Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40% of colorectal cancer patients. The hallmarks of systemic inflammation include an increased production of ...proinflammatory cytokines and acute phase proteins that enter the circulation. While the low-level systemic inflammation is often clinically silent, its consequences are many and may ultimately lead to chronic cancer-associated wasting, cachexia. In this review, we discuss the pathogenesis of cancer-related systemic inflammation, explore the role of systemic inflammation in promoting cancer growth, escaping antitumor defense, and shifting metabolic pathways, and how these changes are related to less favorable outcome.
Thrombosis is the most feared complication of cardiovascular diseases and a main cause of death worldwide, making it a major health-care challenge. Platelets and the coagulation cascade are ...effectively targeted by antithrombotic approaches, which carry an inherent risk of bleeding. Moreover, antithrombotics cannot completely prevent thrombotic events, implicating a therapeutic gap due to a third, not yet adequately addressed mechanism, namely inflammation. In this Review, we discuss how the synergy between inflammation and thrombosis drives thrombotic diseases. We focus on the huge potential of anti-inflammatory strategies to target cardiovascular pathologies. Findings in the past decade have uncovered a sophisticated connection between innate immunity, platelet activation and coagulation, termed immunothrombosis. Immunothrombosis is an important host defence mechanism to limit systemic spreading of pathogens through the bloodstream. However, the aberrant activation of immunothrombosis in cardiovascular diseases causes myocardial infarction, stroke and venous thromboembolism. The clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is supported by the increased risk of cardiovascular events in patients with inflammatory diseases but also during infections, including in COVID-19. Clinical trials in the past 4 years have confirmed the anti-ischaemic effects of anti-inflammatory strategies, backing the concept of a prothrombotic function of inflammation. Targeting inflammation to prevent thrombosis leaves haemostasis mainly unaffected, circumventing the risk of bleeding associated with current approaches. Considering the growing number of anti-inflammatory therapies, it is crucial to appreciate their potential in covering therapeutic gaps in cardiovascular diseases.
Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, ...protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.
A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary ...fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.
Monocyte Conversion During Inflammation and Injury Kratofil, Rachel M; Kubes, Paul; Deniset, Justin F
Arteriosclerosis, thrombosis, and vascular biology,
01/2017, Letnik:
37, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There are 2 subsets of monocytes in ...mice (3 subsets in humans) that are mobilized from the bone marrow and recruited to sites of inflammation, where they carry out their respective functions in promoting inflammation or facilitating tissue repair. Our understanding of the fate of these monocyte subsets at the site of inflammation is constantly evolving. This brief review highlights the plasticity of monocyte subsets and their conversion during inflammation and injury.
Inflammation and its resolution is under-studied in medicine despite being essential for understanding the development of chronic inflammatory disease. In this review article, we discuss the ...resolution of inflammation in both a biological and translational context. We introduce the concept of impaired resolution leading to diseases like rheumatoid arthritis, Crohn's disease, and asthma, as well as the cellular and molecular components that contribute to resolution of joint, gut, and lung inflammation, respectively. Finally, we discuss potential intervention strategies for fostering the resolution process, and their implications for the therapy of inflammatory diseases.
Abstract
The resolution of inflammation (or inflammation-resolution) is an active and highly coordinated process. Inflammation-resolution is governed by several endogenous factors, and specialized ...pro-resolving mediators (SPMs) are one such class of molecules that have robust biological function. Non-resolving inflammation is associated with a variety of human diseases, including atherosclerosis. Moreover, non-resolving inflammation is a hallmark of ageing, an inevitable process associated with increased risk for cardiovascular disease. Uncovering mechanisms as to why inflammation-resolution is impaired in ageing and in disease and identifying useful biomarkers for non-resolving inflammation are unmet needs. Recent work has pointed to a critical role for balanced ratios of SPMs and pro-inflammatory lipids (i.e. leucotrienes and/or specific prostaglandins) as a key determinant of timely inflammation resolution. This review will focus on the accumulating findings that support the role of non-resolving inflammation and imbalanced pro-resolving and pro-inflammatory mediators in atherosclerosis. We aim to provide insight as to why these imbalances occur, the importance of ageing in disease progression, and how haematopoietic function impacts inflammation-resolution and atherosclerosis. We highlight open questions regarding therapeutic strategies and mechanisms of disease to provide a framework for future studies that aim to tackle this important human disease.
Nuclear factor kappa B(NF-κB) has an established role in the regulation of innate immunity and inflammation.NF-κB is also involved in critical mechanisms connecting inflammation and cancer ...development.Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal,gastric and colorectal cancers.This review will explore NF-κB’s function in inflammation-associated gastrointestinal malignancies,highlighting its oncogenic contribution to each step of carcinogenesis.NF-κB’s role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy.
Controlled immune responses to infection and injury involve complex molecular signalling networks with coordinated and often opposing actions. Eicosanoids and related bioactive lipid mediators ...derived from polyunsaturated fatty acids constitute a major bioactive lipid network that is among the most complex and challenging pathways to map in a physiological context. Eicosanoid signalling, similar to cytokine signalling and inflammasome formation, has primarily been viewed as a pro-inflammatory component of the innate immune response; however, recent advances in lipidomics have helped to elucidate unique eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions. This has advanced our overall understanding of the inflammatory response and its therapeutic implications. The induction of a pro-inflammatory and anti-inflammatory eicosanoid storm through the activation of inflammatory receptors by infectious agents is reviewed here.
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