Abstract:The purpose of this study was to identify the biomarkers implicated in the development of intracranial hemorrhage (ICH) and potential regulatory pathways. In the transcriptomic data for patients with ICH, we identified DEmiRNAs and DEmRNAs related to hypoxia, inflammation, and their transcription factors (TFs). An ICH-based miRNA-TF-mRNA regulatory network was thus constructed, and four biomarkers (TIMP1, PLAUR, DDIT3, and CD40) were screened for their association with inflammation or hypoxia by machine learni… Show more
“…In addition to the motif activity changes of transcription factors, with the combinatory treated sample, we observed a decrease in the activity of the transcription factor SP1, known to be involved in inflammatory processes. Moreover, SP3, a transcription factor recognized for its anti-inflammatory effects and closely linked to transcription factor SP1 ( 13 ), exhibited an increase, in the same sample, when compared to the TGF-β-treated sample ( Fig. 4F, G ).…”
We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when used in conjunction with fully covered self-expandable metal stents (FCSEMS) for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohistochemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels. Overall, our findings revealed a dose-dependent decrease in fibrosis-related signaling with higher TA concentrations. The 15 mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30 mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. Use of corticosteroids, specifically TA, together with FCSEMS was effective for the treatment of BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS as a therapeutic option for BBS in humans resulting from various surgical procedures.
“…In addition to the motif activity changes of transcription factors, with the combinatory treated sample, we observed a decrease in the activity of the transcription factor SP1, known to be involved in inflammatory processes. Moreover, SP3, a transcription factor recognized for its anti-inflammatory effects and closely linked to transcription factor SP1 ( 13 ), exhibited an increase, in the same sample, when compared to the TGF-β-treated sample ( Fig. 4F, G ).…”
We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when used in conjunction with fully covered self-expandable metal stents (FCSEMS) for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohistochemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels. Overall, our findings revealed a dose-dependent decrease in fibrosis-related signaling with higher TA concentrations. The 15 mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30 mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. Use of corticosteroids, specifically TA, together with FCSEMS was effective for the treatment of BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS as a therapeutic option for BBS in humans resulting from various surgical procedures.
“…Studies have shown that TIMP1 is related not only to inflammation but also to the indicators of fibrosis. 26 , 27 , 28 , 29 Taken together, the mechanism by which RASSF4 affects fibrosis needs further study. Figure 7 RASSF4 inhibits lipid synthesis and inflammation in hepatocytes.…”
“…Among the top canonical pathways identified by Ingenuity Pathway Analysis (IPA) were phosphatase and tensin homolog (PTEN) signaling as well as ciliary neurotrophic factor (CNTF) signaling, both of which exert distinct immunomodulatory (including inflammatory) effects [91][92][93] and which have been found to be associated with ADrelated neuropathology [94,95]. Furthermore, among the top master regulators identified by IPA were transcription factor Sp3 and chymase 1, both of which have been implicated in inflammatory regulation [96,97] and are present in higher levels in the brains of AD patients [98,99]. Finally, transforming growth factor beta 1 (TGFB1), which was reduced in the Western cohort, is a pleiotropic cytokine with multifarious effects on both innate and adaptive immune function [100] and has been variously described as pro-and anti-inflammatory [101].…”
INTRODUCTIONMediterranean diets may be neuroprotective and prevent cognitive decline relative to Western diets, however the underlying biology is poorly understood.METHODSWe assessed the effects of Western vs. Mediterranean-like diets on RNAseq generated transcriptional profiles in temporal cortex and their relationships with changes in MRI neuroimaging phenotypes, circulating monocyte gene expression, and observations of social isolation and anxiety in 38 socially-housed, middle-aged female cynomolgus macaques.RESULTSDiet resulted in differential expression of seven transcripts (FDR<0.05). Cyclin dependent kinase 14 (CDK14), a proinflammatory regulator, was lower in the Mediterranean group. The remaining six transcripts [i.e., “lunatic fringe” (LFNG), mannose receptor C type 2 (MRC2), solute carrier family 3 member 2 (SLCA32), butyrophilin subfamily 2 member A1 (BTN2A1), katanin regulatory subunit B1 (KATNB1), and transmembrane protein 268 (TMEM268)] were higher in cortex of the Mediterranean group and generally associated with anti-inflammatory/neuroprotective pathways.KATNB1encodes a subcomponent of katanin, important in maintaining microtubule homeostasis.BTN2A1is involved in immunomodulation of γδ T-cells which have anti-neuroinflammatory and neuroprotective effects.CDK14,LFNG,MRC2,andSLCA32are associated with inflammatory pathways. The latter four differentially expressed cortex transcripts were associated with monocyte transcript levels, changes in AD-relevant brain volumes determined by MRI over the course of the study, and social isolation and anxiety.CDK14was positively correlated with monocyte inflammatory transcripts, changes in total brain, gray matter, cortical gray matter volumes, and time alone and anxious behavior, and negatively correlated with changes in total white matter and cerebrospinal fluid (CSF) volumes. In contrast,LFNG,MRC2, andSLCA32were negatively correlated with monocyte inflammatory transcripts and changes in total gray matter volume, and positively correlated with CSF volume changes, and SLCA32 was negatively correlated with time alone.DISCUSSIONCollectively, our results suggest that relative to Western diets, Mediterranean diets confer protection against peripheral and central inflammation which is reflected in preserved brain structure and behavior.
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