Fig 2: P. gingivalis supernatant impairs the osteogenic potential of PDLSC.(A) IL-1 β, IL-6 and IL-8 production was measured using ELISA after PDLSCs were treated with P. gingivalis (P.g.) supernatant’s dilutions (1:500 and 1:50), or untreated cells as control simultaneously for 24 h. IL-1 β, IL-6 and IL-8 is expressed in pg/ml ( ± standard deviation). (B) Western blot analysis showed the protein expression of TLR2, TLR4 and GAPDH was used as the internal control. (C) Confluent PDLSC were stained with Alizarin Red after 21 days of cultivation in osteogenic medium containing P. gingivalis supernatant’s dilutions (1:500 and 1:50) and Alizarin Red was then extracted and measured for light absorbance at 405 nm. *p < 0.05 as determined by unpaired two-tailed t tests. Data from three biologically independent replicates.

Fig 3: Correlation analysis of IL-1 and NFL in serum and cerebrospinal fluid. (A) Correlation analysis of IL-1 in cerebrospinal fluid and serum at different periods. (B) Correlation analysis of NFL in cerebrospinal fluid and serum at different periods. IL-1 = interleukin-1, NFL = nerve fiber layer.

Fig 4: Inflammatory markers and cardiomyocyte passive stiffness in left ventricular biopsies from patients with aortic stenosis (AS), with (+DM) and without concomitant diabetes (−DM). A Schematic representation of intracellular inflammatory signaling pathways. Fpassive: passive stiffness; HMGB1: high mobility group box protein 1; IL: interleukin; NF-κB: nuclear factor kappa B; NLRP3: NOD-like receptor protein 3; RAGE: receptor for advanced glycation end products; TLR: Toll-like receptor. B–D Levels of IL-1, IL-6, and IL-18. Box and whisker plots (median, 25th to 75th percentiles, minimum, and maximum) are displayed on the left axis to represent selected parameters in each group (n = 10 samples per group). The dashed lines represent the mean values of both groups. P-values are derived from unpaired t-tests; *P < 0.05, ****P < 0.0001. The right axis shows the difference between the means ± SEM. E Stretch protocol; SL: sarcomere length. F Cardiomyocyte Fpassive at SL 1.8–2.4 µm in the presence or absence of in vitro treatment with an inhibitor of IL-6 (IL-6inh). Curves are second-order polynomial fits to the means (± SEM; n = 30–36/5 cardiomyocytes/heart per group), *P < 0.05 AS−DM versus AS+DM, ‡P < 0.05 AS−DM alone versus AS−DM after IL-6inh, †P < 0.05 AS+DM alone versus AS+DM after IL-6inh by one-way ANOVA. P-values were corrected for multiple comparisons by the Tukey method. G. Original recordings

Fig 5: The pro-inflammatory phenotype of RRP1-deficient macrophages and the phenotype rescue by RRP1 NOP52 domian.RT-qPCR detection of IL1B (a), IL6 (b) mRNA levels in THP-1 cells upon RRP1 silencing and IL-1β stimulation for the indicated hours. RT-qPCR detection of IL-1b (c) and Il6 (d) mRNA levels in wild-type (WT) or RRP1 knock out (RRP1 KO) RAW 264.7 cells with IL-1β stimulation for the indicated hours. e RT-qPCR detection of Tnfα mRNA levels in WT or RRP1 KO RAW 264.7 cells with murine TNFα (10 ng/ml) stimulation for the indicated hours. f Cell death ratio of WT or RRP1 KO RAW 264.7 cells treated with TCZ. TCZ: Combination of murine TNFα (20 ng/ml), cycloheximide (CHX) (10 μg/ml) and Z-IETD-FMK (2 μM). See methods. Western blotting of the phosphorylation (p-)of the key inflammatory signal pathway molecules in WT and RRP1 KO RAW 264.7 cells respectively stimulated by murine IL-1β (50 ng/ml) (g), TNFα (10 ng/ml) (h), IL-6 (20 ng/ml) (i) for indicated hours. GAPDH serves as loading control. j Western blot (left) and quantitative analysis (right) of the Flag tagged full-length RRP1 (FL), Nop52 and C terminal (Cter) expression in RRP1 KO RAW 264.7 cells. Empty vector (Vector) was transfected as a control. The Flag band intensities were normalized to GAPDH. RT-qPCR detection of IL-1b (k), Il6 (l) mRNAs after over-expressing the Flag tagged full-length RRP1 (FL), Nop52 (Nop52) and C terminal (Cter) in RRP1 KO RAW 264.7 cells followed by IL-1β stimulation. WT and the RRP1 KO cells transfected with empty vector (Vector) were used as controls. Western blotting data are representative of three independent experiments. RT-qPCR and Western bloting quantitative data are presented as means ± SD of (a–e, j right, k, l, n = 3) biologically replicates from three independent experiments with student’s t test (two-tailed unpaired). Cell death data are presented as means ± SD of (n = 4) biologically replicates from three independent experiments with ANOVA-test (two way). Source data are provided as a Source Data file.