Inflammatory bowel disease (IBD), which includes Crohn's Disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract. A key component of the inflammatory pathway in IBD is interleukin 23 (IL-23), which promotes the differentiation and maintenance of Th17 cells. These cells are major contributors to intestinal inflammation and the release of pro-inflammatory cytokines. A dysregulated IL-23/Th17 axis can lead to excessive gut inflammation. Notably, IL-23 affects Th17 cell responses differently in UC and CD, fostering IL-17 production in UC and interferon-gamma (IFN-γ) production in CD. Genetic studies have pinpointed specific variants of the IL-23 receptor (IL23R) gene that confer protection against IBD. The R381Q (rs11209026) variant has been linked to a reduced risk of developing both CD and UC. Additionally, other variants, such as G149R (rs76418789) and V362I (rs41313262), inhibit IL23R function by disrupting intracellular trafficking and protein stability. This disruption results in decreased phosphorylation of downstream signal transducers, such as STAT3 and STAT4, and reduced IL23R expression on the cell surface, ultimately dampening the activation of pro-inflammatory pathways. The protective effects of these genetic variants underscore the IL-23/IL23R pathway as a significant therapeutic target in IBD management. Therapies designed to modulate this pathway have the potential to reduce pro-inflammatory cytokine production and enhance anti-inflammatory mechanisms. Ongoing research into the IL23R gene and its variants continues to provide valuable insights, paving the way for more targeted and effective treatments for IBD patients.

To develop a non-invasive, radiation-free model for early colorectal adenoma prediction using clinical electronic medical record (EMR) data, addressing limitations in current diagnostic approaches for large-scale screening.

Retrospective analysis utilized 92,681 cases with EMR, spanning from 2012 to 2022, as the training cohort. Testing was performed on an independent test cohort of 19,265 cases from 2023. Several classical machine learning algorithms were applied in combination with the BGE-M3 large-language model (LLM) for enhanced semantic feature extraction. Area under the receiver operating characteristic curve (AUC) is the major metric for evaluating model performance. The Shapley additive explanations (SHAP) method was employed to identify the most influential risk factors.

XGBoost algorithm, integrated with BGE-M3, demonstrated superior performance (AUC = 0.9847) in the validation cohort. Notably, when applied to the independent test cohort, XGBoost maintained its strong predictive ability with an AUC of 0.9839 and an average advance prediction time of 6.88 hours, underscoring the effectiveness of the BGE-M3 model. The SHAP analysis further identified 16 high-impact risk factors, highlighting the interplay of genetic, lifestyle, and environmental influences on colorectal adenoma risk.

This study developed a robust machine learning-based model for colorectal adenoma risk prediction, leveraging clinical EMR and LLM. The proposed model demonstrates high predictive accuracy and has the potential to enhance early detection, making it well-suited for large-scale screening programs. By facilitating early identification of individuals at risk, this approach may contribute to reducing the incidence and mortality associated with colorectal cancer.

Rheumatological diseases (RD) in childhood are systemic diseases that occur on the basis of auto-immunity or inflammation, and they can be accompanied by inflammatory bowel disease (IBD). When there is no knowledge of this association, the treatments applied may not be sufficient and/or treatments given for RD may even lead to aggrevation of IBD findings. Thus, early identification of an association is crucial for the correct management of the diseases.

The aim of this study is to show the frequency of IBD in patients with RDs. We also aimed to investigate in which cases IBD should be suspected in children with RDs.

Electronic medical records of the patients who were followed up between 2012 and 2024 with a diagnosis of RD in our Paediatric Rheumatology Unit and diagnosed with IBD were reviewed retrospectively.

Between 2012 and 2024, 20 (3%) of 650 familial Mediterranean fever (FMF) patients, 3 (7.5%) of 40 chronic nonbacterial osteomyelitis (CNO) patients (one of them also had FMF) and 2 (1.2%) of 170 juvenile idiopathic arthritis (JIA) patients were diagnosed with IBD. While 15 (62.5%) of the patients received a RD as the initial diagnosis, 9 (37.5%) of them were initially diagnosed with IBD and then referred to rheumatology for their symptoms. The median age at the diagnosis of RD was 9 years (inter quartile range (IQR), 14.5). The median age at the diagnosis of IBD was 12 years (IQR, 13), and 12 patients (50%) had Crohn's disease (CD), 10 patients (41.6%) ulcerative colitis (UC) and 2 patients (8.4%) undeterminated disease. Although majority of the patients had classical findings of IBD, 4 patients presented with more vague symptoms including treatment-resistant iron deficiency anaemia, perianal abscess, weight loss and growth retardation.

RD and IBD share similar pathological pathways and clinical findings, and IBD can accompany to various RD. The diagnosis of IBD should be considered in the presence of rare and atypical symptoms. Furthermore, RD should also be considered in children with IBD who have complex extraintestinal symptoms. Key Points • RD, especially FMF, JIA and CNO, may be associated with IBD. • Paediatric rheumatologists should consider IBD as a potential diagnosis in the presence of atypical findings that may develop during the course of RD. • The co-existence of RD and IBD is important both in terms of disease progression and treatment decisions.

In the pathogenesis of inflammatory bowel disease (IBD), overstimulation of inflammatory factors can trigger a coagulation cascade, increase the risk of intestinal micro-thrombosis and lead to microcirculation disorders. However, prevention of microcirculation pathways has not received enough attention. Heparin is commonly used in anticoagulant therapy, but oral delivery does not have an excellent anticoagulant effect. To improve the stability of heparin (HEP) in the gastrointestinal tract, zein/tea polyphenol nanospheres with a core-shell structure (EGNs@Z) were developed for oral administration of heparin (HEGNs@Z). The Zein shell has pH-responsive properties and is effective in preventing premature dissolution of heparin. At the same time, EGCG nanospheres (EGNs) play an anti-inflammatory role, jointly improve the vicious cycle between inflammation and microthrombosis. The results of SEM, TEM and FTIR showed that EGNs successfully encapsulated heparin and formed zein shells on the surface of microspheres with a thickness of 50-100 nm. In vitro simulated digestion experiments showed that zein shells prevented the breakdown of microspheres and heparin in a simulated gastric environment, whereas EGNs and HEP were slowly degraded and released in a simulated intestinal environment. Coagulation analysis showed that HEGNs@Z was effective in delaying clotting time. A mouse model of acute colitis has also shown that HEGNs@Z robust promotes colonic epithelial regeneration, inhibits malignant microcirculation, and reduces bleeding risk. These findings reveal that this orally bioavailable multifunctional material may provide a novel, effective and convenient treatment for inflammatory bowel disease.

Ulcerative colitis is an idiopathic gastrointestinal disease described by chronic inflammation of the digestive system. Cytokines may be responsible for immunopathogenesis, mucosal and tissue damage, and even treatment response. In addition to its role in calcium and phosphorus homeostasis and bone health, vitamin D is an immunomodulatory and anti-inflammatory agent. Understanding the role of cytokines may lead to improving the pathogenesis and treatment of this disease, therefore we aimed to investigate the relative gene expression of pro- and anti-inflammatory cytokines in biopsy samples taken from the affected area in the colon of ulcerative colitis patients and its association with serum vitamin D levels. A total of 47 ulcerative colitis patients were enrolled in this case-control study. The case group consisted of 23 patients with treatment-resistant ulcerative colitis, and the control group consisted of 24 ulcerative colitis patients responding to routine treatment. Serum vitamin D levels were measured by ELISA method. Real-time PCR was employed to quantify the relative expression of pro- and anti-inflammatory cytokines in colon biopsy samples from case and control groups. The pro-inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-8, IL-17 A, and IL-33, while the anti-inflammatory cytokines were IL-10, IL-35, and TGF-β. Data are showed as mean ± standard deviation (SD), and p values < 0.05 were considered statistically significant. The mean age of the control group was 45.88 ± 18.51 years, while that of the case group was 41.30 ± 13.01 years. The relative gene expression of TNF-α, IFN-γ, IL-1β, IL-6, IL-8, IL-17 A, IL-33, TGF-β, IL-10, and IL-35, in the case and control groups did not exhibit statistically significant differences (p > 0.05). However, the gene expression levels of the principal pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, were elevated in treatment-resistant patients compared to patients who responded to treatments. No correlation was observed between serum vitamin D levels and the gene expression of pro- and anti-inflammatory cytokines (p > 0.05). The present study did not identify a statistically significant correlation between the expression of pro- or anti-inflammatory cytokines and treatment response. Therefore, routine treatments had no effect on the expression of these cytokines in treatment-resistant patients. Additionally, serum vitamin D levels were not related to the relative expression of pro- and anti-inflammatory cytokines in the affected area of the colon of these patients. Despite the need for further research on the protective and pathological roles of cytokines and vitamin D, regular screening and early and complementary treatment may be beneficial in reducing inflammatory symptoms in these patients.

A comprehensive understanding of the dynamic changes in plasma cells (PCs) during inflammation remains elusive. In this study, we analyzed the distinct responses of PCs across different phases of inflammation in a dextran sodium sulfate (DSS)-induced mouse colitis model. Six-week-old male C57BL/6 mice were treated with 2.2 % DSS in distilled water for 5 days to induce colitis, and colonic tissues were collected at the peak of inflammation, during recovery, and at the end of the recovery phase. Single-cell RNA sequencing was performed to investigate temporal changes in the gut immune environment. PCs were categorized into six subsets, with Ube2c + PCs displaying notable alterations during various inflammatory phases. Genes such as Pycard, Gpx1, Lgals3, and Chchd10 were significantly expressed in Ube2c + PCs and appeared critical in resolving DSS-induced inflammation. Transcription factors (TFs), including Atf4, Cebpg, Jund, and Klf6, exhibited high regulatory activity in Ube2c + PCs across inflammatory stages. Additionally, we identified an interaction between Chchd10 and C1qbp in PCs, which stabilized C1qbp, reduced reactive oxygen species (ROS) production, and potentially enhanced PC survival and function under inflammatory conditions. This study highlights dynamic quasi-temporal gene expression and TF regulation in PCs during colitis, providing insights for future PC-targeted immunotherapy research.

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice. The M2 macrophage population increased and CD8+ T cell population decreased only in the female Ninj1 KO than in the female WT AOM/DSS group. In the female AOM/DSS group, TP treatment exacerbated colon shortening in the Ninj1 KO than in the WT. At week 13 (tumorigenesis stage), male Ninj1 KO mice had fewer tumors, but females showed similar tumors. In the WT AOM/DSS group, females had more M2 macrophages and fewer M1 macrophages than males, but this difference was absent in Ninj1 KO mice. In the Ninj1 KO versus WT group, the expression of pro-inflammatory mediators and Ho-1 and CD8+ T cell populations decreased in both female and male Ninj1 KO mice. In the WT group, M2 macrophage populations were increased by AOM/DSS treatment and decreased by TP treatment. However, neither treatment changed the cell populations in the Ninj1 KO group. These results suggest that Ninj1 is involved in colorectal cancer development in a testosterone-dependent manner, which was different in male and female. This highlights the importance of considering sex disparities in understanding Ninj1's role in cancer pathogenesis.

The ABCC subfamily contains thirteen members. Nine of these transporters are called multidrug resistance proteins (MRPs). The MRPs have been associated with developing ulcerative colitis (UC). This study aimed to evaluate the ABCC expression in UC patients and its role in a dextran sulfate sodium (DSS)-induced colitis mice model under 5-aminosalicylates or methylprednisolone treatment and compared with control without inflammation. DSS-induced colitis mice were treated with 5-aminosalicylates (50 mg/kg 24 h) or methylprednisolone (2 mg/kg 24 h). Human rectal biopsies were obtained from UC patients. The abcc-relative mRNA levels and protein expression were determined by RT-PCR and immunohistochemistry. abcc4, abcc5, and abcc6 mRNA levels were significantly increased in DSS-induced colitis compared to the other groups. The 5-aminosalicylate treatment dramatically increased the abcc2 and abcc3 mRNA levels vs. control. Methylprednisolone treatment increased abcc1 vs. DSS-induced colitis and colitis treated with 5-aminosalicylate. Immunohistochemical analysis revealed down-regulation of ABCC1/ABCC2/ABCC5/ABCC7 in mice colitis vs. control. Treatment with 5-aminosalicylate restored ABCC5 levels, while methylprednisolone restored ABCC2/ABCC5/ABCC7 in colitis mice at similar control levels. Relative mRNA levels of mrp1-5 were increased in active UC patients vs. control. ABCC2/ABCC4/ABCC7 were conspicuously expressed in the mucosa of 5-aminosalicylate and/or methylprednisolone-treated UC patients, while ABCC2/ABCC4/ABCC5/ABCC7 in submucosa, ABCC1/ABCC5/ABCC7 in muscular, and ABCC1/ABCC4/ABCC5/ABCC7 in serosa were expressed vs. controls. This is the first report about the differential up-regulation of the ABCC subfamily gene and protein expression in DSS-induced colitis under aminosalicylates or methylprednisolone treatment.

Ulcerative colitis is a chronic inflammatory bowel disease of the colon mucosa associated with a higher risk of colorectal cancer.

This study classified hematoxylin and eosin (H&E) histological images of ulcerative colitis, normal colon, and colorectal cancer using artificial intelligence (deep learning).

A convolutional neural network (CNN) was designed and trained to classify the three types of diagnosis, including 35 cases of ulcerative colitis (n = 9281 patches), 21 colon control (n = 12,246), and 18 colorectal cancer (n = 63,725). The data were partitioned into training (70%) and validation sets (10%) for training the network, and a test set (20%) to test the performance on the new data. The CNNs included transfer learning from ResNet-18, and a comparison with other CNN models was performed. Explainable artificial intelligence for computer vision was used with the Grad-CAM technique, and additional LAIR1 and TOX2 immunohistochemistry was performed in ulcerative colitis to analyze the immune microenvironment.

Conventional clinicopathological analysis showed that steroid-requiring ulcerative colitis was characterized by higher endoscopic Baron and histologic Geboes scores and LAIR1 expression in the lamina propria, but lower TOX2 expression in isolated lymphoid follicles (all p values < 0.05) compared to mesalazine-responsive ulcerative colitis. The CNN classification accuracy was 99.1% for ulcerative colitis, 99.8% for colorectal cancer, and 99.1% for colon control. The Grad-CAM heatmap confirmed which regions of the images were the most important. The CNNs also differentiated between steroid-requiring and mesalazine-responsive ulcerative colitis based on H&E, LAIR1, and TOX2 staining. Additional classification of 10 new cases of colorectal cancer (adenocarcinoma) were correctly classified.

CNNs are especially suited for image classification in conditions such as ulcerative colitis and colorectal cancer; LAIR1 and TOX2 are relevant immuno-oncology markers in ulcerative colitis.

Background/Objectives: Inflammatory bowel diseases primarily encompass Crohn's disease and ulcerative colitis. Insufficient levels of tryptophan cause an imbalance in the gut microbiota, leading to inflammation in the gastrointestinal tract. The main catabolic pathway of tryptophan is the kynurenine pathway. Our study aims to evaluate serum tryptophan, the kynurenine pathway, and oxidative stress parameters, including total oxidant status and total antioxidant capacity, in patients with Crohn's disease and ulcerative colitis. Methods: The study included 80 follow-up patients in remission diagnosed with Crohn's disease and ulcerative colitis who attended the Gastroenterology Outpatient Clinic, as well as 78 healthy controls. Serum tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and kynurenic acid levels were measured with liquid chromatography and tandem mass spectrometry (LC-MS/MS). All statistical analysis was performed using R version 4.2.1. Statistical Language. Results: Serum tryptophan, 3-hydroxyanthranilic acid, and total antioxidant capacity were lower in patients with ulcerative colitis and Crohn's disease compared to those in the control group. The serum total oxidant status in the control group was significantly lower than in patients with Crohn's disease and ulcerative colitis. Conclusions: The results of our research indicate that tryptophan and kynurenine pathway metabolites could potentially contribute to the pathogenesis of inflammatory bowel diseases.

This study aims to evaluate the correlation between inflammation indices, such as neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR) and deep myometrial infiltration (≥50%) prospectively in patients with endometrial carcinoma, providing insights into the interaction between these parameters MATERIAL AND METHODS: A prospective observational cohort study was conducted at AOU Vanvitelli in Naples, Italy, from August 2023 to March 2024. Data from 161 patients undergoing surgery for endometrial cancer, including preoperative blood counts and histopathological information, were collected. Statistical analyses were performed using R software.

After logistic regression, NLR and MLR showed a statistically significant association with deep myometrial infiltration (NLR log(OR) 0.15, P = .040; MLR log(OR) 0.30, P = .008). However, after multivariate logistic regression which included other risk factors such as grading, histotype, and MSI only NLR retained statistical significance, (Log(Or) 0.18, P = .031).

Our results demonstrate noticeable changes in inflammation indices associated with deep myometrial infiltration in endometrial carcinoma. Moreover, a correlation between NLR and deep myometrial infiltration exists regardless of microsatellite instability, histotype, and grading.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition of unknown etiology, although recent evidence suggests that it is caused by an excessive immune response to mucosal antigens. We determined the anti-inflammatory properties of novel compound DJ-X-013 in vitro in lipopolysaccharide (LPS)-induced macrophages and in an in vivo dextran sodium sulfate (DSS)-induced model of colitis.

To evaluate the anti-inflammatory properties of DJ-X-013, we used LPS-activated RAW 264.7 macrophages in vitro and a DSS-induced experimental model of colitis in vivo. We examine cellular morphology, and tissue architecture by histology, flow cytometry, RT-qPCR, multiplex, and immunoblot analysis to perform cellular and molecular studies. DJ-X-013 treatment altered cell morphology and expression of inflammatory cytokines in LPS-activated macrophages as compared to cells treated with LPS alone. DJ-X-013 also impeded the migration of RAW 264.7 macrophages by modulating cytoskeletal organization and suppressed the expression of NF-κB and inflammatory markers as compared to LPS alone. DJ-X-013 treatment improved body weight, and colon length and attenuated inflammation in the colon of DSS-induced colitis. Intriguingly, DSS-challenged mice treated with DJ-X-013 induced the numbers of myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and natural killer T cells (NKT) in the colon lamina propria (LP) relative to DSS. DJ-X-013 also reduced the influx of neutrophils, TNF-α producing macrophages, restricted the number of Th17 cells, and suppressed inflammatory cytokines and NF-κB in the LP relative to DSS.

DJ-X-013 is proposed to be a therapeutic strategy for ameliorating inflammation and experimental colitis.

The prevalence and incidence of ulcerative colitis (UC) in Korea is increasing. Each patient has a different disease course and treatment response. Recently, with the development of biologic agents, histological remission has become a treatment goal. In this study, we aimed to identify the predictors of histological remission after first-line biologic agent treatment in patients with biologic agent-naïve UC.

We retrospectively analyzed the medical records of 92 patients who had been diagnosed with UC and treated with first-line biologic agent treatment at our center, between 2015 and 2022. The clinical characteristics, laboratory test results, and endoscopic and biopsy findings were analyzed. Histological remission was defined as the absence of cryptitis, crypt abscesses, and inflammatory cells on histology. Univariate and multivariate logistic regression analyses were performed to identify the predictors of histological remission after first-line treatment.

Of the total 92 patients, 25 (27.2%) achieved histological remission. Each cohort had a varied body mass index (BMI) distribution, with a statistically significant overweight ratio, as defined by the Asian-Pacific BMI category of 23-25 kg/m2, of 48.0% in the histological remission cohort (P= 0.026). A causal correlation between the overweight category and histological remission was confirmed (odds ratio, 3.883; 95% confidence interval, 1.141-13.212; P= 0.030).

We confirmed that the overweight category was a predictor of histological remission after first-line treatment with a biological agent. However, as BMI does not account for skeletal muscle mass, future studies are required to confirm the correlation between skeletal muscle mass and histological remission.

The effect of radiation on the ileal pouch is less well studied in patients with inflammatory bowel disease (IBD) and ileal pouch-anal anastomosis.

This retrospective study investigates the impact of external radiation therapy on the outcomes of ileal pouches.

The study included 82 patients with IBD and ileal pouches, of whom 12 received pelvic radiation, 16 abdominal radiation, 14 radiation in other fields, and 40 served as controls with no radiation. Pouch-related outcomes, including pouch failure, worsening of symptoms, pouchitis, and development of strictures, along with changes in Pouch Disease Activity Index (PDAI) scores pre- and post-radiation were assessed.

The pelvic radiation group exhibited a significantly higher rate of pouch failure (25%, p < 0.004) and worsening pouch-related symptoms (75%, p = 0.012) compared to other groups. Although not statistically significant, a higher incidence of pouchitis was observed in the pelvic radiation group (45.5%, p = 0.071). Strictures were more common in the pelvic radiation group (25%, p = 0.043). Logistic regression analysis revealed that pelvic radiation significantly increased the odds of pouch-related adverse outcomes (OR 5.66; 95% confidence interval: 1.61-21.5).

Pelvic radiation significantly impacts the outcomes of ileal pouches in patients with IBD, increasing the risk of pouch failure, symptom exacerbation, and structural complications. These findings underscore the need for careful consideration of radiation therapy in this patient population and highlight the importance of closely monitoring and managing radiation-induced pouch dysfunction.

Sarcopenia, a prevalent comorbidity of inflammatory bowel disease (IBD), is characterized by diminished skeletal muscle mass and strength. Nevertheless, the underlying interconnected mechanisms remain elusive. This study identified distinct expression patterns of sarcopenia-associated genes (SRGs) across individuals with IBD and in samples of normal tissue. By analyzing SRG expression profiles, we effectively segregated 541 IBD samples into three distinct clusters, each marked by its unique immune landscape. To unravel the transcriptional disruptions underlying these clusters, the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm was employed to spotlight key genes linked to each cluster. A diagnostic model based on four key genes (TIMP1, PLAU, PHLDA1, TGFBI) was established using Random Forest and LASSO (least absolute shrinkage and selection operator) algorithms, and validated with the GSE179285 dataset. Moreover, the GSE112366 dataset facilitated the exploration of gene expression dynamics within the ileum mucosa of UC patients pre- and post-Ustekinumab treatment. Additionally, insights into the intricate relationship between immune cells and these pivotal genes were gleaned from the single-cell RNA dataset GSE162335. In conclusion, our findings collectively underscored the pivotal role of sarcopenia-related genes in the pathogenesis of IBD. Their potential as robust biomarkers for future diagnostic and therapeutic strategies is particularly promising, opening avenues for a deeper understanding and improved management of these interconnected conditions.

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, manifest as a result of intricate interactions involving genetic predisposition, environmental factors, intestinal microbiota dynamics, and immune dysregulation, ultimately leading to persistent mucosal inflammation. Addressing this complex pathology requires a nuanced understanding to inform targeted therapeutic strategies. Consequently, our study explored the viability of Aged Garlic Extract (AGE) as an alternative therapeutic regimen for IBD management. Utilizing gas chromatography-mass spectrometry (GC-MS) and scanning electron microscopy (SEM), we characterized AGE, revealing distinctions from Fresh Garlic Extract (FGE), particularly the absence of allicin in AGE and accompanying structural alterations. In In-Vivo experiments employing an IBD rat model, AGE intervention exhibited remarkable antioxidant, antibacterial, and anti-inflammatory properties. Noteworthy outcomes included improved survival rates, mitigation of intestinal damage, restoration of gut microbial diversity, reinforcement of tight junctions, and reversal of mitochondrial dysfunction. Collectively, these effects contributed to the preservation of enterocyte integrity and the attenuation of inflammation. In conclusion, the unique chemical composition of AGE, coupled with its substantial influence on gut microbiota, antioxidant defenses, and inflammatory pathways, positions it as a promising adjunctive therapy for the management of IBD. These observations, synergistically considered with existing research, provide significant insights into the potential utility of AGE in addressing the intricate pathophysiology inherent to IBD. The potential strength of study and rationale of using AGE against IBD includes exploring alternative therapeutic regimens if conventional treatments are associated with side effects, identification of potential hotspots/pathways involved in disease progression and study can provide economically cheaper and naturally occurring alternative to patient community who are struggling to afford expensive medications. These promising findings underscore the necessity for additional investigations to ascertain the feasibility of clinical translation, thereby substantiating the potential therapeutic role of AGE in the management of IBD.

Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.

Crohn's disease (CD) progresses with periods of remission and exacerbations. During exacerbations, chronic inflammation leads to tissue destruction. As a result, intestinal fibrosis may develop in response to the ongoing inflammatory process. Fibrosis in CD should be considered the result of the response of the intestinal wall (over) to the presence of inflammation in the deep structures of the intestinal wall. In the absence of ideal noninvasive methods, endoscopic evaluation in combination with biopsy, histopathological analysis, stool analysis, and blood analysis remains the gold standard for assessing both inflammation and fibrosis in CD. On the contrary, the ability to identify markers of intestinal fibrosis would help to develop new diagnostic and therapeutic methods to detect early stages of fibrosis. It is speculated that miRNAs may, in the future, become biomarkers for early noninvasive diagnosis in the treatment of intestinal fibrosis. The purpose of this review is to summarise existing diagnostic methods for Crohn's disease and present recent scientific reports on molecular testing.

The epithelium lining the intestinal tract serves a multifaceted role. It plays a crucial role in nutrient absorption and immune regulation and also acts as a protective barrier, separating underlying tissues from the gut lumen content. Disruptions in the delicate balance of the gut epithelium trigger inflammatory responses, aggravate conditions such as inflammatory bowel disease, and potentially lead to more severe complications such as colorectal cancer. Maintaining intestinal epithelial homeostasis is vital for overall health, and there is growing interest in identifying nutraceuticals that can strengthen the intestinal epithelium. α-Ketoglutarate, a metabolite of the tricarboxylic acid cycle, displays a variety of bioactive effects, including functioning as an antioxidant, a necessary cofactor for epigenetic modification, and exerting anti-inflammatory effects. This article presents a comprehensive overview of studies investigating the potential of α-ketoglutarate supplementation in preventing dysfunction of the intestinal epithelium.

Bariatric surgery has been reported to produce durable weight loss in the management of obesity; sleeve gastrectomy (SG) is the most common bariatric procedure. Obesity is a common comorbidity of inflammatory bowel disease (IBD), and the impact of IBD on short-term SG outcomes has not been widely reported. This study assessed whether IBD was associated with adverse post-SG outcomes.

Hospitalizations of patients undergoing SG in the United States were identified using the 2010-2020 Nationwide Readmissions Database (NRD) and stratified by IBD diagnosis. The SG cohort was propensity-matched based on age, biological sex, body mass index (BMI), comorbid diabetes, hypertension, depression, chronic obstructive pulmonary disease, and discharge in quarter four. Primary aims were to compare in-hospital mortality, post-operative complications, and all-cause 90-day readmission between patients with and without IBD. Secondary outcomes were length of stay (LOS) and total hospital cost.

A total of 2030 hospitalizations were matched. The odds of complication were 48% higher for hospitalizations of patients with IBD (11.1% vs. 7.8%; aOR 1.48, aOR 95% CI 1.10-2.00, p = .009). The most common complication was nausea (4.9% vs. 3.7%, p = .187). No statistically significant difference was observed for all-cause 90-day readmissions, LOS, or hospital cost.

Hospitalizations of patients with IBD who underwent SG experienced significantly higher post-operative complication rates. However, the similar lengths of stay and readmission rates compared to propensity-matched SG hospitalizations without IBD suggest many complications were minor. SG remains a safe weight loss procedure for patients suffering from IBD and obesity.

The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of "mechanistic granularity" chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others - as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 75% of the world's population still use plant-based medicinal compounds, indicating the ongoing significance of phytochemicals for human health. This study emphasizes the growing body of research investigating the anti-adipogenic and anti-obesity functions of polyphenols. The functions of polyphenols, including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids, are distinct due to changes in chemical diversity and structural characteristics. This review methodically investigates the mechanisms by which naturally occurring polyphenols mediate obesity and metabolic function in immunomodulation. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role, in part, in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function and the effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required to understand the prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes a holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

Impairment of intestinal epithelium is a typical feature of inflammatory bowel disease (IBD) that causes leakage of bacteria and antigens from the intestinal lumen and thus results in persistent immune activation. Hence, healing and regeneration of the damaged gut mucosa is a promising therapeutic approach to achieve deep remission in IBD. Currently, available systemic therapies have moderate effects and are often associated with numerous side effects and malignancies. In this study, we aimed to develop a topical therapy by chemically conjugating a temperature-responsive polymer, i.e., poly(N-isopropylacrylamide), along with hyaluronic acid to obtain a sprayable therapeutic formulation that upon colon instillation adheres to the damaged gut mucosa due to its temperature-induced phase transition and mucoadhesive properties. An ex vivo adhesion experiment demonstrates that this therapeutic formulation forms a thin physical coating on the mucosal lining at a physiological temperature within 5 min. Physicochemical characterization of (P(NIPAM-co-NTBAM)-HA) established this formulation to be biocompatible, hemo-compatible, and non-immunogenic. Prednisolone was encapsulated within the polymer formulation to achieve maximum therapeutic efficacy in the case of IBD-like conditions as assessed in a custom-fabricated perfusion-based ex vivo model system. Histological analysis suggests that the prednisolone-encapsulated polymer formulation nearly restored the mucosal architecture after 2,4,6-trinitrobenzenesulfonic acid-induced damage. Furthermore, a significant (p ≤ 0.001) increase in mRNA levels of Muc-2 and ZO-1 in treated groups further confirmed the mucosal epithelial barrier restoration.

5-androstenediol (ADIOL) functions as a selective estrogen receptor β (ERβ) ligand with a protective effect against many diseases. So, we conducted a novel insight into its role in acetic acid (AA)-induced colitis and investigated its effect on TLR4-Mediated PI3K/Akt and NF-κB Pathways and the potential role of ERβ as contributing mechanisms.

Rats were randomized into 5 Groups; Control, Colitis, Colitis + mesalazine (MLZ), Colitis + ADIOL, and Colitis + ADIOL + PHTPP (ER-β antagonist). The colitis was induced through a rectal enema of acetic acid (AA) on the 8th day. At the end of treatment, colons were collected for macroscopic assessment. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor kappa b (NF-κB), toll-like receptor (TLR4), and phosphorylated Protein kinase B (pAKT) were measured. Besides, Gene expression of interleukin-1beta (IL-1β), metalloproteases 9 (Mmp9), inositol 3 phosphate kinase (PI3K), Neutrophil gelatinase-associated lipocalin (NGAL), ERβ and NLRP6 were assessed. Histopathological and immunohistochemical studies were also investigated.

Compared to the untreated AA group, the disease activity index (DAI) and macroscopic assessment indicators significantly decreased with ADIOL injections. Indeed, ADIOL significantly decreased colonic tissue levels of MDA, TLR4, pAKT, and NF-κB immunostainig while increased SOD activity and β catenin immunostainig. ADIOL mitigated the high genetic expressions of IL1β, NGAL, MMP9, and PI3K while increased ERβ and NLRP6 gene expression. Also, the pathological changes detected in AA groups were markedly ameliorated with ADIOL. The specific ERβ antagonist, PHTPP, largely diminished these protective effects of ADIOL.

ADIOL could be beneficial against AA-induced colitis mostly through activating ERβ.

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the colon's mucosal lining, leading to chronic bowel inflammation. Despite extensive research, the precise molecular mechanisms underlying UC pathogenesis remain elusive. NcRNAs form a category of functional RNA molecules devoid of protein-coding capacity. They have recently surfaced as pivotal modulators of gene expression and integral participants in various pathological processes, particularly those related to inflammatory disorders. The diverse classes of ncRNAs, encompassing miRNAs, circRNAs, and lncRNAs, have been implicated in UC. It highlights their involvement in key UC-related processes, such as immune cell activation, epithelial barrier integrity, and the production of pro-inflammatory mediators. ncRNAs have been identified as potential biomarkers for UC diagnosis and monitoring disease progression, offering promising avenues for personalized medicine. This approach may pave the way for novel, more specific treatments with reduced side effects, addressing the current limitations of conventional therapies. A comprehensive understanding of the interplay between ncRNAs and UC will advance our knowledge of the disease, potentially leading to more effective and personalized treatments for patients suffering from this debilitating condition. This review explores the pivotal role of ncRNAs in the context of UC, shedding light on their possible targets for diagnosis, prognosis, and therapeutic interventions.

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Inflammatory bowel disease, whose major forms are Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gut due to the loss of tolerance toward antigens normally contained in the gut lumen. G protein-coupled receptor (GPR) 120 has gained considerable attention as a potential therapeutic target for metabolic disorders due to its implication in the production of the incretin hormone glucagon-like peptide 1 and the secretion of cholecystokinin. Recent studies have also highlighted the role of GPR120 in regulating immune system activity and inflammation. GPR120, expressed by intestinal epithelial cells, proinflammatory macrophages, enteroendocrine L cells, and CD4+ T cells, suppresses proinflammatory and enhances anti-inflammatory cytokine production, suggesting that GPR120 might have a pivotal role in intestinal inflammation and represent a possible therapeutic target in inflammatory bowel disease. This narrative review aims at summarizing the role of GPR120 in the maintenance of intestinal homeostasis through the analysis of the most recent studies.

The pharmacological approach to treating gastrointestinal diseases is suffering from various challenges. Among such gastrointestinal diseases, ulcerative colitis manifests inflammation at the colon site specifically. Patients suffering from ulcerative colitis notably exhibit thin mucus layers that offer increased permeability for the attacking pathogens. In the majority of ulcerative colitis patients, the conventional treatment options fail in controlling the symptoms of the disease leading to distressing effects on the quality of life. Such a scenario is due to the failure of conventional therapies to target the loaded moiety into specific diseased sites in the colon. Targeted carriers are needed to address this issue and enhance the drug effects. Conventional nanocarriers are mostly readily cleared and have nonspecific targeting. To accumulate the desired concentration of the therapeutic candidates at the inflamed area of the colon, smart nanomaterials with responsive nature have been explored recently that include pH responsive, reactive oxygen species responsive (ROS), enzyme responsive and thermo - responsive smart nanocarrier systems. The formulation of such responsive smart nanocarriers from nanotechnology scaffolds has resulted in the selective release of therapeutic drugs, avoiding systemic absorption and limiting the undesired delivery of targeting drugs into healthy tissues. Recent advancements in the field of responsive nanocarrier systems have resulted in the fabrication of multi-responsive systems i.e. dual responsive nanocarriers and derivitization that has increased the biological tissues and smart nanocarrier's interaction. In addition, it has also led to efficient targeting and significant cellular uptake of the therapeutic moieties. Herein, we have highlighted the latest status of the responsive nanocarrier drug delivery system, its applications for on-demand delivery of drug candidates for ulcerative colitis, and the prospects are underpinned.

Oxidative stress is a major contributor to progressive neurodegenerative disease and may be a key target for the development of novel preventative and therapeutic strategies. Nitroxides have been successfully utilised to study changes in redox status (biological probes) and modulate radical-induced oxidative stress. This study investigates the efficacy of DCTEIO (5,6-dicarboxy-1,1,3,3-tetraethyllisoindolin-2-yloxyl), a stable, kinetically-persistent, nitroxide-based antioxidant, as a retinal neuroprotectant. The preservation of retinal function following an acute ischaemic/reperfusion (I/R) insult in the presence of DCTEIO was quantified by electroretinography (ERG). Inflammatory responses in retinal glia were analysed by GFAP and IBA-1 immunohistochemistry, and retinal integrity assessed by histology. A nitroxide probe combined with flow cytometry provided a rapid technique to assess oxidative stress and the mitigation offered by antioxidant compounds in cultured 661W photoreceptor cells. DCTEIO protected the retina from I/R-induced damage, maintaining retinal function. Histological analysis showed preservation of retinal integrity with reduced disruption and disorganisation of the inner and outer nuclear layers. I/R injury upregulated GFAP expression, indicative of retinal stress, which was significantly blunted by DCTEIO. The number of 'activated' microglia, particularly in the outer retina, in response to cellular stress was also significantly reduced by DCTEIO, potentially suggesting reduced inflammasome activation and cell death. DCTEIO mitigated oxidative stress in 661W retinal cell cultures, in a dose-dependent fashion. Together these findings demonstrate the potential of DCTEIO as a neuroprotective therapeutic for degenerative diseases of the CNS that involve an ROS-mediated component, including those of the retina e.g. age-related macular degeneration and glaucoma.

Ulcerative colitis (UC) is a severe inflammatory bowel disease (IBD) characterized by multifactorial complex disorders triggered by environmental factors, genetic susceptibility, and also gut microbial dysbiosis. Faecalibacterium prausnitzii, Bacteroides faecis, and Roseburia intestinalis are underrepresented species in UC patients, leading to the hypothesis that therapeutic application of those bacteria could ameliorate clinical symptoms and disease severity. Acute colitis was induced in mice by 3.5% DSS, and the commensal bacterial species were administered by oral gavage simultaneously with DSS treatment for up to 7 days. The signs of colonic inflammation, the intestinal barrier integrity, the proportion of regulatory T cells (Tregs), and the expression of pro-inflammatory and anti-inflammatory cytokines were quantified. The concentrations of SCFAs in feces were measured using Gas-liquid chromatography. The gut microbiome was analyzed in all treatment groups at the endpoint of the experiment. Results were benchmarked against a contemporary mesalazine treatment regime. We show that commensal species alone and in combination reduced disease activity index scores, inhibited colon shortening, strengthened the colonic epithelial barrier, and positively modulated tight junction protein expression. The expression level of pro-inflammatory cytokines was significantly reduced. Immune modulation occurred via inhibition of the loss of CD4 +CD25 +Treg cells in the spleen. Our study proofed that therapeutic application of F. prausnitzii, B. faecis, and R. intestinalis significantly ameliorated DSS-induced colitis at the level of clinical symptoms, histological inflammation, and immune status. Our data suggest that these positive effects are mediated by immune-modulatory pathways and influence on Treg/Th17 balance.

Although Zinc pyrithione (ZPT) could lower blood pressure by inducing vasorelaxation, it is unclear if it is able to induce vasorelaxation of mesenteric arterioles in health and ulcerative colitis (UC) to exert anti-colitic action.

The vasorelaxation of the second-order branch of the mesenteric artery from wide type (WT) mice, TRPV1-/-(KO) mice, and TRPV4-/-(KO) mice was determined using a Mulvany-style wire myograph. Calcium imaging and patch clamp were applied to analyze the actions of ZPT in human vascular endothelial cells. Mouse model of UC was used to evaluate the anti-colitic action of ZPT.

ZPT dose-dependently induced mesenteric vasorelaxation predominately through endothelium-dependent hyperpolarization (EDH), which could be attenuated by intracellular Zn2+ and Ca2+ chelators TPEN and BAPTA-AM. The ZPT/EDH-mediated vasorelaxation via TRPV1, TRPV4 and TRPA1 channels was verified by a combination of selective pharmacological inhibitors and TRPV1-KO and TRPV4-KO mice. Moreover. ZPT induced Ca2+ entry via vascular endothelial TRPV1/4 and TRPA1 channels and enhanced membrane non-selective currents through these channels. Notably, ZPT exerted anti-colitic effects by rescuing the impaired acetylcholine (ACh)-induced mesenteric vasorelaxation in colitic mice.

ZPT/Zn2+ induces EDH-mediated mesenteric vasorelaxation through activating endothelial multiple TRPV1/4 and TPPA1 channels in health, and rescues the impaired ACh-induced vasorelaxation to exert anti-colitic action. Our study may open a new avenue of potential vessel-specific targeted therapy for UC.

Inflammatory bowel disease (IBD) is a global public health challenge that affects millions of people. Current medical treatments for IBD are not fully effective and may cause undesirable side effects on patients. Thus, there is an urgent need for safe, simple, and efficacious strategies to treat IBD in clinical settings. Here, we develop an oral polyphenol nanoparticle (PDT) by assembling dexamethasone sodium phosphate (DSP)-loaded poly-β-cyclodextrin with tannic acid via host-guest interactions for treating IBD. This one-step assembly process is rapid (within 10 s), reproducible, and free of harmful chemical agents, which can facilitate its clinical translation. PDT is negatively charged due to the three components, which enable it to specifically target the positively charged inflamed colonic mucosa through electrostatic attraction, thus localizing the drug at the inflamed site to reduce systemic exposure and side effects. Furthermore, PDT exhibits a strong reactive oxygen species (ROS)-scavenging ability derived from the tannic acid component, which can alleviate ROS-mediated inflammatory responses and ameliorate IBD symptoms. Compared with free DSP, PDT demonstrates sustained DSP release behavior in vitro and in vivo, as well as enhanced therapeutic efficacy in a colitis mouse model. These results suggest that PDT might be a potential therapeutic agent for the treatment of IBD. Moreover, this facile polyphenol host-guest assembly strategy may provide a promising drug-delivery platform for treating various diseases STATEMENT OF SIGNIFICANCE: To develop safe and effective treatments for inflammatory bowel disease (IBD), we have designed an oral polyphenol nanoparticle (PDT) using the host-guest assembly of dexamethasone sodium phosphate (DSP)-loaded poly-β-cyclodextrin with tannic acid. Through in vitro and in vivo experiments, PDT has demonstrated remarkable inflammation-targeting, ROS-scavenging, and anti-inflammatory properties, along with sustained release of DSP. Moreover, in an IBD mouse model, PDT has shown significantly improved therapeutic efficacy compared to free DSP. The host-guest assembly strategy employed for PDT is noteworthy for its rapidity, reproducibility, and safety due to the absence of harmful chemicals, holding great promise for designing a diverse range of nanomedicines customized for treating various diseases.

Ulcerative colitis (UC) is a persistent inflammatory disorder that affects the gastrointestinal tract, mainly the colon, which is defined by inflammatory responses and the formation of ulcers. Probiotics have been shown to directly impact various immune cells, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and T and B cells. By interacting with cell surface receptors, they regulate immune cell activity, produce metabolites that influence immune responses, and control the release of cytokines and chemokines.

This article is a comprehensive review wherein we conducted an exhaustive search across published literature, utilizing reputable databases like PubMed and Web of Science. Our focus centered on pertinent keywords, such as "UC," 'DSS," "TNBS," "immune cells," and "inflammatory cytokines," to compile the most current insights regarding the therapeutic potential of probiotics in managing UC.

This overview aims to provide readers with a comprehensive understanding of the effects of probiotics on immune cells in relation to UC. Probiotics have a crucial role in promoting the proliferation of regulatory T cells (Tregs), which are necessary for preserving immunological homeostasis and regulating inflammatory responses. They also decrease the activation of pro-inflammatory cells like T helper 1 (Th1) and Th17 cells, contributing to UC development. Thus, probiotics significantly impact both direct and indirect pathways of immune cell regulation in UC, promoting Treg differentiation, inhibiting pro-inflammatory cell activation, and regulating cytokine and chemokine release.

Probiotics demonstrate significant potential in modulating the immune reactions in UC. Their capacity to modulate different immune cells and inflammation-related processes makes them a promising therapeutic approach for managing UC. However, further studies are warranted to optimize their use and fully elucidate the molecular mechanisms underlying their beneficial effects in UC treatment.

Intestinal inflammation is mediated by a subset of cells populating the intestine, such as enteric glial cells (EGC) and macrophages. Different studies indicate that phytocannabinoids could play a possible role in the treatment of inflammatory bowel disease (IBD) by relieving the symptoms involved in the disease. Phytocannabinoids act through the endocannabinoid system, which is distributed throughout the mammalian body in the cells of the immune system and in the intestinal cells. Our in vitro study analyzed the putative anti-inflammatory effect of nine selected pure cannabinoids in J774A1 macrophage cells and EGCs triggered to undergo inflammation with lipopolysaccharide (LPS). The anti-inflammatory effect of several phytocannabinoids was measured by their ability to reduce TNFα transcription and translation in J774A1 macrophages and to diminish S100B and GFAP secretion and transcription in EGCs. Our results demonstrate that THC at the lower concentrations tested exerted the most effective anti-inflammatory effect in both J774A1 macrophages and EGCs compared to the other phytocannabinoids tested herein. We then performed RNA-seq analysis of EGCs exposed to LPS in the presence or absence of THC or THC-COOH. Transcriptomic analysis of these EGCs revealed 23 differentially expressed genes (DEG) compared to the treatment with only LPS. Pretreatment with THC resulted in 26 DEG, and pretreatment with THC-COOH resulted in 25 DEG. To evaluate which biological pathways were affected by the different phytocannabinoid treatments, we used the Ingenuity platform. We show that THC treatment affects the mTOR and RAR signaling pathway, while THC-COOH mainly affects the IL6 signaling pathway.

Inflammatory Bowel Disease (IBD) is a complex, chronic inflammatory condition affecting the gastrointestinal tract. IBD has been associated with a variety of neurologic manifestations including peripheral nerve involvement, increased risk of thrombotic, demyelinating and events. Furthermore, an evolving association between IBD and neurodegenerative disorders has been recognized, and early data suggests an increased risk of these disorders in patients diagnosed with IBD. The relationship between intestinal inflammatory disease and neuroinflammation is complex, but the bidirectional interaction between the brain-gut-microbiome axis is likely to play an important role in the pathogenesis of these disorders. Identification of common mechanisms and pathways will be key to developing potential therapies. In this review, we discuss the evolving interface between IBD and neurological conditions, with a focus on clinical, mechanistic, and potentially therapeutic implications.

Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules.

In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging.

Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords.

Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions.

Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.

Interleukin-23 (IL-23) is a proinflammatory cytokine produced mainly by macrophages and antigen-presenting cells (APCs) after antigenic stimulation. IL-23 plays a significant role as a mediator of tissue damage. Indeed, the irregularities in IL-23 and its receptor signaling have been implicated in inflammatory bowel disease. IL-23 interacts with both the innate and adaptive immune systems, and IL-23/Th17 appears to be involved in the development of chronic intestinal inflammation. The IL-23/Th17 axis may be a critical driver of this chronic inflammation. This review summarizes the main aspects of IL-23's biological function, cytokines that control cytokine production, effectors of the IL-23 response, and the molecular mechanisms associated with IBD pathogenesis. Although IL-23 modulates and impacts the development, course, and recurrence of the inflammatory response, the etiology and pathophysiology of IBD are not completely understood, but mechanism research shows huge potential for clinical applications as therapeutic targets in IBD treatment.

Few studies have thoroughly assessed the efficacy and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD). Therefore, this systematic review and meta-analysis was performed to further evaluate this association. PubMed, Embase, and the Cochrane databases were searched until April 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of VDZ in the treatment of IBD were included. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome using a random effects model. A total of 12 RCTs, including 4,865 patients, met the inclusion criteria. In the induction phase, VDZ was more effective than placebo for patients with ulcerative colitis and Crohn's disease (CD) in clinical remission (RR=2.09; 95% CI=1.66-2.62) and clinical response (RR=1.54; 95% CI=1.34-1.78). In the maintenance therapy group, VDZ reached higher clinical remission (RR=1.98; 95% CI=1.58-2.49) and clinical response (RR=1.78; 95% CI=1.40-2.26) rates compared with the placebo group. VDZ particularly improved clinical remission (RR=2.07; 95% CI=1.48-2.89) and clinical response (RR=1.84; 95% CI=1.54-2.21) in patients with TNF antagonist failure. In terms of corticosteroid-free remission, VDZ was also more effective than placebo in patients with IBD (RR=1.98; 95% CI=1.51-2.59). In Crohn's patients, VDZ was more effective than placebo in terms of mucosal healing (RR=1.78; 95% CI=1.27-2.51). With respect to adverse events, VDZ significantly reduced the risk of IBD exacerbation compared with the placebo (RR=0.60; 95% CI=0.39-0.93; P=0.023). However, when compared with the placebo, VDZ increased the risk of nasopharyngitis in patients with CD (RR=1.77; 95% CI=1.01-3.10; P=0.045). No significant differences in other adverse events were observed. Although there might be underlying risk, such as selection bias, in the present study it can be safely concluded that VDZ is a safe and effective biological agent for IBD, particularly for patients with TNF antagonist failure.

Lack of public understanding and perception may lead to a general downplaying of inflammatory bowel disorder (IBD) symptoms as they affect a less socially acceptable area of the body, which may be a significant component in the everyday struggles of an individual with IBD.

The aim is to assess the public knowledge of Crohn's disease and ulcerative colitis in Saudi Arabia.

This was an online survey study that examined public knowledge of IBD in Saudi Arabia for the duration between February and March 2023. Participants were invited to participate in this study using social media websites. The questionnaire tool comprised three sections: a sociodemographic characteristics section (seven questions), an awareness section (two questions), and a knowledge section (24 questions). A binary logistic regression analysis was utilized to identify the factors that influenced the participants' knowledge of Crohn's disease and ulcerative colitis.

A total of 630 individuals participated in this study. Around 28% of the participants reported that they had never heard of, read about, or dealt with Crohn's disease. Around 16% of them reported that they had never heard of, read about, or dealt with ulcerative colitis. The mean overall knowledge score of the study participants was 8.3 (standard deviation: 2.4) out of 24, which is equal to 34.6% and represents a weak level of knowledge of IBD. The participants showed a weak level of knowledge for all sub-scales of knowledge related to IBD general knowledge, diet, treatments, and complications. The knowledge sub-scale level ranged between 30% and 36.7%. Females, the participants in the moderate and high-income category, those who lived in urban areas, those with a higher level of education, and those who reported having osteoarthritis were more likely to be knowledgeable about IBD compared to others (p≤0.001).

In Saudi Arabia, a low level of IBD awareness was identified among the general population, supporting findings from other countries. Future research should aim to identify effective educational interventions to increase public awareness of this group of diseases, which would ultimately facilitate early diagnosis and improve patient outcomes.

Inflammatory bowel disease (IBD) is considered a chronic inflammatory and multifactorial disease of the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) are two types of chronic IBD. Although there is no accurate information about IBD pathophysiology, evidence suggests that various factors, including the gut microbiome, environment, genetics, lifestyle, and a dysregulated immune system, may increase susceptibility to IBD. Moreover, inflammatory mediators such as interleukin-6 (IL-6) are involved in the immunopathogenesis of IBDs. IL-6 contributes to T helper 17 (Th17) differentiation, mediating further destructive inflammatory responses in CD and UC. Moreover, Th1-mediated responses participate in IBD, and the antiapoptotic IL-6/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signals are responsible for preserving Th1 cells in the site of inflammation. It has been revealed that fecal bacteria isolated from UC-active and UC-remission patients stimulate the hyperproduction of several cytokines, such as IL-6, tumor necrosis factor-α (TNF-α), IL-10, and IL-12. Given the importance of the IL-6/IL-6R axis, various therapeutic options exist for controlling or treating IBD. Therefore, alternative therapeutic approaches such as modulating the gut microbiome could be beneficial due to the failure of the target therapies so far. This review article summarizes IBD immunopathogenesis focusing on the IL-6/IL-6R axis and discusses available therapeutic approaches based on the gut microbiome alteration and IL-6/IL-6R axis targeting and treatment failure.