke or AD by a Mendelian randomization (MR) study. Read More

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The Circulating Biomarker Fractalkine and Platelet-Derived Growth Factor BB are Correlated with Carotid Plaque Vulnerability Assessed by Computed Tomography Angiography.

J Stroke Cerebrovasc Dis 2022 May 4;31(5):106422. Epub 2022 Mar 4.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.

Objectives: Although studies have demonstrated that inflammatory and lipid/ lipoproteins-related biomarkers, genetic mutations, and epigenetic mechanisms could be candidates for diagnosis and prognosis of ischemic stroke, there is still no consensus on how to identify vulnerable plaques based on circulating biomarkers.

Materials And Methods: Histological and immunohistochemical staining were performed in the aorta sections of ApoE/ and WT mice. Eighty-nine patients who underwent CTA were included in this study. Read More

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Targeting the CCL2-CCR2 axis for atheroprotection.

Eur Heart J 2022 Mar 7. Epub 2022 Mar 7.

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, D-81377 Munich, Germany.

Decades of research have established atherosclerosis as an inflammatory disease. Only recently though, clinical trials provided proof-of-concept evidence for the efficacy of anti-inflammatory strategies with respect to cardiovascular events, thus offering a new paradigm for lowering residual vascular risk. Efforts to target the inflammasome-interleukin-1β-interleukin-6 pathway have been highly successful, but inter-individual variations in drug response, a lack of reduction in all-cause mortality, and a higher rate of infections also highlight the need for a second generation of anti-inflammatory agents targeting atherosclerosis-specific immune mechanisms while minimizing systemic side effects. Read More

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Functional noncoding SNPs in human endothelial cells fine-map vascular trait associations.

Genome Res 2022 03 22;32(3):409-424. Epub 2022 Feb 22.

The Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, Arizona 85721, USA.

Functional consequences of genetic variation in the noncoding human genome are difficult to ascertain despite demonstrated associations to common, complex disease traits. To elucidate properties of functional noncoding SNPs with effects in human endothelial cells (ECs), we utilized our previous molecular quantitative trait locus (molQTL) analysis for transcription factor binding, chromatin accessibility, and H3K27 acetylation to nominate a set of likely functional noncoding SNPs. Together with information from genome-wide association studies (GWASs) for vascular disease traits, we tested the ability of 34,344 variants to perturb enhancer function in ECs using the highly multiplexed STARR-seq assay. Read More

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Genetic Architecture of Stroke of Undetermined Source: Overlap with Known Stroke Etiologies and Associations with Modifiable Risk Factors.

Ann Neurol 2022 05 3;91(5):640-651. Epub 2022 Mar 3.

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.

Objective: Ischemic stroke etiology remains undetermined in 30% of cases. We explored the genetic architecture of stroke classified as undetermined to test if mechanisms and risk factors underlying large-artery atherosclerotic (LAAS), cardioembolic (CES), and small-vessel stroke (SVS) contribute to its pathogenesis.

Methods: We analyzed genome-wide data from 16,851 ischemic stroke cases and 32,473 controls. Read More

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Deep Sequencing of the Rat MCAO Cortexes Reveals Crucial circRNAs Involved in Early Stroke Events and Their Regulatory Networks.

Neural Plast 2021 24;2021:9942537. Epub 2021 Nov 24.

State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Sciences, Shihezi, Xinjiang 832000, China.

Circular RNAs (circRNAs) are highly enriched in the central nervous system and significantly involved in a range of brain-related physiological and pathological processes. Ischemic stroke is a complex disorder caused by multiple factors; however, whether brain-derived circRNAs participate in the complex regulatory networks involved in stroke pathogenesis remains unknown. Here, we successfully constructed a cerebral ischemia-injury model of middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. Read More

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Genetic inhibition of RIPK3 ameliorates functional outcome in controlled cortical impact independent of necroptosis.

Cell Death Dis 2021 11 9;12(11):1064. Epub 2021 Nov 9.

Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

Traumatic brain injury (TBI) is a leading cause of death and disability with no specific effective therapy, in part because disease driving mechanisms remain to be elucidated. Receptor interacting protein kinases (RIPKs) are serine/threonine kinases that assemble multi-molecular complexes that induce apoptosis, necroptosis, inflammasome and nuclear factor kappa B activation. Prior studies using pharmacological inhibitors implicated necroptosis in the pathogenesis of TBI and stroke, but these studies cannot be used to conclusively demonstrate a role for necroptosis because of the possibility of off target effects. Read More

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November 2021

Disorder Genes Regulate the Progression of Ischemic Stroke through the NF-B Signaling Pathway.

Biomed Res Int 2021 27;2021:2464269. Epub 2021 Oct 27.

Department of Neurology, Mianyang Central Hospital, Mianyang 621000, China.

Stroke is an acute cerebrovascular disease, including ischemic and hemorrhagic stroke. Stroke is the second leading cause of death after ischemic heart disease, which accounts for 9% of the global death toll. To explore the molecular mechanisms of the effects of the dysregulated factors, in the GEO database, we obtained transcriptome data from 24 h/72 h of mice with ischemic stroke and 24 h/72 h of normal mice. Read More

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January 2022

Rheumatoid Arthritis and Cardio-Cerebrovascular Disease: A Mendelian Randomization Study.

Front Genet 2021 21;12:745224. Epub 2021 Oct 21.

School of Life Sciences and Technology, Harbin Institute of Technology, Harbin, China.

Significant genetic association exists between rheumatoid arthritis (RA) and cardiovascular disease. The associated mechanisms include common inflammatory mediators, changes in lipoprotein composition and function, immune responses, etc. However, the causality of RA and vascular/heart problems remains unknown. Read More

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October 2021

Role of BET Proteins in Inflammation and CNS Diseases.

Front Mol Biosci 2021 16;8:748449. Epub 2021 Sep 16.

Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, United States.

Bromodomain and extra-terminal domain (BET) proteins consist of four mammalian members (BRD2, BRD3, BRD4, and BRDT), which play a pivotal role in the transcriptional regulation of the inflammatory response. Dysregulated inflammation is a key pathological process in various CNS disorders through multiple mechanisms, including NF-κB and Nrf2 pathways, two well-known master regulators of inflammation. A better mechanistic understanding of the BET proteins' role in regulating the inflammatory process is of great significance since it could reveal novel therapeutic targets to reduce neuroinflammation associated with many CNS diseases. Read More

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September 2021

Complement component 3 from astrocytes mediates retinal ganglion cell loss during neuroinflammation.

Acta Neuropathol 2021 11 6;142(5):899-915. Epub 2021 Sep 6.

Division of Neuroimmunology and Neurological Infections, Johns Hopkins Hospital, Pathology Building 509, 600 N. Wolfe St., Baltimore, Md, 21287, USA.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized by varying degrees of secondary neurodegeneration. Retinal ganglion cells (RGC) are lost in MS in association with optic neuritis but the mechanisms of neuronal injury remain unclear. Complement component C3 has been implicated in retinal and cerebral synaptic pathology that may precede neurodegeneration. Read More

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November 2021

Differential regulation of cerebral microvascular transcription by single and repetitive hypoxic conditioning.

Cond Med 2021 ;4(1):58-68

Departments of Ophthalmology, Louisiana State University School of Medicine, LSUHSC, New Orleans, LA.

Systemic conditioning therapeutics afford brain protection at all levels of organization, occurring autonomously for neurons, glia, vascular smooth muscle, and endothelium, which are mediated systemically for the adaptive and innate immune system. The present study was undertaken to examine acute (3 h) and delayed (2 days) gene expression changes in mouse cerebral microvessels following single hypoxic conditioning (HX1) and repetitive hypoxic conditioning (HX9), the latter for which we showed previously to extend focal stroke tolerance from days to months. Microarray (Illumina) analyses were performed on microvessel-enriched fractions of adult mouse brain obtained from the following five groups (naïve; HX1-3h; HX1-2days; HX9-3h; HX9-2days). Read More

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January 2021

Janus Kinase Inhibition Ameliorates Ischemic Stroke Injury and Neuroinflammation Through Reducing NLRP3 Inflammasome Activation JAK2/STAT3 Pathway Inhibition.

Front Immunol 2021 22;12:714943. Epub 2021 Jul 22.

Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Inflammatory responses play a multiphase role in the pathogenesis of cerebral ischemic stroke (IS). Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, reduces inflammatory responses the JAK2/STAT3 pathway. Based on its anti-inflammatory and immunosuppressive effects, we hypothesized that it may have a protective effect against stroke. Read More

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December 2021

The genetic architecture of plasma kynurenine includes cardiometabolic disease mechanisms associated with the SH2B3 gene.

Sci Rep 2021 08 2;11(1):15652. Epub 2021 Aug 2.

Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, 2220 Pierce Ave, PRB 354B, Nashville, TN, 37232, USA.

Inflammation increases the risk of cardiometabolic disease. Delineating specific inflammatory pathways and biomarkers of their activity could identify the mechanistic underpinnings of the increased risk. Plasma levels of kynurenine, a metabolite involved in inflammation, associates with cardiometabolic disease risk. Read More

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A Mechanistic Model for Yoga as a Preventive and Therapeutic Modality.

Int J Yoga 2021 May-Aug;14(2):152-157. Epub 2021 May 10.

Memphis VA Medical Center, The University of Memphis, Memphis, TN, USA.

Yoga is an ancient Indian technique of healthy living. Numerous studies have corroborated yoga's beneficial effects, including a favorable influence on autonomic function and negative emotions. Extensive research in the last few decades has revealed the critical role that yoga can play in eradicating stress. Read More

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Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke.

Sci Rep 2021 06 25;11(1):13345. Epub 2021 Jun 25.

Department of Tropical Medicine, Army Medical University, Chongqing, China.

No FDA approved pharmacological therapy is available to reduce neuroinflammation following heatstroke. Previous studies have indicated that dexmedetomidine (DEX) could protect against inflammation and brain injury in various inflammation-associated diseases. However, no one has tested whether DEX has neuro-protective effects in heatstroke. Read More

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Pathophysiological Bases of Comorbidity in Migraine.

Front Hum Neurosci 2021 20;15:640574. Epub 2021 Apr 20.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy.

Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. Read More

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Increased synthesis of pro-inflammatory cytokines in C9ORF72 patients.

Amyotroph Lateral Scler Frontotemporal Degener 2021 11 30;22(7-8):517-527. Epub 2021 Apr 30.

Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.

C9ORF72 hexanucleotide expansion is the most common genetic cause of familial amyotrophic lateral sclerosis (ALS)/fronto-temporal dementia (FTD) disease spectrum. Even though three major mechanisms of disease pathogenesis have been proposed, we lack detailed understanding of the factors that influence disease onset and progression. We sought to characterize cerebrospinal fluid and sera of C9ORF72 patients via a multiplex assay of 41 chemokines and cytokines in comparison to neurological controls and sporadic ALS patients. Read More

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November 2021

Beyond Self-Recycling: Cell-Specific Role of Autophagy in Atherosclerosis.

Cells 2021 03 11;10(3). Epub 2021 Mar 11.

Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximillians-Universität (LMU), D-80336 Munich, Germany.

Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis. Read More

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CRIP1 expression in monocytes related to hypertension.

Clin Sci (Lond) 2021 04;135(7):911-924

Clinic of Cardiology, University Heart and Vascular Center Hamburg, Germany.

Hypertension is a complex and multifactorial disorder caused by lifestyle and environmental factors, inflammation and disease-related genetic factors and is a risk factor for stroke, ischemic heart disease and renal failure. Although circulating monocytes and tissue macrophages contribute to the pathogenesis of hypertension, the underlying mechanisms are poorly understood. Cysteine rich protein 1 (CRIP1) is highly expressed in immune cells, and CRIP1 mRNA expression in monocytes associates with blood pressure (BP) and is up-regulated by proinflammatory modulation suggesting a link between CRIP1 and BP regulation through the immune system. Read More

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Genetic and Proteomic Contributions to the Pathophysiology of Moyamoya Angiopathy and Related Vascular Diseases.

Appl Clin Genet 2021 18;14:145-171. Epub 2021 Mar 18.

Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA.

Rationale: This literature review describes the pathophysiological mechanisms of the current classes of proteins, cells, genes, and signaling pathways relevant to moyamoya angiopathy (MA), along with future research directions and implementation of current knowledge in clinical practice.

Objective: This article is intended for physicians diagnosing, treating, and researching MA.

Methods And Results: References were identified using a PubMed/Medline systematic computerized search of the medical literature from January 1, 1957, through August 4, 2020, conducted by the authors, using the key words and various combinations of the key words "moyamoya disease," "moyamoya syndrome," "biomarker," "proteome," "genetics," "stroke," "angiogenesis," "cerebral arteriopathy," "pathophysiology," and "etiology. Read More

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Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 Monoclonal Antibodies.

Curr Med Chem 2021 ;28(36):7427-7445

Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, P.O. Box 2713, Qatar.

Cardiovascular disease (CVD) remains the primary cause of global morbidity and mortality. CVD includes various life-threatening conditions such as myocardial infarction, stroke and peripheral arterial diseases. In this context, atherosclerosis continues to play the principal role in the pathogenesis of these conditions. Read More

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November 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

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. Read More

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January 2021

Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response.

Transl Psychiatry 2021 02 15;11(1):127. Epub 2021 Feb 15.

Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Antidepressant outcomes in older adults with depression is poor, possibly because of comorbidities such as cerebrovascular disease. Therefore, we leveraged multiple genome-wide approaches to understand the genetic architecture of antidepressant response. Our sample included 307 older adults (≥60 years) with current major depression, treated with venlafaxine extended-release for 12 weeks. Read More

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February 2021

CUEDC2 ablation enhances the efficacy of mesenchymal stem cells in ameliorating cerebral ischemia/reperfusion insult.

Aging (Albany NY) 2021 01 20;13(3):4335-4356. Epub 2021 Jan 20.

Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China.

Mesenchymal stem cell (MSC) therapy has been reported to be a promising therapeutic option for cerebral ischemia/reperfusion (I/R) insult. However, the poor survival rate of engrafted MSCs under unfavorable cerebral I/R-induced microenvironment inhibits their efficiency during clinical application. CUE domain-containing 2(CUECD2) exhibits its protective role on cardiomyocytes by mediating the antioxidant capacity. Read More

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January 2021