Soluble Adhesion Molecule-1 Research Articles

Soluble adhesion molecules in serum and peritoneal fluid are associated with pelvic pain in endometriosis

AbstractObjectiveTo investigate the association between soluble adhesion molecules (sE‐cadherin, sE‐selectin, sICAM‐1, sVCAM‐1) in serum and peritoneal fluid and pelvic pain in infertile women with endometriosis.MethodsThis observational study included 86 infertile women undergoing diagnostic laparoscopy, 43 of whom were diagnosed with endometriosis. Pain intensity was evaluated using the visual analog scale (VAS). Levels of soluble adhesion molecules in serum and peritoneal fluid were quantified using ELISA. Statistical analysis included the Mann–Whitney U test for group comparisons, Spearman's rank correlation for associations with VAS scores, and receiver operating characteristic (ROC) curve analysis for diagnostic performance.ResultsSerum sE‐selectin levels were significantly higher in women with pelvic pain (P = 0.022) and correlated with VAS scores (r = 0.271, P = 0.012). Peritoneal sE‐selectin and sICAM‐1 levels were elevated in women with pelvic pain (P = 0.044 and P = 0.029, respectively) and showed positive correlations with VAS scores (r = 0.246, P = 0.022 and r = 0.310, P = 0.004, respectively). Comparing endometriosis and control groups, peritoneal sE‐selectin and sICAM‐1 levels were significantly higher in endometriosis cases with pelvic pain (P = 0.003 and P < 0.001, respectively). ROC analysis revealed the potential diagnostic value of serum sE‐selectin (AUC = 0.698, P = 0.002), serum sICAM‐1 (AUC = 0.721, P < 0.001), and serum sVCAM‐1 (AUC = 0.750, P < 0.001) in distinguishing endometriosis from non‐endometriosis cases.ConclusionElevated levels of sE‐selectin and sICAM‐1 in serum and peritoneal fluid are associated with pelvic pain in women with endometriosis, suggesting their role in pain pathogenesis and potential as biomarkers for pain severity and disease diagnosis. Further research is warranted to explore the underlying mechanisms and validate these findings in larger cohorts.

Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance.

Despite antiretroviral treatment (cART), aging people living with HIV (PWH) are more susceptible to neurocognitive impairment (NCI) probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, transmigration of inflammatory CD16+ monocytes through the altered blood brain barrier (BBB) may exacerbate cerebral small vessel disease (CSVD), a known cause of vascular cognitive impairment. PWH on cART (n=108) and age, sex, and Reynold's cardiovascular risk score-matched uninfected individuals (PWoH, n=111) were enrolled. This is a longitudinal observational study but only cross-sectional data from entry visit are reported. Neuropsychological testing and brain magnetic resonance imaging (MRI) were performed. CSVD was diagnosed by Fazekas score ≥1. Flow cytometric analyses of fresh whole blood were conducted to evaluate circulating levels of monocyte subsets (classical, intermediate, and non-classical) and markers of monocyte activation (CCR2, CD40, PSGL-1, TNFR2 and tissue factor). ELISAs were used to measure sCD14, ICAM, and Osteoprotegerin. Two-way analysis of variance (ANOVA), and linear regression models were performed to study the effects of HIV status, CSVD status, and their interaction to outcome variables such as cognitive score. Two-sample t-tests and correlation analyses were performed between and within PWoH with CSVD and PWH with CSVD participants. PWH with CSVD (n=81) had significantly lower total cognitive scores, higher levels of NCMs and soluble CD14 and intracellular adhesion molecule 1 (ICAM-1) as compared to PWoH with CSVD group (n=68). sCD14 and ICAM1 were positively correlated with each other indicating that monocyte and endothelial activation are associated with each other. Cognition was negatively correlated with NCMs, especially in the PWH with CSVD group. Among other blood biomarkers measured, osteoprotegerin levels showed mild negative correlation with cognitive performance in individuals with CSVD irrespective of HIV status. Elevated levels of NCMs may contribute to neuroinflammation, CSVD and subsequent cognitive impairment. This finding is of particular relevance in aging PWH as both HIV and aging are associated with increased levels of NCMs. NCMs may serve as a potential biomarker to address these comorbidities. Further longitudinal studies are needed to evaluate whether changes in NCM levels are associated with changes in CSVD burden and cognitive impairment.

Gingival inflammation and leukocyte-endothelium cell interactions in women with polycystic ovary syndrome.

Given the link between chronic inflammation and periodontal pathologies and increased cardiovascular risk, this study aims to investigate if gingivitis exacerbates the inflammatory response and subclinical atherosclerotic markers in women with polycystic ovary syndrome (PCOS). For this case-control study, women were assigned to three groups: two PCOS groups (with and without gingivitis) and a control group. Anthropometric and biochemical variables were determined, along with periodontal parameters (probing pocket depth [PPD], clinical attachment level [CAL], bleeding on probing [BOP], plaque index, calculus index, and tooth loss), systemic and neutrophil inflammatory markers (tumor necrosis factor alpha [TNFα], C-reactive protein [CRP], and c-Jun N-terminal kinase [JNK]), systemic oxidative stress mediators (myeloperoxidase [MPO] and glutathione), soluble cellular adhesion molecules, and neutrophil-endothelium cell interactions (rolling flux, velocity, and adhesion). Of 104 women recruited, 68 had PCOS, 24 of whom presented gingivitis, and 36 were controls. PCOS patients presented altered sexual hormone, lipid, and carbohydrate profiles. Levels of systemic inflammatory markers, MPO, and soluble platelet selectin (sP-selectin) were higher, and glutathione levels were lower in PCOS patients. BOP, plaque, and calculus index values were higher in PCOS patients with gingivitis. Neutrophils from PCOS patients showed increased JNK and decreased adhesion under flow conditions, with reduced rolling velocity and increased rolling flux and cellular adhesion, all of which were more pronounced in those with gingivitis. BOP was independently associated with rolling velocity, rolling flux, and cellular adhesion. Neutrophils of PCOS patients with gingivitis exhibit hyperactivity, promoting interaction with the endothelium and potentially contributing to atherosclerotic disease. Currently, there is a high prevalence of diseases that affect tooth-supporting tissues (periodontal diseases) and negatively influence the oral health and quality of life of the adult population. These pathologies lead to movement of the teeth and impairment of chewing function, eventually resulting in the loss of teeth. In recent years, the concept of periodontal medicine has arisen and consists of studying how periodontal diseases can influence our general inflammatory system and how systemic inflammatory pathologies can affect our oral health. In the present study, we evaluate a group of women with polycystic ovary syndrome (PCOS), a condition characterized by alterations of sex hormones and lipid profile and weight gain (body mass index). Our results show a high prevalence of gum inflammation among women with PCOS, which affects the interaction of their leukocytes and endothelial cells. The leukocytes of these women are hyper-responsive, presenting greater endothelial adhesion, lower flow velocity and enhanced rolling compared to those in a PCOS group without gum inflammation or controls. This study has generated a new line of research to analyze how neutrophils from patients with gingivitis exhibit hyperactivity, which promotes their interaction with the endothelium, thus contributing to the development of atherosclerotic disease.

Influence of Emulsion Lipid Droplet Crystallinity on Postprandial Endotoxin Transporters and Atherogenic And Inflammatory Profiles in Healthy Men - A Randomized Double-Blind Crossover Acute Meal Study.

Consumption of high-fat meals is associated with increased endotoxemia, inflammation, and atherogenic profiles, with repeated postprandial responses suggested as contributors to chronically elevated risk factors. However, effects of lipid solid versus liquid state specifically have not been investigated. This exploratory randomized crossover study tests the impact of lipid crystallinity on plasma levels of endotoxin transporters (lipopolysaccharide [LPS] binding protein [LBP] and soluble cluster of differentiation 14 [sCD14]) and select proinflammatory and atherogenic markers (tumor necrosis factor-alpha [TNF-α], C-reactive protein [CRP], interleukin-1-beta [IL-1β], interferon-gamma [IFN-γ], interleukin-6 [IL-6], soluble intercellular adhesion molecule [sICAM], soluble vascular cell adhesion molecule [sVCAM], monocyte chemoattractant protein-1 [MCP-1/CCL2], plasminogen activator inhibitor-1 [PAI-1], and fibrinogen). Fasted healthy men (n = 14, 28 ± 5.5 years, 24.1 ± 2.6kgm-2) consumed two 50g palm stearin oil-in-water emulsions tempered to contain either liquid or crystalline lipid droplets at 37°C on separate occasions with blood sampling at 0, 2-, 4-, and 6-h post-meal. Timepoint data, area under the curve, and peak concentration values are compared. Overall, no treatment effects are seen (p > 0.05). There are significant effects of time, with values decreasing from baseline, for TNF-α, MCP-1/CCL2, PAI-1, and fibrinogen (p < 0.05). Responder analysis pointed to differential treatment effects associated with some participant baseline characteristics but, overall, palm-stearin emulsion droplet crystallinity does not acutely affect plasma endotoxin transporters nor select inflammatory and atherogenic markers.

Role of soluble adhesion molecules (ICAM-1 and E-selectin) in children with sickle cell disease and their association with disease severity and complications

Role of soluble adhesion molecules (ICAM-1 and E-selectin) in children with sickle cell disease and their association with disease severity and complications

T-cell senescence was correlated with early atherosclerosis inpatients with systemic lupus erythematosus.

To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.

Evaluation of low volume sampling devices for a pharmacodynamic biomarker analysis: Challenges and solutions

Low volume sampling technologies have gained popularity as they are minimally invasive, reduce patient burden, enhance population diversity, and have the potential to facilitate decentralized clinical trials. Herein, we validated a Gyrolab assay to measure soluble Mucosal Addressin Cell Adhesion Molecule 1 (sMAdCAM-1) in dried blood samples collected using two low volume sampling devices, Mitra and Tasso-M20. This validated assay was implemented in a proof-of-concept study to compare three low volume sampling devices (Mitra, Tasso-M20 and TassoOne Plus) with serum collected via venipuncture from healthy volunteers receiving etrolizumab. We observed significantly higher concentration of sMAdCAM-1 in dried blood samples collected using Mitra and Tasso-M20 compared to serum in some paired samples, which was attributed to interference from the dried blood extraction buffer. To mitigate this interference, samples required substantial dilution into the appropriate buffer, which negatively impacted the detectability of sMAdCAM-1 with the Gyrolab assay. By employing the Quanterix single molecule array (Simoa), known for its superior assay sensitivity, the interference was minimized in the diluted samples. Both liquid blood collected in TassoOne Plus and dried blood collected using Mitra and Tasso-M20 demonstrated great concordance with serum for sMAdCAM-1 measurement. However, a bias was observed in Mitra dried blood samples, presumably due to the different sample collection sites in comparison with venipuncture and Tasso devices. Our study highlights the potential of low volume sampling technologies for biomarker analysis, and underscores the importance of understanding the challenges and limitations of these technologies before integrating them into clinical studies.

Predictors of the efficacy of vedolizumab in patients with ulcerative colitis.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients' characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50-149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36-127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Clinical efficacy and safety of flexible ureteroscopy and percutaneous nephrolithotomy for large kidney stones: A retrospective comparative study.

Renal stones ranging 20-40 mm are very common in China. Although no large-sample clinical studies have confirmed the clinical efficacy and safety of this method, there is also a lack of comparative data with traditional treatment. To investigate the clinical efficacy of flexible ureteroscopy (FURS) and percutaneous nephrolithotomy (PCNL) by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1 (sVCAM-1) and kidney injury molecule 1 (KIM-1) levels in patients with large kidney stones (> 2 cm in diameter). This single-center observational study was performed at a Chinese hospital between January 1, 2021, and October 30, 2023. All 250 enrolled patients were diagnosed with large kidney stones (> 2 cm) and divided into a FURS group (n = 145) and a PCNL group (n = 105) by the surgical method. The FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous nephrolithotomy. The operation time, time to palinesthesia, intraoperative blood loss, drop in hemoglobin, length of hospital stay, stone clearance rate, and complications were recorded in the two groups. Preoperative and postoperative serum sVCAM-1 levels, erythrocyte sedimentation rate (ESR), urine KIM-1 levels, preoperative and postoperative pain visual analog scale (VAS) and Wisconsin Stone Quality of Life Questionnaire (WISQOL) scores were also documented. All 250 eligible patients completed the follow-up. There were no significant differences in baseline characteristics between the two groups (P > 0.05). The operation time in the FURS group was significantly greater than that in the PCNL group. The time to ambulation, intraoperative blood loss, decrease in hemoglobin, and length of hospital stay were significantly lower in the FURS group than in the PCNL group. The FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative complications. There was no significant difference in antibiotic use between the groups. Postoperative serum sVCAM-1 levels, urine KIM-1 levels, and VAS scores were lower in the FURS group than in the PCNL group, but postoperative ESR and WISQOL scores were greater in the FURS group than in the PCNL group. FURS demonstrated superior clinical efficacy in treating large kidney stones (> 2 cm in diameter) compared PCNL. It not only improved the postoperative stone clearance rate and reduced complications and recovery time but also positively affected serum SCM-1, ESR, and urine KIM-1 levels, subsequent improvement of patient quality of life.

Acute kidney injury is associated with soluble vascular cell adhesion molecule 1 levels and short-term mortality in patients with ischemic stroke

BackgroundThe mechanisms that modulate the onset of acute kidney inlury (AKI) after ischemic stroke (IS) and valuable biomarkers to predict the occurrence and prognosis of AKI among patients with IS are missing. ObjectiveTo evaluate the frequency of AKI and the prognostic validity of clinical and laboratory biomarkers in predicting AKI and short-term mortality after the IS. MethodsNinety-five patients with IS were enrolled. Baseline IS severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and disability was determined after three-month follow-up using the modified Rankin Scale. Patients with IS were also categorized as survivors and non-survivors after the follow-up. Baseline data and laboratory biomarkers were obtained up to 24 h of the admission. ResultsFifteen (15.7 %) patients with IS presented AKI. The proportion of patients with vitamin D deficiency and the mortality were higher among those with AKI than those without AKI (p=0.011 and p-0.009, respectively). Patients with AKI showed higher disability and higher increased soluble vascular cellular adhesion molecule-1 (sVCAM-1) than those without AKI (p=0.029 and p=0.023, respectively). Logistic regression analysis showed that only sVCAM-1 was associated with the occurrence of AKI after IS [odds ratio (OR): 2.715, 95 % confidence intereval (CI): 1.12–6.67, p=0.027]. When both AKI and NIHSS were evaluated as explanatory variables, this panel showed an OR of 5.782 (95 % CI: 1.09–30.43, p<0.001) and correctly classified 83.6 % of cases. ConclusionIn conclusion, sVCAM-1 levels showed a potential useful for prediction of AKI after IS.

Sourdough Bread with Different Fermentation Times: A Randomized Clinical Trial in Subjects with Metabolic Syndrome.

The Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads, with differing fermentation times but similar nutritional profiles, on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. In a double-blind clinical trial, participants were randomized to consume either Elias Boulanger® long-fermentation (48 h) sourdough bread (EBLong) or Elias Boulanger® short-fermentation (2 h) sourdough bread (EBShort) over a two-month period. We assessed clinical parameters, inflammatory biomarkers, satiety-related hormones, and the richness and abundance of gut microbiota at baseline and follow-up. The participants included 31 individuals (mean age, 67, 51.6% female). EBShort was associated with reduced levels of soluble intercellular adhesion molecule (sICAM), and all participants, regardless of the intervention, exhibited a decrease in sICAM and diastolic pressure from baseline (p < 0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. No differences in microbiota richness or abundance were observed. EBShort bread was effective in reducing some inflammation markers. The consumption of sourdough bread may offer potential benefits in reducing inflammation markers in individuals with metabolic syndrome; however, longer fermentation times did not show additional benefits.

Association Between Soluble Cell Adhesion Molecules (sP-Selectin, sE-Selectin, and sICAM-1) and Antibodies Against the Antigens of Proteus mirabilis in Rheumatoid Arthritis Patients.

Objective The purpose of this study was to examine the association between the serum concentration of soluble cell adhesion molecules (CAMs) and antibodies against antigens of Proteus mirabilis (P. mirabilis) in rheumatoid arthritis (RA) patients, taking into consideration the implication of P. mirabilis in the etiopathogenesis of RA. Methods The serum levels of soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 59 RA patients and 36 healthy controls. Using the same ELISA method, the serum levels of class-specific antibodies against hemolysin (HpmB), urease C (UreC), and urease F (UreF) enzymes of P. mirabilis were also measured. Results In this study, increased levels of sP-selectin and sICAM-1 were observed in RA patients, while the levels of sE-selectin were increased in comparison with healthy controls but did not present a statistically significant difference. Moreover, increased levels of antibodies against HpmB, UreC, and UreF of P. mirabilis were found. Additionally, it was observed that the sE-selectin levels presented a significant correlation with IgG antibodies against the UreF antigen (there is no corresponding antigen in human tissue) in all the RA patients. A statistically significant correlation was observed between levels of soluble CAMs and antibodies against P. mirabilis in the different subgroups. Conclusion The observed correlation between soluble CAMs and antibodies against antigens of P. mirabilis, specifically in the subgroup of biologic therapy, indicates that P. mirabilis exists and provokes refractory in the treatment of RA.

Soluble adhesion molecules: Cognitive worsening biomarkers in primary progressive multiple sclerosis?

Soluble adhesion molecules: Cognitive worsening biomarkers in primary progressive multiple sclerosis?

Time-restricted feeding does not improve nephropathy in humanized sickle cell disease mice

Sickle cell disease (SCD) is an autosomal recessive genetic disease caused by a point mutation in the hemoglobin gene. This substitution results in a “sickling” of red blood cells and subsequent vascular and organ damage. Current treatments, while increasing the lifespan of sickle cell patients, has resulted in a higher prevalence of chronic complications like SCD nephropathy. Our group has previously shown that time-restricted feeding (TRF) in chronic high fat fed mice reduces kidney damage. Given the increased kidney damage in SCD, we hypothesize that TRF in humanized SCD mice will attenuate sickle cell nephropathy. To test this hypothesis, we studied 18-22-week-old male SCD mice. Mice underwent 3 weeks of TRF, only having access to food during the active, dark period (Zeitgeber Time (ZT) 12 to 24). The control group had access to food ad libitum (ad-lib). At the end of the 3 weeks, at 21-25 week old ages, 12 hour urine was collected in metabolic cages as well as kidneys and plasma collection at ZT3 (inactive period). Excretion of urinary kidney damage markers (albumin and NGAL-1) showed no difference between TRF and ad-lib in both the active and inactive collection periods. Urinary excretion of endothelin-1 is known to be upregulated in SCD patients; however, TRF did not change this marker in SCD mice. TRF did not change plasma levels of cytokines or soluble adhesion molecules. Histological analysis of kidneys was conducted as an additional marker of kidney damage. We analyzed iron levels in the kidney with Prussian blue staining as well as fibrosis with Masson’s trichrome. TRF did not change kidney iron accumulation or kidney fibrosis. Immunohistochemical staining for CD3+ T cells did not show a difference in glomerular T cell infiltration in the TRF group compared to the ad-lib group. In conclusion, TRF does not appear to have an effect on renal inflammation or kidney function in SCD mice, but future studies need to be completed. R01 DK134562. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction.

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction.

Genotype of dengue virus serotype 1 in relation to severe dengue in Guangzhou, China.

Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV-1). Viral factors such as dengue serotype and genotype are associated with severe dengue (SD). However, none of the studies have investigated the relationship between DENV-1 genotypes and SD. To understand the association between DENV-1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV-1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV-1 genotype. In the case of DENV-1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN-γ, TNF-α, IL-10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T-cell expressed and secreted and growth-related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV-1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines.

Association of objective sleep duration with cognition and brain aging biomarkers in older adults.

The neuropathological mechanisms underlying the association between sleep duration and mild cognitive impairment remain poorly understood. This population-based study included 2032 dementia-free people (age ≥ 60 years; 55.1% women) derived from participants in the Multimodal Interventions to Delay Dementia and Disability in Rural China; of these, data were available in 841 participants for Alzheimer's plasma biomarkers (e.g. amyloid-β, total tau and neurofilament light chain), 1044 for serum microvascular biomarkers (e.g. soluble adhesion molecules) and 834 for brain MRI biomarkers (e.g. whiter matter, grey matter, hippocampus, lacunes, enlarged perivascular spaces and white matter hyperintensity WMH). We used electrocardiogram-based cardiopulmonary coupling analysis to measure sleep duration, a neuropsychological test battery to assess cognitive function and the Petersen's criteria to define mild cognitive impairment. Data were analysed with multivariable logistic and general linear models. In the total sample (n = 2032), 510 participants were defined with mild cognitive impairment, including 438 with amnestic mild cognitive impairment and 72 with non-amnestic mild cognitive impairment. Long sleep duration (>8 versus 6-8 h) was significantly associated with increased likelihoods of mild cognitive impairment and non-amnestic mild cognitive impairment and lower scores in global cognition, verbal fluency, attention and executive function (Bonferroni-corrected P < 0.05). In the subsamples, long sleep duration was associated with higher plasma amyloid-β40 and total tau, a lower amyloid-β42/amyloid-β40 ratio and smaller grey matter volume (Bonferroni-corrected P < 0.05). Sleep duration was not significantly associated with serum-soluble adhesion molecules, white matter hyperintensity volume, global enlarged perivascular spaces and lacunes (P > 0.05). Alzheimer's and neurodegenerative pathologies may represent common pathways linking long sleep duration with mild cognitive impairment and low cognition in older adults.

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders

BackgroundEndothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. MethodsThe study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. ResultsThe total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. ConclusionsIn our study, patients with schizophrenia – including the drug-naïve – have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Angiopoietin-2 is associated with sickle cell complications, including stroke risk, and decreases with hydroxyurea therapy

AbstractHydroxyurea reduces morbidity and mortality in children with sickle cell anemia (SCA). The endothelium is central to SCA-related complications including stroke. However, hydroxyurea’s impact on the endothelium is not well described. To address this gap, we measured plasma levels of endothelial activation markers (angiopoietin-2, P-selectin, soluble endothelial selectin [sE-selectin], soluble intercellular cellular adhesion molecule 1, and soluble vascular endothelial cellular adhesion molecule) by enzyme-linked immunosorbent assay after initiation of hydroxyurea therapy. Samples were collected from Ugandan children with SCA enrolled in a clinical trial evaluating hydroxyurea vs placebo (NOHARM trial). Samples were collected at enrollment; and then after 2, 4, and 12 months of follow-up. Longitudinal changes in biomarker levels were evaluated using linear mixed effects models. Transcranial Doppler (TCD) velocities were measured at 10 to 12 months follow-up to assess cerebral blood flow and primary stroke risk. Mediation analysis was used to explore causal pathways of hydroxyurea-mediated effects on TCD velocities. In total, 798 plasma samples were tested from 205 children (mean enrollment age, 2.2 years). At enrollment, higher levels of angiopoietin-2 were associated with a previous medical history of dactylitis, vaso-occlusive crises, acute chest syndrome, and transfusion (P < .05 for all). Hydroxyurea therapy at a fixed dose of 20 mg/kg per day decreased plasma angiopoietin-2, P-selectin, and sE-selectin levels over the study period (P < .05 for all). Angiopoietin-2 and sE-selectin were associated with higher TCD velocities. Mediation analysis suggests that hydroxyurea decreases TCD velocities through an increase in fetal and total hemoglobin. Increased fetal and total hemoglobin, and decreased white blood cell count may decrease TCD velocity, in part, through an angiopoiten-2–mediated pathway. This trial was registered at www.ClinicalTrials.gov as #NCT01976416.

A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk.

Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort (n = 1,162 total, n = 422 females) suggested that niacin metabolism was associated with incident major adverse cardiovascular events (MACE). Serum levels of the terminal metabolites of excess niacin, N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY), were associated with increased 3-year MACE risk in two validation cohorts (US n = 2,331 total, n = 774 females; European n = 832 total, n = 249 females) (adjusted hazard ratio (HR) (95% confidence interval) for 2PY: 1.64 (1.10-2.42) and 2.02 (1.29-3.18), respectively; for 4PY: 1.89 (1.26-2.84) and 1.99 (1.26-3.14), respectively). Phenome-wide association analysis of the genetic variant rs10496731, which was significantly associated with both 2PY and 4PY levels, revealed an association of this variant with levels of soluble vascular adhesion molecule 1 (sVCAM-1). Further meta-analysis confirmed association of rs10496731 with sVCAM-1 (n = 106,000 total, n = 53,075 females, P = 3.6 × 10-18). Moreover, sVCAM-1 levels were significantly correlated with both 2PY and 4PY in a validation cohort (n = 974 total, n = 333 females) (2PY: rho = 0.13, P = 7.7 × 10-5; 4PY: rho = 0.18, P = 1.1 × 10-8). Lastly, treatment with physiological levels of 4PY, but not its structural isomer 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice. Collectively, these results indicate that the terminal breakdown products of excess niacin, 2PY and 4PY, are both associated with residual CVD risk. They also suggest an inflammation-dependent mechanism underlying the clinical association between 4PY and MACE.