Aarón Domínguez-López

Background/Objectives: MicroRNAs (miRNAs) have emerged as molecular mediators involved in the pathogenesis of rheumatoid arthritis (RA). Given the influence of diet on gene expression and inflammation, plant-based diets represent a potential non-pharmacological strategy for modulating disease activity. This study aimed to explore and validate, through a bioinformatic-guided pilot approach, the regulation of miRNAs associated with RA in response to a 14-day plant-based dietary intervention. Methods: Candidate miRNAs were identified through differential expression analysis of the GSE124373 dataset using GEO2R and were further supported by a literature review. Target gene prediction and functional enrichment analyses were conducted to assess the biological relevance of these findings. Twenty-three RA patients followed a plant-based diet for 14 days. The clinical activity (DAS28-CRP), biochemical markers, and plasma expression of five selected miRNAs (miR-26a-5p, miR-125a-5p, miR-125b-5p, miR-146a-5p, and miR-155-5p) were evaluated before and after the intervention using RT-qPCR. Results: Significant reductions were observed in DAS28-CRP scores, C-reactive protein, glucose, and lipid levels after 14 days of intervention. Three of the five miRNAs (miR-26a-5p, miR-125a-5p, and miR-155-5p) were significantly downregulated post-intervention. Bioinformatic analyses indicated that these miRNAs regulate immune–inflammatory pathways relevant to RA pathogenesis. Conclusions: This pilot study suggests that a short-term plant-based dietary intervention may modulate circulating miRNAs and improve clinical and biochemical parameters in RA patients. These findings support further research into dietary strategies as complementary approaches for RA management.

Obesity is characterized by the excessive accumulation of fat, which triggers a low-grade chronic inflammatory process. Currently, the search for compounds with anti-obesogenic effects that help reduce body weight, as well as associated comorbidities, continues. Among this group of compounds are plant extracts and flavonoids with a great diversity of action mechanisms associated with their beneficial effects, such as anti-inflammatory effects and/or as signaling molecules. In the bark of Tabebuia rosea tree, there are different classes of metabolites with anti-inflammatory properties, such as quercetin. Therefore, the present work studied the effect of the ethanolic extract of T. rosea and quercetin on the mRNA of inflammation markers in obesity compared to the drugs currently used. Total RNA was extracted from epididymal adipose tissue of high-fat diet-induced obese Wistar rats treated with orlistat, phentermine, T. rosea extract, and quercetin. The rats treated with T. rosea and quercetin showed 36 and 31% reductions in body weight compared to the obese control, and they likewise inhibited pro-inflammatory molecules: Il6, Il1b, Il18, Lep, Hif1a, and Nfkb1 without modifying the expression of Socs1 and Socs3. Additionally, only T. rosea overexpressed Lipe. Both T. rosea and quercetin led to a reduction in the expression of pro-inflammatory genes, modifying signaling pathways, which led to the regulation of the obesity-inflammation state.

Context: There is evidence that n-3 polyunsaturated fatty acids (n-3-PUFAs) can inhibit mTORC1, which should potentiate autophagy and eliminate NLRP3 inflammasome activity. Objective: Evaluate the effect of a high-fat or high-fat/fructose diet with and without n-3-PUFAs on hepatic gene expression. Materials and methods: We examined the mRNA expression by RT-PCR of Mtor, Nlrp3, and other 22 genes associated with inflammation in rats livers after a 9-week diet. The dietary regimens were low-fat (control, CD), high-fat (HF), high-fat/fructose (HF-Fr), and also each of these supplemented with n-3-PUFAs (CD-n-3-PUFAs, HF-n-3-PUFAs, and HF-Fr-n-3-PUFAs). These data were processed by GeneMania and STRING databases. Results: Compared to the control, the HF group showed a significant increase (between p < 0.05 and p < 0.0001) in 20 of these genes (Il1b, Il18, Rxra, Nlrp3, Casp1, Il33, Tnf, Acaca, Mtor, Eif2s1, Eif2ak4, Nfkb1, Srebf1, Hif1a, Ppara, Ppard, Pparg, Mlxipl, Fasn y Scd1), and a decrease in Sirt1 (p < 0.05). With the HF-Fr diet, a significant increase (between p < 0.05 and p < 0.005) was also found in the expression of 16 evaluated genes (Srebf1, Mlxipl, Rxra, Abca1, Il33, Nfkb1, Hif1a, Pparg, Casp1, Il1b, Il-18, Tnf, Ppard, Acaca, Fasn, Scd1), along with a decrease in the transcription of Mtor and Elovl6 (p < 0.05). Contrarily, many of the genes whose expression increased with the HF and HF-Fr diets did not significantly increase with the HF-n-3-PUFAs or HF-Fr-n-3-PUFAs diet. Discussion and conclusion: We found the interrelation of the genes for the mTORC1 complex, the NLRP3 inflammasome, and other metabolically important proteins, and that these genes respond to n-3-PUFAs.

Background: Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on TLR2, TLR3, and TLR4 participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of TLR1 to 9 in colonic mucosa of UC patients, according to disease activity. Methods: Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of TLR1 to 9, Tollip, inflammatory cytokines IL6 and TNF were assessed by RT-qPCR with hydrolysis probes. Characterization of TLR9 protein expression was performed by Immunohistochemistry. Results: Toll-like receptors TLR8, TLR9, and IL6 mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to healthy individuals (p < 0.04). In the UC patients group the TLR2, TLR4, TLR8 and TLR9 mRNA levels were found to be significantly lower in patients with quiescent disease, as compared to those with active disease (p < 0.05), whereas TLR5 showed a trend (p = 0.06). IL6 and TNF mRNA levels were significantly higher in the presence of active disease and help to discriminate between quiescent and active disease (p < 0.05). Also, IL6 and TNF mRNA positively correlate with TLRs mRNA with the exception for TLR3, with stronger correlations for TLR5, TLR8, and TLR9 (p < 0.0001). TLR9 protein expression was mainly in the lamina propria infiltrate. Conclusions: This study demonstrates that TLR2, TLR4, TLR8, and TLR9 expression increases in active UC patients, and that the mRNA levels positively correlate with the severity of intestinal inflammation as well as with inflammatory cytokines.