Inflammatory Disorders Research Articles

Effect of genistein supplementation on microenvironment regulation of breast tumors in obese mice

Obesity is an important risk factor for breast cancer in women before and after menopause. Adipocytes, key mediators in the tumor microenvironment, play a pivotal role in the relationship between obesity with cancer. However, the potential of dietary components in modulating this relationship remains underexplored. Genistein, a soy-derived isoflavone, has shown promise in reducing breast cancer risk, attenuating obesity-associated inflammation, and improving insulin resistance. However, there are no reports examining whether genistein has the ability to reduce the effects of obesity on breast tumor development. In this study, we constructed a mammary tumor model in ovariectomized obese mice and examined the effects of genistein on body condition and tumor growth. Moreover, the effects of genistein on the tumor microenvironment were examined via experimental observation of peritumoral adipocytes and macrophages. In addition, we further investigated the effect of genistein on adipocyte and breast cancer cell crosstalk via coculture experiments. Our findings indicate that dietary genistein significantly alleviates obesity, systemic inflammation, and metabolic disorders induced by a high-fat diet in ovariectomized mice. Notably, it also inhibits tumor growth in vivo. The impact of genistein extends to the tumor microenvironment, where it reduces the production of cancer-associated adipocytes (CAAs) and the recruitment of M2d-subtype macrophages. In vitro, genistein mitigates the transition of adipocytes into CAAs and inhibits the expression of inflammatory factors by activating PPAR-γ pathway and degrading nuclear NF-κB. Furthermore, it impedes the acquisition of invasive properties and epithelial‒mesenchymal transition in breast cancer cells under CAA-induced inflammation, disrupting the Wnt3a/β-catenin pathway. Intriguingly, the PPAR-γ inhibitor T0070907 counteracted the effects of genistein in the coculture system, underscoring the specificity of its action. Our study revealed that genistein can mitigate the adverse effects of obesity on breast cancer by modulating the tumor microenvironment. These findings provide new insights into how genistein intake and a soy-based diet can reduce breast cancer risk.

Clinical assessment of the potential use of a novel single-dose prefilled injection device for the administration of Acthar Gel in children: a narrative review.

Acthar® Gel (repository corticotropin injection; Mallinckrodt Pharmaceuticals, NJ, USA) is indicated for the treatment of myriad inflammatory disorders and is currently administered manually via a vial and syringe. The administration of Acthar via a single-dose prefilled injector (SelfJect™) is intended to simplify its subcutaneous (SC) delivery. The purpose of this review was to determine whether SelfJect is suitable for use in pediatric patients through a literature assessment of various factors, including skin depth, needle length and gauge, dosage, force required for injection, and potential harms. Infants and young children, who commonly have skin-to-muscle distances less than the minimum depth of SelfJect administration, may have risk of unintentional intramuscular (IM) injection; however, an inadvertent IM injection poses no additional risk to children because of the bioequivalence between SC and IM administration of Acthar. The needle gauge of SelfJect is acceptable for pediatric patients and aligns with the Centers for Disease Control and Prevention recommendations for SC injections. The dosage delivered by SelfJect is only appropriate for children over 2years of age. Although adolescents would likely be able to achieve the minimum force required to remove the protective cap and deliver a full dose of Acthar with SelfJect, an adult (18years of age and older) should administer SelfJect to pediatric patients. In addition to the commonly reported postmarketing adverse events (AEs) from Acthar administration (e.g., asthenic conditions, fluid retention, insomnia, headache and increased blood glucose), injection site-related AEs common to injection devices may occur with SelfJect use. The risk of needlestick injury from SelfJect is mitigated by a needle guard. In summary, this review of injection device considerations demonstrates that SelfJect is appropriate for use in the pediatric population.

Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota.

Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD. Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs). Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner. These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.

Cardiac Manifestations of Lyme Disease.

Lyme disease (LD) is an inflammatory disorder caused by an infectious bacterial agent and is the most common tick-borne illness in the United States and Europe. About 1.5-10% of adults infected with LD develop cardiac complications. This review summarizes the current knowledge of the epidemiology, pathophysiology, and diagnosis of Lyme carditis (LC), as well as the different manifestations of LD in the cardiovascular system. This review will primarily highlight the effect of LD on the cardiac conduction system and also discuss its effect on the myocardium, pericardium, valves, and coronary arteries. The management and prognosis of LC will be reviewed here as well. While this is a comprehensive review of the current literature on LC, there remain many questions regarding the complex relationship between LD and the heart.

Types, behaviour and therapeutic requirements of inflammatory pouch disorders: Results from the RESERVO study of GETECCU

Background and AimsInflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied. MethodsThis retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term. ResultsOverall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79–6.94, p < 0.0001), biologics (OR 5.45, 2.78–10.6, p < 0.0001) and surgeries (OR 2.65, 1.43–4.89, p < 0.001). ConclusionsChronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch.

Metabolic and Inflammatory Profiles in Children and Adolescents with Autism Spectrum Disorder: A Cross-Sectional Study

Background/Objectives: Autism spectrum disorder (ASD) is associated with several coexisting diseases or comorbidities, including inflammatory and metabolic disorders. In fact, ASD symptoms may be associated with immune system dysfunction. However, studies investigating the peripheral blood levels of immune cells are lacking and have provided mixed findings. In this study, we evaluated the relationship between the intensity level of ASD symptoms and the inflammatory and metabolic profiles in 154 children and adolescents (2–17 years). Methods: Bayesian multilevel models were used to examine the relationship between their symptom intensities and inflammatory/metabolic profiles. Results: Heavier children had higher values for triglyceride and insulin levels. Children with a level 3 of ASD intensity had higher free fatty acids levels. However, when adjusting for ASD intensity, gender, medication use, or weight status, older children appeared to have higher values of triglycerides, insulin levels, and free fatty acids. Conclusions: We concluded that as Brazilian children with ASD became older, they had a higher risk for insulin resistance.

Exploring Endocannabinoid System: Unveiling New Roles in Modulating ER Stress

The endoplasmic reticulum (ER) is the organelle mainly involved in maintaining cellular homeostasis and driving correct protein folding. ER-dependent defects or dysfunctions are associated with the genesis/progression of several pathological conditions, including cancer, inflammation, and neurodegenerative disorders, that are directly or indirectly correlated to a wide set of events collectively named under the term “ER stress”. Despite the recent increase in interest concerning ER activity, further research studies are needed to highlight all the mechanisms responsible for ER failure. In this field, recent discoveries paved the way for the comprehension of the strong interaction between ER stress development and the endocannabinoid system. The activity of the endocannabinoid system is mediated by the activation of cannabinoid receptors (CB), G protein-coupled receptors that induce a decrease in cAMP levels, with downstream anti-inflammatory effects. CB activation drives, in most cases, the recovery of ER homeostasis through the regulation of ER stress hallmarks PERK, ATF6, and IRE1. In this review, we focus on the CB role in modulating ER stress, with particular attention to the cellular processes leading to UPR activation and oxidative stress response extinguishment, and to the mechanisms underlying natural cannabinoids’ modulation of this complex cellular machine.

A mitochondria-targeted nitric oxide probe with large Stokes shift for real-time imaging and evaluation of inflammatory bowel disease in situ

BackgroundInflammatory bowel disease (IBD) is a prevalent inflammatory disorder, and the abnormal expression of nitric oxide (NO) produced by biocatalysis of iNOS enzyme in mitochondria is directly associated with the occurrence and progression of IBD. Activatable fluorescent probes offer promising tools for early diagnosis of IBD, however, inadequate biodistribution and limited targeting properties of these probes in vivo severely impede accurate diagnosis of IBD and real-time evaluation of inflammatory levels in situ. Therefore, it is necessary to designed a highly efficient fluorescent probe towards NO to overcome inadequate biodistribution and achieve accurate diagnosis and evaluation of IBD in situ. ResultsWe designed a highly efficient mitochondria-targeted “turn-on” NIR fluorescent probe Cy-OMe which has excellent targeting properties and imaging ability. The response mechanism is probe Cy-OMe rapidly undergoes N-nitrosation reaction resulting in turn-on NIR fluorescence signal when exposed to NO. Cy-OMe exhibits high sensitivity and specificity in detecting NO content in vitro, owing to its large Stokes shift. Furthermore, the probe Cy-OMe not only efficiently targets mitochondria but also enables precise assessment of fluctuations in endogenous NO concertation across various cell types. Importantly, by virtue of large Stokes shift and excellent mitochondrial targeting ability, Cy-OMe has the capability to specifically evaluate dynamic fluctuations of NO in lipopolysaccharide (LPS)‐stimulated IBD mouse models in situ and Cy-OMe was achieved high-contrast imaging and precision diagnosis of intestinal inflammation diseases. SignificanceCy-OMe can accurately assess fluctuations in NO levels and show high signal fidelity in the diseased intestine region, which has prospects in the non-invasive diagnosis of intestinal inflammation in vivo. At the same time, it is expected to serve as a potential diagnose platform for investigating the physiological processes underlying NO-related inflammatory diseases and promoting understanding of the pathological functions of NO across diverse inflammatory diseases.

Activation of the aryl hydrocarbon receptor via indole derivatives is a common feature in skin bacterial isolates.

The aryl hydrocarbon receptor (AhR) is a ligand-activated receptor implicated in many inflammatory disorders. The skin microbiota plays a crucial role in maintaining epidermal barrier integrity and is thought to modulate skin homeostasis partly through the production of AhR ligands including metabolites of microbial tryptophan metabolism such as indole derivatives. Here, we report the skin microbiota that activate AhR and their unique tryptophan metabolite profiles. Of the bacteria isolated from healthy human skin and screened for the ability to metabolise tryptophan (18 species, five genera), 14 were positive. The tryptophan metabolites of 10 positive and two negative bacteria were then characterised using liquid chromatography-mass spectrometry. Whole genome sequencing confirmed the presence of key genes involved in the indole-3-pyruvic acid pathway within the genomes of indole-3-acetaldehyde, indole-3-acetic acid, and indole-3-aldehyde-producing organisms. A cell-based luciferase reporter gene assay identified functional agonist activity against human AhR in the culture supernatants of 12 of the 18 species tested. High indole derivative-producing organisms induced potent AhR activation. These data demonstrate the relationship between skin microbiota, tryptophan metabolites, and AhR activation.

The Association Between Obesity, Chronic Inflammation, Metabolic Disorders and Mood Disorders Among Patients up to 12 Months After Hospitalization for SARS-CoV-2.

The relationship between BMI, inflammation, and mental health is complex. A high BMI, especially obesity, is associated with chronic inflammation, which can lead to mental disorders such as depression. Inflammatory cytokines affect neurotransmitters and the stress axis, worsening mental health. Obesity and mental disorders can mutually reinforce each other. New findings show that inflammation can lead to neurobiological changes, and the gut microbiota may play a key role. Obesity has been implicated as a factor in the high mortality and duration of influenza-like illnesses, even in people who do not have other chronic diseases that may increase the risk of complications. The aim of this study was to determine the associations between BMI and chronic inflammation, metabolic disorders, depression, and anxiety in patients hospitalized with COVID-19 up to 12 months after hospitalization. The study included 248 participants previously hospitalized for SARS-CoV-2 infection up to 12 months after hospitalization. The study was conducted in a multistage design using a diagnostic survey, anthropometric measurements, and laboratory methods. A statistically significantly higher BDI-II score was observed among women. Statistical analysis showed a statistically significant higher GAD-7 score among women and those over 75 years of age. Higher BMI among subjects is often associated with elevated values of inflammatory markers and immune cells, such as WBC, neutrophils, monocytes, and CRP, as well as higher blood glucose levels. These associations may be related to the chronic inflammation and metabolic disorders that often accompany obesity. Lymphocytes and eosinophils may show more varied relationships depending on individual factors and specific health conditions. It is therefore important to continue research in this area.

Chromatin remodelling drives immune cell-fibroblast communication in heart failure.

Chronic inflammation and tissue fibrosis are common responses that worsen organ function, yet the molecular mechanisms governing their cross-talk are poorly understood. In diseased organs, stress-induced gene expression changes fuel maladaptive cell state transitions1 and pathological interaction between cellular compartments. Although chronic fibroblast activation worsens dysfunction in the lungs, liver, kidneys and heart, and exacerbates many cancers2, the stress-sensing mechanisms initiating transcriptional activation of fibroblasts are poorly understood. Here we show that conditional deletion of the transcriptional co-activator Brd4 in infiltrating Cx3cr1+ macrophages ameliorates heart failure in mice and significantly reduces fibroblast activation. Analysis of single-cell chromatin accessibility and BRD4 occupancy in vivo in Cx3cr1+ cells identified a large enhancer proximal to interleukin-1β (IL-1β, encoded by Il1b), and a series of CRISPR-based deletions revealed the precise stress-dependent regulatory element that controls Il1b expression. Secreted IL-1β activated a fibroblast RELA-dependent (also known as p65) enhancer near the transcription factor MEOX1, resulting in a profibrotic response in human cardiac fibroblasts. In vivo, antibody-mediated IL-1β neutralization improved cardiac function and tissue fibrosis in heart failure. Systemic IL-1β inhibition or targeted Il1b deletion in Cx3cr1+ cells prevented stress-induced Meox1 expression and fibroblast activation. The elucidation of BRD4-dependent cross-talk between a specific immune cell subset and fibroblasts through IL-1β reveals how inflammation drives profibrotic cell states and supports strategies that modulate this process in heart disease and other chronic inflammatory disorders featuring tissue remodelling.

Exploring the effect of peppermint oil massage on pulmonary function in patients with bronchial asthma: insights from a case series

Bronchial asthma (BA) is a chronic inflammatory disorder characterized by airway hyperresponsiveness and obstruction, leading to symptoms such as coughing, wheezing, and shortness of breath. Management typically involves inhaled corticosteroids, but their adverse effects necessitate exploring alternative therapies. Aromatherapy massage, particularly using peppermint oil, may offer therapeutic benefits due to its anti-inflammatory and broncho dilatory properties. This study investigates the impact of upper back massage with peppermint oil on pulmonary function in BA patients. Three female patients with a history of poorly controlled BA participated in this case series. Each patient received a 20-minute upper back massage with peppermint oil daily for 10 days. Pulmonary function tests (PFTs) were conducted before and after the intervention, measuring forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), the FEV1/FVC ratio, peak expiratory flow rate (PEFR), and forced expiratory flow (FEF 25-75%). All patients showed improvement in pulmonary function post-intervention. Case 1: FVC increased from 80% to 97%, FEV1 from 67% to 82%, and PEFR from 72% to 93%. Case 2: FVC improved from 69% to 81%, FEV1 from 64% to 76%, and FEF 25-75% from 40% to 50%. Case 3: FVC rose from 74% to 78%, FEV1 from 55% to 60%, and PEFR from 56% to 63%. Upper back massage using peppermint oil appears to enhance pulmonary function in individuals with bronchial asthma.

The Therapeutic Potential of GLP-1 Receptor Agonists in the Management of Hidradenitis Suppurativa: A Systematic Review of Anti-Inflammatory and Metabolic Effects.

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are synthetic peptides that mimic the natural activity of GLP-1, widely known for lowering blood glucose levels and promoting weight reduction. These characteristics make them a valuable tool in managing type 2 diabetes and obesity-related conditions. Recent findings indicate that GLP1-RAs may also offer therapeutic benefits in managing hidradenitis suppurativa (HS), a chronic inflammatory skin disorder closely associated with metabolic abnormalities, including obesity, diabetes, and dyslipidemia. This review explores the potential role of GLP1-RAs in managing HS. Methods: A systematic review was conducted by searching electronic databases, including MEDLINE and Google Scholar, without date limitations. Key search terms included "GLP-1" or "GLP-1 agonists" combined with "hidradenitis suppurativa" or "acne inversa". Inclusion criteria were set for studies reporting on the use of GLP1-RAs as a treatment for HS, with articles discussing theoretical applications excluded. Data synthesis included findings from 25 relevant studies. Results: The analysis revealed that GLP1-RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients. Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1-RAs were attributed to the suppression of key inflammatory pathways involving TNF-α, IL-17, and NF-κB. Conclusions: GLP1-RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS.

Matched oligoclonal bands: Diagnostic utility and clinical characteristics.

To describe patient clinical characteristics associated with matched oligoclonal bands (OCB). A retrospective review at the University of Utah examined patients with matched OCB from 2015 to 2020. Clinical data, diagnosis, and outcomes were collected. Patients were classified with either multiple sclerosis (MS), other inflammatory neurologic disorder (other-IND), or noninflammatory neurologic disorder (NIND). Of 539 identified patients, 436 (53.4% female) were matched-only, while 103 (43.7% female) were matched + unique. Patients with matched-only bands were older (57.4 ± 16 vs. 52 ± 14.2, p < 0.001) and more likely to have a history of autoimmune disease (40.1% vs. 28.2%, p = 0.024) and/or cancer (28.7% vs. 16.5%, p = 0.012). Patients with matched + unique bands were more likely to have CSF pleocytosis (52.4% vs. 25.9%, p < 0.001), high IgG index (52.2% vs. 7.6%, p < 0.001), and an abnormal MRI (86.9% vs. 63.1%, p < 0.001). More than two-thirds of matched-only patients had NIND, while 33% and 41.7% of matched + unique patients had MS and other-IND, respectively. Patients exhibiting matched-only bands and a high IgG index demonstrated a significantly higher incidence of other-IND compared to those with matched-only bands and a normal IgG index (55.6% vs. 30.4%, p = 0.013). While Kaplan-Meier survival curves demonstrated higher mortality in the matched-only cohort compared to the matched + unique cohort (p = 0.02), multivariable Cox regression analysis showed this difference was not statistically significant when adjusting for various factors. A history of cancer was the significant predictor of increased mortality risk (Hazard ratio = 3.147, 95% CI [2.196, 4.51]). Patients with matched only versus matched + unique OCB have distinct clinical profiles.

The Analysis Study of Effect of Acupuncture on the Treatment of Atopic Itch: A Comprehensive Systematic Review

Background: Atopic dermatitis is a common inflammatory skin disorder characterized by recurrent eczematous lesions and severe itching. Given its chronic nature and association with persistent pruritus, exploring therapies like acupuncture may offer valuable relief and enhance patient outcomes. This systematic review aims to explore the efficacy and mechanisms of acupuncture as a treatment for atopic pruritus based on the literature of the last decade. Methods: The study followed PRISMA 2020 guidelines, reviewing English-language publications from 2014 to 2024. Editorials, duplicate reviews from the same journal, and papers lacking a DOI were excluded. The literature search was conducted using PubMed, SagePub, SpringerLink, and Google Scholar. Result: A total of 630 articles were initially identified through online databases (PubMed, SagePub, SpringerLink, and Google Scholar). After three rounds of screening, eight relevant studies were selected for full-text analysis. Conclusion: Acupuncture shows potential as a noninvasive and effective treatment for reducing pruritus and associated symptoms in patients with atopic dermatitis and other pruritic conditions. The observed benefits, such as decreased itch intensity, improved quality of life, and reduced medication use, underline its value as an adjunct therapy.

Acne vulgaris in adolescents – the review

Acne vulgaris is one of the most common chronic inflammatory skin disorders that affects almost 90% of the adolescents worldwide. Due to its effect on one’s appearance, it causes not only physical but also psychological consequences. The cause of acne involves increased sebum production, hyperkeratinisation of the follicle, bacterial colonization and inflammation, which result in formation of comedones, papules, pustules and nodules. Diet, Body Mass Index, hyperhidrosis and stress can be triggering factors. The pharmacological treatment of acne involves substances administered topically as well as orally. First line of treatment of mild-to-moderate acne involves topical benzoyl peroxide, retinoids, chemical peels, antibiotics and combinations of those agents. The treatment of moderate-to-severe or inflammatory acne consists of oral antibiotics, isotretinoin, oral contraceptives and spironolactone. New therapies are being investigated and show a great potential, however further research should be pursued in order to achieve long-lasting results of the treatment.

Is the identification of caseating granuloma in the intestine indicative of tuberculosis? a rare case of Crohn’s disease

BackgroundCrohn’s disease (CD) is a chronic intestinal inflammatory disorder, the etiology of which remains unknown, and is characterized by symptoms such as chronic abdominal pain, diarrhea, obstruction, and perianal lesions. Histopathology is widely regarded as the preferred method for diagnosing CD, although the histological diagnosis may lack specificity. The identification of granulomas is commonly believed to be the most reliable diagnostic indicator for CD, surpassing all other clinical features in significance. Nevertheless, research indicates that the detection rate of granulomas in CD exhibits considerable variability. Furthermore, granulomas can manifest in various specific infections including tuberculosis and Yersinia, as well as in a range of diseases characterized by macrophage reactions such as sarcoidosis and drug-induced enteritis. Granulomas associated with CD typically do not exhibit necrosis. However, the formation of caseous granulomas may occur as a result of secondary infections related to anti-CD drug treatment or perforation of the intestinal wall.Case presentationIn this study, we present a case of a 28-year-old female patient diagnosed with CD exhibiting histologic granulomas, including both caseating and non-caseating forms, which demonstrated a positive response to medical treatment.ConclusionIn clinical practice, various forms of granulomas may indicate diverse underlying diseases, yet lack specificity. It is suggested that the presence of caseous granulomas should not be considered as a definitive exclusion criterion for the diagnosis when clinical, endoscopic, imaging and other histopathological features are consistent with CD. This study is the first report of caseous granulomas in CD without concomitant tuberculosis infection.

Phillyrin inhibits oxidative stress and neutrophil extracellular trap formation through the KEAP1/NRF2 pathway in gouty arthritis.

Gouty arthritis (GA) is an inflammatory disorder characterized by deposition of monosodium urate (MSU) crystal in joints. Phillyrin, a natural compound with anti-inflammatory properties, shows promise in mitigating inflammatory responses. This study investigates the therapeutic potential of phillyrin in GA and explores its mechanisms of action. GA was induced in mice via intraarticular MSU injection, and joint inflammation, inflammatory cell infiltration, and their level in serum/tissue were assessed. Key proteins in the NF-κB and NLRP3 pathways were examined using western blot analysis. The impact of phillyrin on oxidative stress, neutrophil extracellular trap (NET) formation, and neutrophil accumulation was evaluated by measuring CD11b + Ly6G + cells, MPO, CitH3, extracellular DNA ratio, and oxidative stress markers. In vitro studies assessed the effects of phillyrin on oxidative stress, cell viability, cytokine production, and NET formation in MSU-treated neutrophils. The KEAP1/NRF2 pathway's role was analyzed using ML385, an NRF2 inhibitor. Phillyrin significantly reversed MSU-induced ankle swelling and inflammatory cell infiltration in joint tissues. It suppressed pro-inflammatory cytokines and proteins in the NF-κB and NLRP3 pathways. Phillyrin reduced neutrophil infiltration, evidenced by lower MPO activity and NET formation, marked by reduced CitH3 expression. In vitro, phillyrin inhibited inflammatory marker expression and NET formation without affecting cell viability. It also restored antioxidant enzyme levels and reduced ROS production, regulating the KEAP1/NRF2 pathway, enhancing NRF2 expression and stability. These effects were reversed by NRF2 inhibition with ML385. Phillyrin alleviates GA by reducing joint inflammation, inhibiting NET formation, and suppressing oxidative stress through NRF2 modulation.

Analysis of lipid uptake, storage, and fatty acid oxidation by group 2 innate lymphoid cells.

Group 2 Innate Lymphoid Cells (ILC2) are critical drivers of both innate and adaptive type 2 immune responses, known to orchestrate processes involved in tissue restoration and wound healing. In addition, ILC2 have been implicated in chronic inflammatory barrier disorders in type 2 immunopathologies such as allergic rhinitis and asthma. ILC2 in the context of allergen-driven airway inflammation have recently been shown to influence local and systemic metabolism, as well as being rich in lipid-storing organelles called lipid droplets. However, mechanisms of ILC2 lipid anabolism and catabolism remain largely unknown and the impact of these metabolic processes in regulating ILC2 phenotypes and effector functions has not been extensively characterized. ILC2 phenotypes and effector functions are shaped by their metabolic status, and determining the metabolic requirements of ILC2 is critical in understanding their role in type 2 immune responses and their associated pathophysiology. We detail here a novel experimental method of implementing flow cytometry for large scale analysis of fatty acid uptake, storage of neutral lipids, and fatty acid oxidation in primary murine ILC2 with complementary morphological analysis of lipid storage using confocal microscopy. By combining flow cytometry and confocal microscopy, we can identify the metabolic lipid requirements for ILC2 functions as well as characterize the phenotype of lipid storage in ILC2. Linking lipid metabolism pathways to ILC2 phenotypes and effector functions is critical for the assessment of novel pharmaceutical strategies to regulate ILC2 functions in type 2 immunopathologies.

Gut Microbiome as a Target of Intervention in Inflammatory Bowel Disease Pathogenesis and Therapy

Inflammatory bowel disease (IBD) is a chronic complicated inflammatory gut pathological disorder and is categorized into ulcerative colitis (UC) and Crohn’s disease (CD). Although the cause of IBD is unclear, dysbiosis of the gut microbiota is thought to be a key factor in the disease’s progression. The gut microbiome serves as a metabolic organ and promotes wellness by carrying out several biological activities. Any modification in the makeup of the gut microbiome leads to several pathological conditions, including IBD. In this review, we emphasize the key metabolic processes that control host–microbiome interaction and its impact on host health. We also discuss the association between microbiome dysbiosis (bacteriome, virome, and mycobiome) and the progression of IBD. Finally, we will highlight microbiome-based therapy as a novel and promising strategy to treat and manage IBD.