Intercellular Cell Adhesion Molecule-1 Levels Research Articles

Increased caveolin 1 by human antigen R exacerbates Porphyromonas gingivali-induced atherosclerosis by modulating oxidative stress and inflammatory responses

Objective: Many different types of infectious oral diseases have been identified clinically, including chronic periodontitis. Porphyromonas gingivalis is the main pathogen causing chronic periodontitis, which is closely related to atherosclerosis (AS) and can promote the expression levels of caveolin 1 (Cav-1) and induced ribonucleic acid (RNA)-binding protein human antigen R (HuR). However, the roles of Cav-1 and its relationship with HuR in P. gingivalis-mediated AS progression remain largely unknown. Here, we aimed to detect the role and molecular mechanisms of Cav-1 in P. gingivalis-mediated AS. Material and Methods: To investigate the role of Cav-1 in P. gingivalis-mediated AS, we infected human umbilical vein endothelial cells (HUVECs) with P. gingivalis at a multiplicity of infection of 100:1 for 6, 12, and 24 h to simulate P. gingivalis-induced AS models in vitro and then transfected them with Cav-1 small interfering RNA to silence Cav-1. Combining molecular biology experimental techniques such as cell counting kit-8 assay, enzyme-linked immunosorbent assay, immunofluorescence staining, flow cytometry, Western blotting, and Oil Red O staining, and apolipoprotein E-deficient AS model mice, the impacts of Cav-1 on cell viability, inflammation, oxidative stress, apoptosis, Cav-1 and intercellular cell adhesion molecule-1 (ICAM-1) levels, and atherosclerotic plaque formation were investigated. Then, the relationship between Cav-1 and HuR was investigated through biotin pull-down and RNA immunoprecipitation assays, reverse transcription quantitative polymerase chain reaction, and Western blot. Results: P. gingivalis can induce Cav-1 expression in a time- and dose-dependent manner (P < 0.05). This effect can inhibit the proliferation of HUVECs (P < 0.05). Cav-1 interference repressed inflammatory response, reactive oxygen species (ROS) and ICAM-1 levels, and apoptosis in the HUVECs (P < 0.05). Cav-1 messenger RNA was stabilized by HuR, which can bind to the 3’ untranslated region of Cav-1. Increase in HuR level reversed the effects of Cav-1 silencing on ROS and ICAM-1 levels and apoptosis in the HUVECs (P < 0.05). In addition, the levels of inflammatory response, oxidative stress, and atherosclerotic plaque formation induced by P. gingivalis in the mouse model were significantly reduced after Cav-1 expression was inhibited (P < 0.05). Conclusion: HuR-activated Cav-1 may promote atherosclerotic plaque formation by modulating inflammatory response and oxidative stress, leading to AS.

Comparative study on the immune surveillance injury of blood cerebrospinal fluid barrier induced by exposure to lead acetate and nano-lead sulfide

Objective: To investigate the differences in terms of blood cerebrospinal fluid barrier immune surveillance injury by lead acetate and nano-lead sulfide exposure in order to provide basis for the study of their mechanism of nerve injury caused by exposure to lead and nano lead. Methods: In June 2015, forty-five SPF SD male rats were randomly divided into control group, lead acetate group (20 mg/kg) and nano-lead sulfide group (20 mg/kg), with 15 rats in each group. The rats were intragastric five times a week, for nine weeks. The numbers of CD4(+) T lymphocytes in blood and cerebrospinal fluid were detected by flow cytometry. The levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum and cerebrospinal fluid were detected by ELISA. The expressions and distribution of intercellular cell adhesion molecule-1 (ICAM-1) and CD4(+) T lymphocytes in choroid plexus were detected by laser confocal fluorescence immunoassay. The mRNA expression levels of IL-4, IFN-γ and ICAM-1 in the choroid plexus were detected by real-time PCR. Results: Compared with the control group, the proportion of CD4(+) T lymphocytes in blood of rats in lead acetate group was increased, the proportions of CD4(+) T lymphocytes in cerebrospinal fluid of rats in lead acetate group and nano-lead sulfide group were increased, the contents of IL-4 and IFN-γ in serum of rats in lead acetate group and nano-lead sulfide group were increased, the content of IL-4 in cerebrospinal fluid of rats in lead acetate group and the contents of IL-4 and IFN-γ in cerebrospinal fluid of rats in nano-lead sulfide group were increased, the differences were statistically significant (P<0.05). The fluorescence intensity of ICAM-1 and CD4(+) T lymphocytes in choriochoroid plexus of rats in lead acetate group and nano-lead sulfide group were stronger than those in control group, and the fluorescence intensity of CD4(+) T lymphocytes of rats in nano-lead sulfide group was weaker than that in lead acetate group. Compared with the control group, the mRNA expression levels of ICAM-1, IL-4 and IFN-γ in choriochoroids plexus of rats in lead acetate group and nano-lead sulfide group were increased, and the mRNA expression levels of ICAM-1 and IL-4 in nano-lead sulfide group were higher than those in lead acetate group, while the mRNA expression level of IFN-γ in nano-lead sulfide group was lower than that in lead acetate group (P<0.05) . Conclusion: Exposure to lead and nano-lead sulfide can cause the increase of CD4(+) T lymphocytes, IL-4, IFN-γ and ICAM-1, which may be related to the damage to the immune surveillance of the blood cerebrospinal fluid barrier. And there is a difference in the injury caused by lead and nano-lead sulfide exposure.

Changes in Levels of Serum Cytokines and Chemokines in Perforated Appendicitis in Children.

Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA.

Elevated Levels of Serum Biomarkers Associated with Damage to the CNS Neurons and Endothelial Cells Are Linked with Changes in Brain Connectivity in Breast Cancer Patients with Vestibulo-Atactic Syndrome

Vestibulo-atactic syndrome (VAS), which represents a combination of motor and vestibular disorders, can be manifested as a clinical complication of breast cancer treatment and has a significant impact on patients’ quality of life. The identification of novel potential biomarkers that might help to predict the onset of VAS and its progression could improve the management of this group of patients. In the current study, the levels of intercellular cell adhesion molecule 1 (ICAM-1), platelet/endothelial cell adhesion molecule 1 (PECAM-1), NSE (neuron-specific enolase), and the antibodies recognizing NR-2 subunit of NMDA receptor (NR-2-ab) were measured in the blood serum of BC survivor patients with vestibulo-atactic syndrome (VAS) and associated with the brain connectome data obtained via functional magnetic resonance imaging (fMRI) studies. A total of 21 patients were registered in this open, single-center trial and compared to age-matched healthy female volunteers (control group) (n = 17). BC patients with VAS demonstrated higher serum levels of ICAM-1, PECAM-1, and NSE and a lower value of NR-2-ab, with values of 654.7 ± 184.8, 115.3 ± 37.03, 49.9 ± 103.9, and 0.5 ± 0.3 pg/mL, respectively, as compared to the healthy volunteers, with 230.2 ± 44.8, 62.8 ± 15.6, 15.5 ± 6.4, and 1.4 ± 0.7 pg/mL. According to the fMRI data (employing seed-to-voxel and ROI-to-ROI methods), in BC patients with VAS, significant changes were detected in the functional connectivity in the areas involved in the regulation of postural-tonic reflexes, the coordination of movements, and the regulation of balance. In conclusion, the detected elevated levels of serum biomarkers may reveal damage to the CNS neurons and endothelial cells that is, in turn, associated with the change in the brain connectivity in this group of patients.

Phellopterin cream exerts an anti-inflammatory effect that facilitates diabetes-associated cutaneous wound healing via SIRT1

BackgroundDiabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties. PurposeTo research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers. Study designChemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 − 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action. MethodsThe expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using H&E, qRT–PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions. ResultsHigh levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects. ConclusionIn vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.

Endothelial Biomarkers in Patients Recovered from COVID-19 One Year after Hospital Discharge: A Cross-Sectional Study.

BackgroundCOVID-19 is characterized by endothelial dysfunction and is presumed to have long-term cardiovascular sequelae. In this cross-sectional study, we aimed to explore the serum levels of endothelial biomarkers in patients who recovered from COVID-19 one year after hospital discharge.MethodsIn this clinical follow-up study, 345 COVID-19 survivors from Huanggang, Hubei, and 119 age and gender-matched medical staff as healthy controls were enrolled. A standardized symptom questionnaire was performed, while electrocardiogram and Doppler ultrasound of lower extremities, routine blood tests, biochemical and immunological tests, serum soluble vascular cell adhesion molecule-1(VCAM-1), intercellular cell adhesion molecule-1(ICAM-1), P-selectin, and fractalkine were measured by enzyme-linked immunosorbent assays (ELISA).ResultsAt one year after discharge, 39% of recovers possessed post-COVID syndromes, while a few had abnormal electrocardiogram manifestations, and no deep vein thrombosis was detected in all screened survivors. There were no significant differences in circulatory inflammatory markers (leukocytes, neutrophils, lymphocytes, C-reactive protein and interleukin-6), alanine aminotransferase, estimated glomerular filtration rate, glucose, triglycerides, total cholesterol and D-dimer observed among healthy controls with previously mild or severe infected. Furthermore, serum levels of VCAM-1, ICAM-1, P-selectin, and fractalkine do not significantly differ between survivors and healthy controls.ConclusionsSARS-CoV-2 infection may not impose a higher risk of developing long-term cardiovascular events, even for those recovering from severe illness.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61

ObjectivePsoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. MethodsThe expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. ResultsImmunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. ConclusionThe results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease.

Leptin and proprotein convertase subtilisin kexin 9 (PCSK9) play an important role in regulating blood lipid concentration. Recently, they have been found to show the ability to independently regulate the immune response. Vascular immune response has an important pathological function in the development of coronary heart disease (CHD) and thrombosis. The aim of this study was to explore the relationship between leptin, PCSK9, and vascular endothelial cell related inflammatory factors. First, detailed clinical information were collected and analyzed for 27 patients with stable CHD and corresponding 27 healthy controls. Second, using liquid-phase protein chip technology, leptin, PCSK9, and vascular-related inflammatory factors, such as E-selectin, vascular cell adhesion protein 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-γ), and interleukin-17 (IL-17), were detected on the same platform. Finally, the correlation between leptin, PCSK9, and the inflammatory factors was analyzed. Through collecting clinical information of patients, it was suggested that there was a significant positive correlation between leptin and blood lipid level in CHD. Compared with healthy people, the levels of leptin, PCSK9, E-selectin, and ICAM-1 were significantly high in patients with CHD. There was a high positive correlation between leptin and E-selectin, ICAM-1, IFN-γ, and IL-17. Also, a high positive correlation between PCSK9 and E-selectin, IFN-γ, and IL-17 concentrations was observed. In general, leptin and PCSK9 may not only be able to regulate lipid metabolism, but may also be able to regulate inflammation in CHD.

Correlation of Long Non-coding RNA LncRNA-FA2H-2 With Inflammatory Markers in the Peripheral Blood of Patients With Coronary Heart Disease.

Objective: To characterize the expression of long non-coding RNA LncRNA-FA2H-2 in coronary heart disease (CHD) and its correlation with inflammatory markers.Methods: From December 2018 to December 2020, 316 patients at Henan Provincial People's Hospital who complained of chest tightness or chest pain and had coronary angiography to clarify their coronary artery conditions for definitive diagnoses were selected as the study subjects. Plasma was collected to detect white blood cells (WBCs), total cholesterol (TG), triglyceride cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and C-reactive protein (CRP) levels. Tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) levels were also measured using ELISA. The expression levels of lncRNA-FA2H-2 were measured using quantitative real-time PCR. The data obtained were analyzed by independent sample t-tests, rank sum tests, regression analyses, Pearson's or Spearman's correlation analyses, and receiver operating characteristic curves.Results: (1) Compared with the control group, the differences in age, sex, diabetes, smoking, drinking, body mass index (BMI), WBC, TC, and LDL-C in CHD were not statistically significant, while the differences in hypertension, TG, HDL-C, ApoA1, and CRP were statistically significant. (2) In the grouping of coronary lesion branches, patients with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TC, LDL-C, HDL-C, and ApoA1 differences were not statistically significant, but TG and CRP differences were statistically significant. (3) The relative expressions of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 were significantly upregulated in the CHD group (P < 0.001). (4) The results showed that the relative levels of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. In addition, positive correlations were found between the Gensini score and TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD patients. (5) LncRNA-FA2H-2 relative expression in the CHD group was significantly downregulated (P < 0.001). (6) The differences in the expression levels of LncRNA-FA2H-2 were statistically significant between the two comparative analyses (P < 0.01), except between the 2-branch lesion and 3-branch lesion groups. (7) LncRNA-FA2H-2 was not associated with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TG, TC, LDL-C, HDL-C, and ApoA1 (P > 0.05). (8) A correlation was found between LncRNA-FA2H-2 and MCP-1, and VCAM-1, ICAM-1, IL-6, and Gensini. (9) The results indicated that the relative levels of LncRNA-FA2H-2 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. A negative correlation was found between the Gensini score and LncRNA-FA2H-2. (10) ROC curve analyses of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD showed the area under the curve (AUC) = 0.832 (0.77, 0.893) with a cut-off value of 290.5, a sensitivity of 73%, and a specificity of 64%; AUC = 0.731 (0.653, 0.809) with a cut-off value of 396 and with a sensitivity of 59% and specificity of 79%; AUC = 0.822 (0.757, 0.887) with a cut-off value of 264 and with a sensitivity of 72% and specificity of 83%; AUC = 0.794 (0.715, 0.874) with a cut-off value of 201.5 and with a sensitivity of 75% and specificity of 65%; AUC = 0.760 (0.685, 0.834) with a cut-off value of 328 and with a sensitivity of 55% and specificity of 90%. (11) ROC curve analysis of LncRNA-FA2H-2 in CHD patients showed AUC = 0.834 (0.688, 0.85) with a cut-off value of 3.155 and with a sensitivity of 85% and specificity of 82%. (12) Logistic analyses showed that TNF-α, MCP-1, VCAM-1, IL-6, and LncRNA-FA2H-2 were independent risk factors for CHD.Conclusions: The expression of LncRNA-FA2H-2 was reduced and inversely correlated with inflammation-related factors in CHD patients. LncRNA-FA2H-2 may have potential as an inflammatory marker for risk assessment of CHD development.

Effects of sevoflurane and propofol anesthesia on intraoperative endothelial cell function in patients undergoing laparoscopic cholecystectomy.

ObjectivesTo investigate the effects of sevoflurane and propofol anesthesia on inflammatory or anti-inflammatory responses in patients undergoing laparoscopic cholecystectomy (LC).MethodsPatients undergoing LC (n = 23) were divided into sevoflurane (S) (n = 11) and propofol (P) (n = 12) anesthesia groups. A blood sample was taken before induction (T0), after induction but before pneumoperitoneum (T1), 15 minutes after pneumoperitoneum (T2), immediately after extubation (T3), and 30 minutes after extubation (T4). P-selectin-positive platelets and intercellular cell adhesion molecule-1 (ICAM-1)-positive lymphocytes, and plasma P-selectin, ICAM-1 and thrombomodulin (TM) levels were analyzed.ResultsSevoflurane significantly increased P-selectin expression in platelets at T2, T3, and T4 and in plasma at T1, T2, T3, and T4, but it did not affect ICAM-1 and TM. Propofol had no significant effects on P-selectin, ICAM-1, and TM expression during anesthesia and surgery. P-selectin, ICAM-1, and TM expression was higher in the S compared with P group at T1, T2, and T3 for platelet P-selectin; T2 and T4 for plasma P-selectin; T1 and T2 for lymphocyte ICAM-1; and T1, T2, and T3 for plasma TM.ConclusionsPropofol anesthesia can delay the inflammatory reactions during laparoscopic surgery and better maintain the structure stability and function in vascular endothelial cells.

Regulation of LOX-1 on adhesion molecules and neutrophil infiltration in mouse Aspergillus fumigatus keratitis.

To determine whether lectin-like ox-LDL receptor (LOX-1) regulates adhesion molecules expression and neutrophil infiltration in Aspergillus fumigatus (A. fumigatus) keratitis of C57BL/6 mice. C57BL/6 mice were pretreated with a neutralizing antibody to LOX-1 (5 µg/5 µL) or control nonspecific IgG (5 µg/5 µL), LOX-1 inhibitor Poly-I (2 µg/5 µL) or PBS by subconjunctival injection. Fungal keratitis (FK) mouse models of C57BL/6 mice were established by scraping corneal central epithelium, smearing A. fumigatus on the corneal surface and covering the eye with contact lenses. The corneal response to infection was assessed via clinical score. The mRNA levels of the adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin and E-selectin were tested in control and infected corneas by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 were evaluated by immunofluorescence (IF) and Western blot. Neutrophils were extracted from the abdominal cavity of C57BL/6 mice followed by pretreatment using antibody to LOX-1 (10 µg/mL) or control nonspecific IgG (10 µg/mL), the Poly-I (4 µg/mL) or PBS. The cells were then stimulated with A. fumigatus and tested mRNA and protein levels of lymphocyte function-associated antigen-1 (LFA-1) using RT-PCR and Western blot. IF and myeloperoxidase (MPO) assays were used to assess neutrophil infiltration in mice corneas. Pretreatment of LOX-1 antibody or the Poly-I reduced the degree of inflammation of cornea and decreased the clinical FK score compared with pretreatment of IgG or PBS (both P<0.01). And these pretreatment also displayed an obvious decline in the mRNA levels of ICAM-1, VCAM-1, P-selectin, E-selectin and LFA-1 expression compared with control groups (all P<0.01). Furthermore, pretreated with LOX-1 antibody or Poly-I, the protein levels of ICAM-1 and LFA-1 also decreased compared with control groups (all P<0.05). Neutrophil infiltration in the cornea was significantly reduced after pretreatment of LOX-1 antibody or Poly-I compared with control groups by IF and MPO assays (both P<0.01). Inhibition of LOX-1 can decrease the expression of adhesion molecules and reduce neutrophil infiltration in A. fumigatus infected corneas of C57BL/6 mice.

Radix Paeoniae Rubra Ameliorates Lupus Nephritis in Lupus-Like Symptoms of Mrl Mice by Reducing Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Platelet Endothelial Cell Adhesion Molecule-1 Expression.

Vasculitis is the basic pathological change of systemic lupus erythematosus (SLE). Radix Paeoniae Rubra (RPR), a traditional Chinese herb with the function of reducing blood stasis, has anti-inflammatory and immunoregulatory properties. This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl (MRL/lpr) mice from the perspective of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). Eighteen MRL/lpr lupus model mice were randomly divided into three groups, the model control group, prednisone-treated group, and RPR-treated group, and 6 C57BL/ 6 mice were classified as a control group. After the mice had been treated for 12 weeks, the expression of ICAM-1, VCAM-1 and PECAM-1in the kidney was determined by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). After 12 weeks, there were significant differences in body weight in the model, prednisone and RPR groups compared with the normal group (P <0.05). Pathological observation: Compared with the model group, the proliferation of inflammatory cells infiltrated glomeruli and interstitial cells in prednisone and RPR groups were reduced, and renal pathological damage was reduced. Compared with the model group, urine protein level of prednisone and RPR groups were reduced with no significance (P> 0.05). The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group (P <0.05 or P <0.01). Meanwhile, the immunohistochemistry expressions of ICAM-1 and VCAM- 1 expressed in the kidney were significantly reduced in the prednisone group and RPR group (P <0.01 or P <0.05). However, The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group (prednisone group and RPR group), but these differences were not significant (P>0.05). ICAM-1, VCAM-1 and PECAM-1 expression in the model group was found to be significantly increased. In addition, RPR could reduce the expression of ICAM-1, VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone, which may result in the dosage reduction of prednisone, thus decreasing the toxicity and improving the efficacy of prednisone - based treatment of SLE.

MiR-138 ameliorates myocardial ischemia/reperfusion injury by targeting intercellular cell adhesion molecule 1

Purpose: To explore the effect of miR-138 on regulating intercellular cell adhesion molecule 1 (ICAM-1) expression in endothelial cells to alleviate cardiac ischemia/reperfusion (I/R) injury and its related mechanisms.&#x0D; Methods: The left anterior descending artery of the heart was occluded for 30 min and then perfused for 2 h to induce a rat model of cardiac I/R injury. H9C2 cells were cultured in an anoxic medium without serum to establish the model of hypoxia/reoxygenation (H/R). Triphenyl tetrazolium chloride (TTC) staining was applied to measure myocardial infarction sizes in rat hearts. The mRNA expression levels of miR-138 and ICAM-1 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Dual luciferase reporter assay was used to identify the target of miR-138. The agomiR-138 and miR-138 mimics were transfected into H9C2 cells; exogenous ICAM-1 was also administered, and ROS accumulation, cell viability, and apoptosis were measured. Furthermore, the underlying mechanism was investigated.&#x0D; Results: MiR-138 was downregulated both in vitro and in vivo. AgomiR-138 reduced myocardial infarction area, decreased ROS production and suppressed cell apoptosis in a rat model of cardiac I/R injury. On the other hand, miR-138 mimics increased cell viability, enhanced ROS production and induced cell apoptosis in H/R-induced H9C2 cells. Further analysis verified ICAM-1 as a target of miR- 138. Besides, exogenous ICAM-1 inhibited the protective effect of miR-138 on H/R-induced apoptosis in vitro.&#x0D; Conclusion: MiR-138 may protect against injury of myocardial I/R by targeting ICAM-1. The results also provide insight into miR-138/ICAM-1 axis as new therapeutic targets for myocardial I/R injury.&#x0D; Keywords: Intercellular cell adhesion molecule 1, MicroRNA-138, Myocardial/ischemia reperfusion injury, Reactive oxygen species

Hepcidin protects pulmonary artery hypertension in rats by activating NF-κB/TNF-α pathway.

The pulmonary artery hypertension (PAH) model was established in rats in this study. Therefore, we aimed to elucidate the protective role of Hepcidin in PAH rats and its underlying mechanism. 24 male Sprague Dawley (SD) rats were randomly divided into sham group, PAH group and Hepcidin group, with 8 rats in each group. After animal procedures, hemodynamic parameters and right ventricular hypertrophy indexes were determined in rats. Cytokines in serum samples of rats were detected by enzyme-linked immunosorbent assay (ELISA). Pathological lesions in lung tissues were observed by hematoxylin and eosin (H&E) staining. Finally, Western blot was conducted to detect the protein expressions of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) in lung tissues of rats. Compared with sham group, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were significantly elevated in rats of PAH group (p<0.05). On the contrary, mPAP and RVSP in rats of Hepcidin group were both significantly lower than PAH group (p<0.05). Hepcidin treatment attenuated PAH-induced pathological lesions in lung tissues. ELISA results elucidated that Hepcidin treatment significantly decreased serum levels of TGF-β, TNF-α, IL-1β, and IL-6. In addition, Western blot results demonstrated that protein levels of NF-κB, TNF-α, IL-1β, VCAM-1, ICAM-1, and MCP-1 in Hepcidin group were remarkably lower than those of PAH group. Hepcidin alleviates inflammatory response in PAH rats by inhibiting NF-kB/ TNF-α pathway.

Modulation effect of Acanthopanax senticosus polysaccharides through inflammatory cytokines in protecting immunological liver-injured mice

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1β) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1β and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.

Partial Deletion of Tie2 Affects Microvascular Endothelial Responses to Critical Illness in A Vascular Bed and Organ-Specific Way.

Tyrosine kinase receptor (Tie2) is mainly expressed by endothelial cells. In animal models mimicking critical illness, Tie2 levels in organs are temporarily reduced. Functional consequences of these reduced Tie2 levels on microvascular endothelial behavior are unknown. We investigated the effect of partial deletion of Tie2 on the inflammatory status of endothelial cells in different organs. Newly generated heterozygous Tie2 knockout mice (exon 9 deletion, ΔE9/Tie2) exhibiting 50% reduction in Tie2 mRNA and protein, and wild-type littermate controls (Tie2), were subjected to hemorrhagic shock and resuscitation (HS + R), or challenged with i.p. lipopolysaccharide (LPS). Kidney, liver, lung, heart, brain, and intestine were analyzed for mRNA levels of adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular cell adhesion molecule 1 (ICAM-1), and CD45. Exposure to HS + R did not result in different expression responses of these molecules between organs from Tie2 or Tie2 mice and sham-operated mice. In contrast, the LPS-induced mRNA expression levels of E-selectin, VCAM-1, and ICAM-1, and CD45 in organs were attenuated in Tie2 mice when compared with Tie2 mice in kidney and liver, but not in the other organs studied. Furthermore, reduced expression of E-selectin and VCAM-1 protein, and reduced influx of CD45 cells upon LPS exposure, was visible in a microvascular bed-specific pattern in kidney and liver of Tie2 mice compared with controls. In contrast to the hypothesis that a disbalance in the Ang/Tie2 system leads to increased microvascular inflammation, heterozygous deletion of Tie2 is associated with an organ-restricted, microvascular bed-specific attenuation of endothelial inflammatory response to LPS.

Aldosterone induced up-expression of ICAM-1 and ET-1 in pancreatic islet endothelium may associate with progression of T2D

Previous studies have demonstrated that excess aldosterone impairs glucose metabolism. However, the underlying mechanism is still misty. Aldosterone has been proved a risk factor of fibrosis and inflammation. And the histology of islets from patients with type 2 diabetes (T2D) also displays inflammation and fibrosis. But it is unclear whether aldosterone has direct impact on islet inflammation and fibrosis in T2D. Islet endothelium plays a significant role in the maintenance of islet beta cell function and has a close relationship with islet fibrosis and inflammation. Therefore, we focused on the effect of aldosterone on the islet endothelium. In this study, we utilized a diabetic db/db mouse model and examined serum aldosterone levels, islet macrophages infiltration, and islet fibrosis. After we confirmed that there was an increased expression of intercellular cell adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) in islet of diabetic mice compared with wild type mice. We next determined that aldosterone increased expression of ICAM-1 and ET-1 in both mRNA and protein levels in islet endothelium in vitro. And then we tested the expression of mineralocorticoid receptor (MR) in islet endothelium in vitro and in vivo. Our results showed that aldosterone can up-regulate the expression levels of ICAM-1 and ET-1 through MR. These findings suggest excess aldosterone might participate in islet inflammation and fibrosis in T2D.

Inflammation and Kidney Injury in Diabetic African American Men.

African Americans are disproportionately burdened by diabetic kidney disease (DKD). However, little is known about the cellular and molecular mechanisms underlying the onset and progression of DKD in this population. The goal of the current study was to determine the association between specific inflammation markers and kidney injury in diabetic African American men. To this end, we recruited diabetic patients either with (n = 20) or without (n = 87) diagnosed kidney disease along with age-matched nondiabetic controls (n = 81). Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFR) were used for biochemical assessment of kidney function. We then measured plasma and urinary levels of seven inflammatory markers, including adiponectin, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), interleukin-6 (IL-6), and intercellular cell adhesion molecule-1 (ICAM-1). Plasma levels of TNF-α, TNFR1, and TNFR2 were significantly higher in diabetics with macroalbuminuria compared to nondiabetic controls and diabetics with normoalbuminuria or microalbuminuria. Likewise, urinary levels of ICAM-1 were higher in diabetics with macroalbuminuria compared to the other groups. Indeed, urinary ICAM-1, plasma TNF-α, and adiponectin had moderate positive correlations with UACR while plasma TNFR1 and TNFR2 levels were strongly correlated with kidney injury, indicated by multiple biomarkers of kidney injury. In contrast, though plasma CRP was elevated in diabetic subjects relative to nondiabetic controls, its levels did not correlate with kidney injury. Together, these data suggest that inflammation, particularly that mediated by the TNF-α/NF-κB signaling axis, may play a role in the pathogenesis of DKD in African American men.

The anti-inflammatory and anti-oxidative effects of conbercept in treatment of macular edema secondary to retinal vein occlusion

To investigate the effects of conbercept on inflammatory and oxidative response in macular edema secondary to retinal vein occlusion (RVO-ME). Retinal microvasculature were detected by optical coherence tomographic angiography (OCTA). The inflammation related factors including prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), intercellular cell adhesion molecule-1 (ICAM-1) and macrophage inflammatory protein-1 (MIP-1) were determined in human and mice with RVO-ME. OCTA images showed that capillary non-perfusion, enlargement of the foveal avascular zone, telangiectatic vessels and some forms of intraretinal edema in RVO-ME and all these were alleviated by conbercept treatment. PGE1, PGE2, PGF2a, ICAM-1 and MIP-1 in aqueous fluid extracted from RVO-ME patients was significantly increased compared with non-RVO subjects, intravitreal injection of conbercept partly reduced ICAM-1 and MIP-1 levels but not PGE1, PGE2 and PGF2a. The glutathione level was reduced in aqueous fluid extracted from RVO-ME patients but was restored after conbercept treatment. The inflammation, angiogenesis and ROS generation was increased in RVO-ME mice, conbercept partly inhibited these effects. Mechanistically, conbercept inhibited vascular endothelial growth factor (VEGF), ICAM-1, MIP-1, NOX-1 and NOX-4 protein expressions, but not PGE1, PGE2 and PGF2a expressions. Conbercept alleviates RVO-ME through inhibiting inflammation, angiogenesis and oxidative responses. These findings further reveals the molecular mechanism of conbercept for treatment of RVO-ME.

Effect of Combined Use of Astragaloside IV (AsIV) and Atorvastatin (AV) on Expression of PPAR-γ and Inflammation-Associated Cytokines in Atherosclerosis Rats.

BackgroundThe aim of this study was to assess the effect of combined use of Astragaloside IV(AsIV) and atorvastatin (AV) on the expression of PPAR-γ and inflammation-associated cytokines in atherosclerosis rats.Material/MethodsHigh-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma were detected through automatic biochemical analyzer and the histopathological analysis was performed via HE staining. The levels of oxidized low-density lipoprotein (oxLDL) and tumor necrosis factor-α (TNF-α), and interleukins (IL)-6 and IL-18 in serum were detected by ELISA. The expressions of proliferator-activated receptor-gamma (PPAR-γ), cluster of differentiation 36 (CD36), matrix metalloprotein-9 (MMP-9), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1), and p38 and P-p38 levels were detected by Western blot. RT-PCR was used to detect the mRNA expressions of nuclear factor-κB (NF-κB), PPAR-γ, CD36, MMP-9, ICAM-1, and VCAM-1.ResultsAdministration of AsIV and AV significantly decreased the lipid content and oxLDL in plasma. The levels of TNF-α, IL-6, and IL-18 were significantly decreased in AsIV, AV, and AsIV + AV groups, especially in the AsIV + AV group. Administration decreased the levels of NF-κB, CD36, MMP-9, ICAM-1, VCAM-1, and P-p38 expression and increased the expression of peroxisome PPAR-γ. Compared with the NC group, the atherosclerotic lesions significantly increased in the HD group, while the combined administration significantly inhibited the development of atherosclerotic disease.ConclusionsCombined administration of AV and AsIV showed potent effects against atherosclerosis through the NF-κB/PPARγ pathway, which may be a new therapy for treatment of atherosclerosis in the future.