Brief Disruption of Circadian Rhythms Alters Intestinal Barrier Integrity and Modulates DSS-Induced Colitis Severity in Mice.

Physiological processes in organisms exhibit circadian rhythms that optimize fitness and anticipate environmental changes. Luminal signals such as food or metabolites synchronize bowel activity, and disruptions in these rhythms are linked to metabolic disorders and gastrointestinal inflammation. To characterize the intrinsic intestinal rhythms and assess disruptions due to continuous darkness or light exposure, C57BL/6 mice were exposed to standard light-dark conditions or continuous light/darkness for 48 h, with evaluations at four timepoints. We assessed intestinal morphology, mucus production, nitric oxide levels and permeability. Under standard light: dark cycles, mice showed changes in intestinal morphology consistent with normal tract physiology. Continuous light exposure caused marked alterations in the small intestine´s epithelium and lamina propria, reduced nitric oxide production in the colon, and predominant neutral mucins. Enhanced permeability was indicated by higher FITC-dextran uptake and increased frequency of IgG-coated bacteria. Additionally, the 48 h-disruption influenced DSS-induced colitis with attenuation in L:L group, or exacerbation in D:D group, of clinical signs. These findings highlight the critical role of circadian rhythms in gut histoarchitecture and function, demonstrating that short-term disruptions in light-dark cycles can compromise intestinal barrier integrity and impact inflammatory outcomes.

Proximal jejunal GIST associated with massive gastrointestinal bleeding. Case report.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are rare, reported incidence is between 10 to 15 cases per million of habitants. They are usually located in the stomach (56%), small intestine (32%), colon-rectum (6%), and esophagus (<1%). Its symptoms include nausea, vomiting and abdominal fullness; 30% are asymptomatic. Incidental finding during abdominal surgery or imaging studies is common. Resection with negative margins is the standard treatment. CASE REPORT: A 69-year-old female patient who debuted with massive digestive tract bleeding, requiring surgical treatment. A tumor was detected at jejunum compatible with a GIST.

INTRODUCCIÓN: Los tumores del estroma gastrointestinal (GIST) son poco frecuentes, con una incidencia de 10 a 15 casos por millón de habitantes. Suelen localizarse en el estómago (56%), el intestino delgado (32%), el colon-recto (6%) y el esófago (< 1%). Sus síntomas incluyen náusea, vómito y plenitud abdominal; el 30% son asintomáticos. Es común su hallazgo incidental durante una cirugía abdominal o en estudios de imagen. La resección con márgenes negativos es el tratamiento estándar. CASO CLÍNICO: Mujer de 69 años que debuta con hemorragia masiva de tubo digestivo, requiriendo tratamiento quirúrgico. Se detecta un tumor de yeyuno compatible con GIST.

Asociación de trastornos cutáneos y microorganismos presentes en el tracto intestinal ligados a disbiosis / Association of skin disorders and microorganisms present in the intestinal tract linked to dysbiosis / Associação de doenças de pele e microrganismos presentes no trato intestinal ligados à disbiose

Introducción: Existe una conexión bidireccional entre mecanismos fisiológicos del intestino y la piel que puede asociarse al desarrollo de patologias cutâneas. Objetivo: estudiar la relación entre afecciones cutáneas con la presencia de patógenos intestinales causantes de disbiosis intestinal. Metodología: se realizó un estudio para identificar la presencia de bacterias aeróbicas y anaeróbicas facultativas en un grupo de 45 pacientes (edad de 32,8 ± 18 años) que presentaron distintas afecciones cutáneas diagnosticadas en la consulta de Dermatología de UNIMEL, Caracas, Venezuela. La presencia de bacterias se determinó por cultivo diferencial, y la identificación de microorganismos mediante pruebas bioquímicas convencionales, prueba de filamentización en suero, medios automatizados (VITEK® 2 Compact) y pruebas de aglutinación. Se realizó un análisis estadístico descriptivo de la abundancia relativa de la microbiota gastrointestinal asociada a las afecciones cutáneas presentes (GraphPad Prism versión 8.0.2 para Windows) y análisis multivariado (NMDS) con (software PAST v4.13). Resultados: la presencia de acné, dermatitis atópica y nevus se asoció (p<0.05) al aumento de las colonias de Enterococcus faecium, E. coli, Enteroccocus faecalis y Klepsiella sp. Una disminución significativa en el número de colonias de E. coli (p<0.05) se asoció con la presencia de rosácea y acné inflamatorio mientras que su abundancia se asoció a la presencia de patologías como acantosis nigicans, dermatitis atópica, dermatitis papular y queratosis. La presencia de pseudomonas se relacionó con queratosis y Nevus melanocítico. Conclusión: aunque preliminares, estos resultados sugieren que alteraciones en la composición microbiana intestinal pueden asociarse significativamente a afecciones cutáneas

Introduction: There is a bidirectional connection between physiological mechanisms of the intestine and the skin that can be associated with the development of skin pathologies. Objective: To study the relationship between skin conditions with the presence of intestinal pathogens that cause intestinal dysbiosis. Methodology: a study was carried out to identify the presence of aerobic and facultative anaerobic bacteria in a group of 45 patients (age 32.8 ± 18 years) who presented different skin conditions diagnosed in the Dermatology clinic of UNIMEL, Caracas, Venezuela. The presence of bacteria was determined by differential culture, and the identification of microorganisms by conventional biochemical tests, serum filamentation test, automated media (VITEK® 2 Compact) and agglutination tests. A descriptive statistical analysis of the relative abundance of the gastrointestinal microbiota associated with the present skin conditions was performed (GraphPad Prism version 8.0.2 for Windows) and multivariate analysis (NMDS) with (PAST v4.13 software). Results: the presence of acne, atopic dermatitis and nevus was associated (p<0.05) with the increase in colonies of Enterococcus faecium, E. coli, Enteroccocus faecalis and Klepsiella sp. A significant decrease in the number of E. coli colonies (p<0.05) was associated with the presence of rosacea and inflammatory acne while its abundance was associated with the presence of pathologies such as acanthosis nigicans, atopic dermatitis, papular dermatitis and keratosis. The presence of pseudomonas was related to keratosis and melanocytic nevus. Conclusion: although preliminary, these results suggest that alterations in intestinal microbial composition can be significantly associated with skin conditions.

Introdução: existe uma ligação bidirecional entre mecanismos fisiológicos do intestino e da pele que pode estar associada ao desenvolvimento de patologias cutâneas. Objetivo: estudar a relação entre as condições da pele com a presença de patógenos intestinais causadores de disbiose intestinal. Metodologia: foi realizado um estudo para identificar a presença de bactérias aeróbias e anaeróbias facultativas em um grupo de 45 pacientes (idade 32,8 ± 18 años) que apresentavam diferentes condições de pele diagnosticadas na clínica de Dermatologia da UNIMEL, Caracas, Venezuela. A presença de bactérias foi determinada por cultura diferencial, e a identificação de microrganismos por testes bioquímicos convencionais, teste de filamentação sérica, meios automatizados (VITEK® 2 Compact) e testes de aglutinação. Foi realizada análise estatística descritiva da abundância relativa da microbiota gastrointestinal associada às presentes condições de pele (GraphPad Prism versão 8.0.2 para Windows) e análise multivariada (NMDS) com (software PAST v4.13). Resultados: A presença de acne, dermatite atópica e nevo esteve associada (p<0,05) ao aumento de colônias de Enterococcus faecium, E. coli, Enteroccocus faecalis e Klepsiella sp. Uma diminuição significativa no número de colônias de E. coli (p<0,05) foi associada à presença de rosácea e acne inflamatória, enquanto sua abundância foi associada à presença de patologias como acantose nigicans, dermatite atópica, dermatite papular e ceratose. A presença de pseudomonas foi relacionada à ceratose e ao nevo melanocítico. Conclusão: embora preliminares, estes resultados sugerem que alterações na composição microbiana intestinal podem estar significativamente associadas a doenças da pele.

Asociación de trastornos cutáneos y microorganismos presentes en el tracto intestinal ligados a disbiosis

Introducción: Existe una conexión bidireccional entre mecanismos fisiológicos del intestino y la piel que puede asociarse al desarrollo de patologias cutâneas. Objetivo: Estudiar la relación entre afecciones cutáneas con la presencia de patógenos intestinales causantes de disbiosis intestinal. Metodología: Se realizó un estudio para identificar la presencia de bacterias aeróbicas y anaeróbicas facultativas en un grupo de 45 pacientes (edad de 32,8 ± 18 años) que presentaron distintas afecciones cutáneas diagnosticadas en la consulta de Dermatología de UNIMEL, Caracas, Venezuela. La presencia de bacterias se determinó por cultivo diferencial, y la identificación de microorganismos mediante pruebas bioquímicas convencionales, prueba de filamentización en suero, medios automatizados (VITEK® 2 Compact) y pruebas de aglutinación. Se realizó un análisis estadístico descriptivo de la abundancia relativa de la microbiota gastrointestinal asociada a las afecciones cutáneas presentes (GraphPad Prism versión 8.0.2 para Windows) y análisis multivariado (NMDS) con (software PAST v4.13). Resultados: La presencia de acné, dermatitis atópica y nevus se asoció (p<0.05) al aumento de las colonias de Enterococcus faecium, E. coli, Enteroccocus faecalis y Klepsiella sp. Una disminución significativa en el número de colonias de E. coli (p<0.05) se asoció con la presencia de rosácea y acné inflamatorio mientras que su abundancia se asoció a la presencia de patologías como acantosis nigicans, dermatitis atópica, dermatitis papular y queratosis. La presencia de pseudomonas se relacionó con queratosis y Nevus melanocítico. Conclusión: Aunque preliminares, estos resultados sugieren que alteraciones en la composición microbiana intestinal pueden asociarse significativamente a afecciones cutáneas.

Introduction: There is a bidirectional connection between physiological mechanisms of the intestine and the skin that can be associated with the development of skin pathologies. Objective: To study the relationship between skin conditions with the presence of intestinal pathogens that cause intestinal dysbiosis. Methodology: A study was carried out to identify the presence of aerobic and facultative anaerobic bacteria in a group of 45 patients (age 32.8 ± 18 years) who presented different skin conditions diagnosed in the Dermatology clinic of UNIMEL, Caracas, Venezuela. The presence of bacteria was determined by differential culture, and the identification of microorganisms by conventional biochemical tests, serum filamentation test, automated media (VITEK® 2 Compact) and agglutination tests. A descriptive statistical analysis of the relative abundance of the gastrointestinal microbiota associated with the present skin conditions was performed (GraphPad Prism version 8.0.2 for Windows) and multivariate analysis (NMDS) with (PAST v4.13 software). Results: The presence of acne, atopic dermatitis and nevus was associated (p<0.05) with the increase in colonies of Enterococcus faecium, E. coli, Enteroccocus faecalis and Klepsiella sp. A significant decrease in the number of E. coli colonies (p<0.05) was associated with the presence of rosacea and inflammatory acne while its abundance was associated with the presence of pathologies such as acanthosis nigicans, atopic dermatitis, papular dermatitis and keratosis. The presence of pseudomonas was related to keratosis and melanocytic nevus. Conclusion: Although preliminary, these results suggest that alterations in intestinal microbial composition can be significantly associated with skin conditions.

Introdução: Existe uma ligação bidirecional entre mecanismos fisiológicos do intestino e da pele que pode estar associada ao desenvolvimento de patologias cutâneas. Objetivo: Estudar a relação entre as condições da pele com a presença de patógenos intestinais causadores de disbiose intestinal. Metodologia: Foi realizado um estudo para identificar a presença de bactérias aeróbias e anaeróbias facultativas em um grupo de 45 pacientes (idade 32,8 ± 18 años) que apresentavam diferentes condições de pele diagnosticadas na clínica de Dermatologia da UNIMEL, Caracas, Venezuela. A presença de bactérias foi determinada por cultura diferencial, e a identificação de microrganismos por testes bioquímicos convencionais, teste de filamentação sérica, meios automatizados (VITEK® 2 Compact) e testes de aglutinação. Foi realizada análise estatística descritiva da abundância relativa da microbiota gastrointestinal associada às presentes condições de pele (GraphPad Prism versão 8.0.2 para Windows) e análise multivariada (NMDS) com (software PAST v4.13). Resultados: A presença de acne, dermatite atópica e nevo esteve associada (p<0,05) ao aumento de colônias de Enterococcus faecium, E. coli, Enteroccocus faecalis e Klepsiella sp. Uma diminuição significativa no número de colônias de E. coli (p<0,05) foi associada à presença de rosácea e acne inflamatória, enquanto sua abundância foi associada à presença de patologias como acantose nigicans, dermatite atópica, dermatite papular e ceratose. A presença de pseudomonas foi relacionada à ceratose e ao nevo melanocítico. Conclusão: Embora preliminares, estes resultados sugerem que alterações na composição microbiana intestinal podem estar significativamente associadas a doenças da pele.

Is There an Interplay between Environmental Factors, Microbiota Imbalance, and Cancer Chemotherapy-Associated Intestinal Mucositis?

Interindividual variation in drug efficacy and toxicity is a significant problem, potentially leading to adverse clinical and economic public health outcomes. While pharmacogenetics and pharmacogenomics have long been considered the primary causes of such heterogeneous responses, pharmacomicrobiomics has recently gained attention. The microbiome, a community of microorganisms living in or on the human body, is a critical determinant of drug response and toxicity. Factors such as diet, lifestyle, exposure to xenobiotics, antibiotics use, illness, and genetics can influence the composition of the microbiota. Changes in the intestinal microbiota are particularly influential in drug responsiveness, especially in cancer chemotherapy. The microbiota can modulate an individual's response to a drug, affecting its bioavailability, clinical effect, and toxicity, affecting treatment outcomes and patient quality of life. For instance, the microbiota can convert drugs into active or toxic metabolites, influencing their efficacy and side effects. Alternatively, chemotherapy can also alter the microbiota, creating a bidirectional interplay. Probiotics have shown promise in modulating the microbiome and ameliorating chemotherapy side effects, highlighting the potential for microbiota-targeted interventions in improving cancer treatment outcomes. This opinion paper addresses how environmental factors and chemotherapy-induced dysbiosis impact cancer chemotherapy gastrointestinal toxicity.

Gut membrane proteins as candidate antigens for immunization of mice against the tick Amblyomma sculptum.

Amblyomma sculptum is widely distributed in Brazil and is the main vector of Rickettsia rickettsii, the causative agent of the Brazilian spotted fever (BSF). Tick gut proteins play an essential role in blood feeding, digestion, and protection of gut epithelium. Therefore, many of these were investigated as potential vaccine targets for tick-control strategies. The present study aimed to select transcripts corresponding to putative immunogenic proteins in the A. sculptum gut epithelial membrane, produce recombinant proteins and evaluate them as antigens against A. sculptum infestations. Three gut proteins - AsMucin, AsAPP, and AsLAMP - and a chimeric protein (rAsChimera) based on 22 peptides containing putative B cell epitopes from seven different gut proteins were evaluated as anti-A. sculptum antigens. Mice immunizations revealed that all recombinant targets elicited humoral response with significantly increased IgG levels compared to controls. For rAsChimera, IgG levels remained significantly higher than controls up to 75 days after the end of the immunization. Challenge trials revealed that vaccination with the chimeric protein was the most effective against A. sculptum, inducing 100 % nymph mortality and reaching 80.8 % efficacy against females. The other three proteins did not induce relevant protection, as AsAPP had only 26.6 % efficacy, whereas AsMucin and AsLAMP induced no protection. These data indicate that targeting gut protein immunogenic regions may be an effective strategy for a vaccine formulation againstA. sculptum.

Descriptive study of perineuronal net in enteric nervous system of humans and mice.

Perineuronal nets (PNN) are highly specialized structures of the extracellular matrix around specific groups of neurons in the central nervous system (CNS). They play functions related to optimizing physiological processes and protection neurons against harmful stimuli. Traditionally, their existence was only described in the CNS. However, there was no description of the presence and composition of PNN in the enteric nervous system (ENS) until now. Thus, our aim was to demonstrate the presence and characterize the components of the PNN in the enteric nervous system. Samples of intestinal tissue from mice and humans were analyzed by RT-PCR and immunofluorescence assays. We used a marker (Wisteria floribunda agglutinin) considered as standard for detecting the presence of PNN in the CNS and antibodies for labeling members of the four main PNN-related protein families in the CNS. Our results demonstrated the presence of components of PNN in the ENS of both species; however its molecular composition is species-specific.

Neumatosis quística intestinal, un reto diagnóstico: reporte de caso / Cystic intestinal pneumatosis, a diagnostic challenge: case report

Introducción. La neumatosis quística intestinal se describe como la presencia de gas dentro de la pared intestinal. Es una entidad poco frecuente, con una incidencia del 0,03 % en la población global. Aparece con predilección en el género masculino después de los 45 años yse localiza principalmente en el intestino delgado (42 %) y el colon. Se puede asociar a varias condiciones que en ocasiones requieren manejo quirúrgico. Caso clínico. Se presenta el caso de un hombre 75 años, con antecedente de hipertensión arterial, quien consultó por un cuadro de 15 días de evolución consistente en distensión abdominal, dolor y estreñimiento. En urgencias se solicitó una radiografía de tórax que mostró neumoperitoneo y varios niveles hidroaéreos, por lo que el cirujano de turno consideró una posible ruptura de víscera hueca. Resultados. Fue llevado a laparotomía exploratoria, donde se identificó neumatosis quística intestinal y estómago muy aumentado de tamaño, compatible con gastroparesia. Como resultado del tratamiento brindado, el paciente tuvo un desenlace satisfactorio logrando alta médica, apoyado con cuidados básicos de enfermería. Conclusiones. Si bien los casos de neumatosis quística intestinal son de presentación inusual, se puede encontrar en pacientes con hallazgos imagenológicos de neumoperitoneo. Por eso, se debe realizar un análisis concienzudo de cada paciente e individualizar el caso para el correcto diagnóstico.

Introduction. Cystic pneumatosis intestinalis is described as the presence of gas within the intestinal wall. It is a rare entity, with an incidence of 0.03% in the global population. It appears with a predilection in the male gender after 45 years of age and is located mainly in the small intestine (42%) and the colon. It can be associated with several conditions that sometimes require surgical management. Clinical case. The case of a 75-year-old man with a history of high blood pressure is presented, who consulted for a 15-day history consisting of abdominal distention, pain and constipation. In the emergency room, a chest x-ray was requested, which showed pneumoperitoneum and several air-fluid levels. The surgeon on call considered a possible rupture of the hollow viscus. Results. The patient was taken to exploratory laparotomy, where intestinal cystic pneumatosis and a greatly enlarged stomach were identified, compatible with gastroparesis. As a result of the treatment provided, the patient had a satisfactory outcome, achieving medical discharge, supported with basic nursing care. Conclusions. Although cases of intestinal cystic pneumatosis have an unusual presentation, it can be found in patients with imaging findings of pneumoperitoneum. Therefore, a thorough analysis of each patient must be carried out and the case individualized for the correct diagnosis.

Changes in SOD and NF-κB Levels in Substantia Nigra and the Intestine through Oxidative Stress Effects in a Wistar Rat Model of Ozone Pollution.

This work aimed to elucidate how O3 pollution causes a loss of regulation in the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 based on the association between the antioxidant response of superoxide dismutase (SOD) levels and the nuclear factor kappa light chains of activated B cells (NFκB) as markers of inflammation. Method: Seventy-two Wistar rats were used, divided into six groups that received the following treatments: Control and 7, 15, 30, 60, and 90 days of O3. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD and a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decreased. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to O3 alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This indicates that these factors are critical in the loss of regulation in the inflammatory response; they respond to ozone pollution, which can occur in chronic degenerative diseases.

Time-dependent impact of a high-fat diet on the intestinal barrier of male mice.

BACKGROUND: Excessive saturated fat intake compromises the integrity of the intestinal mucosa, leading to low-grade inflammation, impaired mucosal integrity, and increased intestinal permeability, resulting in the migration of lipopolysaccharide (LPS) to other tissues. AIM: To evaluate the chronic effects (at 10 and 16 wk) of a high-fat diet (HFD) (with 50% energy as fat) on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice. METHODS: Forty adult male mice were divided into four nutritional groups, where the letters refer to the type of diet (control and HFD or HF) and the numbers refer to the period (in weeks) of diet administration: Control diet for 10 wk, HFD for 10 wk, control diet for 16 wk, and HFD for 16 wk. After sacrifice, biochemical, molecular, and stereological analyses were performed. RESULTS: The HF groups were overweight, had gut dysbiosis, had a progressive decrease in occludin immunostaining, and had increased LPS concentrations. Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group, consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake. CONCLUSION: Chronic HFD intake causes overweight, gut dysbiosis, and morphological and functional alterations of the intestinal barrier after 10 or 16 wk. Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.

Effect of Different Levels of Extruded Coffee (Coffea arabica) Pulp Flour on the Productive Performance and Intestinal Morphometry of Cobb 500 Broiler Chickens.

Coffee pulp is a by-product of the coffee industry. Due to conventional management techniques, it represents a severe environmental problem due to its negative impact on the soil (anaerobic fermentation and pH changes), water sources (the infiltration of pollutants into streams, acidification of water sources, and modification of microorganisms), and biodiversity (soil microbiology, fish, crustaceans, and other vertebrates). Therefore, it is essential to develop protocols for the treatment of this waste so that it can be used again in other productive activities under the circular economy approach. This means that all the waste from a production process can be reused, can generate value for the benefit of the producer, and, in turn, mitigate the environmental impact. The objective of this study was to evaluate the replacement of 5 levels of wheat bran (WB) with extruded coffee pulp flour (ECPF) as an alternative to a conventional fiber source in broiler finisher diets. A total of 300 Cobb 500 chickens in the finishing phase were assessed in the study, grouped in 5 treatments: T1, a conventional diet or control treatment (100% WB and 0% ECPF), T2 (75% WB and 25% ECPF), T3 (50% WB and 50% ECPF), T4 (25% WB and 75% ECPF), and T5 (0% WB and 100% ECPF). Feed intake, weight gain, feed conversion ratio (FCR), and intestinal morphometry (villus length: VL, villus width: VW, crypt depth: CD, villus height/crypt depth ratio: V/C, and villus surface area: VSA) were evaluated at the level of the duodenum, jejunum, and ileum. Feed intake decreased correspondingly as the ECPF in the diet was increased, with statistical differences (p < 0.01) between their averages; the most significant weight gain (834.61 g) was evidenced with the T2 treatment, this being statistically different (p < 0.01) from T4 and T5; similarly, the best FCR (1.58) was evidenced with the T2 treatment, followed by the control treatment T1 (with 1.64); however, they were not statistically different (p > 0.05). All treatment results were similar to the VL control samples in the three intestinal portions, except for the T5 in the jejunum, which showed statistical differences from the control. In VW, the treatment results were similar to the control samples of the jejunum and ileum; however, in the duodenum, the T5 results showed the highest value (172.18 µm), being statistically different (p < 0.05) from the other treatments being evaluated. For CD, it was only in the duodenum that the T2 and T3 treatments were similar to the control. Likewise, for V/C in the duodenum, only the T2 results were similar to the control. There was no significant difference in the VSA among the different treatment groups. T2 showed better production parameters without altering the intestinal villi. In conclusion, ECPF is a potential input for use to replace up to 25% of WB in the feed of broilers in the finishing phase.

Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily.

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

Intestinal alterations and mild glucose homeostasis impairments in the offspring born to overweight rats.

The gut plays a crucial role in metabolism by regulating the passage of nutrients, water and microbial-derived substances to the portal circulation. Additionally, it produces incretins, such as glucose-insulinotropic releasing peptide (GIP) and glucagon-like derived peptide 1 (GLP1, encoded by gcg gene) in response to nutrient uptake. We aimed to investigate whether offspring from overweight rats develop anomalies in the barrier function and incretin transcription. We observed pro-inflammatory related changes along with a reduction in Claudin-3 levels resulting in increased gut-permeability in fetuses and offspring from overweight rats. Importantly, we found decreased gip mRNA levels in both fetuses and offspring from overweight rats. Differently, gcg mRNA levels were upregulated in fetuses, downregulated in female offspring and unchanged in male offspring from overweight rats. When cultured with high glucose, intestinal explants showed an increase in gip and gcg mRNA levels in control offspring. In contrast, offspring from overweight rats did not exhibit any response in gip mRNA levels. Additionally, while females showed no response, male offspring from overweight rats did exhibit an upregulation in gcg mRNA levels. Furthermore, female and male offspring from overweight rats showed sex-dependent anomalies when orally challenged with a glucose overload, returning to baseline glucose levels after 120 min. These results open new research questions about the role of the adverse maternal metabolic condition in the programming of impairments in glucose homeostasis, enteroendocrine function and gut barrier function in the offspring from overweight mothers and highlight the importance of a perinatal maternal healthy metabolism.

Microcystin-LR sensitizes the Oncorhynchus mykiss intestinal epithelium and interacts with paralytic shellfish toxins to alter oxidative balance.

In the context of harmful algal blooms, fish can be exposed to the combined effects of more than one toxin. We studied the effects of consecutive exposure to Microcystin-LR (MCLR) in vivo and paralytic shellfish toxins (PST) ex vivo/in vitro (MCLR+PST) in the rainbow trout Oncorhynchus mykiss's middle intestine. We fed juvenile fish with MCLR incorporated in the feed every 12 h and euthanized them 48 h after the first feeding. Immediately, we removed the middle intestine to make ex vivo and in vitro preparations and exposed them to PST for one hour. We analyzed glutathione (GSH) and glutathione disulfide (GSSG) contents, glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), and protein phosphatase 1 (PP1) activities in ex vivo intestinal strips; apical and basolateral ATP-biding cassette subfamily C (Abcc)-mediated transport in ex vivo everted and non- everted sacs; and reactive oxygen species (ROS) production in isolated enterocytes in vitro. MCLR+PST treatment decreased the GSH content, GSH/GSSG ratio, GST activity, and increased ROS production. GR activity remained unchanged, while CAT activity only increased in response to PST. MCLR inhibited PP1 activity and activated Abcc-mediated transport only at the basolateral side of the intestine. Our results show a combined effect of MCLR+PST on the oxidative balance in the O. mykiss middle intestine, which is not affected by the two toxins groups when applied individually. Basolateral Abcc transporters activation by MCLR treatment could lead to an increase in the absorption of toxicants (including MCLR) into the organism. Therefore, MCLR makes the O. mykiss middle intestine more sensitive to possibly co-occurring cyanotoxins like PST.

Perineuronal net in the extrinsic innervation of the distal colon of mice and its remodeling in ulcerative colitis.

The perineuronal net (PNN) is a well-described highly specialized extracellular matrix structure found in the central nervous system. Thus far, no reports of its presence or connection to pathological processes have been described in the peripheral nervous system. Our study demonstrates the presence of a PNN in the spinal afferent innervation of the distal colon of mice and characterizes structural and morphological alterations induced in an ulcerative colitis (UC) model. C57Bl/6 mice were given 3% dextran sulfate sodium (DSS) to induce acute or chronic UC. L6/S1 dorsal root ganglia (DRG) were collected. PNNs were labeled using fluorescein-conjugated Wisteria Floribunda (WFA) l lectin, and calcitonin gene-related peptide (CGRP) immunofluorescence was used to detect DRG neurons. Most DRG cell bodies and their extensions toward peripheral nerves were found surrounded by the PNN-like structure (WFA+), labeling neurons' cytoplasm and the pericellular surfaces. The amount of WFA+ neuronal cell bodies was increased in both acute and chronic UC, and the PNN-like structure around cell bodies was thicker in UC groups. In conclusion, a PNN-like structure around DRG neuronal cell bodies was described and found modulated by UC, as changes in quantity, morphology, and expression profile of the PNN were detected, suggesting a potential role in sensory neuron peripheral sensitization, possibly modulating the pain profile of ulcerative colitis.

Hemorragia digestiva por intususcepción de un lipoma ulcerado en yeyuno / Gastrointestinal bleeding due to ulcerated intussuscepted jejunal lipoma

RESUMEN Los lipomas yeyunales son tumores gastrointestinales benignos e infrecuentes, de origen mesenquimático, compuestos por adipocitos que suelen estar confinados a la submucosa. Generalmente son asintomáticos y se descubren de manera incidental al realizar estudios por imágenes o endoscópicos. Sin embargo, aquellos mayores de 2 cm pueden presentar síntomas como resultado de complicaciones, como intususcepción intestinal, obstrucción o rara vez, hemorragias. Presentamos un caso infrecuente de intususcepción de un lipoma yeyunal ulcerado en un adulto, diagnosticado en el contexto de un cuadro de hemorragia digestiva.

ABSTRACT Jejunal lipomas are rare benign mesenchymal tumors made up of adipocytes confined to the submucosa layer. They are usually asymptomatic and are incidentally found during imaging or endoscopic tests. Those measuring > 2 cm may become symptomatic as a result of complications as intestinal intussusception, obstruction and bleeding. We herein report a rare case of intussusception of an ulcerated jejunal lipoma in an adult patient, that was diagnosticated in the setting of an intestinal hemorrhage.

Dietary glycemic and energy load differentially modulates Schistosoma mansoni-induced granulomatous inflammation and response to antiparasitic chemotherapy.

The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.

Multicentric lymphoma in a donkey with intestinal and bone marrow involvement.

BACKGROUND: Lymphoma is a common neoplasm in horses but is reported much less commonly in donkeys. In this case report, we describe the macroscopic, microscopic and immunohistochemical features of a multicentric lymphoma with intestinal and bone marrow involvement. CASE PRESENTATION: A geriatric female donkey with history of chronic lameness was found dead. Post-mortem examination revealed advanced emaciation, periodontal disease, left front foot laminitis and multiple, soft, white to yellow tan intestinal transmural masses, up to 12 cm in diameter. Cytology suggested a round cell intestinal neoplasm. The femur of the left hint limb was double the size of the normal contralateral, with suspected neoplastic infiltration and replacement of bone marrow and bone. Histologically we diagnosed a lymphoma in the intestine and left femur. Immunohistochemically, the neoplastic cells showed CD3 immunolabelling, supporting a diagnosis of a multicentric T-cell lymphoma. CONCLUSIONS: To the authors' knowledge, this is the first time multicentric lymphoma is diagnosed in donkeys. Further studies of the genetic background, clinical, laboratory, histopathologic, and immunohistochemical, as well as the pathogenesis of lymphoma, is needed to better understand the uniquely low frequency of this neoplasm in donkeys.

Pharmacological evaluation of a traditional Brazilian medicinal plant, Monteverdia ilicifolia. Part I - Preclinical safety study.

ETHNOPHARMACOLOGICAL RELEVANCE: Monteverdia ilicifolia (Maytenus ilicifolia, Celastraceae), known as "espinheira-santa", has been widely used in Brazil to manage mainly gastrointestinal diseases. This species has been listed in the Brazilian Pharmacopeia and in the National List of Essential Medicines (RENAME). Considering that clinical studies about M. ilicifolia are rare, our group has been performing a broader project designed to evaluate the efficacy of M. ilicifolia capsules in a clinical trial, for this reason, approaches to provide safety to those patients are relevant. AIM OF THE STUDY: We aimed to investigate the potential pharmacokinetic interaction and hepatotoxicity and intestinal toxicity of an aqueous extract of M. ilicifolia and its main phytocompounds, catequin, epicatequin, and quercetin. METHODS AND MATERIALS: Slices of liver and intestine of Wistar rats were incubated with different concentrations of M. ilicifolia extract or isolated compounds (catechin, epicatechin and quercetin). Commercial kits were used to evaluate enzyme activities of CYP2D6 and CYP3A4 isoforms, as well as cell viability (MTT) assay and intracellular enzymes leakage, specifically lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were studied. RESULTS: Incubation with M. ilicifolia extract, catechin, epicatechin and quercetin did not affect significantly any evaluated parameter in intestines. The intracellular enzymes leakages, CYP2D6, LDH and AST, were increased with M. ilicifolia extract and quercetin in liver slices. CONCLUSIONS: Our in vitro findings highlighted, for the first time, the potential hepatotoxicity induced by an aqueous extract of M. ilicifolia, consequently this species and its products should be avoided in liver diseases, supporting that studies of safety must be performed including in the context of traditional medicinal plants.

Inhibition of vertebrate complement system by hematophagous arthropods: inhibitory molecules, mechanisms, physiological roles, and applications.

In arthropods, hematophagy has arisen several times throughout evolution. This specialized feeding behavior offered a highly nutritious diet obtained during blood feeds. On the other hand, blood-sucking arthropods must overcome problems brought on by blood intake and digestion. Host blood complement acts on the bite site and is still active after ingestion, so complement activation is a potential threat to the host's skin feeding environment and to the arthropod gut enterocytes. During evolution, blood-sucking arthropods have selected, either in their saliva or gut, anticomplement molecules that inactivate host blood complement. This review presents an overview of the complement system and discusses the arthropod's salivary and gut anticomplement molecules studied to date, exploring their mechanism of action and other aspects related to the arthropod-host-pathogen interface. The possible therapeutic applications of arthropod's anticomplement molecules are also discussed.