Animal Research Research Articles

Efficacy and safety of tanshinone IIA in combination with mesalazine in the treatment of ulcerative colitis: a Systematic review and meta-analysis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC. We reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data. The perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700). This meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy.

Toward a common interpretation of the 3Rs principles in animal research.

Toward a common interpretation of the 3Rs principles in animal research.

Predicting the body weight of crossbred Holstein × Zebu dairy cows using multivariate adaptive regression splines algorithm.

This study aimed to estimate live body weight from body measurements for Holstein × Zebu dairy cows (n = 156) reared under conditions of humid tropics in Mexico using multivariate adaptive regression splines algorithm (MARS) with several train-test proportions. The body measurements included withers height, rump height, hip width, heart girth, body length and diagonal body length. The data were divided into 65:35, 70:30 and 80:20 split data for training and testing sets, respectively. The MARS algorithm was used to construct a prediction model, which predicted the body weight from the body measurements of the test dataset. The results emphasized that the MARS algorithm had an explanation rate for 80:20 train and test set of 0.836 and 0.711, respectively, with minimum Akaike information criterion values. This indicates that it is a reliable way of predicting body weight from body measurements. The results suggest that body weight prediction can be performed with the MARS algorithm in a reliable way, therefore, this algorithm may be a useful tool for animal breeders and researchers in the development of feeding and selection-aimed approaches.

Reproductive and Metabolic Health Following Exposure to Environmental Chemicals: Mechanistic Insights from Mammalian Models.

The decline in human reproductive and metabolic health over the past 50years is associated with exposure to complex mixtures of anthropogenic environmental chemicals (ECs). Real-life EC exposure has varied over time and differs across geographical locations. Health-related issues include declining sperm quality, advanced puberty onset, premature ovarian insufficiency, cancer, obesity, and metabolic syndrome. Prospective animal studies with individual and limited EC mixtures support these observations and provide a means to investigate underlying physiological and molecular mechanisms. The greatest impacts of EC exposure are through programming of the developing embryo and/or fetus, with additional placental effects reported in eutherian mammals. Single-chemical effects and mechanistic studies, including transgenerational epigenetic inheritance, have been undertaken in rodents. Important translational models of human exposure are provided by companion animals, due to a shared environment, and sheep exposed to anthropogenic chemical mixtures present in pastures treated with sewage sludge (biosolids). Future animal research should prioritize EC mixtures that extend beyond a single developmental stage and/or generation. This would provide a more representative platform to investigate genetic and underlying mechanisms that explain sexually dimorphic and individual effects that could facilitate mitigation strategies.

Heart ultrasound and biomechanical evaluation of radiation‐induced heart toxicity using transthoracic echocardiogram (TTE) and dynamic mechanical analysis (DMA)

AbstractRadiation‐induced heart disease (RIHD) is a serious complication but difficult to assess in patients undergoing thoracic radiotherapy (RT). We aim to analyze RIHD using heart ultrasound and elastic modulus, exploring relationships between functional, anatomical or biomechanical changes of the heart and radiation dose.Twenty BALB/c mice were divided into four groups (control, 10 Gy, 20 Gy and 25 Gy) with a single fraction of image‐guided volumetric modulated arc radiotherapy (VMAT) to murine heart on a linear accelerator. Transthoracic echocardiography (TTE) was performed on a small‐animal ultrasound imaging system with a handheld microscan transducer. E‐wave/A‐wave ratio (E/A) and myocardial performance index (MPI) for diastolic performance were noninvasively evaluated weekly, as well as ejection fraction (EF%), fractional shortening (FS%), left ventricle (LV) mass and heart wall thickening for systolic performance. At the end of the fifth week, all mice were sacrificed for elastic modulus measurement on a dynamic mechanical analyzer (DMA) and for histopathological staining. All experiments were conducted in accordance with the local institution's animal research committee guideline.Significant difference was observed in E/A ratio between the control and 25 Gy irradiated groups (1.8±0.5 and 0.7±0.9, respectively; p<0.05), indicating reduced diastolic performance and increased stiffness in left ventricle after high‐dose heart radiation. Diastolic dysfunction in irradiated groups was also observed with significantly increased MPI. In contrast, posterior wall thickness, aortic peak velocity, heart rate, EF and FS were not significantly different after RT. Heart elasticity was reduced substantially with the increased radiation dose. HE and Masson Trichrome staining confirmed more fibrosis deposition in irradiated hearts.RIHD evaluation with ultrasound imaging noninvasively and biomechanical modulus measurement invasively in the image guided, precision dose‐escalated murine heart irradiation is feasible. Increased myocardial stiffness, abnormal diastolic relaxation, more collagen deposition, and reduced tissue elasticity are observed in irradiated heart tissue. This study may facilitate our understanding of RIHD and facilitate improving patients’ quality of life in the future.

TMOD-09. NEWLY DESIGNED TUMOR TREATING FIELDS (TTFIELDS) ARRAYS FOR THE MOUSE HEAD DEMONSTRATE EFFICACY FOR TREATMENT OF GLIOBLASTOMA

Abstract Tumor Treating Fields (TTFields) therapy is a cancer treatment modality based on continuous, non-invasive delivery of electric fields. TTFields therapy is approved for treatment of glioblastoma (GBM), delivered to the patient’s brain by two array pairs placed on the scalp. Further research in animals to expand the knowledge regarding TTFields treatment of GBM is limited, as this is mainly performed in mouse models and arrays for application of TTFields to the mouse head are lacking. The small dimensions and specific geometries of the mouse head make the development of such arrays challenging. The aim of this study was to design arrays that will allow efficient and stable delivery of TTFields to the mouse head. To overcome the small head size, we developed a layout with two arrays situated on the head of the mouse, each divided into two smaller disks, and positioned opposite two arrays on the torso. We identified a thin and transparent adhesive tape (facilitating correct array positioning) with good tackiness and easy removal (without leaving residual adhesive on the skin). The arrays met the minimum treatment requirements: current ≥ 50 mA, usage ≥ 75%, field intensity ≥ 1 V/cm RMS. We then conducted an efficacy study with the new arrays, using GL-261 GBM cells intracranially injected into C57BL/6 mice. Treatment with sham-heat (control) or TTFields was initiated 11 days following tumor inoculation and maintained continuously for 12 days. Efficacy was measured via magnetic resonance imaging (MRI) of tumor volume, showing a decrease of 31% at treatment end in TTFields-treated mice versus the control. Overall, the new arrays are flexible, strongly adherent, deliver TTFields at a sufficient intensity, and showed efficacy for treating GBM in mice.

Physical therapy approach and non-invasive modalities in treatment of vaginal laxity: a literature review.

Pelvic floor physical therapy (PFPT) and noninvasive modalities can be more safe and available treatments for vaginal laxity (VL) with less risk of postsurgical complications. The purpose of this review is to define the concepts of PFPT and noninvasive modalities, examine the evidence supporting those modalities as a treatment for VL, and evaluate their effectiveness. Between 2002 and 2023, clinical studies including women diagnosed with VL were examined in the Web of Science, Cochrane Library, Scopus, and PubMed databases. Exclusion criteria included studies with no outcomes or inadequate data, procedures, suggestions, editorials, book chapters, letters to editors, reviews, meta-analyses, animal research, and articles in languages other than English. Only seventeen studies have been identified. Four studies have demonstrated the impact of PFPT (low- and medium-energy radiofrequency (RF), ultrasound, low-energy laser treatment, par sacral stimulation, the knack method, and pelvic floor exercises), and thirteen studies have discussed the impact of noninvasive modalities (RF, combined multipolar RF with pulsed electromagnetic, combined RF and pulsed electromagnetic field, high-intensity focused ultrasound, CO2 laser, combining multipolar RF and hybrid fractional laser, microfocused ultrasound, and the VIVEVE surface-cooled RF) on vaginal laxity. This review indicates many knowledge areas that must be attempted in order to understand the influence of nonstrengthening physical therapy and noninvasive methods on vaginal laxity. In addition to the mechanisms behind their impacts. In addition, we strongly recommend that more clinical trials of high methodological and interventional quality are required to investigate the efficacy of various physical therapy approaches, including electrical stimulation, biofeedback exertion, acupressure, manual therapy, neuromodulation, core exercise therapy, hydrotherapy, well-designed ultrasound therapy protocols, and vaginal weight training.

Macronutrient interactions and models of obesity: Insights from nutritional geometry.

The global obesity epidemic results from a complex interplay of genetic and environmental factors, with diet being a prominent modifiable element driving weight gain and adiposity. Although excess intake of energetic macronutrients is implicated in causing obesity, ongoing debate centers on whether sugar or fat or both are driving the rising obesity rates. This has led to competing models of obesity such as the "Carbohydrate Insulin Model", the "Energy Balance Model", and the "Fructose Survival Hypothesis". Conflicting evidence from studies designed to focus on individual energetic macronutrients or energy rather than macronutrient mixtures underlies this disagreement. Recent research in humans and animals employing the nutritional geometry framework (NGF) emphasizes the importance of considering interactions among dietary components. Protein interacts with carbohydrates, fats, and dietary energy density to influence both calorie intake ("protein leverage") and, directly and indirectly, metabolic physiology and adiposity. Consideration of these interactions can help to reconcile different models of obesity, and potentially cast new light on obesity interventions.

Implementations of sign- and goal-tracking behavior in humans: A scoping review.

Animal research has identified two major phenotypes in the tendency to attribute incentive salience to a reward-associated cue. Individuals called "sign-trackers" (STs) preferentially approach the cue, assigning both predictive and incentive values to it. In contrast, individuals called "goal-trackers" (GTs) preferentially approach the location of the upcoming reward, assigning only a predictive value to the cue. The ST/GT model has been shown to be relevant to understanding addiction vulnerability and other pathological behaviors in animals. Therefore, recent studies tried to implement this animal model in the human population. This scoping review aimed to identify and map evidence of human sign- and goal-tracking. Studies that explicitly measured human sign- and goal-tracking or related phenomena (e.g., attentional bias induced by reward-related cues), using paradigms in line with the animal model, were eligible for this review. We searched for published, unpublished, and gray literature (PhD theses, posters, conference papers) through the following databases: MEDLINE, Scopus, PsycINFO, Embase, OSF, and Google Scholar. The JBI scoping review methodology was adopted. Screening and extraction were carried out by three reviewers, in pairs. A total of 48 studies were identified. These studies used various experimental paradigms and used the term "sign-tracking" inconsistently, sometimes implicitly or not at all. We conclude that the literature on human sign-tracking is very heterogeneous on many levels. Overall, evidence supports the existence of sign- and goal-tracking behaviors in humans, although further validated research is crucially needed.

Transuterine relocation of pregnant uterine horn segment in an exploratory rat model with implications for tubal ectopic pregnancy

Ectopic pregnancy affects ~ 2% of pregnancies annually in the United States, with no current treatments allowing for the continuation of the pregnancy. Thus, this study sought to initiate an investigation into the potential design of a surgical technique, in an animal model, that could serve as a foundation for future research into the potential of relocating an ectopic embryo into the uterus at the human level. Female Long-Evans rats were randomly assigned to one of two groups: Embryo Relocation (ER; n = 12; underwent embryo relocation surgery) and Normal Pregnancy (NP; n = 12; carried a normal pregnancy; no surgery). Eight rats/group were allowed to carry their pregnancy to term and deliver, while four had their uteri collected at the end of gestation. Briefly, for the ER group, a uterine horn containing 1–2 embryos was translocated to the contralateral horn, which had been incised and cleared of its contents, prior to being wrapped around the relocated horn. Rat weight, food consumption and vaginal impedance of the mothers were measured throughout the experiment. Ultrasounds were performed and fetal heart rates measured on day 20–21 of gestation. Additionally, rat weight of all offspring was measured at adulthood. Our findings indicate that, in the ER group, 15/15 (100%) of the relocated embryos had detectable heart rates at the end of gestation (within the normal range), 14/15 (93%) were delivered vaginally, and 12/14 (86%) survived until adulthood. A significant decrease in rat weight and food consumption was observed only on the day following surgery. Fertility, as measured by vaginal impedance, was minimally impacted by surgery. Moreover, there was no significant difference between groups in average body weight of offspring at adulthood. Histological analysis indicated a thicker placenta in the ER group, attributable to the fetal part of the placenta, potentially indicating compensatory mechanisms. Our findings reflect a successful transuterine embryo relocation followed by vaginal birth and survival of offspring to adulthood, in a rat model. Such findings lay the foundation for future preclinical research in higher animals, with potential implications on a procedure relevant to human ectopic embryo relocation.

Probiotics as an Adjunct Approach to the Prevention and Treatment of Colon Cancer: A Review

Abstract:: One out of every six people in the world is suffering from cancer disease. The major causes of cancer are high consumption of tobacco, high body mass index, and alcoholic beverages with low intake of a healthy diet and limited physical activity. Colon cancer is one of the leading causes of cancer-related morbidity worldwide. In the past few years, probiotics have drawn a lot of interest as potential preventive and therapeutic anticancer agents. This literature review addressed both human and animal research that has explored the association between probiotics and colon cancer. Probiotic administration has remarkable potential for the prevention and treatment of colon cancer through various mechanisms such as inhibiting the growth of cancer cells via apoptosis, improving immune activity, restoring gut microbiota, improving intestinal barrier properties, synthesizing anticarcinogenic compounds, and degrading carcinogenic compounds. Therefore, probiotics emerge as an adjunct therapy, holding the potential to significantly reduce the risk of colorectal cancer.

Evaluation of thiol/disulphide and oxidant-antioxidant status of dairy cows in periparturient and post-partum period.

Thiol/disulphide homeostasis (TDH) has a critical role in many cellular activities such as antioxidant protection. Alterations of oxidative stress in the transition period play an important role in development of some diseases and disorders in dairy cows. The purpose of this study is to assess the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), total thiol, native thiol, disulphide and lipid profile in Simmental and Montofon dairy cows (aged 2-3) before and after calving. Blood samples were collected 233-280 days of pregnancy and the 30 days of post-partum. Serum total thiol, native thiol and disulphide levels were determined as well as TAS, TOS and paraoxonase-1 (PON-1) levels were measured using colorimetric assays. Triglycerides (TG), total cholesterol, HDL cholesterol and LDL cholesterol levels were measured with an automatic analyser. Total thiol (p=0.038) and disulphide (p=0.015) levels were higher after calving compare to pregnancy in Montofon. TAS was found lower (p<0.001), and OSI was higher in both breeds (Montofon p=0.012, Simmental p=0.028) after calving than in pregnancy. When compared between pregnancy and after calving levels in the same breed, HDL was found to be higher after calving (p<0.001) and TG was lower after calving (p=0.020) in Montofon. PON (p=0.090), HDL (p<0.001) and cholesterol levels were found higher (p<0.001) and TG level was lower (p<0.001) after calving in Simmental. According to our results, we observed different responses between two breeds before and after calving. There are few studies about TDH in animal research, and this is the first study in the literature that evaluates the TDH along with oxidative stress and lipid profiles in dairy cows in the periparturient and post-partum period.

Donald Griffin, sentience, and animal research ethics

Donald Griffin, sentience, and animal research ethics

Phage diversity in One Health.

One Health aims to bring together human, animal, and environmental research to achieve optimal health for all. Bacteriophages (phages) are viruses that kill bacteria and their utilisation as biocontrol agents in the environment and as therapeutics for animal and human medicine will aid in the achievement of One Health objectives. Here, we assess the diversity of phages used in One Health in the last 5 years and place them in the context of global phage diversity. Our review shows that 98% of phages applied in One Health belong to the class Caudoviricetes, compared to 85% of sequenced phages belonging to this class. Only three RNA phages from the realm Riboviria have been used in environmental biocontrol and human therapy to date. This emphasises the lack in diversity of phages used commercially and for phage therapy, which may be due to biases in the methods used to both isolate phages and select them for applications. The future of phages as biocontrol agents and therapeutics will depend on the ability to isolate genetically novel dsDNA phages, as well as in improving efforts to isolate ssDNA and RNA phages, as their potential is currently undervalued. Phages have the potential to reduce the burden of antimicrobial resistance, however, we are underutilising the vast diversity of phages present in nature. More research into phage genomics and alternative culture methods is required to fully understand the complex relationships between phages, their hosts, and other organisms in the environment to achieve optimal health for all.

Exploring distinct and joint contributions of the locus coeruleus and the substantia nigra/ventral tegmental area complex to reward and valence processing using high-resolution fMRI

Abstract Dopaminergic neurons in the substantia nigra and the ventral tegmental area (SN/VTA) are classically viewed as key mediators in reward processing, while noradrenergic cells in the locus coeruleus (LC) are thought to modulate (negative) saliency processing. However, this conventional distinction is being revised by more recent research in animals. To explore the respective contributions of both the LC and SN/VTA in reward and valence processing in humans, we assessed fMRI data during stimulus encoding and response phase of a rewarded emotion-discrimination task (n = 38). Participants responded significantly faster to reward predicting and negative valence stimuli compared with their non-salient counterparts. LC activity was overall higher during trials involving reward prospect, and in particular for reward trials featuring positive valence, demonstrating an additive effect of reward and positive valence in LC. Moreover, LC activity was differentially increased for negative compared with positive valence in the response phase, indexing its role in invigorating responses to negative events. The SN/VTA showed increased activity in the response phase of reward trials (neutral valence) and negative valence trials (no reward), which aligns with coding relative saliency of these events in their respective contexts. LC modulations were accompanied by covariations in occipital cortex, suggesting noradrenergic contributions to visual prioritization of salient events. The findings underscore the sensitivity of both LC and SN/VTA to reward prospects and negative valence, challenging the dominant view of SN/VTA’s involvement in merely positive events and emphasizing their essential role in action invigoration above and beyond mere stimulus encoding. The intricate roles of the DA and NA system in reward and emotional valence processing in humans warrant further exploration and validation, given the limitations inherent to neuroimaging of deep brain structures.

Effects of SGLT2 inhibitors on the cardiovascular outcomes in patients with cancer: a systematic review and meta-analysis

Abstract Introduction The incidence of cardiovascular diseases in cancer survivors has gradually increased due to well-documented drug-associated cardiotoxicity and the expanding population resulting from advances in cancer treatment. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have demonstrated efficacy in reducing cardiovascular risk in patients with type 2 diabetes mellitus, independent of glycemic control. Previous bench and animal research, along with several cohort studies, suggest potential benefits of SGLT2 inhibitors on cardiovascular outcomes in patients with cancer, with or without anthracycline therapy. This systematic review and meta-analysis aim to explore the potential of SGLT2 inhibitors as a therapeutic intervention to reduce cardiovascular risks in cancer patients, especially those undergoing chemotherapy. Methods We systematically searched Cochrane, PubMed, and Embase from inception until February 29, 2024, without language restrictions. Observational cohort studies with a follow-up period of at least 1 year were included to analyze the effects of SGLT2 inhibitors on cardiovascular outcomes in type 2 diabetes patients with cancer. Inclusion and exclusion criteria were predefined. Using random-effects models, we calculated odds ratios (OR) and 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the impact of SGLT2 inhibitors on mitigating cardiotoxicity. Primary outcomes of interest were mortality, heart failure hospitalization, sepsis, and diabetic ketoacidosis. Results Six studies involving 2959 patients in the SGLT2i group and 29169 patients in the non-SGLT2i group were included. Type 2 diabetes patients receiving SGLT2i exhibited significantly lower odds of mortality than those without SGLT2i (OR=0.34, 95% CI=[0.26-0.46], I²=77%). Subgroup analysis revealed a similar reduction in mortality among patients on SGLT2i treated with anthracyclines (OR=0.44, 95% CI=[0.23-0.82], I²=69%). Odds ratios for heart failure hospitalization and sepsis were also significantly lower in the SGLT2i group than the non-SGLT2i group (OR=0.46, 95% CI=[0.35-0.60], I²=0%, and OR=0.28, 95% CI=[0.20-0.40], I²=0%, respectively). The risk for diabetic ketoacidosis was not increased in the SGLT2i group (OR=0.66, 95% CI=[0.20-2.17], I²=0%). Conclusion SGLT2 inhibitors demonstrate a reduction in mortality, heart failure hospitalization, and sepsis in type 2 diabetes cancer patients treated with or without anthracyclines in cohort studies. Our findings support the need for further investigation through randomized controlled trials.Forest plots of mortality with subgroupForest plots of other primary outcomes

Experimental models of antibiotic exposure and atopic disease.

In addition to numerous clinical studies, research using experimental models have contributed extensive evidence to the link between antibiotic exposure and atopic disease. A number of mouse models of allergy have been developed and used to uncover the specific effects of various microbiota members and perturbations on allergy development. Studies in mice that lack microbes entirely have also demonstrated the various components of the immune system that require microbial exposure. The importance of the early-life period and the mechanisms by which atopy "protective" species identified in human cohorts promote immune development have been elucidated in mice. Finally, non-animal models involving human-derived cells shed light on specific effects of bacteria on human epithelial and immune responses. When considered alongside clinical cohort studies, experimental model systems have provided crucial evidence for the link between the neonatal gut microbiota and allergic disease, immensely supporting the stewardship of antibiotic administration in infants. The following review aims to describe the range of experimental models used for studying factors that affect the relationship between the gut microbiota and allergic disease and summarize key findings that have come from research in animal and in vitro models.

Animal researchers' views on the publication of negative results and subsequent policy adoptions.

For over a decade, the non-publication of negative results from preclinical studies has been identified as a significant concern in biomedical research. Such underreporting is considered a contributor to the reproducibility crisis in the field and has been recognized by significant journals such as Science and Nature. In response to the consistently high non-publication rates of preclinical animal research in Europe, a survey was conducted among the biomedical research community to gather their views on publishing negative results. Using the EUSurvey platform, over 200 researchers directly working with animals were surveyed. The study aimed to understand the frequency of negative results, the reasons behind their non-publication, and the perceived pros and cons of making such results public. Insights from the survey could guide steps toward promoting transparency in science, refining research methodologies, reducing animal usage in experiments and minimizing research waste.

Tryptophan Metabolites Improve Intestinal Mucosal Barrier via the Aryl Hydrocarbon Receptor-Interleukin-22 Pathway in Murine Dextran Sulfate Sodium-Induced Pouchitis.

Pouchitis is the commonest complication after ileal pouch-anal anastomosis for ulcerative colitis. The protective effect of tryptophan metabolites on the mucosal barrier may be an effective method for treating pouchitis. The role of tryptophan metabolites on pouchitis remained unclear. We aimed to establish a murine model of dextran sulfate sodium-induced pouchitis to examine the roles of tryptophan metabolites in its pathogenesis. This is a study combined clinical patient data and animal research. A total of 22 patients were enrolled: 5 with familial adenomatous polyposis after ileal pouch-anal anastomosis, eight ulcerative colitis patients after ileal pouch-anal anastomosis patients with pouchitis, and 9 ulcerative colitis patients after ileal pouch-anal anastomosis with normal pouch. The demographic data and fecal samples of patients were collected. Male C57BL/6 mice were purchased from a licensed breeder and underwent ileal pouch-anal anastomosis to establish murine model of pouch. The bloods, feces, tissues of mice were collected. This study was performed in an academic medical center in China. The demographic data of patients were observational collected. The mice underwent ileal pouch-anal anastomosis were divided into six groups: control group with chow diet, dextran sulfate sodium, 6-formylindolo[3,2-b] carbazole + dextran sulfate sodium, high tryptophan diet + dextran sulfate sodium, CH-223191 + dextran sulfate sodium, indole-3-carboxaldehyde + dextran sulfate sodium. Animals were sacrificed after dextran sulfate sodium for 7 days. Fecal tryptophan metabolite level and microbiome composition, the severity of pouchitis, intestinal mucosal barrier function, and activation of the aryl hydrocarbon receptor-interleukin 22 pathway were assessed. Patients with pouchitis had lower fecal microbial diversity and indole-3-acetic acid levels. In murine pouchitis model, high-tryptophan diet increased fecal levels of 3-indoleglyoxylic acid, indole-3-aldehyde, and indole. A high-tryptophan diet and intraperitoneal aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole injection alleviated pouchitis. Tryptophan metabolites improved pouch mucosal barriers. aryl hydrocarbon receptor inhibitors exacerbated experimental pouchitis and disrupted the mucosal barrier; however, the aryl hydrocarbon receptor ligand indole-3-carboxaldehyde reversed this effect. This study was limited by small human sample size and lacking an Aryl hydrocarbon receptor knockout mouse model. A high-tryptophan diet and aryl hydrocarbon receptor ligand alleviated dextran sulfate sodium-induced pouchitis in murine ileal pouch-anal anastomosis model, which might be through regulating epithelial tight junctions and promoting goblet-cell differentiation, as well as maintaining the integrity and function of the mucosal barrier. This study provides a rationale for the clinical application of Aryl hydrocarbon receptor ligands in the treatment of pouchitis. See Video Abstract.

Spontaneous hepatocellular and gastric tumours in African clawed frogs (Xenopus laevis).

Three seven-year-old African clawed frogs (Xenopus laevis) from an animal research facility showed weight loss, coelomic distention and an abnormal swimming gait were euthanised on welfare grounds. A complete necropsy of each animal showed a focal, firm, dark brown to green mass with multifocal haemorrhages in the left liver lobe in two animals and a transmural, firm, beige, multilobulated gastric mass in another animal. Additionally, one of the frogs with the hepatic mass had haemocoeloma. Histologically, the hepatic masses were diagnosed as hepatocellular adenomas and the gastric mass as a gastric carcinoma with trans-coelomic metastases. The three tumours were immunophenotyped using the following antibodies: cytokeratin AE1/AE3, vimentin, E-cadherin, P53 and Ki67 and, additionally, for the hepatic tumours only, synaptophysin, Prox-1, S100 and Sox-9. Masson's trichrome, Periodic acid Schiff and Gram stains was also performed in selected cases. One of the hepatocellular adenomas was weakly positively labelled with E-cadherin whereas the other showed variable positivity for Sox-9 only. Vimentin labelled the stroma and sinusoidal endothelia. Interestingly in the liver, the cytokeratin AE1/AE3 labelling was restricted to the biliary epithelium and sinusoidal endothelia. The gastric carcinoma labelled positively with cytokeratin AE1/AE3 only. This report aims to guide laboratory animal veterinarians to accurately diagnose multi-organ masses in amphibians. To the authors' knowledge, this is the first comprehensive morphological study on a case series of hepatocellular and gastric neoplasia in X. laevis.