Inflammatory bowel disease (IBD) is a chronic and relapsing disease caused by a dysregulated immune response to host intestinal microbiota that occurs in genetically predisposed individuals. IBD encompasses two major clinical entities: ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn disease (CD), which might affect any segment of the gastrointestinal tract. Despite the prevalence of IBD is increasing worldwide, therapy remains suboptimal, largely because the variability of causative mechanisms, raising the need to develop individualized therapeutic approaches targeted to each individual patient. In this context, patients-derived intestinal organoids represent an effective tool for advancing our understanding on IBD’ s pathogenesis. Organoid 3D culture systems offer a unique model for dissecting epithelial mechanisms involved IBDs and test individualized therapy, although the lack of a functional immune system and a microbiota, two driving components of the IBD pathogenesis, represent a major barrier for their exploitation in clinical medicine. In this review we have examined how to improve the translational utility of intestinal organoids in IBD and how co-coltures of 3D or 2D organoids and immune cells and/or intestinal microbiota might help to overcome these limitations.

Inflammatory Bowel Disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown but is thought to involve a hypersensitive immune response to environmental antigen, including the microbiota. Diagnosis and monitoring of disease is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on PET and SPECT imaging of inflammatory mediators, and how this may be applied to the microbiota.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, is a disease of chronic inflammatory conditions of the intestinal tract due to disturbance of the inflammation and immune system. Symptoms of IBD include abdominal pain, diarrhea, bleeding, reduced weight, and fatigue. In IBD, the immune system attacks the intestinal tract's inner wall, causing chronic inflammation and tissue damage. In particular, IL-6 and IL-17 act on immune cells, including T cells and macrophages, to amplify the immune responses so that tissue damage and morphological changes occur. Of note, excessive calorie intake and obesity also affect the immune system due to inflammation caused by lipotoxicity and changes in lipids supply. Similarly, individuals with IBD have alterations in liver function after sustained high-fat diet feeding. In addition, excess dietary fat intake, along with alterations in primary and secondary bile acids in the colon, can affect the onset and progression of IBD because inflammatory cytokines contribute to insulin resistance; the factors include the release of inflammatory cytokines, oxidative stress, and changes in intestinal microflora, which may also contribute to the disease progression. However, interfering with de novo fatty acid synthase by deleting the enzyme acetyl-CoA-carboxylase 1 in intestinal epithelial cells leads to the deficiency of epithelial crypt structures and tissue regeneration, which seems to be due to Lgr5+ intestinal stem cell function. Thus, conflicting reports exist regarding high-fat diet effects on IBD animal models. This review will focus on the pathological basis of the link between dietary lipids intake and IBD and cover currently available pharmacological approaches.

IBD, encompassing CD and UC, are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The bidirectional communication between the gut and the brain, known as the GBA, is disrupted in IBD, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBD affects the brain's inflammatory response system, hormonal axis, and BBB integrity, influencing gut microbiota and clinical responses to probiotics. This review aims to explore the links between dysregulations in the GBA, serum biomarkers, and the development of MCI and NDDs. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on NDDs. Studies suggest a potential link between IBD and extraintestinal complications such as MCI and NDDs. Mechanisms include systemic inflammation, BBB dysfunction, autoimmune responses, GBA dysfunction, medication effects, and comorbidities. Serum biomarkers, including vitamin D3, C-reactive protein, high-sensitivity C-reactive protein, vitamin B12, homocysteine, serum amyloid, neuron-specific enolase, neurofilament light chain, S100 proteins, brain-derived neurotrophic factor, IL-6, LP-2 associated phospholipase, prostaglandin E2, IL-1β, and TNF-α, have been investigated for their potential to predict MCI but current results are lacking clarity.

(1) Background: Inflammatory bowel diseases (IBD) involve complex interactions between genetic factors, aberrant immune activation, and gut microbial dysbiosis. While metabolomic studies have focused on feces and serum, fewer investigations have examined the intestinal mucosa despite its crucial role in metabolite absorption and transport. The current study aimed to identify novel mucosal metabolic pathways that are altered during chronic colitis and to determine microbial contributions to such changes. (2) Methods: The chronic Dextran sulfate sodium (DSS) colitis was induced for five weeks in 7-9-week-old wild-type C57BL/6J male mice followed by microbial profiling with targeted 16srRNA sequencing service. Mucosal metabolite measurements were performed by Metabolon (Morrisville, NC). The data were analyzed using the bioinformatic tools Pathview, MetOrigin, and Metaboanalyst. (3) Results: Our novel findings demonstrated increases in several host- and mi-crobe-derived purine, pyrimidine, endocannabinoid, and ceramide metabolites in colitis. Origin analysis revealed microbial-related tryptophan metabolites kynurenine, anthranilate, 5-hydroxyindoleacetate, and C-glycosyltryptophan were significantly increased in colon mucosa during chronic inflammation and strongly correlated with disease activity. (4) Conclusions: These findings offer new insights into the pathophysiology of IBD and provide novel potential targets for microbial-based therapeutics.

Inflammatory Bowel Disease (IBD) is a chronic and progressive inflammatory disorder affecting the gastrointestinal tract (GT) caused by a wide range of genetic, microbial, and environmental factors. IBD is characterized by chronic inflammation, decreased gut microbial diversity and dysbiosis, with a lower amount of beneficial bacteria and a concomitant increase of pathogenic species. It is well known that dysbiosis is closely related to the induction of inflammation and oxidative stress, this last caused by an imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity that leads to cellular ROS accumulation. ROS are responsible for the intestinal epithelium oxidative damage and the increased intestinal permeability found in IBD patients and their reduction could represent a potential therapeutic strategy to limit the IBD progression and alleviate its symptom. Recent evidence highlighted that dietary polyphenols, natural antioxidants, are able to maintain redox equilibrium in the GT preventing gut dysbiosis, intestinal epithelium damage and radical inflammatory responses. Here, we suggest that the relatively new foodomics approaches, together with new technologies for promoting the antioxidative properties of dietary polyphenols, including novel delivery systems, chemical modifications and combination strategies, may provide critical insight to determine the clinical value of polyphenols for IBD therapy and a comprehensive perspective for implementing natural antioxidants as potential IBD candidate treatment.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Inflammatory bowel disease (IBD), a heterogeneous group of recurring inflammatory condi-tions of the digestive system that encompass both ulcerative colitis (UC) and Crohn’s disease (CD), pose a significant public health challenge, currently lacking a definitive cure. The specif-ic etiopathogenesis of IBD is not yet fully understood, but a multifactorial interplay of genetic and environmental factors is suspected. A growing body of evidence supports the involve-ment of intestinal dysbiosis in the development of IBD, including the effects of dysbiosis on the integrity of the intestinal epithelial barrier, modulation of the host immune system, alter-ations in the enteric nervous system, and the perpetuation of chronic inflammation. A com-prehensive understanding of these mechanisms is important to define preventive measures, to develop new effective and lasting treatments and to improve disease outcome. This review examines the complex tri-directional relationship between gut microbiota, mucosal immune system, and intestinal epithelium in IBD. In addition, nonpharmacological and behavioral strategies aimed at restoring a proper microbial-immune relationship will be suggested.

The crosstalk between gut microbiota, intestinal epithelial cells, and innate and adaptive immune system governs the maintenance of the intestinal homeostasis. Any interference in this tight dialogue and in the processes preserving cellular homeostasis (e.g., autophagy) may dysregulate the immune response and impair the clearance of harmful bacteria favoring the dysbiotic alteration of the microbic flora that leads to chronic inflammation. Gut dysbiosis is strongly associated with gastrointestinal inflammatory disorders, among them the inflammatory bowel disease (IBD). This review discusses the current knowledge on IBD, from the genetic background of high-risk patients to the molecular mechanisms underlying the disease, the contribution of the microbic flora, and the role of autophagy in intestinal epithelial cells and provides the state of art regarding the targeted-nutritional approaches aimed to restore the beneficial crosstalk between an “anti-inflammatory” microbiota and the host. Analysis of the molecular pathogenesis of IBD will help identify genetic and diet-associated risk factors and thus suggest personalized strategies to prevent and manage the disease to improve quality of life with long-term maintenance of the remission phase.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in host which influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics; chemotherapeutic drugs and change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromillieu. Ligands released from dying microbes induce TLR mimicry on interaction with TLR abnormally which skew hypoxia and sterile inflammation contributing to severity of disease like IBD autoimmunity and cancer. Various modalities/interventions practiced across the globe and future strategies for microbiota based therapeutic approaches with special emphasis on tumor and inflammatory diseases are reviewed here. Therefore the major aim and scope of this manuscript is to both discuss various modalities/interventions across the globe and to design future microbiota based therapeutic approaches for mitigating the burden with special emphasis on tumor and Inflammatory diseases.

Over the past two decades, a growing body of evidence observations have shown group two innate lymphoid cells (ILC2) to be critical drivers of Type 2 (T2) inflammatory responses associated with allergic inflammatory conditions such as asthma. ILC2 release copious amounts of pro-inflammatory T2 cytokines – interleukin (IL)-4, IL-5, IL-9, and IL-13. This review provides a comprehensive overview of the newly discovered regulatory subtype of ILC2 described in murine and human mucosal tissue and blood. These KLRG1+ILC2 have the capacity to produce the anti-inflammatory cytokine, IL-10. Papers compiled in this review were based on query of PubMed and Google Scholar for articles published from 2000-2023 using keywords “IL-10” and “ILC2”. Studies with topical relevance to IL-10 production by ILC2 were included. ILC2 respond to microenvironmental cues including retinoic acid (RA), IL-2, IL-4, IL-10, IL-33, as well as neuropeptide mediators such as neuromedin-U (NMU), prompting a shift towards IL-10 and away from T2 cytokine production. In contrast, TGF-β attenuates IL-10 production by ILC2. Immune regulation provided by IL-10+ILC2s holds potential significance for management of T2 inflammatory conditions. The observation of context-specific cues which alter phenotype of ILC warrants examining characteristics of ILC subsets to determine the extent of plasticity or whether the current classification of ILCs requires refinement.

Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can drive to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observed that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy of liver diseases..

People with HIV (PWH) experience higher rates of cardiovascular events (CVEs) compared with the general population. A substantial body of evidence supports that select biomarkers of inflammation (soluble CD14 [sCD14], soluble CD163 [sCD163], highly sensitive C-reactive protein [hs-CRP], interleukin-6 [IL-6]), and coagulation (D-dimer) are elevated in PWH and related to increased rates of CVEs. Our previous work showed that smoking compared with nonsmoking was associated with significantly elevated sCD14, a biomarker of monocyte activation. We aimed to explore the effect of electronic cigarette (EC) provision on inflammatory biomarkers in PWH who smoked daily and then switched to an EC. Nineteen PWH were enrolled in a pilot study in which an EC and e-liquid were provided weekly or 8 weeks. Blood specimens for inflammatory biomarker analysis were obtained at baseline (BL) and at week 8. Biomarker levels were high at BL and did not differ significantly at week 8. There were small nonsignificant reductions in sCD163 and CRP levels. Non-significant increases in IL-6, D-dimer and sCD14 levels were also noted. Use of ECs for 8 weeks does not appear to significantly increase or decrease inflammatory biomarker levels in SWH. Further research with larger samples and a control group is needed.

Inflammation is a conserved process that involve the activation of immune and non-immune cells aiming at protecting the host from bacteria, viruses, toxins and injury. However, unresolved inflammation and permanent release of pro-inflammatory mediators are responsible for the promotion of a condition called “low-grade systemic chronic inflammation”, characterized by tissue and organ damages, metabolic changes and increased susceptibility to non-communicable diseases. Several studies have demonstrated that different dietary components may influence modifiable risk factors for diverse chronic human pathologies. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are well recognized anti-inflammatory and immunomodulatory agents able to influence many aspects of the inflammatory process. The aim of this article is to review the recent literature that relates to the modulation of human disease, such as rheumatoid arthritis, by n-3 PUFAs.

Spondyloarthritis comprises of a group of inflammatory diseases of the joints and spine with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Background: Persistent up regulation of NF-κB leads to chronic inflammation and subsequent microglial activation and takes neurons towards death by activating death receptor domains and the p53 pathway. Thus, inhibition of NF-κB may lead to more effective treatment for Parkinson’s disease. Therefore, we have used mangiferin, specific inhibitor of NF-κB in this study. Method: The study utilized male Wistar rats weighing 200-250 gm (n=8 in each group). Stereotactic surgery of rats was done to induce 6-OHDA lesioning in rats. On day 42, rats were subjected to behavioural studies to evaluate effect of mangiferin and their brains were taken out after euthanasia to perform biochemical and molecular studies. Results: Mangiferin significantly increases locomotor parameters in 6-OHDA lesioned rats. It also decreases activity of Cyclooxygenase enzyme which then leads to decrease concentration of inflammatory cytokines. Microglial inflammation was also substantially reduced by reducing MPO concentration. Oxidative stress burden was also reduced after treatment with mangiferin as indicated by increase in Total Antioxidant Capacity, SOD and Catalase and reduction in concentration of MDA. Treatment with mangiferin also reduces burden of oxidative stress by increasing the activity of NRF2/ARE pathway. Activity of Caspase 3 and 9 was also significantly reduced after treatment with mangiferin. Significant decrease in activity of both Cox1 and Cox 2 was also observed. Maximum improvement in all parameters was observed in rats treated with grouping of mangiferin 45mg.kg-1 and levodopa 10mg.kg-1. Treatment with levodopa alone has no significant effect on biochemical and molecular parameters though it significantly improves behavioural parameters. Conclusion and Implications: Results of this study suggest that mangiferin has protective effect in hemi-parkinsonian rats by inhibiting NF-κB. Current treatment of Parkinson’s disease does not target the underlying problem of the disease. Therefore, combination therapy of mangiferin and levodopa can be helpful in better management of Parkison’s.

Purinergic signaling is that nucleotides (especially ATP) and adenosine are utilized as transmitter molecules, which play an important role in the immune system. In the extracellular ventricle, ATP plays a significant role of pro-inflammatory molecules mainly through activating P2 receptors, while adenosine plays the role as anti-inflammatory molecule mainly through activating P1 receptors. As we know，neutrophils are the most abundant immune cells in our circulation and have become an essential part of coordinating a series of complex events during inflammatory diseases. However, due to the destruction of inflammatory substances from neutrophils, the activation of neutrophils is fine-tuned, and purinergic signaling is associated with this process. As a matter of fact, altering the balance between P2 and P1 signals is of great importance for neutrophils to exert immune activities properly. Here, we review the role of purinergic signaling in regulatory function of neutrophils during inflammatory disease, and then discuss the potential contribution of targeted purinergic signals in the treatment of the neutrophil during inflammatory diseases.

Inflammation is a natural protective process through which the immune system responds to injury, infection, or irritation. However, hyperinflammation or long-term inflammatory response can cause various inflammatory diseases. Although idebenone was initially developed for the treatment of cognitive impairment and dementia, it is currently used to treat various diseases. However, its anti-inflammatory effects and regulatory functions in inflammatory diseases is yet to be elucidated. Therefore, this study aimed to investigate the anti-inflammatory effects of idebenone in cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation. Murine models of cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation were generated, followed by treatment with various concentrations of idebenone. Additionally, lipopolysaccharide-stimulated macrophages were treated with idebenone to elucidate its anti-inflammatory effects at the cellular level. Idebenone treatment significantly improved survival rate, protected against tissue damage, and decreased the expression of inflammatory enzymes and cytokines in mice models of sepsis and systemic inflammation. Additionally, idebenone treatment suppressed inflammatory responses in macrophages, inhibited the NF-κB signaling pathway, reduced reactive oxygen species and lipid peroxidation, and normalized the activities of antioxidant enzyme. Idebenone possesses potential therapeutic application as a novel anti-inflammatory agent in systemic inflammatory diseases and sepsis.

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location and disease endotype. We found sexual dimorphism in expression of COVID-19 genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2 and TMPRSS4, were highly upregulated in both sexes. Overall, changes in COVID-19 gene expression were specific to Th2 high molecular endotype of asthma, and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors correlated with loss of club and ciliated cells in Th2 high asthma, while the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) associated with an increase in goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype and changes in epithelial heterogeneity as factors underlying asthmatic susceptibility, or lack thereof, to COVID-19.

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells and fibroblasts, that producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

Bronchial asthma (BA) is considered a chronic inflammatory disorder associated with airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a clinical feature of BA, which promotes the inflammatory responses in bronchial/airway epithelial cells. Smokers and nonsmokers with asthma have been shown to have increases in several OS and inflammatory biomarkers. A few studies suggest a relationship between antioxidant intake from diet/supplements and BA in smoking and nonsmoking asthmatics. Dietary carotenoids and vitamin C (VC) intake might reduce BA risk in smokers and/or non-smokers. Evidence is lacking on the protective role of antioxidant vitamin and/or mineral consumption against BA in smokers and nonsmokers with respect to inflammation and OS biomarkers. Therefore, the aim of this review is to highlight current knowledge regarding the relations between antioxidant intake, BA and its associated biomarkers in smokers and nonsmokers.

The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.

Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

N-palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This study aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. Therapeutic impact of PEA reverberates across diverse physiological systems, as the central nervous system, gastrointestinal tract, vascular network, digestive and respiratory system. Additionally, it was effective in pain management, reduction of inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.

Background: The UK dairy sheep industry is relatively small but growing, particularly for cheese and yogurt products. Anecdotally, sheep milk (SM) is better tolerated by humans than cows’ milk and could have environmental as well as health benefits. All milk contains sub-micron particles called extracellular vesicles (EV) which are mainly derived from the mammary epithelium. Physiologically, milk derived EV are thought to aid development of infant immunity and the microbiome but may also have health benefits to adult humans. Methods: Using sequential ultracentrifugation vesicles of &lt;1µm (LEV) followed by &lt;200nm (sEV) were isolated from six individual sheep during mid lactation. RNA was extracted and microRNA analysed by RTqPCR for sequences previously identified in cows’ milk. Human THP-1 monocytes were differentiated into macrophages and incubated with SM-derived LEV and sEV in the presence of pro-inflammatory LPS to measure effects on secretion of the chemokine CCL-2 or in the presence of DMNQ and fluorescent dihydrorhodamine-1,2,3 to measure reactive oxygen species. Results: LEV induced an increase in ROS in both monocytes and macrophages, whilst sEV decreased DMNQ-mediated ROS in macrophages but not monocytes. Interestingly, the LEV did not induce CCL2 release, however they increased LPS-induced CCL2 secretion in monocytes but not macrophages. miR26a, miR92a, miR125b, miR155, miR223, were identified in both sEV and LEV by RT-qPCR and could be responsible for modulation of ROS and CCL2 expression. Conclusions: These findings suggest that sheep milk can influence human monocyte/macrophage responses and so is worthy of further investigation for its potential human and non-human animal health benefits.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Background: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing PCOS and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M (OSM), a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to PCOS pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the PCOS (n = 32) or the control group (n = 32). Blood samples were obtained between the 3rd and 5th days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein (CRP), low-density lipoprotein, high-density lipoprotein, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin estradiol, and OSM were analyzed. Results: OSM levels were significantly lower, but CRP levels were substantially higher in the PCOS group than in the control group (p = .002, p = .001, respectively). OSM was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = .329, p = .017; ρ = .386, p = .005; ρ = .440, p = .001; ρ = .316, p = .023, respectively). Conversely, there was no correlation between OSM and total testosterone level (ρ = .220; p = .118). In the context of inflammation and metabolic parameters, OSM was inversely correlated with CRP, Homeostatic Model Assessment for Insulin Resistance score (HOMA-IR), and low-density lipoprotein cholesterol (LDL) (ρ = .353, p = .019; ρ = .275, p = .048; ρ = .470, p &lt; .001, respectively). The performance of Oncostatin M for diagnosing PCOS showed 50% sensitivity, 75% specificity, and 63% accuracy (p = .009) in ROC curve analysis. Conclusions: Plasma OSM levels were considerably lower in patients with PCOS than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of PCOS. Thus, OSM may be a novel therapeutic target for PCOS and metabolic complications.

The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individual susceptibility to viral infection. In turn, SARS-CoV-2 can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via ACE2 принимая во внимание его влияние на, other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of LDL, launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of those diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate a crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18 and gasdermin D. Production of these proinflammatory chemokines is a beginning of local and general inflammation, what results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. NLRP3 inflammasome is a critical complex in the mediation of inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP syndrome. Herein presented the article delineate molecular mechanisms of those processes, indicating directions of future advance.

Inflammation is considered an important target for stroke therapy because it induces secondary brain damage after the initial ischemic insult. Peripheral monocytes migrate to the brain parenchyma after a central insult. They then differentiate to macrophages in a positive feedback fashion contributing to damage instead of ischemic resolution and inflammation control. A cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R), decreases neurodegeneration after ischemia with central anti-inflammatory activity. This study aims to determine whether the central anti-inflammatory effect of 4R is effective against peripheral inflammation triggered by brain ischemia. To investigate the anti-inflammatory effect of 4R, we treated macrophages with lipopolysaccharide (LPS) as an inflammatory model, followed by treatment with 4R. Microarray transcriptome analysis of over 30,000 genes identified the differential expression of 393 genes. Genes related to inflammation, cell adhesion, and transcription were validated with qPCR, and reduced expression was determined. Quantification of NF-kB phosphorylation served as a marker for the modulation of inflammation through gene transcription. Our results show that 4R was associated with a reduction in NFKB1 and ITGB5 gene expression, increased phosphorylation of NF-kB, and a decrease in macrophage adhesion in a blood-brain barrier model. These results indicate that 4R can partially modulate the peripheral immune response, making 4R a potential drug against post-ischemic inflammation.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can diminish the quality of life of both children and adults in academic, occupational, and social contexts. The kynurenine pathway (KP) contains a set of enzymatic reactions involved in tryptophan (TRP) degradation. It is known to be associated with the risk of developing ADHD. This review will address the KP and underlying mechanism of inflammation in ADHD. Potential inflammatory biomarkers reported in the most recent studies are summarized. Although a strong neuroimmunological basis has been established due to advances of recent neurobiological research, the pathophysiology of ADHD remains unclear.

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in-depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.

Asthma is the most common chronic disease in children. It is characterized by difficulty in breathing and chronic airway inflammation associated with narrowing of the airways, and airway hyperresponsiveness. If left untreated, asthma can lead to respiratory distress and even death. A number of medications are available and prescribed to manage asthma. Yet despite that, only half of the asthmatic patients are able to control their condition. Extracellular vesicles (EVs) play an important role in transporting contents such as nucleic acids, proteins, and lipids to other cells. While EVs have been extensively studied as biomarkers of various pathological states, evidence indicates that they can play protective and therapeutic roles in mitigating diseases such as cancer, cardiovascular disease and asthma. Here we propose to conduct a systematic review that provides a detailed analysis of the therapeutic effect of EVs in mitigating the primary (inflammation, airway hyperresponsiveness) and secondary outcomes (airway remodelling, molecular indices of cellular signalling, and inflammatory mediators in serum) associated with asthma in preclinical studies.

Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila, and Bifidobacterium spp. are observed. Epigallocatechin gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.

The lethal combination involving TB and HIV, known as 'syndemic’ diseases synergistically act upon one another to magnify the disease burden. Individuals on ART are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic markers still remain a grey area of investigation. Here, we reviewed the latest research developments in IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Cardiovascular disease is the most common cause of death. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases, so anti-inflammatory and antioxidant agents that modulate redox balance have become the targets of research to evaluate their molecular mechanisms and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant effects due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also stands out for its anti-inflammatory activity, possibly interrelated with its antioxidant effect, as well as for its modulation of lipid and glucose metabolism. Considering the potential positive effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, this paper describes the molecular and cellular mechanisms related to the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, especially atherosclerosis.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Background: The systemic inflammatory index (SII) is a new inflammatory marker that has been the subject of various studies in diseases with chronic inflammation. Diabetic nephropathy is also a disease that goes with chronic inflammation. We aimed to evaluate the relationship be-tween SII and diabetic nephropathy. Methods: Patients with diabetes who applied to our outpatient clinic are included in the study. Diabetic patients are divided into two groups: those with diabetic nephropathy and those with-out. In addition, healthy individuals who applied to our clinic for general check-ups during these dates are included as control group. The SII values and other characteristics of the three study groups are compared. Results: The median SII value for those with DKI was 584 (178-4819); for those without DKI, it was 282 (64-618); and for the control group, it was 236 (77.5-617) (p<0.001). SII was significantly and positively correlated with BMI, weight, blood glucose, HbA1c, CRP and creatinine, and neg-atively correlated with glomerular filtration rate (GFR) value. The SII value higher than 336 has 75% sensitivity and 70% specificity in detecting DKI. Conclusion: The SII value could predict diabetic kidney injury in diabetics and it could be used as an adjunctive diagnostic tool.

End-stage renal disease (ESRD) is associated with fatigue and physio-somatic symptoms. The aims of this study are to delineate the associations between severity of fatigue and physio-somatic symptoms and glomerular filtration rate, inflammatory biomarkers, and Wnt/catenin-pathway proteins. The Wnt-pathway related proteins β-catenin, Dickkopf-related protein 1 (DKK1), R-spondin-1, and sclerostin were measured by ELISA technique in 60 ESRD patients and 30 controls. The Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to assess severity of FF symptoms. ESRD is characterized by a significant increase in the total FF score, muscle tension, fatigue, sadness, sleep disorders, GI symptoms, and a flu-like malaise. The total FF score was significantly correlated with serum levels of urea, creatinine, phosphate, and copper (positively), and β-catenin, eGFR, hemoglobin, albumin, and zinc (inversely). The total FF score was associated with the number of total dialysis and weekly dialysis sessions, and these dialysis characteristics were more important in predicting FF scores than eGFR measurements. Partial Least Squares analysis showed that the FF score comprised two factors which are differently associated with biomarkers: a) 43.0% of the variance in fatigue, GI symptoms, muscle tension, sadness, and insomnia is explained by hemoglobin, albumin, zinc, β-catenin, and R-spondin-1; and b) 22.3% of the variance in irritability, concentration and memory impairments by increased copper and cations/chloride ratio, and male sex. ESRD patients show high levels of fatigue and physio-somatic symptoms which are associated with hemodialysis and mediated by dialysis-induced changes in inflammatory pathways, the Wnt/catenin pathway, and copper.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in the rat. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expressions of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

Background: Polycystic ovary syndrome is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Blood samples were obtained between the third and fifth days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0 .017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p &lt; 0.001, respectively). The diagnostic performance of oncostatin M, C-reactive protein, homeostasis model assessment of insulin resistance, and non-high-density lipoprotein cholesterol for polycystic ovary syndrome is as follows: Oncostatin M, sensitivity: 50%, specificity: 75%, Accuracy: 63%, p = 0.009; C-reactive protein, sensitivity: 84%, specificity: 61%, Accuracy: 74%, p = 0.004; homeostasis model assessment of insulin resistance, sensitivity: 72%, specificity: 81%, Accuracy: 77%, p &lt; 0.001; and non-high-density lipoprotein cholesterol; sensitivity: 72%, specificity: 75%, accuracy: 73%, p &lt; 0.001. Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic complications.

Background. The aim of this study is to examine whether biomarkers of the immune-inflammatory response (IRS) and endogenous opioid (EOS) systems are associated with affective symptoms in schizophrenia. Methods. We recruited 115 schizophrenia patients and 43 healthy controls and assessed the Hamilton Depression (HDRS) and Anxiety (HAM-A) rating Scale scores as well as serum levels of interleukin (IL)-6, IL-10, eotaxin (CCL11), high mobility group box 1 (HMGB1), Dickkopf-related protein 1 (DKK1), and mu (MOR) and kappa (KOR) opioid receptors.Results. The HDRS and HAM-A scores are significantly and positively correlated with a) psychosis, hostility, excitation, mannerism, negative symptoms, psychomotor retardation, and formal thought disorders; and b) lowered scores on semantic and episodic memory, executive functions, and attention tests as measured with the Brief Assessment of Cognition in Psychiatry. Both HDRS and HAM-A are significantly increased in non-responders to treatment as compared with partial responders. Both affective scores are strongly associated with latent vectors extracted from all symptoms, reflecting overall severity of psychosis (OSOS), and neurocognitive test scores, reflecting a generalized cognitive decline (G-CoDe). The HDRS score was strongly and positively associated with IL-6, HMGB1, KOR, and MOR levels, and the HAM-A score with IL-6, IL-10, CCL11, HMGB1, KOR, and MOR levels. A single latent trait may be extracted from OSOS, G-CoDe, and the HDRS and HAMA scores, and this latent vector score is strongly predicted by HMGB1, MOR, and DKK1.Conclusion. Immune-inflammatory and EOS pathways contribute to the phenome of schizophrenia, which comprises OSOS, affective, and physiosomatic symptoms, and G-CoDe.

The importance of various markers such as sclerostin, Dickkopf-1 (DKK-1), Irisin, receptor activator of NF-kB ligand (RANKL), and Vitamin D have been well studied in bone metabolism. Additionally, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and Interleukine-6 (IL-6) have been identified to hinder muscle protein synthesis, leading to the loss of muscle and strength. However, a research gap exists in the understanding their role in muscle function and physical activity. Therefore, this study aims to explore the serum levels of sclerostin, DKK-1, irisin, IL-6, RANKL, Vitamin D, and TNF-α and assess their relationships with upper and lower body strength in young adults. In this study, 38 college-aged students 18-23 years participated and completed the protocols. The participants’ lower and upper body strength were assessed by the vertical jump test (Just Jump, Probotic, AL) with a Tendo FitroDyne (Tendo Sports Machines, Trencin, Slovak Republic) and handgrip (HG) dynamometry (Takei Scientific Instruments, Yashiroda, Japan), respectively. Fasting morning blood samples were analyzed for serum levels of the biomarkers by ELISA. The results indicate significant sex differences in sclerostin, DKK-1, irisin, and vitamin D levels (p<0.05). Furthermore, a positive association was observed between sclerostin, DKK-1, and vitamin D, with lower body muscle performance variables (p<0.05). Conversely, a significant negative correlation was observed between TNF-α and upper-body muscle performance variables (p<0.05). The results suggest that these markers may have a distinct effect on muscle performance, underscoring the need for further investigation to elucidate the concept of muscle-bone crosstalk.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

Lichens are a life form in which algae and fungi have a symbiotic relationship. A lichen has various biological activities, including anti-inflammatory and anti-proliferative activities. Inflammation is a response caused by various factors, such as infection by pathogens or tissue damage; excessive reactions can contribute to the etiology of chronic diseases, such as asthma, brain damage, and serious tissue damage. This study demonstrates the anti-inflammatory effect of ethyl acetate extract from Phlebia sp. on NF-κB and AP-1 pathways in the lipopolysaccharide-treated RAW 264.7 cell. Especially, Phlebia sp. extract inhibits the phosphorylation of AP-1 signaling (c-Fos and c-Jun) and its upstream MKK/MAPKs (MKK4, MKK7 and JNK), which induced a decrease in the production of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in downstream of AP-1 signaling. Furthermore, Phlebia sp. extract inhibited the production of final inflammatory effector molecules involved in AP-1 signaling, including nitric oxide (NO) and prostaglandin E2 (PGE2). Here, we report that Phlebia sp. extract has the potential to be developed as an anti-inflammatory agent.

Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients - obs-AMI and MINOCA - NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI, a larger LVEDV and a lower LVEF compared to normoglycemic ones. Conversely, MINOCA patients showed similar myocardial damage, irrespective of glycemia. Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

As symbionts of fungi and algae, lichens produce a variety of secondary products which pharmacological activities. This study aimed to investigate the anti-inflammatory activities of Heterodermia hypoleuca and its main compound, atraric acid. The results confirmed that atraric acid could regulating induced pro-inflammatory cytokine, nitric oxide, induced nitric oxide synthase and cyclooxygenase-2 expression by lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Means while, atraric acid down-regulated expression of phosphorylated IκB, ERK and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results show that atraric acid has an anti-inflammatory effect and its molecular mechanism may be involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its value as a potential therapeutic for inflammatory diseases.

The Fas associated Death Domain (FADD) is an adaptor protein that predominantly transduces apoptosis signal from death receptor (DR) to activate caspases, leading to the initiation of apoptotic signaling and the coordinated removal of damaged, infected, or unwanted cells. In addition to its apoptotic functions, FADD is involved in signaling pathways related to autophagy, cell proliferation, necroptosis, and cellular senescence, indicating its versatile role in cell survival and proliferation. The subcellular localization and intracellular expression of FADD play a crucial role in determining its functional outcomes, thereby highlighting the importance of spatiotemporal mechanisms and regulation. Furthermore, FADD has emerged as a key regulator in inflammatory signaling, contributing to immune responses and cellular homeostasis. This review provides a comprehensive summary and analysis of cellular dynamics of FADD in regulating of programmed cell death and inflammation through distinct molecular mechanisms associated with various signaling pathways.

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section one addresses the relationship between the anti-inflammatory bioactivities of different phospholipids in relation to their structures and compositions. Sections two and three are dedicated to the structures, functions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option due to its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.

Inflammation is the response of the immune system to infection and injury, with complex interactions with the body, tissues and cells, and plays an important role in the initiation and progression of many diseases such as cancer and cardiovascular disease. Traditional excipients functioning as drug delivery systems can reduce the side effects of systemic distribution of inflammatory drugs. Oil phase, a common excipient in nanoemulsions (NEs), has the advantages of assisting the formation of emulsions, loading lipophilic drugs, thermodynamic stability, wide sources, low price and easy availability. In particular, some of them, like linolenic acid and medium chain triglyceride (MCT), also function as inhibitors of systemic inflammation marker and vascular inflammation marker. However, the influences of different oil phases on the construction of NEs and their distribution in vivo have not been fully investigated. Herein, Tween 80 and ethyl alcohol were screened out as emulsifiers and co-emulsifiers, and three different oil phases used in clinical practice widely, including MCT, oleic acid (OA), and ethyl oleate (EO), were selected as the oil phase to prepare NEs delivery platform. Three NEs had consistent size, potential, morphology, excellent stability and mitochondrial localization function. Importantly, they exhibited superior cellular uptake capacity in inflammatory-injuried human umbilical vein endothelial cells and significantly targeted the brain, lung, heart and thoracic aorta in the lipopolysaccharide-induced mouse and zebrafish larvae inflammation models. Meanwhile, the fluorescence intensities of three NEs were different in these organs, suggesting that their differential enrichment might provide alternative delivery platform for disease treatment in the corresponding organs.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

Oligonol is a low-molecular-weight polyphenol derived from lychee fruit. This study was conducted to examine whether oligonol has an ameliorative effect on diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and changes in serum glucose, C-peptide, insulin, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) levels as well as body weight and food and water consumption were assessed. Furthermore, rat pancreases were analyzed for weight, ROS generation, TBARS level, insulin content, and protein expressions of phosphor (p)-p38, p-extracellular-signal regulated kinase 1/2, p-inhibitor of nuclear factor kappa Bα, nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Markers of diabetes were shown to be decreased by oligonol administration and histological damage in the pancreas was also ameliorated. These results indicate that oligonol exerts antidiabetic activities, which may be mediated via antioxidative, stress-related, anti-inflammatory signaling.

Urethral pain syndrome (UPS) is still a pathology in which the diagnosis is formulated as a "diagnosis of exclusion". The exact pathogenetic mechanisms are not yet fully understood and clear recommendations for the prevention and treatment of UPS are absent. The goal of the study was to assess the condition of the tissues in the female urethra in UPS, by using transvaginal ultrasound (TVUS) and cross-polarization optical tomography (CP OCT). TVUS showed an expansion in the diameter of the internal lumen of the urethra, especially in the proximal region compared with the norm. Compression elastography revealed areas with increased stiffness (presence of fibrosis) in urethral and surrounding tissues. When studied with CP OCT it was shown that with UPS, the structure of the tissues in most cases was changed: trophic alterations in the epithelium (hypertrophy or atrophy) and fibrosis of underlying connective tissue were observed. The proximal fragment of the urethra with UPS underwent changes identical to those of the bladder neck. This paper showed that the introduction of new technology — CP OCT — in conjunction with TVUS will allow verification of structural changes in tissues of the lower urinary tract at the level of their architectonics and will help doctors understand better the basics of the UPS pathogenesis.

Chronic kidney disease is a critical health crisis in the US, affecting about 37 million adults. Known as "the silent killer" because it is often undiagnosed until it has reached a stage of progression. Renal dysfunction causes many adverse effects to the body's biological mechanisms, such as fluid electrolyte and pH balance, blood pressure regulation, excretion of toxins and waste, vitamin D metabolism, and hormonal regulation. Many CKD patients experience hyperkalemia, hyperphosphatemia, chronic metabolic acidosis, bone deterioration, blood pressure abnormalities, and edema. Symptoms experienced may be minimized, and the disease's progression may be slowed through an appropriate diet, which is why medical nutrition therapy is a critical aspect of the medical intervention for CKD. The current KDOQI recommendations are proposed as well as the physiological mechanisms behind the recommendations. Current biological explanations of the effects of a whole foods plant-based diet are included for possible contrast with the current renal diet. Strong evidence continues to support the importance of proper nutrition in the prevention and progression of kidney disease.

Objective: A previous study showed that schizophrenia is accompanied by lowered levels of trace/metal elements including cesium. There are no data whether changes in cesium, rubidium and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of schizophrenia. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia) and the cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and CCL11 (eotaxin) in 120 schizophrenia patients and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in schizophrenia patients as compared with controls. Serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β. Moreover, there were significant inverse associations between serum cesium levels and the BPRS, FF, HAM-D and SANS scores and positive correlations between cesium and neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic and semantic memory and executive functions) and neuro-immune pathways as well.

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury, pain, as well as acute and chronic diseases. Since long-term uses of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly-crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) were found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E2 (PGE2) production. In an air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells including neutrophils, monocytes and lymphocytes, and tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a steroid). Notably, PVRE also inhibited PGE2, similar to dexamethasone and indomethacin (an NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS ― NO and COX-2 ― PG pathways, and that PVRE could be a promising anti-inflammatory material for diverse issue injuries.

Background: We aimed to assess the association between DII and PD and the mediation effect of DII in the association of PD with systemic inflammation. Using the National Health and Nutrition Examination Survey (NHANES) 2009-2010, 2011-2012 and 2013-2014, participants that received periodontal exam and provided dietary recall data were included. The inflammatory potential of diet was calculated via DII. Periodontitis was defined according to the 2012 case definition. The clinical outcomes of interest were mean periodontal probing (PPD), mean clinical attachment loss (CAL) and thresholds of PPD and CAL. White blood cells (WBC), segmented neutrophils and C-reactive protein (CRP) were used as proxies for systemic inflammation. The periodontal measures were regressed across DII values using adjusted multivariate linear regression. Adjusted mediation analysis appraised the influence of DII in the association of periodontitis and systemic inflammation. 10,178 participants were included. DII was significantly correlated with mean PPD, mean CAL, thresholds of PPD and CAL, WBC, segmented neutrophils and DII (p&lt;0.01). A linear regression logistic adjusted for multiple confounding variables confirmed the association between DII and mean PPD (B = 0.02, Standard Error [SE]: 0.02, p&lt;0.001) and CAL (B = -0.02, SE: 0.01, p&lt;0.001). The association of mean PPD and mean CAL with both white blood cells and segmented neutrophils were mediated by DII (from 2.1 to 3.5%, p&lt;0.001). In the 2009-2010 subset, the association of mean CAL with serum CRP was mediated by DII (52.0%, p&lt;0.01). In conclusion, inflammatory diet and PD may be associated. Also, the inflammatory diet significantly mediated the association of leukocyte counts and systemic inflammation with periodontitis.

Geniposide is a major ingredient in the herb gardenia, and this study investigated effects of geniposide on lipopolysaccharide-stimulated macrophages (RAW 264.7). Griess reagent assay, Fluo-4 calcium assay, dihydrorhodamine 123 assay, multiplex cytokine assay, quantitative RT-PCR, and flow cytometry assay were done using RAW 264.7. Data showed that geniposide at concentrations of 10, 25, and 50 μM reduced significantly levels of nitric oxide, intracellular Ca2+, and hydrogen peroxide in lipopolysaccharide-stimulated RAW 264.7. Multiplex cytokine assay represented geniposide at concentrations of 10, 25, and 50 μM meaningfully suppressed levels of IL-6, G-CSF, MCP-1 and MIP-1α in RAW 264.7 provoked by lipopolysaccharide; additionally, geniposide at concentrations of 25 and 50 μM meaningfully suppressed levels of TNF-α, IP-10, GM-CSF, and MIP-1β. Flow cytometry assay represented that geniposide reduces significantly the level of phosphorylated P38 MAPK in RAW 264.7 provoked by lipopolysaccharide. Geniposide meaningfully suppressed lipopolysaccharide-induced transcription of inflammatory target genes such as Chop, Jak2, Fas, c-Jun, c-Fos, Stat3, Nos2, Ptgs2, Gadd34, Asc, Xbp1, Nlrp3, and Par-2. Taken together, geniposide exerts anti-inflammatory effects in lipopolysaccharide-stimulated macrophages via calcium-P38 MAPK pathway.

Background: The aim of this study has been to investigate if inflammatory biomarkers such as the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have any correlation with the recurrence of pleomorphic adenomas (PA) in patients afflicted by this disease. Methods: A retrospective multicentre study involving two Italian centres, the Maxillofacial Sur-gery at the Policlinico Federico II in Naples and the ENT and Maxillofacial Surgery at the IRCCS G. Pascale National Cancer Institute in Naples, has been performed. The study, involving 608 pa-tients who had received a diagnosis of PA, was conducted between January 2000 and January 2020. A Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cut-off values for the SII, PLR and NLR. A linear regression model (LRM) and a non-linear logistic re-gression model (NLRM) were realized with respect to the NLR, PLR and SII. Results: The highest performance was achieved by the NLR (cut-off 2.960) with the AUC = 0.91, with an accuracy of 96.1%, sensitivity of 78.4% and specificity of 97.2%, PPV = 64.4% and NPV = 98.6%. The LRM and NLRM including all the haematological parameters did not increase the per-formance in terms of recurrence detection. Conclusion: The NLR is an excellent support tool in predicting the recurrence of PA with a cut-off of 2.960. It can be a good reference point for surgical decision-making and follow-up in clinical practice.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and these efforts continue to be con-troversial. Drug repurposing strategies are a promising alternative to de-novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushroom have been investigated for various allergic diseases. However, antiaging and anti-inflammatory activities of inotodiol under different types of oxidative stress and impact of inotodiol on collagen and hyaluronan synthesis are not sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (the inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulation such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced overexpressions of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role of pure inotodiol/inotodiol concentrate in prevention of skin aging. These results enlighten anti-inflammatory and anti-aging effect of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications.

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

This study focused on the impact of the treatment with the hypomethylating agent 5-Azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD, catalase, CAT, glutathion peroxidase, GPx, and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, and CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, and increased CAT activity compared with healthy subjects, with not changes in SOD, GPx and GRd activities, and AOPP levels. When analyzed the evolution from early- to advanced stages of the disease, the GPx activity, GSSG/GSH ratio, LPO and AOPP increased, with a reduction in CAT. GPx changes were related with the presence of risk factors such as high-risk IPSS-R or mutational score. Besides, there was an increase in IL-2, IL-6, IL-8 and TNF-α plasma levels, with further increase of IL-2 and IL-10 from early to advanced stage of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generates oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.

In the modern world, the problem of antibiotic therapy is acute. Despite the diversity of existing antibiotic drugs, their efficacy decreases as new, resistant forms of pathogenic microorganisms emerge. It is extremely difficult to control such processes and even more difficult to treat severe bacterial infections. In such situations, an individual approach to each patient is required and physicians need parameters to estimate the efficacy of antibiotic therapy. This review discusses the significance of monitoring the content of antibiotics in the blood for this purpose, in combination with the content of inflammatory markers, such as C-reactive protein and procalcitonin. The basic principles of antibiotic therapy, and factors in the resistance of microorganisms to antibiotics, are examined. Approaches to assess the efficacy of antibiotic therapy, as well as methods to detect antibiotics and inflammatory markers in the blood of patients, and comparative assessment of their capabilities and limitations, are described.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion of interleukin (IL)-1β. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL receptor deficient mice. CETP expression did not change lipid-stained lesion areas but decreased macrophage content (CD68), neutrophil accumulation (LY6G) and aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone marrow-derived cells reduces inflammatory features of atherosclerosis. These novel mechanistic observations may help explain the failure of CETP inhibitors to reduce atherosclerotic events in humans.

The bark of Rhus verniciflua Stokes (RVS) is used as a food additive and herbal medicine for various inflammatory disorders and cancer in Eastern Asia. RVS exerted anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, but whether this effect occurs in macrophages after oral administration has not been determined. We used a thioglycollate-induced peritonitis model to obtain macrophages from mice given RVS. We examined the systemic inflammatory response to intraperitoneal LPS. RVS-treated mice had an increased population of peritoneal exudate cells expressing CD11b and SRA. Increased uptake of Alexa Fluor 488-labeled acetylated lipoprotein was observed in monocyte-derived macrophages from RVS-treated mice. When these cells from the RVS group were stimulated with LPS, the levels of tumor necrosis factor (TNF)- and interleukin (IL)-6 in the supernatant decreased, but the level of IL-12 increased. The surface expression of CD86 was reduced, but surface expression of class II MHC molecules was increased. RVS suppressed the serum levels of LPS-induced TNF- and IL-6. RVS enhanced monocyte differentiation in thioglycollate-induced peritonitis by increasing scavenger receptor expression and activity. Macrophages isolated from mice given RVS responded differently to LPS. These findings demonstrate that RVS confers selective anti-inflammatory activity without causing the overall inhibitory effects on immune cells.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

Clinical ketosis is a crucial metabolic disease in dairy cows that is often accompanied by severe lipolysis and inflammation in adipose tissue. Our previous study suggested that the fold change of calmodulin (CaM) was upregulated 2.401-fold in the adipose tissue of cows with clinical ketosis. Therefore, we hypothesize that CaM may regulate lipolysis and inflammatory responses in clinical ketosis cows. To verify the hypothesis, we conducted a thorough veterinary assessment of clinical symptoms and serum β-hydroxybutyrate (BHB) concentration before collecting subcutaneous adipose tissue samples from six healthy and six clinically ketotic Holstein cows at 17 ± 4 days postpartum. Commercial kits were used to test the abundance of BHB, Non-esterified fatty acid (NEFA), Liver function index (LFI), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). We found that Clinical ketosis cows had higher levels of BHB, NEFA, LFI, IL-6, IL-1β, TNF-α, and lower glucose levels compared to healthy cows. Furthermore, the abundance of CaM, toll-like receptor 4 (TLR4), inhibitor of nuclear factor κB kinase subunit β (IKK), phosphorylated nuclear factor κB/nuclear factor κB, (p-NF-κB/NF-κB), adipose triglyceride lipase (ATGL) and phosphorylated hormone-sensitive lipase/hormone-sensitive lipase (p-HSL/HSL) were increased, while that of perilipin-1 (PLIN1) was decreased in the adipose tissue of cows with clinical ketosis. To investigate the mechanistic underlying the responses, we isolated the primary bovine adipocytes from the adipose tissue of healthy cows and induced the inflammatory response mediated by TLR4/IKK/NF-κB with lipopolysaccharide (LPS), in addition to treating with CaM overexpression adenovirus and CaM small interfering RNA. In vitro, LPS upregulated the abundance of CaM, TLR4, IKK, NF-κB, ATGL, p-HSL/HSL, and CaM and downregulated PLIN1. CaM silencing downregulated the abundance of LPS-activated p-HSL/HSL, TLR4, IKK, and NF-κB and upregulated PLIN1 in bovine adipocytes, except for ATGL. By contrast, CaM overexpression upregulated the abundance of LPS-activated p-HSL/HSL, TLR4, IKK, and NF-κB and downregulated PLIN1 expression in bovine adipocytes. In summary, these data suggest that CaM promotes lipolysis in adipocytes through HSL and PINL1 while activating the TLR4/IKK/NF-κB inflammatory pathway to promote an inflammatory response. There is a positive feedback loop between CaM, lipolysis, and inflammation. Overall, inhibiting CaM may act as an adaptive mechanism to alleviate metabolic dysregulation in adipose tissue, contributing to relief from lipolysis and inflammatory response.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory reflex system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through, for example, increased levels of anti-inflammatory cytokines such as IL-4, IL-13 and IL-10. Different phenotypes of schizophrenia may exhibit distinct IRS and CIRS immune profiles.Aims: This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve FEP patients before and after risperidone treatment.Methods: We included 31 antipsychotic-naïve FEP patients who had measurements of IRS and CIRS biomarkers before and after treatment with risperidone for 10 weeks, and 22 healthy controls.Results: Antipsychotic-naive FEP patients showed interrelated increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-12) as compared with the CIRS response (IL-4, IL-13, IL-5 and IL-10). Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement during treatment.Discussion: Our findings indicate that FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS is a new drug target to treat FEP.

Abstract Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the β-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerizes and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes lead to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research, However, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia

Excessive extracellular histones can damage cells despite their importance in DNA structure and gene regulation. We previously showed the harmful effect of histone 3.3 (H3.3) and its acetylated form (AcH3.3) in chronic obstructive pulmonary disease (COPD), but further research is needed to understand the in vivo underlying mechanisms. To investigate this, we administered a single dose of recombinant histones via intra-tracheal instillation in C57BL/6 mice and analyzed the outcomes after 48 hours. Both rH3.3 and rAcH3.3 effectively reached the bronchial and alveolar space. Lung histology revealed severe immune cell infiltration, rupture, damage, and thickening of many alveolar walls. Micro-CT scans showed macroscopic structure changes with a decreased tissue volume to total volume ratio. The administration of rH3.3 and rAcH3.3 induced lung apoptotic activity, as indicated by increased levels of cleavage caspase 3 and 9. Moreover, elevated plasma levels of pro-inflammatory cell mediators, including TNF-alpha, IL-6, MCP-3, and CXCL-1, were observed. The pathological changes and pro-inflammatory cytokine response were more pronounced in animals treated with rAcH3.3, which also exhibited leukocytosis and lymphocytosis. These findings emphasize the crucial role of extracellular H3.3 acetylation in inducing cytotoxicity and a robust, acute inflammatory response similar to what occurs in the lungs of COPD patients.

The “circular bioeconomy” offers numerous opportunities for the health, cosmetic, and nutrition sectors through the potential reuse of Castanea sativa by-products. This abundant and sustainable resource provides valuable bioactive secondary metabolites with antioxidants and anti-inflammatory properties. The transformation of these by-products into high-value products for human health can contribute to sustainable economic growth and reduce the environmental impact of traditional waste disposal practices, thus creating added value from previously underutilized resources. In the present study, we investigated the antioxidant capacity, phytochemical composition and in vitro antioxidant and anti-inflammatory activity of C. sativa burrs (CSB) aqueous extract. The spectrophotometric study yielded optimal total phenolic content (TPC) values, along with significant antioxidant and anti-radical properties. The utilization of UPLC-MS-MS techniques for phytochemical investigation resulted in the identification of a total of 56 metabolites, providing confirmation of the presence of phenolic compounds in CSB. In addition, CSB significantly downregulated pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophage cells without significant cell toxicity.

Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

Microglia are the resident immune cells of the central nervous system. Upon stimulus presentation microglia polarize from a resting to an activated state. Microglial translocator protein 18 kDa (TSPO) is considered as a marker of inflammation. Here, we characterized the role of TSPO by investigating the impact of TSPO deficiency on human microglia. We used TSPO knockout (TSPO-/-) variants of the human C20 microglia cell line. We found a significant reduction in the TSPO-associated protein VDAC1 in TSPO-/- compared to control cells. Moreover, we assessed the impact of TSPO deficiency on calcium levels and the mitochondrial membrane potential. Cytosolic and mitochondrial calcium concentrations were increased in TSPO-/- cell lines, whereas the mitochondrial membrane potential tended to be lower. Assessment of the mitochondrial DNA copy number via RT-PCR revealed a decreased amount of mtDNA in the TSPO-/- cells when compared to controls. Moreover, metabolic profiles of C20 cells were strongly dependent on the glycolytic pathway. However, TSPO depletion did not affect the cellular metabolic profile. Measurement of the mRNA expression levels of the pro-inflammatory mediators revealed an attenuated response to proinflammatory stimuli in TSPO-depleted cells, implying a role of the TSPO protein in the process of microglial polarization.

The risk of developing cardiovascular diseases (CVD) in patients suffering from rheumatoid arthritis (RA) is 1.5 times higher compared to the general population. The objective of this retrospective study was to determine the type of cardiovascular complications that can appear in patients with rheumatoid arthritis. Reducing the cardiovascular risk, through an aggressive management of the traditional and non-traditional risk factors, is another objective of this study. Early diagnosis and initiation of therapeutic measures to reduce the progression rate of rheumatoid arthritis, while also maintaining an active lifestyle, are the most important problems in young patients. We included a number of 200 patients with rheumatoid arthritis, presenting various stages of disease, concomitant with cardiovascular complications. The incidence by gender was higher in women, while men presented a higher incidence of traditional and non-traditional cardiovascular risk factors. All the patients presented an atherogenic coefficient over 2, indicating a significant risk of atherogenesis. An increased incidence of coronary artery disease was found in men. The patients presented cardiac arrhythmias, especially in the active stage of the condition, while the incidence of atrial fibrillation was higher in women. The active stage of the disease was evaluated using inflammatory biomarkers (ESR, PCR). ESR is not a specific tool for diagnosing the disease, but its important role in monitoring the activity of RA should not be ignored. Moreover, ESR has a significant role in monitoring the evolution and determining the prognostic of congestive heart failure. A target treatment prescribed a target treatment to reduce inflammation and prevent exacerbations was prescribed for all patients. However, in daily clinical practice, the screening for RA is poorly done. Thus, patients are often undiagnosed, while the risk factors are not assessed. In conclusion, even nowadays, RA patients continue to present an increased risk of developing CVD.

Three new polyketides (penidihydrocitrinins A–C, 1–3) and 14 known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on microglial activation in LPS-stimulated BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Moreover, compounds 6, 7, and 8 not only suppressed osteoclastogenesis, but also promoted osteoblast mineralization.

Background: Macrophage inflammatory protein-1 alpha (MIP-1α) and C-reactive protein (CRP) are pro-inflammatory biomarkers that quantify clinical and subclinical inflammation in cardiac ischemia in cardiac inflammation and disease. Adiponectin is an anti-inflammatory marker associated with good health. The susceptibility of periodontitis patients to cardiovascular events needs to be evaluated. Objective: This study aims to assess the levels of biomarkers in periodontitis patients with and without acute myocardial infarction (AMI) compared to controls. Material and methods: Pro-inflammatory and anti-inflammatory analytes were examined by collecting unstimulated saliva from three groups (n = 20/each): healthy individuals, individuals with stage III periodontitis, and post-myocardial infarction patients with stage III periodontitis. The samples were collected within 48 hours of AMI. Results: Adiponectin levels were significantly lower in patients with periodontitis with and without AMI compared to controls, while CRP and MIP-1α were significantly higher in patients with periodontitis with and without AMI compared to controls. The highest titers for MIP-1α and CRP were detected among patients with periodontitis with and AMI. Conclusion: Our study provides evidence of the association between periodontitis and salivary analytes that occur in tandem with cardiovascular disease. The lower levels of Adiponectin and higher levels of CRP and MIP-1α in patients with periodontitis indicate that this condition is a potential risk factor for cardiovascular disease. The findings emphasize the importance of early detection and intervention for periodontitis patients to prevent cardiovascular events.

Human sepsis is one of the leading cause of death worldwide and is known to be a harmful damaging host inflammatory condition, primarily caused by endotoxin released by gram-negative bacteria. Despite antibiotics administration being widely used to treat disease, effective targeted therapeutic strategies for the sepsis are still lacking. Here, we demonstrate that CM1, a derivative of natural polyphenol chrysin, exerts anti-inflammatory activity by inducing the ubiquitin-editing protein TNFAIP3 and NAD-dependent deacetylase sirtuin 1 (SIRT1). We found that CM1 attenuated Toll-like receptor 4 (TLR4)-induced the generation of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signaling pathway. In addition, the treatment of macrophages with CM1 induced the expression of TNFAIP3 and SIRT1 in TLR4-stimulated primary macrophages, however the anti-inflammatory properties of CM1 was disappeared by siRNA silencing of TNFAPI3 or by the genetic and pharmacologic inhibition of SIRT1. Importantly, intravenously administration of CM1 resulted in the decreased susceptibility to endotoxin-induced sepsis, leading to inhibition of the generation of proinflammatory cytokines and neutrophils infiltration into lung than control mice. Collectively, these findings suggest that CM1 has the potential to be a treatment candidate for diverse inflammatory diseases including sepsis.

The increased global incidence of myopia requires the establishment of therapeutic approaches. Previous studies have suggested that inflammation plays an important role in the development and progression of myopia. We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJE and PVE lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. Expression levels of IL-6, IL-8, and TNF-α were upregulated in retinal pigment epithelium (RPE) cells treated with IL-6 and TNF-α. FJ extract (FJE) + PV extract (PVE) reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-β1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type Ⅰ collagen expression. Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

Increased soluble endoglin (sENG) were observed in human brain arteriovenous malformations (bAVMs), and overexpression of sENG with vascular endothelial growth factor (VEGF)-A induced dysplastic vessel formation in mouse brain. However, the underlying mechanism of sENG-induced vascular malformations is not clear. While evidence suggests the role of sENG as a pro-inflammatory modulator, increased microglial accumulation and inflammations were observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that sENG with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, there were increased microglial activation around dysplastic vessels with expression of NLRP3, inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs while it decreased IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to release angiogenic/inflammatory responses which may be involved in EC dysfunction. Our study suggests the contribution of microglia in the pathology of sENG-associated vascular malformations.

Chronic kidney disease (CKD) affects approximately 12% of the global population posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of CKD contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in non-dialysis dependent stage 5 CKD patients using semitargeted metabolomics. In a prospective observational design involving 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5’-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in CKD, shedding light on cellular energy production and offering insights for further clinical validation.

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

Alzheimer’s Disease (AD) is a neurodegenerative condition that currently has no known cure. The principles of the expanding field of network medicine (NM) have recently been applied to AD research. The main principle of NM proposes that diseases are much more complicated than one mutation in one gene, and incorporate different genes, connections between genes, and pathways that may include multiple diseases to create full scale disease networks. AD research findings as a result of the application of NM principles have suggested that functional network connectivity, myelination, myeloid cells, and genes and pathways may play an integral role in AD progression, and may be integral to the search for a cure. Different aspects of the AD pathology could be potential targets for drug therapy to slow down or stop the disease from advancing, but more research is needed to reach definitive conclusions. Additionally, the holistic approaches of network pharmacology in traditional Chinese medicine (TCM) research may be viable options for the AD treatment, and may lead to an effective cure for AD in the future.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated dis-ease, but exact pathomechanism remains still unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize, IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, Meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, atopic dermatitis and of healthy control dogs using a competitive canine IL-31 ELISA. Mean serum IL-31 level in dogs with SRMA (n=18) was mildly higher compared to dogs with atopic dermatitis (n=3) and MUO (n=15) and markedly higher than in healthy controls (n=10) and dogs with infectious meningoencephalitis (n=3). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value of dogs with SRMA (n=23) was quite similar to healthy controls (n=8) and did not differ significantly from dogs with MUO (n=19) and infectious meningoencephalitis (n=2). Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 im-mune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

Alzheimer´s Disease (AD) has currently no effective treatment; however, preventive measures can significantly delay the progress/onset of the disease. Thus, accurate and early prediction of risk is an important strategy to alleviate the AD burden. Neuroinflammation is a major factor prompting the onset of the disease. Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, it is affecting gene expression via modulation of non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation can also affect long non-coding RNAs (lncRNAs) expression. While the association between miRNAs and inflammation in AD has been extensively studied, the role of lncRNAs in neurodegenerative diseases has been less explored. In this review, we focus on lncRNAs and inflammation in the context of AD. Furthermore, since plasma-isolated extracellular vesicles (EVs) are increasingly recognized as an effective monitoring strategy of brain pathologies, we have focused on the studies reporting dysregulated lncRNAs in EVs isolated from AD patients and controls. The revised literature shows a positive association between pro-inflammatory lncRNAs and AD. However, the reports evaluating lncRNAs alterations in EVs isolated from plasma of patients and controls, although still limited confirm the value of specific lncRNAs associated with AD as reliable biomarkers. This is an emerging field that will open new avenues to improve risk prediction, patients’ stratification and may lead to the discovery of potential novel therapeutic targets for AD