RESUMEN
The most widely used cancer therapy is radiation therapy, but radiation damage to healthy tissues, particularly the gastrointestinal (GI) system, frequently reduces its effectiveness. This study investigates whether etoricoxib-loaded nanostructured lipid carriers (Et-NLC) could help shield the rat jejunum from radiation damage. Gamma irradiation (6 Gy) was used to damage the jejunum of Wistar albino rats, and then Et or Et-NLC (10 mg/kg b.w.) was administered orally for 14 days. It was found that the amounts of glutathione S-transferase (GST), superoxide dismutase (SOD), and nitric oxide (NO) decreased after irradiation but increased after Et-NLC therapy. Molecular analysis showed radiation-induced expression of microRNA-34a (miR34a), which may be involved in cellular stress response. Et-NLC treatments modulated the expression of miR34a, suggesting possible regulatory roles. Western blot analysis revealed changes in P53, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) levels. Et-NLC treatments decreased TNF-α, IL-6, IL-10, and COX-2 levels, indicating anti-inflammatory actions. DNA fragmentation analysis revealed a decrease in apoptotic activity after Et-NLC treatments. A histopathological examination confirmed that Et-NLC treatments had attenuated radiation damage, which had improved vascularization and reduced inflammation. The findings show that Et-NLC is more effective than Et-alone at reducing damage to the jejunum caused by radiation by controlling inflammation, oxidative stress, and apoptotic activity.
Asunto(s)
Etoricoxib , Yeyuno , Lípidos , MicroARNs , Nanoestructuras , Ratas Wistar , Proteína p53 Supresora de Tumor , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Yeyuno/efectos de la radiación , Yeyuno/patología , Etoricoxib/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Nanoestructuras/química , Masculino , Lípidos/química , Portadores de Fármacos/química , Rayos gamma/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Traumatismos por Radiación/tratamiento farmacológico , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/patologíaAsunto(s)
Flebitis , Humanos , Masculino , Femenino , Anciano , Flebitis/patología , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Linfocitos/patología , Colon/patología , Colon/cirugía , Colon/irrigación sanguínea , Tromboflebitis/patología , Tromboflebitis/diagnóstico , Colon Transverso/patología , Colon Transverso/cirugía , Íleon/patología , Íleon/cirugía , Yeyuno/patología , Yeyuno/cirugíaRESUMEN
AFB1 is a common foodborne toxin known for its potent carcinogenicity. Danshen polysaccharide (DSP) is an active ingredient of Danshen, which has been demonstrated to possess support intestinal homeostasis and anti-inflammatory activities. We utilized New Zealand White rabbits as an animal model to examine the impact of co-exposure to DSP and AFB1 on the intestines, as well as their underlying mechanisms. The results indicate that DSP elevated the abundance of Oscillospira, Coprococcus, Alistipes, Akkermansia, Bacteroides, Odoribacter, Blautia and Parabacteroides, while decreased the abundance of Sutterella, and Desulfovibrio, correcting AFB1-induced intestinal microbiota dysbiosis and enhancing microbial diversity within the gut. Moreover, DSP reduced the levels of diamine oxidase (DAO), D-Lactate, and malondialdehyde (MDA), while upregulating the expression of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), zonula occludens-1 (ZO-1), occludin, claudin-4, mucin-2 (MUC2), and secretory immunoglobulin A (sIgA), thereby alleviating the oxidative stress and intestinal barrier dysfunction induced by AFB1. DSP downregulated jejunal lipopolysaccharide (LPS) levels and the mRNA expression and proteins abundance of toll-like receptor 4 (TLR4), myeloiddifferentiationfactor 88 (MyD88), and nuclear factor kappa-B (NF-κB), thereby inhibiting the jejunal inflammation induced by AFB1. In summary, DSP alleviates AFB1-induced jejunal injury by remodeling the gut microbiota, bolstering antioxidant capabilities within the jejunum, fortifying the intestinal barrier, and suppressing the TLR4-mediated release of pro-inflammatory cytokines.
Asunto(s)
Aflatoxina B1 , Microbioma Gastrointestinal , Yeyuno , Polisacáridos , Salvia miltiorrhiza , Animales , Polisacáridos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Conejos , Salvia miltiorrhiza/química , Aflatoxina B1/toxicidad , Yeyuno/efectos de los fármacos , Yeyuno/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Enfermedades del Yeyuno/inducido químicamente , Enfermedades del Yeyuno/tratamiento farmacológico , Disbiosis/inducido químicamenteRESUMEN
Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25â¯mg/kg and 5â¯mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.
Asunto(s)
Apoptosis , Citrinina , Chaperón BiP del Retículo Endoplásmico , Retículo Endoplásmico , Mucosa Intestinal , Mitocondrias , Animales , Citrinina/toxicidad , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Ocludina/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Yeyuno/efectos de los fármacos , Yeyuno/patología , Animales no ConsanguíneosRESUMEN
Coccidiosis poses significant hazards to animals, particularly in terms of compromised health, reduced productivity, and economic losses in livestock farming. The conventional treatments for coccidiosis often involve synthetic drugs, contributing to concerns about drug resistance and environmental impact. The pressing need for eco-friendly alternatives is highlighted in this study, emphasizing the importance of exploring medicinal plants like Cassia alata leaf extracts (CAE) against Eimeria papillata-induced infection in mice. The CAE exhibited significant phenolic (2.17 ± 0.03 g/100 g) and flavonoid (0.14 ± 0.01 g/100 g) content and demonstrated notable antioxidant activity. In infected mice, the CAE treatment led to a substantial reduction in oocyst output (~6 fold), ameliorating necrotic enteritis and inflammatory changes in the jejunum. Additionally, CAE treatment increased goblet cell numbers (9.3 ± 0.1 / villus) and decreased macrophage infiltration in the intestinal villi. Molecular analyses revealed CAE's positive modulation of MUC2 gene and notably reduced the levels of pro-inflammatory cytokines (specifically IL-1ß, IL-10, and IFN-γ) when contrasted with the infected cohort. Furthermore, CAE treatment significantly reduced nitric oxide levels (44.03 ± 2.4 µmol/mg), showcasing its anti-inflammatory properties. The findings of this study not only contribute to the understanding of CAE's therapeutic potential but also underscore the importance of seeking eco-friendly alternatives in the face of coccidiosis challenges, addressing both the well-being of animals and the sustainability of agricultural practices. RESEARCH HIGHLIGHTS: Cassia alata extract (CAE) exhibited significant phenolic and flavonoid content, displaying notable antioxidant activity. In infected mice, CAE treatment led to a substantial reduction in oocyst output, ameliorating necrotic enteritis and inflammatory changes in the jejunum. CAE treatment increased goblet cell numbers and decreased macrophage infiltration in the intestinal villi, while molecular analyses revealed its positive modulation of the MUC2 gene and notable reduction in pro-inflammatory cytokine levels. Additionally, CAE treatment significantly reduced nitric oxide levels, showcasing its anti-inflammatory properties.
Asunto(s)
Antiinflamatorios , Cassia , Coccidiosis , Citocinas , Eimeria , Yeyuno , Mucina 2 , Extractos Vegetales , Animales , Yeyuno/parasitología , Yeyuno/efectos de los fármacos , Yeyuno/patología , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiosis/parasitología , Ratones , Extractos Vegetales/farmacología , Eimeria/efectos de los fármacos , Cassia/química , Antiinflamatorios/farmacología , Mucina 2/metabolismo , Mucina 2/genética , Citocinas/metabolismo , Hojas de la Planta/química , Modelos Animales de EnfermedadRESUMEN
RESEARCH HIGHLIGHTS: IDS presented pathognomonic dilatation of the jejunum up to Meckel's diverticulum.IDS caused weight loss, decreased egg production, and increased culling and mortality.Chicken parvovirus (ChPV) was consistently detected through PCR assays.Chicken megrivirus (ChMV) was consistently detected through viral metagenomics.
Asunto(s)
Pollos , Infecciones por Parvoviridae , Enfermedades de las Aves de Corral , Animales , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/patología , Pollos/virología , Infecciones por Parvoviridae/veterinaria , Infecciones por Parvoviridae/virología , Femenino , Parvovirus/genética , Parvovirus/aislamiento & purificación , Reacción en Cadena de la Polimerasa/veterinaria , Dilatación Patológica/veterinaria , Dilatación Patológica/virología , Yeyuno/virología , Yeyuno/patología , ParvovirinaeRESUMEN
BACKGROUND/AIM: The aim of this study was to develop an enhanced intestinal toxicity assay with three outputs assessing proliferation, villi morphology and DNA damage after irradiation. MATERIALS AND METHODS: Whole 5 cm jejunal lengths were collected from mice following total body x-ray irradiation (0-15 Gy) at 0-84 h. Tissues were wrapped into swirls for cryopreservation and immunohistochemically stained for EdU, CD31, and γH2AX. A semi-automated image analysis was developed for the proliferation, villi morphology, and DNA damage models. RESULTS: Proliferation assessed via EdU staining varied with cycles of damage repair, hyperproliferation, and homeostasis after radiation, with the time to onset of each cycle variable based on radiation dose. An analysis model evaluating the amount of proliferation per unit length of jejunum analyzed was developed, with a dose-response curve identified at 48 h post treatment. The villi length model measured the length of intact and healthy CD31-stained capillary beds between the crypts and villi tips at 3.5 days post treatment within a 0-10 Gy dose range. The DNA damage model evaluated the intensity of γH2AX staining within cellular nuclei, with a useful dose-response identified at 1 h post-radiation treatment. CONCLUSION: This assay demonstrates flexibility for assessing radiation-induced damage, with analysis of proliferation, villi length, or direct DNA damage achievable at defined time points and within useful radiation dose curves. The software-assisted image analysis allows for rapid, comprehensive, and objective data generation with an assay turnover time of days instead of weeks on samples that are representative of most of the treated jejunum.
Asunto(s)
Proliferación Celular , Daño del ADN , Animales , Ratones , Proliferación Celular/efectos de la radiación , Daño del ADN/efectos de la radiación , Yeyuno/efectos de la radiación , Yeyuno/patología , Tolerancia a Radiación , Mucosa Intestinal/efectos de la radiación , Mucosa Intestinal/patología , Intestinos/efectos de la radiación , Intestinos/patología , Irradiación Corporal Total/efectos adversos , Relación Dosis-Respuesta en la Radiación , Histonas/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
Ochratoxin A (OTA) is a common mycotoxin that causes intestinal injury in humans and various animal species. OTA may lead to intestinal injury in offspring due to the maternal effect. The aim of this study was to investigate the mechanism of embryo injected with OTA induced jejunum injury in ducklings. The results showed that OTA disrupted the jejunum tight junctions in hatching ducklings, and promoted the secretion of inflammatory cytokines. And this inflammatory response was caused by the activation of the TLR4 signaling pathway. Moreover, embryo injected with OTA could cause damage to the intestinal barrier in 21-day-old ducks, characterized by shortened villi, crypt hyperplasia, disrupted intestinal tight junctions, increased level of LPS in the jejunum, activation of the TLR4 signaling pathway, and increased levels of pro-inflammatory cytokines. Meanwhile, OTA induced oxidative stress in the jejunum. And dysbiosis of gut microbiota was mainly characterized by an increased the relative abundance of Bacteroides, Megamonas, Fournierella, and decreased the relative abundance of Alistipes and Weissella. Interestingly, embryo injected with OTA did not induce these changes in the jejunum of antibiotics-treated 21-day-old ducks. In conclusion, embryo injected with OTA induced jejunum injury in ducklings by activating the TLR4 signaling pathway, which involvement of intestinal microbiota.
Asunto(s)
Patos , Microbioma Gastrointestinal , Yeyuno , Ocratoxinas , Transducción de Señal , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , Ocratoxinas/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Yeyuno/efectos de los fármacos , Yeyuno/patología , Embrión no Mamífero/efectos de los fármacos , Citocinas/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Necrotic enteritis (NE) is a potentially fatal poultry disease that causes enormous economic losses in the poultry industry worldwide. The study aimed to evaluate the effects of dietary organic yeast-derived selenium (Se) on immune protection against experimental necrotic enteritis (NE) in commercial broilers. Chickens were fed basal diets supplemented with different Se levels (0.25, 0.50, and 1.00 Se mg/kg). To induce NE, Clostridium perfringens (C. perfringens) was orally administered at 14 days of age post hatch. The results showed that birds fed 0.25 Se mg/kg exhibited significantly increased body weight gain compared with the non-supplemented/infected birds. There were no significant differences in gut lesions between the Se-supplemented groups and the non-supplemented group. The antibody levels against α-toxin and NetB toxin increased with the increase between 0.25 Se mg/kg and 0.50 Se mg/kg. In the jejunal scrapings and spleen, the Se-supplementation groups up-regulated the transcripts for pro-inflammatory cytokines IL-1ß, IL-6, IL-8, iNOS, and LITAF and avian ß-defensin 6, 8, and 13 (AvBD6, 8 and 13). In conclusion, supplementation with organic yeast-derived Se alleviates the negative consequences and provides beneficial protection against experimental NE.
Asunto(s)
Alimentación Animal , Pollos , Infecciones por Clostridium , Clostridium perfringens , Citocinas , Suplementos Dietéticos , Enteritis , Enfermedades de las Aves de Corral , Selenio , Animales , Enteritis/prevención & control , Enteritis/veterinaria , Enteritis/inmunología , Enteritis/microbiología , Selenio/farmacología , Selenio/administración & dosificación , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/inmunología , Clostridium perfringens/inmunología , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/inmunología , Citocinas/metabolismo , Toxinas Bacterianas/inmunología , Necrosis , beta-Defensinas/metabolismo , Yeyuno/efectos de los fármacos , Yeyuno/inmunología , Yeyuno/microbiología , Yeyuno/patología , Bazo/inmunología , Levaduras , Óxido Nítrico Sintasa de Tipo II/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Interleucina-1beta/metabolismo , Anticuerpos Antibacterianos/sangreRESUMEN
Macrophages are one of the important immune cells, which play important roles in innate and adaptive immune. However, the roles of macrophages in food allergy are not thoroughly understood. To investigate the roles of macrophages during food allergy, we focused on the relationship between macrophage polarization and allergic responses induced by tropomyosin (TM) in the present study. Arg 1 and CD206 expressions in the TM group were significantly higher than those of the PBS group, while iNOS and TNF-α expressions were no obvious difference, moreover, the morphology of macrophages stimulated by TM was similar to that of M2 macrophages. These results indicated macrophages were mainly polarized toward M2 phenotypes in vitro. The antibodies, mMCP-1, histamine and cytokines, revealed that macrophages could participate in food allergy, and macrophage polarization was associated with changes in allergic-related factors. The cytokine levels of M2 phenotypes were significantly higher than those of M1 phenotypes in peripheral blood. The mRNA expressions and protein levels of Arg1 and iNOS in the jejunum and peritoneal cells indicated that M2 phenotypes were the major macrophage in these tissues compared with M1 phenotypes. Hence, macrophage polarization plays an important role in food allergy.
Asunto(s)
Arginasa , Hipersensibilidad a los Alimentos , Macrófagos , Ratones Endogámicos BALB C , Palaemonidae , Tropomiosina , Animales , Tropomiosina/inmunología , Hipersensibilidad a los Alimentos/inmunología , Ratones , Macrófagos/inmunología , Arginasa/metabolismo , Palaemonidae/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Lectinas de Unión a Manosa/metabolismo , Femenino , Receptor de Manosa , Yeyuno/inmunología , Yeyuno/patología , Células Cultivadas , Histamina/metabolismo , Activación de MacrófagosRESUMEN
Although there are several types of radiation exposure, it is debated whether lowdoserate (LDR) irradiation (IR) affects the body. Since the small intestine is a radiationsensitive organ, the present study aimed to evaluate how it changes when exposed to LDR IR and identify the genes sensitive to these doses. After undergoing LDR (6.0 mGy/h) γ radiation exposure, intestinal RNA from BALB/c mice was extracted 1 and 24 h later. Mouse whole genome microarrays were used to explore radiationinduced transcriptional alterations. Reverse transcriptionquantitative (RTq) PCR was used to examine time and dosedependent radiation responses. The histopathological status of the jejunum in the radiated mouse was not changed by 10 mGy of LDR IR; however, 23 genes were upregulated in response to LDR IR of the jejunum in mice after 1 and 24 h of exposure. Upregulated genes were selected to validate the results of the RNA sequencing analysis for RTqPCR detection and results showed that only Na+/K+ transporting subunit α4, glucose6phosphatase catalytic subunit 2 (G6PC2), mucin 6 (MUC6) and transient receptor potential cation channel subfamily V member 6 levels significantly increased after 24 h of LDR IR. Furthermore, G6PC2 and MUC6 were notable genes induced by LDR IR exposure according to protein expression via western blot analysis. The mRNA levels of G6PC2 and MUC6 were significantly elevated within 24 h under three conditions: i) Exposure to LDR IR, ii) repeated exposure to LDR IR and iii) exposure to LDR IR in the presence of inflammatory bowel disease. These results could contribute to an improved understanding of immediate radiation reactions and biomarker development to identify radiationsusceptible individuals before histopathological changes become noticeable. However, further investigation into the specific mechanisms involving G6PC2 and MUC6 is required to accomplish this.
Asunto(s)
Glucosa-6-Fosfatasa , Enfermedades Inflamatorias del Intestino , Mucina 6 , Animales , Masculino , Ratones , Relación Dosis-Respuesta en la Radiación , Rayos gamma/efectos adversos , Glucosa-6-Fosfatasa/metabolismo , Glucosa-6-Fosfatasa/genética , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de la radiación , Mucosa Intestinal/patología , Intestinos/efectos de la radiación , Intestinos/patología , Yeyuno/efectos de la radiación , Yeyuno/metabolismo , Yeyuno/patología , Ratones Endogámicos BALB C , Mucina 6/metabolismo , Mucina 6/genéticaRESUMEN
This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. The ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using Western blotting, immunohistochemistry, and qPCR. The results indicated a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure and an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase was observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 showed an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of alpha-synuclein and induces the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.
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Colon , Yeyuno , Ozono , Sustancia Negra , alfa-Sinucleína , Animales , Masculino , Ratas , alfa-Sinucleína/metabolismo , Colon/metabolismo , Colon/efectos de los fármacos , Colon/patología , Inflamación/metabolismo , Inflamación/inducido químicamente , Inflamación/patología , Interleucina-17/metabolismo , Yeyuno/metabolismo , Yeyuno/efectos de los fármacos , Yeyuno/patología , FN-kappa B/metabolismo , Ozono/toxicidad , Ratas Wistar , Sustancia Negra/metabolismo , Sustancia Negra/efectos de los fármacos , Sustancia Negra/patologíaAsunto(s)
Quinasa de Linfoma Anaplásico , Ganglios Linfáticos , Linfoma Folicular , Linfoma Anaplásico de Células Grandes , Humanos , Linfoma Folicular/patología , Ganglios Linfáticos/patología , Linfoma Anaplásico de Células Grandes/patología , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/metabolismo , Quinasa de Linfoma Anaplásico/metabolismo , Quinasa de Linfoma Anaplásico/genética , Yeyuno/patología , Masculino , Mesenterio/patología , Persona de Mediana Edad , FemeninoRESUMEN
Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/ß-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated ß-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.
Asunto(s)
Antioxidantes , Toxinas Bacterianas , Enterotoxinas , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Yeyuno , Morus , Extractos Vegetales , Ratones , Morus/química , Hojas de la Planta/química , Vía de Señalización Wnt , Células Madre/efectos de los fármacos , Células Madre/microbiología , Células Madre/patología , Proteínas de Escherichia coli/metabolismo , Técnicas In Vitro , Extractos Vegetales/farmacología , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Yeyuno/microbiología , Yeyuno/patología , Regeneración , Toxinas Bacterianas/aislamiento & purificación , Enterotoxinas/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Antioxidantes/farmacologíaRESUMEN
This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1ß and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.
Asunto(s)
Antioxidantes , Broussonetia , Estrés Oxidativo , Hojas de la Planta , Polisacáridos , Animales , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Ratas , Masculino , Hojas de la Planta/química , Antioxidantes/farmacología , Broussonetia/química , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Yeyuno/patología , Intestinos/efectos de los fármacos , Intestinos/patología , Dieta , Modelos Animales de Enfermedad , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Especies Reactivas de Oxígeno/metabolismo , Ratas Sprague-Dawley , Peroxidación de Lípido/efectos de los fármacosRESUMEN
Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, in vitro approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl- secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context.
Asunto(s)
COVID-19 , Mucosa Intestinal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , SARS-CoV-2/fisiología , SARS-CoV-2/inmunología , Humanos , Ratones , COVID-19/inmunología , COVID-19/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Yeyuno/inmunología , Yeyuno/metabolismo , Yeyuno/patología , Yeyuno/virología , Simulación del Acoplamiento Molecular , Enterocitos/metabolismo , Enterocitos/virología , Inmunidad Innata , Citocinas/metabolismo , Modelos Animales de Enfermedad , Masculino , Relevancia ClínicaRESUMEN
We report the case of a woman nearing 70 years old who was admitted to the hospital with a complaint of "epigastric distension for 1 month". Her main signs and symptoms were progressive abdominal distension and occasional abdominal pain. Computed tomography suggested an abdominal mass. She had a surgical history of synovial sarcoma (SS) of the lungs. After admission, she was diagnosed with jejunal SS following a puncture biopsy and laparoscopic surgery. This disease usually occurs in the soft tissues of the limbs, and it is extremely rare for SS to originate in the jejunum. The morphologic heterogeneity of SS overlaps with other tumors and makes the diagnosis particularly difficult. Imaging studies usually lack specificity; however, measuring multiple immunohistochemical markers can greatly assist in the diagnosis and differential diagnosis of SS. This case not only enriches our understanding of SS and describes a rare site of origin, but also emphasizes the importance and challenges of achieving an accurate diagnosis. Immunohistochemical and molecular biological testing have important roles in the definitive diagnosis, highlighting the need for precise and innovative diagnostic and therapeutic approaches in SS.