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Introduction: Intestinal ischemia/reperfusion (I/R) injury is associated with high mortality and there is an unmet need for novel therapies. The intestinal expression of cyclooxygenase-2 (COX-2) increases rapidly after mesenteric I/R, but it is still a question of debate whether selective COX-2 inhibitors can mitigate I/R-induced gut injury. Here we aimed to compare the effect of celecoxib and rofecoxib, two selective COX-2 inhibitors, on intestinal I/R-induced injury in rats. Methods: Wistar rats were treated with celecoxib (10 and 100 mg/kg), rofecoxib (5 and 50 mg/kg), or vehicle for 8 days via gavage and then were subjected to sham operation or mesenteric I/R. Small intestinal inflammation and tissue damage were assessed by histology and quantification of inflammatory and tight junction proteins. The intestinal activity of COX enzymes was determined by a COX activity assay. Results: The higher dose of celecoxib reduced the I/R-associated increase in inflammatory mediators (myeloperoxidase, pentraxin 3, COX-2, interleukin-1β) and loss of tight junction proteins (claudin-1, occludin), whereas the lower dose of celecoxib was only marginally effective. However, even high-dose celecoxib failed to prevent the histological injury of the mucosa. In contrast to celecoxib, rofecoxib did not affect intestinal inflammation and injury at any of the tested doses. Neither celecoxib nor rofecoxib affected the I/R-induced changes of HO-1 and PPAR-γ, known off-targets of COX-inhibitors, but celecoxib increased the I/R-induced elevation of Bax/Bcl-2, a marker of apoptosis, whereas rofecoxib reduced the elevation of phospho-Akt. Importantly, high-dose celecoxib, but not rofecoxib, has already reduced intestinal COX-1 activity. Conclusion: Our study provides evidence for the higher anti-inflammatory efficacy of celecoxib compared to rofecoxib in mesenteric I/R injury, which is likely due to its lower selectivity for COX-2. However, even high-dose celecoxib was unable to reduce the mucosal damage. Our results suggest that selective COX-2 inhibitors have only limited therapeutic value in intestinal I/R injury. [ABSTRACT FROM AUTHOR]

Background: Mucormycosis is a highly lethal opportunistic fungal disease caused by ubiquitous molds of the order Mucorales, with Rhizopus, Lichtheimia and Mucor being the most common genera. This rare disease primarily affects immunocompromised patients, with presentations ranging from rhino-orbito-cerebral infections to disseminated mucormycosis with angioinvasion, leading to thrombosis and tissue infarction. Gastrointestinal mucormycosis is the least common clinical presentation and is believed to be secondary to spore ingestion. It can involve multiple components of the gastrointestinal tract, such as the stomach, liver, ileum, and colon, with nonspecific manifestations, including pain, nausea, vomiting, and abdominal distension. The initial clinical presentation may even manifest as gastrointestinal bleeding due to gastric ulceration or intestinal perforation. Case presentation: Here we present the case of a 48-year-old male patient with a 9-year history of human immunodeficiency virus (HIV) infection who was hospitalized in the context of febrile neutropenia and whose acute respiratory infection was documented; therefore, antibiotic treatment was initiated. However, due to persistent febrile peaks and peripheral blood showing documentation of multilineage cytopenias, a bone marrow biopsy was performed, compatible with presenting features of marrow myelodysplasia. During hospitalization, the patient presented left flank abdominal pain, and an abdominal computed tomography (CT) scan revealed signs of intussusception of a small bowel loop at the distal jejunum level, leading to intestinal obstruction with ischemic progression, requiring ileectomy (60 cm). Histopathological analysis of the resected intestine revealed severe transmural ischemic changes associated with venous thrombosis due to fungal structures, with histochemical studies demonstrating the presence of zygomycete (Mucor) fungal structures, leading to the initiation of treatment with amphotericin B. However, despite treatment, the patient experienced progressive clinical deterioration with persistent fever and ventilatory failure, with follow-up tests showing absolute neutropenia and blood cultures positive for yeast, leading to death 52 days after admission. Conclusions: The diagnosis of intestinal mucormycosis may be delayed due to the lack of specificity of the signs and symptoms. Pathologists as well as histopathological studies are essential for timely treatment. [ABSTRACT FROM AUTHOR]

Intestinal ischemia/reperfusion injury (I/R) is a common yet challenging-to-treat condition, presenting a significant clinical challenge. This study aims to investigate the protective mechanisms of Dexmedetomidine (Dex) against I/R injury, with a particular focus on its role in regulating autophagy activity in intestinal neurons and maintaining mitochondrial homeostasis. Experimental findings demonstrate that Dex can mitigate intestinal damage induced by I/R through the modulation of autophagy activity and mitochondrial function in intestinal neurons by suppressing the expression of Nupr1. This discovery sheds light on a new molecular mechanism underlying the potential efficacy of Dex in treating intestinal I/R injury, offering valuable insights for clinical therapy. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: A congenital defect known as intestinal malrotation, which has only rarely been described in adults, is most frequently identified in children. For life-threatening consequences, such as intestinal ischemia and death, to be avoided, prompt detection is essential. We report a rare case of adult intestinal malrotation to emphasize the difficulty in diagnosis and surgical treatment. Case Report: An 18-year-old Saudi woman presented with generalized, gradually intermittent abdominal pain accompanied by nausea, and non-bilious vomiting. An abdominal computed tomography (CT) scan showed that the smallbowel loops were identified at the right side of the abdomen with the duodenojejunal junction at the right side or just right paramedian level as well, the superior mesenteric artery and vein had an inverted relationship, and the cecum was observed in the left lumber region. She was treated by open exploratory laparotomy adhesiolysis, the cecum was mobilized, the small-bowel adhesion under the liver was released, and an appendectomy was carried out. Postoperatively, she was managed with a double antibiotic regimen of ceftriaxone and metronidazole for 7 days. Conclusions: Although intestinal malrotation is uncommon in adults and very difficult to identify, it is frequently encountered in young populations. Adults with long history of vague or unexplained abdominal pain should undergo radiological studies to assess findings of intestinal malrotation. In our case, the result of a CT scan helped to make the diagnosis preoperatively. [ABSTRACT FROM AUTHOR]

Background: Nonocclusive mesenteric ischemia (NOMI) is characterized by intestinal ischemia caused by spasms in the peripheral intestinal vessels without organic obstruction in the main mesenteric vessels. NOMI can be fatal in case of delayed diagnosis and treatment. Although the use of indocyanine green (ICG) fluorescence in assessing intestinal viability during NOMI surgery is well recognized, there is a paucity of reported cases using this technique. Herein, we present a case of NOMI that was successfully managed through accurate diagnosis and resection of the ischemic intestines guided by ICG fluorescence. Case presentation: An 81-year-old man presented with abdominal pain. Contrast-enhanced computed tomography revealed intrahepatic portal vein gas, superior mesenteric vein gas, and terminal ileal edema. Considering these findings, the patient was diagnosed with NOMI and emergency surgery was performed. Intestinal edema was observed 30 cm upstream of the terminal ileum without serosal discoloration. ICG fluorescence revealed areas of normal perfusion as well as mild and moderate hypoperfusion. The small bowel, including the hypoperfusion area, was resected. As no clinical signs of residual bowel ischemia were observed during the postoperative course, a second-look operation was deemed unnecessary. Intraoperative ICG fluorescence and histopathological findings indicated mucosal edema in the mildly hypoperfused area and mucosal necrosis in the moderately hypoperfused area. Conclusions: This case highlights the use of intraoperative ICG fluorescence in the disease. ICG fluorescence is invaluable in assessing the extent of bowel ischemia and guiding precise resection. Thus, future efforts should focus on identifying accumulation of cases and quantification of ICG fluorescence intensity to further improve diagnostic performance. [ABSTRACT FROM AUTHOR]

Background: Examining small bowel loops within the peritoneal cavity poses significant challenges because of their length and overlapping nature. Aims and Objectives: This study aimed to evaluate the utility of computed tomography enteroclysis (CTE) in diagnosing small intestinal diseases and to understand its clinical application. Materials and Methods: The study was conducted from November 2019 to October 2021 in 30 patients undergoing CTE treatment. The day before treatment, bowel preparation included a low-residue diet, lots of fluids, an overnight fast of 8-12 h, and laxatives. A 16-slice Aquilion Lightning computed tomography (CT) scanner was used in general hospitals, and a 128-slice GE Healthcare helical CT scanner was used in multispecialty hospitals. Results: Among the 30 patients, 20 (66.7%) were male, and 10 (33.3%) were female, predominantly aged between 30 and 60 years old. Positive findings were noted in 23 patients (76.7%), including intestinal tuberculosis, inflammatory bowel disease, small bowel obstruction, and neoplastic lesions. Various small intestinal pathologies, such as non-specific edema, intussusception, and ischemic bowel disease, were also identified. Conclusion: This raises the standard of current small bowel imaging by delivering suitable intestinal distension using the enteral volume challenge principle and helps identify and characterize small-bowel problems. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Patients with a history of persistent mesenteric ischemia should not undergo laparoscopy. Mesenteric ischemia must be kept in mind for patients who develop nonspecific abdominal symptoms following laparoscopic surgeries. During laparoscopic cholecystectomy (LC), the rise in Intra‐Abdominal Pressure due to carbon dioxide insufflation can reduce blood flow through splanchnic vessels, potentially leading to intestinal ischemia. A 72‐year‐old woman with a history of diabetes, hypertension, ischemic heart disease, and hyperlipidemia underwent LC. She was discharged but readmitted 4 days later due to peritonitis. Ischemic jejunum loops were found during surgery. [ABSTRACT FROM AUTHOR]

Purpose: Ischemic colitis appears to be a rare but serious complication of COVID-19. About 33.3% hospitalized COVID-19 patients who underwent endoscopy showed features resembling ischemic colitis. The aim of this prospective study was to describe the symptoms, treatment, and outcomes of these patients, particularly their colonoscopy and histologic findings. Patients and methods: We conducted a prospective study on ischemic bowel disease associated with COVID-19 across four centers from December 2022 to January 2023. All cases were identified through a comprehensive search of electronic medical records for procedure-related data. The initial diagnosis of ischemic bowel disease was confirmed using colonoscopy and biopsy findings. After the patients were discharged, a 12-month follow-up was conducted through regular phone interviews to assess their clinical outcomes. Results: Overall, the study included 3 male patients and 9 female patients (age range, 33– 76 years). Abdominal pain and hematochezia always occurred within 2 weeks after COVID-19 infection (average 5.5 days). Gastrointestinal manifestations did not parallel the severity of COVID-19 infection. The descending colon was the most susceptible segment, which was involved in 10 patients (83.33%). Colonoscopy revealed diffuse redness, edema, bleeding, erosion, and ulceration of the intestinal mucosa, similar to the findings of ischemic colitis, and biopsy revealed crypt atrophy, reduction, and interstitial bleeding. All patients were self-limited without converting to chronic changes in the next 12 months. Conclusion: SARS-CoV-2 infection may induce transient acute colon ischemia within 2 weeks, accompanied by severe clinical symptoms such as acute abdominal pain and hematochezia, which are self-limiting and do not lead to chronic symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Mucormycosis is a highly lethal opportunistic fungal disease caused by ubiquitous molds of the order Mucorales, with Rhizopus, Lichtheimia and Mucor being the most common genera. This rare disease primarily affects immunocompromised patients, with presentations ranging from rhino-orbito-cerebral infections to disseminated mucormycosis with angioinvasion, leading to thrombosis and tissue infarction. Gastrointestinal mucormycosis is the least common clinical presentation and is believed to be secondary to spore ingestion. It can involve multiple components of the gastrointestinal tract, such as the stomach, liver, ileum, and colon, with nonspecific manifestations, including pain, nausea, vomiting, and abdominal distension. The initial clinical presentation may even manifest as gastrointestinal bleeding due to gastric ulceration or intestinal perforation. Case presentation Here we present the case of a 48-year-old male patient with a 9-year history of human immunodeficiency virus (HIV) infection who was hospitalized in the context of febrile neutropenia and whose acute respiratory infection was documented; therefore, antibiotic treatment was initiated. However, due to persistent febrile peaks and peripheral blood showing documentation of multilineage cytopenias, a bone marrow biopsy was performed, compatible with presenting features of marrow myelodysplasia. During hospitalization, the patient presented left flank abdominal pain, and an abdominal computed tomography (CT) scan revealed signs of intussusception of a small bowel loop at the distal jejunum level, leading to intestinal obstruction with ischemic progression, requiring ileectomy (60 cm). Histopathological analysis of the resected intestine revealed severe transmural ischemic changes associated with venous thrombosis due to fungal structures, with histochemical studies demonstrating the presence of zygomycete (Mucor) fungal structures, leading to the initiation of treatment with amphotericin B. However, despite treatment, the patient experienced progressive clinical deterioration with persistent fever and ventilatory failure, with follow-up tests showing absolute neutropenia and blood cultures positive for yeast, leading to death 52 days after admission. Conclusions The diagnosis of intestinal mucormycosis may be delayed due to the lack of specificity of the signs and symptoms. Pathologists as well as histopathological studies are essential for timely treatment.

Aim: The objective of the study was to assess the impact of ozone (O3) and trimetazidine on the intestines following ischemia–reperfusion (I/R) injury through the investigation of endoplasmic reticulum stress. Methods: Forty Sprague Dawley rats were separated into five groups. The groups were named as follows: control, O3, I/R, I/R + trimetazidine (TMZ), and I/R + O3. The control group had laparotomy and exploration of the superior mesenteric artery (SMA) only. Furthermore, alongside laparotomy and SMA exploration, an intraperitoneal (i.p.) administration of a 0.7 mg/kg ozone–oxygen (O3-O2) combination was given to the O3 group. In the experimental groups, the SMA was blocked with the silk suture ligation technique for a duration of 1 h and then restored to normal blood flow for another hour. In the I/R + O3 group, ozone was delivered i.p. at a dosage of 0.7 mg/kg, 30 min after ischemia. In the I/R + TMZ group, a dose of 20 mg/kg/day of trimetazidine was administered orally via gavage for a duration of 7 days, beginning 1 week prior to the induction of ischemia. Intestinal tissues were taken to assess indicators of intestinal mucosal injury and oxidative stress. Results: The level of the lipid peroxidation marker malondialdehyde (MDA) was significantly reduced in the experimental groups as compared to the I/R group (p < 0.05). The experimental groups had considerably greater levels of glutathione (GSH), which reflects antioxidant capacity, compared to the I/R group (p < 0.05). Nevertheless, the concentration of GSH was observed to be increased in the I/R + O3 group in comparison to the I/R + TMZ group (p < 0.05). The histopathological damage score showed a substantial decrease in the experimental groups as compared to the I/R group (p < 0.05). The I/R + O3 group had the lowest injury score. The experimental groups exhibited significantly reduced positivity of the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78 compared to the I/R group (p < 0.05). Conclusions: The findings provide evidence for the potential advantages of utilizing ozone therapy in the treatment of intestinal ischemia–reperfusion injury. Additionally, they propose that ozone should be assessed in more extensive clinical trials in the future as a therapeutic agent that can disrupt endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

The irreversible pan‐HER tyrosine kinase inhibitor neratinib is approved for patients with HER2‐positive, early‐stage and metastatic breast cancer (BC). Neratinib‐associated diarrhea is the most common reason for early discontinuation. Preclinical studies identified mechanisms of neratinib‐induced diarrhea and rationale for prophylactic and preventive measures. We studied effects of neratinib on rat intestines and conducted a phase 2 study of colon pathogenesis in patients with HER2‐positive BC treated with neratinib (NCT04366713). Colon samples from female albino Wistar rats receiving neratinib or vehicle were examined for histopathological changes. Patients with HER2‐positive BC received neratinib 240 mg once daily for up to 1 year. Colonoscopy biopsies were collected at baseline and at Day 28 to identify changes consistent with rat pathologies. Rat colons were markedly altered in appearance, with similar short circuit currents (Isc) and responses to carbachol and forskolin. Mucosal barrier loss and/or significant increase in secretory propensity in neratinib‐ versus control‐treated animals were not seen. Two of four endpoint‐evaluable patients presented with mild pathological changes, largely comparable with the rat model. Preclinical evidence supports an inflammatory component of neratinib‐induced diarrhea without mucosal barrier function loss. Colonoscopy findings in patients with BC indicate mild or no pathological changes in the colon due to neratinib treatment. [ABSTRACT FROM AUTHOR]

We present a case of a 60-year-old male with known seropositive rheumatoid arthritis and cerebral vasculitis who presented to the emergency room with abrupt onset lower back and abdominal pain. The patient developed peritonitis which led to an abdominal laparotomy where jejunal ischemia, necrosis, and perforation were found, requiring bowel resection. On pathology examination, the patient had mesenteric vessel intramural inflammation indicative of vasculitis. He developed an anastomotic leak on postoperative Day 4 and elected hospice care. A high index of suspicion for mesenteric vasculitis should be considered in patients presenting with abdominal pain in the setting of known rheumatoid arthritis associated vasculitis, especially patients with long-standing rheumatoid arthritis. The high mortality represented by gastrointestinal involvement in rheumatoid arthritis associated vasculitis warrants investigation in high-risk patients, despite its low prevalence. Treatment may consist of high-dose corticosteroids, immunosuppressive agents, biologic therapies that target the underlying autoimmune process, and in severe cases, bowel resection. [ABSTRACT FROM AUTHOR]

Ischemic bowel disease is considered a high‐risk factor for infection from anaerobic bacteria, as the ischemic bowel is the perfect ground for their development. Herein, we present the case of an advance stage colon cancer patient with a rare cause of gastrointestinal bleeding and bacteremia due to Clostridium paraputrificum, a rare anaerobic Gram‐positive bacterium. The patient had presented with several episodes of hematochezia in the context of chronic superior mesenteric‐portal vein tumor thrombosis and rupture of ectopic varices, and the bacteremia was an unexpected complication of the bowel ischemia due to a combination of arterial ischemia and venous congestion. [ABSTRACT FROM AUTHOR]

The flavonoid-rich fraction of bergamot juice (BJe) has demonstrated anti-inflammatory and antioxidant activities. The aim of work was to test the beneficial effects of BJe on the modulation of the ileum inflammation caused by intestinal ischemia/reperfusion (I/R) injury in mice. To understand the cellular mechanisms by which BJe may decrease the development of intestinal I/R injury, we have evaluated the activation of signaling transduction pathways that can be induced by reactive oxygen species production. Superior mesenteric artery and celiac trunk were occluded for 30 min and reperfused for 1 h. The animals were sacrificed after 1 h of reperfusion, for both histological and molecular examinations of the ileum tissue. The experimental results demonstrated that BJe was able to reduce histological damage, cytokines production, adhesion molecules expression, neutrophil infiltration and oxidative stress by a mechanism involved both NF-kB and MAP kinases pathways. This study indicates that BJe could represent a new treatment against inflammatory events of intestinal I/R injury. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of D-dimer, platelet-lymphocyte rate (PLR) and CT signs for intestinal ischemia in patients with bowel obstruction. Methods: We retrospectively analyzed the clinical and imaging data of 105 patients diagnosed with bowel obstruction, and performed univariate and multivariate analyses to determine the independent risk factors for intestinal ischemia in patients with bowel obstruction. Moreover, the receiver operating characteristic curve (ROC) was plotted to examine the diagnostic value of D-dimer, PLR and CT signs in patients with bowel obstruction. Besides, Kappa tests were used to assess inter-observer agreement. Results: We included 56 men (53%) and 49 women (47%) with mean age of 66.05 ± 16 years. Univariate and multivariate analyses showed that D-dimer, PLR and two significant CT signs (i.e., increased unenhanced bowel-wall attenuation and mesenteric haziness) were independent risk factors for intestinal ischemia in patients with bowel obstruction. ROC analysis showed that the combined use of D-dimer, PLR and the said two CT signs had better performance than single indicators in predicting intestinal ischemia in patients with bowel obstruction. The area under the curve (AUC) of the joint model III was 0.925 [95%CI: 0.876–0.975], with a sensitivity of 79.2% [95CI%: 67.2–91.1] and a specificity of 91.2% [95%CI: 83.7–98.9]. Conclusion: The combined use of D-dimer, PLR and CT signs has high diagnostic value for intestinal ischemia in patients with bowel obstruction and will prompt surgical exploration to evaluate intestinal blood flow. [ABSTRACT FROM AUTHOR]

Objectives: Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury. Methods: Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR. Key findings: SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL. Conclusions: SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: Complex gastroschisis is a rare variant characterized by intrauterine closure of the abdominal defect, which can be accompanied by atresia, necrosis, and, in most cases, lead to short bowel syndrome. This is the first case of gastroschisis presenting as a whirl pattern of loops and raises suspicion of intestinal ischemia and atresia. Case Report: A newborn at 38 weeks of gestation with a prenatal diagnosis of complex gastroschisis presented with a whirl pattern of gastroschisis and jejunal atresia. The newborn was treated with staged closure of the defect and underwent a second surgical procedure for correction of jejunal atresia, with a successful outcome observed during 2 years of follow-up. Conclusion: Whirl pattern gastroschisis is a rare presentation of complex gastroschisis, and its diagnosis can be made prenatally, allowing for the preparation of medical and surgical management at birth. It is necessary to actively search for the presence of intestinal atresia or ischemia in this type of presentation. [ABSTRACT FROM AUTHOR]

Key Clinical Message Patients with a history of persistent mesenteric ischemia should not undergo laparoscopy. Mesenteric ischemia must be kept in mind for patients who develop nonspecific abdominal symptoms following laparoscopic surgeries. Abstract During laparoscopic cholecystectomy (LC), the rise in Intra‐Abdominal Pressure due to carbon dioxide insufflation can reduce blood flow through splanchnic vessels, potentially leading to intestinal ischemia. A 72‐year‐old woman with a history of diabetes, hypertension, ischemic heart disease, and hyperlipidemia underwent LC. She was discharged but readmitted 4 days later due to peritonitis. Ischemic jejunum loops were found during surgery.

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation. [ABSTRACT FROM AUTHOR]

Objective: Orchitis is a common reproductive disease of male animals, which has serious implications to human and animal reproduction. Additionally, phlorizin (PHN), a common polyphenol in apples and strawberries, has a variety of biological activities, including antioxidant, anti-inflammatory, anti-diabetic, and anti-aging activities. We aimed to determine the protective effects and potential mechanisms of PHN in lipopolysaccharide (LPS)-induced acute orchitis in mice. Method: After 21 days of PHN pretreatment, mice were injected with LPS to induce testicular inflammation, and then the changes of testicular tissue structure, expression of inflammatory factors, testosterone level, expression of testosterone-related genes, adhesion gene and protein expression were detected, and the structural changes in the intestinal flora after PHN treatment were further detected by 16SRNA. Result: Our results demonstrated that PHN treatment reduced LPS-induced testicular injury and body and testicular weight losses. The mRNA expression levels of pro-inflammatory cytokines-related genes and antioxidant enzyme activity were also decreased and elevated, respectively, by PHN administration; however, PHN treatment also reduced the LPS-induced decrease in testosterone levels in the testes. Additionally, further studies found that PHN increased the expression of marker proteins zonula occludens-1 (ZO-1) and occludin associated with the blood testosterone barrier compared with that in LPS treatment groups. To further examine the potential mechanisms of the protective effect of PHN on LPS-induced testicular injury, we compared the differences of gut microbiota compositions between the 100mg/kg PHN treatment group and the control group using 16SRNA. Metagenomic analyses indicated that the abundances of Bacteroidetes, Muribaculaceae, Lactobacillaceae, uncultured bacterium f Muribaculaceae, and Lactobacillus in the PHN treatment group improved, while potential microbes that can induce intestinal diseases, including Verrucomicrobia, Epsilonbacteraeota, Akkermansiaceae, and Akkermansia decreased in the PHN treatment group. Conclusion: Our results indicate that PHN pretreatment might alleviate orchitis by altering the composition of gut microflora, which may provide a reference for reducing the occurrence of acute orchitis in male animals. [ABSTRACT FROM AUTHOR]

Introduction: Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms. Methods: To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation. Results: Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats. Discussion: Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats. [ABSTRACT FROM AUTHOR]

Exposure to passive heat (acclimation) and exercise under hot conditions (acclimatization), known as heat acclimation (HA), are methods that athletes include in their routines to promote faster recovery and enhance physiological adaptations and performance under hot conditions. Despite the potential positive effects of HA on health and physical performance in the heat, these stimuli can negatively affect gut health, impairing its functionality and contributing to gut dysbiosis. Blood redistribution to active muscles and peripheral vascularization exist during exercise and HA stimulus, promoting intestinal ischemia. Gastrointestinal ischemia can impair intestinal permeability and aggravate systemic endotoxemia in athletes during exercise. Systemic endotoxemia elevates the immune system as an inflammatory responses in athletes, impairing their adaptive capacity to exercise and their HA tolerance. Better gut microbiota health could benefit exercise performance and heat tolerance in athletes. This article suggests that: (1) the intestinal modifications induced by heat stress (HS), leading to dysbiosis and altered intestinal permeability in athletes, can decrease health, and (2) a previously acquired microbial dysbiosis and/or leaky gut condition in the athlete can negatively exacerbate the systemic effects of HA. Maintaining or improving the healthy gut microbiota in athletes can positively regulate the intestinal permeability, reduce endotoxemic levels, and control the systemic inflammatory response. In conclusion, strategies based on positive daily habits (nutrition, probiotics, hydration, chronoregulation, etc.) and preventing microbial dysbiosis can minimize the potentially undesired effects of applying HA, favoring thermotolerance and performance enhancement in athletes. [ABSTRACT FROM AUTHOR]

Background: Severe acute pancreatitis (SAP) is an inflammatory disorder affecting the gastrointestinal system. Intestinal injury plays an important role in the treatment of severe acute pancreatitis. In this study, we mainly investigated the role of S1PR2 in regulating macrophage pyroptosis in the intestinal injury of severe acute pancreatitis. Methods: The SAP model was constructed us ing cerulein and lipopolysaccharide, and the expression of S1PR2 was inhibited by JTE-013 to detect the degree of pancreatitis and intestinal tissue damage in mice. Meanwhile, the level of pyroptosis-related protein was detected by western blot, the level of related mRNA was detected by PCR, and the level of serum inflammatory factors was detected by ELISA. In vitro experiments, LPS+ATP was used to construct the pyroptosis model of THP-1. After knockdown and overexpression of S1PR2, the pyroptosis proteins level was detected by western blot, the related mRNA level was detected by PCR, and the level of cell supernatant inflammatory factors were detected by ELISA. A rescue experiment was used to verify the sufficient necessity of the RhoA/ROCK pathway in S1PR2-induced pyroptosis. Meanwhile, THP-1 and FHC were cocultured to verify that cytokines released by THP-1 after damage could regulate FHC damage. Results: Our results demonstrated that JTE-013 effectively attenuated intestinal injury and inflammation in mice with SAP. Furthermore, we observed a significant reduction in the expression of pyroptosis-related proteins within the intestinal tissue of SAP mice upon treatment with JTE-013. We confirmed the involvement of S1PR2 in THP-1 cell pyroptosis in vitro. Specifically, activation of S1PR2 triggered pyroptosis in THP-1 cells through the RhoA/ROCK signaling pathway. Moreover, it was observed that inflammatory factors released during THP-1 cell pyroptosis exerted an impact on cohesin expression in FHC cells. Conclusion: The involvement of S1PR2 in SAP-induced intestinal mucosal injury may be attributed to its regulation of macrophage pyroptosis. [ABSTRACT FROM AUTHOR]

Introduction: Chyloperitoneum arises from lymph leakage into the abdominal cavity, leading to an accumulation of milky fluid rich in triglycerides. Diagnosis can be challenging, and mortality rates vary depending on the underlying cause, with intestinal volvulus being just one potential acute cause. Despite its rarity, our case series highlights chyloperitoneum associated with non-ischemic small bowel volvulus. The aims of our study include assessing the incidence of this association and evaluating diagnostic and therapeutic approaches. Material and Methods: We present two cases of acute abdominal peritonitis with suspected small bowel volvulus identified via contrast-enhanced computed tomography (CT). Emergency laparotomy revealed milky-free fluid and bowel volvulus. Additionally, we conducted a systematic review up to 31 October 2023, identifying 15 previously reported cases of small bowel volvulus and chyloperitoneum in adults (via the PRISMA scheme). Conclusions: Clarifying the etiopathogenetic mechanism of chyloperitoneum requires specific diagnostic tools. Magnetic resonance imaging (MRI) may be useful in non-emergency situations, while contrast-enhanced CT is employed in emergencies. Although small bowel volvulus infrequently causes chyloperitoneum, prompt treatment is necessary. The volvulus determines lymphatic flow obstruction at the base of the mesentery, with exudation and chyle accumulation in the abdominal cavity. Derotation of the volvulus alone may resolve chyloperitoneum without intestinal ischemia. [ABSTRACT FROM AUTHOR]

Acute mesenteric ischemia (AMI) is a rare medical-surgical emergency that must be treated early due to its high morbidity and mortality. It corresponds to a sudden interruption of the blood supply to a segment of the intestine, producing ischemia, cell damage, intestinal necrosis and eventually death if it is not treated. The main etiology of this condition is embolic-type arterial occlusion, followed by thrombotic, nonocclusive, and venous thrombotic. It is an infrequent pathology with a low incidence of 12 per 100,000 inhabitants in international series. During the information collection, no data was found on the Chilean population since before 1983. Its main symptom is colicky abdominal pain with a sudden onset, vomiting and diarrhea that begins after the pain. On physical examination, signs of shock and abdominal distention may be noted. Hemodynamically unstable patients should be urgently taken to exploratory laparotomy as soon as the condition is suspected, and in stable patients, an angio-CT should be requested to confirm the diagnosis and plan treatment. There are two methods to treat this pathology, open surgery and endovascular or minimally invasive surgery. The form of therapy depends on the preoperative or intraoperative findings and the type of etiology. Finally, with the advancement of these new methods, the mortality rate has decreased in the last decade. [ABSTRACT FROM AUTHOR]

Introduction. Paradoxical embolism is a thrombotic event originating in the venous circulation, which manifests as arterial embolism through an anatomical cardiac or pulmonary defect. It is mainly associated with stroke, also presenting as acute myocardial infarction, renal infarction, and other ischemic events. Clinical case. A 47-year-old patient was admitted due to abdominal pain, which required emergency surgical management, finding significant intestinal ischemia. Additional studies found protein S deficiency and evidence of a patent foramen ovale. Discussion. Arterial thrombosis is known as unusual thrombosis; this situation requires to rule out associated thrombophilia or other prothrombotic diseases. Protein S deficiency is a rare thrombophilia, which in adults causes venous thrombosis. In the presence of anatomical defects, such as a patent foramen ovale, it can progress to arterial embolism, presenting a picture of paradoxical embolism. The study work of these patients requires imaging that demonstrates the aforementioned defect, as well as the possible origin of the emboli. Management is based on full anticoagulation, treatment of existing thrombotic manifestations, and management of the anatomical defect. Conclusions. Paradoxical embolism should be suspected in case of unusual thrombosis. It requires exhaustive studies based on imaging, and management should consist of anticoagulation and closure of the defect. [ABSTRACT FROM AUTHOR]

Objective: Management of emergency care Background: Several factors have been reported as possible predictors of intestinal necrosis in patients with portal venous gas (PVG). We describe potential indicators of intestinal necrosis in PVG identified by contrasting 3 episodes of PVG in a patient on hemodialysis against previously verified factors. Case Report: An 82-year-old woman undergoing hemodialysis was admitted to our hospital thrice for acute abdominal pain. On first admission, she was alert, with a body temperature of 36.3°C, blood pressure (BP) of 125/53 mmHg, pulse rate of 60/min, respiratory rate of 18/min, and 100% oxygen saturation on room air. Computed tomography (CT) revealed PVG, intestinal distension, poor bowel wall enhancement, bubble-like pneumatosis in the intestinal wall, and minimal ascites. PVG caused by intestinal ischemia was diagnosed, and she recovered after bowel rest and hydration. Three months later, she had a second episode of abdominal pain. BP was 115/56 mmHg. CT revealed PVG and a slight accumulation of ascites, without pneumatosis in the intestinal wall. She again recovered after conservative measures. Ten months later, the patient experienced a third episode of abdominal pain, with BP of 107/52 mmHg. CT imaging indicated PVG, considerable ascites, and linear pneumatosis of the intestinal walls. Despite receiving conservative treatment, the patient died. 11 ILC3LII ICll vvaio. UCj^ILC I CL.CI VII Ig LUI I3CI VailVC LICaUIICIIL, LI IC paLICIIL UICU. Conclusions: A large accumulation of ascites and linear pneumatosis in the intestinal walls could be potential indicators of intestinal necrosis in patients with PVG caused by intestinal ischemia. As previously reported, hypotension was further confirmed to be a reliable predictor of intestinal necrosis. [ABSTRACT FROM AUTHOR]

Su (var) 3–9, enhancer of seste, trithorax (SET)-domain bifurcated histone lysine methyltransferase (SETDB1) plays a crucial role in maintaining intestinal stem cell homeostasis; however, its physiological function in epithelial injury is largely unknown. In this study, we investigated the role of SETDB1 in epithelial regeneration using an intestinal ischemia/reperfusion injury (IRI) mouse model. Jejunum tissues were sampled after 75 min of ischemia followed by 3, 24, and 48 h of reperfusion. Morphological evaluations were performed using light microscopy and electron microscopy, and the involvement of SETDB1 in epithelial remodeling was investigated by immunohistochemistry. Expression of SETDB1 was increased following 24 h of reperfusion and localized in not only the crypt bottom but also in the transit amplifying zone and part of the villi. Changes in cell lineage, repression of cell adhesion molecule expression, and decreased histone H3 methylation status were detected in the crypts at the same time. Electron microscopy also revealed aberrant alignment of crypt nuclei and fusion of adjacent villi. Furthermore, increased SETDB1 expression and epithelial remodeling were confirmed with loss of stem cells, suggesting SETDB1 affects epithelial cell plasticity. In addition, crypt elongation and increased numbers of Ki-67 positive cells indicated active cell proliferation after IRI; however, the expression of PCNA was decreased compared to sham mouse jejunum. These morphological changes and the aberrant expression of proliferation markers were prevented by sinefungin, a histone methyltransferase inhibitor. In summary, SETDB1 plays a crucial role in changes in the epithelial structure after IRI-induced stem cell loss. [ABSTRACT FROM AUTHOR]

Ischemic gut injury is common in the intensive care unit, impairs gut barrier function, and contributes to multiorgan dysfunction. One novel intervention to mitigate ischemic gut injury is the direct luminal delivery of oxygen microbubbles (OMB). Formulations of OMB can be modified to control the rate of oxygen delivery. This project examined whether luminal delivery of pectin-modified OMB (OMBp5) can reduce ischemic gut injury in a rodent model. The OMBp5 formulation was adapted to improve delivery of oxygen along the length of small intestine. Adult Sprague–Dawley rats (n = 24) were randomly allocated to three groups: sham-surgery (SS), intestinal ischemia (II), and intestinal ischemia plus luminal delivery of OMBp5 (II + O). Ischemia-reperfusion injury was induced by superior mesenteric artery occlusion for 45 min followed by reperfusion for 30 min. Outcome data included macroscopic score of mucosal injury, the histological score of gut injury, and plasma biomarkers of intestinal injury. Macroscopic, microscopic data, and intestinal injury biomarker results demonstrated minimal intestinal damage in the SS group and constant damage in the II group. II + O group had a significantly improved macroscopic score throughout the gut mucosa (P = 0.04) than the II. The mean histological score of gut injury for the II + O group was significantly improved on the II group (P ≤ 0.01) in the proximal intestine only, within 30 cm of delivery. No differences were observed in plasma biomarkers of intestinal injury following OMBp5 treatment. This proof-of-concept study has demonstrated that luminal OMBp5 decreases ischemic injury to the proximal small intestine. There is a need to improve oxygen delivery over the full length of the intestine. These findings support further studies with clinically relevant end points, such as systemic inflammation and vital organ dysfunction. [ABSTRACT FROM AUTHOR]

Intestinal ultrasound is a non-invasive, safe, and cost-effective technique to study the small and large intestines. In addition to conventional B-mode and color doppler imaging, new US tools have been developed in more recent years that provide auxiliary data on many GI conditions, improving the diagnosis and assessment of relevant outcomes. We have reviewed the more recent literature (from 2010 onwards) on auxiliary tools in bowel ultrasound such as elastography techniques, CEUS, SICUS, and the potential contribution by artificial intelligence (AI) to overcome current intestinal ultrasound limitations. For this scoping review, we performed an extensive literature search on PubMed and EMBASE to identify studies published until December 2023 and investigating the application of elastography techniques, CEUS, SICUS, and AI in the ultrasonographic assessment of the small and large intestines. Multiparametric intestinal ultrasound shows promising capabilities in Crohn's disease, while less is known about the role in ulcerative colitis. Despite some evidence, the CEUS role as a point-of-care examination tool for rare conditions such as intestinal GvHD and ischemic small bowel disease seems promising, possibly avoiding the need to perform further cross-sectional imaging. The use of AI in intestinal ultrasound is still anecdotical and limited to acute appendicitis. [ABSTRACT FROM AUTHOR]

Macrophages play key roles in tissue homeostasis, defense, disease, and repair. Macrophages are highly plastic and exhibit distinct functional phenotypes based on micro-environmental stimuli. In spite of several advancements in understanding macrophage biology and their different functional phenotypes in various physiological and pathological conditions, currently available treatment strategies targeting macrophages are limited. Macrophages' high plasticity and diverse functional roles—including tissue injury and wound healing mechanisms—mark them as potential targets to mine for efficient therapeutics to treat diseases. Despite mounting evidence on association of gut leakage with several extraintestinal diseases, there is no targeted standard therapy to treat gut leakage. Therefore, there is an urgent need to develop therapeutic strategies to treat this condition. Macrophages are the cells that play the largest role in interacting with the gut microbiota in the intestinal compartment and exert their intended functions in injury and repair mechanisms. In this review, we have summarized the current knowledge on the origins and phenotypes of macrophages. The specific role of macrophages in intestinal barrier function, their role in tissue repair mechanisms, and their association with gut microbiota are discussed. In addition, currently available therapies and the putative tissue repair mediators of macrophages for treating microbiota dysbiosis induced gut leakage are also discussed. The overall aim of this review is to convey the intense need to screen for microbiota induced macrophage-released prorepair mediators, which could lead to the identification of potential candidates that could be developed for treating the leaky gut and associated diseases. Intestinal macrophages are potential candidates to treat gut leakage. [ABSTRACT FROM AUTHOR]

In acute intestinal ischemia, the progression of ischemia varies across different layers of intestinal tissue. We established a mouse model and used swept‐source optical coherence tomography (OCT) to observe the intestinal ischemic process longitudinally in different tissue layers. Employing a method that combines asymmetric gradient filtering with adaptive weighting, we eliminated the vessel trailing phenomenon in OCT angiograms, reducing the confounding effects of superficial vessels on the imaging of deeper vasculature. We quantitatively assessed changes in vascular perfusion density (VPD), vessel length, and vessel average diameter across various intestinal layers. Our results showed a significant reduction in VPD in all layers during ischemia. The mucosa layer experienced the most significant impact, primarily due to disrupted capillary blood flow, followed by the submucosa layer, where vascular constriction or decreased velocity was the primary factor. [ABSTRACT FROM AUTHOR]

Background: We created and validated a computed tomography (CT)-based radiomic model using both clinical factors and the radiomic signature for assessing the strangulation risk of acute intestinal obstruction. This would assist surgeons in accurately predicting intestinal ischemia and strangulation in patients with intestinal obstruction. Methods: We recruited 289 patients with acute intestinal obstruction admitted in the Affiliated Hospital of Qingdao University from January 2019 to February 2022. The patients were allocated to a training (n = 226) and validation cohort (n = 63). Radiomic features were collected from CT images, and the radiomic signature was extracted and used to calculate a radiomic score (Rad-score). A nomogram was constructed using the clinical features and the Rad-score, and the performance of the clinical, radiomics, and nomogram models was assessed in the two cohorts. Results: Six robust features were used to construct the radiomic signature. The nomogram incorporating hemoglobin levels, C-reactive protein levels, American Society of Anesthesiologists score, time of obstruction, CT image of mesenteric fluid (P < 0.05), and the signature demonstrated good predictive ability for intestinal ischemia in patients with acute intestinal obstruction, with areas under the curve of 0.892 (95% confidence interval, 0.837–0.947) and 0.781 (95% confidence interval, 0.619–0.944) for the training and validation sets, respectively. The decision curve analysis showed that this model outperformed the clinical and radiomic signature models. Conclusion: The radiomic nomogram may effectively predict intestinal ischemia in patients with acute intestinal disease and may assist clinical decision-making.

A 71-year-old woman was admitted to the hospital after consuming food due to acute malnutrition and abdominal pain. Reduced patency of all jejunoileal branches and the superior mesenteric artery was observed in the abdominal computed tomography scan. Abdominal angina was caused by atherosclerosis, the frequent use of triptans for recurrent migraines, the JAK2 mutation, and a high platelet count. The patient's complete parenteral nutrition was not spared, despite the development of a collateral circulation preventing fatal acute ischemia. [ABSTRACT FROM AUTHOR]

Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGCs) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network density and glial activity were examined by Gene Set Enrichment Analysis, three-dimensional (3-D) volume imaging, and Western blot and its function in regulating epithelial restitution was assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate (FA), and in vitro by coculture assay. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Furthermore, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that the proximity of a specific functional population of EGC to wounded intestinal epithelium contributes to intestinal barrier restitution following ischemic injury. [ABSTRACT FROM AUTHOR]

Acute proximal superior mesenteric artery (SMA) occlusion is highly lethal, and adjuncts are needed to mitigate ischemic injury until definitive therapy. We hypothesized that raising mean arterial pressure (MAP) >90 mmHg with norepinephrine may delay irreversible bowel ischemia by increasing gastroduodenal artery (GDA) flow despite possible pressor-induced vasospasm. 12 anesthetized swine underwent laparotomy, GDA flow probe placement, and proximal SMA exposure and clamping. Animals were randomized between conventional therapy (CT) versus targeted MAP >90 mmHg (MAP push; MP) where norepinephrine was titrated after 45 min of SMA occlusion. Animals were followed until bowel death or 4 h. Kaplan–Meier bowel survival, mean normalized GDA flow, and histology were compared. 12 swine (mean 57.8 ± 7.6 kgs) were included, six per group. Baseline weight, HR, MAP and GDA flows were not different. Within 5 min following SMA clamping, all 12 animals had an increase in MAP without other intervention from 81.7 to 105.5 mmHg (29.1%, P < 0.01) with a concomitant 74.9% increase in GDA flow as compared to baseline (P < 0.01). Beyond 45 min postclamp, MAP was greater in the MP group as intended, as were GDA flows. Median time to irreversibly ischemic bowel was 31% longer for MAP push animals (CT: 178 versus MP: 233 min, P = 0.006), Hazard Ratio of CT 8.85 (95% CI: 1.86-42.06); 3/6 MP animals versus 0/6 CT animals with bowel survived to predetermined end point. In this swine model of acute complete proximal SMA occlusion, increasing MAP >90 mmHg with norepinephrine was associated with an increase in macrovascular blood flow through the GDA and bowel survival. Norepinephrine was not associated with worse bowel survival and a MAP push may increase the time window where ischemic bowel can be salvaged. [ABSTRACT FROM AUTHOR]

Owl monkeys are small nocturnal new world primates in the genus Aotus that are most used in biomedical research for malaria. Cardiomyopathy and nephropathy are well-described common diseases contributing to their morbidity and mortality; less is known about lesions affecting the gastrointestinal tract. Records from a 14-year period (2008-2022) at the Keeling Center for Comparative Medicine and Research were queried to identify instances of spontaneous gastrointestinal disease that directly contributed to the cause of death from the 235 adult owl monkeys submitted for necropsy. Of the 235, 10.6% (25/235) had gastrointestinal disease listed as a significant factor that contributed to morbidity and mortality. Diagnoses included candidiasis (3/25), gastric bloat (4/25), and intestinal incarceration and ischemia secondary (11/25), which included intussusception (4/25), mesenteric rent (3/25), strangulating lipoma (2/25), intestinal torsion (1/25), and an inguinal hernia (1/25). Intestinal adenocarcinomas affecting the jejunum (4/25) were the most common neoplasia diagnosis. Oral squamous cell carcinoma (1/25) and intestinal lymphoma (2/25) were also diagnosed. This report provides evidence of spontaneous lesions in the species that contribute to morbidity and mortality. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal ischemia and reperfusion (IIR) injury is closely associated with oxidative stress. Evidence shows that oral supplementation with glutamine and citrulline alleviates IIR-induced jejunal damage. We investigated the effects of a combination of glutamine, citrulline, and antioxidant vitamins on IIR-induced jejunal damage, oxidative stress, and inflammation. Method: Male Wistar rats that underwent 60 min of superior mesenteric artery occlusion were orally administered glutamine plus citrulline (GC), vitamin C plus E (CE), or a combination of GC and CE 15 min before and 3, 9, and 21 h after reperfusion. Healthy rats without IIR were used as controls. Results: After reperfusion for 24 h, rats with IIR showed lower levels of red blood cells, hemoglobin, serum glucose, and jejunal DNA and increased white blood cell counts compared to controls (1-way ANOVA with the least significant difference, P < 0.05). The IIR-induced decrease in serum albumin and increase in plasma interleukin-6 and jejunal thiobarbituric acid-reactive substances (TBARS) were significantly reversed by GC and/or CE. The results of the 2-way ANOVA indicated that GC was the main factor that increased jejunal villus height and muscularis DNA, and CE was the main factor that increased jejunal muscularis protein and decreased jejunal proinflammatory cytokine levels and myeloperoxidase activity. In addition, GC and CE are the main factors that decrease plasma proinflammatory cytokine levels and the jejunal apoptotic index. Conclusion: Oral post-treatment supplementation with glutamine and citrulline, combined with vitamins C and E, may alleviate IIR-induced oxidative stress, inflammation, and jejunal damage. [ABSTRACT FROM AUTHOR]

It is quite common for portal vein thrombosis to occur in subjects who present predisposing conditions such as cirrhosis, hepatobiliary malignancies, infectious or inflammatory abdominal diseases, or hematologic disorders. The incidence of idiopathic portal vein thrombosis in non-cirrhotic patients remains low, and despite the intensive workup that is performed in these cases, in up to 25% of cases, there is no identifiable cause. If portal vein thrombosis is untreated, complications arise and include portal hypertension, cavernous transformation of the portal vein, gastroesophageal and even small intestinal varices, septic thrombosis, or intestinal ischemia. However, intestinal ischemia develops as a consequence of arterial thrombosis or embolism, and the thrombosis of the mesenteric vein accounts for about 10% of cases of intestinal ischemia. Although acute superior mesenteric vein thrombosis can cause acute intestinal ischemia, its chronic form is less likely to cause acute intestinal ischemia, considering the possibility of developing collateral drainage. Ileus due to mesenteric venous thrombosis is rare, and only a small number of cases have been reported to date. Most patients experience a distinct episode of acute abdominal pain due to ischemia, and in the second phase, they develop an obstruction/ileus. Acute superior mesenteric venous thrombosis is a rare condition that is still associated with a high mortality rate. The management of such cases of superior mesenteric venous thrombosis is clinically challenging due to their insidious onset and rapid development. A prompt and accurate diagnosis followed by a timely surgical treatment is important to save patient lives, improve the patient survival rate, and conserve as much of the patient's bowel as possible, thus leading to fewer sequelae. [ABSTRACT FROM AUTHOR]

Intestinal ischemia‒reperfusion (I/R) injury is a common pathological process in patients undergoing gastrointestinal surgery, leading to local intestinal damage and increased microvascular permeability, eventually causing extraintestinal multiple organ dysfunction or sepsis. The NLRP3-mediated inflammatory response is associated with I/R injury. Methane saline (MS) has anti-pyroptosis properties. This study aims to explore the protective effect of MS on intestinal I/R injury and its potential mechanisms. After MS pretreatment, the in vivo model was established by temporarily clipping the mouse superior mesentery artery with a noninvasive vascular clamp, and the in vitro model was established by OGD/R on Caco-2 cells. The results of HE and TUNEL staining showed intestinal barrier damage after I/R injury, which was consistent with the IHC staining results of tight junction proteins. Moreover, the expression of the NLRP3 signaling pathway was increased after I/R injury, and inhibition of NLRP3 activation reduced Caco-2 cell injury, indicating that NLRP3-mediated pyroptosis was one of the main forms of cell death after I/R injury. Subsequently, we found that MS treatment ameliorated intestinal barrier function after I/R injury by suppressing NLRP3-mediated pyroptosis. MS treatment also reduced mitochondria-associated membrane (MAM) formation, which was considered to be a platform for activation of the NLRP3 inflammasome. Importantly, MS reduced ER stress, which was related to the PERK signaling pathway. Knocking down PERK, a key protein involved in ER stress and MAM formation, reversed the protective effect of MS, indicating that MS suppressed NLRP3 by reducing ER stress and MAM formation. In conclusion, we believe that MS suppresses MAMs and activation of the NLRP3 inflammasome by regulating the PERK signaling pathway to ameliorate intestinal I/R injury. [ABSTRACT FROM AUTHOR]

Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and mechanisms is of great importance to improve treatment outcomes. Apigenin-7-O-Glucoside (AGL) is a sugar derivative of apigenin natural product with various pharmacological activities to protect against intestinal diseases. In this study, we synthesized two amphiphilic molecules, namely DTPA-N10–10 and mPEG-TK-DA, which can scavenge free radicals and reactive oxygen species (ROS). They were successfully encapsulated AGL through self-assembly, resulting in the formation of multi-site ROS scavenging nanoparticles called PDN@AGL. In vitro and in vivo experiments demonstrated that PDN@AGL could protect intestinal tissues by reducing lipid peroxidation, lowering ROS levels and inhibiting ferroptosis during II/R injury. Furthermore, our study revealed, for the first time, that the regulation of the ATF3/SLC7A11 pathway by PDN@AGL may play a crucial role in mitigating II/R injury. In conclusion, our study confirmed the beneficial effects of PDN@AGL in combating II/R injury through the ATF3/SLC7A11-mediated regulation of ferroptosis and oxidative stress. These findings lay the groundwork for the potential application of PDN@AGL in the treatment of II/R injury. [Display omitted] • The multi-site ROS scavenging nanoparticle PDN@AGL for alleviate II/R injury was constructed. • PDN@AGL protects intestine by mitigating lipid peroxidation, reducing ROS and inhibiting ferroptosis during II/R injury. • PDN@AGL involves in ATF3/SLC7A11 signaling pathway which is crucial in combating II/R injury. • The biosafety of PDN@AGL prospects the potential clinical translation based on its superb treatment outcomes. [ABSTRACT FROM AUTHOR]

Mesenteric ischemia is a group of disorders requiring prompt identification, supportive care, and treatment. Chronic mesenteric ischemia can develop into acute mesenteric ischemia, which has high mortality. Acute mesenteric ischemia can be occlusive (caused by arterial embolism, arterial thrombosis, or mesenteric venous thrombosis) or nonocclusive, with treatment depending on the underlying cause. [ABSTRACT FROM AUTHOR]

Intestinal ischemia/reperfusion (I/R) injury is a life‐threatening condition with no effective treatment currently available. Curcumin (CCM), a polyphenol compound in Curcuma Longa, reportedly has positive effects against intestinal I/R injury. However, the mechanism underlying the protective effect of CCM against intestinal I/R injury has not been fully clarified. To determine whether the protective effect of CCM was mediated by epigenetic effects on Wnt/β‐catenin signaling, the effect of CCM was examined in vivo and in vitro. An intestinal I/R model was established in Sprague–Dawley (SD) rats with superior mesenteric artery occlusion, and Caco‐2 cells were subjected to hypoxia/reoxygenation (H/R) for in vivo simulation of I/R. The results showed that CCM significantly reduced inflammatory, cell apoptosis, and oxidative stress induced by I/R insult in vivo and in vitro. Western blot analysis showed that CCM preconditioning reduced the protein levels of β‐catenin, p‐GSK3β, and cyclin‐D1 and increased the protein level of GSK3β compared with the I/R group. Overexpressing β‐catenin aggravated H/R injury, and knocking down β‐catenin relieved H/R injury by improving intestinal permeability and reducing the cell apoptosis. Moreover, Naked cuticle homolog 2(NKD2) mRNA and protein levels were upregulated in the CCM‐pretreated group. 5‐aza‐2′‐deoxycytidine (5‐AZA) treatment improved intestinal epithelial barrier impairment induced by H/R. Besides, the protein levels of total β‐catenin, phosphor‐β‐catenin and cyclin‐D1 were reduced after overexpressing NKD2 in Caco‐2 cells following H/R insult. In conclusion, Our study suggests that CCM could attenuate intestinal I/R injury in vitro and in vivo by suppressing the Wnt/β‐catenin signaling pathway via inhibition of NKD2 methylation. [ABSTRACT FROM AUTHOR]

Introduction: Brain death (BD) leads to complex hemodynamic and inflammatory alterations which may compromise organ perfusion and induce morphologic and functional damage in various organs. The intestine is particularly sensitive to hypoperfusion and donor hypotension usually precludes intestinal donation. Previous studies reported inflammatory intestinal changes following BD but information on mucosal integrity and perfusion are lacking. Methods: BD was induced in mice by inflating an epidural balloon catheter. Controls underwent only anesthesia and tracheostomy. Intestinal perfusion was assessed using laser-Doppler flowmetry. Intestinal injury was assessed after 2 h of BD by the Chiu-Park score and morphometry. Intestinal tight junction (TJ) proteins (claudin-1, claudin-3, occludin, tricellulin) and inflammatory activation (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) were also analyzed and compared with the control group. Results: Although blood pressure decreased in BD mice, intestinal perfusion remained similar between BD and sham mice. Histologically, mucosal injury was absent/minimal and TJs appeared well maintained in both groups. Conclusion: BD may trigger intrinsic, autoregulatory mechanisms to preserve microvascular tissue perfusion and mucosal integrity despite a mild hypotension. [ABSTRACT FROM AUTHOR]

Background: Cardiac ischemia/reperfusion (I/R) injury has been shown to impose deleterious effects not only on the heart but also on the brain. Our previous study demonstrated that pretreatment with a mitochondrial fusion promoter (M1) provided central neuroprotective effects following cardiac I/R injury. Objective: To investigate the effects of M1 given during the ischemic phase and M1 given at the beginning of reperfusion on brain pathologies following cardiac I/R. Methods: Male Wistar rats were randomly divided into either a sham operation (n = 6) or cardiac I/R injury (n = 18) group. Rats with cardiac I/R injury were then randomly divided into 3 subgroups: 1) Control, 2) M1 treatment during cardiac ischemia (2 mg/kg, intravenous (i.v.)), and 3) M1 treatment at the beginning of reperfusion (2 mg/kg, i.v.). After euthanasia, the brain of each rat was removed for further analysis. Results: Cardiac I/R injury caused brain mitochondrial dynamic imbalance, brain mitochondrial dysfunction, brain apoptosis, microglial dysmorphology, brain inflammation, tau hyperphosphorylation, and synaptic dysplasticity. M1 treatment at both time points effectively improved these parameters. M1 given during the ischemic phase had greater efficacy with regard to preventing brain mitochondrial dysfunction and suppressing brain inflammation, when compared to M1 given at the beginning of reperfusion. Conclusions: Our findings suggest that treatment with this mitochondrial fusion promoter prevents mitochondrial dynamic imbalance in the brain of rats with cardiac I/R injury, thereby attenuating brain pathologies. Interestingly, giving the mitochondrial fusion promoter during the ischemic phase exerted greater neuroprotection than if given at the beginning of reperfusion. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is one of the most common comorbidities of patients undergoing surgery. Colorectal surgery is frequently associated with postoperative complications, and diabetic patients represent a population that presents a high risk of developing such complications. Understanding the interrelationships between neoplastic disease and diabetes, as well as the pathophysiological mechanisms underlying postoperative complications, are essential for effective therapeutic management. Genetic predispositions, alterations in the gut microbiota, inflammatory response, ischemic, thrombotic and infectious processes contribute significantly to the development of severe surgical complications, such as anastomotic fistulas. Postoperative ileus, characterized by gastrointestinal dysmotility, is common in diabetic patients due to neuropathic dysfunction and altered intestinal metabolism. In addition, diabetic patients are at increased risk of intestinal ischemia, requiring specific perioperative care. The strategies to avoid these complications assume an adequate surgical technique, a personalized anesthesia management, and last but not least, the best possible glycemic control. This article highlights the importance of a better understanding of the interaction between diabetes and postoperative complications, in order to obtain good results with an important impact on the patient's health and well-being. [ABSTRACT FROM AUTHOR]