Ulcer Model Research Articles

Boswellia Extract Promotes Healing and Resolving Inflammation in Oral Ulcers of Rat.

Recurrent aphthous ulcers significantly impact patients' quality of life due to their painful and recurrent nature, necessitating more effective treatments. This study explores the therapeutic potential of Boswellia to treat recurrent aphthous ulcers by its anti-inflammatory and healing promotion effect in a rat oral ulcer model. Network pharmacology techniques were employed to elucidate Boswellia's active components and potential targets. Intersecting targets of Boswellia and oral ulcer-related genes were screened for protein-protein interaction network analysis and functional enrichment. An oral ulcer model in rats was used and rats were treated with Boswellia extract. The healing process was monitored by measuring the ulcer area and body weight changes. Histological analysis was performed, and the role of Boswellia in macrophage polarization was investigated through gene expression analysis and protein array tests. The underlying mechanism involving PPARγ activation was also explored. Network pharmacology analysis revealed Boswellia's interaction with key genes and pathways associated with inflammation and lipid metabolism, such as MAPK3, PPARG, and PTGS2. Boswellia extract significantly accelerated oral ulcer healing and recovered weight loss in rats. Histological examinations revealed reduced tissue swelling and inflammatory cell infiltration in treated groups. Furthermore, Boswellia extract decreased infiltration of M1 macrophage presence while increasing M2 macrophage, indicating an inflammation-resolving effect. Invitro studies showed that Boswellia extract enhanced M2-related gene expression and decreased pro-inflammatory cytokines, which is PPARγ dependent. Boswellia extract promotes oral ulcer healing and resolves inflammation, primarily through the modulation of macrophage polarization via PPARγ activation.

Protective effect of low-dose lactulose in dextran sulfate sodium induced ulcerative colitis model of rats

Although low-dose lactulose has shown a good theoretical foundation for the treatment of ulcerative colitis (UC) in previous studies, the exact effects and mechanism remain unclear. The rats were randomly distributed into 5 groups, i.e., normal drinking water was provided for an initial 14 days in blank control group, 4% dextran sulfate sodium was used for modeling in the remaining 4 groups. During the 15-24th day, rats in the blank control group were administered with 0.9% saline (0.5 ml/d) by gavage. In the rest 4 groups, rats were administered 0.9% saline (0.5 ml/d, UC model), mesalazine (400 mg/kg/d), lactulose (1000 mg/kg/d), and lactulose + mesalazine (two-drug combination) by gavage. In addition to symptoms and pathological changes, serum IL-6, TNF-α, and High-sensitivity C-reactive protein(Hs-CRP) by ELISA analysis, mRNA and protein expression levels of TLR-2, TLR-4, Nuclear factor-κB(NF-κB), IL-6, and TNF-α in colon tissues by RT-qPCR and WB analyses respectively. Meanwhile, short-chain fatty acid(SCFAs) and intestinal flora were analyzed. Low-dose lactulose improved symptoms (diarrhea, blood in stool, weight loss) and pathological inflammation. In addition to serum IL-6, TNF-α, and Hs-CRP, the mRNA and protein expression levels of TLR-2, TLR-4, NF-κB, IL-6 and TNF-α in the colon were down-regulated with the intervention of lactulose.Meanwhile, lactulose decreased the ileocecal PH, increased SCFAs and altered the intestinal flora. Low-dose lactulose may be beneficial to UC by regulating TLRs/NF-κB pathway, reducing ileocecal PH, increasing SCFAs, regulating intestinal flora and improving the intestinal mucosal barrier. Meanwhile, low-dose lactulose and mesalazine may have additive effects upon combination.

P0451 Using a machine learning model to assess agreement between inflammation in the rectosigmoid and entire colon in patients with ulcerative colitis

Abstract Background Limited endoscopy of the rectosigmoid colon is sometimes used to assess endpoints in clinical trials for ulcerative colitis (UC). However, there is inherent inter- and intra-rater variability in endoscopic assessment of inflammation, and regulatory agencies have suggested that full colonoscopy is preferred1,2,3. We used a machine learning (ML) model to compare the degree of inflammation of full-length endoscopy videos to that seen in the distal colon and rectum. Methods We used a previously developed ML model that predicts the endoscopy subscore4, a component of the modified Mayo Score, and applied it to 49 full-length endoscopy videos randomly selected and stratified by endoscopic severity from the Phase 3 induction trial for mirikizumab in UC (NCT03518086). Each video was preprocessed by a human reviewer to identify the point of maximal extent and the end of the procedure. The withdrawal portion of the videos were divided into 15, 30, or 60 second clips (a series of smaller segments of video), and the ML model generated an endoscopy subscore for each clip (clip-level endoscopy subscore) and for the entire video (video-level endoscopy subscore). We assigned the final two clips during withdrawal as an assessment of the sigmoid and rectum. Therefore, in this analysis, we compared the ML endoscopy subscore grade of the final two clips to the video-level endoscopy subscore. Kappa statistics of variability between scores were performed. Results There was substantial agreement between the video-level endoscopy subscore and that of the last 2 clips (Table 1). For 60-second clips, the agreement rate between the video-level endoscopy subscore and clip 1 was 0.67 and that with clip 2 was 0.76. When comparing the video-level endoscopy subscore to clip 1 or clip 2, the agreement rate was 0.86, and this was greater than the agreement rate when looking at the higher grade of clip 1 or clip 2 (0.73). The 60 second clips had greater agreement rates than 30 second or 15 second clips (Table 1 and 2). The endoscopy subscores of clip 1 or clip 2 had excellent agreement with video-level grades 0-3 (Table 2), and this was best observed with 60 second clips (Table 2A, kappa 0.944). Conclusion The ML model demonstrated excellent agreement between clip-level endoscopy subscore assessments of the distal most portion of the withdrawal videos compared to the video-level endoscopy subscore, and this was best observed with 60 second clips. These findings support the use of distal colon and rectum assessment to determine the grade degree of endoscopic inflammation of the full colonoscopy. We propose further prospective study of the use of this ML model in this setting. References Feagan, B. G., Khanna, R., Sandborn, W. J., Vermeire, S., Reinisch, W., Su, C., . . . & Sands, B. E. (2021). Agreement between local and central reading of endoscopic disease activity in ulcerative colitis: Results from the tofacitinib OCTAVE trials. Alimentary Pharmacology & Therapeutics, 54(11-12), 1442-1453. Hashash, J. G., Yu Ci Ng, F., Farraye, F. A., Wang, Y., Colucci, D. R., Baxi, S., . . . & Melmed, G. Y. (2024). Inter-and intraobserver variability on endoscopic scoring systems in crohn’s disease and ulcerative colitis: A systematic review and meta-analysis. Inflammatory Bowel Diseases, izae051. Food and Drug Administration. Ulcerative Colitis: Developing Drugs for Treatment [Internet]. 2022 [cited 2024 Oct 17]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ulcerative-colitis-developing-drugs-treatment Rubin, D. T., Gottlieb, K., Colombel, J. F., Schott, J. P., Erisson, L., Prucka, B., . . . & McGill, J. (2023). Development of a novel ulcerative colitis Endoscopic Mayo Score prediction model using machine learning. Gastro Hep Advances, 2(7), 935-942.

P0264 Using a machine learning model to grade clip-level endoscopic inflammation reveals the heterogeneity of mucosal inflammation in ulcerative colitis

Abstract Background Endoscopic assessment of inflammation in ulcerative colitis (UC) is a therapeutic endpoint in clinical trials1 but can be limited by inter- and intra-observer variability2 and lack of sensitivity to detect the degree of inflammation throughout the colon3. We used a machine learning (ML) model to grade inflammation of full-length endoscopy videos at the clip-level (a series of smaller segments of video) in order to evaluate the uniformity of mucosal inflammation. Methods We used a previously developed ML model that predicts the endoscopy subscore4, a component of the modified Mayo Score, and applied it to 49 full-length endoscopy videos randomly selected and stratified by endoscopic severity from the Phase 3 induction trial for mirikizumab in UC (NCT03518086). A human reviewer identified the point of maximal extent and the end of the procedure to isolate the withdrawal portion of the video which was then divided into 15, 30, or 60 second clips, and the model generated an endoscopy subscore for each clip (clip-level endoscopy subscore) and for the entire video (video-level endoscopy subscore). Variability of inflammation between clips were calculated. Results Assessment of the endoscopy subscore on individual video clips during withdrawal demonstrated a patchy distribution of inflammation severity, and this was consistent regardless of the video-level endoscopic severity (Fig. 1). Notably, the segment with the most severe inflammation did not always occur proximally (Fig. 1). The variability of inflammation was greater in 15-second (Fig. 1A) than 30-second (Fig. 1B) or 60-second (Fig. 1C) clips. Video-level endoscopy subscores of 1-3 did contain the spectrum of clip-level endoscopy subscore grades of 0-3, but the greatest proportion of clips correlated with the video-level endoscopy subscore (Fig. 2). Conclusion Using a novel ML model to determine video-level and clip-level endoscopy subscores using colonoscopy videos in patients with moderate-to-severe UC, we identify heterogeneity of inflammatory activity, and this was best observed with clips at 15-second intervals. These findings provide insight into inter- and intra-rater variability of endoscopy subscore assessments by human readers and highlight relevant data that are not captured by a single video-level score. Further study is needed to optimize assessment of inflammation in this setting. References Food and Drug Administration. Ulcerative Colitis: Developing Drugs for Treatment [Internet]. 2022 [cited 2024 Oct 17]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ulcerative-colitis-developing-drugs-treatment Hashash, J. G., Yu Ci Ng, F., Farraye, F. A., Wang, Y., Colucci, D. R., Baxi, S., . . . & Melmed, G. Y. (2024). Inter-and intraobserver variability on endoscopic scoring systems in crohn’s disease and ulcerative colitis: A systematic review and meta-analysis. Inflammatory Bowel Diseases, izae051. Vuyyuru, S. K., Ma, C., Nguyen, T. M., Zou, G., Peyrin-Biroulet, L., Danese, S., . . . & Jairath, V. (2024). Differential efficacy of medical therapies for ulcerative colitis according to disease extent: Patient-level analysis from multiple randomized controlled trials. EClinicalMedicine, 72. Rubin, D. T., Gottlieb, K., Colombel, J. F., Schott, J. P., Erisson, L., Prucka, B., . . . & McGill, J. (2023). Development of a novel ulcerative colitis endoscopic mayo score prediction model using machine learning. Gastro Hep Advances, 2(7), 935-942.

A fusion model of manually extracted visual features and deep learning features for rebleeding risk stratification in peptic ulcers.

We propose a multi-feature fusion model based on manually extracted features and deep learning features from endoscopic images for grading rebleeding risk of peptic ulcers. Based on the endoscopic appearance of peptic ulcers, color features were extracted to distinguish active bleeding (Forrest I) from non-bleeding ulcers (Forrest II and III). The edge and texture features were used to describe the morphology and appearance of the ulcers in different grades. By integrating deep features extracted from a deep learning network with manually extracted visual features, a multi-feature representation of endoscopic images was created to predict the risk of rebleeding of peptic ulcers. In a dataset consisting of 3573 images from 708 patients with Forrest classification, the proposed multi-feature fusion model achieved an accuracy of 74.94% in the 6-level rebleeding risk classification task, outperforming the experienced physicians who had a classification accuracy of 59.9% (P<0.05). The F1 scores of the model for identifying Forrest Ib, IIa, and III ulcers were 90.16%, 75.44%, and 77.13%, respectively, demonstrating particularly good performance of the model for Forrest Ib ulcers. Compared with the first model for peptic ulcer rebleeding classification, the proposed model had improved F1 scores by 5.8%. In the simplified 3-level risk (high-risk, low-risk, and non-endoscopic treatment) classification task, the model achieved F1 scores of 93.74%, 81.30%, and 73.59%, respectively. The proposed multi-feature fusion model integrating deep features from CNNs with manually extracted visual features effectively improves the accuracy of rebleeding risk classification for peptic ulcers, thus providing an efficient diagnostic tool for clinical assessment of rebleeding risks of peptic ulcers.

Rapid-release and user-friendly costunolide/dehydrocostuslactone hydrophilic nanofibers: Therapeutic effects on acute gastric ulcers.

Gastric ulcers often cause postprandial epigastric pain, especially in acute cases. Abnormal motility, with about 50 % of patients having delayed gastric emptying, contributes to ulcer development. Costunolide (COS) and dehydrocostuslactone (DEH), derived from "Mu xiang" herbs, show potential in treating ulcers and regulating gastrointestinal motility. However, their poor solubility and bioavailability limit in vivo use. This study uses electrospinning to develop hydrophilic nanofibers loaded with COS and DEH in a polyvinylpyrrolidone (PVP) matrix for treating acute gastric ulcers. The production process for costunolide / dehydrocostuslactone nanofibers (COS/DEH/NFs) was optimized, characterized, and tested in pharmacodynamic studies. The results showed that COS and DEH remained in a non-crystalline state within COS/DEH/NFs, enhancing their in vitro release. With 21 % drug incorporation, COS/DEH/NFs released over 70 % of COS and more than 50 % of DEH within 20 min in body fluids. In treatment, COS/DEH/NFs suppressed pro-inflammatory cytokines, resisted oxidative stress, promoted gastric mucosal repair, and enhanced gastrointestinal motility. In a mouse model of acute gastric ulcer, high-dose COS/DEH/NFs achieved a 77.09 % ulcer inhibition rate, and low-dose COS/DEH/NFs resulted in gastric residual and intestinal propulsion rates of 73.55 % and 69.89 %, respectively. The drug loading of COS/DEH/NFs is 14.76 ± 0.26 %, with an encapsulation efficiency of 68.77 ± 1.14 %. COS/DEH/NFs is a new choice for treating acute gastric ulcers with gastrointestinal bloating due to its convenience and swallow-free use, providing rapid symptom relief.

Evaluation of the antiulcer activity of ethanolic extract and solvent fractions of Calendula tripterocarpa Rupr. in experimental rats and their DART-ToF-MS profiling

In this study, antiulcer activity of ethanolic extract and solvent fractions of the aerial part of Calendula tripterocarpa was investigated using ethanol-induced model of gastric ulceration in rats. The results showed that ethyl acetate, non-polar components and diethyl ether fractions have a remarkable antiulcerogenic activity; because they exhibited control-ulcer protection by 85.2%, 77.7% and 62.9%, respectively. The acute toxicity study showed that the extract is highly safe; the median lethal dose (LD50) was more than 5000 mg/kg. Moreover, the obtained results were confirmed by the sub-chronic toxicity and showed no alteration in the liver and kidney functions. Our data suggests that C. tripterocarpa possesses significant antiulcer activity and it can be used as a source for an antiulcer drug. Around 100 compounds are elucidated from this plant using direct analysis in real-time of flight-mass spectrometry for the first time, of which four well-known compounds were not isolated or reported previously.

Anti-ulcerogenic activity of the marine-pearl derived medicine mukta Pishti in Rat model of pylorus ligation-induced peptic ulcer.

Mukta Pishti (MKP) is a traditional Ayurvedic medicine described in classical textbook 'Rasatarangini' and synthesized from marine pearls following classical methodology. MKP is used as therapeutic medicine against hyperacidity, irritable bowel syndrome, and gastric ulcers. Here, we explored the therapeutic properties of MKP in alleviating peptic ulcer in male Wistar rat model of pylorus ligation. Physicochemical properties of MKP were explored using scanning electron microscope, electron dispersive X-ray, dynamic light scattering, and Fourier-transform-infrared (FTIR)-spectroscopy analysis. Animals were orally treated twice daily with dosages of MKP, over a period of 15 days. The animals underwent 6h pylorus ligation for the induction of peptic ulcers and analyzed for biochemical changes in gastric content, gross and histopathological changes in the stomach region. Physicochemical analysis showed 0.1-30μm particles size for MKP, with elemental composition of oxygen, calcium, silica, carbon, phosphorus, and sodium. FTIR-spectroscopy indicated presence of aragonite crystals in MKP with capability of physically binding to gastric mucin molecules. Additionally, MKP treatment modulated gastric pH in simulated digestion model but did not affect the overall gastric content and total/free acidity levels in the in vivo pylorus ligation model. However, MKP treatment in rats significantly reduced ulcer index in stomach region and protected it against epithelial damages, hemorrhages and edema induced by pylorus ligation. MKP alleviated peptic ulcer induced by pylorus ligation in the male Wistar rats. Further research is warranted to elucidate the precise mode of action and long-term safety of Mukta Pishti.

Human artificial chromosome carrying R-spondin1 and IL-22 expression cassettes in rejuvenated MSCs enhances therapeutic efficacy in ulcerative colitis model mice.

Ulcerative colitis (UC) is an incurable intestinal disease, with current treatments mainly focused on inflammation control and, in severe cases, surgical resection. Recent studies have highlighted the need for new therapies that promote tissue regeneration. R-spondin-1 (RSPO1) and interleukin-22 (IL-22) have shown anti-inflammatory and regenerative effects in UC models, but have short half-lives and poor targeting abilities. Another therapeutic tool, mesenchymal stem cells (MSCs), offer promising migratory and homing capabilities; however, the preparation of homogeneous therapeutic MSCs at sufficient levels in vitro is challenging. Therefore, we developed a novel line of MSCs (HAC-MSC) with significant therapeutic effects in dextran sodium sulfate (DSS)-induced colitis mice. Construction of HAC-MSC involved a two-part strategy: 1) establishment of a non-integrating human artificial chromosome (HAC) vector carrying therapeutic genes encoding IL22 and RSPO1; and 2) transfer of the HAC to previously characterized rejuvenated MSCs (rej-MSCs) prepared using Sendai virus technology for prolonged proliferation capacity in vitro. HAC-MSC stably and efficiently produced therapeutic factors in vitro and, following intraperitoneal administration to DSS-induced colitis mice, showed continuous expression of the therapeutic factors over 5 days. Additionally, HAC-MSC-treated mice showed alleviation of the disease activity index score, reduced depth of injury, and promotion of intestinal growth compared with MSC-treated mice. Furthermore, effective treatment with HAC-MSC required only a fraction (1 %-10 %) of the number of cells needed for conventional MSC therapy. These findings highlight the outstanding potential of rej-MSCs carrying therapeutic factor-loaded HACs as a cell therapy tool with prospective applications in the treatment of UC and other diseases.

Gastroprotective properties of flavonoid-rich extract of Pulicaria odora against ethanol-induced gastric ulcer in mice.

Pulicaria odora has been traditionally used in northeastern Algeria for treating gastrointestinal disorders, particularly ulcers. This study aimed to assess the gastroprotective, anti-inflammatory, and antioxidant properties of a crude hydroalcoholic extract derived from the leaves of Pulicaria odora, as well as its subsequent fractions. The gastroprotective effect was studied in an ethanol-induced ulcer model in mice. The in vitro antioxidant activity was quantified via the DPPH, and ABTS methods. In vitro anti-inflammatory activity was investigated through the human red blood cell membrane stabilization method and the bovine serum albumin denaturation method. The in vivo anti-inflammatory properties of the crude extract were assessed in mice via a carrageenan-induced acute paw edema model. The crude extract significantly inhibited gastric ulcer formation in a dose-dependent manner, achieving a reduction of up to 99.91% at a dose of 200mg/kg. Among the fractions, the aqueous fraction exhibited the most potent gastroprotective effect, with a notable dose-dependent response and high ulcer inhibition rates (95.56% at 50mg/kg). Additionally, the crude extract displayed strong in vitro and in vivo anti-inflammatory activity and a high free radical scavenging capacity; with IC50 values comparable to those of ascorbic acid. LC-ESI-MSn analysis led to the identification of nine flavonoid derivatives, which were subsequently subjected to molecular docking techniques to predict their antiulcer activity. These results suggest that both glycosylated and aglycone flavonoids derived from P. odora have the potential to inhibit gastric acid secretion by targeting the proton pump.

Suppression of TRIM72-mediated endoplasmic reticulum stress facilitates FOXM1 promotion of diabetic ulcer healing.

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.

Indomethacin-Induced Gastric Ulcer in Rats: Gastroprotectivity of Muscari neglectum in Water.

Background and Objectives: The plant Muscari Mill. is employed in both raw and cooked forms for the treatment of gastric diseases, as an expectorant, and for the treatment of warts and the enhancement of urine. A review of the scientific literature revealed no studies investigating the effect of Muscari neglectum (MN) water extract on gastric diseases. The objective of this study was to determine the effect of a water extract of the MN plant on indomethacin-induced gastric ulcer in rats, using a series of biochemical (SOD, CAT, GSH and MDA levels) and histopathological parameters. Methods: 60 male Sprague Dawley rats were utilized for the purposes of evaluating the acute toxicity and gastric ulcer models, with a total of 36 rats employed for these experiments (n = 6). The rats were divided into six groups: intact; indomethacin; famotidine; indomethacin and MN (100, 200, 400 mg/kg). Results: The Gastric tissue examinations at biochemical, macroscopic and pathological levels showed that MN extracts effectively prevented indo-methacin-induced gastric mucosal damage. The 400 mg/kg dose exhibited the most effective antiulcer effect, with a 69% protective efficacy. This dose caused an increase in the SOD, CAT and GSH levels and a decrease in the MDA levels compared to the IND group. Furthermore, an LC-MS/MS analysis was conducted on the water extract of MN, resulting in the identification of 14 phenolic compounds. Conclusions: Biochemical analyses and histopathological examinations demonstrated that the water extract of MN exhibited a beneficial protective effect against gastric ulceration due to its high antioxidant content.

Simulation in podiatry teaching and learning: A scoping review.

In podiatry, there are a variety of clinical tasks that require precision and skill and it is expected that clinicians will obtain these skills during their training. Simulation is a dynamic teaching tool used in healthcare to enhance skill and knowledge acquisition. Currently, the extent and nature of the research on the use of simulation in podiatry teaching and learning are not clear. A scoping review was conducted to identify the extent and nature of research activity on the use of simulation in podiatry teaching and learning and identify gaps in the existing literature. Any research relating to simulation use in podiatry teaching including various designs and focusing on simulations aimed at improving podiatry teaching or learning were eligible for inclusion. A systematic search was conducted on February 14, 2024 of the following databases: Embase (via Embase.com), MEDLINE (via PubMed), CINAHL, and the Web of Science. Additional papers were identified via bibliographies of included studies. Content analysis of content relating to podiatry teaching and learning was performed and grouped into broad themes, then further narrowing to six themes. A total of 21 research studies were deemed eligible for inclusion focusing on diverse aspects of podiatry simulation utilized in high-income countries exclusively. Conducted between 1997 and 2023, these studies were categorized into six key themes: skill improvement, communication and professionalism, clinical competencies and patient safety, educational enhancement, and anatomy and histology education. The simulations, carried out by or assessed for podiatry professionals, staff, or students, ranged from high-fidelity medical mannequins to low-fidelity simulations such as a grapefruit model of a diabetes-related foot ulcer. Overall, the findings suggest that simulation teaching in podiatry, whether through direct skill enhancement or through educational impact assessments, holds potential in improving competency, confidence, and educational outcomes in podiatry practice. This scoping review identified a small yet diverse evidence base for simulation modalities in podiatry education, demonstrating gaps in long-term effects and comparative effectiveness studies. It highlights the urgent need for research focused on longitudinal impacts, evaluating various simulation technologies and standardizing best practices to improve podiatry education and align with clinical and patient care needs.

Anti-inflammatory activity of Ziziphus jujuba hydroalcoholic extract in acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a common gastrointestinal (GI) disorder characterized by chronic inflammation. Current treatments primarily focus on symptom management, but they have inherent limitations. Global attention is increasingly directed towards exploring herbal remedies as complementary approaches. This study aims to investigate the effects of the hydroalcoholic extract of jujuba on an experimental model of ulcerative colitis. In this study, 15 male BALB/c mice were divided into three experimental groups. The first group served as the untreated UC model, acting as the positive control (PC). The second group received treatment with the hydroalcoholic extract of Ziziphus jujuba, while the third group was treated with mesalamine. UC was induced by injecting 100 μL of 4 % acetic acid (AA) intra-rectally several times. Treatment commenced after the onset of symptoms such as diarrhea and bloody stools. The mice were eventually euthanized ethically, and their spleen and intestinal tissues were collected for analysis. Evaluations included the Disease Activity Index (DAI), myeloperoxidase activity (MPO), nitric oxide (NO) levels, cytokine levels (IL-1β, IL-6, TNF-α), and gene expression (iNOS, COX-2, and cytokines). The hydroalcoholic extract of the jujuba plant significantly reduced MPO, NO, the DAI, and the production and expression of inflammatory cytokines, as well as the genes iNOS and COX-2, in the group receiving this extract compared to the positive control group (p<0.05). The study demonstrates that the hydroalcoholic extract of Ziziphus jujuba significantly reduces inflammation markers such as TNF-α, NO, MPO, IL-1β, and IL-6 in a mouse model of ulcerative colitis. Additionally, itdownregulates the expression of pro-inflammatory genes, including iNOS and COX-2. These findings suggest that Z.jujuba extract has potential as an effective anti-inflammatory treatment for managing ulcerative colitis symptoms.

Phytochemical Investigation and Antiulcer Potential of Strychnos Nux vomica Seed Extract in Adult Wistar Rats

The current work sought to assess the possible anti-ulcer efficacy of Strychnos nux-vomica methanolic seed extracts in rats by conducting a thorough phytochemical analysis. This study aims to indicate and discover beneficial molecules present in the seeds with the potential for its medicinal use. This work aimed to determine the primary phytochemicals that have antiulcer properties while maintaining safe profiles at dosages that work. Strychnine is the main phytoconstituent, and it is present in 0.65 % of Nux vomica seeds and is responsible for gastric ulcer activity. When given in 0.05%, it shows therapeutic action. The methanolic seed extract's phytochemical screening identified alkaloids, flavonoids, tannins, and glycosides. Wistar rat models of ulceration produced by methanol were used to evaluate the anti-ulcer efficacy. Four groups of rats were used: control, ulcer-induced (indomethacin induced ulcer), conventional therapy (20 mg/kg omeprazole), and test treatment (50 mg/kg and 100 mg/kg of S. nux-vomica methanolic extract). The outcomes showed that rats treated with S. nux-vomica extract had a significantly lower ulcer index than the control group (p &lt; 0.01). In particular, the ulcer index dropped by 63% in the 100 mg/kg group, which was similar to the omeprazole therapy as a whole (p&gt; 0.05). Reduced stomach mucosal injury was further confirmed by histopathological investigation in the groups who received extract treatment. The originality of this work consists in the safe therapeutic application of S. nux-vomica seeds, usually recognized for their poisonous qualities, in the treatment of stomach ulcers. The findings imply that the S. nux-vomica seed methanolic extract has strong antiulcer properties, providing a unique therapeutic option for ulcer treatment.

Anti-ulcer activity of &lt;i&gt;Trianthema portulacastrum&lt;/i&gt; leaves in rats using an experimental ulcer model

Anti-ulcer activity of &lt;i&gt;Trianthema portulacastrum&lt;/i&gt; leaves in rats using an experimental ulcer model

Inhibition of the Wnt/β‑catenin signaling pathway and SOX9 by XAV939 did not alleviate inflammation in a dextran sulfate sodium‑induced ulcerative colitis model.

The Wnt/β-catenin signaling pathway has been reported to be hyperactivated during the pathogenesis of ulcerative colitis (UC). The present study aimed to explore the therapeutic efficacy of the Wnt/β-catenin signaling inhibitor XAV939 in mitigating UC symptoms. Utilizing a dextran sulfate sodium (DSS)-induced UC mouse model, the present study aimed to evaluate the impact of XAV939 on intestinal morphology through hematoxylin and eosin staining and to measure the expression levels of critical proteins in the Wnt/β-catenin signaling cascade. XAV939 did not exert a significant influence on the morphological features and inflammatory status of the intestinal epithelium. However, XAV939 was found to effectively suppress the Wnt/β-catenin signaling pathway and its downstream target SOX9. This suppression implied a reduction in the differentiation of intestinal stem cells into secretory cell progenitor cells. Additionally, XAV939 was ineffective at reversing the DSS-induced decrease in expression levels of Villin and peroxisome proliferator-activated receptor γ, which suggested that it did not facilitate the differentiation of intestinal absorptive cells. The present findings indicated that the Wnt/β-catenin signaling pathway may not be the predominant mechanism in the pathogenesis of DSS-induced UC.

A gelatin/acrylamide-based hydrogel for smart drug release monitoring and radiation-induced wound repair in breast cancer

Radiotherapy is a common local treatment for breast cancer, and while it is effective in targeting tumor cells, it inevitably causes significant side effects. These include excessive production of reactive oxygen species (ROS), repeated inflammatory, and severe skin ulceration, all of which can hinder the wound healing process. As a result, there is a pressing need for multifunctional medical dressings that can support wound repair following radiotherapy. In this study, we introduced a novel double-network interpenetrating hydrogel (GEMC), which combined gelatin grafted dopamine (GEDA), acrylamide, nano-clay (NC), and curcumin loaded nanoparticles (CCNPs). Unlike traditional single-function hydrogels, the GEMC hydrogel offered a combination of antioxidant properties, tissue adhesion, and real time drug tracking, effectively addressing the multifaceted challenges of wound healing after radiotherapy. The GEMC hydrogel exhibited impressive antioxidant activity and superior mechanical properties, which collectively improve the support and protection of wounded surfaces. Furthermore, GEMC promoted skin regeneration, angiogenesis and reduced inflammatory in a mouse model of radiotherapy-induced skin ulceration. These results highlight the hydrogel's potential to accelerate would healing and enhance the effectiveness of post-radiotherapy wound care, providing a promising new approach to improving the quality of skin recovery following radiotherapy.

Co-Administration of Vitamin U and Antacids in Diets Relieves Gastric Ulcers in Finishing Pigs.

One hundred and forty [(Landrace × Yorkshire) × Duroc] barrows and gilts (86.5 ± 1.5 kg) were used in a 28-day experiment in a randomised complete block design. A model of gastric ulcer was established by adding aspirin to the diet or by fasting. The five dietary treatments were TRT1 (basal diet), TRT2 (basal diet + fasting), TRT3 (basal diet + 0.05% vitamin U and antacids (VA)), TRT4 (basal diet + aspirin + fasting) and TRT5 (basal diet + aspirin + fasting + 0.1% VA). The active ingredients of VA are vitamin U 50 mg/g, magnesium oxide MgO 60 mg/g, sodium carbonate Na2CO3 70 mg/g. The result showed a significant increase in final body weight (p = 0.047) and average daily gain (p = 0.033) in TRT5 compared with TRT1 and TRT2 (p < 0.05). There was no significant difference in carcass scores among treatment groups (p > 0.05). The stomach keratinisation score was significantly higher in TRT2 and TRT4 than that in TRT3 (p = 0.032). Stomach keratinisation score decreased from 1.9 to 1.4 in TRT5 compared with TRT4 (p > 0.05). In conclusion, the addition of VA to the diet can improve the degree of gastric ulcer to a certain extent and effectively improve growth performance.

Changes in the lipid balance in the gastric mucosa in rats under acute stress

BACKGROUND: Stress gastric ulcers are a type of peptic ulcer that develops in response to severe physiological or psychological stress. The causes of stress ulcers in the gaster have not yet been fully studied. AIM: To evaluate the composition of lipids in the gastric mucosa in rats under acute stress. MATERIALS AND METHODS: All rats included in the study (n=30) were divided into two groups. Group 1 (main group, n=20) included animals with a model of stress gastric ulcer created by stimulation with electrical impulses for 12 h. Group 2 (control group, n=10) included animals with no manipulations. At the end of the experiment, the effective and total concentration in blood serum of all animals was measured, followed by the calculation of the albumin binding reserve, and the plasma toxicity index. We also visually assessed the degree of damage to the gastric mucosa and determined the lipid composition. RESULTS: Our study showed that a stressful situation led to endogenous intoxication in group 1. A decrease in the level of phosphatidylcholine by 16.3% and phosphatidylserine by 18.6% in stressed rats demonstrates the destruction of the cell membrane associated with apoptosis, which macroscopically manifested as spot hemorrhages, erosions, and ulcers in the gastric mucosa. An increase in monoacylglycerol by 34.4% and diacylglycerol by 53.4% in group 1 indicates an increase in membrane permeability and induction of regenerative processes. CONCLUSION: In a stressful situation, a decrease in both total and effective albumin concentrations contributes to endogenous intoxication, leading to lipid imbalance, cell membrane damage, and the development of acute gastric mucosal injury.