Safety and effectiveness of additional triamcinolone acetonide with endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: A pilot study.

Objectives: Radial incision and cutting (RIC) is being investigated as an alternative endoscopic dilation method for lower intestinal tract stenosis, providing a high technical success rate and improving subjective symptoms. However, several patients develop re-stenosis following RIC. In this pilot study, we aimed to evaluate the safety and efficacy of triamcinolone acetonide (TA) addition after RIC. Methods: RIC with TA was performed in 20 patients with lower gastrointestinal tract stenosis. We evaluated the rate of adverse events 2 months after RIC with TA. We investigated the short- and long-term prognoses, as well as the improvement in subjective symptoms, using a visual analog scale. Results: The delayed bleeding rate after RIC was 23.8%. Endoscopic hemostasis was achieved in all patients with delayed bleeding. No perforations were observed. The cumulative re-stenosis-free, re-intervention-free, and surgery-free rates 1 year after RIC were 52.9%, 63.7%, and 85.2%, respectively. Subjective symptoms, including abdominal pain, abdominal bloating, nausea, and dyschezia, significantly improved after RIC with TA. Conclusion: Although additional TA administration after RIC could be safe, additional TA may not be effective on luminal patency after dilation. Further investigation is warranted.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription "Er-Xian Decoction" documented in the esteemed "Clinical Manual of Chinese Medical Prescription". While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. AIM OF THE STUDY: This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. MATERIALS AND METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. RESULTS: ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1ß and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. CONCLUSION: ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

A case of gastrointestinal perforation following transarterial embolization for an intramural hematoma after cold snare polypectomy of an adenoma in the transverse colon.

We encountered a case of a large hematoma developing with perforation shortly after a cold snare polypectomy for a colorectal adenoma. The patient underwent cold snare polypectomy for a 3-mm type Is lesion in the transverse colon at another facility. Two hours later, she visited the emergency room due to abdominal pain. Contrast-enhanced computed tomography revealed a 70 mm, high-intensity mass in the transverse colon with contrast extravasation. We attempted transcatheter arterial embolization to stop the bleeding. Several hours later, the anemia had not worsened, but the severe abdominal pain persisted. Urgent laparoscopic right hemicolectomy was performed due to the possibility of gastrointestinal perforation. The surgery was successfully completed. Pathology reports confirmed the presence of an intramural hematoma in the proximal transverse colon with hemorrhagic infiltration of all layers, along with extensive ischemic changes. A perforation was identified in this area, with mucosal defects observed near the hole, possibly due to cold snare polypectomy.

Instruções em bulas destinadas ao uso de medicamentos para dispepsia e constipação durante a lactação / Instructions in package inserts intended for the use of medicines for dyspepsia and constipation during lactation / Instrucciones en prospectos destinados al uso de medicamentos para la dispepsia y el estreñimiento durante la lactancia

Introdução: A segurança e eficácia do uso de medicamentos durante a lactação são preocupações para mães e profissionais de saúde. Esta pesquisa analisa as orientações das bulas de medicamentos comumente prescritos para dispepsia e constipação, que visa fornecer informações essenciais para orientar as decisões terapêuticas durante esse período crucial da maternidade. Objetivos: Analisar as informações das bulas sobre contraindicações de medicamentos para dispepsia e constipação durante a amamentação, verificando se estão de acordo com as evidências científicas. Métodos: Medicamentos para dispepsia e constipação foram selecionados de acordo com a classificação da Anatomical Therapeutic Chemical (ATC) e o registro ativo no Brasil. A presença de contraindicações para o uso de medicamentos nas bulas do profissional de saúde e do paciente foi comparada com as informações contidas no manual técnico do Ministério da Saúde, Medicamentos e Leite Materno, LactMed, UptoDate, Micromedex, Documento Científico da Sociedade Brasileira de Pediatria e Reprotox. Resultados: Nenhuma informação sobre o uso durante a amamentação foi encontrada em 20,0 e 24,3% das bulas para dispepsia e constipação, respectivamente. A concordância entre as bulas dos medicamentos para dispepsia e as fontes consultadas foi baixa (27,2% das bulas contraindicavam o medicamento na lactação, enquanto nas fontes o percentual de contraindicação variou de 0 a 8,3%). Com relação a medicamentos para constipação, 26,3% das bulas os contraindicavam, enquanto nas fontes o percentual variou de 0 a 4,8%. Conclusões: O estudo mostrou que pelo menos duas em cada dez bulas para dispepsia e constipação não fornecem informações adequadas sobre o uso desses medicamentos em lactentes, e também que houve baixa concordância entre o texto das bulas e as fontes de referência quanto à compatibilidade do medicamento com a amamentação.

Introduction: The safety and effectiveness of medication use during lactation are concerns for mothers and healthcare professionals. This research analyzes the instructions on the leaflets of medications commonly prescribed for dyspepsia and constipation, which aims to provide essential information to guide therapeutic decisions during this crucial period of motherhood. Objectives: To analyze the information in package inserts about contraindications of drugs for dyspepsia and constipation during breastfeeding, verifying whether these are consistent with scientific evidence. Methods: Drugs for dyspepsia and constipation were selected according to the Anatomical Therapeutic Chemical (ATC) classification and active registry in Brazil. The presence of contraindications for the use of medications in the health professional's and patient's package inserts was compared with the information in the technical manual of the Ministry of Health, Medications and Mothers' Milk, LactMed, UptoDate, Micromedex, Documento Científico da Sociedade Brasileira de Pediatria and Reprotox. Results: No information about use during breastfeeding was found in 20.0 and 24.3% of leaflets for dyspepsia and constipation, respectively. The agreement between the leaflets of medications for dyspepsia and the sources consulted was low (27.2% of the leaflets contraindicated the medication during lactation, while in the sources the percentage of contraindication varied from 0 to 8.3%). In relation to medicines for constipation, 26.3% of the leaflets contraindicated them, while in the sources the percentage ranged from 0 to 4.8%. Conclusions: The study pointed out that at least two out of every ten package inserts for dyspepsia and constipation do not provide adequate information on the use of these drugs in infants, and also shows low concordance between the text of the package inserts and the reference sources regarding compatibility of the drug with breastfeeding.

Introducción: La seguridad y eficacia del uso de medicamentos durante la lactancia son preocupaciones para las madres y los profesionales de la salud. Esta investigación analiza las instrucciones contenidas en los prospectos de medicamentos comúnmente recetados para la dispepsia y el estreñimiento, con el objetivo de proporcionar información esencial para guiar las decisiones terapéuticas durante este período crucial de la maternidad. Objetivos: Analizar la información contenida en los prospectos sobre las contraindicaciones de los medicamentos para la dispepsia y el estreñimiento durante la lactancia, verificando si estas son consistentes con la evidencia científica. Métodos: Se seleccionaron medicamentos para la dispepsia y el estreñimiento de acuerdo con la clasificación ATC y el registro activo en Brasil. Se comparó la presencia de contraindicaciones para el uso de medicamentos en los prospectos del profesional de la salud y del paciente con la información del manual técnico del Ministerio de Salud, Medicamentos y Leche Materna, LactMed, UptoDate, Micromedex, Documento Científico da Sociedade Brasileira de Pediatria y Reprotox. Resultados: No se encontró información sobre su uso durante la lactancia en el 20% y el 24,3% de los prospectos para dispepsia y estreñimiento, respectivamente. La concordancia entre los prospectos de los medicamentos para la dispepsia y las fuentes consultadas fue baja (el 27,2% de los prospectos contraindicaba el medicamento durante la lactancia, mientras que en las fuentes el porcentaje de contraindicación variaba del 0% al 8,3%). Con relación a los medicamentos para el estreñimiento, el 26,3% de los prospectos los contraindicaba, mientras que en las fuentes el porcentaje osciló entre el 0% y el 4,8%. Conclusiones: El estudio señaló que al menos dos de cada diez prospectos para dispepsia y estreñimiento no brindan información adecuada sobre el uso de estos medicamentos en lactantes, y también muestra la baja concordancia entre el texto de los prospectos y la referencia. fuentes sobre la compatibilidad del fármaco con la lactancia.

GZMA suppressed GPX4-mediated ferroptosis to improve intestinal mucosal barrier function in inflammatory bowel disease.

BACKGROUND: Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. METHODS: Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. RESULTS: Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. CONCLUSION: These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD.

ß-glucan regulates the intestinal immunity of pearl gentian grouper via the nuclear factor kappa B signaling pathway.

The preceding study observed that yeast ß-glucan supplementation enhanced intestinal health and augmented disease resistance in pearl gentian grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀), which occurred concurrently with the activation of the nuclear factor kappa B (NFκB) signaling pathway. Thus, we hypothesized that ß-glucan improves intestinal health in grouper by modulating the NFκB pathway. Accordingly, the present study examined the effects of NFκB pathway disruption using a specific inhibitor on the intestinal health of pearl gentian grouper that had been injected with ß-glucan. The experimental groups were as follows, (1) CD group: PBS injected; (2) ßG group: ß-glucan injected at a dose of 80 mg/kg; (3) PDTC group: NFκB inhibitor PDTC injected at a dose of 30 mg/kg; (4) ßG + PDTC group: a combination of ß-glucan (80 mg/kg) and PDTC (30 mg/kg) injected together. The results demonstrated that ß-glucan-induced increases in mRNA expression levels of NFκB inhibitor α (iκbα) and p65, the degradation and phosphorylation of IκBα, and the phosphorylation of NFκB p65 were significantly inhibited following NFκB inhibition using PDTC in the intestine of grouper. The PDTC injection resulted in a significant reduction in the ß-glucan-induced increase in mucin levels. The ß-glucan-induced elevation of alkaline phosphatase (AKP) activity, component 3 (C3) content, and inflammatory factors were significantly suppressed following NFκB inhibition. The ßG + PDTC treatment resulted in a restoration of catalase (CAT) enzyme activity to the level observed in the CD treatment, while total antioxidant capacity (T-AOC) was decreased to the level of the ßG treatment. The ß-glucan-induced downregulation of caspase8 (casp8) was reversed following NFκB inhibition, as well as the mRNA levels of casp3 and casp9 being elevated to a greater extent. In conclusion, the ß-glucan-regulated intestinal immunity in grouper may be mediated by the NFκB pathway. Furthermore, the inhibitory effect of ß-glucan on apoptosis and oxidative stress may not be related to the NFκB signaling pathway.

Deficiency of SLC26A3 promotes jejunal barrier damage in metabolic disease-susceptible transgenic pigs.

Intestinal disorders are common in metabolic syndrome. However, their pathogenesis is still not fully understood. Pig and human intestines are highly similar in terms of associated metabolic processes. Here, we successfully constructed a metabolic disease-susceptible transgenic (TG) Bama pig model by knocking in three humanized disease risk genes with the CRISPR/Cas9 technique to assess its potential as a model for human intestinal diseases and explore the possible pathological mechanisms involved. We found that jejunal barrier integrity was disrupted and that the infiltration of inflammatory cells increased in TG pigs after high-fat and high-sucrose diet (HFHSD) treatment. We revealed significant differences in the transcriptome, associated microbiome profiles and microbial metabolite short-chain fatty acid (SCFA) content of the jejunum of TG pigs. Notably, we found that SLC26A3 was significantly downregulated in TG pigs. Knockdown or overexpression of the SLC26A3 gene in IPEC-J2 cells significantly affected the expression of MUC2, MUC13 and occludin. Furthermore, in vitro experiments further verified that CDX2 directly regulated the expression of SLC26A3. Mechanistically, CDX2 mediated intestinal barrier function by enhancing the expression of SLC26A3 by binding to its promoter region between -1120 and - 1070 bp. TG pigs represent a promising model that provides new insights into preclinical research on human intestinal metabolic diseases associated with metabolic disorders and revealed that SLC26A3 may be a potential therapeutic target for intestinal metabolic diseases.

Low temperature alleviated the adverse effects of simulated transport stress on the intestinal health in Chinese soft-shelled turtle Pelodiscus sinensis.

Transport stress always poses a threat to aquatic animals. Transportation under low temperatures was often used to relieve transport stress in practical production of Chinese soft-shelled turtle Pelodiscus sinensis, but their effect on the turtle's intestinal barrier remains unclear. In this study, P. sinensis (initial weight 200 ± 20 g) were exposed to simulated transport stress for 12 h at control (30 °C) and low (20 °C) temperature, and then recovery for 24 h, and each treatment had 4 replicates with each replicate containing 4 turtles. The results showed that transportation induced obvious morphological and histological damages in intestinal villus, with a down-regulated expression of the tight junction related genes. Besides turtles in transport group showed an oxidative stress in intestine, which stimulated a physiological detoxification response together with apoptosis. Low temperature transport plays a mitigative effect on the transport stress of turtle intestine via relieved stress response. Specifically, the intestinal villus/crypt (V/C) ratio and the expression of tight junction genes in the low-temperature group were significantly higher compared to the control temperature group, while stress response parameters such as intestinal cortisol levels and hsp expression were significantly lower in the low-temperature group. Additionally, low temperature alleviated oxidative damage and apoptosis caused by transport stress relative to the control temperature group. However, the protective effect of low temperature on P. sinensis intestine was limited, especially after the temperature recovery stage. Overall, the findings of the present study demonstrated that transport stress would induce the disruption of intestinal integrity and oxidative damage, also activated the mucosal immunity and antioxidant enzyme system response of turtles. It was also suggested that low temperature could alleviate the adverse effects of transport stress on intestinal integrity through modulation of oxidative status and apoptosis, whereas much less impact after temperature recovery.

Not your typical abdominal pain: Case report of a fisherman presenting to the trauma & emergency surgery department with intestinal perforation due to an eel fish.

BACKGROUND: Traumatic intestinal perforation by foreign bodies is rare, with cases involving live fish being exceedingly uncommon, with only one reported case to date. We present a unique case of a 55-year-old fisherman who presented to the Emergency Department with traumatic intestinal perforation due to an eel fish accidentally entering his rectum. Despite initial reluctance to seek medical attention, prompt intervention was crucial to addressing peritonitis. CASE PRESENTATION: The patient presented with severe abdominal pain and signs of peritonitis. X-ray findings confirmed pneumoperitoneum. Urgent laparotomy revealed a live eel fish and a 5 cm sigmoid colon perforation, necessitating a sigmoid colostomy. DISCUSSION: Early recognition of traumatic intestinal perforation is vital for prompt management. Diagnosis can be challenging, emphasizing the need for thorough history-taking and imaging. Surgical intervention aims to repair the intestinal perforation, prevent complications and promote healing. CONCLUSION: This case highlights the importance of considering unusual causes of abdominal pain, particularly in relevant occupational history. Prompt surgical intervention is crucial for favorable clinical outcomes.

A weighted and cumulative point system for accurate scoring of intestinal pathology in a piglet model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a serious condition in premature infants, in which a portion of the intestine undergoes inflammation and necrosis. The preterm pig develops NEC spontaneously, making it a suitable model for exploring novel NEC treatments. We aimed to revise the intestinal scoring system to more accurately describe the diversity of NEC lesions in the preterm piglet model. We included 333 preterm piglets from four experiments, each delivered via cesarean section. The piglets were fed either a gently processed (GP) or harshly processed (HP) milk formula for 96 h before euthanasia. At necropsy, the gastrointestinal tract was assessed with 1) an established 6-grade score and 2) a descriptive approach focusing on the distribution and severity of hyperemia, hemorrhage, pneumatosis intestinalis (intramural gas), and necrosis. Subsequently, the descriptive registrations were converted into a weighted and cumulative point (WCP) score. Compared to the 6-grade score, the WCP score enabled a greater segregation of severity levels, especially among organs with more prominent NEC lesions. IL-1ß in small intestinal lesions and both IL-8 and IL-1ß in colon lesions correlated positively with the WCP scale. A histopathological grade system (0-8) was established and revealed mucosal pathology in lesion biopsies, which were not recognized macroscopically. Finally, the WCP score showed a higher NEC-promoting effect of the HP formula compared to the GP formula. The descriptive registrations and extended score range of this revised intestinal scoring system enhance the accuracy of describing NEC lesions in preterm pigs. This approach may increase the efficiency of preclinical NEC experiments.

Comprehensive efficacy of nano-formulated mixed probiotics on broiler chickens' performance and Salmonella Typhimurium challenge.

The increasing recognition of the potential advantages beyond nanoencapsulation of probiotics gained great attention owing to effective properties. Hence, we provided the most in-depth look into the influence of nanoformulated multi strain probiotics; BLB-NPs comprising Bacillus subtilis ATCC19659, Lactobacillus plantarum ATCC8014 and Bifidobacterium bifidum ATCC29521 on growth performance, antioxidant status and intestinal immunity supporting the defense against Salmonella Typhimurium (S. Typhimurium) challenge in broilers chickens. A total of 2,800 one-day-old male Ross 308 boiler chicks were divided into 7 groups; 1 control without additives, 3 probiotics [fed control diets mixed with B. subtilis, L. plantarum and B. bifidum (BLB) at concentrations of 1 × 104 (BLBI), 1 × 106 (BLBII) and 1 × 108 (BLBIII) CFU /kg diet, respectively] and 3 nanoencapsulated probiotics [fed control diets supplemented with BLB loaded nanoparticles (BLB-NPs) at concentrations of 1 × 104 (BLB-NPsI), 1 × 106 (BLB-NPsII) and 1 × 108 (BLB-NPsIII) CFU /kg diet, respectively]. All previous groups were challenged at d 22 of age with S. Typhimurium. Birds fed BLB-NPs II and III exhibited better weight gain and FCR simultaneously with upregulation in nutrients transporters genes (LAT-1, PepT-1, CAT-1 and SGLT1) even after S. Typhimurium challenge. Upregulation of immmune related genes (IL-1ß, IL-6, IL-8, MyD88, NF-kB, CCL20, CXCLi2, TLR-2, TLR-4 and SOCS1) was prominently subsided in BLB-NPsIII fed group. The strengthening ability of BLB-NPs for broilers' intestinal barriers was evidenced by augmented expression of JAM, MUC-2, occludin and FABP-2 genes, diminished S. Typhimurium counts and suppressed its virulence related genes (HilA and SopD) with restored histopathological pictures of cecum. Notably, post dietary inclusion of higher levels of BLB-NPsIII, the abundance of beneficial Biofidobacterium and Lactobacillus species was dominated over harmful E. coli ones. Birds fortified with BLB-NPs displayed potent antioxidant potential signified by boosting serum and intestinal antioxidant markers alongside reducing oxidative ones. Overall, the abovementioned positive outcomes of BLB-NPs encouraged their potential application in poultry feed to attain superior performance and elicit protective immunity against S. Typhimurium infection.

Evaluating the effectiveness of Toxfin and Novasil as dietary aflatoxin-binding agents in broilers for sustaining hepatic antioxidant capacity and intestinal health status during aflatoxin B1 exposure.

To assess the efficacy of Toxfin and Novasil as aflatoxin-binding agents in broilers exposed to aflatoxin B1 (AFB1) from 11 to 30 days, 288 mixed-sex Ross 308 broiler chickens were randomly allocated to four dietary groups: control feed, control feed + 0.25 mg/kg AFB1, AFB1 feed + 0.3% Toxfin, and AFB1 feed + 0.3% Novasil. The evaluation encompassed growth performance for the grower (11-20 days), finisher (21-30 days), and overall (11-30 days) phases, carcass characteristics, serum biochemical components, liver function enzymes, hepatic antioxidant capacity, AFB1 residue in the liver and kidney, and ileal morphology at 30 days, and apparent nutrient digestibility during 29-30 days. Exposure to AFB1 significantly resulted in reduced growth efficiency, lowered carcass yields, liver hypertrophy, impaired metabolic and hepatic functions, liver oxidative stress, disrupted ileum architecture, diminished nutrient digestibility, and accumulated AFB1 in the liver and kidney. Conversely, supplementation of Toxfin or Novasil significantly augmented body weight gain (BWG) and reduced feed conversion ratio (FCR) during the finisher and overall phases, elevated BWG in the grower phase, heightened levels of glucose, hepatic protein, and glutathione peroxidase, declined malondialdehyde content, improved apparent metabolizable energy, and lowered AFB1 residues in the liver and kidney. Furthermore, Toxfin inclusion significantly reduced FCR during the grower phase, enhanced European production efficiency factor during the grower and overall phases, augmented dressing percentage, declined proportional liver weight, elevated concentrations of total protein, albumin, and total antioxidant capacity, heightened villus surface area, and boosted crude protein digestibility. To conclude, incorporating 0.3% Toxfin into broilers' feeds confers a more effectual safeguard than Novasil against the deleterious consequences of AFB1 exposure.

Investigating the mechanism of enhanced medicinal effects of Terminalia chebula fruit after processing based on intestinal flora and metabolomics.

BACKGROUND AND OBJECTIVE: Terminalia chebula is a classical medicine for the treatment of lingering dysentery, and both raw and processed T. chebula can alleviate ulcerative colitis (UC). The therapeutic efficacy of T. chebula is enhanced after processing, but the mechanism that processing improves this efficacy is still unknown. We investigated the medicinal effects of raw and processed T. chebula on dextran sulfate sodium (DSS)-induced UC model rats using intestinal flora and metabolomics analyses, in order to elucidate the mechanism by which processing enhances the therapeutic effect. METHODS: The major constituents of raw and processed T. chebula were detected by high-performance liquid chromatography (HPLC). UC model was replicated using the DSS method, and then UC rats were administered raw and processed T. chebula. The general physical signs, disease activity index (DAI) scores, colon histopathological morphology, and the expressions of inflammatory cytokines were used to evaluate the therapeutic effect of T. chebula. In addition, 16 s rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) were used to characterize the intestinal flora and contents of short-chain fatty acids (SCFAs). Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to identify the nontargeted fecal metabolites. RESULTS: Raw and processed T. chebula significantly improved the general physical signs and colon inflammatory symptoms and decreased DAI scores of UC rats. Both raw and processed T. chebula mitigated intestinal flora disorders in UC rats, increasing probiotic bacteria, including Lactobacillus and Romboutsia. However, the effect of processed T. chebula was more pronounced. Moreover, the levels of SCFAs of DSS-induced UC rats were restored after drug administration, and the processed T. chebula had a better regulatory effect than raw T. chebula. In the fecal nontargeted metabolomics analysis, differential metabolites such as lipids and amino acids were identified. The processed T. chebula can regulate purine metabolism and other pathways to improve UC, and the levels of the disordered metabolites gradually approached those of the control group. CONCLUSION: Raw and processed T. chebula had the capacity to mitigate DSS-induced UC by rebalancing the intestinal flora, restoring the contents of SCFAs, and regulating fecal metabolites, while processed T. chebula showed preferable effects.

ChanLingGao alleviates intestinal mucosal barrier damage and suppresses the onset and progression of Colorectal cancer in AOM/DSS murine model.

BACKGROUND: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown. PURPOSE: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms. METHODS: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/ß-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC. RESULTS: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/ß-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/ß-catenin pathway. CONCLUSIONS: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG.

Rifaximin alleviates MCD diet-induced NASH in mice by restoring the gut microbiota and intestinal barrier.

AIMS: Due to the increasing global incidence rate of nonalcoholic steatohepatitis (NASH) combined with the lack of effective treatment methods for this disease, there is an urgent need to find new treatment strategies. The aim of this study was to investigate the efficacy of rifaximin in preventing and treating NASH and the related mechanism. MATERIALS AND METHODS: A NASH model was constructed by feeding male C57BL/6 mice a methionine-choline-deficient (MCD) diet for 4 weeks. Rifaximin was administered for 1 week before MCD diet feeding or during the last week of MCD diet feeding to investigate its preventive or therapeutic effects. Liver pathology, hepatic enzyme levels and metabolic indices were measured to evaluate the effects of rifaximin on NASH. Intestinal barrier integrity was measured via the Ussing chamber system and western blotting. 16S rDNA sequencing was conducted to investigate the fecal microbiota composition. Western blotting was performed to evaluate peroxisome proliferator activated receptor (PPAR)α and PPARγ protein levels. KEY FINDINGS: Rifaximin effectively alleviated MCD diet-induced NASH. The microbiota composition in MCD diet-fed mice was significantly altered, and intestinal barrier integrity was disrupted. Dysbiosis and intestinal barrier dysfunction were reversed by rifaximin. In addition, rifaximin modulated PPARα and PPARγ expression in the liver. SIGNIFICANCE: Rifaximin effectively alleviated MCD diet-induced NASH by restoring the gut microbiota and reversing intestinal barrier dysfunction, suggesting that rifaximin treatment is a new approach for preventing and treating NASH.

Development of an intestinal epithelial cell line and organoids derived from the same swine and characterization of their antiviral responses.

Intestinal homeostasis and integrity are important factors for maintaining host health. This study established intestinal epithelial cell lines and organoids from the same swine jejunal crypts to develop seamless swine intestinal in vitro evaluation systems. The study evaluated the proliferative capacity and tight junction formation of the epithelial cell line and characterized the cell differentiation potential of the intestinal organoids. The evaluation systems were subsequently exposed to the Toll-like receptor 3 (TLR3) agonist poly(I:C) to simulate viral infections and assess the antiviral responses. The results demonstrated no differences in the response to type I interferons. There were, however, significant differences in the expression of interferon-stimulated genes. This study collectively introduced a flexible evaluation system using cell lines and organoids and revealed notable differences in the expression of interferon-stimulated genes, highlighting the complexity of the immune responses in these in vitro systems and the importance of intestinal heterogeneity in assessing viral responses.

Regulation effect of the intestinal flora and intervention strategies targeting the intestinal flora in alleviation of pulmonary fibrosis development.

Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the "gut-lung axis". This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.

Effect of Morchella esculenta polysaccharides on the rectal microbiota of mice challenged with lipopolysaccharides.

Introduction: Intestinal dysfunction poses a severe problem by preventing the digestion and absorption of nutrients. The gut, being the most vital organ for these processes, plays a crucial role in ensuring our body receives the nutrients it needs. We explored the mitigating effect of Morchella esculenta polysaccharides (MEP) on intestinal injury induced by lipopolysaccharides (LPS) through the modulation of intestinal flora. Methods: For this purpose, Kunming mice (KM) were divided into three groups, namely, PC, PM, and PY. Group PY was treated with MEP, while groups PM and PY were induced with LPS. Results: The results showed that weight loss in the PM group was significantly greater than that in the PY group (P < 0.05), and the organ indexes of the lung and spleen in the PM group were significantly higher than those in the PC (P < 0.01) and PY (P < 0.05) groups. LPS caused severe injuries in KM mice in the PM group, characterized by broken villi. However, MEP treatment could alleviate this damage in the PY group, resulting in relatively intact villi. The serum analysis showed that tumor necrosis factor alpha (TNF-ɑ) (P < 0.01), interleukin 6 (IL-6) (P < 0.01), and 3,4-methylenedioxyamphetamine (MDA) (P < 0.05) levels were significantly higher in the PM group, while IL-10 (P < 0.001), superoxide dismutase (SOD) (P < 0.01) and glutathione peroxidase (GSH-Px) (P < 0.01) were significantly lower in that group. Interestingly, supplementation with MEP could lower the levels of TNF-ɑ, IL-10, IL-6, MDA while increasing the levels of superoxide dismutase (SOD) (P < 0.01) and GSH-Px. The gut microbiota analysis yielded 630,323 raw reads and 554,062 clean reads, identifying 3,390 amplicon sequencing variants (ASVs). One phylum and five genera were notably different among animal groups, including Escherichia_Shigella, Limosilactobacillus, unclassified_Geminicoccaceae, unclassified_Rhodobacteraceae, and Parabacteroides (P. distasonis). Discussion: In conclusion, we found that MEP could mitigate the intestinal damage caused by LPS by modulating the inflammatory response, oxidative resistance, and intestinal flora of KM mice. Our results may provide insights into novel treatment options for intestine-related diseases.

Late presentation of midgut malrotation with obstruction in a 5-year-old female: A case report.

Midgut malrotations are rarely diagnosed beyond infancy. Delays in recognition and diagnosis can result in death. Here, we report the case of a 5-year-old girl who presented with a 1-year history of intermittent abdominal pain and vomiting. An abdominal computed tomography scan with contrast confirmed the diagnosis of midgut malrotation with obstruction; therefore, the Ladd procedure was performed, and the child was discharged uneventfully. Clinicians must maintain a high level of suspicion because this diagnosis is unusual in this age group.

Monocyte-driven inflamm-aging reduces intestinal barrier function in females.

BACKGROUND: The intestinal barrier encompasses physical and immunological components that act to compartmentalize luminal contents, such as bacteria and endotoxins, from the host. It has been proposed that an age-related decline of intestinal barrier function may allow for the passage of luminal contents into the bloodstream, triggering a low-grade systemic inflammation termed inflamm-aging. Although there is mounting evidence to support this hypothesis in model species, it is unclear if this phenomenon occurs in humans. In addition, despite being well-established that biological sex impacts aging physiology, its influence on intestinal barrier function and inflamm-aging has not been explored. RESULTS: In this study, we observed sex differences in markers of intestinal barrier integrity, where females had increased epithelial permeability throughout life as compared to males. With age, females had an age-associated increase in circulating bacterial products and metabolites such as LPS and kynurenine, suggesting reduced barrier function. Females also had age-associated increases in established markers of inflamm-aging, including peripheral blood monocytes as well as TNF and CRP. To determine if impaired barrier function was driving inflamm-aging, we performed a mediation analysis. The results show that the loss of intestinal barrier integrity was not the mediator of inflamm-aging in humans. Instead, persistent, low-grade inflammation with age preceded the increase in circulating bacterial products, which we confirmed using animal models. We found, as in humans, that sex modified age-associated increases in circulating monocytes in mice, and that inflammation mediates the loss of intestinal barrier function. CONCLUSION: Taken together, our results suggest that higher basal intestinal permeability in combination with age-associated inflammation, increases circulating LPS in females. Thus, targeting barrier permeability in females may slow the progression of inflamm-aging, but is unlikely to prevent it.