Progressive Inflammatory Disease Research Articles

HMGB1: key mediator in digestive system diseases.

High Mobility Group Box 1 (HMGB1), a multifunctional non-histone protein, and its involvement in various physiological and pathological contexts has garnered significant attention. Given HMGB1's central function in modulating key biological activities, such as inflammatory responses and cellular death, its contribution to the pathogenesis of digestive system diseases has become a focus of growing interest. This review aims to comprehensively explore the mechanisms by which HMGB1 contributes to the progression of inflammatory bowel disease (IBD), liver disorders, and pancreatitis. Furthermore, we explore the prospective clinical applications and outline future research directions for HMGB1 in digestive diseases, providing fresh perspectives that highlight the necessity of ongoing studies to understand its role in these conditions.

The unique reactivity of EKODE lipid peroxidation products allows in vivo detection of inflammation.

Lipid peroxidation is a complex biochemical process associated with oxidative stress, and its products play crucial roles in cellular signaling and the pathophysiology of many diseases. Among the diverse array of lipid peroxidation (LPO) products, epoxyketooctadecenoic acids (EKODEs) have emerged as intriguing molecules with potential impacts on inflammatory diseases. EKODEs arise from linoleic acid reacting with reactive oxygen and nitrogen species present during inflammation. A hallmark of many LPO products is an electrophilic chemical functionality that can react with different biological nucleophiles to form adducts that impact a broad swath of physiologic processes. Here, we present the identification of reactivity patterns exhibited by the EKODE class of LPO products that arise due to the unique chemistry of the EKODE electrophiles, namely α, β-unsaturated epoxyketones of variable regiochemistry. Our initial investigations with models of the EKODE reactive core showed that surrogates of lysine did not react, and histidine nucleophiles formed reversible Michael adducts. However, when models of cysteine nucleophiles were tested, a unique reactivity profile emerged where rapid Michael addition was followed by slow rearrangement and epoxide opening at an unpredicted electrophilic site, affording what we postulated to be an advanced lipoxidation end product (ALE). After confirming the EKODE reactivity in model systems, we produced polyclonal antibodies of a stable epitope of the EKODE-based ALE and used these antibodies to investigate an approach for in vivo monitoring of inflammatory disease progression.

Nepetin limits NLRP3 inflammasome activation and alleviates NLRP3-driven inflammatory diseases via PINK1-dependent mitophagy.

The NLRP3 inflammasome plays a pivotal role in the progression of inflammatory diseases. Mitochondrial damage, oxidative stress and mitochondrial DNA (mtDNA) leak are the key upstream factors for NLRP3 inflammasome activation. Nepetin (Nep), a naturally occurring flavonoid found with anti-inflammatory properties; however, whether it can affect the NLRP3 inflammasome activation and its precise anti-inflammatory mechanism remains unclear. In this study, we demonstrated that Nep enhances PINK1-mediated ubiquitin phosphorylation, which promotes mitophagy and subsequently inhibits NLRP3 inflammasome activation and pyroptosis in macrophages. The administration of Nep to macrophages alleviated of mitochondrial damage, reduced mitochondrial superoxide production, restored mitochondrial membrane potential and prevented the mtDNA leakage. These findings provide compelling evidence for the antioxidant effect of Nep. Furthermore, the pivotal function of mitophagy in the NLRP3 inflammasome inhibitory impact of Nep was substantiated through the utilisation of mitophagy inhibitors and siRNA techniques. Notably, Nep increased survival and reduced organ damage in mice with systemic inflammation by inhibiting NLRP3 inflammasome activation. In addition, Nep suppressed NLRP3 inflammasome activation in obese mice, which led to reduced white adipose and liver inflammation, thereby ameliorating insulin resistance. In conclusion, our findings suggest that Nep is a potent NLRP3 inflammasome inhibitor and a promising candidate for the development of anti-inflammatory therapies.

Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients.

Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. Lead variants from GWAS were determined using FUMA. Loci with p<1e-5 were identified for post-hoc candidate identification. Transcriptome-wide association studies (TWAS) identified loci in cis and trans to the lead variants. Serum from phenotyped individuals with CP from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) was assessed for BDNF levels using Meso Scale Discovery Immunoassay. We identified four pain systems defined by candidate genes: 1) Pancreas-associated injury/stress mitigation genes include: REG gene cluster, CTRC, NEURL3 and HSF22. 2) Neural development and axon guidance tracing genes include: SNPO, RGMA, MAML1 and DOK6 (part of the RET complex). 3) Genes linked to psychiatric stress disorders include TMEM65, RBFOX1, and ZNF385D. 4) Genes in the dorsal horn pain-modulating BDNF/neuropathic pathway included SYNPR, NTF3 and RBFOX1. In an independent cohort BDNF was significantly elevated in patients with constant-severe pain. Extension and expansion of this exploratory study may identify pathway- and mechanism-dependent targets for individualized pain treatments in CP patients. PERSPECTIVE: Pain is the most distressing and debilitating feature of chronic pancreatitis. Yet many patients with chronic pancreatitis have little or no pain. The North American Pancreatitis Study II (NAPS2) includes over 1250 pancreatitis patients of all progressive stages with all clinical and phenotypic characteristics carefully recorded. Pain did not correlate well with disease stage, inflammation, fibrosis or other features. Here we spit the patients into groups with the most severe pain and/or chronic pain syndromes and compared them genetically with patients reporting mild or minimal pain. Although some genetic variants associated with pain were expressed in cells (1) of the pancreas, most genetic variants were linked to genes expressed in the nervous system cells associated with (2) neural development and axon guidance (as needed for the descending inhibition pathway), (3) psychiatric stress disorders, and (4) cells regulating sensory nerves associated with BDNF and neuropathic pain. Similar and overlapping genetic variants in systems 2 -4 are also seen in pain syndromes form other organs. The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.

Cognitive changes in patients with relapse-free MS treated with high efficacy therapies: the predictive value of paramagnetic rim lesions

BackgroundHigh-efficacy disease-modifying therapies (HETs) have substantially improved multiple sclerosis (MS) management, yet ongoing cognitive decline remains a concern. This study aims to assess Symbol Digit Modalities Test (SDMT) changes in...

Lactobacillus fermentum 016 Alleviates Mice Colitis by Modulating Oxidative Stress, Gut Microbiota, and Microbial Metabolism

Ulcerative colitis (UC) is a chronic and progressive inflammatory gastrointestinal disease closely associated with gut microbiota dysbiosis and metabolic homeostasis disruption. Although targeted microbial therapies are an emerging intervention strategy for inflammatory bowel disease (IBD), the mechanisms by which specific probiotics, such as Lactobacillus fermentum 016 (LF), alleviate UC remain unclear. The current study evaluated the effects of LF supplementation on gut health in a basal model using C57BL/6 mice. Subsequently, the preventive effects and mechanisms of LF supplementation on DSS-induced UC were systematically investigated. According to our findings, LF supplementation revealed immunoregulatory capabilities with significantly altered gut the composition of microbiota and metabolic activities, particularly enhancing tryptophan metabolism. In the UC model, LF supplementation effectively mitigated weight loss, increased the disease activity index (DAI), and alleviated diarrhea, rectal bleeding, and colon shortening. Moreover, it reduced colonic pathological damage and histological injury scores. LF intervention improved antioxidant markers and intestinal mucosal barrier function with the activation of the Nrf2–Keap1 signaling pathway and regulation of systemic inflammatory markers, i.e., IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-10. Importantly, LF supplementation reversed metabolic disturbances by significantly increasing the abundance of beneficial genera (e.g., g_Dubosiella, g_Faecalibaculum, g_Odoribacter, g_Candidatus_saccharimonas, g_Roseburia, and g_Eubacterium_xylanophilum_group) and elevating tryptophan metabolites (e.g., melatonin, kynurenic acid, 3-indoleacetic acid, 5-methoxytryptophan, and 5-hydroxyindoleacetic acid). In conclusion, Lactobacillus fermentum 016 exhibits potential for regulating gut microbiota homeostasis, enhancing tryptophan metabolism, and alleviating UC, providing critical insights for developing probiotic-based precision therapeutic strategies for IBD.

Advances in Research on Marine Natural Products for Modulating the Inflammatory Microenvironment.

In recent years, marine natural products (MNPs) have emerged as crucial sources of lead compounds for the advancement of anti-inflammatory drugs due to their abundant diversity, complexity, and distinctiveness. Inflammatory microenvironments (IMEs) are pervasive pathological features in the etiology of various chronic diseases, referring to the localized milieu or ecosystem where inflammatory responses occur, and they play a pivotal role in the onset and progression of inflammatory diseases. Uncontrolled IMEs can lead to dysregulation of inflammatory mediators within signaling pathways, thereby exerting detrimental effects on human health and even contributing to the development of inflammatory diseases such as cancer. Currently, inflammation treatment predominantly relies on chemical drugs. Nevertheless, these existing therapies are constrained by their numerous side effects and slow remission of symptoms. Consequently, there is an urgent need for the discovery and development of new drugs that exhibit minimal side effects while exerting potent anti-inflammatory effects. This article extensively explored the activities and mechanisms of MNPs (covering studies from 2010 to 2024) regulating key signaling pathways and inflammatory mediators in the IME, which establishes a theoretical basis for the further development of anti-inflammatory drugs.

P1312 Clickable nanozyme enhances colonization of Saccharomyces boulardii by spatiotemporal guidance for ameliorating inflammatory bowel disease

Abstract Background Compelling evidence indicates that dysregulated in the gut microbiota significantly contribute to the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions aimed at modulating the microbiota offer potential alternative approaches for treating IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability. Methods Here, we developed azido (N3)-modified Prussian blue nanozyme (PB@N3) spatio-temporal guidance enhances the targeted colonization of probiotics to alleviate intestinal inflammation. First, IVIS and Photoacoustic imaging demonstrated clickable PB@N3 targets intestinal inflammation, simultaneously, it scavenges reactive oxygen species (ROS). Subsequently, utilizing click chemistry “N3-DBCO” to spatio-temporally guide targeted colonization of dibenzocyclooctyne (DBCO)-modified Saccharomyces boulardii (S.Br@DBCO). The therapeutic effects of PB@N3 + S.Br@DBCO were verified by using the dextran sulfate sodium (DSS)-induced colitis mice model. Weight loss, fecal conditions, colon length and histopathological changes were monitored. Results PB@N3 targets and anchors to inflamed region. The "click" reaction between PB@N3 and S.Br@DBCO has excellent specificity and efficacy both in vivo and in vitro. Despite the complex physiological environment of IBD, "click" reaction can prolong the retention time of probiotics in the intestine. Dextran sulfate sodium (DSS)-induced colitis mice model, demonstrates that the combination of PB@N3 and S.Br@DBCO effectively enhances the colonization of probiotics, restores intestinal barrier function, and alleviates intestinal inflammation. Conclusion This is the first time that “click” chemistry was employed to combine fungal probiotics and nanozyme. PB@N3 spatio-temporal guidance enhances targeted colonization of S.Br@DBCO provides a promising medical treatment strategy for IBD.

Genome analysis of Bifidobacterium adolescentis and investigation of its effects on inflammation and intestinal barrier function

Numerous studies have confirmed that gut microbiota is a key driver in the occurrence and progression of inflammatory bowel disease (IBD). Based on the bacterial collection constructed in our previous studies, we founded that Bifidobacterium adolescentis AF91-08b2A has the potential beneficial function. We designed cohort studies, genomic studies and animal experiments to further explore the probiotic function of Bifidobacterium adolescentis AF91-08b2A and its therapeutic effect on IBD. The depletion of B. adolescentis in individuals with IBD suggested its significance for intestinal health. Genomic analysis highlighted the probiotic attributes of B. adolescentis AF91-08b2A, including resistance to antibiotics and stress, and metabolic pathways related to energy and carbohydrate metabolism, which are likely to enhance its therapeutic efficacy. In DSS-induced mice colitis model, the strain significantly enhanced the disease activity index (DAI), curbed weight loss, and attenuated colonic damage. It effectively modulated the immune response by reducing the levels of pro-inflammatory cytokines such as IL-6, IL-1β, IL-17A, IFN-γ, and TNF-α, while promoting the secretion of anti-inflammatory cytokines like IL-4, IL-10, and TGF-β1. The restoration of tight junction proteins ZO-1, occludin, and claudin-2 by B. adolescentis AF91-08b2A demonstrated its capacity to safeguard the intestinal epithelial barrier. Collectively, our findings indicate B. adolescentis AF91-08b2A as a valuable therapeutic option for UC, with its multifaceted approach to reducing inflammation and fortifying the intestinal barrier.

P0122 The Potential Role of Circulating Cytokines and Chemokines To Predict Intestinal Failure in Patients Affected by Short Bowel Syndrome

Abstract Background Short bowel syndrome (SBS) is a life-altering and life-threatening disease resulting from massive small bowel resections, often occurring in patients with Crohn's disease (CD), a severe chronic gastrointestinal disorder characterized by the infiltration of inflammatory cells into the intestinal mucosa and submucosa. Several cytokines and chemokines play a crucial role in the development and progression of inflammatory bowel disease by recruiting inflammatory cells1,2. Currently, no biomarkers indicate a higher risk of developing SBS or intestinal failure (IF); thus, the present study aims to evaluate the circulating cytokine/chemokine profile in patients affected by IF/SBS and CD patients at high risk of developing IF, to identify disease severity-related biomarkers. Methods A total of 150 CD patients were enrolled in this study, and they were stratified into four subgroups based on the disease severity: SBS patients with IF and parenteral nutrition (A1 group) or without IF and inactive disease (A3 group); CD patients with high (B group) or low risk of IF (C2 group). Circulating cytokines and chemokines levels were determined using the human 27-PLEX assay on sera collected from patients at the moment of the enrollment (T0, n=70) and after 6 months (T6M, n=10). Results Among inflammatory cytokines, high levels of RANTES, PDGF-BB, IP-10, MIP-1β, IL-9, and EOTAXIN were detected in all groups, while the levels of anti-inflammatory interleukins such as IL-4 and IL-13 resulted low in all patients at T0 (fig.1). At T6M, a general reduction of all the enhanced inflammatory markers was detected in all the groups except for RANTES, whose levels were almost unchanged and even increased in the A3 group. On the contrary, IP-10, which appears explicitly increased in the A1 group, is the most significantly reduced in all groups at T6M (fig.2). Conclusion Our results show a difference in the levels of circulating cytokines/chemokines profiles among the different groups of patients. In particular, IP-10, EOTAXIN, and PDGF-BB are significantly higher in the A1, A3, and C2 groups, respectively, while IL-9, RANTES, and MIP-1β levels present a similar profile at T0. After 6 months, a general reduction of all the analyzed inflammatory markers was recorded in all the groups. In particular, IP-10 shows the most relevant reduction, while RANTES levels remain almost unaltered at T6M. Literature data confirmed a role for these cytokines/chemokines in CD severity and progression3,4. However, to validate these preliminary data and potentially find a biomarker for IF prediction, more samples will be collected and analyzed.

P0094 The Role Of Sdf2l1 On Intestinal Physiology And Inflammatory Bowel Disease

Abstract Background The intestinal tract, as the body's largest mucosal surface, is exposed to various factors, requiring specialized epithelial and immune cell interactions to maintain homeostasis. These interactions, along with a dynamic microenvironment, induce endoplasmic reticulum (ER) stress. While the ER employs coping mechanisms to preserve cellular integrity, unresolved ER stress is a key driver in the development and progression of chronic inflammatory bowel disease (IBD).1 An important player in the ER-resident unfolded protein response is stromal derived growth factor 2-like 1 (Sdf2l1), a chaperone protein that ensures proper protein folding and prevents the accumulation of misfolded proteins.2,3 Furthermore, Sdf2l1 is highly expressed in the intestine, thus we hypothesize that Sdf2l1 plays a pivotal role in the pathogenesis of IBD. Methods To investigate the role of Sdf2l1 in the gastrointestinal system, we used wildtype or conditional Sdf2l1 knockout mice lacking Sdf2l1 in intestinal epithelial cells (Sdf2l1ΔIE) and ex vivo organoid systems. Results No baseline differences were found in the intestinal mucosa of Sdf2l1-deficient mice, but molecular differences in ER stress responses were evident in small intestinal organoids. When ER stress was induced with IL-22, Sdf2l1ΔIE organoids showed significantly higher NFκB expression, suggesting enhanced UPR activation or compromised stress coping. Under tunicamycin treatment, Sdf2l1-deficient organoids had increased Hspa5/Grp78 expression, indicating elevated ER stress. Sdf2l1 is needed for proper UPR initiation, as it forms a complex with GRP78. In these deficient organoids, IRE1 signaling was impaired, as shown by reduced Xbp1s expression. Conclusion Insufficient activation of the UPR due to Sdf2l1 deficiency and the associated ER stress potentially leads to inflammatory reactions in the cells. Impaired cell integrity disrupts intestinal homeostasis and can lead to an imbalance of pro- and anti-inflammatory processes, thus favoring the pathophysiology of IBD.

Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles

Polymeric nanoparticles (NPs) are promising tools used for immunomodulation and drug delivery in various disease contexts. The interaction between NP surfaces and plasma-resident biomolecules results in the formation of a biomolecular corona, which varies patient-to-patient and as a function of disease state. This study investigates how the progression of acute systemic inflammatory disease influences NP corona compositions and the corresponding effects on innate immune cell interactions, phenotypes, and cytokine responses. NP coronas alter cell associations in a disease-dependent manner, induce differential co-stimulatory and co-inhibitory molecule expression, and influence cytokine release. Integrated multi-omics analysis of proteomics, lipidomics, metabolomics, and cytokine datasets highlight a set of differentially enriched TLR4 ligands that correlate with dynamic NP corona-mediated immune activation. Pharmacological inhibition and genetic knockout studies validate that NP coronas mediate this response through TLR4/MyD88/NF-κB signaling. Our findings illuminate the personalized nature of corona formation under a dynamic inflammatory condition and its impact on NP-mediated immune activation profiles and inflammation, suggesting that disease progression-related alterations in plasma composition can manifest in the corona to cause unintended toxicity and altered therapeutic efficacy.

P1181 Liver fibrosis predicts response to advanced therapy in inflammatory bowel disease: a new personalized treatment approach?

Abstract Background Crohn's disease (CD) and ulcerative colitis (UC) are chronic and progressive inflammatory bowel diseases (IBD). It is estimated that up to 30-50% of patients with IBD develop intestinal fibrosis leading to complications such as strictures. Liver fibrosis occurs up to 16.7% of patients with IBD. However, the impact of liver fibrosis on the response to therapy in patients with IBD is unknown. Our aim was to investigate the association between liver fibrosis before starting an advanced therapy and response to treatment in IBD. Methods We conducted a retrospective analysis of data that were prospectively gathered from consecutive patients with a confirmed diagnosis of UC or CD, spanning from November 2021 to December 2023. All patients who started an advanced therapy (biological therapy and small molecule drugs) and had transaminase concentrations, body mass index (BMI), history of diabetes, and platelet counts available were eligible. Several scores of liver fibrosis were measured including AST/ALT ratio (AAR), AAR platelet ratio index (AARPRI)1, AST to platelet ratio index (APRI), body mass index AST/ALT ratio and diabetes mellitus score (BARD), fibrosis index based on four factors (FIB -4)2, and modified FIB-4 (m-FIB4)3. All available clinical (partial Mayo score, PMS, for UC and Harvey-Bradshaw index, HBI, for CD), biochemical (fecal calprotectin, FC), and endoscopic (endoscopic Mayo score for UC and simple endoscopic score for Crohn's Disease (SES-CD) and Rutgeert’s score for CD) data at 6 months were collected. A logistic regression multivariate analysis was performed to identify any correlation between scores of liver fibrosis at baseline and response to advanced therapies. Analyses were subjected to correction using the false discovery rate (FDR) method. Results In total, 122 patients were included in the analysis. Patient key demographic and treatment information as well as clinical remission, FC normalization and endoscopic remission at 6 months are summarized in table. Two UC patients (2.7%) were hospitalized. Five patients (4.1%) underwent surgery (2 UC-related and 3 CD related). No cases of neoplasia or death occurred. In the multivariate analysis, mFIB-4 at baseline was a predictor of clinical activity at 6 months in CD (FDR=0.08), while AARPRI at baseline predicted clinical activity at 6 months in UC (FDR=0.08) (Figure). Conclusion Patients with IBD and concomitant liver fibrosis have a lower rate of clinical remission after 6 months of advanced therapy. Scores of liver fibrosis could predict the response to therapy. Further prospective studies are warranted to implement their use in clinical practice

P0622 Total emulsifier intake, but not ultra-processed food consumption is higher in patients with Inflammatory Bowel Disease compared to healthy controls

Abstract Background Ultra-processed food (UPF) intake, which often contains emulsifiers that might affect the intestinal barrier, has been linked to inflammatory bowel disease (IBD) incidence and progression.1 Here, we assessed intake of UPFs, emulsifiers and macronutrients in patients with IBD and healthy controls. Methods Dietary intake was cross-sectionally calculated from Food Frequency Questionnaires (FFQs) and food logs. Two 24-hour dietary recalls in IBD patients attending the infusion unit were compared to two prospective logs from healthy controls from the FOAM study.2 Kruskal Wallis with post-hoc Dunn test was used for continuous data, and Fisher exact test for proportions, with Bonferroni correction for multiple testing. Results We included 186 subjects (Table 1). Assessing food logs, UPF intake was similar in all groups, yet emulsifier intake was higher in UC and CD compared to controls (p=0.03 and p=0.0004, resp). Compared to controls, higher intakes of E402 (UC p=0.02, CD p=0.002), E411 (both p=0.01), E471 (UC p=0.02, CD p=0.0009), as well as carrageenan E407 (UC p=0.001, CD p=0.002), and xanthan gum E415 (UC p=0.03, CD p=0.01) were seen (Fig 1). Intake of E476 was higher in CD compared to controls (p=0.02), while intake of guar gum E412 was higher in UC compared to controls (p=0.02). The proportion of non-consumers of E402 was higher in controls (100%) compared to IBD (CD 83%, UC 67%, p=0.03). Sugar intake was higher in UC (p=0.004) compared to controls. When comparing FFQs, a higher intake of deli meat in CD was seen, compared to UC (p=0.04). Compared to controls, soft drink (UC p=0.0005, CD p=0.001), meat (UC p=0.02, CD p=0.04), and butter intake (UC p=0.03, CD p= 0.005) was higher in IBD. However, intake of breakfast cereals (UC p=6e-13, CD p=1e-10), legumes (UC p=2e-04, CD p=1e-05), meat substitutes (UC 6e-04, CD p=0.02), whole grain pasta and rice (UC p=2e-6, CD p=4e-5), and fibre (UC p=0.01, CD p=0.002) was lower in UC and CD. Coffee (p=0.03), potato (p=0.01), deli meat (p=3e-04), and sodium intake (p=0.02) was higher in CD patients than controls, while nut and seed intake was lower (p=3e-04). For UC, polysaccharide intake was lower in UC than controls (p=0.007). There was no correlation between C-reactive protein and intake of UPFs, emulsifiers, macronutrients or total energy intake (p&amp;gt;0.1). Conclusion We show higher intakes of emulsifiers in patients with IBD compared to controls, while UPF intake was comparable. The concomitant increased intake of specific emulsifiers such as carrageenan and guar gum that have previously been associated with disruption of the intestinal barrier, warrant further investigation into their role in the propagation and maintenance of gut inflammation.

A Modified Procedure to Improve Pancreatic Drainage in Chronic Pancreatitis with Pancreatic Head Dominant Disease.

Chronic pancreatitis is a debilitating and progressive inflammatory disease with an altered quality of life due to severe abdominal pain. Pancreaticoduodenectomy is a surgical option for patients with bulky disease involving the head of the pancreas, especially when this disease has progressed to stricture of the bile duct, duodenum, or both. A long term issue associated with this procedure is stricture of the pancreatic anastomosis. Re-operative and endoscopic interventions are difficult related to difficulty in reaching the anastomosis endoscopically. We describe a variation of this procedure with potential to lead to longer term improvement in drainage of the residual pancreas. We reviewed electronic medical records of patients undergoing pancreaticoduodenectomy for chronic pancreatitis performed by one surgeon at the University of Minnesota Medical Center, Minneapolis, MN, between 2014 and 2023. Information gathered from the patients' records included preoperative demographics, perioperative outcomes, and postoperative follow up information. The described procedure was performed in eight patients between 2014 and 2023. Three patients have died since surgery at 1.5, 5.5, and 8 years postop, with no deaths related to pancreatitis or surgical complications. Of the remaining five patients, median time from surgery is 7.5 years. We describe a surgical technique which may reduce the risk of pancreaticojejunal stricture in patients undergoing pancreaticoduodenectomy for chronic pancreatitis. In a small series of patients, this procedure can be performed safely with acceptable results.

Serum Nutrients, Periodontitis and Biological Ageing.

Telomeres are nucleotide sequences found at the end of chromosomes, and their shortening is associated with chronological and biological ageing, oxidative stress and malnutrition. Shorter telomeres have been shown to be associated with periodontitis. Dietary nutrients are also influential factors in the aetiology and progression of periodontitis and other chronic inflammatory diseases. We tested the hypothesis that blood serum levels of folate, vitamin D, vitamin E, cis-β-carotene and/or β-cryptoxanthin are associated with telomere lengths and periodontitis and that these relationships are modified by factors that also affect periodontitis (e.g., age, sex, smoking, race/ethnicity). Laboratory and demographic data collected by the NHANES 1999-2002 survey of 10,793 study participants were analysed. The data included age (binned every 10 years starting at age 30), race/ethnicity (White, Black, Hispanic), sex (male, female), periodontitis (none/mild, moderate/severe), vitamin levels (low, medium, high), telomere lengths (base pairs) and smoking (yes, no). Statistical analyses were performed with ANOVA tests. Periodontitis was significantly associated with vitamin D, vitamin E and cis-β-carotene. Telomere length was significantly associated with vitamin E and cis-β-carotene. There were statistically significant interactions between the following vitamins and covariates on telomere length: folate and sex, vitamin D and periodontitis, vitamin D and race/ethnicity and vitamin E and sex. Certain blood nutrients may disrupt biological ageing, with periodontitis as a co-morbidity. Some of these relationships are modified by demographic variables such as sex and race/ethnicity.

Integrating machine learning and structure-based approaches for repurposing potent tyrosine protein kinase Src inhibitors to treat inflammatory disorders

Tyrosine-protein kinase Src plays a key role in cell proliferation and growth under favorable conditions, but its overexpression and genetic mutations can lead to the progression of various inflammatory diseases. Due to the specificity and selectivity problems of previously discovered inhibitors like dasatinib and bosutinib, we employed an integrated machine learning and structure-based drug repurposing strategy to find novel, targeted, and non-toxic Src kinase inhibitors. Different machine learning models including random forest (RF), k-nearest neighbors (K-NN), decision tree, and support vector machine (SVM), were trained using already available bioactivity data of Src kinase targeting compounds. The performance evaluation of these models demonstrated SVM as the best model, which was further utilized to shortlist 51 highly potent compounds by screening an FDA-approved library of 1040 drugs. Molecular docking and molecular dynamic simulation were subsequently employed to evaluate the binding affinity and stability of the proposed compounds. Orlistat, acarbose and afatinib were identified as the potent leads, demonstrating stable conformations and stronger interactions, validated by root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG), and hydrogen bond analyses. Molecular Mechanics/Generalized Born Surface Area (MMGBSA) analysis validated their binding affinities by providing comparably lower binding free energies for orlistat (− 33.4743 ± 3.8908), acarbose (− 19.5455 ± 5.4702), and afatinib (− 36.4944 ± 5.4929) than the control, dasatinib (− 13.7785 ± 5.8058). Finally, toxicity analysis revealed orlistat and acarbose as the possible safer therapeutics by eliminating afatinib as it showed significant toxicity concerns. Our investigation supports the advance computational methods utilization in the field of drug discovery and suggest further experimental validation of proposed inhibitors of Src kinase for their safer use against inflammatory diseases. The ultimate aim of this study is to advance the development of effective treatments for inflammatory diseases, linked with Src overexpression.

Penerapan Terapi Myra E Levine Melalui Aplikasi Tehnik Relaksasi Otot Progresif Terhadap Intensitas Nyeri Pada Kasus Rematik Di Puskesmas Bermani Ulu Kabupaten Rejang Lebong

Rheumatoid Arthritis is a progressive, systematic and chronic inflammatory disease that initially affects the synovial joints accompanied by edema, congestion of vascular exudate and cellular infiltration (Risnanto &amp; Isnani, 2014). The impact of Rheumatoid Arthritis can cause discomfort, pain and limited physical mobility so that there is a risk of disability and loss of movement (Elviani et al., 2021). Progressive muscle relaxation therapy is a muscle stretching and breathing exercise that is done to produce a response that can reduce sympathetic nerve activity so that it can reduce pain. The general purpose of this case study is to apply Myra E Levine's nursing theory to Rheumatic Patients by performing and teaching Progressive Muscle Relaxation Techniques to reduce pain intensity, this study was also conducted to determine whether Myra E Levine's theory can be applied to Rheumatic patients by providing Progressive Muscle Relaxation Technique therapy. This case study method is a qualitative method with a Case study research strategy. The type of case study when carrying out nursing care is Case study research by applying Myra E Levine's nursing model theory to patients suffering from Rheumatic. The results of nursing care for Rheumatic patients using Myra E Levine's nursing theory include: Assessment, Tropihicognosis Decisions, hypotheses and compiling interventions, implementation and evaluation of nursing. Tropihicognosis Decision, found in patients namely Chronic Pain (related to the inflammatory process) and Anxiety (related to changes in health status. While the hypothesis and nursing interventions that are compiled are directed at helping to reduce pain intensity with Progressive Muscle Relaxation Technique therapy through the Conservation Model approach.Myra E Levine's nursing model theory can be applied and applied well in nursing focusing on Rheumatism cases. Suggestions for health workers are for Progressive Muscle Relaxation Technique therapy in patients with rheumatism to reduce pain intensity so as to increase mobilization ability and reduce activity disorders due to uncontrolled pain.

Food Is Medicine: Diet Assessment Tools in Adult Inflammatory Bowel Disease Research.

Diet significantly impacts the onset and progression of inflammatory bowel disease (IBD), and diet offers unique opportunities for treatment and preventative purposes. However, despite growing interest, no diet has been conclusively associated with improved long-term clinical and endoscopic outcomes in IBD, and evidence-based dietary guidelines for IBD remain scarce. This narrative review critically examines dietary assessment methods tailored to the unique needs of IBD, highlighting opportunities for precision and inclusivity. We conducted a comprehensive literature review using search terms related to diet, diet assessment, nutrition, food, sex, gender, equity, and IBD. The identified dietary assessment tools evaluated nutritional quality, dietary patterns, food processing, lifestyle interactions, inflammatory potential, and effects of specific nutrients. Advanced methods, including biomarkers, multi-omics approaches, and digital tools, were highlighted as being complementary to traditional approaches, offering enhanced precision and real-time monitoring. Women remain under-represented in dietary research but face unique nutritional needs due to hormonal cycles, pregnancy, and higher malnutrition risks in IBD. Traditional diet assessment methods remain valuable but are often limited by misreporting biases. Advanced approaches may provide greater precision, enabling real-time monitoring and personalised dietary tracking. Incorporating considerations of sex, gender, age, ethnicity, socioeconomic, and sustainability enhances the relevance and applicability of these methods. Addressing these multifaceted aspects of dietary assessment in IBD can facilitate robust interventional trials. Diet assessment tools are essential for developing personalised dietary interventions in IBD, informing evidence-based guidelines, and improving health outcomes and quality of life in IBD.

Gut microbiota and inflammasome-mediated pyroptosis: a bibliometric analysis from 2014 to 2023.

The role of gut microbiota in inflammatory disease development and progression has been recognized more recently. Inflammasome-mediated pyroptosis in involved in these diseases. This complex relationship between gut microbiota and inflammasome-mediated pyroptosis provides an important field of research. Bibliometric analysis provides a comprehensive understanding of this relationship, offering valuable insights into emerging research trends. Leveraging data spanning from 2014 to 2023 sourced from the Web of Science Core Collection, our analysis was conducted using advanced tools such as SCImago Graphica, VOSviewer, and CiteSpace software. Visualizations were created using GraphPad Prism software. We explored the nuanced aspects of research hotspots, collaborative networks, and developing trends in this field. A global bibliometric analysis identified 520 relevant studies spanning 41 countries and 887 institutions. Over the past decade, publication trends have shown consistent growth, with China and the United States leading the research output. Southern Medical University and Nanjing Medical University in China emerged as leading institutions in this filed. Prominent contributors include Jia Sun, Yuan Zhang, Wei Chen, Jing Wang, and Hongtao Liu from China, alongside Eicke Latz from Germany. High-impact journals such as Frontiers in Immunology and Nature Communications have been pivotal in disseminating research in this domain. Keyword analysis highlighted a primary focus on gut microbiota, NLRP3 inflammasome, pyroptosis pathways, and inflammatory diseases, themes that persist in recent studies. Furthermore, burst keyword analysis identified "butyrate" as the sole term currently experiencing a marked increase in research interest. Research has been deeply focused on the gut microbiota and inflammasome triggered pyroptosis in years. Over the past decade, the exploration of how gut microbiota and NLRP3 or NLRP6 inflammasome-mediated pyroptosis has been an area of interest. Future investigations in this filed may primarily revolve around understanding the correlation between butyrate and NLRP3 inflammasome induced pyroptosis in relation to conditions. However, an in-depth analysis, through studies is crucial to uncover and elucidate the complex mechanisms linking these elements.