RESUMEN
BACKGROUND: Clonorchis sinensis is a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensis infection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown. METHODS: Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples. RESULTS: Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcus abundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensis may promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair. CONCLUSIONS: This study provides comprehensive insights into the pathological effects of C. sinensis infection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensis pathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions.
Title: L'infection par Clonorchis sinensis induit des changements pathologiques dans l'épithélium des voies biliaires félines et modifie la composition du microbiote biliaire. Abstract: Contexte : Clonorchis sinensis est une douve zoonotique du foie qui habite les voies biliaires du foie humain pendant des périodes prolongées, conduisant au cholangiocarcinome. Des recherches récentes indiquent des associations entre une altération du microbiote biliaire et des pathologies des voies biliaires. Cependant, les impacts de l'infection par C. sinensis sur l'épithélium des voies biliaires et les effets ultérieurs sur le microbiote biliaire restent inconnus. Méthodes : Des échantillons de voies biliaires félines ont été prélevés sur des chats non infectés et infectés par C. sinensis. Un examen histopathologique a été réalisé pour évaluer les modifications épithéliales, la fibrose, la mucine et la prolifération cellulaire à l'aide de la coloration à l'hématoxyline-éosine et de l'immunohistochimie. De plus, la composition du microbiote biliaire a été analysée par séquençage du gène de l'ARNr 16S. Des analyses statistiques ont été menées pour comparer la diversité microbienne et l'abondance relative entre les échantillons infectés et non infectés. Résultats : L'analyse histopathologique des voies biliaires félines infectées a révélé une hyperplasie épithéliale importante caractérisée par une prolifération cellulaire accrue. De plus, une fibrose péricanalaire et une fibrose du collagène ont été observées dans les échantillons infectés par rapport aux témoins non infectés. La richesse microbienne biliaire diminue avec la progression de la maladie par rapport aux témoins non infectés. L'abondance des streptocoques est positivement corrélée à la gravité de la maladie, dominant les communautés dans les échantillons avec cancer. L'analyse fonctionnelle prédictive suggère que C. sinensis pourrait favoriser les lésions des voies biliaires en augmentant les gènes microbiens pour le métabolisme des glucides, la réplication et la réparation. Conclusions : Cette étude fournit des informations complètes sur les effets pathologiques de l'infection à C. sinensis sur l'épithélium des voies biliaires félines et son influence sur la composition du microbiote biliaire. Ces nouvelles découvertes donnent un aperçu sur la pathogenèse de C. sinensis et pourraient éclairer le développement thérapeutique contre la clonorchiase humaine. Des recherches supplémentaires sont nécessaires pour élucider les mécanismes sous-jacents à l'origine de ces changements et leurs implications sur les interactions hôte-parasite.
Asunto(s)
Conductos Biliares , Enfermedades de los Gatos , Clonorquiasis , Clonorchis sinensis , Microbiota , ARN Ribosómico 16S , Animales , Gatos , Clonorquiasis/parasitología , Clonorquiasis/veterinaria , Clonorchis sinensis/fisiología , Conductos Biliares/parasitología , Conductos Biliares/patología , Enfermedades de los Gatos/parasitología , Enfermedades de los Gatos/microbiología , ARN Ribosómico 16S/genética , Epitelio/microbiología , Epitelio/patología , Fibrosis , Proliferación Celular , MasculinoRESUMEN
BACKGROUND/AIM: Cigarette smoke has been shown to induce a phenotype in humans known as "acquired cystic fibrosis". This occurs because the cystic fibrosis transmembrane conductance regulator (CFTR) functions are impaired systemically due to the deleterious effects of smoke components. Elucidation of cigarette smoke effects on the tracheal epithelium is important. The aim of this study was to develop an ex vivo sheep tracheal model to investigate tracheal ion function. In this model, the epithelial sodium channel (ENaC) is inhibited after exposure to cigarette smoke extract (CSE) as a proof of principle. MATERIALS AND METHODS: Tracheas were isolated from healthy sheep and the tracheal epithelium was surgically excised. Tissues were mounted in Ussing chambers and the short circuit current (Isc) was measured after incubation with 5% CSE in PBS or PBS alone for 30 min. The function of ENaC was investigated by the addition of amiloride (10-5M) apically. Western blot analysis was performed to assess differences in ENaC quantity after CSE exposure. Some specimens were stained with H&E for detection of histological alterations. RESULTS: The amiloride effect on normal epithelium led to a significant decrease in Isc [ΔI=33±5.92 µA/cm2; p<0.001 versus control experiments (ΔI=1.44±0.71 µA/cm2)]. After incubation with CSE, ENaC Isc was significantly reduced (ΔI=14.80±1.96 µA/cm2; p<0.001). No differences in αENaC expression were observed between CSE-exposed and normal tracheal epithelium. Histological images post CSE incubation revealed decreases in the height of the epithelium, with basal cell hyperplasia and loss of ciliated cells. CONCLUSION: Reduced ENaC inhibition by amiloride after CSE incubation could be due to alterations in the tracheal epithelium.
Asunto(s)
Canales Epiteliales de Sodio , Tráquea , Animales , Canales Epiteliales de Sodio/metabolismo , Ovinos , Tráquea/metabolismo , Tráquea/efectos de los fármacos , Tráquea/patología , Proyectos Piloto , Humo/efectos adversos , Amilorida/farmacología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/patología , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Epitelio/patologíaRESUMEN
OBJECTIVE: In recent years, the clinical efficacy of medications for adenoid hypertrophy has been demonstrated. Topical nasal steroids have effects to shrink hypertrophic adenoids and improve symptoms of associated diseases. However, the mechanism which topical steroid administrations cause adenoid shrinkage remains unclear, herein, sensitivity for topical steroids in the mucosal epithelium of adenoids was evaluated histologically by comparing with tonsils. METHODS: Histological analysis was performed on adenoids and tonsils removed from 32 pediatric patients with adenoid hypertrophy. In hematoxylin-eosin-stained specimens, the morphology of the mucosal epithelium and eosinophil infiltration were evaluated. The expression of the glucocorticoid receptor (GR), interleukin (IL)-4, and IL-25 in the mucosal epithelium was evaluated, and the staining intensity was scored as 0 (none), 1 (weak), and 2 (strong). The number of eosinophils and expression scores of GR, IL-4, and IL-25 were statistically compared between adenoids and tonsils and analyzed correlations with adenoids sizes. RESULTS: Adenoids were covered with ciliated epithelium, and eosinophils in the mucosal epithelium and submucosal area was higher than tonsils (p < 0.05). GR expression in the most superficial layer of the mucosal epithelium was observed in adenoids, and the expression intensity score was higher than that in tonsils (p < 0.05). IL-4 and IL-25 were more widely expressed in the mucosal epithelium of adenoids than in tonsils, and their expression intensity scores were also higher than in tonsils (p < 0.05). A correlation was found between adenoid size and the intensity of IL-25 expression in the adenoid epithelium (p < 0.05). CONCLUSION: Eosinophilic inflammations in adenoids mucosal epithelium could be one of etiology of adenoid hypertrophy, and the GR and eosinophilic inflammation in the adenoids mucosal epithelium might be target of topical nasal steroids to shrink hypertrophic adenoids.
Asunto(s)
Tonsila Faríngea , Eosinófilos , Hipertrofia , Tonsila Palatina , Receptores de Glucocorticoides , Humanos , Tonsila Faríngea/patología , Tonsila Faríngea/metabolismo , Receptores de Glucocorticoides/metabolismo , Masculino , Niño , Femenino , Eosinófilos/metabolismo , Preescolar , Tonsila Palatina/patología , Interleucina-17/metabolismo , Membrana Mucosa/patología , Membrana Mucosa/metabolismo , Interleucina-4/metabolismo , Epitelio/patología , Epitelio/metabolismo , Glucocorticoides , Citocinas/metabolismo , AdolescenteRESUMEN
To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria.
Asunto(s)
Membrana Mucosa , Vagina , Humanos , Femenino , Vagina/patología , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Membrana Mucosa/patología , Adulto Joven , Anciano , China , Factores de Edad , Adolescente , Índice de Masa Corporal , Epitelio/patologíaRESUMEN
At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5ß1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium.
Asunto(s)
Ascitis , Fibrina , Fibrinógeno , Integrina alfa5beta1 , Neoplasias Ováricas , Esferoides Celulares , Microambiente Tumoral , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Ascitis/patología , Ascitis/metabolismo , Integrina alfa5beta1/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Fibrinógeno/metabolismo , Fibrina/metabolismo , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/patología , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Línea Celular Tumoral , Receptores de Vitronectina/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Adhesión Celular , Peritoneo/patología , Peritoneo/metabolismo , Epitelio/metabolismo , Epitelio/patología , Cadherinas/metabolismo , Células Tumorales CultivadasRESUMEN
Emperipolesis is a cell-within-cell phenomenon distinct from phagocytosis more often described in Rosai-Dorfman disease, where usually lymphocytes or other bone marrow cells (plasma cells, erythroblasts or neutrophils) are entirely surrounded but not engulfed by macrophages as the host cell, but occasionally megakaryocytes and neoplastic could be. Mesothelial cell has been described in a couple of cases of lymphomas affecting serous membranes, but never described in pleuritis. In the present work, the first case of emperipolesis by mesothelial cells in a patient with self-limited pleural effusion was demonstrated by immunohistochemistry and Electron Microscopy studies.
Asunto(s)
Emperipolesis , Histiocitosis Sinusal , Humanos , Persona de Mediana Edad , Células Epiteliales/patología , Células Epiteliales/ultraestructura , Epitelio/patología , Epitelio/ultraestructura , Histiocitosis Sinusal/patología , Histiocitosis Sinusal/complicaciones , Inmunohistoquímica , Derrame Pleural/patologíaRESUMEN
OBJECTIVE: Needle biopsy is a common technique used to obtain cell and tissue samples for diagnostics. Currently, two biopsy methods are widely used: (i) fine-needle aspiration biopsy (FNAB) and (ii) core needle biopsy (CNB). However, these methods have limitations. Recently, we developed ultrasound-enhanced fine-needle aspiration biopsy (USeFNAB), which employs a needle that flexurally oscillates at an ultrasonic frequency of â¼32 kHz. The needle motion contributes to increased tissue collection while preserving cells and tissue constructs for pathological assessment. Previously, USeFNAB has been investigated only in ex vivo animal tissue. The present study was aimed at determining the feasibility of using USeFNAB in human epithelial and lymphoid tissue. METHODS: Needle biopsy samples were acquired using FNAB, CNB and USeFNAB on ex vivo human tonsils (N = 10). The tissue yield and quality were quantified by weight measurement and blinded pathologists' assessments. The biopsy methods were then compared. RESULTS: The results revealed sample mass increases of, on average, 2.3- and 5.4-fold with USeFNAB compared with the state-of-the-art FNAB and CNB, respectively. The quality of tissue fragments collected by USeFNAB was equivalent to that collected by the state-of-the-art methods in terms of morphology and immunohistochemical stainings made from cell blocks as judged by pathologists. CONCLUSION: Our study indicates that USeFNAB is a promising method that could improve tissue yield to ensure sufficient material for ancillary histochemical and molecular studies for diagnostic pathology, thereby potentially increasing diagnostic accuracy.
Asunto(s)
Tejido Linfoide , Tonsila Palatina , Humanos , Tonsila Palatina/patología , Tonsila Palatina/diagnóstico por imagen , Tejido Linfoide/patología , Tejido Linfoide/diagnóstico por imagen , Biopsia con Aguja Fina/métodos , Estudios de Factibilidad , Ultrasonografía Intervencional/métodos , Biopsia Guiada por Imagen/métodos , Epitelio/patologíaRESUMEN
BACKGROUND: Gallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown. METHODS: A prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium. RESULTS: Gallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism. CONCLUSION: Our study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis.
Asunto(s)
Enfermedades de los Perros , Enfermedades de la Vesícula Biliar , Vesícula Biliar , Lipogénesis , Mucocele , Animales , Perros , Mucocele/metabolismo , Mucocele/patología , Vesícula Biliar/metabolismo , Vesícula Biliar/patología , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Enfermedades de la Vesícula Biliar/metabolismo , Enfermedades de la Vesícula Biliar/patología , Enfermedades de la Vesícula Biliar/veterinaria , Femenino , Estudios de Casos y Controles , Masculino , Lipidosis/metabolismo , Lipidosis/patología , Estudios Prospectivos , Epitelio/metabolismo , Epitelio/patología , Metabolismo de los LípidosRESUMEN
The objective of this study to examine the effects of curcumin and gallic acid use against oxidative stress damage in the autologous intraperitoneal ovarian transplantation model created in rats on ovarian follicle reserve, ovarian surface epithelium, and oxidant-antioxidant systems. 42 adult female Sprague Dawley rats (n=7) were allocated into 6 groups. Group 1 served as the control. In Group 2, rats underwent ovarian transplantation (TR) to their peritoneal walls. Group 3 received corn oil (CO) (0.5â¯ml/day) one day before and 14 days after transplantation. Group 4 was administered curcumin (CUR) (100â¯mg/kg/day), Group 5 received gallic acid (GA) (20â¯mg/kg/day), and Group 6 was treated with a combination of curcumin and gallic acid via oral gavage after transplantation. Rats were sacrificed on the 14th postoperative day, and blood along with ovaries were collected for analysis. The removed ovaries were analyzed at light microscopic, fluorescence microscopic, and biochemical levels. In Group 2 and Group 3, while serum and tissue Total Oxidant Levels (TOS) and Oxidative Stress Index (OSI) increased, serum Total Antioxidant Levels (TAS) decreased statistically significantly (pË0.05) compared to the other groups (Groups 1, 4, 5, and 6). The ovarian follicle reserve was preserved and the changes in the ovarian surface epithelium and histopathological findings were reduced in the antioxidant-treated groups (Groups 4, 5, and 6). In addition, immunofluorescence examination revealed that the expression of Cytochrome C and Caspase 3 was stronger and Ki-67 was weaker in Groups 2 and 3, in comparison to the groups that were given antioxidants. It can be said that curcumin and gallic acid have a histological and biochemical protective effect against ischemia-reperfusion injury due to ovarian transplantation, and this effect is stronger when these two antioxidants are applied together compared to individual use.
Asunto(s)
Antioxidantes , Curcumina , Ácido Gálico , Folículo Ovárico , Reserva Ovárica , Ovario , Estrés Oxidativo , Ratas Sprague-Dawley , Animales , Femenino , Ácido Gálico/farmacología , Curcumina/farmacología , Estrés Oxidativo/efectos de los fármacos , Ovario/efectos de los fármacos , Ovario/patología , Ovario/metabolismo , Ratas , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismo , Folículo Ovárico/patología , Reserva Ovárica/efectos de los fármacos , Antioxidantes/farmacología , Epitelio/efectos de los fármacos , Epitelio/patología , Epitelio/metabolismo , Trasplante Autólogo , Sinergismo FarmacológicoRESUMEN
The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal infection nor pelvic inflammatory disease and thus it was selected for further characterization. We show that human Fallopian tubes express the IL-17C receptor on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.
Asunto(s)
Trompas Uterinas , Gonorrea , Inflamación , Interleucina-17 , Neisseria gonorrhoeae , Adulto , Femenino , Humanos , Citocinas/metabolismo , Epitelio/patología , Epitelio/microbiología , Trompas Uterinas/microbiología , Trompas Uterinas/patología , Trompas Uterinas/inmunología , Gonorrea/inmunología , Gonorrea/microbiología , Gonorrea/patología , Inflamación/patología , Inflamación/microbiología , Interleucina-17/metabolismo , Neisseria gonorrhoeae/inmunología , Neisseria gonorrhoeae/patogenicidad , Enfermedad Inflamatoria Pélvica/microbiología , Enfermedad Inflamatoria Pélvica/patología , Enfermedad Inflamatoria Pélvica/inmunología , Receptores de Interleucina-17/metabolismo , Receptores de Interleucina-17/genéticaRESUMEN
Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix (ECM) destruction within the salivary and lacrimal glands, followed by immune cell infiltration. In this review, we have assessed the current understanding of epithelial-mesenchymal transition (EMT)-associated changes within the salivary epithelium potentially involved in salivary dysfunction and SjD pathogenesis. We performed a PubMed literature review pertaining to the determination of pathogenic events that lead to EMT-related epithelial dysfunction and signaling in SjD. Molecular patterns of epithelial dysfunction in SjD salivary glands share commonalities with EMT mediating wound healing. Pathological changes altering salivary gland integrity and function may precede direct immune involvement while perpetuating MMP9-mediated ECM destruction, inflammatory mediator expression, and eventual immune cell infiltration. Dysregulation of EMT-associated factors is present in the salivary epithelium of SjD and may be significant in initiating and perpetuating the disease. In this review, we further highlight the gap regarding mechanisms that drive epithelial dysfunction in salivary glands in the early or subclinical pre-lymphocytic infiltration stages of SjD.
Asunto(s)
Transición Epitelial-Mesenquimal , Glándulas Salivales , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/patología , Síndrome de Sjögren/metabolismo , Glándulas Salivales/patología , Glándulas Salivales/metabolismo , Animales , Epitelio/patología , Epitelio/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Transducción de Señal , Matriz Extracelular/metabolismoRESUMEN
Mesothelial cells with reactive hyperplasia are difficult to distinguish from malignant mesothelioma cells based on cell morphology. This study aimed to identify and validate potential biomarkers that distinguish mesothelial cells from mesothelioma cells through machine learning combined with immunohistochemistry. It integrated the gene expression matrix from three Gene Expression Omnibus data sets (GSE2549, GSE12345, and GSE51024) to analyze the differently expressed genes between normal and mesothelioma tissues. Then, three machine learning algorithms, least absolute shrinkage and selection operator, support vector machine recursive feature elimination, and random forest were used to screen and obtain four shared candidate markers, including ACADL, EMP2, GPD1L, and HMMR. The receiver operating characteristic curve analysis showed that the area under the curve for distinguishing normal mesothelial cells from mesothelioma was 0.976, 0.943, 0.962, and 0.956, respectively. The expression and diagnostic performance of these candidate genes were validated in two additional independent data sets (GSE42977 and GSE112154), indicating that the performances of ACADL, GPD1L, and HMMR were consistent between the training and validation data sets. Finally, the optimal candidate marker ACADL was verified by immunohistochemistry assay. Acyl-CoA dehydrogenase long chain (ACADL) was stained strongly in mesothelial cells, especially for reactive hyperplasic mesothelial cells, but was negative in malignant mesothelioma cells. Therefore, ACADL has the potential to be used as a specific marker of reactive hyperplasic mesothelial cells in the differential diagnosis of mesothelioma.
Asunto(s)
Biomarcadores de Tumor , Biología Computacional , Aprendizaje Automático , Mesotelioma Maligno , Mesotelioma , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mesotelioma/genética , Mesotelioma/patología , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Biología Computacional/métodos , Mesotelioma Maligno/genética , Mesotelioma Maligno/patología , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Epitelio/metabolismo , Epitelio/patologíaAsunto(s)
Hiperplasia , Mesotelioma , Neoplasias Testiculares , Humanos , Mesotelioma/patología , Mesotelioma/diagnóstico , Hiperplasia/patología , Hiperplasia/diagnóstico , Neoplasias Testiculares/patología , Neoplasias Testiculares/diagnóstico , Masculino , Diagnóstico Diferencial , Epitelio/patología , Persona de Mediana Edad , AncianoRESUMEN
Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment.
Asunto(s)
Enfermedades Autoinmunes , Esofagitis , Masculino , Femenino , Humanos , Esofagitis/complicaciones , Esofagitis/patología , Epitelio/patologíaRESUMEN
Loss of the cell-cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E-cadherin deficiency drives DGC formation remains elusive. Therefore, we investigated the consequences of E-cadherin loss on gastric epithelial organization utilizing a human gastric organoid model and histological analyses of early-stage DGC lesions. E-cadherin depletion from gastric organoids recapitulates DGC initiation, with progressive loss of a single-layered architecture and detachment of individual cells. We found that E-cadherin deficiency in gastric epithelia does not lead to a general loss of epithelial cohesion but disrupts the spindle orientation machinery. This leads to a loss of planar cell division orientation and, consequently, daughter cells are positioned outside of the gastric epithelial layer. Although basally delaminated cells fail to detach and instead reintegrate into the epithelium, apically mispositioned daughter cells can trigger the gradual loss of the single-layered epithelial architecture. This impaired architecture hampers reintegration of mispositioned daughter cells and enables basally delaminated cells to disseminate into the surrounding matrix. Taken together, our findings describe how E-cadherin deficiency disrupts gastric epithelial architecture through displacement of dividing cells and provide new insights in the onset of DGC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Asunto(s)
División Celular , Organoides , Neoplasias Gástricas , Células de Riñón Canino Madin Darby , Animales , Perros , Estómago/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Epitelio/metabolismo , Epitelio/patología , Proliferación CelularRESUMEN
The prevalence of Light-emitting diodes (LEDs) has exposed us to an excessive amount of blue light (BL) which causes various ophthalmic diseases. Previous studies have shown that conjunctiva is vulnerable to BL. In this study, we aimed to investigate the underlying mechanism of BL-induced injury in conjunctiva. We placed C57BL/6 mice and human conjunctival epithelial cell lines (HCECs) under BL (440 nm ± 15 nm, 0.2 mW/cm2) to establish a BL injury model in vivo and in vitro. Immunohistochemistry and MDA assay were used to identify lipid peroxidation (LPO) in vivo. HE staining was applied to detect morphological damage of conjunctival epithelium. DCFH-DA, C11-BODIPY 581/591, Calcein-AM, and FeRhoNox™-1 probes were performed to identify ferroptosis levels in vitro. Real-time qPCR and Western blotting techniques were employed to uncover signaling pathways of blue light-induced ferroptosis. Our findings demonstrated that BL affected tear film instability and induced conjunctival epithelium injury in vivo. Ferrostatin-1 significantly alleviated blue light-induced ferroptosis in vivo and in vitro. BL downregulates the levels of solute carrier family 7 member 11 (SLC7A11), Ferritin heavy chain (FTH1), and glutathione peroxidase (GPX4) by inhibiting the activation and translocation of the Signal transducer and activator of transcription 3 (STAT3) from inducing Fe2+ burst, ROS and LPO accumulation, ultimately resulting in ferroptosis. This study will offer new insight into BL-induced conjunctival injury and LED-induced dry eye.
Asunto(s)
Luz Azul , Conjuntiva , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Factor de Transcripción STAT3 , Animales , Humanos , Ratones , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Línea Celular , Conjuntiva/metabolismo , Conjuntiva/efectos de la radiación , Conjuntiva/patología , Ciclohexilaminas , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Células Epiteliales/patología , Epitelio/efectos de la radiación , Epitelio/metabolismo , Epitelio/patología , Ferroptosis/efectos de la radiación , Peroxidación de Lípido/efectos de la radiación , Ratones Endogámicos C57BL , Fenilendiaminas/farmacología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de la radiación , Factor de Transcripción STAT3/metabolismoRESUMEN
OBJECTIVE: This study compared a dual-wavelength diode laser and an Er, Cr:YSGG laser in oral soft tissue incisions to determine the most effective and safest laser system at the histopathological level. METHODOLOGY: The (810 and 980 nm) dual-wavelength diode laser was used at 1.5 W and 2.5 W (CW) power settings, and the (2780 nm) Er, Cr:YSGG laser was used at 2.5 W and 3.5 W (PW) power settings. Both laser systems were used to incise the tissues of freshly dissected sheep tongue pieces to obtain the following histopathological criteria: epithelial tissue changes, connective tissue changes, and lateral thermal damage extent by optical microscopy. RESULTS: The epithelial and connective tissue damage scores were significantly higher in the dual-wavelength diode laser groups than in the Er, Cr:YSGG laser groups (P<0.001), and there was a significant difference between some groups. The extent of lateral thermal damage was also significantly higher in the diode laser groups than in the Er, Cr: YSGG laser groups (P<0.001), and there was a significant difference between groups. Group 2 (2.5 W) of the diode laser was the highest for all three criteria, while group 3 (2.5 W) of the Er, Cr:YSGG laser was the lowest. CONCLUSION: The Er, Cr:YSGG laser with an output power of 2.5 W is, histologically, the most effective and safest laser for oral soft tissue incision. The dual-wavelength diode laser causes more damage than the Er, Cr:YSGG laser, but it can be used with a low output power and 1 mm safety distance in excisional biopsy.
Asunto(s)
Láseres de Semiconductores , Láseres de Estado Sólido , Márgenes de Escisión , Lengua , Animales , Láseres de Semiconductores/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Lengua/cirugía , Lengua/patología , Reproducibilidad de los Resultados , Ovinos , Tejido Conectivo/patología , Epitelio/patología , Valores de Referencia , Procedimientos Quirúrgicos Orales/métodos , Mucosa Bucal/patología , Mucosa Bucal/cirugía , Estadísticas no Paramétricas , Terapia por Láser/métodos , Terapia por Láser/instrumentaciónRESUMEN
SUMMARY: Barrett's esophagus is a condition where the distal third of the esophagus changes its epithelial lining from non- keratinized stratified squamous to simple columnar. This cross-sectional descriptive study was conducted to characterize the esophageal mucosa in the third trimester of pregnancy and determine possible variants in its development and was carried out in the Morphology Laboratory of the Health Faculty of the Industrial University of Santander, Colombia, with 45 human fetuses in the third trimester of gestation (weeks 25-40). A section of the distal esophagus and the first portion of the cardial region of the stomach were obtained, and the histological sections were subjected to a fixation process with 5 % formaldehyde solution. The sections were stained with hematoxylin and eosin and were evaluated for the presence of epithelial change or glands in the esophageal lamina propria. The change from non- keratinized stratified squamous epithelium to simple columnar epithelium was observed in the esophageal mucosa in five fetuses (11.1 %). In 15 cases (33.3 %), the presence of mucous glands underlying the epithelium was determined. In two fetuses, simple columnar epithelium was observed in the esophageal mucosa and underlying submucosal glands (4.4 %). The lack of replacement of the columnar epithelium by squamous epithelium in the distal third of the esophagus and the presence of mucous glands in the last third of gestation may suggest the presentation of Barret's esophagus in adulthood and thus, a predisposition to develop esophageal adenocarcinoma.
El esófago de Barrett es una afección en la que el tercio distal del esófago cambia su revestimiento epitelial de escamoso estratificado no queratinizado a columnar simple. Este estudio descriptivo de corte transversal tiene como objetivo caracterizar la mucosa esofágica en el tercer trimestre del embarazo y determinar posibles variantes en su desarrollo y se realizó en el laboratorio de Morfología de la Facultad de Salud de la Universidad Industrial de Santander-Colombia, con 45 fetos humanos en el tercer trimestre de gestación (semanas 25-40). Se obtuvo una sección del esófago distal y la primera porción de la región cardial del estómago y las secciones histológicas se sometieron a un proceso de fijación con solución de formaldehído al 5 %. Los cortes se tiñeron con hematoxilina y eosina y se evaluaron determinando la presencia de cambio epitelial y glándulas en la lámina propia del esófago. El cambio de epitelio escamoso estratificado no queratinizado a epitelio cilíndrico simple se observó en la mucosa esofágica en cinco fetos (11,1 %). En 15 casos (33,3 %) se determinó la presencia de glándulas mucosas subyacentes al epitelio. En dos fetos se observó epitelio cilíndrico simple en la mucosa esofágica y glándulas submucosas subyacentes (4,4 %). La falta de reemplazo del epitelio cilíndrico por epitelio escamoso en el tercio distal del esófago y la presencia de glándulas mucosas en el último tercio de la gestación pueden sugerir la presentación de esófago de Barrett en la edad adulta y una predisposición a desarrollar adenocarcinoma de esófago.
Asunto(s)
Humanos , Esófago de Barrett/etiología , Mucosa Esofágica/patología , Esófago de Barrett/complicaciones , Neoplasias Esofágicas/etiología , Adenocarcinoma/etiología , Estudios Transversales , Epitelio/patología , Feto , Metaplasia/patologíaRESUMEN
Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign lesion composed of monocytes and mesothelial cells that is most often encountered during cardiothoracic surgery. We describe a case in a 71-year-old man with known aortic valve stenosis who presented with gradual onset dyspnea over a few weeks, made worse with minimal exertion. A transesophageal echocardiogram revealed severe aortic stenosis and mild pericardial effusion. The patient underwent aortic valve replacement, coronary artery bypass, and amputation of the left atrial appendage. Histological examination of a 0.8 cm blood clot received along with the atrial appendage showed an aggregation of bland cells with features of monocytes associated with small strands and nodules of mesothelial cells, fat cells, fibrin and a minute fragment of bone. Immunohistochemical analysis showed that the monocytic cells were positive for CD4 and CD68 (strong) and negative for calretinin and keratin. By contrast, the mesothelial cells were positive for calretinin and keratin and negative for all other markers. In sum, the morphologic and immunohistochemical findings support the diagnosis of MICE. Based on our review of the literature, about 60 cases of MICE have been reported previously which we have tabulated. We also discuss the differential diagnosis.