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Cryptosporidiosis has been proposed to be one of the major causes of diarrhoeal disease in humans worldwide that possesses zoonotic concern. Thereby, this study investigated the potential effects of s-Methylcysteine (SMC) on the parasite in vivo followed by the measurement of cytokines, oxidative stress parameters, and an investigation of the major histopathological changes. Sixty male Swiss albino mice weighing 20–25 g were allocated equally into five groups and orally administered saline only (control), SMC only (SMC50) (50 mg/kg b.w.), and 104Cryptosporidium parvum oocysts per mouse via an esophageal tube (C + ve untreated). The fourth and fifth groups (C + SMC25, C + SMC50) administrated 104C. parvum oocysts combined with SMC25 (low dose) and 50 (high dose) mg/kg b.w., respectively. At days 7 and 14 post-infection (PI), the feces was collected from each group in order to count C. parvum oocysts. After two weeks of treatment, the animals were euthanized and the serum was collected for biochemical analysis. Next, the intestinal, spleen, and liver sections were dissected for histopathological examination. The results revealed lower oocyst numbers in the C + SMC25 and C + SMC50 groups compared to the infected untreated group. Moreover, higher doses of SMC treatment significantly reduced the enteritis induced by C. parvum in a dose-dependent manner. The hepatic lesions were also mitigated as demonstrated in C + SMC25 and C + SMC50 groups unlike the infected group via lowering the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes and increasing albumin and globulin serum levels. SMC administration also reduced cytokines production (SAP, TNF-α, IL-6, and IFN-γ) mediated by Cryptosporidium infection in contrast to the infected untreated group. There were marked lymphoid depletion and amyloidosis observed in the infected untreated group, while the treated groups showed obvious increase in the lymphoid elements. Moreover, the scoring of intestinal parasites, hepatic, and splenic lesions in the SMC-treated groups exhibited significantly lower pathological lesions in different organs in a dose-dependent manner, compared to the infected untreated group. Our results also revealed a significant change in the malondialdehyde content with an elevation of glutathione and superoxide dismutase in the intestines collected from C + SMC25 and C + SMC50 mice relative to the untreated group. Taken together, our results indicated that SMC could be a promising effective compound for treating and declining C. parvum infestation via restoring structural alterations in different tissues, enhancing antioxidant enzymes, and suppressing the cytokines liberation.

Objective(s): Intestinal ischemia-reperfusion is a major problem, which may lead to multiorgan failure and death. The aim of this study was to evaluate the protective effects of dexmedetomidine on cell proliferation, antioxidant system, cell death, and structural integrity in intestinal injury induced by ischemia-reperfusion in rats. Materials and Methods: Animals were randomized into three groups: group A, sham-operated or control; group B, intestinal ischemia/reperfusion (IR); and group C, intestinal IR pretreated with 50 μg of dexmedetomidine. Intestine tissue was collected from all rats 30 min after desufflation, and fresh frozen for histological and biochemical evaluation. Results: The intestinal tissue of group B rats showed a significant decrease in the antioxidant enzyme activities. However, these enzyme activities were improved by the administration of dexmedetomidine. Inhibiting the protein expression of MCP7, PAR2, P-JAK, P-STAT1, and P-STAT3 proved the protective effect of dexmedetomidine. The immunohistochemical staining revealed its protective effect by maintaining the normal structural integrity, less caspase-3 immuno reactivity, and increased cell proliferation count in the intestinal tissues. Conclusions: Intraperitoneal injection of dexmedetomidine significantly protected intestine IR injury in rats by inhibiting the inflammatory response, intestinal epithelial apoptosis, and maintaining structural integrity of intestinal cells.

Abstract Background Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain. Methods We used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 102), medium (3 × 103), and high (3 × 104) parasite loads were generated by infecting C57BL/6 mice with “Y”-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey’s multiple comparison post-test, Kruskal–Wallis test with Dunn’s multiple comparison, χ2 test and Spearman correlation. Results High parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines. Conclusions These experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

Gastrointestinal mucositis induced during cancer treatment is considered a serious dose-limiting side effect of chemotherapy and/or radiotherapy. Frequently, interruption of the cancer treatment due to this pathology leads to a reduction in cure rates, increase of treatment costs and decrease life quality of the patient. Natural products such as Bidens pilosa L. (Asteraceae), represent a potential alternative for the treatment of mucositis given its anti-inflammatory properties. In this study, B. pilosa glycolic extract was formulated (BPF) with poloxamer, a mucoadhesive copolymer, was used for treatment of 5-fluorouracil (5-FU)-induced mucositis in mice. As expected, animals only treated with 5-FU (200 mg/kg) presented marked weight loss, reduction of intestinal villi, crypts and muscular layer, which was associated with severe disruption of crypts, edema, inflammatory infiltrate and vacuolization in the intestinal tissue, as compared to the control group and healthy animals only treated with BPF. On the other hand, the treatment of intestinal mucositis-bearing mice with BPF (75, 100 or 125 mg/kg) managed to mitigate clinical and pathologic changes, noticeably at 100 mg/kg. This dose led to the restoration of intestinal proliferative activity through increasing Ki-67 levels; modulated the expression of Bax, Bcl2 and p53 apoptotic markers protecting intestinal cells from cell death. Moreover, this treatment regulated lipid peroxidation and inflammatory infiltration. No acute toxic effects were observed with this formulation. This work demonstrated that BPF was safe and effective against 5-FU-induced intestinal mucositis in mice. Additional studies are already in progress to further characterize the mechanisms involved in the protective effects of this technological formulation toward the development of a new medicine for the prevention and treatment of intestinal injury in patients undergoing chemotherapy/radiotherapy.

Soybean meal (SBM) is an acceptable replacement for unsustainable marine fish meal (FM) in aquaculture. However, we previously reported that high dietary SBM supplementation causes intestinal inflammatory injury in yellow drum ( Nibea albiflora ). Accordingly, a 4-week SBM-induced enteritis (SBMIE) in yellow drum trial was conducted first, followed by a 4-week additive-supplemented reparative experiment to evaluate the reparative effect of five additives on SBMIE in yellow drum. The control diet comprised 50% FM protein substituted with SBM. The additive-supplemented diet was added with 0.02% curcumin (SBMC), 0.05% berberine (SBM-BBR), 0.5% tea polyphenols (SBM-TPS), 1% taurine (SBM-TAU), or 0.8% glutamine (SBM-GLU) based on the control diet, respectively. The weight gain (WG), specific growth rate (SGR), feed efficiency ratio (FER), and survival rate (SR) of fish fed the additive-supplemented diets were significantly higher than those of fish fed the SBM diet. The WG, SGR, and FER of fish fed the SBMC, SBM-GLU and SBM-TAU diets were significantly higher than those of fish fed other diets. Moreover, fish fed the additive-supplemented diets SBMC and SBM-GLU, exhibited significantly increased intestinal villus height (IVH), intestinal muscular thickness (IMRT), and intestinal mucosal thickness (IMLT) and significantly decreased crypt depth (CD) in comparison with those fed the SBM diets. The relative expression of intestinal tight junction factors ( ocln, zo1 ), cytoskeletal factors ( f-actin, arp2/3 ), and anti-inflammatory cytokine s (il10, tgfb) mRNA was remarkably elevated in fish fed additive-supplemented diets than those of fish fed the SBM diet. Whereas, the relative expression of intestinal myosin light chain kinase ( mlck ) and pro-inflammatory cytokines ( il1, il6, tnfa ) mRNA was markedly lower in fish fed the additive-supplemented diets. The highest relative expression of intestinal ocln , f-actin , and arp2/3 and the lowest relative expression of intestinal mlck were found in fish fed the SBMC diet. Hence, all five dietary additives effectively repaired the intestinal injury induced by SBM, with curcumin exhibiting the strongest repair effect for SBMIE in yellow drum., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Wang, Zeng, Tan, Chen, Hu, Xu and Xu.)

Fermented foods have protective effects on body health. In our previously study, we found Lactiplantibacillus plantarum fermentation enhanced antioxidant activity of kiwifruit in vitro digestion. Then, in this work we explored the protective effect of fermented kiwi on intestinal injury induced by acute lipopolysaccharide (LPS) stress. Compared to non-fermented kiwi pulp (KP), Lactiplantibacillus plantarum fermented kiwi pulp (FKP-LP) contained more peptides, hormones and vitamins contents, lesser nucleic acid and carbohydrate contents. FKP-LP could relieve the intestinal injury by improving morphological of tight junction and upregulating tight junction proteins mRNA expression. Fermented kiwi maintained the mitochondrial morphology, mitochondrial respiratory function, and mitochondrial homeostasis, and relieved the LPS induced injury by regulating the contents of energy substances, and the respiratory chain complex enzyme activity through the pathway of AMPK and its downstream factors including PGC-1α, NRF1, NRF2, TFAM, and ULK2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: Enteral nutrition is the key therapy in septic patients. Different formulas of enteral nutrition have various effects on gastrointestinal sepsis. Therefore, we investigated the effects of enteral nutrition supplemented with octanoic acid on lipopolysaccharide-induced intestinal injury and explored the potential mechanism., Methods: First, to investigate the effects of enteral nutrition supplemented with octanoic acid on lipopolysaccharide-induced intestinal injury, rats were randomly divided into four groups: sham, lipopolysaccharide, lipopolysaccharide + enteral nutrition, and lipopolysaccharide + enteral nutrition + octanoic acid. Then, to explore whether enteral nutrition supplemented with octanoic acid can prevent lipopolysaccharide-induced intestinal injury via the peroxisome proliferator-activated receptor γ/STAT-1/myeloid differentiation factor 88 pathway, rats were randomly divided into five groups: sham, lipopolysaccharide, lipopolysaccharide + enteral nutrition + octanoic acid, lipopolysaccharide + enteral nutrition + octanoic acid + SR202, and lipopolysaccharide + pioglitazone. All rats received nutritional support for 3 d. We examined the serum levels of inflammatory factors, pathologic changes, goblet cell density, intestinal tight junction protein expression, and the peroxisome proliferator-activated receptor γ/STAT-1/myeloid differentiation factor 88 pathway in the ileum and colon. The effect of octanoic acid on intestinal epithelium injury was also explored in vitro., Results: Enteral nutrition supplemented with octanoic acid significantly decreased the serum levels of inflammatory factors and prevented intestinal barrier dysfunction compared with enteral nutrition alone (P < 0.05). Inhibiting the peroxisome proliferator-activated receptor γ/STAT-1/myeloid differentiation factor 88 pathway exacerbated effects of enteral nutrition supplemented with octanoic acid on intestinal injury (P < 0.05). Activation of the peroxisome proliferator-activated receptor γ/STAT-1/myeloid differentiation factor 88 pathway prevented intestinal injury (P < 0.05). Octanoic acid also exerted a similar effect on intestinal epithelium injury in vitro., Conclusions: Enteral nutrition supplemented with octanoic acid prevents lipopolysaccharide-induced intestinal injury via the peroxisome proliferator-activated receptor γ/STAT-1/myeloid differentiation factor 88 pathway., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chun Cao reports financial support was provided by National Natural Science Foundation of China. Chun Cao reports financial support was provided by Suzhou Municipal Science and Technology Bureau., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae&#95;NK3B31&#95;group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Ma, Cui, Zhang, Li, Liu, Xie, Luo, Tang and Zhai.)

LncRNAs have been reported to play an important role in various diseases. However, their role in the radiation‐induced intestinal injury is unknown. The goal of the present study was to analyse the potential mechanistic role of lncRNAs in the radiation‐induced intestinal injury. Mice were divided into two groups: Control (non‐irradiated) and irradiated. Irradiated mice were administered 14 Gy of abdominal irradiation (ABI) and were assessed 3.5 days after irradiation. Changes to the jejuna of ABI mice were analysed using RNA‐Seq for alterations to both lncRNA and mRNA. These results were validated using qRT‐PCR. LncRNAs targets were predicted based on analysis of lncRNAs‐miRNAs‐mRNAs interaction. 29 007 lncRNAs and 17 142 mRNAs were detected in the two groups. At 3.5 days post‐irradiation, 91 lncRNAs and 57 lncRNAs were significantly up‐ and downregulated respectively. Similarly, 752 mRNAs and 400 mRNAs were significantly up‐ and downregulated respectively. qRT‐PCR was used to verify the altered expression of four lncRNAs (ENSMUST00000173070, AK157361, AK083183, AK038898) and four mRNAs (Mboat1, Nek10, Ccl24, Cyp2c55). Gene ontology and KEGG pathway analyses indicated the predicted genes were mainly involved in the VEGF signalling pathway. This study reveals that the expression of lncRNAs was altered in the jejuna of mice post‐irradiation. Moreover, it provides a resource for the study of lncRNAs in the radiation‐induced intestinal injury. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway is involved in various inflammatory processes including IBD. However, the mechanisms through which purine metabolism modulates IBD remain to be established. Here, we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)–interleukin (IL)‐22 pathway. In mice, blockade of ectonucleotidases (NTPDases), critical enzymes for purine metabolism by hydrolysis of extracellular adenosine 5′‐triphosphate (eATP) into adenosine, exacerbates dextran‐sulfate sodium‐induced intestinal injury. This exacerbation of colitis is associated with reduction of colonic IL‐22‐producing ILC3s, which afford essential protection against intestinal inflammation, and is rescued by exogenous IL‐22. Mechanistically, activation of ILC3s for IL‐22 production is reciprocally mediated by eATP and adenosine. These findings reveal that the NTPDase‐mediated balance between eATP and adenosine regulates ILC3 cell function to provide protection against intestinal injury and suggest potential therapeutic strategies for treating IBD by targeting the purine–ILC3 axis. The purine metabolic pathway has been indicated to be involved in Inflammatory bowel disease, but the mechanisms remain to be established. We have found in this research that metabolic regulation of eATP into adenosine by NTPDases promotes ILC3–IL‐22 protection against acute intestinal epithelial injury. These findings suggest that targeting the purine‐ILC3 axis could represent new therapeutic strategies against intestinal injury and inflammation. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is the most frequently prescribed anti-tumor drug, but has been reported to result in intestinal injury. Although some progress has been made in understanding the intestinal toxicity of 5-FU, confusion remains about animal models of 5-FU-induced intestinal injury, especially the dosage of 5-FU. This study aims to assess the dose-response relationship between the severity of intestinal injury and different doses of 5-FU, and to determine a proper dosing for the murine model. We found that mice in the 5-FU groups gradually lost body weight over time. Increasing doses of 5-FU resulted in more severe diarrhea, with a concomitant increase in mortality. Histopathological damage was more severe in mice that received higher doses of 5-FU. In addition, plasma diamine oxidase (DAO) activity decreased in experimental mice with intestinal injury in a dose-dependent way. TUNEL and western blot analysis showed cell apoptosis in the ileum and colon related to 5-FU dosage. However, administration of 200 and 400 mg/kg 5-FU caused extremely high mortality, severe diarrhea and histopathological damage, but 25 mg/kg 5-FU did not result in significant intestinal injury. The severity of intestinal injury induced by 5-FU appeared to be dose-dependent and we concluded that the proper dosage of 5-FU to induce a murine model with intestinal mucositis ranged from 50 mg/kg to 100 mg/kg. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of bifidobacteria on intestinal injury and flora in a mouse model of ulcerative colitis (UC). Methods: Mouse model of UC was produced using dextran sulphate sodium (DSS). The mice were divided into seven groups, viz, reference group, MRS-L medium-negative control group, mesalaminepositive control group, high dose bifidobacteria (MIMBb75) group, middle dose MIMBb75 group and low dose MIMBb75 group. Normal mice were used as control. All mice were sacrificed at day 7 of treatment, and colon length, hemoglobin concentration and intestinal flora were determined. Results: Bifidobacteria inhibited UC-induced decreases in mice hemoglobin and UC-induced colon shortening. In addition, it augmented the diversity of intestinal flora and increased the number of bacteroides and Clostridium leptum. Conclusion: Bifidobacteria plays a therapeutic role in UC via regulation of intestinal microflora. [ABSTRACT FROM AUTHOR]

The fast growing applications of ZnO nanoparticles (NPs) in food sector and other fields enhance the exposure possibility of human beings to ZnO NPs including via oral administration route. Although the oral toxicity of ZnO NPs has been studied, most of the research was performed on the normal animal models. Therefore, the understanding of the biological consequence of ZnO NPs on the population with diseases, especially gastrointestinal disease, is extremely limited. In this study, a mice model of inflammatory bowel disease (IBD) induced by indomethacin has been developed to comprehensively investigated the bioeffects of ZnO NPs on the specific population. The effect of the intestinal inflammation/injury on the distribution and toxicity of orally administrated ZnO NPs (nZnO, 20 nm × 100 nm and mZnO, ∼200 nm) in mice were analyzed. The results showed that there was a difference in the distribution of Zn and the essential trace elements (Fe and Cu) between the IBD mice and the normal mice. We also observed an obvious size effect. Higher hepatic Zn was detected in the IBD mice post-exposure to ZnO NPs, especially bigger ZnO NPs. In addition, the histopathological examination of main organs and biological parameters analysis showed that ZnO NPs caused slight toxicity to the liver and kidneys in the IBD mice. Our findings highlight the importance of the health status of animals on the bioeffects of nanomaterials. [ABSTRACT FROM AUTHOR]

Background: Low splanchnic perfusion is an immediate effect of pneumoperitoneum-induced intra-abdominal hypertension (IAH). Anatomical structure results in the intestinal mucosa being the area most sensitive to hypoperfusion. The relationship between intestinal injury and clinical parameters of tissue perfusion [abdominal perfusion pressure (APP), gastric intramucosal pH (pHi) and lactic acid (Lc)] has not been previously studied. This study aimed to monitorize intestinal pathogenesis through sequential ileal biopsies and to measure APP, pHi, and Lc levels at different pneumoperitoneum-induced intra-abdominal pressures (20, 30, and 40 mmHg) to evaluate the potential relationships between them.Materials and Methods: Fifty pigs were divided into four groups; a control group (C) and three experimental groups with different pneumoperitoneum-induced levels [20 mmHg (G20), 30 mmHg (G30), and 40 mmHg (G40)], that were maintained for 3 and 5 h. APP, pHi, and Lc were measured and ileal biopsies taken laparoscopically every 30 min. The mucosal damage was graded using the standardized Park's Score and animals were classified as injured (I+) or uninjured (I-).Results: Different histopathological lesions were observed in groups G20, G30, and G40 but no damage observed in group C. A 33.3% of animals in G20 and G30 were I+ after 3 h, while 93.3% were injured in G40. After 5 h, histopathological lesions were no longer seen in some animals in G20 and only 10% were I+. Conversely, in G30 I+ pigs increased to 80% while those in G40 remained at 93.3% I+. The I+ animals had significantly lower APP and pHi than those I-. Lc was the clinical parameter that showed the earliest differences, with significantly higher figures in I+ animals.Conclusions: The evolution of intestinal injuries from pneumoperitoneum-induced IAH depends on the degree of IAP. These damages may be associated with decreases in APP and pHi, and increases in Lc. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the intra- and postoperative gastrointestinal complications following abdominal sacrocolpopexy and determine the possible causes. Methods: A total of 86 patients who underwent abdominal sacrocolpopexy due to symptomatic pelvic organ prolapse between January 2014 and January 2016 at İzmir Tepecik Training and Research Hospital Obstetrics and Gynecology Clinic were retrospectively reviewed using the hospital information system. Patients were divided into two groups: those with and without prolonged length of hospital stay. They were evaluated in terms of gastrointestinal complications and risk factors. Results: The reason for prolonged hospitalization was nausea and vomiting in 24 (88%) of 27 patients. The symptoms in these patients were recovered with hydration, stopping of oral intake, and administration of antiemetics. Nasogastric decompression and parenteral nutrition were required in three (11%) patients due to clinical and radiological evidence of ileus. The parameter that significantly prolonged the length of hospital stay was prior abdominal surgery (p < 0.05). Conclusion: There were obvious gastrointestinal complications in three out of 27 patients with prolonged length of hospital stay. These findings may be beneficial for preoperative patient counselling. [ABSTRACT FROM AUTHOR]

Objective Cardiopulmonary bypass (CPB) surgery commonly threatens the heart and remote organs with ischemia-reperfusion injury. Transient episodes of ischemia to nonvital tissue, known as remote ischemic preconditioning (RIPC), is thought to help local and remote vital organs to withstand subsequent ischemic insults. Design Prospective, randomized, double-blinded control trial. Setting Tertiary referral academic teaching hospital. Participants Thirty patients undergoing elective CPB surgery Intervention RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control (sham cuff). Measurements and Main Results Primary outcome was the occurrence of intestinal injury, as measured by an increase in intestinal fatty acid binding protein (I-FABP). Secondary outcomes included incidence of gastrointestinal complications and duration of intensive care unit (ICU) stay. RIPC did not affect serum IFABP levels at the end of surgery and on the first postoperative day (p = 0.697 and p = 0.461, respectively). For all patients, mean I-FABP levels significantly increased at the end of surgery and decreased to under baseline levels on the first postoperative day (from a mean [± standard deviation] baseline value of 764 ± 492 pg/mL to 2,002 ± 974 pg/mL and decreased to 568 ± 319 pg/mL, p < 0.001). All patients remained clinically absent of gastrointestinal complications until hospital discharge. Duration of ICU stay was not correlated with I-FABP levels at the end of surgery. Neither duration of CPB nor duration of aortic clamping significantly correlated with postoperative I-FABP levels. Conclusions These findings suggest that RIPC does not affect intestinal injury in patients undergoing CPB surgery. In patients undergoing cardiac surgery, intestinal injury appears to be moderate and transient without any clinical relevant complication. [ABSTRACT FROM AUTHOR]

Here we investigated the influence of LPS-induced gut injury on antioxidant homeostasis, mitochondrial (mt) function and the level of mitophagy in piglets. The results showed that LPS-induced intestinal injury decreased the transepithelial electrical resistance, increased the paracellular permeability of F1TC dextran 4kDa, and decreased the expression of claudin-1, occludin and zonula occludens-1 in the jejunum compared with the control group. LPS decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and increased the content of malondialdehyde in the jejunum. Meanwhile, the expression of SOD-related genes (Cu/Zn-SOD, Mn-SOD) and GSH-Px-related genes (GPX-1, GPX-4) declined in LPS-challenged pigs compared with the control. LPS also increased TNF-α, IL-6, IL-8 and IL-1β mRNA expression. LPS induced mt dysfunction, as demonstrated by increased reactive oxygen species production and decreased membrane potential of intestinal mitochondria, intestinal content of mt DNA and activities of the intestinal mt respiratory chain. Furthermore, LPS induced an increase in expression of mitophagy related proteins, PTEN-induced putative kinase (PINK 1) and Parkin in the intestinal mitochondria, as well as an enhancement of the ratio of light chain 3-II (LC3-II) to LC3-I content in the jejunal mucosa. These results suggested that LPS-induced intestinal injury accompanied by disrupted antioxidant homeostasis, caused mt dysfunction and triggered mitophagy. [ABSTRACT FROM AUTHOR]

Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR) on postoperative cognitive dysfunction (POCD) and intestinal injury induced by cardiopulmonary bypass (CPB) and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4+IL-17+ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100β, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4+IL-17+ cells was also significantly increased. Conclusion: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy. [ABSTRACT FROM AUTHOR]

Adenosine deaminase acting on RNA 1 (ADAR1), a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), has been identified as a modulator of immune responses. However, the role of ADAR1 in small intestinal homeostasis during sepsis remains unclear. In this study, we examined the role of ADAR1 on intestinal inflammation in a murine model of sepsis. We found that ADAR1 was highly expressed in “septic” macrophages and small intestinal tissue of septic mice. Deletion of ADAR1 in “septic” macrophages led to rapid apoptosis. In addition, suppression of ADAR1 in “septic” macrophages significantly enhanced inflammation, while over-expression of ADAR1 significantly suppressed the level of inflammatory cytokines. Furthermore, suppression of ADAR1 in septic mice significantly enhanced inflammation and intestinal damage, while enhanced ADAR1 expression resulted in reduced damage and inflammation. Finally, over-expression of ADAR1 improved survival of septic mice. In conclusion, we have identified a novel ADAR1 protective effect for maintaining intestinal homeostasis. Our findings may provide a new targeted therapy for sepsis treatment. [ABSTRACT FROM AUTHOR]

Background: An understanding of the factors that influence intestinal wall integrity during the transition from fetal to neonatal life is important to elucidate and minimize potential contributions to the development of intestinal pathologies in vulnerable newborns.Objective: To assess the factors affecting intestinal wall integrity of late preterm and term newborns at birth.Methods: The concentrations of serum intestinal fatty acid-binding protein (I-FABP) as biomarker of intestinal wall injury, superoxide dismutase (SOD), and glutathione peroxidase (Gpx) as parameters of oxidative stress, and blood gas analyses were measured in the arterial cord blood of 80 newborns, delivered by spontaneous vaginal delivery (labor group) or elective cesarean delivery (non-labor group).Results: Compared with the non-labor group, I-FABP, SOD, and Gpx levels were significantly higher in the labor group. I-FABP concentration was inversely correlated with pH and BE and positively correlated with SOD and Gpx concentrations, second stage of labor duration, and active pushing time.Conclusions: This study demonstrates that oxidative stress at birth and prolonged second stage of labor may lead to the intestinal injury, which is reflected in increased serum concentration of I-FABP. [ABSTRACT FROM AUTHOR]

In the past 15 years, multiple clinical studies have identified a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). With some variability, most of these studies indicate that up to one-third of all cases of NEC involving very low-birth weight infants may occur within 24-48h after receiving a RBC transfusion. There is also evidence that the risk of such transfusion-associated NEC may be higher in infants transfused with the greatest severity of anemia. In this article, we summarize the clinical evidence pertaining to these issues; specifically, the contribution of RBC transfusions, and the contribution of severity of underlying anemia, to the pathogenesis of a type of NEC potentially termed, "transfusion/anemia-associated NEC." [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is the most toxic mycotoxin contaminant, which is widely present in crops and poses a major safety hazard to animal and human health. To alleviate the cytotoxic effects of AFB1 on the intestine, we tested the protective effects of porcine β-defensin-2 (pBD-2). Results demonstrated that pBD-2 inhibited oxidative stress induced by AFB1 via decreasing the levels of ROS and enhancing the expression of antioxidant factors SOD-2 and NQO-1. In addition, pBD-2 attenuated AFB1-induced intestinal porcine epithelial cell line-J2 (IPEC-J2) injury through blocking mitochondria-mediated apoptosis. In vivo, pBD-2 treatment restored the intestinal mucosal structure and reduced the expression levels of apoptosis factors caspase-3 and Bax/Bcl-2. In conclusion, these results indicated that pBD-2 can alleviate AFB1-induced intestinal mucosal injury by inhibiting oxidative stress and mitochondria-mediated apoptosis. This study provides an effective strategy in developing pBD-2 as green feed additive to prevent AFB1 damage to animals. • Effects of pBD-2 on AFB1-induced intestinal mucosal injury were evaluated. • pBD-2 inhibited oxidative stress on AFB1-induced intestinal mucosal injury. • pBD-2 inhibited apoptosis on AFB1-induced intestinal mucosal injury. • pBD-2 can restore AFB1-induced intestinal mucosal structural damage. [ABSTRACT FROM AUTHOR]

Dachaihu decoction (DCH), a classic formula for Yangming and Shaoyang Syndrome Complex recorded in "Treatise on Cold Damage", has been widely used in treating intestinal disorders and inflammatory diseases with few side effects in China. However, the mechanism of DCH on septic intestinal injury (SII) remains to be explored. This study aimed to clarify the mechanism of DCH on SII. SII model of rat, established by cecal ligation and puncture (CLP), was used to study the effect of DCH on SII. 24 h mortality was recorded. Histological changes were observed by H&E staining. The expression of tight junction protein ZO-1 (ZO-1) and mucin2 (MUC2) was determined by immunohistochemical analysis. Secretory IgA (sIgA), diamine oxidase (DAO) and intestinal fatty acid binding protein (iFABP) were determined by enzyme-linked immunosorbent assay (ELISA). IL-1β, IL-6 and TNF-α were measured by ELISA and quantitative Real-time PCR (RT-qPCR). The gut microbiota was analyzed by 16S rRNA sequencing. The potential targets and pathways of DCH in treating SII were analyzed by integrative analysis of transcriptomic and metabolomic methods. Total glutathione (T-GSH), GSH, GSSG (reduced form of GSH), GSH peroxidase (GPX), superoxide dismutase (SOD), malonaldehyde (MDA) and indicators of hepatic and renal function were measured by biochemical kits. Medium dose of DCH improved 24 h mortality of SII rats, reduced the pathological changes of ileum, and increased the expression levels of ZO-1, MUC2 and sIgA. DCH decreased DAO, iFABP of serum and IL-1β, IL-6, TNF-α of ileum. DCH improved α- and β-diversity and modulated the structure of gut microbiota, with Escherichia_Shigella decreased and Bacteroides and Ruminococcus increased. GSH metabolism was identified as the key pathway of DCH on SII by integrative analysis of transcriptome and metabolome. GSH/GSSG and the most common indicators of oxidative stress, were validated. Antioxidative T-GSH, GSH, GPX and SOD were increased, while MDA, the mark of lipid peroxidation was downregulated by DCH. Eventually, DCH was proved to be safe and hepato- and nephro-protective. DCH ameliorated septic intestinal injury possibly by modulating the gut microbiota and enhancing glutathione metabolism of SII rats, without hepatotoxicity and nephrotoxicity. [Display omitted] • The intestine is the prior target and "motor" of sepsis. • DCH increased ileum ZO-1, muc2, sIgA and decreased inflammatory cytokines of septic intestinal injury (SII) of rats. • DCH modulated the gut microbiota of SII rats. • The underlying mechanism might be enhanced GSH metabolism as revealed by joint analysis of transcriptomics and metabolomics. [ABSTRACT FROM AUTHOR]

Intestinal barrier dysfunction often exists in the heat stroke (HS) pathological process, which increases intestinal permeability and induces endotoxemia. The upregulation of MLCK is a crucial player affecting intestinal permeability. This study aimed to explore whether inhibiting myosin light chain kinase (MLCK) can improve HS-induced intestinal injury in rats. Twelve-week-old Wistar male rats were divided into three groups: the control group, the HS model group, and the treatment group [HS model + ML-7 (MLCK inhibitor)]. HS impaired the tight junctions in the rat gut and increased permeability. Additionally, increased inflammatory factors in serum, activation of apoptosis, and downregulation of tight junction proteins were observed in intestinal cells. ML-7 significantly inhibited the MLCK/p-MLC2 signaling pathway, increased the expression of tight junction proteins, reduced intestinal permeability, reduced apoptosis and alleviated the intestinal damage caused by HS. ML-7 inhibited HS-induced apoptosis of intestinal epithelial cells by regulating the ERK/p38/HSP70 axis. Furthermore, inhibition of MLCK upregulated HSP70 expression through activation of the ERK pathway and inhibited cell apoptosis by abolishing the p38 MAPK pathway. In conclusion, inhibiting the MLCK/p-MLC2 signaling pathway reduces HS-induced intestinal permeability and protects the intestinal mucosal barrier. • Inhibiting myosin light chain kinase can improve HS-induced intestinal injury in rats. • Heat stress impaired the tight junction of the rat gut and increased permeability. • ML-7 could inhibit the heat stress apoptosis of intestinal epithelial cells by regulating the ERK/p38/HSP70 axis. [ABSTRACT FROM AUTHOR]

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin and possesses antioxidant and anti-inflammatory properties. The catabolism of C3G in the gastrointestinal tract could produce bioactive phenolic metabolites, such as protocatechuic acid, phloroglucinaldehyde, vanillic acid, and ferulic acid, which enhance C3G bioavailability and contribute to both mucosal barrier and microbiota. To get an overview of the function and mechanisms of C3G and its phenolic metabolites, we review the accumulated data of the absorption and catabolism of C3G in the gastrointestine, and attempt to give crosstalk between the phenolic metabolites, gut microbiota, and mucosal innate immune signaling pathways.

This study was aimed at investigating whether dietary copper/zinc-loaded montmorillonite (Cu/Zn-Mt) could alleviate Escherichia coli LPS-induced intestinal injury through pro- and anti-inflammatory signaling pathways (TLRs, NLRs and TGF-β1) in weaned piglets. Eighteen 21-d-old pigs were randomly divided into three groups (control, LPS and LPS + Cu/Zn-Mt). After 21 d of feeding, pigs in the LPS group and LPS + Cu/Zn-Mt group received i.p. administration of LPS, whereas pigs in the control group received saline. At 4 h post-injection, jejunum samples were collected for analysis. The results indicated that, compared with the LPS group, supplemental Cu/Zn-Mt increased transepithelial electrical resistance, the expressions of anti-inflammatory cytokines (TGF-β1) in mRNA and protein levels, and decreased FD4 and the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8 and IL-1β). The pro-inflammatory signaling pathways results demonstrated that Cu/Zn-Mt supplementation decreased the mRNA levels of TLR4 and its downstream signals (MyD88, IRAK1, TRAF6) but had no effect on NOD1 and NOD2 signals. Cu/Zn-Mt supplementation did not affect NF-κB p65 mRNA abundance, but down-regulated its protein expression. The anti-inflammatory signaling pathways results showed supplemental Cu/Zn-Mt also increased TβRII, Smad4 and Smad7 mRNA expressions. These findings suggested dietary Cu/Zn-Mt attenuated LPS-induced intestinal injury by alleviating intestinal inflammation, influencing TLR4-MyD88 and TGF-β1 signaling pathways in weaned pig. [ABSTRACT FROM AUTHOR]

Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2-/-) mice and wild-type (Nrf2+/+) C57BL/6J mice following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout promoted the survival of irradiated mice, protected the crypt-villus structure of the small intestine, and elevated peripheral blood lymphocyte count and thymus coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of intestinal epithelial cells (IECs) of irradiated Nrf2-/- mice were decreased. Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells including Ki67+ transient amplifying cells, Villin+ enterocytes, and lysozyme+ Paneth cells. Nuclear factor-κB (NF-κB) was accumulated in the crypt base nuclei of the small intestine, and the mRNA expression of NF-κB target genes Bcl-2, uPA, and Xiap of the small intestine from irradiated Nrf2-/- mice were increased. Collectively, Nrf2 knockout has the protective effect on small intestine damage following abdominal irradiation by prompting the proliferation and differentiation of Lgr5+ intestinal stem cells and activation of NF-κB. [ABSTRACT FROM AUTHOR]

Heparanase, a heparan sulfate (HS)–specific endoglycosidase, plays an important role in inflammation and mediates acute pulmonary and renal injuries during sepsis. To explore its role in septic intestinal injury, a non-anticoagulant heparanase inhibitor, N -desulfated/re- N -acetylated heparin (NAH), was administrated to a mouse sepsis model induced by cecal ligation and puncture (CLP). Immunohistochemical staining revealed massive shedding of HS from the intestinal mucosal surfaces after CLP, and effective inhibition of heparanase by NAH was confirmed by markedly reduced HS shedding. Following CLP, intestinal expression of heparanase was increased, whereas pretreatment with NAH reduced the sepsis-induced upregulation of heparanase expression. Meanwhile, CLP led to shedding of syndecan-1 and upregulated expression of proteases such as matrix metalloprotease-9 and urokinase-type plasminogen activator in the intestine, whereas NAH markedly suppressed syndecan-1 shedding and protease upregulation following CLP. In addition, pretreatment with NAH attenuated intestinal injury, inhibited neutrophil infiltration and suppressed the production of inflammatory cytokines (tumor necrosis factor–α, interleukin-1β, and interleukin-6) in the intestine during sepsis, and it also significantly reduced the elevation of inflammatory cytokines in the serum 24 hr after CLP. Our findings demonstrate that the activation of intestinal heparanase contributes to intestinal injury during early sepsis by facilitating the destruction of mucosal epithelial glycocalyx and promoting inflammatory responses. [ABSTRACT FROM AUTHOR]

Cytokines and growth factors play diverse roles in the uninflamed fetal/neonatal intestinal mucosa and in the development of inflammatory bowel injury during necrotizing enterocolitis (NEC). During gestational development and the early neonatal period, the fetal/premature intestine is exposed to high levels of many “inflammatory” cytokines and growth factors, first via swallowed amniotic fluid in utero and then, after birth, in colostrum and mother’s milk. This article reviews the dual, seemingly counter-intuitive roles of cytokines, where these agents play a “trophic” role and promote maturation of the uninflamed mucosa, but can also cause inflammation and promote intestinal injury during NEC. [ABSTRACT FROM AUTHOR]

Background: Acute necrotizing pancreatitis (ANP) is often complicated by multiple organ failure. The small intestine is frequently damaged during ANP. Capillary leakage in multiple organs during ANP is one of the most important causes of multiple organ dysfunction. Damage to the capillary endothelial barrier and impaired water transportation could lead to capillary leakage in ANP. Methods: Sprague–Dawley (SD) rats were randomized into a control group, the ANP group, the culture media treated group, or the bone marrow-derived mesenchymal stem cell (BMSC)-treated group (30 rats in each group). Ten rats in each group were sacrificed at 6, 12, and 24 h after induction of experimental models. Serum, ascites, pancreatic, and small intestinal samples were collected. The levels of serum and ascites albumin and amylases were measured, pancreatic histology was assessed, and the connection changes between vessel endothelial cells were evaluated using scanning electron microscopy (SEM). Capillary leakage in small intestinal tissue was observed visually by tracking fluorescein isothiocyanate (FITC)-albumin, and was measured by the Evans blue extravasation method. The location and expression of aquaporin 1 (AQP1) in the small intestine was analyzed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot. Results: The outcomes showed that the level of serum and ascites amylase is elevated. Conversely, the level of serum albumin is decreased while ascites albumin is elevated. There is damage to pancreatic tissue, and the small intestinal capillary endothelial barrier was aggravated. Furthermore, the expression of AQP1 was reduced significantly after induced ANP. Following treatment with MSCs, the elevation of amylase and the decrease of serum albumin were inhibited, the damage to pancreatic tissue and the level of small intestinal capillary leakage was alleviated, and the downregulation of AQP1 was reversed. Conclusions: In conclusion, MSC therapy could alleviate small intestinal injury in rats with ANP, the mechanism of which might be related to reduction of damage to the small intestinal capillary endothelial barrier, and increased expression of AQP1 in the small intestine. [ABSTRACT FROM AUTHOR]

Acute inflammatory injury is the primary cause of sepsis, leading to various organ failures. Bazedoxifene (BAZ) has been proven to have anti-inflammatory effects. However, its effects on sepsis-induced intestinal injury are unclear. Here, we demonstrated the beneficial effects of BAZ on intestinal injury and explored the underlying mechanisms using cecal ligation and perforation (CLP)-mediated sepsis mouse model and in vitro cultured intestinal epithelial MODE-K cells. We found that BAZ elevated the survival rate of septic mice and attenuated CLP-triggered intestinal damage. BAZ inhibited intestinal inflammation and restored the impaired intestinal barriers in CLP mice. The mechanistic study in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated MODE-K cells showed that BAZ significantly downregulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1β (IL-1β), caspase-1, and gasdermin D (GSDMD), and markedly reduced the phosphorylation of molecules in the nuclear factor kappa B (NF-κB) pathway. Moreover, BAZ prominently rescued the decreased viability of MODE-K cells and reduced lactate dehydrogenase (LDH) release upon LPS/ATP challenge. However, BAZ did not affect the inflammasome assembly, as evidenced by the lack of changes in ASC (apoptosis speck-like protein containing a CARD) speck formation. Our results suggest that BAZ relieves inflammation and intestinal barrier function disruption by suppressing the NF-κB/NLRP3 signaling pathways. Therefore, BAZ is a potential therapeutic candidate for treating intestinal injury in sepsis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether selenomethionine (SeMet) could attenuate intestinal injury in rabbits induced by ochratoxin A (OTA). Sixty 35-day-old IRA rabbits with similar weights were randomly assigned to the control group, OTA group (0.2 mg OTA/kg b.w), OTA+ 0.2 mg/kg Se (0.2 mg OTA/kg b.w + 0.2 mg SeMet/kg feed), OTA+ 0.4 mg/kg Se (0.2 mg OTA/kg b.w + 0.4 mg SeMet/kg feed) and OTA+ 0.6 mg/kg Se (0.2 mg OTA/kg b.w + 0.6 mg SeMet/kg feed). The rabbits were examined after oral administration of different doses of SeMet for 21 days and were intragastrically administered OTA for 7 consecutive days. The results showed that pretreatment with different doses of SeMet protected against the changes in serum biochemical indicators and the decline in production performance caused by OTA exposure. In addition, the activities of SOD, GSH-PX and T-AOC were significantly increased, and the levels of MDA and ROS were decreased after SeMet pretreatment; thus, oxidative damage in rabbit jejunum tissue due to OTA exposure was inhibited. SeMet stimulates Nrf2 and inhibits the NF-κB signalling pathway; the anti-inflammatory response and antioxidative stress in rabbits were improved, and the intestinal barrier damage caused by OTA exposure was improved. In summary, SeMet alleviates OTA-induced intestinal toxicity in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation. Moreover, 0.4 mg/kg SeMet induced the most significant improvement. • Selenomethionine (SeMet) improves the production performance and serum biochemical indices in ochratoxin A (OTA)-exposed rabbits. • SeMet improves intestinal morphology and intestinal cell proliferation in OTA-exposed rabbits. • SeMet alleviates intestinal mucosal inflammation and mucosal oxidative stress in OTA-exposed rabbits. • SeMet alleviates OTA-induced intestinal toxicity in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation. Moreover, 0.4 mg/kg SeMet induced the most significant improvement. [ABSTRACT FROM AUTHOR]

The production and application of nanoplastics has been increased during decades, and the enterotoxicity caused by their bioaccumulation has attracted vast attention. Maltol was proved to exert a protective effect on gut damage induced by carbon tetrachloride and cisplatin, indicating its confrontation with nanoplastics-induced intestinal toxicity. To explore the ameliorative effects of maltol on polystyrene nanoplastics (PS)-mediated enterotoxicity and the underlying mechanism, the mice were exposed to PS (100 mg/kg), combining with or without the treatment of maltol treatment at 50 and 100 mg/kg. We found PS exposure caused intestinal barrier damage and enterocyte apoptosis, while lysosomal dysfunction and autophagic substrate degradation arrest in enterocytes of mice were also observed. In addition, PS exacerbated the disturbance of the intestinal microbial community, affected the abundance of lysosome and apoptosis-related bacterial genes, and decreased the number of known short-chain fatty acid (SCFA) producing bacteria. However, those alterations were improved by the maltol treatment. Maltol also protected the human intestinal Caco-2 cells from PS-induce damages. Mechanistic studies showed maltol promoted TFEB nuclear translocation through the AMPK/mTOR signaling pathway to restore lysosomal function and reduce autophagy dependent apoptosis. The findings in the present work might help to elucidate the potential molecular mechanisms of PS-induced enterotoxicity. For the first time to our knowledge, the protective effect of maltol on PS-induced intestinal injury was studied from multiple perspectives, which provided a potential therapeutic approach for diseases caused by environmental pollution. Molecular mechanism of maltol on signaling crosstalk in PS-induced intestinal injury. [Display omitted] • PS triggered autophagy-dependent apoptosis and lysosome dysfunction in the colon. • PS damaged the intestinal barrier and intestinal microbiota in mice. • Maltol might reduce PS-induced intestinal damage by targeting AMPK. [ABSTRACT FROM AUTHOR]

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H 2 O 2 )-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Objectives: Inflammatory bowel diseases (IBDs) are a multiple inflammatory status in small intestines and colon. Bromelain and Papain were cysteine proteases enzymes extracted from pineapple and papaya, and possess antioxidant and anti-inflammatory characteristics. Therefore, this comparative work aimed to examine the anti-inflammatory and antioxidant effect of bromelain and papain in intestinal inflammation of rats and to evaluate the most potent effect of both types of enzymes., Methods: Forty rats were used in this study (8 rats/group), G1: control group, G2: (Indo group) intestinal inflammation was induced by two doses of Indomethacin (7.5 mg/kg body weight) apart 24 h. G3: (Indomethacin + Bromelain) intestinal inflamed rats treated by oral dose of bromelain (1000 mg/kg/day). G4: (Indomethacin + Papain) intestinal inflamed rats treated by oral dose of papain (800 mg/kg/day). G5: (Indomethacin + Sulfasalazine) intestinal inflamed rats treated by oral dose of sulfasalazine (500 mg/kg/day). Oxidative stress and inflammatory markers were measured along with histological assessment., Results: Indomethacin-induced intestinal inflammation (in both Jejunum and Ileum) characterized by increased oxidative stress biomarkers: Xanthine oxidase, Catalase, Glutathione reductase, and Protein carbonyl and Inflammatory biomarkers: Tumor necrosis factor-α, Interleukin-10, Monocyte chemoattractant protein-1, Nuclear factor-kappa β, C-reactive protein, and Prostaglandin E2, as compared to control rats. On the other hand, administering either bromelain or Papain would effectively decrease symptoms of intestinal inflammation and modulate biomarkers of oxidative stress and pro-inflammatory cytokines., Conclusion: Comparing results revealed that bromelain showed the most potent protective effect and possesses an apparent role in protection against the development of intestinal inflammation., (Copyright: © International Journal of Health Sciences.)