Search

Recent studies have gradually elucidated the pathogenesis of inflammatory bowel disease; thus, the Janus kinase (JAK)-signal transducers and activators of transcription pathway are strongly involved in the pathophysiology of inflammatory bowel disease. Generally, Janus kinase inhibitors are being used for the treatment of rheumatoid arthritis and other immunological diseases, with the therapeutic promising effects. Currently, in Japan, three Janus kinase inhibitors, namely tofacitinib, filgotinib, and upadacitinib, are available for the treatment of patients with active ulcerative colitis. Therefore, evaluating the efficacy and safety of each JAK inhibitor is essential for determining the role of JAK inhibitors in future therapeutic strategies for inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing protocols of donor stool may diminish the bacterial viability of transplanted material. This study assessed the effect of four processing techniques for donor stool (i.e., anaerobic and aerobic, both direct processing and after temporary cool storage) on bacterial viability. By combining anaerobic culturing on customized media for anaerobes with 16S rRNA sequencing, we could successfully culture and identify the majority of the bacteria present in raw fecal suspensions. We show that direct anaerobic processing of donor stool is superior to aerobic processing conditions for preserving the bacterial viability of obligate anaerobes and butyrate-producing bacteria related to the clinical response to FMT in ulcerative colitis patients, including Faecalibacterium, Eubacterium hallii, and Blautia. The effect of oxygen exposure during stool processing decreased when the samples were stored long-term. Our results confirm the importance of sample conditioning to preserve the bacterial viability of oxygen-sensitive gut bacteria. Anaerobic processing of donor stool may lead to increased clinical success of FMT, which should further be investigated in clinical trials. [ABSTRACT FROM AUTHOR]

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting. The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD. In a retrospective study, we examined the medical records of 5739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022. Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in the general population in Northern Italy in 2021 was 0.18% (p = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 patients with MS, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (p = 0.004). As for therapy, significant differences were found in mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, p < 0.0001) and anti-TNF treatment (0% cases vs. 26.6% controls, p = 0.03, respectively) at the time of MS diagnosis. Moreover, a Kaplan–Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (p = 0.02). In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone. [ABSTRACT FROM AUTHOR]

5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of Escherichia coli, which could be ameliorated by treatment with 5-ASA. However, 5-ASA was no longer able to reduce inflammation, restore epithelial hypoxia, or blunt an expansion of E. coli in DSS-treated mice that lacked Pparg expression specifically in the intestinal epithelium. These data suggest that the anti-inflammatory activity of 5-ASA requires activation of epithelial PPAR-γ signaling, thus pointing to the intestinal epithelium as a potential target for therapeutic intervention in ulcerative colitis.IMPORTANCE An expansion of Enterobacterales in the fecal microbiota is a microbial signature of dysbiosis that is linked to many noncommunicable diseases, including ulcerative colitis. Here, we used Escherichia coli, a representative of the Enterobacterales, to show that its dysbiotic expansion during colitis can be remediated by modulating host epithelial metabolism. Dextran sulfate sodium (DSS)-induced colitis reduced mitochondrial activity in the colonic epithelium, thereby increasing the amount of oxygen available to fuel an E. coli expansion through aerobic respiration. Activation of epithelial peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling with 5-aminosalicylic acid (5-ASA) was sufficient to restore mitochondrial activity and blunt a dysbiotic E. coli expansion. These data identify the host's epithelial metabolism as a potential treatment target to remediate microbial signatures of dysbiosis, such as a dysbiotic E. coli expansion in the fecal microbiota.

Background and aims: Clostridioides difficile infection (CDI) induces intense acute inflammatory responses through toxin release. A combination of antibiotic and anti-inflammatory agents is sometimes recommended in severe, non-responsive cases, although clinical trials have been inconclusive, raising concerns about potential complications. This study aims to investigate the effect of budesonide and mesalamine in the treatment of CDI in a murine model, by evaluating the combination of fidaxomicin and these anti-inflammatory drugs. Method: C57BL/6 J female mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or culture media by gavage. After the challenge, mice received placebo, fidaxomicin alone (20 mg/kg), or fidaxomicin combined with mesalamine (200, 400 mg/kg) or budesonide (0.2, 1, 10 mg/kg) for 5 days. The mice were monitored for 7 days with weight and survival. Colon and cecum tissues were harvested for histological assessment. Results: CDI of mice caused 80% mortality. Fidaxomicin completely protected against CDI in all parameters (weight, survival and pathscores). Mortality rates were up to 90%, 70% in budesonide(10 mg/kg) and mesalamine (400 mg/kg) treatment group, respectively. Budesonide (0.02,0.1 and 1 mg/kg) adjunction to fidaxomicin worsened the disease outcome according to all tested parameters. While mesalamine in combination with fidaxomicin (200, 400 mg/kg) did not lead to any deaths during CDI treatment, it did not provide additional benefits. Conclusions: Anti-inflammatory drugs including corticosteroid therapy may worsen the incidence and severity of CDI in this mouse model. These studies may have important clinical implications for understanding the role of anti-inflammatory/ corticosteroid therapy in CDI and inflammatory bowel disease management.

Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBDs), which have a pivotal role in weakening the quality of lives of suffering patients. According to some recent studies, significant changes in dietary patterns may have contributed to the increased prevalence of UC. Potential renal acid load (PRAL) is an index used to estimate dietary acid load of the diet. The aim of the current study is to investigate the association between PRAL and odds of UC. The current case–control study included 62 newly diagnosed cases of UC and 124 healthy controls. Dietary habits of participants in the last year were collected with a valid food frequency questionnaire (FFQ). Thereafter, PRAL score was calculated based on a formula containing the dietary intake of protein, phosphorus, potassium, calcium, and magnesium. Participants were categorized according to quartiles of PRAL. Multivariable logistic regression models were used to estimate the odds' ratio (OR) with 95% confidence intervals (CIs) of UC across quartiles of PRAL. The results of the current study indicated that in the crude model, participants in the fourth quartile of PRAL had 2.51 time higher odds of UC compared with those in the first quartile of the PRAL [(OR 2.51; 95% CI 1.03–6.14), (P = 0.043)]. After adjustment for age and biological gender, this positive association remained significant [(OR 2.99; 95% CI 1.16–7.72), (P = 0.023)]. In the final model, after further adjustment for BMI, current smoking, education, Helicobacter pylori infection, and dietary intakes of total energy, omega-3 fatty acids, trans-fatty acids, and total dietary fiber, the odds of UC in the highest quartile of PRAL was significantly higher compared to the lowest quartile [(OR 3.08; 95% CI 1.01–9.39), (P = 0.048)]. So, we observed that higher dietary acid load assessed by PRAL score is associated with greater odds of UC. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial. [ABSTRACT FROM AUTHOR]

This study reports on developing a simple, cost-effective, highly sensitive spectrophotometric method for measuring mesalazine (MSZ). The method utilizes the oxidative coupling of MSZ with syringic acid (4-hydroxy 3,5-dimethoxybenzoic acid) in the presence of dissolved oxygen under alkaline conditions to form a stable indophenol dye with a characteristic blue color, which can be measured at 615 nm. Beer's law was found to be obeyed over the range of 1.25–50 µg·mL−1, with a molar absorptivity of 0.53 × 104 mol−1·L−1·cm−1. Moreover, the method exhibited excellent sensitivity, with a limit of detection (LOD) of 0.093 µg·mL−1 and a limit of quantitation (LOQ) of 0.282 µg·mL−1. The proposed method was found to be selective, as it could effectively detect MSZ in the presence of certain interfering species. The proposed method was validated according to current ICH guidelines and demonstrated good accuracy, with recoveries ranging between 98 and 100% and a relative standard deviation of less than 0.6%. Overall, this method provides a promising tool for the sensitive and accurate determination of MSZ in its pure form, pharmaceutical formulations, and biological samples. [ABSTRACT FROM AUTHOR]

(1) Background: Ulcerative colitis (UC) is a disease caused by noninfectious chronic inflammation characterized by varying degrees of inflammation affecting the colon or its entire mucosal surface. Current therapeutic strategies rely on the suppression of the immune response, which is effective, but can have detrimental effects. Recently, different plant polysaccharides and their degradation products have received increasing attention due to their prominent biological activities. The aim of this research was to evaluate the mitigation of inflammation exhibited by tamarind seed polysaccharide hydrolysate (TSPH) ingestion in colitis mice. (2) Methods: TSPH was obtained from the hydrolysis of tamarind seed polysaccharide (TSP) by trifluoroacetic acid (TFA). The structure and physical properties of TSPH were characterized by ultraviolet spectroscopy (UV), thin-layer chromatography (TLC), fourier transform infrared spectroscopy (FT-IR), and High-Performance Liquid Chromatography and Electrospray Ionization Mass Spectrometry (HPLC–ESI/MS) analysis. Then, the alleviative effects of the action of TSPH on 2.5% dextran sodium sulfate (DSS)-induced colitis mice were investigated. (3) Results: TSPH restored pathological lesions in the colon and inhibited the over-secretion of pro-inflammatory cytokines in UC mice. The relative expression level of mRNA for colonic tight junction proteins was increased. These findings suggested that TSPH could reduce inflammation in the colon. Additionally, the structure of the gut microbiota was also altered, with beneficial bacteria, including Prevotella and Blautia, significantly enriched by TSPH. Moreover, the richness of Blautia was positively correlated with acetic acid. (4) Conclusions: In conclusion, TSPH suppressed colonic inflammation, alleviated imbalances in the intestinal flora and regulated bacterial metabolites. Thus, this also implies that TSPH has the potential to be a functional food against colitis. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from the origin cell and able to circulate into the bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also play a role in IBD. In this review, we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment. [ABSTRACT FROM AUTHOR]

Background: Mesalamine is one of the most-used drugs in inflammatory bowel disease (IBD), especially ulcerative colitis. Regulatory agencies have listed mesalamine as an unsafe drug in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency based on the risk of hemolysis, although scientific evidence is lacking. The occurrence of acute and/or chronic hemolytic anemia in IBD patients with G6PD deficiency exposed to mesalamine was evaluated. Methods: In this multicenter study, IBD patients with G6PD deficiency (cases) receiving mesalamine were retrospectively evaluated for acute, and prospectively for chronic, hemolysis. The presence of hemolytic anemia was based on red blood cell and reticulocyte count, hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and haptoglobin levels. Cases were compared with controls (IBD patients with normal G6PD). Results: A total of 453 IBD patients (mean age 52.1 ± 16.0 years; 58.5% female) were enrolled. Ulcerative colitis was present in 75% of patients. G6PD deficiency was detected in 17% of patients. Oral mesalamine was used in 67.9% of ulcerative colitis and in 32.4% of Crohn's disease cases. None of the 78 IBD patients with G6PD deficiency receiving mesalamine underwent hospitalization or specific treatment for acute hemolytic anemia. Relevant differences in chronic hemolysis markers were not observed in 30 cases compared with 112 controls receiving mesalamine (≤4500 mg/day). Marker modifications were also observed in mesalamine-free cases, consistent with the basal rate of erythrophagocytosis in G6PD deficiency. Ex vivo experiments showed the release of methemoglobin by G6PD deficient RBCs upon mesalamine challenge, only above 2.5 mg/mL, a concentration never reached in the clinical setting. Conclusions: This study provides, for the first time, evidence that mesalamine is safe in G6PD deficiency at a dosage of up to 4500 mg/day. [ABSTRACT FROM AUTHOR]

Objectives: The goal of the study was to treat ulcerative colitis by targeting drug delivery to the colon via the novel ingredient's guar gum and pH-dependent polymer sodium alginate. The drug was released at a high pH in the colon due to the sodium alginates. Guar gum was a novel ingredient that was used as a release retarder, binder, and swelling agent. The galactomannan enzyme naturally degrades the guar gum. Because this enzyme is only found in the human body's GIT colon, the tablet colon is naturally target-specific. Materials and Methods: The tablet was prepared through wet granulation using an IPA solution. The formed granules subjected to the pre-formulation studies had free flow ability and a uniform size or shape. After the pre-formulations, the tablets were formed using the ZP-17 machine, and post-compression studies such as the hardness test, friability test, weight variation test, and thickness or diameter test were performed. Results: The precompression and post-compression studies, including the hardness test, friability test, weight variation test, and thickness or diameter test, were in the specification. The disintegration test was performed on the tablets, but due to the swelling nature of guar gum, they did not disintegrate. The dissolution studies were performed for 24 hr using acidic and basic buffers. The drug releases at a basic pH of 7.4 in the presence of the galactomannose enzyme, which shows its pH dependence and colon targeting. The various kinetic models were used to release kinetic models. According to the kinetic release studies, the R2 explained that formulations were controlled releases and followed the zero order, which is independent of drug concentration. [ABSTRACT FROM AUTHOR]

Chemoprevention is one of the ways to fight colorectal cancer, which is a huge challenge in oncology. Numerous pieces of evidence indicate that chronic inflammation in the course of Crohn's disease or ulcerative colitis (UC) is a significant cancer risk factor. Epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), including mesalazine, has beneficial effects on colitis-associated colorectal cancer. Mesalazine is a first-line therapy for UC and is also widely used for maintaining remission in UC. Data showed that mesalazine has antiproliferative properties associated with cyclooxygenase (COX) inhibition but can also act through COX-independent pathways. This review summarizes knowledge about mesalazine's molecular mechanisms of action and chemopreventive effect by which it could interfere with colorectal cancer cell proliferation and survival. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are immune-mediated abnormalities of the gastrointestinal tract and primarily include ulcerative colitis (UC) and Crohn's disease (CD). Environmental and genetic variables are part of the disease's etiology. Antibiotics, steroids, amino-salicylate and immunomodulators have all been used to decrease the signs of illness and maintain the recovery. Unfortunately, it has been discovered that prolonged use of these medicines causes serious toxicities, which discourages consumers. The anti-UC campaigns are primarily targeted at oxidative stress or inflammation, which increases the anti-inflammatory cytokine levels and suppresses the pro-inflammatory cytokine levels. Herbal medicines may have advantages due to their high patient acceptance, efficacy, relative safety and low cost. Numerous studies have shown the usefulness of herbal medicines in treating UC and these have achieved widespread patient approval. The research on herbal therapy is insufficient, complicated and perplexing and it is unquestionably linked to both hazards and benefits. To increase the quality and safety of herbal medicine treatments for UC, more carefully controlled clinical trials are required. [ABSTRACT FROM AUTHOR]

Limited data suggest that older patients with ulcerative colitis (UC) irrespective of late-onset UC or disease diagnosed before the age of 60 years, should largely receive similar corticosteroid-sparing agents to as those prescribed to younger patients. Typically, mesalamine is recommended as a first-line agent for induction or maintenance therapy, with biological treatments recommended for more severe disease. The risk profile for adverse drug events should be taken into consideration when selecting an appropriate therapy, for example, immunosuppressants may exacerbate infection risks. [ABSTRACT FROM AUTHOR]

Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis). The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy for the treatment of these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin fibrillation. To induce fibrillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50 °C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration-dependent manner (different ratios (1:0.1, 1:0.5, 1:1, and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid fibrils and destabilized pre-formed fibrils. In addition, our molecular docking study confirmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our findings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICI) are effective against various malignancies. However, adverse events including diarrhea and colitis can lead to significant morbidity and mortality. Recommendations for the management of ICI mediated diarrhea and colitis include steroids and biologics. Given their associated risks, this study evaluated the role of the non-immunosuppressive agents, mesalamine and or cholestyramine. Methods: This is a retrospective, descriptive, single-center study of adults who developed ICI diarrhea and colitis between 2010 and 2020 at MD Anderson Cancer Center. Clinical data and outcomes were compared between those treated with the non-immunosuppressive therapies mesalamine and/or cholestyramine alone versus those who received additional immunosuppression with steroids and biologics. Results: Our sample comprised 66 patients wherein, the mean age was 63 years, 71% were males, and 97% had stage III/IV cancers. Fourteen patients were treated successfully with non-immunosuppressive therapy. They had grade 1–3 diarrhea and 1–2 colitis with no difference in the rate of histologic colitis compared to those who received immunosuppressive therapy. They had less CTLA-4 inhibitor-based therapy (36% vs. 73%, p = 0.034), delayed onset of symptoms (159 vs. 64 days, p = 0.011), lower fecal calprotectin levels (56 vs. 234, p = 0.012) and were more likely to resume ICI therapy (64% vs. 25%, p = 0.006). Conclusion: Mesalamine and/or cholestyramine may be effective for mild ICI diarrhea and colitis among patients with delayed symptom onset with lower colonic inflammatory burden. Prospective studies randomizing patients with mild colitis between mesalamine/cholestyramine and immunosuppressive treatment are warranted to assess their efficacy and safety. [ABSTRACT FROM AUTHOR]

The analyses presented here provide further supporting evidence for the effectiveness of OPRM as induction therapy in patients with moderately active UC. Conclusion The new analyses presented here provide further evidence that OPRM is an effective treatment for the induction of remission in patients with moderately active UC. Keywords: aminosalicylates; delayed-release; effectiveness; inflammatory bowel disease; mesalamine EN aminosalicylates delayed-release effectiveness inflammatory bowel disease mesalamine 516 519 4 07/27/23 20230701 NES 230701 New meta-analyses are presented that provide further evidence supporting the effectiveness of oral prolonged-release mesalazine compared to other oral mesalazines as induction therapy in patients with moderately active ulcerative colitis. [Extracted from the article]

Background: The ethanolic extract of Laurus nobilis possesses an anti-inflammatory effect, which will protect against acetic acid-induced Ulcerative colitis by inhibiting endogenous free radicals. Objectives: The work has been undertaken to explore the efficacy and safety of ethanolic leaf extract of Laurus nobilis in treating acetic acid-induced Ulcerative colitis by estimating the biochemical, physical parameters, and histopathological studies. Materials and Methods: The plant powder of L. nobilis was extracted using 70% ethanol, and a phytochemical investigation was performed. Male and Female Wistar albino rats were divided into six groups and pretreated with saline, saline followed by ulcer induction, two doses of extracts (100mg/kg and 200mg/kg b.w), and sulfasalazine (one day) followed by ulcer induction and one low dose extract treatment without inducing ulcer. Results: The phytochemical investigation of the extract confirms the presence of flavonoids. The biochemical estimations showed increased SOD, CAT, and GSH and decreased levels of TBARS in extract-treated groups compared to the acetic acid-induced group. The physical parameters like Crypt abscesses, gross mucosal inflammation, wet weight of the colon, diarrhea, and activity score have also shown better results in extract-treated groups showing a protective effect. Histopathological results further confirmed the therapeutic effect of the extract. Conclusion: The protective effect of ethanolic leaf extract of Laurus nobilis has been proved. The therapeutic effect was mainly due to flavonoids, and the low-dose extract was more potent than the high-dose extract. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to evaluate possible therapeutic effects of moxifloxacin against acetic acid-induced colitis in a rat model. Methods: Forty adult Wistar rats were separated into 4 groups, including the negative control group, acetic acid (AA) group, AA + sulfasalazine (100 mg/kg/day) group, and AA+ moxifloxacin (MFX) (8 mg/kg/day) group. Experimental colitis was induced in rats by rectal administration of (4%v/v) acetic acid. Rats with colitis were received either MFX 8mg/kg/day or sulfasalazine 100mg/kg orally for 7days. The parameters measured are macroscopical assessment, colon weight (indicator of edema) and the measurement of concentrations of the proinflammatory cytokine TNF-α, oxidative stress marker malondialdehyde (MDA), adhesion molecule selectin and the inflammatory mediator NF-κB in colonic tissue homogenate. Results: This study had shown that AA elevate macroscopical scores, colon weight and biochemical homogenate parameters and all measured parameters were significantly reduced by both moxifloxacin and sulfasalazine with nonsignificant difference between them. Conclusion: The study explain that moxifloxacin possesses therapeutic potential in in AA induced colitis and its anti-inflammatory actions may involve inhibition of NF-κB inflammatory pathways including TNF-α pathway with its downstream inflammatory process such as elevation of adhesion molecule synthesis and oxidative species overproduction in the colonic tissues. [ABSTRACT FROM AUTHOR]

Recent findings suggest a key role for reactive oxygen species (ROS) in the pathogenesis and progression of ulcerative colitis (UC). Several studies have also highlighted the efficacy of citrate functionalized Mn3O4 nanoparticles as redox medicine against a number of ROS-mediated disorders. Here we show that synthesized nanoparticles consisting of chitosan functionalized tri-manganese tetroxide (Mn3O4) can restore redox balance in a mouse model of UC induced by dextran sulfate sodium (DSS). Our in-vitro characterization of the developed nanoparticle confirms critical electronic transitions in the nanoparticle to be important for the redox buffering activity in the animal model. A careful administration of the developed nanoparticle not only reduces inflammatory markers in the animals, but also reduces the mortality rate from the induced disease. This study provides a proof of concept for the use of nanomaterial with synergistic anti-inflammatory and redox buffering capacity to prevent and treat ulcerative colitis. Chitosan- Mn3O4 nanoparticles are characterized and shown to counteract redox imbalance and inflammation, and reduce mortality in a mouse model of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1‐kestose is effective for active ulcerative colitis remains controversial. Aims: This randomised, double‐blind, placebo‐controlled pilot trial investigated the efficacy of 1‐kestose against active ulcerative colitis. Methods: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1‐kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. Results: The clinical activity index at week 8 was significantly lower in the 1‐kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1‐kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha‐diversity in the 1‐kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short‐chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. Discussion: Oral 1‐kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome. [ABSTRACT FROM AUTHOR]

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Aim: To report efficacy and infection rates in patients receiving tofacitinib induction treatment, by baseline corticosteroid status. Methods: We evaluated efficacy and safety data from OCTAVE Induction 1&2 in patients with moderately-to-severely active ulcerative colitis who received tofacitinib 10 mg twice daily or placebo for 8 weeks, based on induction baseline oral corticosteroid use (Corticosteroid-Yes/No) and dose (< 20/ ≥ 20 mg/day). Infections of interest included serious infections, herpes zoster (HZ), and adjudicated opportunistic infections (OIs). Results: At OCTAVE Induction 1&2 baseline, 478/1092 (43.8%) patients were receiving corticosteroids. Tofacitinib demonstrated significant induction efficacy versus placebo for both Corticosteroid-Yes and Corticosteroid-No. With adjustment for prior tumor necrosis factor inhibitor and immunosuppressant failure, there were no statistically significant differences in remission and clinical response rates for Corticosteroid-Yes versus Corticosteroid-No. Among tofacitinib-treated patients, HZ and OIs occurred more frequently in Corticosteroid-Yes versus Corticosteroid-No, regardless of dose (< 20 mg vs. ≥ 20 mg). Infection incidence rates (regardless of severity/seriousness) during tofacitinib induction were generally similar regardless of baseline corticosteroid use. The proportion of tofacitinib-treated patients with HZ was 0.2% for Corticosteroid-No versus 1.1% for Corticosteroid-Yes < 20 mg and 1.0% for Corticosteroid-Yes ≥ 20 mg. Two out of three patients had HZ OIs. Conclusions: Tofacitinib induction efficacy (clinical response and remission) was similar in baseline corticosteroid subgroups. Infections of interest were rare; HZ and OIs occurred more frequently among those receiving tofacitinib and corticosteroids versus those receiving tofacitinib without corticosteroids. Trial Registration: http://www.clinicaltrials.gov (NCT01465763[21/10/2011]; NCT01458951[21/10/2011]). [ABSTRACT FROM AUTHOR]

BACKGROUND: Ulcerative colitis is a gastrointestinal disease closely related to intestinal epithelial barrier damage and intestinal microbiome imbalance; however, effective treatment methods are currently limited. Rehmannia glutinosa polysaccharide (RGP) is an important active ingredient with a wide range of pharmacological activities, although its protective effect on colitis remains to be explored. In the present study, we verified the in vitro anti‐inflammatory effect of RGP, and observed the ameliorating effect of RGP on dextran sulfate sodium‐induced colitis in mice. RESULTS: The results showed that (i) RGP attenuates lipopolysaccharide‐induced overexpression of inflammatory factors in RAW264.7 cells; (ii) RGP improves the pathological damage caused by DSS, including weight loss, increased disease activity index and intestinal tissue ulcers; (iii) RGP improves tight junction proteins to protects the tightness of the intestinal epithelium; (iv) RGP inhibits the expression of inflammatory factors through the nuclear factor‐kappa B pathway, and improved the of intestinal tissues inflammation; and (v) RGP can maintain the species diversity of intestinal microbes, increase the content of short‐chain fatty acids and then restore the imbalance of intestinal microecology. CONCLUSION: RGP can improve the intestinal microbiota to strengthen the intestinal epithelial barrier and protect against DSS‐induced colitis. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator-activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.