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1.
Maresin-1 and Inflammatory Disease.
Saito-Sasaki, N, Sawada, Y, Nakamura, M
International journal of molecular sciences. 2022;(3)
Abstract
Inflammation is an essential action to protect the host human body from external, harmful antigens and microorganisms. However, an excessive inflammation reaction sometimes exceeds tissue damage and can disrupt organ functions. Therefore, anti-inflammatory action and resolution mechanisms need to be clarified. Dietary foods are an essential daily lifestyle that influences various human physiological processes and pathological conditions. Especially, omega-3 fatty acids in the diet ameliorate chronic inflammatory skin diseases. Recent studies have identified that omega-3 fatty acid derivatives, such as the resolvin series, showed strong anti-inflammatory actions in various inflammatory diseases. Maresin-1 is a derivative of one of the representative omega-3 fatty acids, i.e., docosahexaenoic acid (DHA), and has shown beneficial action in inflammatory disease models. In this review, we summarize the detailed actions of maresin-1 in immune cells and inflammatory diseases.
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An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19.
Argano, C, Mallaci Bocchio, R, Lo Monaco, M, Scibetta, S, Natoli, G, Cavezzi, A, Troiani, E, Corrao, S
International journal of molecular sciences. 2022;(5)
Abstract
Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.
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The design and discovery of phospholipase A2 inhibitors for the treatment of inflammatory diseases.
Batsika, CS, Gerogiannopoulou, AD, Mantzourani, C, Vasilakaki, S, Kokotos, G
Expert opinion on drug discovery. 2021;(11):1287-1305
Abstract
AREAS COVERED This review article summarizes the most important synthetic PLA2 inhibitors developed to target each one of the four major types of human PLA2 (cytosolic cPLA2, calcium-independent iPLA2, secreted sPLA2, and lipoprotein-associated Lp-PLA2), discussing their in vitro and in vivo activities as well as their recent applications and therapeutic properties. Recent findings on the role of PLA2 in the pathobiology of COVID-19 are also discussed. EXPERT OPINION Although a number of PLA2 inhibitors have entered clinical trials, none has reached the market yet. Lipoprotein-associated PLA2 is now considered a biomarker of vascular inflammation rather than a therapeutic target for inhibitors like darapladib. Inhibitors of cytosolic PLA2 may find topical applications for diseases like atopic dermatitis and psoriasis. Inhibitors of secreted PLA2, varespladib and varespladib methyl, are under investigation for repositioning in snakebite envenoming. A deeper understanding of PLA2 enzymes is needed for the development of novel selective inhibitors. Lipidomic technologies combined with medicinal chemistry approaches may be useful tools toward this goal.
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Human gut-microbiome interplay: Analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management.
Jiang, Z, Li, L, Chen, J, Wei, G, Ji, Y, Chen, X, Liu, J, Huo, J
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2021;:104946
Abstract
Microorganisms have been known to coexist in various parts of human body including the gut. The interactions between microbes and the surrounding tissues of the host are critical for fine fettle of the gut. The incidence of such microorganisms tends to vary among specific type of cancer affected individuals. Such microbial communities of specific tumor sites in cancer affected individuals could plausibly be used as prognostic and/or diagnostic markers for tumors associated with that specific site. Microorganisms of intestinal and non-intestinal origins including Helicobacter pylori can target several organs, act as carcinogens and promote cancer. It is interesting to note that diets causing inflammation can also increase the cancer risk. Yet, dietary supplementation with prebiotics and probiotics can reduce the incidence of cancer. Therefore, both diet and microbial community of the gut have dual roles of prevention and oncogenesis. Hence, this review intends to summarize certain important details related to gut microbiome and cancer.
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5.
Effects of grape products on inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.
Ghalishourani, SS, Farzollahpour, F, Shirinbakhshmasoleh, M, Kolahdouz, S, Ghaedi, E, Behrouzian, M, Haghighian, HK, Campbell, MS, Asbaghi, O, Moodi, V
Phytotherapy research : PTR. 2021;(9):4898-4912
Abstract
This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to determine the effects of grapes and grape products on inflammation and oxidative stress among adults. PubMed, Scopus, ISI Web of Science, and Cochrane Library databases were searched up to July 2020 to identify RCTs investigating the effects of grape and grape products on inflammatory and oxidative stress markers. Weighted mean differences (WMD) were pooled using a random-effects model. Of the 8,962 identified studies, 24 RCTs (27 arms) were included in the statistical analysis. Grape products significantly reduced serum C-reactive protein (CRP) levels (WMD: -0.35 mg/L; 95% CI: -0.62, -0.09, p = .008), but they had no significant effect on serum tumor necrosis factor-alpha (TNF-α) (WMD = -1.08 pg/ml; 95% CI: -2.29, 0.11, p = .07), interleukin-6 (IL-6) (WMD = 0.13 pg/ml; 95% CI: -0.35, 0.60, p = .60), total antioxidant capacity (TAC) (WMD = 0.15; 95% CI: -0.35, 0.65, p = .54), or malondialdehyde (MDA) (WMD = 0.14; 95% CI: -0.64, 0.92, p = .72). The analysis indicated possible decreasing effects of grapes and grape products on CRP, but they might not be able to change IL-6, TNF-α, TAC, and MDA concentrations. Nonetheless, further studies are warranted before definitive conclusions may be reached.
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Strategies to DAMPen COVID-19-mediated lung and systemic inflammation and vascular injury.
Bime, C, Casanova, NG, Nikolich-Zugich, J, Knox, KS, Camp, SM, Garcia, JGN
Translational research : the journal of laboratory and clinical medicine. 2021;:37-48
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Abstract
Approximately 15%-20% of patients infected with SARS-CoV-2 coronavirus (COVID-19) progress beyond mild and self-limited disease to require supplemental oxygen for severe pneumonia; 5% of COVID-19-infected patients further develop acute respiratory distress syndrome (ARDS) and multiorgan failure. Despite mortality rates surpassing 40%, key insights into COVID-19-induced ARDS pathology have not been fully elucidated and multiple unmet needs remain. This review focuses on the unmet need for effective therapies that target unchecked innate immunity-driven inflammation which drives unchecked vascular permeability, multiorgan dysfunction and ARDS mortality. Additional unmet needs including the lack of insights into factors predicting pathogenic hyperinflammatory viral host responses, limited approaches to address the vast disease heterogeneity in ARDS, and the absence of clinically-useful ARDS biomarkers. We review unmet needs persisting in COVID-19-induced ARDS in the context of the potential role for damage-associated molecular pattern proteins in lung and systemic hyperinflammatory host responses to SARS-CoV-2 infection that ultimately drive multiorgan dysfunction and ARDS mortality. Insights into promising stratification-enhancing, biomarker-based strategies in COVID-19 and non-COVID ARDS may enable the design of successful clinical trials of promising therapies.
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Pathophysiology of Obesity.
Kessler, C
The Nursing clinics of North America. 2021;(4):465-478
Abstract
As obesity continues a relentless march across the globe, researchers are beginning to unlock the complicated interplay among obesity, its ensuing inflammation, and downstream complications. It is becoming clear that obesity is a chronic, multifactorial, inflammatory disease of maladaptive adipose tissue mass involving complex links among genetics, hormonal-signaling, and the environment. Understanding the intricate pathogenesis of obesity and its sequela will go a long way to discovering better treatment options and lessen anti-obesity bias.
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Glucocorticoid-Like Activity of Escin: A New Mechanism for an Old Drug.
Gallelli, L, Cione, E, Wang, T, Zhang, L
Drug design, development and therapy. 2021;:699-704
Abstract
Saponins are a group of compounds used in clinical practice in the management of several diseases. Escin is a natural mixture of triterpene saponins which mainly consist of several isoforms, in which the α- and β-escin are predominant. β-escin is the major active compound that exerts a therapeutic effect by relieving tissue edema, promoting venous drainage, and reducing inflammation. In this review, we describe the features of its glucocorticoid-like activity that could explain its clinical effects. Using PubMed, Embase Cochrane library and reference lists for articles published until October 01, 2020, we documented that escin is likely able to exert its anti-inflammatory and anti-edematous effects through a glucocorticoid-like activity, but without the development of glucocorticoid-like adverse drug reactions.
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Asthma and obesity: endotoxin another insult to add to injury?
Lad, N, Murphy, AM, Parenti, C, Nelson, CP, Williams, NC, Sharpe, GR, McTernan, PG
Clinical science (London, England : 1979). 2021;(24):2729-2748
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Abstract
Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.
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Energy Provisioning and Inflammasome Activation: The Pivotal Role of AMPK in Sterile Inflammation and Associated Metabolic Disorders.
Shrungeswara, AH, Unnikrishnan, MK
Anti-inflammatory & anti-allergy agents in medicinal chemistry. 2021;(2):107-117
Abstract
BACKGROUND Body defenses and metabolic processes probably co-evolved in such a way that rapid, energy-intensive acute inflammatory repair is functionally integrated with energy allocation in a starvation/ infection / injury-prone primitive environment. Disruptive metabolic surplus, aggravated by sedentary lifestyle induces chronic under-activation of AMPK, the master regulator of intracellular energy homeostasis. Sudden increase in chronic, dysregulated 'sterile' inflammatory disorders probably results from a shift towards calorie rich, sanitized, cushioned, injury/ infection free environment, repositioning inflammatory repair pathways towards chronic, non-microbial, 'sterile', 'low grade', and 'parainflammation'. AMPK, (at the helm of energy provisioning) supervises the metabolic regulation of inflammasome activation, a common denominator in lifestyle disorders. DISCUSSION In this review, we discuss various pathways linking AMPK under-activation and inflammasome activation. AMPK under-activation, the possible norm in energy-rich sedentary lifestyle, could be the central agency that stimulates inflammasome activation by multiple pathways such as 1: decreasing autophagy, and accumulation of intracellular DAMPs, (particulate crystalline molecules, advanced glycation end-products, oxidized lipids, etc.) 2: stimulating a glycolytic shift (pro-inflammatory) in metabolism, 3: promoting NF-kB activation and decreasing Nrf2 activation, 4: increasing reactive oxygen species (ROS) formation, Unfolded Protein Response (UPR) and Endoplasmic Reticulum (ER) stress. CONCLUSION The 'inverse energy crisis' associated with calorie-rich, sedentary lifestyle, advocates dietary and pharmacological interventions for treating chronic metabolic disorders by overcoming / reversing AMPK under-activation.