Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.

Probiotics have been established to exert a positive impact on the treatment of various diseases. Indeed, these active microorganisms have garnered significant attention in recent years for their potential to prevent and treat illnesses. Their beneficial effects have been hypothesized to be linked to their released extracellular vesicles. These nanoscale structures, secreted during the growth and metabolism of probiotics, possess favorable biocompatibility and targeting properties, thereby promoting intercellular material transport and signaling. This article aimed to review the bioactive components and functions of these probiotics vesicles, highlighting their role in the treatment of various diseases and discussing their potential future applications. By exploring the mechanisms of probiotic extracellular vesicles in disease development, this review aimed to provide a theoretical reference for further research on their therapeutic potential. © 2025 Society of Chemical Industry.

Inflammatory bowel disease (IBD) is a chronic, progressive, immune-mediated, gastrointestinal inflammatory disease with increasing occurrences in children. Collagen triple helix repeat containing 1 (CTHRC1), a migration-promoting protein, acts as a tumor-promoting factor in malignant tumors. However, functions and mechanisms of CTHRC1 in children with IBD remain unclear. This study aimed to determine the effects and mechanisms of CTHRC1 on dextran sodium sulfate (DSS)-treated HT-29 cells. HT-29 control cells were exposed to 2% DSS to develop an in vitro IBD model. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to assess CTHRC1 expression in serum of children with IBD and HT-29 cells. Cell viability and apoptosis were assessed using MTT and flow cytometry (FCM). Expressions of cleaved-Caspase3 and Caspase3 were determined by western blotting. The cytokine production (TNF-α, IL-1β and IL-6) in HT-29 cells was measured by ELISA assay. Activation or inactivation of NF-κB signaling pathway was confirmed by western blot assay. Results showed that CTHRC1 expression was upregulated in the IBD serum and HT-29 control cells. The level of CTHRC1 was lower in CTHRC1-siRNA transfected cells than in control siRNA-treated cells. Notably, silence of CTHRC1 markedly enhanced HT-29 cells viability, decreased apoptotic cells, suppressed cleaved-Caspase3 expression, inhibited cleaved-Caspase3/Caspase3 ratio, reduced the production of inflammatory cytokines, and blocked NF-κB signaling pathway induced by DSS. However, these effects were reversed following diprovocim treatment. Thus, that knockdown of CTHRC1 alleviated DSS-induced HT-29 cell injury by inhibiting the NF-κB signaling pathway in vitro, providing a new therapeutic target for IBD in children.

The online version contains supplementary material available at 10.1007/s10616-025-00705-x.

Chimeric antigen receptor (CAR)-engineered cell therapies have made significant progress in haematological cancer treatment. This success has motivated researchers to investigate its potential applications in non-cancerous diseases, with substantial strides already made in this field.

This review summarises the latest research on CAR-engineered cell therapies, with a particular focus on CAR-T cell therapy for non-cancerous diseases, including but not limited to infectious diseases, autoimmune diseases, cardiac diseases and immune-mediated disorders in transplantation. Additionally, the review discusses the current obstacles that need to be addressed for broader clinical applications.

With ongoing research and continuous improvements, CAR-engineered cell therapy holds promise as a potent tool for treating various diseases in the future.

CAR-engineered cell therapy has expanded beyond cancer to treat autoimmune diseases, infections, cardiac diseases, and transplant-related rejection. The CAR platform is diverse, with various cell types such as CAR-T, CAR-NK, and CAR-M potentially suited for different disease contexts. The safety, efficacy, and practicality of CAR cell therapy in non-cancer diseases remain challenging, requiring further technological optimization and clinical translation.

Inflammatory bowel disease (IBD), a chronic gastrointestinal disorder, often emerges during childhood and poses significant challenges due to its adverse effects on growth, development, and psychosocial well-being. Circular RNAs (circRNAs) have been implicated in the pathogenesis of diverse diseases. However, the specific biological role and mechanisms of circRNA OMA1 in children with IBD remain largely unexplored. This study investigates the functions and mechanistic pathways of circRNA OMA1 in the progression of IBD. Quantitative real-time PCR (qRT-PCR) was employed to quantify circRNA OMA1 and miR-654-3p expression levels in the serum of children with IBD and in HT-29 cells. Downstream miRNA and mRNA targets of circRNA OMA1 were predicted using StarBase and validated via luciferase reporter assays. An in vitro IBD model was established by treating the human colonic epithelial cell line (HT-29) with 2% dextran sulfate sodium (DSS). Cell viability and apoptosis were assessed using the MTT assay and flow cytometry, respectively. Expression of the apoptosis-related protein cleaved caspase-3 was analyzed via western blotting, and proinflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were measured using ELISA. The expression of circRNA OMA1 was notably lower in the serum of children with IBD and in DSS-treated HT-29 cells than in healthy controls, whereas miR-654-3p expression was upregulated. Bioinformatics analyses revealed a direct interaction between circRNA OMA1 and miR-654-3p. Overexpression of circRNA OMA1 through plasmid transfection increased circRNA OMA1 levels and suppressed miR-654-3p expression in HT-29 cells under both basal and DSS-stimulated conditions. Conversely, transfection with a miR-654-3p mimic reversed these effects. Upregulation of circRNA OMA1 ameliorated DSS-induced injury in HT-29 cells by enhancing cell viability, reducing apoptosis, and downregulating cleaved caspase-3 expression. Moreover, circRNA OMA1 overexpression inhibited the secretion of inflammatory cytokines TNF-α, IL-1β, and IL-6. However, these protective effects were partially reversed by treatment with the miR-654-3p mimic. Additionally, miR-654-3p was shown to directly target RAF1, negatively regulating its expression. The proliferation-promoting and apoptosis-suppressing effects of miR-654-3p inhibitor treatment were mitigated by RAF1-siRNA. Conclusion: Upregulation of circRNA OMA1 alleviates DSS-induced colonic cell apoptosis and inflammation by modulating the miR-654-3p/RAF1 axis. These findings suggest that circRNA OMA1 could be a promising biomarker for the diagnosis and treatment of IBD.

The online version contains supplementary material available at 10.1007/s10616-025-00703-z.

Impaired intestinal epithelial barrier function is closely associated with the pathogenesis of ulcerative colitis (UC). Atractylenolide-I (AT-I), a major sesquiterpene derived from the herb Atractylodes macrocephala Koidz., has been reported to alleviate DSS-induced colitis in mice. This study aims to investigated the protective effects of AT-1 on intestinal epithelial barrier function and elucidate it's underlying mechanisms. In vivo, an acute colitis model was established in mice, and transcriptomic analysis to identify differentially expressed genes. In vitro, overexpression plasmids and recombinant protein were used to evaluate their effects on intestinal barrier function, and further analysis of its potential mechanisms.The study found that AT-1 ameliorate DSS-induced acute ulcerative colitis, exhibiting protective effects on the intestinal barrier. Transcriptomic analysis revealed that AT-1 significantly modulated the expression of S100A8 and S100A9. Further investigations indicated that S100A9, rather than S100A8, mediated the expression of tight junction proteins, meanwhile, AT-1 reduces neutrophil activation and subsequent release of S100A9. Mechanistically, recombinant human S100A9 protein was found to induce a decrease in intracellular Ca2+ concentration, while AT-1 regulated the expression of tight junction proteins via modulation of the AMPK/mTOR signaling pathway. AT-1 enhances the recovery of DSS-induced intestinal barrier dysfunction by regulating the recombinant human S100A9 protein-mediated AMPK/mTOR signaling pathway. This study provides new insights into the pathogenesis of ulcerative colitis and suggests potential therapeutic strategies for its treatment.

Jasonia glutinosa (L.) DC., commonly known in Spain as "Rock Tea", is a medicinal plant native to the Iberian Peninsula, southern France, and Morocco. It has traditionally been used as a digestive, analgesic, antimicrobial, antidepressant, or for respiratory diseases. This narrative review aims to scientifically validate the ethnopharmacological uses of J. glutinosa as a medicinal plant, emphasizing the relationship between its traditional applications, pharmacological activities, and mechanisms of action based on experimental evidence. A comprehensive search was conducted in various electronic databases to gather information on its traditional uses, phytochemical composition, and in vitro, ex vivo, and in vivo studies related to pharmacological properties. The literature review uncovered significant findings regarding the pharmacological and molecular mechanisms of this medicinal plant in various experimental models, particularly highlighting its spasmolytic, anti-inflammatory, and antioxidant properties.

Exocrine pancreatic insufficiency (EPI) is a major cause of maldigestion and malnutrition, resulting from primary pancreatic diseases or other conditions. As the prevalence of EPI continues to rise, accurate identification of its etiology has become critical for the diagnosis and treatment of pancreatic secretory insufficiency. EPI can result from both pancreatic and non-pancreatic disorders. Pancreatic disorders include acute and chronic pancreatitis, pancreatic tumors, cystic fibrosis, procedures that involve pancreatic resection, and other rare causes. Non-pancreatic disorders of EPI include diabetes mellitus, celiac disease, inflammatory bowel disease, gastrointestinal and esophagectomy surgery, as well as advanced patient age. This review aims to provide a comprehensive analysis of the literature on EPI etiology, with a thorough overview to support its consideration as a potential diagnosis.

Interleukin-1 receptor 2 (IL1R2) and C-C motif chemokine receptor 2 (CCR2) as critical mediators of immune modulation and inflammation. This study aims to evaluate their functions in dextran sulfate sodium (DSS)-induced intestinal injury.

A DSS-induced intestinal injury model was established in C57BL/6 mice. Pharmacological inhibitors targeting IL1R2 or CCR2 were administered. Adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes were isolated and loaded with IL1R2-siRNA, which were then administered to intestinal epithelial cells (IEC-6) or DSS-challenged mice.

IL1R2 and CCR2 were upregulated in DSS-treated colon tissues. Pharmacological inhibition of IL1R2 or CCR2 improved body weight, restored colon length, reduced serum TNF-α and IL-6 levels, and preserved epithelial integrity in mice. miR-128-3p enriched in ADMSC-derived exosomes significantly reduced CCR2 expression in IEC-6 cells. Further loading of an IL1R2 siRNA in these exosomes led to a simultaneous inhibition of IL1R2. These exosomes reduced lipopolysaccharide-induced apoptosis and inflammation in IEC-6 cells and improved histological outcomes in DSS-challenged mice.

IL1R2 and CCR2 are key mediators of inflammation in DSS-induced intestinal injury. Dual inhibition of IL1R2 and CCR2 holds great promise for alleviating inflammatory responses and improving histological presentations in inflammatory bowel disease.

Macadamia nut oil (MO) fatty acids are mainly composed of oleic acid and palmitoleic acid, which have a variety of health benefits. This study established an ulcerative colitis (UC) mouse model using dextran sulfate sodium (DSS), and the ameliorative effects of MO on UC were investigated. The results revealed that MO supplementation mitigated weight loss and colon shortening, increased goblet cell counts, and alleviated histopathologic changes in UC mice. MO significantly increased the intestinal antioxidant levels in UC mice. Moreover, Nrf2 and Ho-1 mRNA and protein expression levels were significantly upregulated in UC mice following treatment with low- and high-dose MO. In contrast, expression levels of Keap1 were significantly downregulated. Lastly, MO inhibited the inflammatory factors (TNF-α, IL-6 and IL-1β) expression in UC mice. These results indicate that MO could enhance colonic antioxidant levels, induce apoptosis, and activate the Nrf2/Ho-1 pathway, thereby ameliorating the pathological injuries associated with UC.

Bitter taste receptors (TAS2Rs) are expressed in extraoral tissues, exerting several functions and generating a whole-body chemosensory and protective system. TAS2Rs expression has been observed in the gastrointestinal tract, although their role is poorly understood. This study aims to investigate the role of TAS2R38 and 46 in human intestinal smooth muscle cells (HISMCs) after activation with the specific bitter ligands phenylthiocarbamide and absinthin, respectively. We found that TAS2R38 and 46 activation by phenylthiocarbamide (PTC) and absinthin, respectively, induces a rapid membrane depolarization and increase of cytosolic calcium levels due to internal storage in the IP3 pathway, resulting in an accelerated cell contraction. Overall, this study unravels, for the first time, the contractile impact of these TAS2R subtypes on intestinal smooth muscle cells, suggesting their involvement in gut peristalsis and recommending these receptors as possible targets for new therapies.

Prior research has established the significance of spleen volume (SV) in the pathogenesis and advancement of ulcerative colitis (UC) and Crohn's disease (CD). Nevertheless, these investigations are predominantly observational, thereby leaving their causal associations ambiguous. Moreover, the breadth of existing research is constrained by various uncontrollable variables in clinical settings. This study aims to deduce the causal link between SV and the susceptibility to UC and CD through a genetic perspective. The objective of this study was to investigate the genetic association between SV and inflammatory bowel disease (IBD) risk using Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) associated with SV were used as instrumental variables. Genetic associations for UC and CD were extracted from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), the FinnGen study, and other publicly available genome-wide association studies (GWAS). Methods such as inverse variance weighted, Bayesian weighted Mendelian randomization (BWMR), contamination mixture (ConMix), along with sensitivity analyses and the Steiger test were used in the study. A meta-analysis was conducted to synthesize the results. The study found that genetically predicted SV was associated with an increased risk of UC in the IIBDGC dataset (OR = 1. 223, 95% CI: 1. 055-1. 417, P = 0. 008), FinnGen (OR = 1. 169, 95% CI: 1. 003-1. 363, P = 0. 045), the GWAS study by Sakaue S (OR = 1. 188, 95% CI: 1. 008-1. 399, P = 0. 040), and in the meta-analysis (OR = 1. 115, 95% CI: 1. 014-1. 227, P = 0. 025). Similarly, genetically predicted SV was associated with an increased risk of CD in the IIBDGC dataset (OR = 1. 235, 95% CI: 1. 026-1. 488, P = 0. 026), FinnGen (OR = 1. 308, 95% CI: 1. 026-1. 667, P = 0. 030), the GWAS study by Zorina-Lichtenwalter K (OR = 1. 316, 95% CI: 1. 037-1. 670, P = 0. 024), and in the meta-analysis (OR = 1. 272, 95% CI: 1. 133-1. 428, P < 0. 001). According to the meta-analysis results, for each standard unit increase in SV, the risk of developing UC increases by 11. 5%, and the risk of developing CD increases by 27. 2%. This study presents findings that suggest a positive causal association between SV and the onset of IBD.

To investigate the causal relationship between inflammatory bowel disease (IBD) and uveitis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis utilizing summary data from genome-wide association studies (GWAS). The primary statistical analysis was performed using the inverse-variance weighted (IVW) method. False discovery rate (FDR) correction was used to control for false positives in multiple testing. In addition, sensitivity analyses were carried out using the MR Egger intercept test and Cochran's Q test. The MR analysis revealed that genetically determined IBD (OR = 1.141, 95% CI 1.080-1.205, P = 2.21 × 10-6, PFDR = 6.90 × 10-6), ulcerative colitis (UC) (OR = 1.113, 95% CI 1.032-1.201, P = 0.006, PFDR = 0.009), and Crohn's diseases (CD) (OR = 1.073, 95% CI 1.017-1.133, P = 0.010, PFDR = 0.011) had a causal effect on uveitis. Conversely, the reverse MR analysis did not reveal significant causal link of uveitis on IBD, including its two subtypes. Furthermore, the results of the MR-Egger and weighted median methods were consistent with the IVW method. No evidence of heterogeneity or pleiotropy was detected by sensitivity analysis. Our findings confirm that IBD and its main subtypes had a causal connection with uveitis. Further research is needed to elucidate the underlying pathophysiological mechanisms driving this association.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that may progress to colorectal cancer (CRC), presenting significant challenges to global health. With shifts in lifestyle, the incidence of both conditions continues to rise, underscoring the urgent need for effective treatments. While traditional therapies can be effective, their high recurrence rates and associated adverse reactions limit their broader application. Luteolin, a flavonoid derived from natural plants, has emerged as a promising focus in both IBD and CRC research due to its multi-target therapeutic potential. This article reviews the molecular mechanisms and signaling pathways through which luteolin regulates immune cell differentiation, mitigates inflammation and oxidative stress, modulates gut microbiota, and restores intestinal mucosal barrier function in IBD. In the context of CRC, luteolin demonstrates significant anti-tumor effects by inhibiting cancer cell proliferation, inducing apoptosis, and suppressing cell migration and invasion. Notably, luteolin has demonstrated significant improvements in IBD symptoms by influencing the differentiation of T cell subsets, decreasing the expression of inflammatory mediators, activating antioxidant pathways, and enhancing the structure of gut microbiota. Furthermore, advancements in formulation technology, such as the use of polymer micelles and responsive nanoparticles, have greatly improved the bioavailability and efficacy of luteolin. However, further investigation is needed to address the bioavailability and potential toxicity of luteolin, particularly in the critical transition from IBD to CRC. This article emphasizes the potential of luteolin in the treatment of IBD and CRC and anticipates its promising prospects for future clinical applications as a natural therapeutic agent.

This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune and rheumatic immune diseases through randomized controlled trials (RCTs).

Two researchers conducted a comprehensive search of Chinese and English databases from their inception until Dec. 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software.

A total of 42 relevant RCTs, involving 2,183 participants, were ultimately included in this study. These RCTs encompassed four types of rheumatic immune and bone diseases, namely rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic sclerosis arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease, multiple sclerosis, primary Sjögren's syndrome (PSS). The systematic review indicates that MSC transplantation may improve spondyloarthritis, RA, PSS. The meta-analysis reveals that MSC transplantation significantly improved symptoms in patients with OA [VAS (visual analogue scale): bone marrow: SMD = - 0.95, 95% CI - 1.55 to - 0.36, P = 0.002; umbilical cord: SMD = - 1.25, 95% CI - 2.04 to - 0.46, P = 0.002; adipose tissue: SMD = -1.26, 95% CI -1.99 to - 0.52, P = 0.0009)], SLE [Systemic lupus erythematosus disease activity index (SLEDAI): SMD = - 2.32, 95% CI - 3.59 to - 1.06, P = 0.0003], inflammatory bowel disease [clinical efficacy: RR = 2.02, 95% CI 1.53 to 2.67, P < 0.00001]. However, MSC transplantation may not improve the symptoms of multiple sclerosis and systemic sclerosis (Ssc). Importantly, MSC transplantation did not increase the incidence of adverse events (OA: RR = 1.23, 95% CI 0.93 to 1.65, P = 0.15; SLE: RR = 0.83, 95% CI 0.28 to 2.51, P = 0.76; Inflammatory bowel disease: RR = 0.99, 95% CI 0.81 to 1.22, P = 0.96; Multiple sclerosis: RR = 1.12, 95% CI 0.81 to 1.53, P = 0.50), supporting its safety profile across the included studies. These findings suggest that MSC transplantation holds promise for several rheumatic and autoimmune diseases while highlighting areas where further research is warranted.

MSC transplantation may have the potential to treat autoimmune and rheumatic immune diseases. Moreover. MSC transplantation appears to be relatively safe and could be considered as a viable alternative treatment option for autoimmune and rheumatic immune diseases.

Adoptive immunotherapy using engineered T cells expressing chimeric antigen receptors has shown remarkable success in treating patients with hematological malignancies. However, realizing broader therapeutic applications of engineered T cells in other diseases requires further exploration in clinical investigations. In this review, we highlight recent advances in the engineering of T cells in non-oncology areas, including autoimmune and inflammatory diseases, infections, fibrosis, hemophilia, and aging. Chimeric antigen receptor immunotherapy has shown good outcomes in non-oncology areas, but many challenges remain in improving its safety and efficacy and and expanding its application to the treatment of non-oncological diseases.

The endocannabinoid system (ECS), composed of receptors, endocannabinoids, and enzymes that regulate biosynthesis and degradation, plays a fundamental role in the physiology and pathology of the gastrointestinal tract, particularly in the small and large intestine and liver. Specifically, cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R), located principally in the nervous system and immune cells, orchestrate processes such as intestinal motility, intestinal and hepatic inflammation, and energy metabolism, respectively. The main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), influence appetite, body weight regulation, and inflammatory states and thus have implications in obesity, non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS). Recent studies have highlighted the therapeutic potential of targeting the ECS to modulate gastrointestinal and metabolic diseases. In particular, peripheral CB1R antagonists and CB2R agonists have shown efficacy in treating intestinal inflammation, reducing hepatic steatosis, and controlling IBS symptoms. Moreover, the ECS is emerging as a potential target for the treatment of colorectal cancer, acting on cell proliferation and apoptosis. This review highlights the opportunity to exploit the endocannabinoid system in the search for innovative therapeutic strategies, emphasizing the importance of a targeted approach to optimize treatment efficacy and minimize side effects.

Inflammatory bowel disease (IBD) and colorectal cancer (CRC), as two of the major human intestinal diseases, provide challenges for the medical field. Suppressor of cytokine signaling 3 (SOCS3), a protein molecule that negatively regulates cytokine signaling through multiple pathways, is involved in the regulation of various inflammatory diseases and tumors. In IBD, SOCS3 acts on a variety of cells to repair mucosal damage and balance the immune response, including epithelial cells, macrophages, dendritic cells, neutrophils, and T cells. In CRC, SOCS3 is inextricably linked to tumor cell proliferation, invasion, metastasis, and drug resistance. Therefore, it is crucial to systematically investigate the pathogenic involvement of SOCS3 in IBD and CRC. This article reviews the mechanisms and pathways by which SOCS3 is involved in the inhibition of IBD and the mitigation of CRC, and details the therapeutic options for targeting SOCS3.

The clinical efficacies of Ulcerative colitis (UC) are far from satisfactory. Fucoxanthin (FUC) is a marine carotenoid that is abundant in seaweed and microalgae. It has been reported that FUC can possess anti-inflammatory and antioxidant. However, its mechanism and role in UC is yet to be clarified. This study aimed to investigate the protective effect and potential mechanism of FUC extracted from the diatom Phaeodactylum tricornutm on dextran sodium sulfate (DSS) -induced colitis.

Animal UC model was induced by DSS and cellular model was established by TNF-α. Immunohistochemical staining, Western blot, RT-qPCR, and immunofluorescence were used to assess the inflammatory responses and epithelial barrier in vivo and in vitro models.

The results showed that FUC attenuates DSS-induced colitis by ameliorating the epithelial mucosal barrier. Moreover, FUC possessed antioxidant and anti-inflammatory effects on NCM460 cells. JAK/STAT activator RO8191 could reverse these changes.

FUC exerted anti-inflammatory and antioxidant effects via the JAK2/STAT3 signaling pathway, and served as a potential therapeutic agent for the treatment of UC.

Maintaining effective disease control in patients with inflammatory bowel disease (IBD) is both a significant goal and challenge. Drawing on the Common-Sense Model of Self-Regulation (CSM) and related research, this study investigates how IBD activity status influences disease control through both direct and indirect pathways.

A cross-sectional survey was conducted among 310 IBD patients who attended a tertiary general hospital, the leader of the IBD Alliance Group in Chongqing City, between March and August 2024. Structural equation modeling (SEM) was utilized to assess the role and magnitude of various influencing factor pathways. Relying on AMOS26 software, the path effects and magnitude of various factors in the disease control process were analyzed using structural equation modeling (SEM) to test hypothetical models.

A total of 306 valid questionnaires were collected, with a mean IBD-control score of 12.14 ± 3.665. There was a negative link between disease activity and IBD-control (P < 0.01) and a positive correlation between chronic illness management self-efficacy, IBD self-management behavior, and IBD-control (P < 0.01). Path analysis showed that IBD activity negatively predicted IBD control (β = -0.715, P = 0.01). Chronic disease management self-efficacy partially mediated this relationship (β = -0.071, P = 0.012). A significant chain-mediated pathway was identified, where IBD activity affected IBD control via self-efficacy guided by self-management behavior (β = -0.025, P = 0.007). However, the pathway where IBD activity influenced control through self-efficacy and subsequently self-management behavior showed only marginal significance (P = 0.074).

Effective self-management behaviors improve IBD control. High disease activity may reduce chronic disease management self-efficacy, impairing IBD control. Positive feedback loops involving self-management behaviors and enhanced self-efficacy are crucial for better disease control, as patients who perceive positive outcomes are more motivated to maintain these behaviors.

Ulcerative colitis (UC) remains an intractable and relapsing disease featured by intestinal inflammation. The anti-UC activity of Akkermansia muciniphila (AKK), an intestinal microorganism, has been widely investigated. The current work is to explore the impacts of AKK on UC and its possible reaction mechanism. In vivo UC model was induced by dextran sulfate sodium (DSS) and phorbol-12-myristate-13-acetate (PMA)-induced THP-1-M0 and raw264.7 macrophages were treated by lipopolysaccharide (LPS). H&E staining evaluated tissue damage. Inflammatory and oxidative stress levels were assessed by relevant kits. The high-throughput analysis of fatty acids was performed by the LC/MS method. RT-qPCR and Western blot detected related gene expression. Flow cytometry measured cell apoptosis and macrophage polarization. Energy metabolism was detected by ELISA, related assay kits, JC-1 staining, and Western blot. AKK reduced the pathological damage of mice colon tissues, alleviated oxidative stress and inflammatory response, upregulated the expression of Occludin-1 and SCFAs receptors, and stimulated M1 to M2 macrophage polarization in vivo. After FFAR2 was silenced, the promoting role of AKK in the viability and M1 to M2 macrophage polarization and the inhibitory role in oxidative stress, inflammation, apoptosis, energy metabolism disorder, necroptosis, and pyroptosis were both reverted. Conclusively, AKK might mediate SCFAs-SLC52A2/FFAR2 pathways to exert protective activities against intestinal inflammatory response in UC, suggesting that AKK might represent a novel and promising candidate for UC therapy.

Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing conditions characterized by dysregulated immune responses and persistent intestinal inflammation. This review aims to examine new potential therapeutic targets in IBD starting from the STRIDE-II statements. Key targets now include clinical remission, endoscopic remission, and biomarker normalization (such as C-reactive protein and fecal calprotectin). Moreover, histologic remission, transmural remission, and in the future molecular targets are emerging as important indicators of sustained disease control. The treatment goals for inflammatory bowel disease are varied: to relieve symptoms, prevent permanent intestinal damage, promote inflammation remission, and minimize complications. Consequently, the therapeutic targets have evolved to become broader and more ambitious. Integrating these advanced therapeutic targets has the potential to redefine IBD management by promoting deeper disease control and improved patient outcomes. Further research is essential to validate these strategies and optimize their clinical implementation.

The gut-microbiome-brain axis (GMBA) implies the connection between inflammatory bowel disease (IBD) and Alzheimer's disease (AD). We aimed to comprehensively explore the relation between IBD (and its subtypes) and AD, early-onset AD (EOAD) and late-onset AD (LOAD) from a genetic pleiotropy perspective.

Relying on summary statistics (N = 472,868 for AD, 185,204 for EOAD, 191,061 for LOAD, 59,957 for IBD, 45,975 for CD, and 40,266 for UC), we first performed Mendelian Randomization to examine the causal association between IBD and AD by leveraging vertical pleiotropy. Then, we estimated global and local genetic correlations, followed by cross-trait association analysis to identify SNPs and genes with horizontal pleiotropy. Particularly, we utilized multi-trait colocalization analysis to assess the role of microbes in the common genetic etiology underlying the two types of diseases. Finally, we conducted functional enrichment analysis for pleiotropic genes.

We discovered suggestively causal relations between IBD (and its subtypes) and EOAD (ORIBD = 1.06 [1.01-1.11], ORCD = 1.05 [1.01-1.10], ORUC = 1.08 [1.01-1.15]) as well as between UC and LOAD (OR = 1.04 [1.01-1.08]), and discovered 44 local regions showing suggestively significant genetic correlations between IBD (and its subtypes) and AD (and EODA and LOAD). We further detected substantial genetic overlap, as characterized by 182  AD-associated, 3 EOAD-associated and 51 LOAD-associated pleiotropic SNPs as well as 291 pleiotropic genes. Pleiotropic genes more likely enriched in the GMBA-relevant tissues such as brain, intestine and esophagus. Moreover, we identified three microorganisms related to these disease pairs, including the Catenibacterium, Clostridia, and Prevotella species.

The suggestively causal associations and shared genetic basis between IBD and its subtypes with AD, EOAD and LOAD may commonly drive their co-occurrence, and gut microbes might partly explain the shared genetic etiology. Further studies are warranted to elaborate the possibly biological mechanisms underlying the two types of diseases.

N7-methylguanosine (m7G) modification is one of the most prevalent forms of chemical modification in RNA molecules, which plays an important role in biological processes such as RNA stability, translation regulation and ribosome recognition. Methyl-transferation of m7G modification is catalyzed by the enzyme complex of methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4), and Quaking (QKI) recognizes internal m7G methylated mRNA and regulates mRNA translation and stabilization. Recent studies have found that m7G modification - related enzymes are associated with the onset and progression of digestive cancer, such as colorectal cancer, liver cancer, and other digestive diseases such as ulcerative colitis. This review will focus on the latest research progress on the roles of m7G methyltransferase METTL1/WDR4 and recognized enzyme QKI in digestive diseases.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), decreases quality of life and causes disability. The underlying processes are not fully understood. This study uses Mendelian randomization (MR) analysis to identify cytokines that may be associated with UC and CD, aiding in early diagnosis and treatment decisions. Methods Genome-wide association study (GWAS) data for inflammatory cytokine levels were obtained from a cohort of 14,824 individuals of European descent. The outcome data were then analyzed using summary-level GWAS data for UC and CD from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The analysis was primarily conducted using inverse-variance weighted (IVW) methods, with MR-Egger and weighted median serving as supplementary analyses. Sensitivity analyses included Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis.The inflammatory cytokines were subjected to additional scrutiny through the application of the Steiger test and reverse Mendelian randomization analysis. Subsequently, multivariable Mendelian randomization (MVMR) was employed to examine the associations of metabolites on UC and CD, in conjunction with linkage disequilibrium score regression (LDSC) and colocalization analysis. After FDR correction, we identified significant genetic associations of two inflammatory proteins (CXCL5 and CXCL9) with UC, and CXCL5 and IL-18R1 with CD. These findings were further validated by MVMR. Colocalization analyses demonstrated substantial genetic overlap between inflammatory proteins and IBD, with CXCL5 showing strong evidence of shared genetic variants with UC, and CXCL9 exhibiting genetic colocalization with CD, suggesting common genetic determinants underlying these inflammatory protein-IBD relationships. The current work presents evidence that presents evidence of significant associations between seven inflammatory protein factors and UC, as well as three inflammatory protein factors and CD. These findings provide novel insights into the biological mechanisms of IBD, and have implications for the screening, prevention, and treatment of IBD.

Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis. The MM delivery system features an external mucosal coating composed of hyaluronic acid and epigallocatechin gallate, along with internal microspheres of highly biocompatible polyserine modified alginates encapsulating with the engineered probiotics. The MM delivery system effectively protects engineered bacteria harsh environment in stomach and significantly improves intestinal adhesion of the probiotics, extending colonization up to 24 h, and does not affect the entry of biomarker or release of Avcystatin. It exhibits notable diagnostic and therapeutic efficacy in inflammatory bowel disease models, thus facilitating the advancement of live biotherapeutic products toward clinical application.

Dysbiosis caused by dietary changes can alter the intestinal bacterial species and is closely associated with inflammatory bowel disease (IBD). Among the possible treatment options, postbiotics, which act to balance the constituent intestinal microflora, have gained substantial attention. Herein, we investigated the anti-inflammatory effects of heat-killed Lactiplantibacillus argentoratensis (hk-LA) BBLB001 isolated from a marine environment using both cell (Caco2/RAW264.7 cell co-culture) and animal (dextran sodium sulfate [DSS]-induced colitis in mice) models. hk-LA BBLB001 markedly reduced IL-8 secretion in Caco-2 cell culture medium after lipopolysaccharide-mediated stimulation of RAW264.7 cells by enhancing the expression of cell adhesion factors.The body weight loss, reduced inflammatory cytokine levels in the serum and colon tissues, colon shortening, and myeloperoxidase activation caused by DSS in mice were alleviated by hk-LA BBLB001. Similar to that in the intestinal cell model, the gene and protein expressions of cell adhesion molecules in the colon tissue were increased upon hk-LA BBLB001 treatment in DSS-induced colitis mice. We observed increased mucin expression and secretory IgA concentration in colon tissues, suggesting that hk-LA BBLB001 intake may benefit pathogen defense and the regulation of intestinal commensal bacteria. Thus, hk-LA BBLB001 may serve as an instrumental postbiotic material in IBD treatment.

Background/Objectives: Elderly populations are under-represented in inflammatory bowel disease (IBD) clinical trials, with limited data on phenotype, treatment patterns, outcomes, and comorbidities. The main objective of this study was to evaluate, in an elderly cohort with IBD, demographic and disease characteristics, comorbidity, polypharmacy, and treatment patterns according to the development of IBD at or before old age. Secondarily, the same analysis was performed based on the type of IBD: ulcerative colitis (UC) or Crohn's disease (CD). Materials and Methods: Observational, single-center, retrospective study including patients diagnosed with IBD and aged 65 years or older seen at the IBD office of the Regional University Hospital of Malaga between September and November 2022. Data were recorded on demographic, disease-related, and IBD treatment-related variables, comorbidities, and polypharmacy. A descriptive and analytical study was undertaken according to the age of IBD onset and type of IBD. Results: Of the patients included, 50.8% were male, 55.1% had CD, and 44.9% UC. IBD onset was before age 65 years in 69.5% and ≥65 years in 30.5%. Elderly with IBD who debuted <65 presented longer disease duration (19.67 ± 9.82 years) and required more IBD-related surgeries (37.8%); elderly with IBD who debuted ≥65 were older (77.69 ± 6.26 years), with no differences in the other variables. According to the type of IBD, elderly UC patients were older (74.55 ± 6.9 years), used more aminosalicylates (77.4%), and had higher rates of polypharmacy (90.6%). Elderly patients with CD had higher IBD activity (moderate/severe in 72.3%), used more biologic drugs (58.5%), and required more IBD-related surgeries (44.6%). Conclusions: Elderly patients who develop IBD before or after the age of 65 years are overall very similar in baseline and disease-related characteristics. Elderly with CD have higher IBD activity and require more biologic drugs and IBD-related surgeries. Elderly with UC are older and have higher rates of polypharmacy and aminosalicylate use.

Gut immunity is essential for maintaining intestinal health. Recent studies have identified that intracellular liquid-liquid phase separation (LLPS) may play a significant role in regulating gut immunity, however, the underlying mechanisms remain unclear. LLPS refers to droplet condensates formed through intracellular molecular interactions, which are crucial for the formation of membraneless organelles and biomolecules. LLPS can contribute to the formation of tight junctions between intestinal epithelial cells and influence the colonization of probiotics in the intestine, thereby protecting the intestinal immune system by maintaining the integrity of the intestinal barrier and the stability of the microbiota. Additionally, LLPS can affect the microclusters on the plasma membrane of T cells, resulting in increased density and reduced mobility, which in turn influences T cell functionality. The occurrence of intracellular LLPS is intricately associated with the initiation and progression of gut immunity. This review introduces the mechanism of LLPS in gut immunity and analyzes future research directions and potential applications of this phenomenon.

Transient receptor potential melastatin 7 (TRPM7) has been emerged as a potent drug target for immunomodulation with ion conductance and kinase activities. The research is projected to characterize the influences of TRPM7 on the course of ulcerative colitis (UC) and dissect the latent response mechanisms. The in vivo murine model and in vitro cell model of UC were both stimulated by DSS. RT-qPCR and western blotting tested the abundance of TRPM7. Colonic damage was estimated by Hematoxylin-eosin staining, calculation of colon length, measurement of DAI and MPO assay kit. CCK-8 method and TUNEL staining severally ascertained cell activity and apoptosis. ELISA method assayed the inflammatory levels and relevant assay kits determined oxidative stress levels. FITC-dextran flux, immunohistochemistry, TEER as well as western blotting evaluated intestinal barrier function. Immunofluorescence staining and western blotting appraised NLR family pyrin domain containing 3 (NLRP3)-dependent pyroptosis. Depleted TRPM7 retarded inflammation, oxidative damage as well as intestinal barrier damage both in vitro and in vivo. TRPM7 reduction repressed the pyroptosis mediated by NLRP3 inflammasome. NLRP3 agonist nigericin partly abolished the protection elicited by TRPM7 silencing against inflammation, oxidative damage as well as intestinal barrier damage in vitro. Collectively, TRPM7 deletion might possess the therapeutic potential in UC, the working mechanism of which might involve the inactivation of NLRP3-dependent pyroptosis.

Inflammatory bowel disease (IBD) is a chronic and recurrent disease caused by immune response disorders that disrupt the intestinal lumen symbiotic ecosystem and dysregulate mucosal immune functions. Current therapies available for IBD primarily focus on symptom management, making early diagnosis and prompt intervention challenging. The development of genetically engineered bacteria using synthetic biology presents a new strategy for addressing these challenges. In this review, we present recent breakthroughs in the field of engineered bacteria for the treatment and detection of IBD and describe how bacteria can be genetically modified to produce therapeutic molecules or execute diagnostic functions. In particular, we discuss the challenges faced in translating live bacterial therapeutics from bacterial design to delivery strategies for further clinical applications.

Inflammatory bowel disease (IBD) is a chronic immune-inflammatory disease. Gut microbes, intestinal immunity, and gut barrier function play a critical role in IBD. Growing evidence suggests that synbiotic may offer therapeutic benefits for individuals with colitis, suggesting an alternative therapy against colitis. With this in mind, we creatively prepared a new synbiotic combination consisting of a probiotic strain (Limosilactobacillus reuteri) along with one prebiotic chitooligosaccharides (COS). The protective effects of the synbiotic on DSS-induced colitis and the underlying mechanisms were investigated. We demonstrated that the synbiotic ameliorated colitis in mice, as evidenced by a significant remission in body weight loss and colon shortening, and a decreased disease activity index (DAI). Notably, synbiotic reduced the intestinal inflammation and injury by synergistically decreasing inflammatory factors, inhibiting TLR4/Myd88/NF-κB/NLRP3 signaling, preventing macrophage infiltration, and enhancing the integrity of the intestinal barrier. Moreover, synbiotic selectively promoted the growth of beneficial bacteria (e.g., Akkermansia, Lactobacillus) but decreased the pathogenic bacteria (e.g., Helicobacter). BugBase's analysis supported its ameliorated role in reducing pathogenic bacteria. Collectively, our findings revealed the novel synbiotic had a potential to treat colitis, which was associated with its anti-inflammatory and microbiota-balancing properties. This study will contribute to the development of functional synbiotic products for IBD therapy and will provide valuable insights into their mechanisms.

Micronutrient deficiencies are common in inflammatory bowel disease (IBD). The aim of this study was to evaluate micronutrient deficiencies and identify muscular status of patients with IBD. From June 2019 to October 2021, a total of 105 patients with IBD were enrolled prospectively. To obtain objective data, micronutrients were measured in the patients' serum, and body composition analysis was performed using bioelectrical impedance analysis. There were 51 patients with ulcerative colitis (UC) and 54 with Crohn's disease (CD), while the gender ratio (M: F) was 54:51. The average age was 37 ± 18 years, which was significantly lower in patients with CD than UC (29 ± 16 vs. 45 ± 16, p < 0.001). Iron and magnesium were lower in patients with CD compared to UC, respectively (63.3 ± 42.5 vs. 82.8 ± 44.0 µg/dL, p = 0.024, 2.08 ± 0.15 vs. 2.15 ± 0.19 mg/dL, p = 0.036). Vitamin D levels showed insufficiency in patients with UC and deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567). In the UC and CD patient groups, skeletal muscle index (SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC (SMI: 32.8 ± 4.7 vs. 35.8 ± 5.5%, p < 0.004, adjusted skeletal muscle: 7.0 ± 1.5 vs. 8.2 ± 1.9 kg/m2, p < 0.001). In conclusion, decreased trace elements, specifically iron, magnesium, and vitamin D, as well as skeletal muscle mass were observed to be prominent in patients with CD as compared to UC.

Observational studies have discovered a contradictory phenomenon between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between H. pylori and IBD, including ulcerative colitis (UC) and Crohn's disease (CD).

We conducted a Mendelian randomization (MR) study with two sample Genome-Wide Association Studies (GWAS) to determine whether there is a causal relationship between H. pylori infection and IBD, as well as the possible pathogenic factors that may be involved. The reliability of the main MR assumptions was examined through a series of sensitivity analyses.

Two genetic variants (SNPs) previously identified were employed as instrumental variables (IVs) for H. pylori infection. GWAS data for IBD, UC, and CD were obtained from the recent DF10 release10 of the FinnGen study. Our findings indicated a significant association between H. pylori seropositivity and an increased risk of IBD and UC (IBD: OR: 1.16, 95% CI, 1.03-1.31, P < 0.05; UC: OR: 1.22, 95% CI, 1.08-1.37, P < 0.001) while no causal relationship with CD (P > 0.05). Analysis of the main virulence pathogenic factors revealed a causal relationship between cytotoxin-associated protein A (CagA) and IBD and UC (IBD: OR: 1. 06, 95% CI, 1.001-1.11, P < 0.05; UC: OR: 1.07, 95% CI, 1.004-1.14, P < 0.05), while no correlation was found for vacuolar cytotoxin A (VacA) (P > 0.05). After applying the False Discovery Rate (FDR) correction, the causal relationship between CagA and the risk of IBD or UC was no longer statistically significant.

This study suggests a potential causal relationship between H. pylori infection and IBD, particularly UC. The effect may be more pronounced in individuals with previous H. pylori infections.

Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.

Altechromone A, also known as 2,5-dimethyl-7-hydroxychromone, is a hydroxyketone containing one hydroxyl and one ketone group. In this study, we isolated Altechromone A from the marine-derived fungus Penicillium Chrysogenum (XY-14-0-4). Previous reports show that Altechromone A has various activities including tumor suppression, antibacterial, and antiviral activities. However, there is no study about its anti-inflammatory activity in inflammatory bowel disease (IBD). Here, we assess the anti-inflammatory activity, especially in IBD, and its potential mechanism using the zebrafish model. Our results indicated that Altechromone A has anti-inflammatory activity in a CuSO4-, tail-cutting-, and LPS-induced inflammatory model in zebrafish, respectively. In addition, Altechromone A greatly reduced the number of neutrophils, improved intestinal motility and efflux efficiency, alleviated intestinal damage, and reduced reactive oxygen species production in the TNBS-induced IBD zebrafish model. The transcriptomics sequencing and real-time qPCR indicated that Altechromone A inhibited the expression of pro-inflammatory genes including TNF-α, NF-κB, IL-1, IL-1β, IL-6, and NLRP3. Therefore, these data indicate that Altechromone A exhibits therapeutic effects in IBD by inhibiting the inflammatory response.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

As the therapeutic landscape for inflammatory bowel disease (IBD) continues to expand, a need exists to understand how patients perceive and value different attributes associated with their disease as well as with current and emerging treatments. These insights can inform the development and regulation of effective interventions for IBD, benefiting various stakeholders including healthcare professionals, drug developers, regulators, Health Technology Assessment bodies, payers, and ultimately patients suffering from IBD. In response to this, the present patient preference study was developed with the aim to (1) determine the relative preference weights for IBD treatment and disease related attributes, and (2) explain how preferences may differ across patients with different characteristics (preference heterogeneity).

The patient preference study (PPS) was developed through an 8-step process, with each step being informed by an advisory board. This process included: (1) stated preference method selection, (2) attribute and level development (including a scoping literature review, focus group discussions, and advisory board meetings), (3) choice task construction, (4) sample size estimation, (5) survey implementation, (6) piloting, (7) translation, and (8) pre-testing. The resulting discrete choice experiment (DCE) survey comprises 14 attributes with between two and five varying levels. Participants will answer 15 DCE questions with a partial profile design, where each of the choice questions encompasses two hypothetical treatment profiles showing four attributes. Additionally, questions about patients' socio-demographic and clinical characteristics, as well as contextual factors are implemented. The survey is available in 15 different languages and aims to minimally recruit 700 patients globally.

This protocol gives valuable insights toward preference researchers and decision-makers on how PPS design can be transparently reported, demonstrating solutions to remaining gaps in preference research. Results of the PPS will provide evidence regarding the disease and treatment related characteristics that are most important for IBD patients, and how these may differ across patients with different characteristics. These findings will yield valuable insights applicable to preference research, drug development, regulatory approval, and reimbursement processes, enabling decision making across the medicinal product life cycle that is aligned with the true needs of IBD patients.

Protein post-translational modification (PTM) is a covalent process that occurs in proteins during or after translation through the addition or removal of one or more functional groups, and has a profound effect on protein function. Glycosylation is one of the most common PTMs, in which polysaccharides are transferred to specific amino acid residues in proteins by glycosyltransferases. A growing body of evidence suggests that glycosylation is essential for the unfolding of various functional activities in organisms, such as playing a key role in the regulation of protein function, cell adhesion and immune escape. Aberrant glycosylation is also closely associated with the development of various diseases. Abnormal glycosylation patterns are closely linked to the emergence of various health conditions, including cancer, inflammation, autoimmune disorders, and several other diseases. However, the underlying composition and structure of the glycosylated residues have not been determined. It is imperative to fully understand the internal structure and differential expression of glycosylation, and to incorporate advanced detection technologies to keep the knowledge advancing. Investigations on the clinical applications of glycosylation focused on sensitive and promising biomarkers, development of more effective small molecule targeted drugs and emerging vaccines. These studies provide a new area for novel therapeutic strategies based on glycosylation.