scholarly journals Inflammatory Effects of Bothrops Phospholipases A2: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 868
Author(s):  
Vanessa Moreira ◽  
Elbio Leiguez ◽  
Priscila Motta Janovits ◽  
Rodrigo Maia-Marques ◽  
Cristina Maria Fernandes ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Therapeutic Agents ◽  
Lipid Mediators ◽  
Major Protein ◽  
Phospholipases A2 ◽  
Snake Envenomation ◽  
Structural And Functional Properties

Phospholipases A2s (PLA2s) constitute one of the major protein groups present in the venoms of viperid and crotalid snakes. Snake venom PLA2s (svPLA2s) exhibit a remarkable functional diversity, as they have been described to induce a myriad of toxic effects. Local inflammation is an important characteristic of snakebite envenomation inflicted by viperid and crotalid species and diverse svPLA2s have been studied for their proinflammatory properties. Moreover, based on their molecular, structural, and functional properties, the viperid svPLA2s are classified into the group IIA secreted PLA2s, which encompasses mammalian inflammatory sPLA2s. Thus, research on svPLA2s has attained paramount importance for better understanding the role of this class of enzymes in snake envenomation and the participation of GIIA sPLA2s in pathophysiological conditions and for the development of new therapeutic agents. In this review, we highlight studies that have identified the inflammatory activities of svPLA2s, in particular, those from Bothrops genus snakes, which are major medically important snakes in Latin America, and we describe recent advances in our collective understanding of the mechanisms underlying their inflammatory effects. We also discuss studies that dissect the action of these venom enzymes in inflammatory cells focusing on molecular mechanisms and signaling pathways involved in the biosynthesis of lipid mediators and lipid accumulation in immunocompetent cells.

scholarly journals Monoclonal Antibodies as Neurological Therapeutics

2021 ◽  
Vol 14 (2) ◽  
pp. 92
Author(s):  
Panagiotis Gklinos ◽  
Miranta Papadopoulou ◽  
Vid Stanulovic ◽  
Dimos D. Mitsikostas ◽  
Dimitrios Papadopoulos
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Therapeutic Agents ◽  
Medical Specialties ◽  
Specific Effects ◽  
Different Types ◽  
Neurological Conditions ◽  
Disease Pathways

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

scholarly journals Mechanism of lncRNA H19 in the Regulation of Lipid Accumulation and Inflammatory Response in Macrophages

2020 ◽  
Author(s):  
Xue-Mei Wang ◽  
Xiao-Ming Gao ◽  
Fen Liu ◽  
Ying Cao ◽  
Jie-Ying Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lipid Accumulation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Cholesterol Concentration ◽  
Abca1 Expression ◽  
Intracellular Lipid Accumulation ◽  
Oil Red O Staining ◽  
Oil Red O

Abstract Background and aims: Lipid accumulation of macrophages caused by oxidative stress is the key reason for the early pathological changes of atherosclerosis. LncRNA H19 repression downregulated NF-κB activation, upregulated ABCA1 expression, intracellular lipid accumulation increased, but the role of lncRNA H19 in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how lncRNA H19 affects lipid accumulation of macrophages by regulating lipid metabolism and inflammatory response.Methods and results: THP-1 macrophages were cultured with ox-LDL to form foam cells. THP-1-derived macrophages were incubated with H19 siRNA or not. Oil Red O staining was used for the determination lipid accumulation in macrophages. Enzymatic methods were performed to analyze cholesterol concentration. Both western blot and qRT-PCR were applied to detect target gene expression. ELISA was used to examine the levels of oxidative and inflammatory mediators. We found that lncRNA H19 repression reduced lipid accumulation by elevating efficiency of RCT and via upregulation of ABCA1 and PPARα expression in THP-1 derived macrophages. Further, lncRNA H19 repression upregulated PGC-1α and downregulated NF-κB signaling pathway.Conclusion: These results suggest that lncRNA H19 repression inhibits atherosclerosis by promoting RCT process and reducing inflammatory response via PGC-1α and NF-κB pathways, respectively.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

scholarly journals Pro-Resolving Lipid Mediators in the Pathophysiology of Asthma

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 284 ◽  
Author(s):  
Oxana Kytikova ◽  
Tatyana Novgorodtseva ◽  
Yulia Denisenko ◽  
Marina Antonyuk ◽  
Tatyana Gvozdenko
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Inflammatory Reaction ◽  
Therapeutic Agents ◽  
Biological Action ◽  
Lipid Mediators ◽  
Bronchial Obstruction ◽  
Specialized Metabolites ◽  
Docosahexaenoic Acids

Asthma is one of the most important medical and social problems of our time due to the prevalence and the complexity of its treatment. Chronic inflammation that is characteristic of asthma is accompanied by bronchial obstruction, which involves various lipid mediators produced from n-6 and n-3 polyunsaturated fatty acids (PUFAs). The review is devoted to modern ideas about the PUFA metabolites—eicosanoids (leukotrienes, prostaglandins, thromboxanes) and specialized pro-resolving lipid mediators (SPMs) maresins, lipoxins, resolvins, protectins. The latest advances in clinical lipidomics for identifying and disclosing the mechanism of synthesis and the biological action of SPMs have been given. The current views on the peculiarities of the inflammatory reaction in asthma and the role of highly specialized metabolites of arachidonic, eicosapentaenoic and docosahexaenoic acids in this process have been described. The possibility of using SPMs as therapeutic agents aimed at controlling the resolution of inflammation in asthma is discussed.

Preventive Role of Resveratrol Against Inflammatory Cytokines and Related Diseases

2019 ◽  
Vol 25 (12) ◽  
pp. 1345-1371 ◽  
Author(s):  
Tanzir Rafe ◽  
Parvez Ahmed Shawon ◽  
Liyad Salem ◽  
Nafij Imtiyaj Chowdhury ◽  
Farjana Kabir ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Human Subjects ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Long Run

Background:Immunity is the ultimate barrier between foreign stimuli and a host cell. Unwanted immune responses can threaten the host cells and may eventually damage a vital organ. Overproduction of inflammatory cytokines may also lead to autoimmune diseases. Inflammatory cells and pro-inflammatory cytokines can eventually progress to renal, cardiac, brain, hepatic, pancreatic and ocular inflammation that can result in severe damage in the long run. Evidence also suggests that inflammation may lead to atherosclerosis, Alzheimer’s, hypertension, stroke, cysts and cancers.Methods:This study was designed to correlate the possible molecular mechanisms for inflammatory diseases and prevent biochemical changes owing to inflammatory cytokines by using Resveratrol. Therefore, we searched and accumulated very recent literature on inflammatory disorders and Resveratrol. We scoured PubMed, Scopus, Science Direct, PLoS One and Google Scholar to gather papers and related information.Results:Reports show that inflammatory diseases are very complex, as multiple cascade systems are involved; therefore, they are quite difficult to cure. However, our literature search also correlates some possible molecular interactions by which inflammation can be prevented. We noticed that Resveratrol is a potent lead component and has multiple activities against harmful inflammatory cytokines and related microRNA. Our study also suggests that the anti-inflammatory properties of Resveratrol have been highly studied on animal models, cell lines and human subjects and proven to be very effective in reducing inflammatory cell production and pro-inflammatory cytokine accumulation. Our tables and figures also demonstrate recent findings and possible preventive activities to minimize inflammatory diseases.Conclusion:This study would outline the role of harmful inflammatory cytokines as well as how they accelerate pathophysiology and progress to an inflammatory disorder. Therefore, this study might show a potential therapeutic value of using Resveratrol by health professionals in preventing inflammatory disorders.

Morphometric study of eosinophils, mast cells, macrophages and fibrosis in the colon of chronic chagasic patients with and without megacolon

Parasitology ◽  
2007 ◽  
Vol 134 (6) ◽  
pp. 789-796 ◽  
Author(s):  
A. B. M. da SILVEIRA ◽  
S. J. ADAD ◽  
R. CORREA-OLIVEIRA ◽  
J. B. FURNESS ◽  
D. D'AVILA REIS
Keyword(s):  
Mast Cells ◽  
Cell Damage ◽  
Continuous Process ◽  
Positive Association ◽  
Inflammatory Cells ◽  
Therapeutic Agents ◽  
Morphometric Study ◽  
Chagasic Megacolon ◽  
Histology And Immunohistochemistry

SUMMARYThe mechanisms involved in the pathogenesis of chagasic megacolon are not completely characterized. Although autoimmunity may play a role in the pathogenesis of Chagas' disease, recent studies suggest a positive association of tissue parasitism, inflammation, and severity of lesions. The aim of this study was to evaluate the role of inflammatory cells and the occurrence of fibrosis in the colon of chagasic patients with and without megacolon. Samples from 26 patients were randomly selected and paraffin-embedded tissue blocks were sectioned and evaluated by histology and immunohistochemistry to analyse the occurrence and relation among eosinophils, mast cells, macrophages and fibrosis. Section analyses showed that the presence of eosinophils and mast cells in the analysed inflammatory cells has a direct correlation with fibrosis density in the chagasic megacolon. These data suggest that the megacolon's pathogenesis is based on a continuous process of cell damage. Our data propose that eosinophils, mast cells and macrophages may have a direct connection with the occurrence of fibrosis in the colon of chagasic patients. We believe that potential therapeutic agents against these cells could avoid the fibrosis process and contribute to prevent the development of chagasic megacolon.

scholarly journals Structural and Functional Peculiarities of Cytoplasmic Tropomyosin Isoforms, the Products of TPM1 and TPM4 Genes

2021 ◽  
Vol 22 (10) ◽  
pp. 5141
Author(s):  
Marina Marchenko ◽  
Victoria Nefedova ◽  
Natalia Artemova ◽  
Sergey Kleymenov ◽  
Dmitrii Levitsky ◽  
...  
Keyword(s):  
Functional Properties ◽  
Coiled Coil ◽  
Major Protein ◽  
Protein Dimers ◽  
Protein Partners ◽  
Sequence Variations ◽  
Structural And Functional Properties ◽  
Alternatively Spliced ◽  
Alternatively Spliced Exons

Tropomyosin (Tpm) is one of the major protein partners of actin. Tpm molecules are α-helical coiled-coil protein dimers forming a continuous head-to-tail polymer along the actin filament. Human cells produce a large number of Tpm isoforms that are thought to play a significant role in determining actin cytoskeletal functions. Even though the role of these Tpm isoforms in different non-muscle cells is more or less studied in many laboratories, little is known about their structural and functional properties. In the present work, we have applied various methods to investigate the properties of five cytoplasmic Tpm isoforms (Tpm1.5, Tpm 1.6, Tpm1.7, Tpm1.12, and Tpm 4.2), which are the products of two different genes, TPM1 and TPM4, and also significantly differ by alternatively spliced exons: N-terminal exons 1a2b or 1b, internal exons 6a or 6b, and C-terminal exons 9a, 9c or 9d. Our results demonstrate that structural and functional properties of these Tpm isoforms are quite different depending on sequence variations in alternatively spliced regions of their molecules. The revealed differences can be important in further studies to explain why various Tpm isoforms interact uniquely with actin filaments, thus playing an important role in the organization and dynamics of the cytoskeleton.

scholarly journals A Novel Role for Brain Natriuretic Peptide: Inhibition of IL-1β Secretion via Downregulation of NF-kB/Erk 1/2 and NALP3/ASC/Caspase-1 Activation in Human THP-1 Monocyte

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Letizia Mezzasoma ◽  
Cinzia Antognelli ◽  
Vincenzo Nicola Talesa
Keyword(s):  
Immune Responses ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Therapeutic Agents ◽  
Peptide Receptor ◽  
Caspase 1 ◽  
Wide Range

Interleukin-1β (IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents. IL-1β is a strong regulator of Brain Natriuretic Peptide (BNP), a hormone involved in cardiovascular homeostasis by guanylyl cyclase Natriuretic Peptide Receptor (NPR-1). An emerging role of BNP in inflammation and immunity, although proposed, remains largely unexplored. Here, we newly demonstrated that, in human THP-1 monocytes, LPS/ATP-induced IL-1β secretion is strongly inhibited by BNP/NPR-1/cGMP axis at all the molecular mechanisms that tightly control its production and release, NF-kB, ERK 1/2, and all the elements of NALP3/ASC/Caspase-1 inflammasome cascade, and that NALP3 inflammasome inhibition is directly related to BNP deregulatory effect on NF-kB/ERK 1/2 activation. Our findings reveal a novel potent anti-inflammatory and immunomodulatory role for BNP and open new alleys of investigation for a possible employment of this endogenous agent in the treatment of inflammatory/immune-related and IL-1β/NF-kB/ERK1/2/NALP3/ASC/Caspase-1-associated diseases.

scholarly journals Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Siyuan Luan ◽  
Xiaoxi Zeng ◽  
Chao Zhang ◽  
Jiajun Qiu ◽  
Yushang Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Esophageal Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Benefit ◽  
Therapeutic Agents ◽  
Development Of Resistance ◽  
Cellular Components

Drug resistance represents the major obstacle to get the maximum therapeutic benefit for patients with esophageal cancer since numerous patients are inherently or adaptively resistant to therapeutic agents. Notably, increasing evidence has demonstrated that drug resistance is closely related to the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic and ever-changing complex biological network whose diverse cellular and non-cellular components influence hallmarks and fates of tumor cells from the outside, and this is responsible for the development of resistance to conventional therapeutic agents to some extent. Indeed, the formation of drug resistance in esophageal cancer should be considered as a multifactorial process involving not only cancer cells themselves but cancer stem cells, tumor-associated stromal cells, hypoxia, soluble factors, extracellular vesicles, etc. Accordingly, combination therapy targeting tumor cells and tumor-favorable microenvironment represents a promising strategy to address drug resistance and get better therapeutic responses for patients with esophageal cancer. In this review, we mainly focus our discussion on molecular mechanisms that underlie the role of TME in drug resistance in esophageal cancer. We also discuss the opportunities and challenges for therapeutically targeting tumor-favorable microenvironment, such as membrane proteins, pivotal signaling pathways, and cytokines, to attenuate drug resistance in esophageal cancer.

scholarly journals Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Olga Tsave ◽  
Savvas Petanidis ◽  
Efrosini Kioseoglou ◽  
Maria P. Yavropoulou ◽  
John G. Yovos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Chemical Reactivity ◽  
Inflammatory Cells ◽  
T Cell Signaling ◽  
Cell Immunotherapy ◽  
Molecular Immunology ◽  
Anti Inflammatory

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs.

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