RESUMEN
Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of α-Syn in different tissues and detected phospho-α-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and impaired gut transit followed at 6 mo, preceding motor symptoms. The SncaG51D mice thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies.
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Modelos Animales de Enfermedad , Técnicas de Sustitución del Gen , Enfermedad de Parkinson , alfa-Sinucleína , Animales , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Ratones , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/patología , Ratones Transgénicos , Fosforilación , Trastornos del Olfato/genética , Trastornos del Olfato/metabolismo , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/patología , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/fisiopatología , Humanos , MasculinoRESUMEN
Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is a prime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to a markedly better improvement in the symptoms in women compared to men, although they showed a more pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with a generally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future.
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Esófago de Barrett , Humanos , Femenino , Masculino , Factores Sexuales , Esófago de Barrett/patología , Esófago de Barrett/diagnóstico , Esófago de Barrett/terapia , Reflujo Gastroesofágico/patología , Reflujo Gastroesofágico/diagnóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Acalasia del Esófago/patología , Acalasia del Esófago/genética , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/fisiopatología , Acalasia del Esófago/cirugía , Tracto Gastrointestinal Superior/patología , Enfermedades Gastrointestinales/patología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/genética , Inestabilidad de Microsatélites , Adenocarcinoma/patología , Adenocarcinoma/genética , Adenocarcinoma/cirugíaRESUMEN
In this editorial, we comment on three articles published in a recent issue of World Journal of Gastroenterology. There is a pressing need for new research on autophagy's role in gastrointestinal (GI) disorders, and also novel insights into some liver conditions, such as metabolic dysfunction-associated fatty liver disease (MAFLD) and acute liver failure (ALF). Despite advancements, understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete. Moreover, MAFLD's pathogenesis, encompassing hepatic steatosis and metabolic dysregulation, require further elucidation. Similarly, the mechanisms underlying ALF, a severe hepatic dysfunction, are poorly understood. Innovative studies exploring the interplay between autophagy and GI disorders, as well as defined mechanisms of MAFLD and ALF, are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.
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Autofagia , Fallo Hepático Agudo , Humanos , Fallo Hepático Agudo/metabolismo , Fallo Hepático Agudo/patología , Fallo Hepático Agudo/etiología , Hígado/patología , Hígado/metabolismo , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/etiología , Hígado Graso/metabolismo , Hígado Graso/patologíaRESUMEN
BACKGROUND AND HYPOTHESIS: The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. STUDY DESIGN: Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. STUDY RESULTS: The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. CONCLUSIONS: These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases.
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Encéfalo , Enfermedades Gastrointestinales , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/patología , Esquizofrenia/diagnóstico por imagen , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/patología , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Comorbilidad , Mapas de Interacción de Proteínas/genéticaRESUMEN
INTRODUCTION: Presence of deep infiltrating bowel endometriosis (DE) is associated with occurrence of dyschezia and gastrointestinal symptoms. The degree of the disease, the lesion length, and the location, that is, lesion-to-anal-verge distance (LAVD) of DE, as well as the severity of the symptoms appear to be correlated. Nevertheless, it is not yet known to what extent the size and LAVD of bowel DE influence the severity of gastrointestinal symptoms. The present study aims to evaluate a possible correlation of lesion location (LAVD) and size (according to the #Enzian classification) with preoperative symptoms. MATERIAL AND METHODS: In this prospective study, premenopausal patients with histologically confirmed DE undergoing modified limited nerve-vessel sparing rectal segmental bowel resection or full-thickness discoid resection were evaluated. Extent of endometriosis was defined according to the #Enzian classification during surgery. The primary outcome measure was the correlation between lesion size and location with the GI function impairment reflected by presurgical lower anterior resection syndrome (LARS) scores; the secondary outcome was differences in presurgical numeric rating scale pain scores of dyschezia, dyspareunia, and dysmenorrhea as well as the impact of concomitant DE of other locations on symptom intensity. RESULTS: Of 162 consecutive patients, 151 were included in the final analysis. No significant correlation was observed between lesion size (#Enzian compartments C1/C2/C3) or LAVD and GI dysfunction reflected by LARS-like symptoms (p = 0.314 and p = 0.185, respectively) or pain symptoms (dyschezia, p = 0.440; dyspareunia, p = 0.136; and dysmenorrhea p = 0.221). Furthermore, no significant correlation was observed between lesion size and GI dysfunction when merging two severity grades (#Enzian compartments C1 plus C2 vs. C3; p = 0.611). In addition, LAVD did not affect the degree of dyschezia (p = 0.892), dyspareunia (p = 0.395), or dysmenorrhea (p = 0.705). Finally, the presence of concomitant DE lesions infiltrating the vagina/rectovaginal space (#Enzian compartment A) and/or sacrouterine ligaments/parametrium (#Enzian compartment B) did not alter the severity of preoperative dyschezia (p = 0.493) or dysmenorrhea (p = 0.128) but showed a trend toward affecting gastrointestinal function (p = 0.078) and was significantly associated with dyspareunia (p = 0.035). CONCLUSIONS: In present study, we could not find a correlation between colorectal DE lesion size and location (LAVD) and gastrointestinal function impairment or intensity of dyschezia and dysmenorrhea. Additional involvement of vagina/rectovaginal space (#Enzian compartment A) and/or sacrouterine ligaments/parametrium (#Enzian compartment B) exerts a significant impact on the degree of dyspareunia in women with colorectal DE.
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Endometriosis , Humanos , Femenino , Endometriosis/patología , Endometriosis/complicaciones , Endometriosis/cirugía , Adulto , Estudios Prospectivos , Enfermedades del Recto/patología , Enfermedades del Recto/cirugía , Dismenorrea/etiología , Enfermedades Intestinales/patología , Enfermedades Intestinales/cirugía , Dispareunia/etiología , Dimensión del Dolor , Enfermedades Gastrointestinales/patologíaRESUMEN
In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.
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Autofagia , Enfermedades Gastrointestinales , Mitocondrias , Mitofagia , Humanos , Autofagia/fisiología , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/fisiopatología , Mitocondrias/metabolismo , Mitocondrias/patología , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/metabolismo , AnimalesRESUMEN
BACKGROUND/AIM: Cancer remains a major global health challenge, with an estimated 10 million cancer-related deaths in 2020, hindering efforts to extend life expectancy. Cisplatin, an effective platinum-based chemotherapeutic agent used against various malignancies, has numerous side effects. Ganoderma lucidum is a traditional Chinese medicine with extensive historical use and proven biological activity. This study investigated the effects of G. lucidum on cisplatin-induced nephrotoxicity and gastrointestinal toxicity. MATERIALS AND METHODS: RAW264.7 cells were treated with cisplatin, G. lucidum, or both. Cytotoxicity and antioxidant capacity were measured. Slc:ICR (ICR) mice were treated with cisplatin, G. lucidum, or both. The survival rate and physiological data were measured. RESULTS: G. lucidum suppressed cisplatin-induced cytotoxicity and apoptosis in RAW264.7 cells. G. lucidum suppressed cisplatin-induced nephrotoxicity and gastrointestinal toxicity via its antioxidant effects in ICR mice. CONCLUSION: The suppressive mechanism of G. lucidum may be mediated via its antioxidant effects. These findings indicate its potential to reduce the side effects of cisplatin.
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Apoptosis , Cisplatino , Reishi , Animales , Cisplatino/efectos adversos , Ratones , Reishi/química , Apoptosis/efectos de los fármacos , Células RAW 264.7 , Antineoplásicos/efectos adversos , Antioxidantes/farmacología , Ratones Endogámicos ICR , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/patologíaRESUMEN
The gastrointestinal (GI) tract is an organ actively involved in mechanical processes, where it detects forces via a mechanosensation mechanism. Mechanosensation relies on specialized cells termed mechanoreceptors, which convert mechanical forces into electrochemical signals via mechanosensors. The mechanosensitive Piezo1 and Piezo2 are widely expressed in various mechanosensitive cells that respond to GI mechanical forces by altering transmembrane ionic currents, such as epithelial cells, enterochromaffin cells, and intrinsic and extrinsic enteric neurons. This review highlights recent research advances on mechanosensitive Piezo channels in GI physiology and pathology. Specifically, the latest insights on the role of Piezo channels in the intestinal barrier, GI motility, and intestinal mechanosensation are summarized. Additionally, an overview of Piezo channels in the pathogenesis of GI disorders, including irritable bowel syndrome, inflammatory bowel disease, and GI cancers, is provided. Overall, the presence of mechanosensitive Piezo channels offers a promising new perspective for the treatment of various GI disorders.
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Tracto Gastrointestinal , Canales Iónicos , Mecanotransducción Celular , Humanos , Canales Iónicos/metabolismo , Animales , Tracto Gastrointestinal/metabolismo , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/fisiopatología , Enfermedades Gastrointestinales/patología , Motilidad Gastrointestinal/fisiologíaRESUMEN
Enteric glial cells (EGCs) are an essential component of the enteric nervous system (ENS) and play key roles in gastrointestinal development, homeostasis, and disease. Derived from neural crest cells, EGCs undergo complex differentiation processes regulated by various signalling pathways. Being among the most dynamic cells of the digestive system, EGCs react to cues in their surrounding microenvironment and communicate with various cell types and systems within the gut. Morphological studies and recent single cell RNA sequencing studies have unveiled heterogeneity among EGC populations with implications for regional functions and roles in diseases. In gastrointestinal disorders, including inflammatory bowel disease (IBD), infections and cancer, EGCs modulate neuroplasticity, immune responses and tumorigenesis. Recent evidence suggests that EGCs respond plastically to the microenvironmental cues, adapting their phenotype and functions in disease states and taking on a crucial role. They exhibit molecular abnormalities and alter communication with other intestinal cell types, underscoring their therapeutic potential as targets. This review delves into the multifaceted roles of EGCs, particularly emphasizing their interactions with various cell types in the gut and their significant contributions to gastrointestinal disorders. Understanding the complex roles of EGCs in gastrointestinal physiology and pathology will be crucial for the development of novel therapeutic strategies for gastrointestinal disorders.
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Sistema Nervioso Entérico , Neuroglía , Humanos , Neuroglía/fisiología , Sistema Nervioso Entérico/patología , Animales , Enfermedades Gastrointestinales/patologíaRESUMEN
Organoid models have recently been utilized to study 3D human-derived tissue systems to uncover tissue architecture and adult stem cell biology. Patient-derived organoids unambiguously provide the most suitable in vitro system to study disease biology with the actual genetic background. With the advent of much improved and innovative approaches, patient-derived organoids can potentially be used in regenerative medicine. Various human tissues were explored to develop organoids due to their multifold advantage over the conventional in vitro cell line culture approach and in vivo models. Gastrointestinal (GI) tissues have been widely studied to establish organoids and organ-on-chip for screening drugs, nutraceuticals, and other small molecules having therapeutic potential. The function of channel proteins, transporters, and transmembrane proteins was also explained. The successful application of genome editing in organoids using the CRISPR-Cas approach has been reported recently. GI diseases such as Celiac disease (CeD), Inflammatory bowel disease (IBD), and common GI cancers have been investigated using several patient-derived organoid models. Recent advancements on organoid bio-banking and 3D bio-printing contributed significantly in personalized disease management and therapeutics. This article reviews the available literature on investigations and translational applications of patient-derived GI organoid models, notably on elucidating gut-microbial interaction and epigenetic modifications.
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Enfermedades Gastrointestinales , Organoides , Humanos , Organoides/metabolismo , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/terapia , Enfermedades Gastrointestinales/metabolismo , Investigación Biomédica Traslacional , Animales , Investigación Biomédica , Edición Génica/métodos , Modelos BiológicosRESUMEN
This review addresses the need for innovative co-culture systems integrating the enteric nervous system (ENS) with intestinal organoids. The breakthroughs achieved through these techniques will pave the way for a transformative era in gastrointestinal (GI) disease modeling and treatment strategies. This review serves as an introduction to the companion protocol paper featured in this journal. The protocol outlines the isolation and co-culture of myenteric and submucosal neurons with small intestinal organoids. This review provides an overview of the intestinal organoid culture field to establish a solid foundation for effective protocol application. Remarkably, the ENS surpasses the number of neurons in the spinal cord. Referred to as the "second brain", the ENS orchestrates pivotal roles in GI functions, including motility, blood flow, and secretion. The ENS is organized into myenteric and submucosal plexuses. These plexuses house diverse subtypes of neurons. Due to its proximity to the gut musculature and its cell type complexity, there are methodological intricacies in studying the ENS. Diverse approaches such as primary cell cultures, three-dimensional (3D) neurospheres, and induced ENS cells offer diverse insights into the multifaceted functionality of the ENS. The ENS exhibits dynamic interactions with the intestinal epithelium, the muscle layer, and the immune system, influencing epithelial physiology, motility, immune responses, and the microbiome. Neurotransmitters, including acetylcholine (ACh), serotonin (5-HT), and vasoactive intestinal peptide (VIP), play pivotal roles in these intricate interactions. Understanding these dynamics is imperative, as the ENS is implicated in various diseases, ranging from neuropathies to GI disorders and neurodegenerative diseases. The emergence of organoid technology presents an unprecedented opportunity to study ENS interactions within the complex milieu of the small and large intestines. This manuscript underscores the urgent need for standardized protocols and advanced techniques to unravel the complexities of the ENS and its dynamic relationship with the gut ecosystem. The insights gleaned from such endeavors hold the potential to revolutionize GI disease modeling and treatment paradigms.
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Técnicas de Cocultivo , Sistema Nervioso Entérico , Enfermedades Gastrointestinales , Organoides , Humanos , Técnicas de Cocultivo/métodos , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/terapia , Animales , Modelos Biológicos , Neuronas/metabolismo , IntestinosRESUMEN
BACKGROUND AND STUDY AIMS: Gastrointestinal adverse reaction to food (GARF) is reported frequently in the general population and even more in patients with disorders of the gut brain axis. However, there is a significant difference between self-reported and objective proven GARF. The aim of the study was to characterize a mucosal correlate of GARF by endoscopic confocal laser endomicroscopy (eCLE) with duodenal food challenge (DFC). PATIENTS AND METHODS: In an observational and proof of concept study we evaluated 71 patients with disorders of the gut brain axis without (group I, n=19) and with (group II, n=52) GARF by eCLE and DFC. Spontaneous and food induced transfer of fluorescein into duodenal lumen was detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. RESULTS: According to Rom IV, the patients (group I/II) could be classified as irritable bowel syndrome (IBS) 32%/31%, functional abdominal pain without changes in bowel movement 47 %/48 %, functional abdominal bloating/distension 0 %/10 %, functional diarrhea 5 %/ 2 %, and unspecified functional bowel disorder 16 %/10 %, respectively. 21 %/27 % of the patients responded with a fluorescein leakage into the duodenal lumen before and 74 %/69 % following to DFC. Frequency rank order of food components that induced a response were soy (55.5 %/60 %), wheat (60 %/45.5 %), egg (35.7 %/8.3), milk (30 %/18.2 %) and yeast (10 %/6.6 %), respectively. Histology of duodenal biopsies, number, form and distribution of intraepithelial lymphocytes and mucosal mast cells as well as mast cell function were normal. Overall, 14 %/79 % reported main symptom benefit following a food exclusion therapy according to eCLE and DFC that was significant different between the groups. CONCLUSION: The results of our study indicate that eCLE with DFC is a technique to clinically evaluate patients with disorders of the gut brain axis and GARF resulting in a high proportion of patients reporting symptom benefit upon food exclusion dietary advice focussed on the results of eCLE.
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Microscopía Confocal , Humanos , Microscopía Confocal/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/etiología , Anciano , Endoscopía Gastrointestinal/efectos adversos , Endoscopía Gastrointestinal/métodos , Alimentos/efectos adversos , Hipersensibilidad a los Alimentos , Mucosa Intestinal/patologíaRESUMEN
Olympus Corporation developed texture and color enhancement imaging (TXI) as a novel image-enhancing endoscopic technique. This topic highlights a series of hot-topic articles that investigated the efficacy of TXI for gastrointestinal disease identification in the clinical setting. A randomized controlled trial demonstrated improvements in the colorectal adenoma detection rate (ADR) and the mean number of adenomas per procedure (MAP) of TXI compared with those of white-light imaging (WLI) observation (58.7% vs 42.7%, adjusted relative risk 1.35, 95%CI: 1.17-1.56; 1.36 vs 0.89, adjusted incident risk ratio 1.48, 95%CI: 1.22-1.80, respectively). A cross-over study also showed that the colorectal MAP and ADR in TXI were higher than those in WLI (1.5 vs 1.0, adjusted odds ratio 1.4, 95%CI: 1.2-1.6; 58.2% vs 46.8%, 1.5, 1.0-2.3, respectively). A randomized controlled trial demonstrated non-inferiority of TXI to narrow-band imaging in the colorectal mean number of adenomas and sessile serrated lesions per procedure (0.29 vs 0.30, difference for non-inferiority -0.01, 95%CI: -0.10 to 0.08). A cohort study found that scoring for ulcerative colitis severity using TXI could predict relapse of ulcerative colitis. A cross-sectional study found that TXI improved the gastric cancer detection rate compared to WLI (0.71% vs 0.29%). A cross-sectional study revealed that the sensitivity and accuracy for active Helicobacter pylori gastritis in TXI were higher than those of WLI (69.2% vs 52.5% and 85.3% vs 78.7%, respectively). In conclusion, TXI can improve gastrointestinal lesion detection and qualitative diagnosis. Therefore, further studies on the efficacy of TXI in clinical practice are required.
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Enfermedades Gastrointestinales , Humanos , Enfermedades Gastrointestinales/diagnóstico por imagen , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/patología , Aumento de la Imagen/métodos , Adenoma/diagnóstico por imagen , Adenoma/patología , Imagen de Banda Estrecha/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Colonoscopía/métodos , ColorRESUMEN
Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.
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Endoscopía Capsular , Endoscopía Capsular/métodos , Humanos , Animales , Rayos Infrarrojos , Técnicas Biosensibles/métodos , Ratones , Diseño de Equipo , Imagen Óptica/métodos , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/diagnóstico por imagen , Enfermedades Gastrointestinales/patología , FluorescenciaRESUMEN
This review aims to present a comprehensive overview of the current landscape of artificial intelligence (AI) applications in the analysis of tubular gastrointestinal biopsies. These publications cover a spectrum of conditions, ranging from inflammatory ailments to malignancies. Moving beyond the conventional diagnosis based on hematoxylin and eosin-stained whole-slide images, the review explores additional implications of AI, including its involvement in interpreting immunohistochemical results, molecular subtyping, and the identification of cellular spatial biomarkers. Furthermore, the review examines how AI can contribute to enhancing the quality and control of diagnostic processes, introducing new workflow options, and addressing the limitations and caveats associated with current AI platforms in this context.
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Inteligencia Artificial , Tracto Gastrointestinal , Flujo de Trabajo , Humanos , Biopsia/métodos , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/metabolismo , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/diagnósticoRESUMEN
In the summer of 2023, ingestion of Astylus atromaculatus (pollen beetle) was linked to spontaneous fatal disease in grazing cattle and sheep in Argentina and Uruguay. While the disease was experimentally reproduced in sheep and guinea pigs in the 1970's, no experimental reproductions have been attempted in cattle, and controversy exists as to whether this insect is indeed noxious to cattle and at which dose. Here, we demonstrate that A. atromaculatus causes acute fatal disease in Hereford calves at single oral dosages of 2.5, 4.5, 10.0, and 15.0 g of insect/kg body weight. Death or severe disease necessitating euthanasia occurred at 38 to 48 hours postinoculation regardless of the dose, suggesting that the single fatal dosage is likely <2.5 g/kg body weight (this dose representing approximately 850 mL of intact beetles in a 100 kg calf). Clinically, the disease was characterized by acute anorexia, prolonged recumbency, reluctance to move, listlessness/apathy, depression, ruminal hypomotility and tympany, hypothermia, bruxism with frothing at the mouth, and mucoid diarrhea progressing to death. Hematologic and biochemical alterations included hemoconcentration, stress/acute inflammatory leukogram, negative energy balance, and ketosis. The pathological hallmark of this experimental disease is acute necrotizing omaso-reticulo-rumenitis, fibrinohemorrhagic enteritis, and exfoliative colitis with intralesional chitinous insect fragments. While A. atromaculatus might contain a gastrointestinal toxin or pathogen, extensive toxicological testing failed to identify a causative toxin. Other pathomechanisms such as direct physical damage caused by insect fragments on the alimentary tract seem plausible, although further studies are needed to elucidate the pathogenesis of A. atromaculatus-associated disease.
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Enfermedades de los Bovinos , Escarabajos , Enfermedades Gastrointestinales , Animales , Enfermedades Gastrointestinales/veterinaria , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/parasitología , Bovinos , Enfermedades de los Bovinos/patología , Enfermedades de los Bovinos/parasitología , Administración Oral , Femenino , MasculinoRESUMEN
OBJECTIVES: Small fiber neuropathy (SFN) affects the fibers involved in cutaneous and visceral pain and temperature sensation and are a crucial part of the autonomic nervous system. Autonomic dysfunction secondary to SFN and autoimmune receptor antibodies is being increasingly recognized, and gastrointestinal (GI) manifestations include constipation, early satiety, nausea, vomiting, and diarrhea. Enteric nervous system involvement may be a possible explanation of abnormal GI motility patterns seen in these patients. METHODS: Children suspected to have SFN based on symptoms underwent skin biopsy at the Child Neurology clinic at Arnold Palmer Hospital for Children, which was processed at Therapath™ Neuropathology. SFN was diagnosed using epidermal nerve fiber density values that were below 5th percentile from the left distal leg (calf) as reported per Therapath™ laboratory. RESULTS: Twenty-six patients were diagnosed with SFN. Retrospective chart review was performed, including demographic data, clinical characteristics, and evaluation. A majority of patients were white adolescent females. Autonomic dysfunction, including orthostasis and temperature dysregulation were seen in 61.5% of patients (p = 0.124). Somatosensory symptoms, including pain or numbness were seen in 85% of patients (p < 0.001). GI symptoms were present in 85% of patients (p < 0.001) with constipation being the most common symptom seen in 50% of patients. This correlated with the motility testing results. CONCLUSIONS: Pediatric patients with SFN commonly have GI symptoms, which may be the main presenting symptom. It is important to recognize and look for symptoms of small fiber neuropathy in children with refractory GI symptoms that may explain multisystemic complaints often seen in these patients.
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Enfermedades Gastrointestinales , Neuropatía de Fibras Pequeñas , Femenino , Adolescente , Humanos , Niño , Neuropatía de Fibras Pequeñas/diagnóstico , Neuropatía de Fibras Pequeñas/etiología , Estudios Retrospectivos , Fibras Nerviosas/patología , Piel/patología , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/patología , Biopsia , Estreñimiento/diagnóstico , Estreñimiento/etiología , Estreñimiento/patologíaRESUMEN
Ferroptosis is a form of nonapoptotic cell death that involves iron-dependent phospholipid peroxidation induced by accumulation of reactive oxygen species, and results in plasma membrane damage and the release of damage-associated molecular patterns. Ferroptosis has been implicated in aging and immunity, as well as disease states including intestinal and liver conditions and cancer. To date, several ferroptosis-associated genes and pathways have been implicated in liver disease. Although ferroptotic cell death is associated with dysfunction of the intestinal epithelium, the underlying molecular basis is poorly understood. As the mechanisms regulating ferroptosis become further elucidated, there is clear potential to use ferroptosis to achieve therapeutic benefit.
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Ferroptosis , Enfermedades Gastrointestinales , Especies Reactivas de Oxígeno , Humanos , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/patología , Enfermedades Gastrointestinales/fisiopatología , Especies Reactivas de Oxígeno/metabolismo , Animales , Hierro/metabolismo , Transducción de Señal , Peroxidación de LípidoRESUMEN
Adenovirus can cause severe disease in hematopoietic stem cell transplant (HSCT) patients. Histopathologic features of this infection in gastrointestinal biopsies and their distinction from graft-versus-host disease (GVHD) have been incompletely studied. We retrospectively identified patients with gastrointestinal adenovirus infection. H&E-stained sections were reviewed and the histologic features were recorded. The extent of immunostaining was determined using a semiquantitative scale and a maximum number of positive cells per high-power field. Information regarding the clinical course and endoscopic findings were obtained from the electronic medical records. The study group included 32 HSCT patients. Most (81%) presented with diarrhea and detectable virus in the serum. Twenty patients had multiorgan involvement in the gastrointestinal tract, mostly in the duodenum (62%) and colon (56%). Characteristic features included apoptotic epithelial cells with nuclear disarray (84%) and tufted aggregates of degenerating epithelial cells (69%), the latter of which was more commonly seen in the study population more than a control group of HSCT patients with GI involvement by GVHD. Viral inclusions were limited to the superficial epithelium in 59% of samples, and the density of viral inclusions within biopsies was variable (grade 1: 40%, grade 2: 38%, and grade 3: 22%). Following therapy, 10 patients (30%) improved and 14 (42%) had progressive disease. Patients with disease progression were often older (64 vs. 36 years, P =0.01) with higher serologic viral loads, prior history of GVHD, multifocal involvement, and increased number and density of immunoreactive nuclei. Adenovirus infection elicits a spectrum of histologic changes that can simulate or occur in combination with gastrointestinal GVHD. Patients with progressive disease are more likely to have high viral loads and more extensive infection of the gastrointestinal tract.
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Infecciones por Adenoviridae , Enfermedades Gastrointestinales , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Adenoviridae , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/patología , Trasplante de Células Madre/efectos adversos , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/patología , Infecciones por Adenoviridae/complicacionesRESUMEN
OBJECTIVE: This article aimed to analyze upper endoscopic findings in the HIV patient population to elucidate the upper-gastrointestinal complications related to HIV infection. Gastrointestinal (GI) disorders in individuals living with HIV/AIDS exhibit diverse and often nonspecific manifestations, imposing substantial morbidity and mortality burdens. Endoscopic evaluation with biopsies is essential in the diagnosis and management of these conditions. Delayed treatment due to undetected GI abnormalities during endoscopic examinations can lead to poorer health outcomes. METHODS: This systematic review has determined the findings of upper-GI endoscopy of HIV-infected patients. Online databases of PubMed, Web of Science, Jisc Library Hub Discover, and Library of Congress have been searched using relevant keyword combinations. We have retrieved all the pertinent papers and reports published in English and screened them against inclusion/exclusion criteria for data extraction in two steps. First, titles/abstracts have been evaluated and then full-text screening has been performed by independent researchers. This study has adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. RESULTS: In this review, 24 articles have been included in the final analysis. The study has focused on the characteristics of participants and the findings of endoscopic evaluations. The participants of the study have been HIV-positive patients, and the majority of them have undergone endoscopy due to gastrointestinal symptoms. The biopsy regions primarily targeted have been observed to be the esophagus, stomach, and duodenum. The most common result of the biopsy specimens has been chronic active gastritis. CONCLUSION: To improve clinical practice, this systematic review sought to provide an up-to-date reference for upper gastrointestinal endoscopic findings of HIV-infected persons. Our results are in line with earlier research showing how effective endoscopy is for determining a precise diagnosis and directing care. The majority of HIV patients with gastrointestinal symptoms have been found to have opportunistic infections and persistent active gastritis as well as mucosal abnormalities of the upper gastrointestinal tract. Studies have shown that endoscopic and histological assessment can aid in the early detection and management of issues involving the upper gastrointestinal tract.