Herein, we aimed to identify blood biomarkers that compensate for the poor specificity of D-dimer in the diagnosis of deep vein thrombosis (DVT). S100A8 was identified by conducting protein microarray analysis of blood samples from patients with and without DVT. We used ELISA to detect S100A8, VCAM-1, and ICAM-1 expression levels in human blood and evaluated their correlations. Additionally, we employed human recombinant protein S100A8 to induce human umbilical vein endothelial cells and examined the role of the TLR4/MAPK/VCAM-1 and ICAM-1 signaling axes in the pathogenic mechanism of S100A8. Simultaneously, we constructed a rat model of thrombosis induced by inferior vena cava stenosis and detected levels of S100A8, VCAM-1, and ICAM-1 in the blood of DVT rats using ELISA. The associations of thrombus tissue, neutrophils, and CD68-positive cells with S100A8 and p38MAPK, TLR4, and VCAM-1 expression levels in vein walls were explored. The results revealed that blood S100A8 was significantly upregulated during the acute phase of DVT and activated p38MAPK expression by combining with TLR4 to enhance the expression and secretion of VCAM-1 and ICAM-1, thereby affecting the occurrence and development of DVT. Therefore, S100A8 could be a potential biomarker for early diagnosis and screening of DVT.

The aim of this study was to determine plasma levels of three adhesion molecules that may contribute to the development of diabetic retinopathy; soluble endothelial selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), in young adults, aged 15-34 years at diagnosis of diabetes, to find potential predictors for development of retinopathy, and to evaluate their relation to diabetes associated autoantibodies. Participants with type 1 (n = 169) and type 2 diabetes (n = 83) were selected from the complications trial of the Diabetes Incidence Study in Sweden and classified in two subgroups according to presence (n = 80) or absence (n = 172) of retinopathy as determined by retinal photography at follow-up 8-10 years after diagnosis of diabetes. Blood samples were collected at diagnosis in 1987-88. The levels of sE-selectin, sICAM-1, and sVCAM-1 were analysed by enzyme-linked immunosorbent assay and islet cell antibodies by a prolonged two-colour immunofluorescent assay. Mean HbA1c (p<0.001) and clinical characteristics: mean body mass index (p = 0.019), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.003), male gender (p = 0.026), and young age at diagnosis of diabetes (p = 0.015) remained associated with development of retinopathy in type 1 diabetes. However, in a multivariate analysis only HbA1c remained as a risk factor. sE-selectin was significantly higher in the group with type 2 diabetes and retinopathy, compared to the group with type 2 diabetes without retinopathy (p = 0.04). Regarding sE-selectin, sICAM-1, and sVCAM-1 in participants with type 1 diabetes, no differences were observed between the groups with or without retinopathy. This trial confirmed the role of HbA1c and clinical characteristics as predictors for development of retinopathy in type 1 diabetes. sE-selectin stands out as a potential predictor for development of retinopathy in type 2 diabetes, whereas a predictive role for sICAM-1 and sVCAM-1 could not be identified neither for type 1 nor type 2 diabetes.

BACKGROUND: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL\'s anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters.
METHODS: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma\'s anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity.
RESULTS: ApoB-depleted plasma\'s anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman\'s r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013).
CONCLUSIONS: ApoB-depleted plasma\'s anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

BACKGROUND: Previous studies showed that the concentrations of selected chemokines are locally elevated in samples collected from the lumen of intracranial aneurysms (IA). Our objective was to determine whether the observed differences in analyte concentrations were influenced by the origin of the blood samples (i.e. cerebral versus peripheral), thus providing insight into the localised nature of these alterations and their significance in IA pathogenesis.
METHODS: This prospective study included 24 patients with IA who underwent endovascular embolisation. Concentrations of selected analytes were analysed in blood samples from the IA lumen, feeding artery, and aorta. The analytes included MPO, Lipocalin-2/NGAL, sICAM-1, sVCAM-1, and serum amyloid A.
RESULTS: Higher median plasma concentrations of MPO, lipocalin-2/NGAL, sVCAM-1, and SAA were found in samples obtained from the IA lumen and the feeding artery compared to the aorta. The concentration of sICAM-1 was significantly higher in the IA compared to the aorta, but did not differ between the proximal artery and the aorta. No significant differences in any analyte concentration were observed between the IA and the proximal artery.
CONCLUSIONS: These findings suggest that the IA and the proximal vessel share similarities in the local immunological environment, which is different from that observed in the aorta. Further studies are needed to fully understand and elucidate these observations.

OBJECTIVE: Several epidemiological studies have linked lead (Pb) exposure to induced oxidative stress and the promotion of inflammatory response. We performed a within-subjects study (repeated measures study) to evaluate the relationship between the concentration of blood lead (B-Pb) and toenail lead (T-Pb) and circulating markers of inflammation.
METHODS: We evaluated the associations between B-Pb concentrations and T-Pb concentrations and circulating markers of inflammation, soluble intracellular adhesion molecule-1 (s-ICAM-1), soluble vascular adhesion molecule-1 (s-VCAM-1), and high-sensitivity C-reactive protein (hs-CRP) on 158 traffic enforcers from the Metropolitan Manila Development Authority (MMDA) traffic enforcer\'s health study. Linear mixed-effects models with random subject-specific intercepts were fitted to estimate the association between B-Pb and T-Pb exposure and circulating markers of inflammation, adjusting for confounding factors.
RESULTS: Traffic enforcers were middle-aged men (89.4%) with a mean age (± SD) of 37.1 years ± 8.9 years and had a total of 293 valid markers of inflammation measurements. B-Pb concentration was related to increased hs-CRP levels. A 10% increase in B-Pb was associated with a 5.7% increase in hs-CRP level [95% confidence interval (95% CI): 1.3-10.1]. However, B-Pb was not associated with s-ICAM-1 and s-VCAM-1. Furthermore, no associations were observed between T-Pb and all the circulating markers of inflammation.
CONCLUSIONS: Low-level B-Pb may increase hs-CRP among traffic enforcers. Moreover, the study suggests that Pb via the oxidative and inflammation pathways may have an essential role in the development of cardiovascular disease. Furthermore, MMDA and the Department of Labor and Employment can use our study\'s findings as evidence to conduct routine screening of blood heavy metals, especially Pb, among MMDA and other traffic enforcers as part of their yearly medical examination.

Polypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment.
We conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response.
The results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group.
Our study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.

Background: Biomarkers can help understand the impact of achieving therapeutic goals in developing vascular diseases in diabetics. Aim: To assess the association between lipid and glycemic profiles and endothelial biomarkers in diabetics. Methods: Cross-sectional study that evaluated lipid and glycemic levels and biomarkers (VCAM-1, Sdc-1, FGF-23 and KIM-1 in diabetics. Results: Higher VCAM-1 levels were associated with higher low-density lipoprotein cholesterol and non-high-density lipoprotein (HDL) cholesterol levels (in the group with inadequate glycohemoglobin A1c [HbA1c] levels), with higher glycemic levels (in the group with inadequate HDL cholesterol levels) and with lower HDL cholesterol levels (both groups). VCAM-1 was independently associated with not achieving adequate HbA1c levels. Conclusion: In uncontrolled diabetics, VCAM-1 was independently associated with having inadequate HbA1c levels, suggesting they may already have endothelial damage.

Although clinical examination still represents the gold standard for the differential diagnosis of prolonged disorders of consciousness (pDoC), the introduction of innovative markers is essential for diagnosis and prognosis, due to the problem of covert cognition. We evaluated the brain-derived neurotrophic factor protein (BDNF) and the soluble cell adhesion molecules proteins (CAMs) in a cohort of prolonged disorders of consciousness patients to identify a possible application in the clinical context. Furthermore, peripheral blood determinations were correlated with imaging parameters such as white matter hyperintensities (WMH), cranial standardized uptake value (cSUV), electroencephalography (EEG) data and clinical setting. Our results, although preliminary, identify BDNF as a possible blood marker for the diagnosis of pDoC (p value 0.001), the soluble CAMs proteins CD44, Vcam-1, E-selectin (p value < 0.01) and Icam-3 (p value < 0.05) showed a higher peripheral blood value in pDoC compared with control. Finally, soluble Ncam protein could find useful applications in the clinical evolution of the pDoC, showing high levels in the MCS and EMCS subgroups (p value < 0. 001) compared to VS/UWS.

Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL-6, TNF-α, CRP), and expression levels of endothelial markers (ICAM-1, VCAM-1, NF-κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6-k-PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM-1 and VCAM-1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6-k-PGF1α and lower levels of TXB2 and ET were observed in high-dose group, suggesting that pro- and anti-thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti-inflammatory and blood flow-enhancing characteristics.

OBJECTIVE: This study aimed to evaluate the efficacy of montelukast in conjunction with non-biologic disease modifying anti-rheumatic drugs (nDMARDs) in rheumatoid arthritis (RA) patients.
METHODS: This study was a single-center randomized double-blinded placebo-controlled study. Adult RA patients were included if they had moderate to severe disease activity and were receiving monotherapy or combination of nDMARDs. Eligible patients were randomized, in 1:1 ratio, to receive either 10 mg montelukast or placebo, once daily for 16 weeks. The primary endpoint was the change in the 28-joints disease activity score (DAS28) 16 weeks after treatment. The patients\' quality of life (QoL) was assessed by the Arabic version of the Health Assessment Questionnaire-Disability Index. Moreover, serum levels of vascular adhesion molecule-1 (VCAM-1) were measured.
RESULTS: A total of 87 patients completed the study; 44 in the montelukast arm and 43 in the control arm. After 16 weeks of treatment, disease activity decreased significantly in the montelukast arm with mean change in DAS28 (95% CIs) of -1.5 (-1.7, -1.2) while the control arm showed no improvement (0.2 (0.0, 0.4), p < 0.01). The QoL of the patients improved significantly from baseline in the montelukast arm (p < 0.01) but not in the control arm (p = 0.08). The median (IQR) serum levels of VCAM-1 were significantly lower in the montelukast arm (22.8 (15.0-32.7)) than in the control arm (28.9 (15.4-42.8), p = 0.004).
CONCLUSIONS: The co-administration of montelukast with nDMARDs in RA patients enhanced the anti-rheumatic effect which was reflected clinically by decreased disease activity.