Luis Manuel Amezcua Guerra

Background: Hyperuricemia and gout are closely associated with alterations in gut microbiota function. Short-chain fatty acids (SCFAs) produced by intestinal microorganisms may modulate immune responses and inflammation relevant to gout pathophysiology. This study evaluated fecal SCFA concentrations, their associations with dietary purine intake, and the relationship between Akkermansia spp. and Prevotella spp. abundance and fecal SCFA profiles across the clinical spectrum of hyperuricemia. Methods: This cross-sectional study included 380 Mexican adults: normouricemic controls (n = 141), individuals with asymptomatic hyperuricemia (AH; n = 98), and patients with gout (n = 141). Fecal SCFAs were quantified by GC-FID and bacterial abundance by qPCR. Dietary intake was assessed by semi-quantitative food frequency questionnaire and classified by purine content. Between-group differences were evaluated by the Kruskal–Wallis test (Benjamini–Hochberg correction); multivariable linear regression adjusted for age, sex, and BMI was used to assess associations, including a pre-specified dietary purine intake per clinical group interaction term. Results: Fecal acetate and propionate were significantly higher in gout patients than controls, whereas AH individuals had significantly higher butyrate. Moderate-purine food intake showed opposing associations with fecal acetate in controls (β = +3.61, p = 0.019) and gout patients (β = −4.59, p = 0.036), with a significant interaction (p = 0.004). Exploratory analyses revealed a positive association between Prevotella spp. abundance and fecal acetate exclusively in the gout group (β = 0.085, p = 0.020). Conclusion: These findings suggest distinct fecal SCFA profiles across stages of urate-related disease, with a disease-specific gut metabolic response to dietary purine intake potentially contributing to the inflammatory environment of established gout. Longitudinal studies with whole-microbiome profiling are needed to establish causality.

Rheumatoid arthritis (RA) involves alterations in cytotoxic lymphoid differentiation, yet the precise phenotypic remodeling of circulating helper T cells and natural killer (NK) cells remains incompletely understood. We evaluated circulating CD4⁺CD28⁺ and CD4⁺CD28⁻ T-cell subsets and NKG2A⁺CD56⁺ NK cells, alongside granule-mediated cytotoxic markers (granzyme B and perforin) and the surface-bound death receptor Fas ligand (FasL), in 28 female patients with RA and 12 age-matched healthy female controls using multiparameter flow cytometry. CD4⁺CD28⁻ cells were increased in RA compared with controls (16.6% versus 6.5% of CD4⁺ cells). Within CD4⁺CD28⁻ cells, granzyme B positivity was markedly lower in RA (5.0% versus 62.0%), whereas FasL expression was higher (40.3% versus 22.5%). RA patients also exhibited a higher proportion of circulating NKG2A⁺CD56⁺ NK cells (6.1% versus 2.7% of PBMCs) with substantially lower granzyme B expression (8.4% versus 55.6%). Higher disease activity (DAS28-CRP) correlated positively with total NKG2A⁺CD56⁺ NK cell frequencies and intracellular perforin expression in both CD4⁺CD28⁺ T cells and NKG2A⁺CD56⁺ NK cells, as well as lower FasL expression in CD4⁺CD28⁻ cells. These findings support a disease-associated phenotypic remodeling of circulating cytotoxic markers in RA, characterized by shifted granzyme B and FasL expressions in CD4⁺CD28⁻ T cells and NKG2A⁺CD56⁺ NK cells, although whether these profiles translate into altered cytotoxic kinetics remains to be functionally determined.

Bedside pressure–flow variables in cardiogenic shock (CS) incompletely characterize ventricular energetics and coupling. We prospectively derived bedside pressure–volume (PV) loop surrogates from paired pulmonary artery catheter and echocardiographic data in 68 patients (263 paired assessments) with acute myocardial infarction–related CS (AMI-CS) or heart failure–related CS (HF-CS) during microaxial support, intra-aortic balloon pump (IABP) support, or medical therapy. In AMI-CS with microaxial support, arterial elastance decreased (−1.22 mm Hg/ml) with improved coupling (ventriculoarterial coupling [VAC] −1.42), stroke work increased (+140 mm Hg·ml), and pressure–volume area declined (PVA −103 mm Hg·ml), yielding an efficiency rise from ~32% to ~40%, suggesting unloading. In HF-CS, microaxial support reduced elastance modestly (−0.35) with probable efficiency gain (+5%) but heterogeneous PVA changes. In AMI-CS treated with IABP, coupling improved (VAC −0.42) with modest energetic augmentation, whereas HF-CS showed pressure and energy amplification (end-systolic pressure +23.9 mm Hg; PVA +220.6 mm Hg ·ml). Without mechanical support, AMI-CS demonstrated reduced elastance and pressure, while HF-CS exhibited ventricular dilation (end-diastolic volume [EDV]/end-systolic volume ESV increase) with higher energetic demand. Pressure–volume–derived metrics identify device-specific energetic signatures not fully captured by conventional hemodynamic assessment and may provide mechanistic insight into ventricular unloading strategies; validation against conductance catheter–derived PV measurements remains warranted.

This study aimed to evaluate whether serum from patients with primary antiphospholipid syndrome (APS) is associated with changes in the expression of long non-coding RNAs (lncRNAs) in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured with serum from 12 female patients with APS or 8 age-matched healthy female controls. The expression levels of HIF1A-AS1, OIP5-AS1, and GAS5 were quantified by RT-qPCR. Exposure of HUVECs to APS serum was associated with reduced expression of HIF1A-AS1 and OIP5-AS1 compared with cells stimulated with control serum. The median HIF1A-AS1 expression levels were 0.08 a.u. (interquartile range, 0.06–0.10) in APS-stimulated cells versus 0.14 a.u. (0.08–0.16) in controls (p = 0.044). Likewise, OIP5-AS1 levels were 0.09 a.u. (0.01–0.16) in APS-stimulated cells versus 2.24 a.u. (0.70–3.55) in controls (p = 0.018). In contrast, GAS5 expression did not differ significantly between groups (340 a.u. (310–3940 versus 358 a.u. (163–445); p = 0.290). In this proof-of-concept study, serum from APS patients was associated with selective downregulation of HIF1A-AS1 and OIP5-AS1 in endothelial cells. These findings support a potential link between circulating APS-related factors and endothelial lncRNA expression; however, no mechanistic or functional conclusions can be drawn.

Introduction: Aortic valve sclerosis (AVSc) is an active pathological process driven by extracellular matrix remodeling, consistent with a potentially reversible early stage of aortic valve disease. Methods: In this cross-sectional study of 168 participants (29, normal aortic valve [NAV]; 98, AVSc; 41, aortic stenosis [AS]), serum levels of matrix metalloproteinase (MMP)-1, -2, -3, and -9, tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor (TNF), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-β) were measured. Multivariable adjustments were performed. Results: Compared with AS, AVSc was associated with higher circulating MMP-9 levels, with MMP-9 also increased relative to NAV. TIMP-1 concentrations were reduced in AVSc compared with both AS and NAV. TNF levels were higher in AVSc than in AS, while IL-6 and TGF-β did not differ among groups. Notably, MMP-9/TIMP-1 ratio was markedly increased in AVSc. Discussion: Our findings suggest that AVSc may exhibit an active proteolytic and inflammatory profile amenable to targeted anti-inflammatory and anti-proteolytic interventions.

Objectives: Takayasu arteritis (TAK) is a large-vessel vasculitis characterized by chronic vascular inflammation and extracellular matrix (ECM) remodeling. Long non-coding RNAs (lncRNAs) have emerged as epigenetic regulators of inflammatory and structural vascular processes. This study aimed to evaluate whether lncRNA HOTAIR (HOX transcript antisense RNA) expression in peripheral blood mononuclear cells (PBMCs) is associated with circulating mediators involved in ECM turnover in patients with TAK. Methods: Fifty-three patients with angiographically confirmed TAK and 53 age- and sex-matched healthy controls were recruited. HOTAIR expression in PBMCs was quantified by reverse transcription-quantitative polymerase chain reaction. Serum concentrations of matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinases-1 (TIMP-1), TIMP-3, extracellular matrix metalloproteinase inducer (EMMPRIN)/CD147, and galectin-3 were measured using enzyme-linked immunosorbent assays. Results: Compared with controls, TAK patients exhibited significantly higher serum levels of MMP-2 (2245 [1929–2646] vs. 1868 [1576–2355] pg/mL; p=0.036), TIMP-1 (2811 [2644–3216] vs. 2588 [2309–2770] pg/mL; p=0.006), and EMMPRIN/CD147 (1494 [1264–2115] vs. 1310 [1132–1655] pg/mL; p=0.035), along with a reduced MMP-9/TIMP-1 ratio (0.88 [0.61–1.28] vs. 1.18 [0.91–1.41]; p=0.006). HOTAIR expression was markedly downregulated in TAK patients (8.05 [2.52–24.54] vs. 36.09 [30.08–43.85] arbitrary units; p=0.006) and was not associated with disease activity. Notably, HOTAIR expression inversely correlated with circulating MMP-2 (Spearman’s rho -0.276) and EMMPRIN/CD147 (Spearman’s rho -0.280) levels. Conclusion: TAK displays a circulating proteolytic profile consistent with enhanced ECM turnover and vascular remodeling. The marked downregulation of HOTAIR supports the involvement of epigenetic mechanisms in TAK and suggests a potential association between reduced HOTAIR expression and MMP-mediated vascular injury.