Background/Objectives: RA is a chronic autoimmune disease characterized by systemic inflammation and progressive joint damage. Plant-based dietary interventions have recently emerged as complementary anti-inflammatory therapy for active RA. However, the molecular anti-inflammatory mechanisms of plant-based dietary patterns in these patients are still poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators of inflammation in chronic diseases. Thus, this study aimed to evaluate the expression of lncRNAs and inflammatory genes in relation to the clinical response to following a plant-based dietary intervention in patients with active RA. Methods: A two-phase whole-blood gene expression analysis was conducted for patients with active RA before and after a 14-day plant-based dietary intervention. In the discovery phase, seven patients showing the greatest reduction in disease activity (DAS28-CRP) were selected, and the expression of 84 inflammatory genes and 84 lncRNAs was analyzed using RT² Profiler PCR Array platforms. In the validation phase, by adding 14 patients, we assessed 21 participants. Results: NUTM2A-AS1 was the only significantly overexpressed lncRNA in the discovery phase (p = 0.0435), while CCR3 was the only inflammatory gene showing significant expression change (p = 0.0156). In the validation phase, both NUTM2A-AS1 and CCR3 maintained the same pattern of overexpression, confirming their modulation after the 14-day plant-based dietary intervention (p = 0.0131 and p < 0.001, respectively). Conclusions: This study showed that a 14-day plant-based diet was sufficient to modify the inflammatory circuits in patients with active RA, suggesting a potential dietary-mediated inflammatory modulation mechanism involving NUTM2A-AS1 and CCR3. Further studies are required to validate new hypotheses on the biological significance of the regulation of these transcripts and its clinical implications in RA management.

The role of leukotrienes (LTs) in the pathogenesis of systemic sclerosis (SSc) needs clarification. We analyzed the association of salivary (sa) and plasma (p) levels (pg/mL) of cysteinyl-leukotrienes (CysLT) and LTB4 with SSc vascular manifestations and nailfold capillaroscopy (NFC) in a cross-sectional study. Patients and healthy controls were evaluated for vascular manifestations and NFC. LTs were compared between groups as follows: SSc with or SSc without vascular features and controls, and by NFC parameters. Twenty SSc patients and 16 volunteers were recruited; Raynaud’s phenomenon (RP) history (SSc: saCysLT 99.4 ± 21.8 vs. controls: 23.05 ± 23.7, p = 0.01), RP at examination (SSc: saCysLT 129.3 ± 24.6 vs. controls: 23.05 ± 22.46, p = 0.01; pCysLT SSc: 87.5 ± 11.2 vs. controls: 32.37 ± 10.75, p = 0.002), capillary loss (saCysLT 138.6 ± 26.7 vs. 23.05 ± 21.6, p = 0.0007; saLTB4 3380.9 ± 426.6 vs. 1216.33 ± 346.1, p = 0.0005), “late” scleroderma pattern vs. controls (saCysLT 205.6 ± 32 vs. 23 ± 19.6, p = 0.0002; saLTB4 4564.9 ± 503.6 vs. 1216.3 ± 308.3; p < 0.0001) were all significant. Late patterns had higher levels (saCysLT, p = 0.002; LTB4 p = 0.0006) compared to active and early patterns (LTB4, p = 0.0006), and giant capillaries (p = 0.01) showed higher levels of LTs. Levels of pCysLT were higher in patients with RP at examination vs. patients without RP; saCysLT and LTB4 were higher in SSc group with vs. without capillary loss. LTs could be involved in the pathophysiology of vascular abnormalities. Further research is required to determine if blocking LTs could be a therapeutic target for SSc vascular manifestations.

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.