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Obstrucción Intestinal , Intestino Delgado , Necrosis , Tomografía Computarizada por Rayos X , Humanos , Obstrucción Intestinal/diagnóstico por imagen , Necrosis/diagnóstico por imagen , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/patología , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Adulto , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
Recent evidence indicates that liver cirrhosis (LC) is a reversible condition, but there is no established intervention against liver fibrosis. Although the gut microbiota is considered involved in the pathogenesis of LC, the underlying mechanisms remain unclear. Although the antibiotic, rifaximin (RFX), is effective for hepatic encephalopathy (HE) with LC, the impact of RFX on intestinal bacteria is unknown. We investigated the bacterial compositions along the GI tract under RFX treatment using a murine LC model. RFX improved liver fibrosis and hyperammonemia and altered the bacterial composition in the small intestine. The efficacy of RFX was associated with increases in specific bacterial genera, including Akkermansia. Administration of a commensal strain of Akkermansia muciniphila improved liver fibrosis and hyperammonemia with changing bacterial composition in the small intestine. This study proposed a new concept "small intestine-liver axis" in the pathophysiology of LC and oral A. muciniphila administration is a promising microbial intervention.
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Akkermansia , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Intestino Delgado , Cirrosis Hepática , Rifaximina , Animales , Ratones , Intestino Delgado/microbiología , Intestino Delgado/patología , Cirrosis Hepática/microbiología , Rifaximina/uso terapéutico , Rifaximina/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Verrucomicrobia , Ratones Endogámicos C57BL , Hígado/patología , Hígado/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , ARN Ribosómico 16S/genéticaRESUMEN
Cancer continues to pose a significant global health challenge, with gastrointestinal (GI) cancers among the most prevalent and deadly forms. These cancers often lead to high mortality rates and demand the use of potent cytotoxic chemotherapeutics. For example, 5-fluorouracil (5-FU) forms the backbone of chemotherapy regimens for various GI cancers, including colorectal cancer. While these chemotherapeutics efficiently kill cancer cells, they frequently cause off-target effects such as chemotherapy-induced mucositis (CIM), characterized by debilitating symptoms like pain, nausea, and diarrhoea, necessitating medical intervention. In this study, we elucidated the potential of melatonin and misoprostol to reduce 5-FU-induced small intestinal mucositis. Morphological and cellular changes in the jejunum, along with colonic faecal water content were quantified in rats as markers for CIM. Additionally, the effects of melatonin were investigated in vitro on 5-FU treated murine intestinal organoids. The results showed that melatonin prevented villus atrophy in the rat jejunal mucosa and upheld cell viability in murine intestinal organoids. In contrast, misoprostol alone or in combination with melatonin did not significantly affect CIM caused by 5-FU. These in vivo and in vitro experiments provided promising insights that melatonin may be used as a preventive and/or adjuvant combination therapy to prevent and reduce CIM, holding the potential to enhance cancer treatment outcomes and improve patient quality-of-life.
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Fluorouracilo , Intestino Delgado , Melatonina , Mucositis , Organoides , Animales , Melatonina/farmacología , Ratas , Organoides/efectos de los fármacos , Fluorouracilo/efectos adversos , Fluorouracilo/farmacología , Ratones , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Mucositis/inducido químicamente , Mucositis/patología , Mucositis/prevención & control , Mucositis/tratamiento farmacológico , Masculino , Atrofia/inducido químicamente , Atrofia/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patologíaAsunto(s)
Atrofia , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare , Humanos , Persona de Mediana Edad , Intestino Delgado/microbiología , Intestino Delgado/patología , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/diagnóstico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológicoRESUMEN
This study explores the impact of royal jelly (RJ) on small intestinal epigenomic changes. RJ, produced by honeybees, is known for its effects on metabolic diseases. The hypothesis is that RJ induces epigenomic modifications in small intestinal epithelial cells, affecting gene expression and contributing to metabolic health. Male db/m and db/db mice were used to examine RJ's effects through mRNA sequencing and CUT&Tag methods. This study focused on histone modifications and gene expression changes, with statistical significance set at p < 0.05. RJ administration improved insulin sensitivity and lipid metabolism without affecting body weight. GO and KEGG pathway analyses showed significant enrichment in metabolic processes, cellular components, and molecular functions. RJ altered histone modifications, increasing H3K27me3 and decreasing H3K23Ac in genes associated with the G2M checkpoint. These genes, including Smc2, Mcm3, Ccnd1, Rasal2, Mcm6, and Mad2l1, are linked to cancer progression and metabolic regulation. RJ induces beneficial epigenomic changes in small intestinal epithelial cells, improving metabolic health and reducing cancer-associated gene expression. These findings highlight RJ's potential as a therapeutic agent for metabolic disorders. Further research is needed to fully understand the mechanisms behind these effects and their implications for human health.
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Epigenómica , Ácidos Grasos , Intestino Delgado , Animales , Ácidos Grasos/metabolismo , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Ratones , Masculino , Epigenómica/métodos , Histonas/metabolismo , Epigénesis Genética/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
Newborn lambs are susceptible to pathogenic bacterial infections leading to enteritis, which affects their growth and development and causes losses in sheep production. It has been reported that N6-methyladenosine (m6A) is closely related to innate immunity, but the effect of m6A on sheep small intestinal epithelial cells (IECs) and the mechanism involved have not been elucidated. Here, we investigated the effects of m6A on lipopolysaccharide (LPS)-induced inflammatory responses, apoptosis and oxidative stress in primary sheep IECs. First, the extracted IECs were identified by immunofluorescence using the epithelial cell signature protein cytokeratin 18 (CK18), and the cellular activity of IECs induced by different concentrations of LPS was determined by the CCK8 assay. Meanwhile, LPS could induce the upregulation of mRNA and protein levels of IECs cytokines IL1ß, IL6 and TNFα and the apoptosis marker genes caspase-3, caspase-9, Bax, and apoptosis rate, reactive oxygen species (ROS) levels and mRNA levels of CAT, Mn-SOD and CuZn-SOD, and METTL3 were found to be upregulated during induction. It was hypothesized that METTL3 may have a potential effect on the induction of IECs by LPS. Overexpression and knockdown of METTL3 in IECs revealed that a low-level expression of METTL3 could reduce the inflammatory response, apoptosis and ROS levels in LPS-induced IECs to some extent. The results suggest that METTL3 may be a genetic marker for potential resistance to cellular damage.
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Apoptosis , Células Epiteliales , Intestino Delgado , Lipopolisacáridos , Metiltransferasas , Animales , Lipopolisacáridos/toxicidad , Ovinos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Metiltransferasas/metabolismo , Metiltransferasas/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Intestino Delgado/metabolismo , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Citocinas/metabolismo , Citocinas/genética , Células CultivadasRESUMEN
Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50⯵g/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients' daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.
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Ratones Endogámicos C57BL , Microplásticos , Poliestirenos , Animales , Microplásticos/toxicidad , Ratones , Poliestirenos/toxicidad , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/efectos de la radiación , Intestinos/efectos de la radiación , Intestinos/efectos de los fármacos , Intestinos/patología , Intestino Delgado/efectos de la radiación , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Traumatismos por Radiación/patologíaRESUMEN
BACKGROUND: Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes. METHODS: This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23-87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups. RESULTS: Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P < 0.05), and the rate of splenectomy was significantly lower in the exacerbated group than in the unchanged group (5% vs. 39%, respectively; P < 0.01). In multivariate analysis, exacerbation of esophageal varices and absence of splenectomy were significantly associated with PHE exacerbation. The rate of gastrointestinal bleeding after follow-up CE was significantly high in the exacerbated group (log-rank, P = 0.037). CONCLUSIONS: Exacerbation of esophageal varices and splenectomy were significantly associated with exacerbation of PHE. Exacerbated PHE requires specific attention to prevent gastrointestinal bleeding.
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Endoscopía Capsular , Progresión de la Enfermedad , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Hipertensión Portal , Humanos , Hipertensión Portal/etiología , Hipertensión Portal/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Hemorragia Gastrointestinal/etiología , Anciano de 80 o más Años , Várices Esofágicas y Gástricas/etiología , Adulto Joven , Esplenectomía , Enfermedades Intestinales/etiología , Enfermedades Intestinales/complicaciones , Intestino Delgado/patología , Intestino Delgado/diagnóstico por imagenRESUMEN
INTRODUCTION AND PURPOSE OF THE STUDY: Small bowel obstruction (SBO) accounts for a substantial proportion of emergency surgical admissions. Malignancy is a common cause of obstruction, either due to a primary tumour or intra-abdominal metastases. However, little is known regarding the current treatment or outcomes of patients with malignant SBO. This study aimed to characterise the treatment of malignant SBO and identify areas for potential improvement and compare overall survival of patients with malignant SBO to patients with non-malignant SBO. MATERIALS AND METHODS: This was a subgroup analysis of a multicentre observational study of patients admitted with SBO. Details regarding these patients' diagnoses, treatments, and outcomes up to 1-year after admission were recorded. The primary outcome was overall survival in patients with malignant SBO. RESULTS: A total of 316 patients with small bowel obstruction were included, of whom 33 (10.4%) had malignant SBO. Out of the 33 patients with malignant SBO, 20 patients (60.6%) were treated with palliative intent although only 7 patients were seen by a palliative team during admission. Nutritional assessments were performed on 12 patients, and 11 of these patients received parenteral nutrition. 23 patients underwent surgery, with the most common surgical interventions being loop ileostomies (9 patients) and gastrointestinal bypasses (9 patients). 4 patients underwent right hemicolectomies, with a primary anastomosis formed and 1 patient had a right hemicolectomy with a terminal ileostomy. Median survival was 114 days, and no difference was seen in survival between patients treated with or without palliative intent. CONCLUSION: Malignant SBO is associated with significant risks of short-term complications and a poor prognosis. Consideration should be given to the early involvement of senior decision-makers upon patient admission is essential for optimal management and setting expectation for a realistic outcome.
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Obstrucción Intestinal , Intestino Delgado , Cuidados Paliativos , Humanos , Obstrucción Intestinal/etiología , Obstrucción Intestinal/mortalidad , Obstrucción Intestinal/cirugía , Masculino , Femenino , Anciano , Persona de Mediana Edad , Intestino Delgado/patología , Anciano de 80 o más Años , Resultado del Tratamiento , Adulto , Estudios de Cohortes , Tasa de Supervivencia , Neoplasias Intestinales/mortalidad , Neoplasias Intestinales/complicaciones , Neoplasias Intestinales/patología , Neoplasias Intestinales/cirugíaRESUMEN
Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.
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Lesión Pulmonar Aguda , Movimiento Celular , Interleucina-17 , Pulmón , Ratones Endogámicos C57BL , Sepsis , Animales , Sepsis/inmunología , Sepsis/complicaciones , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Ratones , Interleucina-17/metabolismo , Interleucina-17/inmunología , Pulmón/inmunología , Pulmón/patología , Masculino , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Vía de Señalización Wnt/inmunología , Macrófagos Alveolares/inmunología , Intestino Delgado/inmunología , Intestino Delgado/patología , Linfocitos Intraepiteliales/inmunología , Modelos Animales de Enfermedad , Antígenos Ly/metabolismo , Memoria InmunológicaRESUMEN
The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Exosomas , Ferroptosis , Flores , Mucosa Gástrica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Mucosa Intestinal , Intestino Delgado , Peroxidación de Lípido , Nanopartículas , Animales , Ferroptosis/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Administración Oral , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Flores/química , Nanopartículas/química , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Humanos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Macracanthorhynchus hirudinaceus (Pallas, 1781) is a zoonotic acanthocephalan that parasitizes the small intestine of wild boars. It is a pathogenic that causes economic losses, and poses a public health threat due to increased emergence. PURPOSE: The aims of this study is describes histopathologically the damage caused by M. hirudinaceus in the small intestine of wild boar Sus scrofa Linnaeus, 1758, and molecularly characterize this parasite (sequences, haplotypes, phylogeny) for the first time in Elazig city, Türkiye. RESULTS: A high prevalence of infection was obtained. Upon separating the worms, it was discovered that there were ulcers resembling craters in the center, of the small intestine mucosa, surrounded by edema. The intestine wall where the parasite attached was damaged, with the villi epithelium and lamina propria in the mucosa being destroyed. The genomic DNA was isolated from all M. hirudinaceus samples, and PCR amplified the 489 bp gene fragments were sequenced and confirmed that all 21 sequences were M. hirudinaceus. The haplotype analysis of the sequences revealed the presence of a central star-shaped haplotype, in addition to four other haplotypes. CONCLUSION: After conducting sequence analysis, the genetic differences between the M. hirudinaceus sequences obtained in this study and those reported from Europe and Japan suggest that this parasite is endemic to Türkiye's local wild boar population. Also, four haplotypes were identified, distinguishing it from other haplotypes by 1-5 mutation steps. It is essential to consider the worm's sequences and the formation of haplotypes, since these intrinsic characteristics may impact in the epidemiology and pathology of the worm in the future.
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Acantocéfalos , Filogenia , Sus scrofa , Enfermedades de los Porcinos , Animales , Acantocéfalos/genética , Acantocéfalos/clasificación , Acantocéfalos/aislamiento & purificación , Enfermedades de los Porcinos/parasitología , Enfermedades de los Porcinos/epidemiología , Sus scrofa/parasitología , Porcinos , Intestino Delgado/parasitología , Intestino Delgado/patología , Helmintiasis Animal/parasitología , Helmintiasis Animal/epidemiología , Haplotipos , ADN de Helmintos/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. METHODS: We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. RESULTS: CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. CONCLUSION: While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.
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Apoptosis , Ceramidas , Ratones Endogámicos C57BL , Anticuerpos de Cadena Única , Animales , Anticuerpos de Cadena Única/inmunología , Femenino , Ratones , Masculino , Ceramidas/metabolismo , Apoptosis/efectos de los fármacos , Síndrome de Radiación Aguda/patología , Síndrome de Radiación Aguda/tratamiento farmacológico , Síndrome de Radiación Aguda/prevención & control , Humanos , Armas Nucleares , Protectores contra Radiación/farmacología , Protectores contra Radiación/uso terapéutico , Intestino Delgado/patología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/efectos de la radiaciónRESUMEN
Enteric duplication has cystic and tubular varieties. A male infant presented with a large cystic, well-demarcated mass in the right flank. On exploratory laparotomy, multiple cystic and tubular lesions were present adjacent to the mesenteric border of the small bowel along with malrotation of the small bowel. The tubule-cystic structure was excised along with the involved normal bowel segment and Ladd's procedure was performed. Histopathological evaluation revealed an intestinal duplication cyst. The occurrence of midgut malrotation and volvulus along with duplication is uncommon. The cyst's substantial size could have been an aetiological factor for malrotation and volvulus. The child's small bowel had adapted remarkably with time. This case highlights a new variant of duplication cysts.
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Vólvulo Intestinal , Humanos , Masculino , Lactante , Vólvulo Intestinal/cirugía , Vólvulo Intestinal/diagnóstico , Intestino Delgado/anomalías , Intestino Delgado/cirugía , Intestino Delgado/patología , Quistes/cirugía , Laparotomía/métodos , Anomalías del Sistema Digestivo/cirugía , Anomalías del Sistema Digestivo/complicaciones , Anomalías del Sistema Digestivo/diagnóstico por imagenAsunto(s)
Linfoma de Células B Grandes Difuso , Neoplasias Primarias Múltiples , Humanos , Masculino , Anciano , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/genética , Linfoma de Células T/patología , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/genética , Intestino Delgado/patología , Ciclofosfamida/uso terapéutico , Vincristina/uso terapéutico , Doxorrubicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diagnóstico Diferencial , Prednisona/uso terapéuticoRESUMEN
The consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague-Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.
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Dronabinol , Fructosa , Intestino Delgado , Ratas Sprague-Dawley , Animales , Dronabinol/farmacología , Fructosa/farmacología , Ratas , Masculino , Intestino Delgado/metabolismo , Intestino Delgado/patología , Intestino Delgado/efectos de los fármacos , DietaRESUMEN
EP4 prostanoid receptor (EP4R) contributes to the intestinal epithelial Cl- secretion, and inhibition of prostaglandin E (PGE) production by non-steroidal anti-inflammatory drugs (NSAIDs) plays a central role in NSAID-induced enteropathy. Although M3 muscarinic acetylcholine receptor (M3R) also contributes to the intestinal epithelial Cl- secretion, it remains unclear whether M3R is involved in NSAID-induced enteropathy due to a lack of selective agents. The present study explored how M3R is involved in the regulation of the intestinal epithelial Cl- secretion and its pathophysiological role in NSAID-induced enteropathy. Using the novel highly-selective M3 positive allosteric modulator PAM-369 that we recently developed, we evaluated the role of M3R in the intestinal epithelial secretion ex vivo by measuring the short circuit current (Isc) of intestinal epithelium with a Ussing chamber system and examined whether or not M3R protects against small intestinal injury in indomethacin-treated mice. Both the PGE1 derivative misoprostol and carbachol similarly increased the Isc in a concentration-dependent manner. The Isc increases were abolished either by receptor antagonists (an EP4R antagonist and a M3R antagonist, respectively) or by removal of extracellular Cl-. PAM-369 enhanced the carbachol-induced Isc by potentiating M3R, which could contribute to enhanced intestinal epithelial secretion. Treatment with PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. Importantly, the M3R expression was significantly up-regulated, and PAM-369 potentiation of M3R was augmented in indomethacin-treated mice compared to untreated mice. These findings show that M3R plays a role in maintaining the intestinal epithelial secretion, which could contribute to protection against indomethacin-induced small intestinal injury. M3R is a promising target for treating or preventing NSAID-induced enteropathy. KEY MESSAGES: PAM-369, the M3 positive allosteric modulator, was used to potentiate M3R. PAM-369 enhanced carbachol-induced Isc in mouse ileum. PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. M3R is a promising target for treating or preventing NSAID-induced enteropathy.
Asunto(s)
Indometacina , Intestino Delgado , Receptor Muscarínico M3 , Animales , Masculino , Ratones , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/efectos adversos , Carbacol/farmacología , Indometacina/efectos adversos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Intestino Delgado/lesiones , Ratones Endogámicos C57BL , Misoprostol/farmacología , Receptor Muscarínico M3/metabolismoRESUMEN
BACKGROUND/AIMS: The endoscopic features of small-bowel gastrointestinal stromal tumors (GISTs) are not well defined. The objective of this study was to describe the endoscopic features of GISTs of the small intestine detected via single-balloon enteroscopy (SBE). MATERIALS AND METHODS: Patients with surgically confirmed small intestinal GISTs from January 2014 to September 2022 were retrospectively analyzed. The hospital's electronic medical record system was used to retrieve the patients' data, including their demographics, clinical symptoms, hemoglobin on admission, endoscopic and computerized tomography findings, clinicopathological findings, and surgical management data. RESULTS: In total, 46 GIST patients (23 men and 23 women) with overt bleeding were included, with a mean age of 52 years (23-80 years). The typical duration of the symptoms was 48 hours. Four patients (8.70%) had lesions in the duodenum, 32 (69.56%) had lesions in the jejunum, 8 (17.39%) had lesions in the ileum, and 2 (4.35%) had lesions around the junction of the jejunum and ileum. Out of the 46 patients, 27 underwent SBE, and GISTs were visualized in 25, while the lesions could not be visualized in the remaining 2. Submucosal round (n = 13), submucosal sessile (n = 8), and invasive/penetrating (n = 4) were among the endoscopic tumor features. Twenty patients exhibited submucosal protuberant lesions, with ulceration, vascular nodules/congestion, or erosion on the surface, and 5 patients presented ulcerative infiltrative lesions. The multiple logistic regression analysis indicated that the invasive/penetrating characteristics of GISTs under SBE evaluation are significantly correlated with the risk level of GIST malignancy (P < .05). CONCLUSION: A variety of endoscopic characteristics could be observed during the preoperative SBE evaluation of small-intestine GISTs.
Asunto(s)
Tumores del Estroma Gastrointestinal , Intestino Delgado , Enteroscopia de Balón Individual , Humanos , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/diagnóstico , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Anciano , Adulto , Anciano de 80 o más Años , Enteroscopia de Balón Individual/métodos , Intestino Delgado/patología , Intestino Delgado/diagnóstico por imagen , Adulto Joven , Hemorragia Gastrointestinal/etiología , Neoplasias Intestinales/patología , Neoplasias Intestinales/cirugía , Neoplasias Intestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/diagnóstico por imagen , Neoplasias Gastrointestinales/cirugíaRESUMEN
Diagnosing small bowel adenocarcinomas presents challenges due to non-specific symptoms, rarity and gastroscopy and colonoscopy's limited small intestine access, highlighting targeted diagnostic procedures' necessity. We present a late-diagnosed metastatic small bowel adenocarcinoma case in a man in his 80s who had asymptomatic mild iron-deficiency anaemia 1 year before diagnosis, with no active bleeding found on endoscopies. He experienced a single rectal bleeding episode 9 months prediagnosis, with subsequent severe iron-deficiency anaemia and no clear gastrointestinal source identified on gastroscopy. For 2 months, he had intermittent postprandial diarrhoea without abdominal pain, infectious or inflammatory causes. He experienced significant weight loss over 3 months prediagnosis. Subsequent gastroscopy indicated duodenal-gastric food retropulsion, suggesting a downstream blockage. Magnetic resonance enterography showed proximal jejunum thickening. Push enteroscopy confirmed jejunum adenocarcinoma. CT scans detected liver and peritoneal metastases. After one chemotherapy cycle, his condition worsened, leading to his passing 2 months post diagnosis.