Ulcer Index Research Articles

The relationship between dietary phytochemical index and novel anthropometric indices and the severity of diabetic foot ulcers in adults with type 2 diabetes: a cross-sectional study

BackgroundResearch on the relationship between dietary phytochemical intake and the anthropometric indices as well as the diabetic foot ulcers (DFUs) remains inconsistent. We aimed to investigate the associations of dietary phytochemical index (DPI) with the novel anthropometric indices and the severity of DFUs.MethodsThis cross-sectional study was conducted on 339 adults with type 2 diabetes. Dietary intake was assessed using three 24-hour dietary recalls. To quantify the phytochemical content of the diet, the DPI estimation was done through an equation proposed by McCarty. The International Working Group on the Diabetic Foot (IWGDF) criteria and Wagner classification system were applied to assess DFUs. New anthropometric indices including a body shape index (ABSI), body roundness index (BRI) and abdominal volume index (AVI) were calculated based on formulas. We employed analysis of variance (ANOVA), analysis of covariance (ANCOVA) and logistic regression to explore associations between DPI and the anthropometric indices and DFU variables.ResultsOur results revealed no significant association between DPI and the foot ulcer indices, following adjusting for the possible covariates. Furthermore, we also examined the relationship between diabetic neuropathy, as measured by monofilament score, and the DPI. Similarly, we did not find any substantial relationship between the DPI and monofilament score (OR: 1.18; 95% CI: 0.66–2.09; Ptrend = 0.56), as well as biochemical indices. Our analysis did not reveal any significant associations between the DPI and ABSI (OR: 0.70; 95% CI: 0.35–1.38; Ptrend = 0.30), BRI (OR: 0.80; 95% CI: 0.33–1.95; Ptrend = 0.59), and AVI (OR: 1.99; 95% CI: 0.92–4.33; Ptrend = 0.08).ConclusionsOur study revealed no significant links between the DPI and foot ulcer indices, neuropathy measures, and anthropometric indices. These findings imply that factors beyond dietary phytochemical intake may exert greater influence on the development of foot ulcers in diabetes.

Troxerutin effect on gastric ulcers induced by ketorolac in rats: Relation with oxidative stress

Gastric ulcers are an essential side effect associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Free radicals are one of the important mechanisms contributing to the development of gastric ulcers caused by NSAIDs. This prompted us to choose troxerutin, which has antioxidant and anti-inflammatory effects, especially with a lack of studies investigating the preventive effect of troxerutin on gastric ulcers. Twenty-nine rats were divided into five groups: A Vehicle group, a Keto group (30 mg/kg of ketorolac), and two troxerutin groups (150 mg/kg or 200 mg/kg of troxerutin, respectively). A Miso group was used as a reference with (100 μg/kg of misoprostol). Troxerutin and misoprostol were administered orally 1 h before ketorolac. The ulcer index was determined considering the numbers and severity of ulcerations. Gastric tissue inflammation was evaluation microscopically. Both thiobarbituric acid reactive substance levels and catalase activity were measured as markers of oxidative stress in gastric tissue. Our data showed an improvement in ulcer indices with troxerutin and misoprostol compared with ketorolac, with improvement in gastric inflammation observed with misoprostol but not with troxerutin. These results were accompanied by a reduction in gastric oxidative stress induced by ketorolac with both troxerutin and misoprostol. This study highlights, for the first time, the antioxidant effect of troxerutin on gastric ulcers. This effect may contribute to the good prevention of ketorolac-induced gastric ulcers.

Synthesis and Biological Evaluation of Gastroprotective Polymer Conjugates of Aceclofenac

: Nonsteroidal anti-inflammatory drugs account for a sizeable fraction of the drugs prescribed worldwide. If consumed for a long time, they can cause ulcers and lifethreatening side effects. Since the acidic group present in NSAIDs is mainly responsible for these side effects, the scientists try to synthesize polymer drug conjugates that avoid these side effects but still retain the potency of the parent drug. Macromolecular drug conjugates of aceclofenac were prepared by employing pectin, β cyclodextrin, deacetylated chitin (chitosan) and albumin (egg and bovine serum). The prepared conjugates were characterized and tested for their anti-inflammatory, antinociceptive and antiulcerogenic activity. Further experimentation was undertaken to analyze the behavior of compounds and their stability in hydrolytic conditions. Test compound A1, a pectin conjugate of aceclofenac, exhibited significant antinociceptive and anti-inflammatory activity with a significant decrease in ulcer index (4.45±0.24) as against aceclofenac (8.61±0.40) or vehicle (12.39±0.44) treated group. A novel and safer polymer drug conjugate of aceclofenac has been synthesized and evaluated.

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study

IntroductionCrohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier...

Trefoil Factor 3 in human serum as a predictor of disease activity in Egyptian ulcerative colitis patients and its role in colorectal cancer

Ulcerative colitis (UC), a chronic idiopathic inflammatory disease, is caused by abnormal immune response to intestinal microflora. Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. The gold standard to establish diagnosis and assess disease activity remains endoscopy and histopathology. Non-invasive biomarkers are required for timely diagnosis of CRC and to assess disease activity as endoscopic assessment is not accepted by most patients. Enhanced trefoil factor 3 (TFF3) expression is seen following gastrointestinal tract injury. In the current study, the significance of serum TFF3 as a potential diagnostic biomarker of disease activity in naїve UC patients, and its diagnostic accuracy in CRC patients were investigated. We collected serum and fecal samples from 20 cases with active UC, 20 CRC patients, and 20 normal controls. TFF3 levels were higher in patients with active UC than in controls (p<0.001). TFF3 cut-off value of 7.9 ng/ml could predict disease activity with sensitivity and specificity of 90% and 100%, respectively. However, the combination of TFF3, C-reactive protein (CRP), and fecal calprotectin (FC) was able to predict disease activity better than each biomarker alone by raising the sensitivity and specificity to 100%. There was no correlation between TFF3, FC, and endoscopic activity in UC assessed by ulcerative colitis endoscopic index of severity (UCEIS). In the CRC patient group, the serum level of TFF3 was significantly higher when compared to controls (p=0.012). TFF3 and the degree of dysplasia were significantly correlated (r=0.496, p=0.026). At a cut-off value of 5.9 ng/ml, serum TFF3 had a diagnostic sensitivity and specificity for CRC of 82% and 90%, respectively. In conclusion, serum TFF3 may be used as a non-invasive biomarker to predict disease activity in UC both alone and in combination with CRP and FC and it could have a potential role in diagnosis of CRC.

Effectiveness and safety of upadacitinib in acute severe ulcerative colitis patients from single Chinese IBD Center: a monocentric study

Upadacitinib is an oral new selective JAK1 inhibitor that has been approved for treating adult patients with moderately to severely active ulcerative colitis. However, a growing number of studies are needed on the effectiveness of upadacitinib in the treatment of acute severe ulcerative colitis. This study was mainly aimed to describe the clinical and endoscopic effectiveness of upadacitinib 45 mg in Chinese acute severe ulcerative colitis patients following eight weeks of treatment. In this study, we examined all patients with acute severe ulcerative colitis from Xijing IBD Center, Xi’an, China, with acute severe ulcerative colitis. All patients were initially given oral upadacitinib 45 mg. Clinical indicators, C-reactive protein, and erythrocyte sedimentation rates were collected. Clinical response and clinical remission were assessed using modified Mayo. Endoscopic evaluation was performed carried out using the Mayo Endoscopic Score and Ulcerative colitis endoscopic index of severity score. A total of 14 patients who received upadacitinib were included in the study period. All patients exhibited a clinical response to 45 mg upadacitinib initially. All patients completed the 8-week induction. The clinical remission rate was 28.6% after eight weeks. Two patients revealed endoscopic remission at 14.3%. The pathology improved in 50.0% of patients. The 8-week surgical resection rate was 7.1%, with the 16-week surgical resection rate being 14.3%. Adverse events included herpes simplex virus infection and increased thrombin time. The results of our study support the short-term effectiveness and safety of upadacitinib in acute severe ulcerative colitis, providing new choices for patients’ treatment. However, more extended investigation needs to be performed on the long-term effectiveness and safety.

β-Citronellol: a potential anti-inflammatory and gastro-protective agent-mechanistic insights into its modulatory effects on COX-II, 5-LOX, eNOS, and ICAM-1 pathways through in vitro, in vivo, in silico, and network pharmacology studies.

The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro, in vivo assays and in silico approaches. In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1ml from 1% w/v) and Formaldehyde (0.1ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100mg/kg, using indomethacin-induced (25mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). β-Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400µg/mL. Citronellol decreased rat's paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE2, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100mg/kg) increased gastric PGE2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. The anti-inflammatory, anti-oxidant, and gastro-protective effects of β-Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.

Evaluation of Immediate Release Tri-Layer Tablets for Analgesic and Antiulcer Properties in Experimental Animals.

Using animals as a test subject, we aimed to determine whether tri-layer tablets filled with ibuprofen and ranitidine had any effect on pain or ulcers. The effectiveness against ulcers caused by acetic acid and cold stress was tested. Six rats made up each of the four groups that were randomly assigned. As a control, I was given a solvent and placed in the group. The second group served as the control, while groups III and IV were used to evaluate 100 mg and 200 mg tri-layer tablets, respectively. The oral gavage method was used to administer all medications. It was shown that the number of writhing was 5.12 in the T2 group compared to the control group, indicating a decrease in the medication-treated groups. The heated technique demonstrated the substantial analgesic activity of the medication under examination. After 120 minutes, the drug-treated groups had a latency time that was 9.8 seconds longer than the control group. Treatment with the experimental medicine lowered the ulcer index in an ulcer model generated by acetic acid. T2 had a value that was 0.43 lower than the control group. T2 group showed a significant reduction in ulcer index to 0.33 in ulcers generated by cold restraint stress. This study provides support for the use of multilayered tablets in the treatment of pain and ulcer disorders, since it demonstrated the analgesic and antiulcer benefits of the test medicine in animal models. More studies to determine the exact mechanism are necessary.

Long-term real-world data of ustekinumab in ulcerative colitis: the Stockholm Ustekinumab Study (STOCUSTE).

Ustekinumab (UST) is an anti-interleukin-12/23 antibody used in the treatment of inflammatory bowel disease. This study includes patients treated at four hospitals in Stockholm to provide long-term real-world data. Retrospective study including patients diagnosed with ulcerative colitis and treated with UST between the years 2019 and 2021. Patients were followed until withdrawal of treatment, or until a predefined end of study, 31 July 2021. Disease activity was assessed with Physician Global Assessment (PGA); Ulcerative Colitis Endoscopic Index of Severity (UCEIS), laboratory parameters, and drug persistence. The primary outcome was steroid-free remission (PGA = 0) and response (decrease PGA ≥ 1 from baseline) at 3 and 12 months, respectively. A total of 96 patients, 44 women and 52 men were included. The patients had either extensive colitis (69%), left-sided colitis (29%), or proctitis (3%). All but two patients were anti-TNF-experienced; 94 (98%) had failed ≥1, 59 (61%) ≥ 2, and 34 (35%) had failed ≥ 3 anti-TNF drugs. In addition, 28 (29%) had failed vedolizumab. At inclusion, 92/96 patients (96%) had active disease and four patients were in remission. Among patients who were treated with UST, 9/71 (13%) were in steroid-free remission at 3 months, and 26/33 (78%) were at 12 months. Withdrawal rates at 3 and 12 months, were 12 and 26%, respectively, mainly due to persisting disease activity (20%). In this group of patients with difficult-to-treat ulcerative colitis, UST was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile.

Umbilical cord mesenchymal stem cells in ulcerative colitis treatment: efficacy and possible mechanisms

BackgroundMesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms.MethodsThis prospective, self-controlled clinical study was conducted at Henan Provincial People’s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation.ResultsForty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy.ConclusionUMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines.Trial registrationThe study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Natural History and Longitudinal Outcomes of Patients with Mild-to-Moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: A Single-Center, Retrospective Study.

Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3years. A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.

The Role of Vitamin D Levels in Optimizing Treatment for Pediatric Inflammatory Bowel Disease (IBD) Patients and an Examination Into Different Factors That Influence IBD Treatment Outcomes.

Background Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn's Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children's Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions.

Four intestinal ultrasound scores and bowel wall thickness alone correlated well with pediatric ulcerative colitis disease activity.

Intestinal ultrasound (IUS) is a noninvasive tool in ulcerative colitis (UC), but scoring systems have mostly been developed for adults, Crohn's disease, and flaring UC. Our aim was to evaluate the performance of bowel wall thickness (BWT) and four IUS scores in pediatric patients with newly diagnosed UC. Patients <18 years old with suspected UC were prospectively enrolled. Baseline IUS was done, and ulcerative colitis intestinal ultrasound score (UC-IUS), Milan criteria, simple pediatric activity ultrasound score (SPAUSS), and Civatelli index were calculated. Mayo endoscopic segment subscore, pediatric ulcerative colitis activity index (PUCAI), and biomarkers were correlated with IUS using nonparametric and receiver operating characteristic analyses. Fifty-two patients (56% male, median age 13.9 years, interquartile range [IQR] 11.2-16.3) with 206 colon segments were included. Patients who needed hospitalization (n = 27/52) had significantly worse IUS (BWT and all scores) compared to those not hospitalized. For all patients, IUS scores and BWT significantly correlated with baseline endoscopic, clinical, and biochemical disease activity (rho = 0.32-0.67, p < 0.05). BWT (τb = 0.53), UC-IUS (τb = 0.55), and Milan (τb = 0.52) had the strongest endoscopic correlations. For differentiating between endoscopic disease severity, BWT, UC-IUS, and Milan, had the highest areas under the curve (0.89-0.93). Using BWT alone, a thinner cut-off had improved sensitivity while maintaining high specificity: ≥2.5 mm for moderate/severe endoscopic inflammation (sensitivity 66%; specificity 94%) and ≥3.5 mm for severe endoscopic inflammation (sensitivity 92%; specificity 86%). BWT and all four IUS scores correlated well with endoscopic, clinical, and biochemical disease activity, and was another useful marker of severity in identifying patients needing hospitalization. Pediatric patients needed a thinner BWT cut-off, which should be accounted for when developing pediatric-specific scores. BWT alone may be just as clinically useful as composite US scores.

Subjective and objective sleep quality assessment in adolescent patients with inflammatory bowel disease

ObjectivesThere is a link between inflammatory bowel disease (IBD) and poor sleep quality that is presumed to be multifactorial. The purpose of this study was to identify factors that impact sleep quality in this group including clinical disease activity, depression, anxiety, quality of life, and disordered social media use through questionnaires. MethodsThis prospective study analyzed sleep quality in adolescent patients ages 13 to 18 with a diagnosis of IBD using objective data from wrist actigraphy and subjective report from the Pittsburgh Sleep Quality Index (PSQI). Additional screeners including the Short Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index, Pediatric Quality of Life Inventory Gastrointestinal Symptoms Module, Generalized Anxiety Disorder 7-item screener, Patient Health Questionnaire depression screener, and Social Media Disorder scale were also collected. ResultsTwenty-three subjects enrolled and 16 completed questionnaires. 62.5 % of participants were in clinical remission and the remaining 37.5 % had mild to severe clinical IBD activity. Poor subjective sleep quality was associated with a shorter duration of sleep time and an increased clinical disease activity score. Patients in clinical remission slept for a longer duration than those with mild IBD activity. ConclusionsThis study did not identify a significant relationship between sleep quality and psychosocial factors in the adolescent population with IBD, though their influence cannot be discounted. There was a connection between the presence of disease activity and shorter sleep duration. Similarly, PSQI scores correlated with sleep time but not sleep quality.

Design, Molecular Docking, Synthesis, and ADME Studies of Novel Amide Derivatives of Diflunisal and Aspirin Compounds as Preferential Selective Cox-2 Inhibitor

The synthesize of novel NSAI compounds (Aspirin and diflunisal derivatives) as a preferential selective COX-2 inhibitors, and evaluate their anti-inflammatory, safety and G.I.T. side effects. Aspirin and diflunisal conjugated with selected moiety of heterocyclic rings to enhance anti-inflammatory activity with preferential COX-2 selectivity, decrease GIT side effects, this aim achieved by 4-(4-Fluorophenyl) isoxazol-5-amine conjugation. The produced derivatives underwent IR and 1H-NMR spectra analysis, and a melting point and Rf measurement were used to verify their purity. The preliminary pharmacological activity showed that compounds 2and 6 have significantly more anti-inflammatory outcome than all synthesized compounds, in which Compound (2) showed a highest anti-inflammatory action with low gastric effects, and compound (6) showed a good anti-inflammatory activity with lowest ulcer index. ADME study showed all ligands was pargeted to passive absorbed orally except compound (7) was failed, so they showed good bioavailability except compound (7) fail might due to its high molecular &gt; 500. According to a docking research, the docked compounds' PLP fitness on COX-2 ranged from (66.55 to 88.43). while (51.44 to 78.88) on COX-1, consequently they might show preferentially selective COX-2 inhibitors. Compound (6) showed highest COX -2 affinity (88.43) even celecoxib (83.35), but compound (6) showed higher affinity fox COX-1than celecoxib. While compounds (3 and 7) produced lowest COX-2 affinity (66.55 and 66.75) respectively. The all of studies, anti-inflammatory, ulcer index, ADME and molecular docking results showed good correlation in respect to compounds (6 and 2).

Anti-ulcerogenic Potential of Kalanchoë gastonis-bonnieri Extracts in Male ICR Mice Model of Ethanol-induced Gastric Ulcers.

Peptic ulcers (PU) are a breach in the mucosa of the digestive tract and are related to several factors including an altered immune system and an unbalanced diet. Current treatment carries to long-term complications; therefore, the use of medicinal plants is an alternative for several inflammatory diseases including ulcerative lesions. Kalanchoë gastonis-bonnieri, is a succulent plant and, has been used in traditional medicine against gastric ulcers, inflammation, and cancer among others. The main goal of this work was to analyze the anti-ulcerogenic potential of extracts from leaves of K. gastonis-bonnieri in an assay of ethanol-induced gastric ulcers. An ethanolic extract was obtained by maceration from fresh leaves of K. gastonis-bonnieri, and fractions were obtained through bipartition and chemical fractioning. The chemical characterization of the extract was made through HPLC, GC-MS, and NMR. Total extract and fractions showed an anti-ulcerogenic effect in specimens of male ICR mice with a gastric ulcer index (UI) of 3.27-5.47. The recorded effect is attributed to the presence of terpenoid compounds such as β-Amyrin acetate, which showed antioxidant properties and lessened formations of ulcers induced by ethanol administration in mice stomach.

Co-delivery of a curcumin and asafoetida as a bioavailable complex using fenugreek galactomannan hydrogel scaffold alleviates inflammatory bowel disease on experimental animals

IntroductionInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder characterised by the disruption of the epithelial barrier and formation of mucosal ulceration. Though the current treatment mainly includes synthetic drugs, herein, we hypothesised that a co-delivery of bioavailable and water-soluble forms of turmeric extract (curcumin) along with asafoetida oleo-gum-resin (hereinafter referred to as ‘CUAS’) may have synergistic effects to alleviate IBD safely. MethodsThe study was conducted in two phases. In the first phase, bioavailability of the formulation was investigated and in the second phase, its effect on 2,4,6- trinitrobenzene sulfonic acid (TNBS)-induced IBD model of rats were investigated. In this model, Wistar rats (n = 30) were randomised into 5 groups, [Group I-control, Group II–TNBS treated IBD group (100 mg/kg; intrarectal), Group III-Standard drug (Sulfasalazine; 50 mg/kg b. wt. orally), Group IV – standard curcumin complex (UC; 200 mg/kg b. wt.), Group V –Curcumin/asafoetida co-delivery form (CUAS; 200 mg/kg b. wt.)]. IBD was induced to group II to V animals, and then treated with the respective drugs for 24 days. Then the animals were sacrificed and various biochemical parameters including ulcer index, antioxidant levels, oxidative stress markers, and histopathological analysis of the colon were carried out. ResultsThe results revealed a significant reduction (P < 0.05) of the clinical manifestations related to IBD, along with a significant reduction (P < 0.05) for the ulcer index, oxidative stress, and significant enhancement (P < 0.05) in endogenous antioxidant enzyme levels among CUAS treated animals. Histopathological observations also showed a significant reduction in TNBS-induced colon lesions. No necrosis, cellular infiltration, haemorrhage, or oedema was observed among the CUAS-treated animals, indicating better gastroprotective effect of CUAS compared to the standard curcumin treatment. ConclusionsThe enhanced effect of CUAS was attributed to the improved bioavailability (22.8-fold) of CUAS compared to standard curcumin treated group.

Circadian clock component PER2 negatively regulates CD4+ T cell IFN-γ production in ulcerative colitis

Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4+ T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4+ T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4+ T cells of UC patients compared with that in Crohn’s disease (CD) patients and healthy controls (HC). Notably, PER2 expression was significantly recovered in UC patients in remission (R-UC) compared to that in active UC patients (A-UC) but not in CD patients. It was negatively correlated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Crohn’s Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn’s disease (SES-CD), and C-reactive protein (CRP), respectively. Overexpression of PER2 markedly inhibited IFN-γ production in UC CD4+ T cells. RNA-seq analysis showed that overexpression of PER2 could repress the expression of a disintegrin and metalloproteinase 12 (ADAM12), a costimulatory molecule that determines Th1 cell fate. Mechanistically, cleavage under targets and tagmentation (CUT&Tag) analysis revealed that PER2 down-regulated ADAM12 expression by reducing its binding activity, thereby suppressing IFN-γ production in UC CD4+ T cells. Additionally, our data further demonstrated that ADAM12 was upregulated in CD4+ T cells and inflamed mucosa of A-UC patients compared to HC. Our study reveals a critical role of PER2 in regulating CD4+ T cell differentiation and highlights its potential as a therapeutic target for UC treatment.

Association of fatigue with disease activity and clinical manifestations in patients with Crohn’s disease and ulcerative colitis: an observational cross-sectional study in the United States

Background Fatigue imposes a socioeconomic burden on patients with Crohn’s disease (CD) and ulcerative colitis (UC). We assessed the prevalence of fatigue among patients with CD or UC and identified disease activity measures associated with fatigue. Methods Data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed separately for CD and UC. Fatigue was defined based on a subjective and dichotomic questionnaire. Patients indicated if they experienced fatigue within the last week. The overall prevalence of fatigue was analyzed using descriptive and contingency tables. Demographics, clinical characteristics, disease activity (measures include Physician’s Global Assessment for both CD and UC, short CD Activity Index for CD, and Ulcerative Colitis Disease Activity Index for UC), symptoms, and patient-reported outcomes were compared between patients with and without fatigue. Multivariable logistic regression models were constructed to identify symptoms and disease activity measures associated with fatigue. Results The study included 903 patients with CD and 443 patients with UC. Fatigue was reported in 47.7% of patients with CD and 40.9% of patients with UC. In patients with CD, abdominal pain, bowel incontinence, depressive symptoms, reduced general well-being, and night-time bowel movements were associated with fatigue. In patients with UC, depressive symptoms, reduced general well-being, moderate or severe disease activity by the physician’s global assessment, and night-time bowel movements were significantly associated with fatigue. Conclusions Fatigue is a common symptom among patients with CD or UC and is associated with higher levels of disease activity and reduced general well-being.

Deep learning model using stool pictures for predicting endoscopic mucosal inflammation in patients with ulcerative colitis.

Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photos of patients with UC (DLSUC) to predict endoscopic mucosal inflammation. This was a prospective multicenter study conducted in six tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photos of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2161 stool pictures from 306 patients and tested on 1047 stool images from 126 patients. The ulcerative colitis endoscopic index of severity (UCEIS) was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal). The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong's P=0.458]). When rectal sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P=0.002). DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photos are a useful monitoring tool for typical UC.