Uric Acid Neuroprotection Associated to IL-6/STAT3 Signaling Pathway Activation in Rat Ischemic Stroke

Aliena‐Valero, Alicia; Rius‐Pérez, Sergio; Baixauli-Martín, Júlia; Torregrosa, Germán; Chamorro, Ángel; Pérez, Salvador; Salom, Juan B.

doi:10.1007/s12035-020-02115-w

Cited by 32 publications

(21 citation statements)

References 99 publications

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“…Some crucial inflammatory cytokines, such as IL-6, IL-1β, can upregulate the CA-sensing receptor, which can control blood CA homeostasis and is a promoter and responder of inflammation (24,29). Meanwhile, IL-6 and TNF-a are essential inflammatory cytokines, positively associated with SUA levels (30)(31)(32). Therefore, when UA crystallizes in joints, an elevated level of SUA may cause inflammatory arthritis (33,34).…”

Section: Discussionmentioning

confidence: 99%

Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12–19 Years: A Cross-Sectional Study

Luo

Jin

et al. 2022

Front. Med.

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AimsEvidence of a link between total calcium (CA) and serum uric acid (SUA) is absent in adolescents. Thus, this study aimed to determine the relationship between total CA levels and SUA levels in United States adolescents.MethodsA cross-sectional study analyzed a sample composed of 8,309 United States adolescents aged 12–19 years from the National Health and Nutrition Examination Survey database (1999–2006 survey cycle). Multivariable linear regression analyses and multivariable logistic regression analyses were used to assess the correlation of total CA with SUA levels and hyperuricemia. Furthermore, the dose-response relationship of total CA and SUA levels was analyzed using smooth curve fitting (penalized spline method).ResultsAccording to multivariable linear regression analysis, every 1 mg/dL increase in total CA level is associated with a 0.33 mg/dL (β = 0.33, 95% CI: 0.27–0.40, p < 0.001) increase in SUA. Multivariable logistic regression analyses showed that every 0.1 mg/dL increase in total CA level is linked with an 8% increased risk of hyperuricemia (OR = 1.08, 95% CI: 1.06–1.10, p < 0.001). The analyses of smooth curve fitting revealed that total CA levels were linearly correlated with SUA levels (Pnon–linearity = 0.152). The results were highly stable in all subgroups. The interaction analysis results presented that race/ethnicity had an interactive role in associating total CA with SUA levels.ConclusionsIn United States adolescents, total CA levels were linearly and positively correlated with SUA levels.

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Section: Discussionmentioning

confidence: 99%

Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12–19 Years: A Cross-Sectional Study

Luo

Jin

et al. 2022

Front. Med.

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“…Microglia play an important role in this process. Microglia can be activated by neurotoxic substances such as cell fragments, reactive oxygen species, and NO produced by neuronal necrosis caused by cerebral ischemia; this can then produce a large number of inflammatory factors such as interleukin 6 (IL6), interleukin 1β (IL1β), and tumor necrosis factor alpha (TNF-α), causing local brain tissue inflammation, infiltration, and damage ( Yu et al, 2016 ; Koizumi et al, 2019 ; Aliena-Valero et al, 2021 ). Excessive activation of microglia releases a large amount of pro-inflammatory factors, which is a direct factor that aggravates cerebral ischemia-reperfusion injury ( Klement et al, 2018 ; Naveed et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Combination of Systems Pharmacology and Experimental Evaluation to Explore the Mechanism of Synergistic Action of Frankincense-Myrrh in the Treatment of Cerebrovascular Diseases

et al. 2022

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Frankincense-Myrrh is a classic drug pair that promotes blood circulation, and eliminates blood stasis. The combination of the two drugs has a definite clinical effect on the treatment of cerebrovascular diseases (CBVDs), but its mechanism of action and compatibility have not been elucidated. In this study, the bioactive components, core targets, and possible synergistic mechanisms of Frankincense-Myrrh in the treatment of CBVDs are explored through systems pharmacology combined with in vivo and in vitro experiments. Comparing target genes of components in Frankincense and Myrrh with CBVD-related genes, common genes were identified; 15 core target genes of Frankincense-Myrrh for the treatment of CBVDs were then identified using protein-protein interaction (PPI) analysis. It was also predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis that the molecular mechanism of Frankincense-Myrrh action on CBVDs was mainly related to the regulation of neurotrophic factors and inflammatory responses. Frankincense-Myrrh significantly improved neurological function, decreased infarct volume, alleviated histopathological damage, inhibited microglial expression, and promoted the expression of neurons in middle cerebral artery occlusion (MCAO)-induced rats. The results of this study not only provide important theoretical support and experimental basis for the synergistic effect of Frankincense-Myrrh, but also provide new ideas for the prevention and treatment of cerebral ischemic injuries.

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“…One study found the reactive astrocytes are responsible for the elevated SOCS3 levels in the hippocampus following an ischemic insult in rats. VEGFA is a known brain marker for brain swelling following AIS and is upregulated in edema-rich regions [ 91 ]. When we take the expression results of the target genes of the picked miRNAs into consideration, which were altered in the investigated brain regions and spleen and liver, we assume that, somehow, a trigger as a communication signal might be released on purpose or accidentally to induce gene expression changes in the investigated non-affected regions after ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Transient Focal Cerebral Ischemia Leads to miRNA Alterations in Different Brain Regions, Blood Serum, Liver, and Spleen

Voelz

Ebrahimy

Zhao

et al. 2021

IJMS

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Ischemic stroke is characterized by an occlusion of a cerebral blood vessel resulting in neuronal cell death due to nutritional and oxygen deficiency. Additionally, post-ischemic cell death is augmented after reperfusion. These events are paralleled by dysregulated miRNA expression profiles in the peri-infarct area. Understanding the underlying molecular mechanism in the peri-infarct region is crucial for developing promising therapeutics. Utilizing a tMCAo (transient Middle Cerebral Artery occlusion) model in rats, we studied the expression levels of the miRNAs (miR) 223-3p, 155-5p, 3473, and 448-5p in the cortex, amygdala, thalamus, and hippocampus of both the ipsi- and contralateral hemispheres. Additionally, the levels in the blood serum, spleen, and liver and the expression of their target genes, namely, Nlrp3, Socs1, Socs3, and Vegfa, were assessed. We observed an increase in all miRNAs on the ipsilateral side of the cerebral cortex in a time-dependent manner and increased miRNAs levels (miR-223-3p, miR-3473, and miR-448-5p) in the contralateral hemisphere after 72 h. Besides the cerebral cortex, the amygdala presented increased expression levels, whereas the thalamus and hippocampus showed no alterations. Different levels of the investigated miRNAs were detected in blood serum, liver, and spleen. The gene targets were altered not only in the peri-infarct area of the cortex but selectively increased in the investigated non-affected brain regions along with the spleen and liver during the reperfusion time up to 72 h. Our results suggest a supra-regional influence of miRNAs following ischemic stroke, which should be studied to further identify whether miRNAs are transported or locally upregulated.

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Uric Acid Neuroprotection Associated to IL-6/STAT3 Signaling Pathway Activation in Rat Ischemic Stroke

Cited by 32 publications

References 99 publications

Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12–19 Years: A Cross-Sectional Study

Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12–19 Years: A Cross-Sectional Study

Combination of Systems Pharmacology and Experimental Evaluation to Explore the Mechanism of Synergistic Action of Frankincense-Myrrh in the Treatment of Cerebrovascular Diseases

Transient Focal Cerebral Ischemia Leads to miRNA Alterations in Different Brain Regions, Blood Serum, Liver, and Spleen

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