Animated abstract: The Pathogenic Subpopulation of Th17 Cells in Obesity

Author(s):Natalia Todosenko, Maria Vulf*, Kristina Yurova, Daria Skuratovskaia, Olga Khaziakhmatova, Natalia Gazatova, Olga Melashchenko, Olga Urazova and Larisa Litvinova

Obesity is a metabolic disease characterized by a chronic subclinical inflammatory response associated with an imbalance/dysregulation of cellular homeostasis in response to excessive nutrient intake and accumulation. CD4+ T-lymphocytes form different populations, Th1, Th2, Th9, Th17, Th22, and Treg cells, which have phenotypic and functional differences. Despite the active study of Th17 cells in severe disorders, their role in metabolic disorders, particularly in obesity, is not well understood. Th17 lymphocytes, depending on the microenvironment, can form pathogenic and nonpathogenic subpopulations. Systemic inflammation induces the reprogramming of the transcriptome of normal Th17 cells formed in epithelial tissues, which acquire new properties. A zone of overlapping states exists between IL-17A-producing cells, which does not allow a clear boundary between non-pathogenic Th17 and pathogenic Th17 lymphocytes. We assume that in obesity, the pool of inflammatory pathogenic Th17 cells with cytotoxic potential is a fraction of terminally differentiated memory lymphocytes which is responsible for developing autoimmune reactions.

Read the article: http://bit.ly/3iTEMWX

Animated abstract: Dietary Technologies to Optimize Healing from Injury-Induced Inflammation

Author(s):Barry Sears*, Mary Perry and Asish K. Saha*

Abstract

Inflammation is an acute adaptive response to injury. However, if the initial inflammatory response to an injury is not completely healed, it becomes chronic low-level inflammation that is strongly associated with many chronic disease states, including metabolic (obesity and diabetes), cardiovascular, auto-immune, and neurogenerative disorders as well as cancer. The healing process is far more complex than the initiation of inflammation. Within that complexity of healing is a sequence of events that are under profound dietary control and can be defined by specific blood markers. Those molecular events of the healing process that are under significant dietary control are termed as the Resolution Response. The purpose of this review is to describe the molecular components of the Resolution Response and how different dietary factors can either optimize or inhibit their actions. In particular, those dietary components that optimize the Resolution Response include a calorie-restricted, protein-adequate, moderate-carbohydrate, low-fat diet referred to as the Zone diet, omega-3 fatty acids, and polyphenols. The appropriate combination of these dietary interventions constitutes the foundation of Pro-Resolution Nutrition. The effect of these dietary components the actions of NF-κB, AMPK, eicosanoids, and resolvins are described in this review, as well as ranges of appropriate blood markers that indicate success in optimizing the Resolution Response by dietary interventions.

Read the article here: http://bit.ly/3Jk7Phb

Editors choice: Chronic Kidney Disease, Metabolic Syndrome, and Cardiovascular Risk: Insights and Associated Mechanistic Pathways

Author(s):Thaís Rodrigues Nogueira*, Camila Santos Marreiros and Betânia de Jesus e Silva de Almendra Freitas

Abstract

This study is a narrative review that aims to address the conceptual, characteristic, pathophysiological, and mechanistic aspects that define the profile of metabolic syndrome and chronic kidney disease. The objective was to investigate current knowledge and elucidate, through discussions on the topic, the main interrelated paths. This review was carried out unsystematically, from March to May 2020, by means of a survey of the literature indexed in the PubMed, Web of Science, and Scopus (Elsevier®) databases. The scientific materials collected showed that the cross-talk between the diseases in question is mainly based on the conditions of resistance to insulin action, endothelial dysfunction, activation pathways of the Renin- Angiotensin-Aldosterone System, and adipokine imbalance, also emphasizing the influence of atherosclerotic events in kidney damage. Furthermore, it was reinforced that inflammatory processes play an important role in the worsening and evolution of the clinical condition of patients, especially when they have underlying pathologies chronically treated for subclinical inflammation. It is expected that more original research will propose investigating other possible interactions with a view to standardized treatment of these diseases or nutritional management.

Download and read: http://bit.ly/3gubX2h

Open Access Article – Interleukin 6 Concentration in Synovial Fluid of Patients with Inflammatory and Degenerative Arthritis

Author(s):Anna Mihailova*

Volume 18, Issue 3, 2022

Published on: 25 March, 2022

Page: [230 – 233]

Pages: 4

DOI: 10.2174/1874471015666220128113319

Abstract

Aim: The present study aims to compare interleukin 6 concentration in synovial fluid in patients with known types of arthritis.

Background: Persistent synovitis without known markers, such as Rheumatoid Factor (RF), Anti- Citrullinated Protein Antibodies (ACPA), and genetic markers as HLA-B27, is not uncommon. It is valuable to determine the presence of chronic inflammation and put it in correlation with agerelated changes, which are especially relevant for middle-aged patients with mono- or oligoarthritis, when the dilemma to start disease-modifying drugs for inflammatory disease often is present. Interleukin 6 (IL-6) plays a significant role in chronic inflammation.

Objectives: IL-6 concentration in synovial fluid reflects the presence and activity of joint inflammation.

Methods: Synovial fluid was obtained from 101 patients with chronic synovitis. IL-6 concentration was determined by the immunochemical luminescence method.

Results: The median IL-6 concentration in synovial fluid in patients with osteoarthritis (OA) was 138.0 pg/ml (interquartile range (IQR) 43.4 to 296.0); in patients with rheumatoid arthritis was 2516.5 pg/ml, (IQR 1136.0 to 25058.0); in reactive arthritis 2281.0 pg/ml (IQR 1392.0 to 8652.0); psoriatic arthritis 1964.0 pg/ml (IQR 754.0 to 7300.0); ankylosing spondylitis 2776.0 pg/ml (IQR 514.7, 3944.0); in a group with negative RF, ACPA and HLA-B27 inflammatory arthritis 2163.0 pg/ml (IQR 822.0 to 7875.0). There is statistically significant difference of IL-6 concentration comparing OA and each inflammatory arthritis group, p<0.0001.

Conclusion: IL-6 detection in the synovial fluid is helpful in arthritis evaluation. The results show that an IL-6 level over 1000 pg/ml suggests the diagnosis of inflammatory arthritis. Read now: https://bit.ly/3QUmno0

Aims & Scope – Recent Advances in Inflammation & Allergy Drug Discovery

(Recent Patents on Inflammation & Allergy Drug Discovery)

ISSN (Print): 2772-2708
ISSN (Online): 2772-2716

Volume 15, Issue 2, 2021

Aims & Scope

Recent Advances in Inflammation & Allergy Drug Discovery publishes full-length/mini-reviews, research articles, letters, case reports, perspectives, systematic reviews and thematic issues on inflammation and allergy research, including new strategies of diagnosis, treatment and prevention of allergic and inflammatory diseases. The journal covers all pharmacological aspects of inflammation and allergy, including mediators of inflammation and allergy, as well as cellular processes and molecular mechanisms involved in inflammation, immune dysfunction and allergies in every area of medicine. Articles on important and recent patents in the field are also included in the journal. The journal is essential reading for all researchers involved in inflammation and allergy drug design and discovery. Read now: https://bit.ly/3PHo0oZ

Article by Disease | Statins in Aortic Disease

Bentham Cardiovascular Disorders Collection | Cardiovascular Disorders | Aortic Coarctation 

 

Abstract:

Background: Numerous studies indicate that statins have multiple beneficial actions (known as ‘pleiotropic actions’) on cardiovascular system through the improvement of endothelial dysfunction, inflammation, oxidative stress, excessive arterial thrombosis, and stabilization of the atherosclerotic plaque. Aortic disease primarily consists of aortic valve stenosis, aortic valve regurgitation, aneurysm disease, and genetic disorders such as Marfan syndrome, bicuspid aortic valve and aortic coarctation. Many studies have revealed the cardioprotective actions of statins in aortic disease.

Objective: Our aim was to present current data concerning the value of treatment with statins in aortic diseases.

Methods: A thorough search of PubMed and the Cochrane Database was conducted to identify the studies and novel articles related to the use of statins in aortic disease.

Results: Numerous studies in animals and humans indicate a beneficial effect of treatment with statins in the previous conditions apart from a few conflicting data.

Conclusion: There is a need of further investigation in this field, especially for the estimation of the optimal type and dose of statins required in each clinical condition of aortic disease.

 

Read out more at: http://www.eurekaselect.com/node/157165/article

Press Release | Tumor necrosis associate with atherosclerotic lipid accumulation

 

The article by Dr. Alexander N. Orekhov et al. is published in Current Pharmaceutical Design, 2018

Inflammation is currently a well-documented component of atheroslcerosis pathogenesis, which plays a role at each stage of the disease development. Local activation of endothelial cells causing increase endothelial permeability, infiltration of intima with atherogenic low-density lipoprotein (LDL), and recruitment of circulating immune cells is regarded as a first step of atherosclerotic plaque development. Circulating modified LDL is immunogenic, and forms highly atherogenic aggregates with antibodies that are later accumulated in the arterial wall. In growing plaques, circulating monocytes are attracted to the lesions site by cytokine signalling. In the arterial wall, monocyte-derived macrophages play an active role in lipid accumulation, internalizing large associates of lipoprotein particles by means of phagocytosis. Phagocytic cells with cytoplasm filled by stored lipid droplets called foam cells can be found in developing plaques in large quantities. There is evidence that lipid accumulation in the arterial wall cells in its turn activates cytokine signalling leading to a vicious cycle and further aggravating the disease. However, the immune response in atherosclerosis is not limited to enhanced inflammation, since anti-inflammatory cytokines and alternatively-activated (M2) macrophages are also present in atherosclerotic plaques. Anti-inflammatory M2 macrophages are likely to be responsible for hte resolution of the inflammatory response and tissue remodelling observed in advancing plaques. At later stages of lesion development, lipofibrous plaquest with high lipid contents and cell counts give rise to fibrous plaques that contain less cells and lipids, but more extracellular matrix material.

Although the involvement of cytokines in atherosclerotic lesion development is currently beyond doubt, quantitative evaluation of the expression of pro- and anti-inflammatory cytokines in the plaque remains to be studied in detail. In this study, we analyzed the distribution of two cytokines, pro-inflammatory TNFα and anti-inflammatory CCL18, in sections of human carotid atherosclerotic plaques at different stages of development. Our results demonstrated that both pro- and anti-inflammatory cytokines were present in the plaques, although differently distributed and likely expressed by different cells, and appeared to be enriched as compared to grossly normal intima taken as a control. To test whether the expression of TNFα and CCL18 is increased in atherosclerotic lesions, we performed gene expression analysis by means of quantitative PCR. We found that the expression of both cytokines was indeed increased in different types of atherosclerotic lesions. Moreover, it followed a bell-shaped distribution across the 4 studied plaque stages, gradually increasing from the early initial lesions to fatty streaks, reaching maximum in lipofibrous plaques, and decreasing again in fibrous plaques. This distribution was consistent with our previously published observations of bell-shaped changes of atherosclerotic lesion cellularity, proliferative activity, collagen synthesis and lipid content at different stages of the development. For TNFα, the maximal increase in atherosclerotic lesions reached 2 folds as compared to normal tissue, while for CCL18, this number was 1.5 folds.

We next investigated the relationship between pro- and anti-inflammatory cytokine production and lipid accumulation in cells. To that end, we used cultured human monocyte-derived macrophages with lipid accumulation induced by incubation with atherogenic LDL obtained from atheroslcerosis patients’ blood serum. Non-atherogenic LDL obtained from healthy donors, which did not cause cholesterol accumulation in cultured cells, was used as a control. We found that cholesterol accumulation in macrophages caused by atherogenic LDL treatment was associated with up-regulation of both TNFα and CCL18. The increase in relative gene expression was statistically significant (p=0.05 for TNFα and p=0.023 for CCL18) as compared to non-atherogenic LDL treatment.

In this work, we report the increased expression of pro-inflammatory cytokine TNFα and anti-inflammatory CCL18 in human atherosclerotic lesions, which could be observed microscopically and in gene expression analysis by means of quantitative PCR. Furthermore, we demonstrate that the increase of pro- and anti-inflammatory cytokines expression is associated with cholesterol accumulation caused by atherogenic LDL in cultured cells. It is likely that lipid accumulation is the trigger of cytokine expression in atherosclerotic lesions, since the maximum of expression is observed in atherosclerotic lesions most enriched in lipids. We discuss the implications of these findings for atheroslcerosis pathogenesis, postulating that a splash of cytokine signalling occurs in lesions with the highest lipid contents. We hypothesize that both pro- and anti-inflammatory responses take place in human atherosclerotic lesions, but are probably characterized by different dynamics. While pro-inflammatory signalling occurs rapidly in response to triggering stimuli and is transient, anti-inflammatory response is relatively slow and long-lasting. Under favorable conditions, resolution of inflammation should lead to a healing process and plaque stabilization, while chronic inflammation may aggravate the disease development.

Browse the Article at: http://www.eurekaselect.com/165293/article

Press Release | Modified LDL particles activate inflammatory pathways in monocyte-derived macrophages

The article by Dr. . Alexander N. Orekhov et al. is published in Current Pharmaceutical Design, 2018

 

One of the main characteristics of atherosclerosis is the accumulation of lipids in the intimal layer of the arterial wall. In atherosclerotic plaques, phagocytic cells, such as macrophages, engulf atherogenic low-density lipoprotein (LDL) particles, but are unable to process them, and thus become foam cells, having cytoplasm packed with lipid droplets. Foam cells are characterized by several typical features: they have decreased ability to migrate, while displaying enhanced production of pro-inflammatory cytokines. Therefore foam cells participate in maintaining chronic inflammation in the lesion. Such changes of phenotype in comparison to normal macrophages should be based on changes in gene expression patterns of these cells. The study of foam cell formation is of key importance to our understanding of atherosclerosis pathogenesis and for the development of novel diagnostic and therapeutic tools. However, little is known so far on gene expression changes that take place during conversion of macrophages to foam cells.

Previous studies have shown several clusters of genes up- or down-regulated in macrophages in response to oxidized LDL, which is known to be atherogenic. Among the up-regulated genes were scavenger receptors SCA and CD36, nuclear receptors PPARγ, LXRα and RXRγ, and cholesterol efflux protein ABCA1. Regarding the inflammatory response, modified LDL appeared to trigger up-regulation of genes with anti-inflammatory activities, such as IL1-RA, DSCR1, annexin 1, and the Burton’s tyrosine kinase repressor SH3 protein, and down-regulation of a number of pro-inflammatory genes, including leukotriene A4 hydrolase, cathepsin G, elastase 2, RNase A family 2 and 3 proteins, cytochromeb-245, and CD64. However, modern powerful tools, such as transcriptome analysis, may provide more detailed data on change of gene expression patterns during atherosclerotic plaque development and reveal causative relationships between gene expression patterns and pathologic phenotypic alterations.

We performed a transcriptome analysis of macrophages treated with atherogenic LDL that causes intracellular cholesterol accumulation. We used the strategy of upstream analysis for causal interpretation of the expression changes. This strategy has three major steps: (1) analysis of promoters and enhancers of identified differentially expressed genes to identify transcription factors involved in the process under study; (2) reconstruction of signaling pathways that activate these transcription factors; and (3) identification of master-regulators of these pathways.

In this study, we used human monocyte-derived macrophages treated with different lipoprotein-containing samples : high-density lipoprotein (HDL), native LDL, which does not induce cholesterol accumulation in cultured cells, and 3 types of modified atherogenic LDL (oxidized LDL, acetylated LDL and desialylated LDL). In this experiment, low concentrations of native LDL and HDL did not increase the total or esterified cholesterol content in cultured macrophages. After incubation with the substances, mRNA was isolated from the cells and analysed using high-throughput sequencing on HiSeq 1500.

In this study, we discovered 27 transcription factors, including c-Ets, GR-alpha, BRCA1, E2F-1, E2F-6 and EGR-1, that were potentially responsible for the changes in gene expression induced by modified atherogenic LDL. These transcription factors were used for identifying the master-regulators (genes and proteins) responsible for regulation of large cascades of differentially expressed genes. The most reliable of identified master-regulators were IL7R, TIGIT, CXCL8, F2RL1, EIF2AK3, IL7, TSPYL2, ANXA1, DUSP1 and IL15. In the Discussion section of our paper, we give more detail on each of these master-regulators. In general, the genes that were up-regulated in response to lipid accumulation in macrophages induced by atherogenic LDL were mostly involved in inflammation and immune response, and not in cholesterol metabolism. Our results suggest a possibility that it is not cholesterol accumulation that causes an innate immunity response, but rather the immune response is a consequence of a cellular reaction to modified LDL. These results highlight the importance of the inflammatory component in the pathogenesis of atherosclerosis.

Browse the article details at: Modified LDL Particles Activate Inflammatory Pathways in Monocyte-derived Macrophages: Transcriptome Analysis

ARTICLE BY DISEASE – The Prevalence of the Classical and Non-Classical Cardiovascular Risk Factors in Multiple Sclerosis Patients

 

ARTICLE BY DISEASE ON “ACOUSTIC NEUROMA”

 

Background: Inflammation is known to play a role in cererovascular risk. Multiple sclerosis (MS) is a neurodegenerative disease that is initially characterized by inflammatory changes in the brain. We hypothesized that due to chronic inflammation, MS patients would present with a higher levels of cardiovascular (CV) risk factors than non-MS patients.

Methods: We performed a retrospective chart review on 206 MS patients and 142 control patients suffering from meningiomas and acoustic neuromas, non inflammatory, non autoimmune diseases of the brain. The obtained data included fasting lipid profiles, plasma glucose, systolic and diastolic blood pressure (BP), serum levels of homocysteine and uric acid, data on iron status, smoking habit, and list of medications. In addition, data on indicators of MS disease severity was obtained for MS patients.

Results: MS patients had significantly higher total plasma cholesterol, p = 0.01, and plasma high density lipoprotein, P <0.001, but lower plasma glucose, P <0.001, and systolic BP, P = 0.001, than non-MS patients. In addition, MS patients had lower erythrocyte sedimentation rate and serum vitamin B12, but higher serum folic acid and vitamin D3 than non-MS patients. A positive correlation was observed between plasma glucose and the extended disability status scale (EDSS), P = 0.008, and between plasma glucose and the rate of clinical relapse, P = 0.001.

Conclusion: The MS pathophysiology may be among factors for the lower CV risk factors in MS patients. Future studies should examine whether the chronic use of many pharmacological agents influence CV risk factors in MS patients.

 

For more details, please visit: http://www.eurekaselect.com/node/107982/article

ARTICLES BY DISEASE – The Prevalence of the Classical and Non-Classical Cardiovascular Risk Factors in Multiple Sclerosis Patients

ARTICLE BY DISEASE ON “ACOUSTIC NEUROMA”

 

Abstract:

Background: Inflammation is known to play a role in cererovascular risk. Multiple sclerosis (MS) is a neurodegenerative disease that is initially characterized by inflammatory changes in the brain. We hypothesized that due to chronic inflammation, MS patients would present with a higher levels of cardiovascular (CV) risk factors than non-MS patients.

Methods: We performed a retrospective chart review on 206 MS patients and 142 control patients suffering from meningiomas and acoustic neuromas, non inflammatory, non autoimmune diseases of the brain. The obtained data included fasting lipid profiles, plasma glucose, systolic and diastolic blood pressure (BP), serum levels of homocysteine and uric acid, data on iron status, smoking habit, and list of medications. In addition, data on indicators of MS disease severity was obtained for MS patients.

Results: MS patients had significantly higher total plasma cholesterol, p = 0.01, and plasma high density lipoprotein, P <0.001, but lower plasma glucose, P <0.001, and systolic BP, P = 0.001, than non-MS patients. In addition, MS patients had lower erythrocyte sedimentation rate and serum vitamin B12, but higher serum folic acid and vitamin D3 than non-MS patients. A positive correlation was observed between plasma glucose and the extended disability status scale (EDSS), P = 0.008, and between plasma glucose and the rate of clinical relapse, P = 0.001.

Conclusion: The MS pathophysiology may be among factors for the lower CV risk factors in MS patients. Future studies should examine whether the chronic use of many pharmacological agents influence CV risk factors in MS patients

For more details, please visit: http://www.eurekaselect.com/node/107982/article