ovalbumin and Atherosclerosis

Childhood trauma may contribute to poorer premorbid social and academic adjustment which may be a risk factor for schizophrenia.. We explored the relationship between premorbid adjustment and childhood trauma, timing of childhood trauma's moderating role as well as the association of clinical and treatment-related confounders with premorbid adjustment.. Type of childhood trauma was assessed with the Childhood Trauma Questionnaire, short-form and premorbid adjustment using the Premorbid Adjustment Scale. Timing of childhood trauma was assessed using the Life Events Checklist and life events timeline. Linear regression analyses were used to assess the moderating effect of timing of childhood trauma. Clinical and treatment-related confounders were entered into sequential hierarchical regression models to identify independent predictors of premorbid adjustment across key life stages.. Childhood physical neglect was associated with poorer premorbid academic functioning during childhood and early adolescence, and poorer premorbid social functioning during early and late adolescence. By hierarchical regression modelling (. In patients with FES, childhood physical neglect may contribute to poorer premorbid social functioning during early adolescence. This may provide us with an opportunity to identify and treat at-risk individuals earlier.. Utilization of pharmacy services including telehealth, may allow clinical pharmacists to collaboratively provide remote services without jeopardizing patient outcomes. Larger studies are needed to confirm these findings, and display the long-term impact and satisfaction of these services.. Treatment of Staphylococcus aureus IE in IDUs on methadone treatment requires the use of high daptomycin daily doses in order to achieve satisfactory pharmacodynamic parameters. Close monitoring of the daptomycin plasma concentration is suggested.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antineoplastic Agents, Alkylating; Area Under Curve; Atherosclerosis; B7-H1 Antigen; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Calgranulin B; Cause of Death; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Combined Modality Therapy; Comorbidity; Cost-Benefit Analysis; COVID-19; COVID-19 Vaccines; CRISPR-Cas Systems; Daptomycin; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance, Neoplasm; Drug Therapy, Combination; Endocarditis, Bacterial; Enzyme Inhibitors; Extracellular Matrix; Female; Ferritins; Fibrin Fibrinogen Degradation Products; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; Gene Targeting; Glioblastoma; Half-Life; Health Status; Heterocyclic Compounds, 1-Ring; Hospital Mortality; Humans; Interleukin-6; L-Lactate Dehydrogenase; Lung; Lung Diseases, Interstitial; Male; Matrix Metalloproteinase 13; Methadone; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbial Sensitivity Tests; Microglia; Middle Aged; Neuroendocrine Tumors; Octreotide; Opiate Substitution Treatment; Ovalbumin; Oxygen; Oxygen Inhalation Therapy; p38 Mitogen-Activated Protein Kinases; Parkinson Disease; Partial Pressure; Phenotype; Plaque, Atherosclerotic; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prospective Studies; Quality of Life; Radiotherapy Dosage; Radiotherapy, Conformal; SARS-CoV-2; Severity of Illness Index; Spike Glycoprotein, Coronavirus; Staphylococcal Infections; Staphylococcus aureus; Surveys and Questionnaires; Survival Rate; Sweden; Temozolomide; Tissue Distribution; Tomography, X-Ray Computed; Treatment Outcome; Tumor-Associated Macrophages; Young Adult

Allergic asthma and atherosclerosis represent different directions of inflammatory responses of CD4. We aimed to investigate the roles of curcumin in asthma-accelerated atherosclerosis plaque formation, and the change of CD4. Six to eight-week-old apolipoprotein E. The accelerated atherosclerosis was induced by allergic asthma accompanied by increased T helper cell (Th)2 and Th17 cells and decreased regulatory T cells (Tregs) in the spleen. After the 8-week treatment with curcumin, the lesion areas in the aortic root in asthmatic mice significantly improved, and the elevated Th2 and Th17 cells significantly decreased, but Tregs markedly increased. Although curcumin treatment markedly reduced the interleukin (IL)-4 and IL-13 in serum and spleen, the elevated IL-17A did not decrease. Moreover, Th1 cells showed no significant change between different groups. The mRNA expression levels of M1 macrophage-related inflammatory factors IL-6, iNOS and IL-1β were markedly elevated in the spleens of asthmatic mice, but significantly decreased after the 8-week treatment with curcumin.. Curcumin ameliorated the aggravation of atherosclerotic lesions and stabilised plaque by modulating the balance of Th2/Tregs in asthmatic apoE

Topics: Animals; Asthma; Atherosclerosis; Curcumin; Interleukins; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Ovalbumin; Plaque, Atherosclerotic; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Th2 Cells

Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4(+) T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Antiasthmatic medication can efficiently mitigate atherosclerotic lesion pathology.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Budesonide; Chronic Disease; Disease Progression; Glucocorticoids; Hypersensitivity; Inflammation; Ketotifen; Male; Mast Cells; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Pneumonia

The chronic inflammation of atherosclerosis is regulated by Th1, while allergic asthma is controlled by Th2. The direct relationship between atherosclerosis and asthma is contradictory. The aim of this study was to investigate the role of allergic asthma in atherosclerotic plaque formation and the change of CD4(+) T cells subsets.. Six-week C57BL/6J or apoE(-/-) mice were sensitized on day 0, 7 and 14, then exposed to aerosolized 1% Ovalbumin (OVA) or PBS 30min/day, 3 times/week for 8 or 16weeks from day 14 onward. The results showed that allergic asthma mice models were successfully established and the accelerated atherosclerosis induced by allergic asthma accompanied with increased Th2 and Th17 cells but not Th1 cells in spleen. Moreover, the expression and production of Th2 and Th17 biomarkers including IL-4 and IL-17A were significantly elevated in asthmatic apoE(-/-) mice. After 8-week treated with the neutralizing antibody of IL-4 or IL-17A, the lesion area in the aortic root of asthmatic apoE(-/-) mice was markedly decreased, and more dramatical result was observed after the combined treatment with IL-4 and IL-17A mAbs. The expression of IgE and FcεRIα in the aortic root of apoE(-/-) mice was markedly increased but was significantly reduced after 8-week treatment with IL-4 mAb.. Allergic asthma accelerates atherosclerosis by modulating the balance of Teff/Treg cells in apoE(-/-) mice, which is associated with increased Th2 and Th17 cells but not Th1 cells.

Topics: Animals; Antibodies, Monoclonal; Apolipoproteins E; Asthma; Atherosclerosis; Biomarkers; Gene Expression; Immunization; Immunoglobulin E; Interleukin-17; Interleukin-4; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Plaque, Atherosclerotic; Receptors, IgE; Spleen; Th1 Cells; Th17 Cells; Th2 Cells

The immunoinflammatory response plays a critical role in the development and progression of atherosclerosis. Recent studies suggested an important role for regulatory T (Treg) cells in the inhibition of disease-related vascular inflammation. We hypothesized that induction of a specific Treg cell response to atherosclerosis-relevant antigens would be an attractive strategy to limit the development and progression of atherosclerosis through the promotion of immune tolerance.. Young or old Apoe-/- mice were subcutaneously infused for 2 weeks with either a control ovalbumin (OVA) peptide or with apolipoprotein B100 (ApoB100)-derived peptides without adjuvant. Atherosclerosis development, progression and immunologic status were assessed at 8 weeks after the end of the infusion. Treatment with ApoB100 peptides led to significant reduction of lesion development in young Apoe-/- mice (P=0.001 versus OVA group) and abrogated atherosclerosis progression in old Apoe-/- mice with already established lesions (0% progression in ApoB100 versus 17% in OVA group, P<0.005). Limitation of plaque progression was associated with reduced vascular inflammation and increased collagen content, indicative of plaque stabilization. Infusion of ApoB100 peptides did not alterantibody production but promoted a specific Treg cell response, which was associated with a reduction of both T helper type 1-related and T helper type 2-related cytokines. Interestingly, depletion of CD4+CD25+ Treg cells abrogated ApoB100 peptides-dependent immune modulation and atheroprotection.. Subcutaneous infusion of adjuvant-free ApoB100-derived peptides to Apoe-/- mice reduces atherosclerosis through the induction of a specific Treg cell response.

Topics: Animals; Apolipoprotein B-100; Apolipoproteins E; Atherosclerosis; Cells, Cultured; Cytokines; Disease Models, Animal; Disease Progression; Female; Humans; Immune Tolerance; Immunotherapy; Infusions, Subcutaneous; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Peptides; T-Lymphocytes, Regulatory; Time Factors

Atherosclerosis is an inflammatory disease. Autoimmune responses to low-density lipoproteins (LDL) contribute to its progression, whereas immunization with LDL may induce atheroprotective or proatherogenic responses. The objective of this study was to develop an atheroprotective vaccine by targeting a peptide of the LDL protein constituent apolipoprotein B-100 (apoB-100) to the nasal mucosa to induce a protective mucosal immune response.. A peptide comprising amino acids 3136 to 3155 of apoB-100 (p210) was fused to the B subunit of cholera toxin (CTB), which binds to a ganglioside on mucosal epithelia. The effect of nasal administration of the p210-CTB fusion protein on atherogenesis was compared with that of an ovalbumin peptide fused to CTB and with untreated controls. Immunization with p210-CTB for 12 weeks caused a 35% reduction in aortic lesion size in Apoe(-/-) mice. This effect was accompanied by induction of regulatory T cells that markedly suppressed effector T cells rechallenged with apoB-100 and increased numbers of interleukin (IL)-10(+) CD4(+) T cells. Furthermore, a peptide-specific antibody response was observed. Atheroprotection was also documented in apoe(-/-) mice lacking functional transforming growth factor-beta receptors on T cells.. Nasal administration of an apoB-100 peptide fused to CTB attenuates atherosclerosis and induces regulatory Tr1 cells that inhibit T effector responses to apoB-100.

Topics: Administration, Intranasal; Aerosols; Animals; Aortic Diseases; Apolipoprotein B-100; Apolipoproteins E; Atherosclerosis; Cholera Toxin; Disease Models, Animal; Female; Forkhead Transcription Factors; Humans; Immunity, Cellular; Immunity, Humoral; Immunity, Mucosal; Immunoconjugates; Interleukin-10; Mice; Mice, Knockout; Nasal Mucosa; Ovalbumin; Peptide Fragments; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; RNA, Messenger; T-Lymphocytes, Regulatory; Vaccines, Synthetic

Glucosamine sulfate (GS) is a glycosaminoglycan with anti-inflammatory and immunoregulatory properties. Here we set out to explore the effect of GS administration on markers of systemic and local inflammation in rabbits with atherosclerosis aggravated by chronic arthritis. Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intra-articular injections of ovalbumin in previously immunized rabbits. A group of these rabbits was treated prophylactically with oral GS (500 mg.kg(-1).day(-1)), and, when the animals were killed, serum was extracted and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, the femoral arteries, thoracic aorta, and synovial membranes were examined in gene expression studies and histologically. GS administration reduced circulating levels of the C-reactive protein and of interleukin-6. GS also lowered nuclear factor-kappaB activation in PBMC, and it downregulated the expression of both the CCL2 (monocyte chemoattractant protein) and cyclooxygenase-2 genes in these cells. Lesions at the femoral wall were milder after GS treatment, as reflected by the intimal-to-media thickened ratio and the absence of aortic lesions. Indeed, GS also attenuated the histological lesions in synovial tissue. In a combined rabbit model of chronic arthritis and atherosclerosis, orally administered GS reduced the markers of inflammation in peripheral blood, as well as the femoral and synovial membrane lesions. GS also prevented the development of inflammation-associated aortic lesions. These results suggest an atheroprotective effect of GS.

Topics: Animals; Arthritis, Experimental; Atherosclerosis; C-Reactive Protein; Chemokine CCL2; Chronic Disease; Cyclooxygenase 2; Electrophoretic Mobility Shift Assay; Femoral Artery; Glucosamine; Immunohistochemistry; Inflammation; Interleukin-6; Lipids; Male; Monocytes; NF-kappa B; Ovalbumin; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA; Synovial Membrane

To test the hypothesis that stimulation of chymase secretion may contribute to plaque vulnerability and inhibition of chymase activity may enhance plaque stability.. Sixty eight-week-old male Syrian golden hamsters were randomly divided into normal control group, high-cholesterol (HC) treated group, HC+ovalbumin treated group and HC+tranilast treated group. The normal control group received a normal diet while the other three intervention groups received a high-cholesterol diet for 15 weeks. Hamsters in the HC+ovalbumin treated group underwent transcatheter pharmacological triggering at the end of week 15 after antigen sensitization and those in the HC+tranilast treated group were given tranilast intragastrically for 3 weeks before euthanasia. Serological, ultrasonographic, pathologic, immunohistochemical, and gene expression studies were performed in all animals. The total number of mast cells, proportion of degranulated mast cells and the number of extracellular granules in plaques, the apoptosis rate of vascular smooth cells, the local activities of chymase, the concentration of Ang II and the expression levels of inflammatory markers as well as plaque vulnerability index all increased significantly in HC+ovalbumin treated group, but remarkably decreased in HC+tranilast treated group, in comparison with the HC treated group. These results suggest that stimulation of chymase secretion contributes to plaque vulnerability while inhibition of chymase activity enhances plaque stability. We conclude that chymase activity provides a promising therapeutic target in the stabilization of atherosclerotic plaques.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta; Apoptosis; Atherosclerosis; Body Weight; Cell Degranulation; Cholesterol; Chymases; Cricetinae; Disease Models, Animal; Disease Progression; Immunohistochemistry; Inflammation; Inflammation Mediators; Lipids; Male; Mast Cells; Mesocricetus; Microscopy, Electron, Transmission; ortho-Aminobenzoates; Ovalbumin; Peptidyl-Dipeptidase A; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rupture; Time Factors; Ultrasonography, Doppler, Duplex

Recent reports suggest dyslipidemia impairs dendritic cell (DC) function and adaptive immunity. This study aimed to characterize the effect of hypercholesterolemia on antigen-presenting cell function of DCs and DC-dependent CD4(+) T-cell responses. DCs incubated in vitro with acetylated low-density lipoprotein cholesterol with or without an acyl-coenzyme A:cholesterol acyl-transferase inhibitor maintained their ability to prime CD4(+) T cells. Analysis of T-cell proliferation and interferon-gamma and tumor necrosis factor-alpha production after ex vivo coculture of naïve CD4(+) T cells with splenic, inguinal, or iliac DCs from low-density lipoprotein receptor-deficient (LDLR(-/-)) or apolipoprotein E-deficient (ApoE(-/-)) mice fed an atherogenic diet highlighted DC efficacy in effector T-cell generation under hypercholesterolemic conditions. Adoptive transfer of carboxyfluorescein diacetate, succinimidyl ester (CFSE)-labeled naïve CD4(+) T cells in LDLR(-/-) recipients and subsequent immunization demonstrated effective priming of naïve T cells in hypercholesterolemic mice. CFSE dilution analyses revealed that hypercholesterolemic DCs were equipotent in naïve CD4(+) T-cell priming efficacy with normocholesterolemic DCs. Quantitative real-time PCR and flow cytometric analyses demonstrated that DC expression of multiple molecules involved in antigen processing, presentation, and T-cell stimulation remained unaltered by dyslipidemia. Finally, endogenous antigen-primed CD4(+) T cells responded equivalently to a secondary ex vivo antigenic challenge, regardless of whether they were primed in vivo under hypercholesterolemic or control conditions, demonstrating that all essential steps in CD4(+) T-cell responses remain intact under atherogenic conditions. This study affirms that the adaptive immune response prevails under the hypercholesterolemic conditions present in atherosclerosis. In particular, DCs remain functional antigen-presenting cells and maintain their ability to prime CD4(+) T cells even when cholesterol-loaded.

Topics: Adoptive Transfer; Animals; Antigen Presentation; Apolipoproteins E; Atherosclerosis; CD11c Antigen; CD4-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Cholesterol, Dietary; Cholesterol, LDL; Coculture Techniques; Dendritic Cells; Disease Models, Animal; Hypercholesterolemia; Interferon-gamma; Lipoproteins, LDL; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Ovalbumin; Receptors, Antigen, T-Cell; Receptors, LDL; Tumor Necrosis Factor-alpha

Dietary phytosterols significantly reduce atherosclerosis in apo E-deficient mice. Because atherosclerosis is a chronic inflammatory disease, we investigated whether the antiatherogenic effects of phytosterols are associated with reductions in proinflammatory cytokine production as well as the effect of this diet on global immunocompetence. Apolipoprotein (apo) E-deficient mice were fed a cholesterol-supplemented diet in the presence or absence of 2% dietary phytosterols for 14 wk and then immunized with ovalbumin. The relations between plasma lipid concentrations, atherosclerotic lesions, and cytokine production and proinflammatory stimuli or foreign antigens were characterized. Phytosterol-enriched diets were strongly associated with reduced plasma cholesterol concentrations and atherosclerosis in conjunction with higher anti-inflammatory [interleukin (IL)-10] and lower proinflammatory cytokine [IL-6, tumor necrosis factor (TNF)-alpha] production. In contrast, development of cytokine and chemokine responses to ovalbumin was as strong as or even improved in the phytosterol-treated mice relative to controls. The antiatherogenic effects of dietary phytosterols in apo E-knockout mice were associated with beneficial alterations in both lipoprotein metabolism and inflammatory pathways. Decreased capacity to mount proinflammatory cytokine and chemokine responses to inflammatory stimuli did not interfere with the global immunocompetence of such mice. Thus, the desirable suppression of proinflammatory cytokine production that was associated with inhibition of atherogenesis did not impair the capacity to mount responses to foreign antigens.

Topics: Animal Feed; Animals; Antigens; Apolipoproteins E; Atherosclerosis; Cell Division; Cytokines; Food, Fortified; Homeostasis; Interleukin-12; Interleukin-12 Subunit p40; Interleukin-6; Male; Mice; Mice, Knockout; Ovalbumin; Phytosterols; Protein Subunits; Spleen; Tumor Necrosis Factor-alpha