Background: In this exploratory study, we aimed to evaluate the dynamics of angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), soluble Endoglin (sEng), and sFlt-1/PlGF, PlGF/sFlt-1, and sEng/PlGF ratios] and oxidative stress [8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and 8-epi-PGF2α/PlGF ratio] mediator levels in women with suspected or confirmed pre-eclampsia (PE) at least two times during pregnancy. We also wanted to identify the possible correlations between 8-epi-PGF2α and angiogenic mediator levels at the time of inclusion of pregnant women. Methods: We included 40 pregnant women with suspected or confirmed PE, with a mean age of 29 years (range between 18 and 41 years) and gestational age between 18 and 28 weeks at inclusion in this study. The Enzyme-Linked Immunosorbent Assay (ELISA) method to measure the levels of serum angiogenic and oxidative stress mediators was used. Results: The evaluation of baseline sFlt-1/PlGF ratios using a cut-off of 38 suggested that 25 pregnant women had a sFlt-1/PlGF ratio of >38 (sFlt-1/PlGF ratio of >38 group) and 15 had a sFlt-1/PlGF ratio of ≤38 (sFlt-1/PlGF ratio of ≤38 group). The increases in sFlt-1/PlGF ratio in the sFlt-1/PlGF ratio of >38 group were caused by both an increase in sFlt-1 (2.04-fold) and a decrease in PlGF levels (2.55-fold). The 8-epi-PGF2α median levels were higher in the sFlt-1/PlGF ratio of >38 group (1.62-fold). During follow-up after pregnancy, we observed that the mean values of sFlt-1 and sEng and the median values of 8-epi-PGF2α and sFlt-1/PlGF, sEng/PlGF, and 8-epi-PGF2α/PlGF ratios increased directly proportional to gestational age for each measurement time until delivery in both groups. For five women who had a sFlt-1/PlGF ratio ≤38 at inclusion, sFlt-1/PlGF ratio was observed to increase to >38 later in pregnancy. We observed that, in the sFlt-1/PlGF ratio >38 group, baseline 8-epi-PGF2α levels better correlated with angiogenic mediator levels. Conclusions: Our study shows that 33.33% of pregnant women evaluated for suspected or confirmed PE with a sFlt-1/PlGF ratio of ≤38 displayed a rise in sFlt-1/PlGF ratio in subsequent weeks. In addition, together with angiogenic mediators, 8-epi-PGF2 α can be utilized as an independent predictor factor to help clinicians identify or predict which pregnant women will develop PE.

OBJECTIVE: To assess the potential of five inflammatory and six angiogenic/antiangiogenic plasma proteins for predicting imminent spontaneous preterm delivery (SPTD; ≤14 days of sampling), microbial invasion of the amniotic cavity and/or intraamniotic inflammation (MIAC/IAI), and composite neonatal morbidity and mortality (CNMM) in women with early preterm premature rupture of membranes (PPROM).
METHODS: This retrospective cohort study included 76 singleton pregnant women with early PPROM (23-30 weeks). Amniotic fluid obtained via amniocentesis was cultured for microorganism detection and assayed for interleukin-6 to define IAI (≥2.6 ng/mL). Plasma C4a, endoglin, endostatin, IGFBP-1, IGFBP-2, MMP-9, PlGF, S100A8, S100A9, S100 A8/A9, and VEGFR-1 levels were determined using ELISA.
RESULTS: Multivariate logistic regression analyses revealed significant associations between (i) high levels of plasma S100A8/A9, SPTD ≤14 days after sampling, and shorter sampling-to-delivery intervals; (ii) elevated plasma MMP-9, S100A9, and S100A8/A9 levels and MIAC/IAI, and (iii) decreased plasma endoglin levels and increased CNMM risk, while adjusting for gestational age at sampling (or delivery) and tocolytic use. The area under the curves of the aforementioned proteins ranged from 0.655 to 0.731 for each outcome. Notably, the SPTD risk increased significantly with increasing plasma S100A8/A9 levels (P for trend < .05).
CONCLUSIONS: Plasma S100A8/A9, MMP-9, S100A9, and endoglin may represent valuable biomarkers associated with SPTD, MIAC/IAI, and CNMM in women with early PPROM. Owing to their less invasive nature, repeatability, and fair-to-moderate diagnostic accuracy, these biomarkers may contribute to risk stratification of PPROM-related complications in the clinical setting.

To compare the level of pro and anti-inflammatory cytokines, and angiogenic mediators between Rheumatoid arthritis (RA) patients with and without subclinical synovitis (SS) in remission state, to find the correlation of these mediators with Greyscale synovitis (GSS) and power Doppler (PD) scores, and to find the probable predictor/s of SS.
52 RA patients in remission state were recruited and subdivided into with and without SS group by Ultrasonography (USG) of 14 joints. Total GSS and PD scoring was done. The serum levels of the pro/anti-inflammatory cytokines and angiogenic mediators were compared between groups, and correlation and regression analysis were done with GSS and PD scores.
63.46% patients had USG evidence of SS. Patients with SS had significantly higher levels of pro-inflammatory and angiogenic mediators [matrix-metalloproteinase -3 (p = 0.0001), Tumour necrosis factor-α (p = 0.0001), Interleukin (IL)-6 (p = 0.001), IL-1b (p = 0.0001), IL-17 (p = 0.0005), IL-33 (p = 0.0003), Tie-2 (p = 0.0001), vascular endothelial growth factor (VEGF (p = 0.03)], and lower anti-inflammatory cytokines [IL-27 (p = 0.0003), IL-10(p = 0.0001)]. A strong positive correlation of GSS score was noted with IL-17(r = 0.7), IL-6 (r = 0.7), IL-1b (r = 0.7), and IL-33 (r = 0.6). Multiple linear regression model identified IL-17 and IL-6 as predictors of GSS score, and TNF-α and VEGF as predictors of PD score. IL-17 level > 249 picogram/millilitre (pg/ml) could predict the SS with high specificity (89.5%).
Patients with SS in the remission state of RA showed altered expression of some of the pro/anti-inflammatory/angiogenic markers compared to those not having SS. IL-17, IL-6, VEGF, and TNF-α could be the predictors of USG synovial scores.

Angiogenesis is an early and key event in the pathogenesis of rheumatoid arthritis (RA) and is crucial for the proliferation of synovial tissue and the formation of pannus. This process is regulated by both angiogenesis-stimulating factors and angiogenesis inhibitors, the basis for the \"on-off hypothesis of angiogenesis.\" In RA, inflammation, immune imbalance, and hypoxia can further turn on the switch for blood vessel formation and induce angiogenesis. The new vasculature can recruit white blood cells, induce immune imbalance, and aggravate inflammation. At the same time, it also can provide oxygen and nutrients for the proliferating synovial tissue, which can accelerate the process of RA. The current therapies for RA mainly target the inflammatory response of autoimmune activation. Although these therapies have been greatly improved, there are still many patients whose RA is difficult to treat or who do not fully respond to treatment. Therefore, new innovative therapies are still urgently needed. This review covers the mechanism of synovial angiogenesis in RA, including the detailed process of angiogenesis and the relationship between inflammation, immune imbalance, hypoxia, and synovial angiogenesis, respectively. At the same time, in the context of the development of angiogenesis inhibition therapy for cancer, we also discuss similar treatment strategies for RA, especially the combination of targeted angiogenesis inhibition therapy and immunotherapy.

Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an \"ideal bridge\", linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05-5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:105-1:104 v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis.