Inflammatory Disease Of Colon Research Articles

Post-hospitalization Short Versus Long Steroid Taper Strategies in Patients With Acute Severe Ulcerative Colitis: A Comparison of Clinical Outcomes.

Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge. We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t-tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC. A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P  = .003) was noted to be the only independent predictor for rehospitalization with ASUC. This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes.

A retrospective analysis of perioperative complications of lateral approach lumbar interbody fusion in patients with prior abdominal surgery or a history of colonic inflammatory disease

BACKGROUND CONTEXTLateral approaches for lumbar interbody fusion (LIF) allow for access to the lumbar spine and disk space by passing through a retroperitoneal corridor either pre- or trans-psoas. A contraindication for this approach is the presence of retroperitoneal scarring that may occur from prior surgical intervention in the retroperitoneal space or from inflammatory conditions with fibrotic changes and pose challenges for the mobilization and visualization needed in this approach. However, there is a paucity of evidence on the prevalence of surgical complications following lateral fusion surgery in patients with a history of abdominal surgery. PURPOSEThe primary aim of this study is to describe the association between surgical complications following lateral interbody fusion surgery and prior abdominal surgical. STUDY DESIGNRetrospective study. PATIENT SAMPLEPatients over the age of 18 who underwent lateral lumbar interbody fusion at a large, tertiary care center between 2011 and 2019 were included in the study. OUTCOME MEASURESThe primary outcome included medical, surgical, and thigh-related complications either in the intraoperative or 90-day postoperative periods. Additional outcome metrics included readmission rates, length of stay, and operative duration. METHODSThe electronic health records of 250 patients were reviewed for demographic information, surgical data, complications, and readmission following surgery. The association of patient and surgical factors to complication rate was analyzed using multivariable logistic regression. Statistical analysis was performed using R statistical software (R, Vienna, Austria). RESULTSOf 250 lateral interbody fusion patients, 62.8% had a prior abdominal surgery and 13.8% had a history of colonic disease. The most common perioperative complication was transient thigh or groin pain/sensory changes (n=62, 24.8%). A multivariable logistic regression considering prior abdominal surgery, age, BMI, history of colonic disease, multilevel surgery, and the approach relative to psoas found no significant association between surgical complication rates and colonic disease (OR 0.40, 95% CI 0.02–2.22) or a history of prior abdominal surgeries (OR 0.56, 95% CI 0.20–1.55). Further, the invasiveness of prior abdominal surgeries showed no association with overall spine complication rate, lateral-specific complications, or readmission rates (p>.05). CONCLUSIONThough retroperitoneal scarring is an important consideration for lateral approaches to the lumbar spine, this study found no association between lateral lumbar approach complication rates and prior abdominal surgery. Further study is needed to determine the impact of inflammatory colonic disease on lateral approach spine surgery.

RARE CASE OF ASCARIASIS DETECTED BY COLONOSCOPY ON THE BACKGROUND OF ELEVATED LEVELS OF FECAL CALPROTECTIN

Introduction: The causative agents of ascariasis in humans are two species: Ascaris lumbricoides and Ascaris suum. For diagnosis, a fecal sample is most often examined. In some cases, the parasite can be identified when coming out with the intestinal passage, and very rarely up on colonoscopy. Aim to present a rare case of ascariasis where the diagnosis was made by colonoscopy on the background of elevated levels of fecal calprotectin (f-CP). Case presentation: A colonoscopy was performed on a 52-year-old female patient due to elevated f-CP. The patient had no complaints. The colonoscopy did not detect pathological changes of the intestinal mucosa, but documented larval stages of Ascaris spp. freely moving in the lumen of the large intestine. The patient was treated with albendazole. Subsequent parasitological examinations of fecal samples were negative. Discussion: In developed countries, the transmission of Ascaris lumbricoides is greatly reduced. On the background of a very limited transmission of Ascaris lumbricoides, many authors consider that most of the sporadic cases of ascariasis are due to Ascaris suum. In the case described by us, the f-CP levels normalized after the treatment, and for this reason, we cannot categorically reject the relationship between Ascaris infection and elevated f-CP levels. Conclusion: The presented clinical case is of interest due to the unusual way of diagnosi ascariasis. In the absence of clinical symptoms, and pathological changes of blood and biochemical parameters, except for elevated fecal calprotectin, inflammatory colon disease was suspected and was colonoscopy performed on this occasion.

Aerogels as Carriers for Oral Administration of Drugs: An Approach towards Colonic Delivery.

Polysaccharide aerogels have emerged as a highly promising technology in the field of oral drug delivery. These nanoporous, ultralight materials, derived from natural polysaccharides such as cellulose, starch, or chitin, have significant potential in colonic drug delivery due to their unique properties. The particular degradability of polysaccharide-based materials by the colonic microbiota makes them attractive to produce systems to load, protect, and release drugs in a controlled manner, with the capability to precisely target the colon. This would allow the local treatment of gastrointestinal pathologies such as colon cancer or inflammatory bowel diseases. Despite their great potential, these applications of polysaccharide aerogels have not been widely explored. This review aims to consolidate the available knowledge on the use of polysaccharides for oral drug delivery and their performance, the production methods for polysaccharide-based aerogels, the drug loading possibilities, and the capacity of these nanostructured systems to target colonic regions.

Colonic stem cell from severe ulcerative colitis maintains environment-independent immune activation by altering chromatin accessibility and global m6A loss

Abstract Ulcerative colitis (UC) is a chronic inflammatory disease of colon, which is characterized by cryptarchitectural distortion. Alternation of colonic stem cell (CoSC) contributed to the occurrence of UC, yet the regulatory mechanisms remain unclear. To investigate the dysregulation of transcriptional and post-transcriptional regulation, we performed RNA-seq, ATAC-seq, and m6A meRIP-seq analysis of the cultured CoSCs that were isolated from UC patients. The transcriptome analysis revealed distinct expression signatures of UC patients in mild and severe stages. We observed abnormal activation of immune and extracellular matrix-related genes in patients affected by severe UC. The chromatin accessibility at the promoter regions of these genes was also specifically increased in the severe stage. In addition, we identified that a global loss of RNA m6A modification in the severe stage was accompanied by higher expression of the m6A demethylase FTO. The aberrant activation of a large number of immune and extracellular matrix-related genes, including IL4R, HLA-DPA1, and COL6A1, was related to both the gain of chromatin accessibility and the loss of m6A in severe UC patients. Our finding revealed an environment-independent immune activation of CoSCs in UC and provided FTO as a potential therapeutic target.

Chemical Characterization of Different Extracts from Artemisia annua and Their Antioxidant, Enzyme Inhibitory and Anti-Inflammatory Properties.

Artemisia annua L. (Asteraceae Family) is an important plant in Asia that has been used for treating different diseases, including fever due to malaria, wounds, tubercolisis, scabues, pain, convulsions, diabetes, and inflammation. In this study we aimed to evaluate the effects of different polarity extracts (hexane, dichloromethane, ethyl acetate, ethanol, ethanol/water (70 %) and water) from A. annua against the burden of inflammation and oxidative stress occurring in colon tissue exposed to LPS. In parallel, chemical composition, antiradical, and enzyme inhibition effects against α-amylase, α-glucosidase, tyrosinase, and cholinesterases were evaluated. The water extract contained the highest content of the total phenolic with 34.59 mg gallic acid equivalent (GAE)/g extract, while the hexane had the highest content of the total flavonoid (20.06 mg rutin equivalent (RE)/g extract). In antioxidant assays, the polar extracts (ethanol, ethanol/water and water) exhibited stronger radical scavenging and reducing power abilities when compared to non-polar extracts. The hexane extract showed the best AChE, tyrosinase and glucosidase inhibitory effects. All extracts revealed effective anti-inflammatory agents, as demonstrated by the blunting effects on COX-2 and TNFα gene expression. These effects seemed to be not related to the only phenolic content. However, it is worthy of interest to highlight how the higher potency against LPS-induced gene expression was shown by the water extract ; thus suggesting a potential phytotherapy application in the management of clinical symptoms related to inflammatory colon diseases, although future in vivo studies are needed to confirm such in vitro and ex vivo observations.

[Computed tomography and magnetic resonance imaging of colonic diseases].

Early diagnosis of aluminal colonic disease is of essential clinical importance to start timely optimised therapy and detect complications early. This paper aims to provide an overview of the use of radiological methods in diagnosing neoplastic and inflammatory luminal diseases of the colon. Characteristic morphological features are discussed and compared. Based on an extensive literature review, the current state of knowledge regarding the imaging diagnosis of luminal pathologies of the colon and their importance in patient management is presented. Technological advances in imaging have made the diagnosis of neoplastic and inflammatory colonic diseases using abdominal computed tomography and magnetic resonance imaging the established standard. Imaging is performed as part of the initial diagnosis in clinically symptomatic patients, to exclude complications, as afollow-up assessment under therapy and as an optional screening method in asymptomatic individuals. Accurate knowledge of the radiological manifestations of the numerous luminal disease patterns, the typical distribution pattern and characteristic bowel wall changes are essential to improve diagnostic decision-making.

Segmental Colitis Associated with Diverticulosis (SCAD).

A distinctive, possibly "novel" form of a segmental inflammatory colonic disease process associated with diverticular disease (so-called SCAD or segmental-colitis-associated-diverticulosis) is reviewed. Although this phenotype of inflammatory colonic disease was initially recognized decades ago, mainly in the elderly, recent evidence from long term natural history studies along with meta-analyses confirms that its clinical course is usually benign and drug-responsive. Interestingly, its appearance in some treated with monoclonal agents (eg., ipilimumab associated colitis) or infected with coronavirus-19 may have critical implications for its pathogenesis. This review further explores the implications of recognition of this pattern of colonic inflammatory disease, with relevance for physicians involved in both clinical practice and clinical trials of newer therapeutic agents.

KIAA0317 regulates SOCS1 stability to ameliorate colonic inflammation.

Dysregulated cytokine signalling is a hallmark of inflammatory bowel diseases. Inflammatory responses of the colon are regulated by the suppressor of cytokine signalling (SOCS) proteins. SOCS1 is a key member of this family, and its function is critical in maintaining an appropriate inflammatory response through the JAK/STAT signalling pathway. Dysregulation of SOCS1 protein has been identified as a causal element in colonic inflammatory diseases. Despite this, it remains unclear how SOCS1 protein is regulated. Here, we identify that SOCS1 protein is targeted for degradation by the ubiquitin proteasome system, mediated by the E3 ubiquitin ligase KIAA0317 during experimental colonic inflammation. We characterize the mechanism of protein-protein interaction and ubiquitin conjugation to SOCS1 and demonstrate that the modulation of SOCS1 protein level leads to stark effects on JAK/STAT inflammatory signalling. Together, these results provide insight into the regulation of colonic inflammation through a new mechanism of ubiquitin-based control of SOCS1 protein.

The Homeostatic Protein Fam3D Orchestrates Colon Mucosal Protection Against Infection, Inflammation, and Carcinogenesis

Fam3D (FAM3D in human) is a homeostatic protein expressed mainly in gastrointestinal tract that plays an essential role in promoting colon mucosal development and homeostasis. However, the mechanistic basis for the action of Fam3D, particularly its relationship to colon mucosal development and microbiome balance, is less clear. In this study, Fam3D expression was increased in colon epithelial cells of germ-free (GF) <i>Fam3D^+/+</i> mice following <i>E. coli</i> infection and GF <i>Fam3D^-/-</i> mice were more susceptible to <i>E. coli</i> colonization in the colon. In chemically induced colitis and colon cancer, GF <i>Fam3D^-/-</i> mice showed more severe inflammatory responses, colon mucosal damage, and tumorigenesis. Unlike SPF mice, GF <i>Fam3D^-/-</i> mice exhibited decreased production of the gut barrier protein Muc2. Mechanism study revealed that in colon epithelial cells, LPS upregulated Fam3D expression through TLR4, while Fam3D promoted Muc2 production through Fpr1 and Fpr2. In addition, Fam3D also upregulated the expression of MAP kinase phosphatase 1 (MKP-1) which is crucial for restraining inflammatory responses. Fam3D deficiency reduced MKP-1 expression, thereby increasing IL-1β and TNF-α production in colon mucosa of GF mice. Thus, Fam3D is critical in colon homeostasis and constitutes a therapeutic target for inflammatory colon diseases.

Colonocyte keratin 7 is expressed de novo in inflammatory bowel diseases and associated with pathological changes and drug-resistance

The clinical course of IBD, characterized by relapses and remissions, is difficult to predict. Initial diagnosis can be challenging, and novel disease markers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein not expressed in the colonic epithelium but has been reported in IBD-associated colorectal tumors. Our aim was to analyze whether K7 is expressed in chronic colonic inflammatory diseases and evaluate its potential as a novel biomarker. K7 was analyzed in two patient cohorts using immunohistochemistry-stained colon samples and single-cell quantitative digital pathology methods. K7 was correlated to pathological changes and clinical patient characteristics. Our data shows that K7 is expressed de novo in the colonic epithelium of ulcerative colitis and Crohn’s disease IBD patients, but not in collagenous or lymphocytic colitis. K7 mRNA expression was significantly increased in colons of IBD patients compared to controls when assessed in publicly available datasets. While K7 increased in areas with inflammatory activity, it was not expressed in specific crypt compartments and did not correlate with neutrophils or stool calprotectin. K7 was increased in areas proximal to pathological alterations and was most pronounced in drug-resistant ulcerative colitis. In conclusion, colonic epithelial K7 is neo-expressed selectively in IBD patients and could be investigated for its potential as a disease biomarker.

Selenocoxib-3, a novel anti-inflammatory therapeutic effectively resolves colitis.

Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling [elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by H & E staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.

Role of Microbial Metabolites of Histidine in the Development of Colitis.

Colitis is a chronic relapsing inflammatory disease of colon. Clinical studies show that meat-rich diet plays a critical role in the relapse of colitis. However, it is unclear whether the microbial metabolites of histidine, which is an amino acid widely found in meat, have an impact on the health of the intestine. Six metabolites of histidine are given to IEC-6 cells. The cell activity measurement shows that imidazole propionate (IMP) is the most detrimental metabolite. Then, IMP is injected to mice by rectal administration, with blood and colon tissues collected for the measurement of colitis related parameters. The results show that treatment with IMP significantly increased NF-κB, iNOS, and IL-6, decreased number of goblet cell, and inhibited expressions of miR-146b. However, overexpression of miR-146b in mice rescues the decline of the physical condition. Additionally, Notch receptor 1 (Notch1) is identified as a target gene of miR-146b. Further analysis shows that miR-146b restored the abundance of goblet cells by regulating Notch1 signaling pathway. IMP is able to induce intestinal inflammation, impairs the intestinal barrier, and affects the proliferation of goblet cells. The underlined mechanism may partially contribute to the dysregulation of miR-146b/Notch1 axis.

Delta-tocotrienol 13′-Carboxychromanol, a Vitamin E Metabolite, Interacts With Gut Microbes As Indicated by Its Anti-colitis Synergy With a Lactic Acid Bacterium in Mice

ObjectivesUlcerative colitis (UC) is an inflammatory colonic disease and microbial dysbiosis is one of its risk factors. We recently showed that delta-tocotrienol 13’-carboxychromanol (dTE-13’), a metabolite of the natural vitamin E form dTE, inhibited colitis-associated tumorigenesis in mice, modulated their gut microbes and increased the relative abundance of a lactic acid bacterium. Interestingly, a subspecies of this bacterium named Lactococcus lactis subsp. cremori (L. cremoris), has been reported to attenuate UC in mice. Therefore, we reasoned that combining dTE-13’ with L. cremoris may offer synergistic protection against UC in mice.MethodsWe fed male balb/c mice with either 0.04% (w/w) dTE-13’ in diet, or 5 × 108 CFU L. cremoris through gavage or a combination of both for 7 days. Then we induced UC in these mice by adding 2% dextran sulfate sodium to their drinking water. All treatments continued along with UC for an additional 9 days till animal sacrifice. To assess the anti-UC effects of the combination, we evaluated mice's colitis symptoms, colonic tissue damage, and cytokine levels. To further understand the role of gut microbes underlying the anti-UC effects of the combination, we processed fecal samples to analyze changes in microbial composition, and level of dTE-13’ metabolites, and performed in vitro anaerobic incubation using mouse's cecum microbes.ResultsCompared to the controls, dTE-13’ + L. cremoris offered superior protection against UC as indicated by milder clinical symptoms, less tissue damage and decreased colonic inflammation, while neither dTE-13’ nor L. cremoris alone showed significant benefits. Mechanistically, combination rendered gut microbes resistant to UC-induced microbial dysbiosis and increased the fecal level of a reduced dTE-13’ metabolite. Preliminary observations from the anaerobic study suggested that gut microbes pre-selected by dTE-13’ in the animal study were capable of reducing the compound, and L. cremoris appeared to promote the microbiota-mediated metabolism.ConclusionsOur study demonstrated the benefits of dTE-13’ + L. cremoris against colitis. It offered a new perspective of developing anti-UC therapies by combining dietary compounds with bacteria, and presented the first evidence that gut microbes can metabolize dTE-13’, a metabolite of vitamin E.Funding SourcesPurdue Center for Cancer Research.

Inflammation suppresses DLG2 expression decreasing inflammasome formation

PurposeLoss of expression of DLG2 has been identified in a number of cancers to contribute to the disease by resulting in increased tumor cell proliferation and poor survival. In light of the previous evidence that DLG2 alters the cell cycle and affects proliferation, combined with indications that DLG2 is involved in NLRP3 inflammasome axis we speculated that DLG2 has an immune function. So far, there is no data that clearly elucidates this role, and this study was designed to investigate DLG2 in inflammatory colon disease and in colon cancer as well as its impact on inflammasome induction.MethodsThe DLG2 expression levels were established in publicly available inflammation, colon cancer and mouse model datasets. The overexpression and silencing of DLG2 in colon cancer cells were used to determine the effect of DLG2 expression on the activation of the inflammasome and subsequent cytokine release.ResultsThe expression of DLG2 is repressed in inflammatory colon diseases IBD and Ulcerative colitis as well as colorectal cancer tissue compared to healthy individuals. We subsequently show that induction with inflammatory agents in cell and animal models results in a biphasic alteration of DLG2 with an initial increase followed by an ensuing decrease. DLG2 overexpression leads to a significant increase in expression of IL1B, IκBζ and BAX, components that result in inflammasome formation. DLG2 silencing in THP1 cells resulted in increased release of IL-6 into the microenvironment which once used to treat bystander COLO205 cells resulted in an increase in STAT3 phosphorylation and an increase proliferating cells and more cells in the G2/M phase. Restoration of DLG2 to the colon resulted in reduced AKT and S6 signaling.ConclusionDLG2 expression is altered in response to inflammation in the gut as well as colon cancer, resulting in altered ability to form inflammasomes.Trial registrationNCT03072641.

Engineering designer biologics in plant cells for oral treatment of inflammatory bowel disease (IBD)

Inflammatory bowel disease (IBD), including the two most common subtypes: Crohn’s disease (CD) and ulcerative colitis (UC), represents a group of intestinal disorders that cause prolonged inflammation of the digestive tract. The current treatment strategies, including the conventional anti‐inflammatory medications and the new biological drugs targeting the pro‐inflammatory cytokine tumor necrosis factor alpha (TNFα), have limited therapeutic efficacy and adverse drug reactions resulted from systemic administration. Colon‐targeted oral delivery of anti‐TNFα agents is highly desirable for the treatment of IBD, as it improves drugs’ efficacy while reducing systemic toxicity. Plant cell culture has emerged as a safe and cost‐effective bioproduction platform for therapeutic proteins. A unique feature of the plant cells is that they could serve not only as the “bio‐factory,” but also the oral delivery vehicle for recombinant biologics. Recent advances have demonstrated that plant cell walls, made primarily of cellulose microfibrils, can act as an excellent natural capsule for oral delivery of biologic drugs. This project aims to leverage two unique posttranslational modifications – “glycosyl‐phosphatidylinositol (GPI) anchor” and “plant‐specific hydroxyproline (Hyp)‐O‐glycosylation” – to strategically design and engineer novel anti‐TNFα biomolecules in plant cells to develop a new class of oral biologic drugs for the treatment of UC. The designer anti‐TNFα biomolecules consist of three functional domains: a N‐terminal single‐chain fragment variable (scFv) of an anti‐TNFα antibody, a proprietary Hyp‐O‐glycosylation module comprised of tandem repeats of the “Ser‐Pro” motif, or (SP)n (n= 5 to 30), and a C‐terminal GPI anchor. While the GPI anchor “displays” the expressed anti‐TNFα biomolecules at the plant cell surface to presumably create a high local concentration of the biologics, the (SP)n glycomodule stabilizes the protein from degradation during both the bioproduction and oral delivery processes. Designer anti‐TNFα biomolecules consisting of different sizes of the (SP)n glycomodule are investigated for their accumulations in tobacco BY‐2 cells, biological activity, and stability in a simulated gastric fluid, which determines the (SP)20 module as an optimal design for the biomolecules. The therapeutic effectiveness of the orally administrated designer anti‐TNFα biologic (optimal design) in mitigating the UC symptom is assessed in a dextran sulfate sodium (DSS)‐induced colitis mouse model. The immune‐modulatory effects of the anti‐TNFα biologics are determined by histopathological analysis and assay of the inflammatory markers. The research may develops a new platform to produce effective oral biologic drugs for the treatment of UC and other inflammatory diseases of colon.

Mechanism investigation of fermented egg-milk peptides on colonic inflammatory diseases: based on in vivo and in silico research.

Fermented egg-milk peptides (FEMPs) could alleviate the symptoms of inflammatory diseases but the underlying regulating mechanism of effective ingredients is unclear now. Our research was designed to confirm the protective function of FEMP, then analyze the potential targets and pathways that could be regulated by digested FEMP (dFEMP). The results showed that FEMP could ease the inflammatory symptoms in the colon, repair the damage of inflammation, and decrease the level of pro-inflammatory cytokines (decreased by 31.81% TNF-α, 60.20% IL-1β, 85.65% IL-6). The results of in silico experiments revealed that dFEMP could influence many inflammation-related targets. Most targets affected the inflammation-related function and participated in the inflammatory signaling pathways, such as the T cell receptor (TCR) signaling pathway. Besides, molecular docking results revealed that hydrogen-bonding and salt bridges played vital roles in the dFEMP-target interactions. Combining in vivo experiments with in silico experiments, this study can prove a new theory for research between the bioactive peptides and inflammation.

Oral nanozyme-engineered probiotics for the treatment of ulcerative colitis.

Probiotic-based therapy for ulcerative colitis (UC) is a novel and promising approach that has gained much popularity in recent years. However, probiotics may be easily captured and destroyed by the harsh in vivo environment, which limits their application prospects to a large extent. This work introduces a versatile facile approach for decorating individual probiotics with nanozyme coatings, named Pt-Lipid@EcN. A bimolecular lipid coating is deposited on the surface of probiotics used in the oral treatment of UC using simple self-assembly with a liposome under cytocompatible conditions, and it acts as armor to effectively protect the probiotics from strong digestive acids and enzymes. The obtained results indicated that the liposome-coated Escherichia coli Nissle (EcN) 1917 could significantly improve the colonization rate of the microorganisms in the intestinal tract. We also explored the specific mechanism of Pt-Lipid@EcN to improve the behavior of murine UC models, including reduction of inflammatory effects and histological injury, and regulation of epithelial barrier homeostasis in the intestine. The nanozyme-shielded probiotic exhibited enhanced anti-inflammatory ability in vivo, introducing novel strategies for the application of nanozyme biomedicine in the treatment of colonic inflammatory diseases.

An Extracellular Matrix-Liposome Composite, a Novel Extracellular Matrix Delivery System for Accelerated Tissue Regeneration.

The unfolded states of fibronectin (FN) subsequently induce the formation of an extracellular matrix (ECM) fibrillar network, which is necessary to generate new substitutive tissues. Here, the authors demonstrate that negatively charged small unilamellar vesicles (SUVs) qualify as candidates for FN delivery due to their remarkable effects on the autonomous binding and unfolding of FN, which leads to increased tissue regeneration. In vitro experiments revealed that the FN-SUV complex remarkably increased the attachment, differentiation, and migration of fibroblasts. The potential utilization of this complex in vivo to treat inflammatory colon diseases is also described based on results obtained for ameliorated conditions in rats with ulcerative colitis (UC) that had been treated with the FN-SUV complex. Their findings provide a new ECM-delivery platform for ECM-based therapeutic applications and suggest that properly designed SUVs may be an unprecedented FN-delivery system that is highly effective in treating UC and inflammatory bowel diseases.

Modulation of Gut Barrier Functions in Ulcerative Colitis by Hyaluronic Acid System.

The active stages of intestinal inflammation and the pathogenesis of ulcerative colitis are associated with superficial mucosal damage and intermittent wounding that leads to epithelial barrier defects and increased permeability. The standard therapeutic interventions for colitis have focused mainly on maintaining the remission levels of the disease. Nonetheless, such treatment strategies (using anti‐inflammatory, immunomodulatory agents) do not address colitis' root cause, especially the mucosal damage and dysregulated intestinal barrier functions. Restoration of barrier functionality by mucosal healing or physical barrier protecting strategies shall be considered as an initial event in the disease suppression and progression. Herein, a biphasic hyaluronan (HA) enema suspension, naïve‐HA systems that protect the dysregulated gut epithelium by decreasing the inflammation, permeability, and helping in maintaining the epithelial barrier integrity in the dextran sodium sulfate‐induced colitis mice model is reported. Furthermore, HA‐based system modulates intestinal epithelial junctional proteins and regulatory signaling pathways, resulting in attenuation of inflammation and mucosal protection. The results suggest that HA‐based system can be delivered as an enema to act as a barrier protecting system for managing distal colonic inflammatory diseases, including colitis.