Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients.

Aim: ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). Methods: 43 patients were randomized to pentoxifylline (PTX) 400 mg thrice daily (n = 22) or placebo (n = 21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) were assessed at baseline and 2 months. Results: After 2 months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p = 0.032. Conclusion: PTX for 2 months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. Clinical Trial Registration: NCT04367935 (ClinicalTrials.gov).

This study examined the effect and the safety of a drug called pentoxifylline in patients who have recently had a heart attack. Pentoxifylline can possibly reduce inflammation and is used for patients with blood flow issues. The study involved 43 participants, 22 receiving pentoxifylline and 21 receiving a placebo for 2 months. We measured different markers related to inflammation and heart health before and after. Overall, there was no significant difference between the groups, but patients who received pentoxifylline experienced less inflammation according to only one of the markers measured. This study concluded that the prescription of pentoxifylline after a heart attack is safe, well-tolerated and without notable side effects. Still, we recommend larger and longer studies to be sure of its effect.

Diabetic Endothelial Cell Glycogen Synthase Kinase 3ß Activation Induces VCAM1 Ectodomain Shedding.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been found to be associated with poor cardiovascular disease (CVD) outcomes, supporting VCAM1's role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1's release or its interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane-bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs). Still, the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from an inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3ß, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3ß activation in control ECs increased ADAM10/17 and VCAM1. A GSK3ß inhibitor reduced active GSK3ß and VCAM1 ectodomain shedding. These findings suggest diabetic ECs with elevated GSK3ß activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3ß inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease, particularly in diabetes, holds significant therapeutic potential.

Soluble Vascular Cell Adhesion Molecule-1 as an Inflammation-Related Biomarker of Coronary Slow Flow.

Background: Coronary slow flow (CSF) is an angiographic entity characterized by delayed coronary opacification with no evident obstructive lesion in the epicardial coronary artery. Several studies have shown that the occurrence and development of CSF may be closely related to inflammation. Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a biomarker related to inflammation. The aim of this study was to evaluate the correlation between plasma soluble VCAM-1 level and CSF occurrence and thus the predictive value of VCAM-1 for CSF. Methods: Forty-six CSF patients and thirty control subjects were enrolled. Corrected thrombolysis in myocardial infarction frame count (cTFC) was used to diagnose CSF. Functional status and quality of life were determined by the Seattle Angina Questionnaire (SAQ). Echocardiography was used to evaluate the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV). The plasma levels of sVCAM-1, IL-6, and TNF-α were quantified by enzyme-linked immunosorbent assay. Results: Compared with the control group, the physical limitation score by the SAQ, the LV global longitudinal strain (GLS), mitral E, and mitral E/A decreased in patients with CSF, while the plasma IL-6 and TNF-α levels increased. The plasma sVCAM-1 level in the CSF group was significantly higher than that in the control group (186.03 ± 83.21 vs. 82.43 ± 42.12 ng/mL, p < 0.001), positively correlated with mean cTFC (r = 0.57, p < 0.001), and negatively correlated with the physical limitation score (r = −0.32, p = 0.004). Logistic regression analyses confirmed that plasma sVCAM-1 level (OR = 1.07, 95%CI: 1.03−1.11) is an independent predictor of CSF, and the receiver operating characteristic curve analysis showed that plasma sVCAM-1 levels had statistical significance in predicting CSF (area under curve = 0.88, p < 0.001). When the sVCAM-1 level was higher than 111.57 ng/mL, the sensitivity for predicting CSF was 87% and the specificity was 73%. Conclusions: Plasma sVCAM-1 level can be used to predict CSF and was associated with the clinical symptoms of patients. It may serve as a potential biomarker for CSF in the future.

Change of serum D-D, sVCAM-1 and P-selectin after limb fractures surgery and their relationship with thrombosis / 中国医师杂志

Objective:To investigate the relationship between change of serum D-dimer (D-D), soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin and thrombosis after limb fracture surgery.Methods:289 patients with limb fractures who were treated in the emergency department of Shulan (Hangzhou) Hospital from January 2021 to January 2022 were selected as the study subjects. They were divided into deep vein thrombosis (DVT) group ( n=62) and non-DVT group ( n=227) according to whether DVT occurred after operation. The levels of prothrombin time (PT), activated partial prothrombin time (APTT), D-D, sVCAM-1 and P-selectin were measured before and after operation in all patients. The levels of PT, APTT, D-D, sVCAM-1 and P-selectin were compared between DVT group and non-DVT group. Logistic sequential stepwise regression analysis was used to analyze the risk factors of postoperative thrombosis in patients with limb fractures. Results:There was no statistically significant difference in PT and APTT between 289 patients with limb fractures after operation and before operation (all P>0.05), while the levels of serum D-D, sVCAM-1 and P-selectin after operation were higher than that before operation (all P<0.05). There was no significant difference in general data between DVT group and non-DVT group (all P>0.05); There was no statistically significant difference in PT and APTT before and after operation between DVT group and non-DVT group (all P>0.05). The levels of serum D-D, sVCAM-1 and P-selectin before and after operation in DVT group were higher than those in non-DVT group (all P<0.05). Logistic sequential stepwise regression analysis showed that high levels of D-D, sVCAM-1 and P-selectin were risk factors for thrombosis after limb fracture surgery (all P<0.05). Conclusions:High levels of D-D, sVCAM-1 and P-selectin are risk factors for thrombosis after limb fracture surgery.

[Influence factors of deep venous thromboembolism after knee arthroplasty and significance of changes of serum nets and sVCAM-1 levels].

OBJECTIVE: To investigate the relationship between the changes of serum neutrophil extracellular traps (NETs), soluble vascular cell adhesion molecule-1(sVCAM-1) and deep venous thromboembolism after knee arthroplasty. METHODS: From May 2017 to April 2020, 30 patients with deep venous thromboembolism after knee arthroplasty were retrospectively selected as the observation group, and 60 patients without deep venous thromboembolism after knee arthroplasty in the same period were randomly selected as the control group. The clinical data, serum levels of nets and sVCAM-1 before and 1, 3 and 5 days after operation were compared between the two groups. Logistic regression model was used to analyze the influencing factors of deep venous thromboembolism after knee arthroplasty; Pearson correlation was used to analyze the relationship between serum nets and sVCAM-1 levels;Draw the receiver operating characteristic curve(ROC) to obtain the area under the curve(AUC), and analyze the diagnostic value of serum nets and sVCAM-1 levels for deep vein thromboembolism after knee arthroplasty. RESULTS: There were statistically significant differences between two groups in age, body mass index, and postoperative knee elevation and flexion ratio(P<0.05). The level of serum NETs and sVCAM-1 on the 1st and 3rd day after surgery of the observation group were higher than the control group(P<0.05). Logistic regression analysis showed that age, body mass index, knee flexion position, serum nets and sVCAM-1 levels at 1 and 3 days after operation were all the influencing factors of DVT after knee arthroplasty (P<0.05);Pearson correlation analysis showed that there was a positive correlation between the levels of serum NETs and sVCAM-1 in patients with deep venous thromboembolism after knee arthroplasty 1 and 3 days after operation(P<0.05). The ROC curve of predicting deep venous thromboembolism after knee arthroplasty by serum nets and sVCAM-1 levels at 1 and 3 days after operation was drawn, the results showed that the AUC of serum nets and sVCAM-1 levels at 1 day after operation was higher than that at 3 days after operation, which had a good predictive effect. CONCLUSION: The influencing factors of deep vein thromboembolism after knee arthroplasty are age, body mass index, postoperative knee elevation and flexion, postoperative serum NETs and sVCAM-1 levels, especially postoperative serum NETs and sVCAM-1 levels. Changes can be used as potential biomarkers for predicting postoperative deep vein thromboembolism, and clinical attention should be paid to it.

Evidence that blood-CSF barrier transport, but not inflammatory biomarkers, change in migraine, while CSF sVCAM1 associates with migraine frequency and CSF fibrinogen.

OBJECTIVE: Our objective is to explore whether blood-cerebrospinal fluid (CSF) barrier biomarkers differ in episodic migraine (EM) or chronic migraine (CM) from controls. BACKGROUND: Reports of blood-brain barrier and blood-cerebrospinal fluid barrier (BCSFB) disruption in migraine vary. Our hypothesis is that investigation of biomarkers associated with blood, CSF, brain, cell adhesion, and inflammation will help elucidate migraine pathophysiology. METHODS: We recruited 14 control volunteers without headache disorders and 42 individuals with EM or CM as classified using the International Classification of Headache Disorders, 3rd edition, criteria in a cross-sectional study located at our Pasadena and Stanford headache research centers in California. Blood and lumbar CSF samples were collected once from those diagnosed with CM or those with EM during two states: during a typical migraine, before rescue therapy, with at least 6/10 level of pain (ictal); and when migraine free for at least 48 h (interictal). The average number of headaches per month over the previous year was estimated by those with EM; this enabled comparison of biomarker changes between controls and three headache frequency groups: <2 per month, 2-14 per month, and CM. Blood and CSF biomarkers were determined using antibody-based methods. RESULTS: Antimigraine medication was only taken by the EM and CM groups. Compared to controls, the migraine group had significantly higher mean CSF-blood quotients of albumin (Qalb : mean ± standard deviation (SD): 5.6 ± 2.3 vs. 4.1 ± 1.9) and fibrinogen (Qfib mean ± SD: 1615 ± 99.0 vs. 86.1 ± 55.0). Mean CSF but not plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were significantly higher in those with more frequent migraine: (4.5 ng/mL ± 1.1 in those with <2 headache days a month; 5.5 ± 1.9 with 2-14 days a month; and 7.1 ± 2.9 in CM), while the Qfib ratio was inversely related to headache frequency. We did not find any difference in individuals with EM or CM from controls for CSF cell count, total protein, matrix metalloproteinase-9, soluble platelet-derived growth factor receptor ß, tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6, IL-8, IL-10, or C-reactive protein. CONCLUSIONS: The higher Qalb and Qfib ratios may indicate that the transport of these blood-derived proteins is disturbed at the BCSFB in persons with migraine. These changes most likely occur at the choroid plexus epithelium, as there are no signs of typical endothelial barrier disruption. The most striking finding in this hypothesis-generating study of migraine pathophysiology is that sVCAM-1 levels in CSF may be a biomarker of higher frequency of migraine and CM. An effect from migraine medications cannot be excluded, but there is no known mechanism to suggest they have a role in altering the CSF biomarkers.

Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment.

The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247.

[Cerebral perfusion, arterial hypertension and endothelial dysfunction in rheumatoid arthritis]. / Mozgovaia perfuziia, arterial'naia gipertenziia i éndotelial'naia disfunktsiia pri revmatoidnom artrite.

To study the relationship between cerebral perfusion with arterial hypertension (AH) and the state of endothelium in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Seventy-eight patients with RA were divided into two groups: with- and without AH.The functional methods included ultrasonic duplex angioscanning and dopplerografy of the extracranial and intracranial arteries of the head and neck and daily 24 hour monitoring of arterial blood pressure (BP). C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), von Willebrand Factor antigen (vWF AG), interleukin-8 (Il-8), rheumatoid factor (RF) IgG, endothelin-1 (ET-1) were determined by immunoenzyme analysis and velocity of sedimentation (VS). The dysfunction of endothelium was evaluated by calculation of the number of desquamated endotheliocytes cells (DE). RESULTS: AH occurred in 46 (59%) patients. Cerebral hypoperfusion was observed in patients with RA in whom the reduction in the high-speed indices of blood flow were correlated with BP increase. There were negative correlations between the linear speed of blood flow on the common carotid arteries and average day and night systolic BP, average day and night diastolic BP, indices of time systolic BP and diastolic BP and avariability of BP. The same results were established for the intracranial arteries: inverse correlations between the linear speed on the anterior cerebral arteries and average day systolic BP. The signs of endothelial dysfunction represented by significant differences among the indices of activation of endothelium in RA patients in comparison with the control group were shown. Content of ET-1, sVCAM-1, vWF AG, Il-8, CRP was higher in RA. The number of DE was significantly higher as well. These indices showed significant differences depending on RA activity. Correlation analysis revealed that the markers of endothelium activation sVCAM-1, vWF AG were positively correlated with the indices of immune inflammation. CONCLUSION: An increase in the activity of inflammatory process in RA leads to endothelial dysfunction, which contributes to the increase in the peripheral vascular resistance of cerebral arteries, reduction in the high-speed indices of blood flow, growth of BP variability and the increase in load by pressure.

Effect of Radiation on the Expression of CVD-related miRNAs, Inflammation and Endothelial Dysfunction of HUVECs.

BACKGROUND/AIM: Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. RESULTS: Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. CONCLUSION: RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.

[Endothelial damage and circadian blood pressure profile in rheumatoid arthritis].

AIM: To study the influence of the state of endothelium on the daily profile of arterial pressure (AP) in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: In 70 RA pts carried out C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), antigen von Willebrand Factor (AG WF), interleukin-8 (Il-8), rheumatoid factor (RF), IgG, endotheline-1 (ET-1), number of desquamated endotheliocytes cells (DE), VS, activity of renin by immunoenzyme analysis. The dysfunction of endothelium was evaluated by calculation of DE. The functional methods included the daily monitoring of arterial pressure (AP). RESULTS: Arterial hypertension (AH) occurred in 40 (57.1%) pts. RA pts are revealed the signs of endothelial dysfunction, about which significant differences among the indices of activation of endothelium in comparison with control group testify. ET-1, sVCAM-1, vWF AG, Il-8, CRP content was higher in RA pts. Reliably above there was a number of DE. Reliable differences according to these indices depending of RA activity were discovered. With conducting of correlation analysis it is revealed, that markers of the activation of endothelium: sVCAM-1, vWF AG positively correlated with increasing RF IgG and indices of the immune inflammation: CRP, and DE number. In patients suffering from RA, showed signs of endothelial dysfunction. The positive correlation between endothelial damage and daily profile of AP show the relationship of these processes. CONCLUSION: Positive correlations between the damage of endothelium and disturbance of AP daily profile testify about the interrelation of these processes.

Correlation of serum sICAM-1 and sVCAM-1 levels with severity of and prognosis of thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the correlation between levels of serum soluble intercellular adhesion molecule-1(sICAM-1), soluble vascular cell adhesion molecule-1(sVCAM-1)and the severity of thyroid-associated ophthalmopathy(TAO). <p>METHODS: A total of 120 patients with TAO admitted to the hospital from August 2016 to March 2018 were selected and included in the study. According to the clinical activity score(CAS), the patients were divided into active stage group and inactive stage group. According to the severity, they were divided into mild group, moderate group and severe group. There were 90 healthy persons were selected as the control group at the same time. The general data, serum sICAM-1 and sVCAM-1 levels were compared among groups and the correlation of sICAM-1 and sVCAM-1 levels with the severity of TAO was analyzed. <p>RESULTS: There were no significant differences in the clinical basic data of patients in between the different clinical active stage groups and the control group, and between the different severity groups and the control group(<i>P</i>>0.05). The levels of serum sICAM-1 and sVCAM-1 in the active stage group were significantly higher than those in the inactive stage group and the control group(<i>P</i><0.01). The levels of serum sICAM-1 and sVCAM-1 in active stage patients of different severity groups were significantly higher than those in inactive stage patients and of control groups(<i>P</i><0.01). There were no significant differences in levels of serum sICAM-1 and sVCAM-1 in inactive stage patients of different severity groups. The levels of serum sICAM-1 and sVCAM-1 in active stage patients of different severity groups increased gradually with the severity of the disease. There was no significant correlation between levels of serum sICAM-1 and sVCAM-1 in inactive stage patients and the severity of disease(<i>r</i>=0.102, 0.095, <i>P</i>=0.135, 0.167). Levels of serum sICAM-1 and sVCAM-1 in active stage patients were positively correlated to severity of disease(<i>r</i>=0.695, 0.824, <i>P</i>=0.005, 0.002).<p>CONCLUSION: The levels of serum sICAM-1 and sVCAM-1 in inactive patients will not increase with the severity of the disease. However, the levels in patients with active disease will increase with the severity of the disease, which can be used for clinical diagnosis and staging of TAO and monitoring of the prognosis.

Clinical effect of Shenqi-Tongmai decoction in stable angina pectoris patients with Qi-deficiency-blood-stasis syndrome and the influence on levels of serum associated adhesion factors / 国际中医中药杂志

Objective To investigate the effect of Shenqi-Tongmai decoction in Stable Angina pectoris Patients with Qi-deficiency-blood-stasis syndrome and the influence on serum associated adhesion factors. Methods A total of 110 patients with stable angina pectoris treated in the department of cardiology of traditional Chinese medicine hospital of Xinle city from Feb. 2015 to Feb. 2017 were divided into 2 groups according to the number random table method, with 55 in each group. All the patients were given the standardized treatment with western medicine, and the treatment group were aditionally treated with the Shenqi-Tongmai decoction. All the patients were treated for a course of 4 weeks. The TCM syndrome score, Seattle angina questionnaire (SAQ) score, electrocardiographic examination index and serum soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) level of the two groups before and after treatment were compared, and the clinical curative effect of the two groups was compared. Results The TCM syndrome score (7.1 ± 2.2 vs. 11.4 ± 3.0, t=8.590), serum sICAM-1 (227.69 ± 42.81 ng/ml vs. 275.33 ± 48.62 ng/ml, t=5.454) level, serum sVCAM-1 (272.04 ± 39.87 ng/ml vs. 296.58 ± 42.60 ng/ml, t=3.127) level and lead ecg ST segment down number (2.7 ± 0.6 vs. 3.2 ± 0.6, t=4.067), T wave of low lead numbers (1.7 ± 0.3 vs. 2.1 ± 0.3, t=6.807), numbers of T wave inversion lead (1.7 ± 0.3 vs. 2.1 ± 0.2, t=9.908) of the treatment group were significantly lower than those of the control group (P<0.01). The SAQ scores (76.8 ± 10.5 vs. 67.4 ± 10.1, t=4.805) was higher than that of the control group (P<0.01). The curative effect of angina pectoris and electrocardiogram of the treatment group were 91.0% (50/55) and 92.7%(51/55), and the control group were 76.4% (42/55) and 78.2% (43/55). The difference was statistically significant between the two groups (χ2=4.251, 4.681, P<0.05). Conclusions Traditional Chinese medicine Shenqi-Tongmai decoction can effectively improve the SAQ scores and TCM syndrome score and electrocardiogram examination index, improve the clinical curative effect in the treatment of Stable Angina pectoris based on the western medicine (Qi-deficiency-blood-stasis syndrome) and its mechanism may be related to improving of the serum levels of sICAM 1, sVCAM 1.

Polymorphisms of the TNF-α gene interact with plasma fatty acids on inflammatory biomarker profile: a population-based, cross-sectional study in São Paulo, Brazil.

The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1ß (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.

[Influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline].

Objective: To investigate influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline (PTX). Methods: Totally 180 SD rats were divided into sham injury group, simple electrical burn group, and treatment group according to the random number table, with 60 rats in each group. The electrical current was applied to the outside proximal part of left forelimb of rats and exited from the outside proximal part of right hind limb of rats. Rats in simple electrical burn group and treatment group were inflicted with high-voltage electrical burn wounds of 1cm×1cm at current entrances and exits, with the voltage regulator and experimental transformer. Rats in sham injury group were sham injured through connecting the same equipments without electricity. At 2 min post injury, rats in sham injury group and simple electrical burn group were intraperitoneally injected with 2 mL normal saline, and rats in treatment group were injected with 2 mL PTX injection (50 mg/mL). At 15 min before injury and 5 min, 1 h, 2 h, 4 h, and 8 h post injury, 10 rats in each group were selected to collect blood of heart respectively. Serum were separated from the blood to determine the level of soluble vascular cell adhesion molecule-1(sVCAM-1) with enzyme-linked immunosorbent assay method. The number of adhesional leukocyte in mesenteric venule of rats was determined with Bradford variable projection microscope system. The microcirculation perfusion on serosal surface of small intestine of rats was detected with laser Doppler perfusion imager. Data were processed with analysis of variance of factorial design and LSD test. Results: (1) At 5 min, 1 h, 2 h, 4 h, 8 h post injury, the serum content of sVCAM-1 in rats of simple electrical burn group were (8 502±1 158), (11 793±3 310), (9 960±2 146), (9 708±1 429), (7 292±1 386) ng/mL respectively, higher than that in sham injury group and treatment group [ (1 897±946), (1 882±940), (1 882±938), (1 888±946), (1 884±942) ng/mL, and (6 840±1 558), (6 742±2 465), (5 625±2 593), (2 373±1 463), (5 187±2 797) ng/mL, respectively, with P values below 0.001]. The serum content of sVCAM-1 in rats of sham injury group and treatment group at all time points post injury, except 4 h post injury of treatment group, was higher than that of the same group at 15 min before injury (with P values below 0.001). (2) At all time points post injury, the number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group was higher than that in sham injury group and treatment group (with P values below 0.001). The number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group and treatment group at all time points post injury was higher than that of the same group at 15 min before injury (with P values below 0.001). (3) At all time points post injury, the microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group was lower than that in sham injury group and treatment group (with P values below 0.001). The microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group and treatment group at all time points post injury was lower than that of the same group at 15 min before injury (with P values below 0.001). Conclusions: High-voltage electrical burns can increase the serum content of sVCAM-1, the number of adhesional leukocyte in mesenteric venule, and reduce microcirculation perfusion on serosal surface of small intestine of rats. PTX can inhibit secretion of serum sVCAM-1, reduce the number of adhensional leukocyte in mesenteric venule to alleviate microcirculation disturbance caused by high-voltage electrical burns.

Expression of sICAM-1, sVCAM-1 and miRNA-146a in serum of patients with thyroid associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study serum soluble intercellular adhesion molecules -1(sICAM-1), soluble vascular cell adhesion molecule -1(sVCAM-1)and expression of miRNA-146a in peripheral blood mononuclear cells(PBMC)and its significance in patients with thyroid associated ophthalmopathy(TAO). <p>METHODS: From June 2014 to December 2015 in our hospital, 37 patients with TAO(TAO group), 40 patients with hyperthyroidism without TAO(non eye disease group)and 30 healthy people(control group)were enrolled and the serum concentrations of sICAM-1, sVCAM-1 and expression of miRNA-146a in PBMC were detected. <p>RESULTS: The serum sICAM-1 and sVCAM-1 of TAO group were 366.14±67.28g/L, 211.07±27.45g/L level was significantly higher than those of non eye disease group(286.62±51.09μg/L, 179.83±25.09μg/L)and healthy group(234.51±38.969μg/L, 164.51±22.57μg/L)(<i>P</i><0.05). In TAO group, miRNA-146a(0.071±0.016)in PBMC was lower than that in non eye disease group(0.381±0.084)and healthy group(1.105±0.216)(<i>P</i><0.05). The serum levels of sICAM-1 and sVCAM-1 were significantly higher in non eye disease group than in healthy group(<i>P</i><0.05), and the expression of RNA-146a in PBMC was lower in the non eye disease group than in the healthy group(<i>P</i><0.05). The serum levels of sICAM-1 and sVCAM-1 in the mild TAO group were significantly lower than those in the moderate-severe groups and extremely severe group(<i>P</i><0.05), and the miRNA-146a expression in the mild TAO group was higher than those in the moderate-severe group and extremely severe group(<i>P</i><0.05). The serum levels of sICAM-1 and sVCAM-1 were significantly lower in the moderate-severe group than those in the extremely severe group(<i>P</i><0.05), and the expression of miRNA-146a in the moderate -severe group was significantly higher than that in the extremely severe group(<i>P</i><0.05). <p>CONCLUSION: Serum sICAM-1, sVCAM-1 in TAO patients is with high expression, miRNA-146a in PBMC in TAO patients with low expression, and related to the degree of patient's condition.

Influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline / 中华烧伤杂志

Objective@#To investigate influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline (PTX).@*Methods@#Totally 180 SD rats were divided into sham injury group, simple electrical burn group, and treatment group according to the random number table, with 60 rats in each group. The electrical current was applied to the outside proximal part of left forelimb of rats and exited from the outside proximal part of right hind limb of rats. Rats in simple electrical burn group and treatment group were inflicted with high-voltage electrical burn wounds of 1cm×1cm at current entrances and exits, with the voltage regulator and experimental transformer. Rats in sham injury group were sham injured through connecting the same equipments without electricity. At 2 min post injury, rats in sham injury group and simple electrical burn group were intraperitoneally injected with 2 mL normal saline, and rats in treatment group were injected with 2 mL PTX injection (50 mg/mL). At 15 min before injury and 5 min, 1 h, 2 h, 4 h, and 8 h post injury, 10 rats in each group were selected to collect blood of heart respectively. Serum were separated from the blood to determine the level of soluble vascular cell adhesion molecule-1(sVCAM-1) with enzyme-linked immunosorbent assay method. The number of adhesional leukocyte in mesenteric venule of rats was determined with Bradford variable projection microscope system. The microcirculation perfusion on serosal surface of small intestine of rats was detected with laser Doppler perfusion imager. Data were processed with analysis of variance of factorial design and LSD test.@*Results@#(1) At 5 min, 1 h, 2 h, 4 h, 8 h post injury, the serum content of sVCAM-1 in rats of simple electrical burn group were (8 502±1 158), (11 793±3 310), (9 960±2 146), (9 708±1 429), (7 292±1 386) ng/mL respectively, higher than that in sham injury group and treatment group [ (1 897±946), (1 882±940), (1 882±938), (1 888±946), (1 884±942) ng/mL, and (6 840±1 558), (6 742±2 465), (5 625±2 593), (2 373±1 463), (5 187±2 797) ng/mL, respectively, with P values below 0.001]. The serum content of sVCAM-1 in rats of sham injury group and treatment group at all time points post injury, except 4 h post injury of treatment group, was higher than that of the same group at 15 min before injury (with P values below 0.001). (2) At all time points post injury, the number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group was higher than that in sham injury group and treatment group (with P values below 0.001). The number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group and treatment group at all time points post injury was higher than that of the same group at 15 min before injury (with P values below 0.001). (3) At all time points post injury, the microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group was lower than that in sham injury group and treatment group (with P values below 0.001). The microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group and treatment group at all time points post injury was lower than that of the same group at 15 min before injury (with P values below 0.001).@*Conclusions@#High-voltage electrical burns can increase the serum content of sVCAM-1, the number of adhesional leukocyte in mesenteric venule, and reduce microcirculation perfusion on serosal surface of small intestine of rats. PTX can inhibit secretion of serum sVCAM-1, reduce the number of adhensional leukocyte in mesenteric venule to alleviate microcirculation disturbance caused by high-voltage electrical burns.

Treatment of low frequency decreased sensorineural hearing loss by postaural injection of Methylprednisolone / 中国耳鼻咽喉头颈外科

OBJECTIVE To analyze the effect of postaural injection in treating SNHL and the influence on ROS,sVCAM-1 levels.METHODS 242 low frequency descent sensorineural hearing loss patients from Jan.2010 to Jul.2016 in our hospital were selected as the research sbjects.They were randomly divided into two groups(n=121).All patients were treated with ginkgo biloba extract intravenous drip.The control group was treated with Methylprednisolone intravenous drip,while the observation group was treated with postaural injection of Methylprednisolone.The clinical effects between the two groups were compared after 14 days of treatment.The ABR result,serum ROS,sVCAM-1 levels were also copmpared before and after treatment.RESULTS The effective rates of 2 groups were 82.64％,61.16％ respectively,which indicated significant difference (P＜0.05).The Ⅰ and Ⅴ waves of observation group were decreased,and they was significantly lower than that of the control group(P＜0.05),the R-R interval between Ⅰ and Ⅴ waves of the 2 groups showed no significant difference (P＞0.05).After treatment,the serum ROS level of 2 groups were (0.66 ± 0.38) ng/ml,(2.31± 1.12) ng/ml respectively,the sVCAM-1 level of two groups were (230.5 ±26.4) ng/ml,(312.6 ±47.2) ng/ml respectively,the observation group was significantly lower than that of the control group (t=10.985,11.953,P＜0.05).CONCLUSION Methylprednisolone can improve the clinical effect in treating low frequency descent SNHLby improving the concentration of drugs in ear and increasing the activity of Na+/K+-ATP enzyme in blood vessel;It can also decrease ROS and sVCAM-1 level,alleviate oxidative stress,reduce vascular endothelial damage,which is worthy of recommendation.

Effects of Capparis Spinosa Total Alkaloid on Vascular Endothelial Growth Factor, Endothelin-1 and Soluble Vascular Cell Adhesion Molecule-1 Levels in Mice with Systemic Sclerosis / 医药导报

Objective To observe the effects of Capparis spinosa total alkaloid on vascular endothelial growth factor (VEGF),endothelin-1(ET-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in systemic sclerosis (SSc) mouse model and explore the therapeutic mechanism of Capparis spinosa total alkaloid for the treatment of SSc. Methods A total of 90 BALB/c mice were randomly divided into blank control group,model control group,penicillamine (125 mg·kg-1) group and Capparis spinosa total alkaloid low(225 mg·kg-1),medium(450 mg·kg-1) and high(900 mg·kg-1) dose group. Except for the blank control group,SSc mouse model was established by daily subcutaneous injection of bleomycin in the back of the mice.After establishing model successfully,Capparis spinosa total alkaloid emulsifiable paste was externally applied with Capparis spinosa total alkaloid group,ground substance was externally applied to the mice in blank control group and model control groups,penicillamine was intragastrically administrated in the penicillamine group for 60 days,once daily.After the treatment,the content of VEGF in skin tissue and ET-1,sVCAM-1 in serum were measured by ELISA. Results The levels of VEGF and ET-1 were significantly decreased in Capparis spinosa total alkaloid high dose group as compared with model control group(P<0.05, P<0.01),but the content of sVCAM-1 wasn't influenced(P>0.05). Conclusion Capparis spinosa total alkaloid is effective in adjusting abnormal expression of VEGF and ET-1 in SSc mice.

Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia.

Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion.