microRNA-mRNA Networks Linked to Inflammation and Immune System Regulation in Inflammatory Bowel Disease.

The molecular processes linked to the development and progression of Crohn's disease (CD) and ulcerative colitis (UC) are not completely understood. MicroRNAs (miRNAs) regulate gene expression and are indicated as diagnostic, prognostic, and predictive biomarkers in chronic degenerative diseases. Our objectives included the identification of global miRNA expression in CD and UC, as well as miRNA target genes, miRNA-mRNA interaction networks, and biological functions associated with these different forms of inflammatory bowel disease (IBD). METHODS: By performing a comprehensive meta-analysis, we integrated miRNA expression data from nine studies in IBD. We obtained detailed information on significantly deregulated miRNAs (fold change, FC ≥ 2 and p < 0.05), sample type and number, and platform applied for analysis in the training and validation sets. Further bioinformatic analyses were performed to identify miRNA target genes, by using the microRNA Data Integration Portal tool. We also sought to identify statistically enriched pathways of genes regulated by miRNAs using ToppGene Suite. Additional analyses were performed to filter for genes expressed in intestinal tissue using the European Bioinformatics Institute (EBI) database. RESULTS: Our findings showed the upregulation of 15 miRNAs in CD and 33 in UC. Conversely, six miRNAs were downregulated in CD, while seven were downregulated in UC. These results indicate a greater deregulation of miRNAs in UC compared to CD. Of note, miRNA target genes were enriched for immune system regulation pathways. Among significantly deregulated miRNAs with a higher number of miRNA-target gene interactions, we identified miR-199a-5p and miR-362-3p altered in CD, while among UC case patients, miRNA-target gene interactions were higher for miR-155-5p. CONCLUSIONS: The identified miRNAs play roles in regulating genes associated with immune system regulation and inflammation in IBD. Such miRNAs and their target genes have the potential to serve as clinically relevant biomarkers. These findings hold promise for enhancing the accuracy of diagnoses and facilitating the development of personalized treatment strategies for individuals with various forms of IBD.

Bidens pilosa (Black Jack) Standardized Extract Ameliorates Acute TNBS-induced Intestinal Inflammation in Rats.

Bidens pilosa is an herb popularly used to treat inflammation, hemorrhoids, fever, and gastric ulcers with reported pharmacological activities and chemical composition that sustain its selection as a potential intestinal anti-inflammatory product. Based on this, we examined the effects of a B. pilosa fatty acid-standardized supercritical preparation on the intestinal inflammatory process induced by trinitrobenzenesulphonic acid in rats, using either preventative or curative treatments. We also investigated the safety of plant extract by acute and sub-chronic toxicological analysis. The intestinal anti-inflammatory activity was related to modulation of the immune response, increasing IL-10 production and reducing IL-1ß, IL-6, and TNF-α level, the oxidative stress, and the MUC production in the inflamed colon. Optic, scanning, and transmission electron microscopy (TEM) analysis supported the beneficial effects promoted by B. pilosa, which were closely related to downregulation of heparanase, Hsp70, Mapk 3, and NF-κB signaling and with the presence of long-chain fatty acids in extract. Our data suggest that B. pilosa supercritical preparation is a chemically standardized preparation potentially useful as complementary intestinal anti-inflammatory agent to treat inflammatory bowel disease.

Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation.

AIM: Etiopathogenesis of inflammatory bowel disease is unclear and results from a complex interplay of genetic, microbial, environmental and immune factors. Elucidating the mechanisms that drive IBD depends on the detailed characterization of human inflammatory mediators in animal models. Therefore, we studied how intestinal inflammation affects heparanase, NF-κB and Hsp70 gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. Moreover, we investigated the relationships among these genes with colonic cytokines levels (IL-1ß, TNF-α, IL-6, INF-γ and IL-10) and oxidative stress that have fundamental role in IBD. MATERIAL AND METHODS: Macroscopic parameters (diarrhea, extension of lesion, colonic weight/length ratio and damage score), biochemical markers (myeloperoxidase and alkaline phosphatase activities, and glutathione, IL-1ß, TNF-α, IL-6, INF-γ and IL-10 levels), gene expressions (heparanase, NF-κB and Hsp70), and microscopic evaluations (optic, electronic scanning and transmission microscopic) were performed in rats. KEY FINDINGS: Expression of heparanase, Hsp70 and NF-κB and oxidative stress were increased by inflammatory process and differentially modulated by sulphasalazine, prednisolone and azathioprine treatments. Protective effects of drugs were also related to differential modulation of cytokine changes induced by inflammatory process, showing different mechanisms to control inflammation. SIGNIFICANCE: Heparanase, NF-κB and Hsp70 gene expression participate in the inflammatory response induced by TNBS and represent pharmacological targets of the intestinal anti-inflammatory drugs. In addition, current drugs used to treat IBD (sulphasalazine, prednisolone and azathioprine) differentially modulate heparanase, NF-κB and Hsp70 gene expression, cytokine production and oxidative stress.

Anti-inflammatory and analgesic potential of hydrolyzed extract of Agave sisalana Perrine ex Engelm., Asparagaceae / Potencial anti-inflamatório e analgésico do extrato hidrolisado de Agave sisalana Perrine ex Engelm, Asparagaceae

The hemolytic, anti-inflammatory and antinociceptive properties from hydrolyzed extract Agave sisalana Perrine ex Engelm., Asparagaceae (HEAS) was evaluated on classic inflammation models. Male Swiss mice and male Wistars rats received HEAS (500 mg/kg) in two administration p.o. and i.p. in saline solution 0.9 percent. The acid hydrolysis inhibited the hemolytic action of saponins due to the retreat of side chain sugar. The treatment of the ear induced oedema by xylene with HEAS significantly reduced in two routes 13±1.5 and 10±0.63 mg, respectively, p.o. and i.p., in comparison with controls 27±1.5 saline and 13.5±1.2 AAS. The HEAS also diminished edema induced by carrageenin 43±1.58 mg (p.o.) and 17±1.26 mg (i.p.), when compared with control groups 52±1.58 mg (saline) and 10.05±1.58 (indomethacin). HEAS showed analgesic effects in abdominal constrictions 30.7 percent (p.o.), 88.7 percent (i.p.) comparable to that produced by (AAS) 70.6 percent. However in granuloma cotton pellet a chronic model of inflammation just the i.p. pathway decreased granulomatous tissue (20.4±1.32 mg) compared with controls 30.5±2.53 mg (saline) and 20.2±2.18 mg (dexamethasone). These data suggest that HEAS has anti-inflammatory and analgesic activity on acute and chronic processes.

As propriedades hemolítica, anti-inflamatória e antinociceptiva do extrato hidrolisado de Agave sisalana Perrine ex Engelm, Aparagaceae (HEAS) foram avaliadas em modelos clássicos de inflamação. Camundongos Swiss e ratos Wistars machos receberam HEAS (500 mg/kg) em duas vias de administração p.o e i.p em solução salina 0.9 por cento. A hidrólise ácida inibiu a ação hemolítica das saponinas através da retirada das cadeias laterais de açúcar. O tratamento com HEAS reduziu significativamente o edema de orelha induzido por xilol em duas vias 13±1.5 e 10±0.63 mg respectivamente, p.o e i.p, em comparação com os controles 27±1.5 salina e 13.5±1.2 AAS. O HEAS também diminuiu o edema induzido por carragenina 43±1.58 mg (p.o) e 17±1.26 mg (i.p), quando comparado com os grupos controle 52±1.58 (salina) e 10.05±1.58 (indometacina). HEAS apresentou efeito analgésico em modelo de contorções abdominais 30.7 por cento (p.o), 88.7 por cento (i.p) comparado com aquele produzido pelo (AAS) 70.6 por cento. Contudo, no modelo crônico de inflamação granuloma cotton pellet apenas a via i.p diminuiu o tecido granulomatoso (20.4±1.32 mg) comparado com os controles 30.5±2.53 (salina) e 20.2±2.18 mg (dexametasona). Esses dados sugerem que o HEAS possui atividades anti-inflamatória e analgésica em processos agudos e crônicos.