Airway remodelling in obstructive sleep apnea encompasses diverse histopathological and neuromuscular alterations, yet surface-level epithelial changes and ionic characteristics remain insufficiently studied. Using time-of-flight secondary ion mass spectrometry, this study identified disrupted epithelial ionic homeostasis in the upper airway. Inferior turbinate specimens were collected from 18 patients with obstructive sleep apnea and 22 controls undergoing upper airway surgery. Compared with controls, specimens from patients with obstructive sleep apnea demonstrated significantly elevated sodium-to-potassium ratios (1.66 ± 1.38 vs. 0.83 ± 0.38, p = 0.033), with a marginal association persisting after adjustment for age and body mass index (p = 0.057). Immunohistochemistry revealed reduced sodium-potassium adenosine triphosphatase expression in the epithelium of obstructive sleep apnea specimens (p = 0.0077), while histology showed epithelial metaplasia and inflammatory changes. Among several machine learning classifiers, the random forest model achieved the highest diagnostic performance, yielding an area under the curve of 0.7928 and consistently identifying the sodium-to-potassium ratio as the most discriminative feature. Together, these findings demonstrate that disrupted sodium-to-potassium balance and diminished sodium-potassium adenosine triphosphatase expression constitute epithelial signatures in obstructive sleep apnea. Such ionic dysregulation may impair membrane potential and pharyngeal muscle responsiveness, thereby promoting airway collapsibility. Given the established role of ion channels in neuromuscular regulation, the epithelial sodium-to-potassium ratio may represent not only a diagnostic biomarker but also a potential predictor of therapeutic response to potassium channel-targeted interventions.

Iron oxide nanoparticles attract attention in the scientific community due to the wide range of their unique physico-chemical properties obtained during various synthesis methods. However, their effects on the body when administered orally have not been sufficiently studied. This work was aimed to study of morphological and morphometric characteristics of the gastric mucosa of laboratory mice using synthetic and biogenic iron oxide nanoparticles as a feed additive. Materials and methods. Nanoparticles of synthetic and biogenic iron origin were used in the work. The laboratory mice (n = 55) were allocated into 3 groups: 1 group of mice (n = 15) were intact animals that received standard feeding; group 2 (n = 20) fed food with synthetic nanoparticles; group 3 (n = 20) fed food with biogenic nanoparticles. The biological material (mouse stomach) was sampled on days 1, 22, and 36. Histological sections were stained with hematoxylin-eosin and Perls. Morphometric analysis of the drugs was performed in the program “ViodeoTesT - Morphology 7.0”. Results. Upon oral administration of iron oxide nanoparticles into the body, lymphohistiocytic infiltration, hemorrhages, enlargement of the gastric glands, cysts, and dystrophic changes in the cells of the columnar epithelium were detected in both groups. At the same time, foci of atrophic gastritis and pronounced foci of destruction of the gastric glands were noted in animals of group 3 on day 36. Conclusion. The entry of both synthetic and biogenic iron oxide nanoparticles into the gastrointestinal tract for 36 days causes pathological changes in the stomach tissue in the form of epithelial metaplasia with dystrophic changes in the gastric glands.

Early growth response 2 as a target of IL-13/STAT6 signaling induces the goblet cell metaplasia of allergic airway epithelia.

Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease characterized by progressive epithelial metaplasia and widespread fibrosis. Alveolar microcysts develop near terminal airways in IPF and are linked to poor outcome. Using HTII-280 as a short-term lineage marker of AT2-derived AT0 (SFTPC + /SCGB3A2 + ) and basaloid (KRT17⁺) cells, together with organoids and spatial transcriptomics (Xenium), we highlight epithelial similarities between respiratory bronchioles (RBs) and alveolar microcysts both having AT0, SCGB3A2+, and basaloid/basal cells (BCs), albeit with expanded BCs in IPF microcysts. The AT0- and AT2-derived BCs strongly express the collagenase, matrix metalloproteinase protein-1, MMP1 in organoids - mirroring in situ BCs lining IPF microcysts, but distinct from MMP1 low BCs in large airways or normal lungs. Expression of MMP1 correlates with basal cell hypoxia pathway activity. MMP1 high AT2-derived BCs and IPF BCs promoted type 1 collagen degradation ex vivo and in vivo after xenotransplantation, forming microcystic structures that were abrogated by concurrent MMP inhibitor treatment. Notably, a Frizzled 5 WNT agonist antibody reversed the MMP1 high state of AT2-derived BCs, raising a possible therapeutic approach. These findings suggest AT2 transdifferentiation to basaloid/basal cells is uncommon in normal lungs but can expand as a potential source of alveolar destruction, likely contributing to the pernicious course of IPF.

Chronic cholecystitis is a persistent inflammatory disorder of the gall bladder, commonly arising from recurrent mild or subclinical bouts of acute cholecystitis. It is marked by mucosal atrophy, fibrotic thickening, and distortion of the gallbladder wall. The condition is strongly associated with gall stones, whose continuous mechanical irritation and intermittent obstruction lead to progressive fibrosis, structural alteration, and chronic inflammation . Laparoscopic or open cholecystectomy operations are the common operations done in AL nassiriya city due to acute or chronic calculus cholecystitis. Chronic calculus cholecystitis may be associated with malignant changes because of chronic irritation, which is usually preceded by metaplasia due to irritation, dysplasia, carcinoma in situ, and then invasive carcinoma. 360 patients undergoing successful laparoscopic or open cholecystectomy for chronic calculus cholecystitis, all gall bladders are sent for histopathological examination to detect any malignant changes. Several cases of chronic calculus cholecystitis have developed malignant changes. Tubular adenocarcinoma, most frequently observed in women with gallstones, exhibits a downward invasive growth pattern and carries a poor prognosis. Chronic cholecystitis and epithelial metaplasia are commonly present, while undifferentiated carcinomas also prevalent among females with gallstones, demonstrate the most adverse clinical outcomes. Patients with chronic calculus cholecystitis should be treated by laparoscopic or open cholecystoctomy as soon as possible to prevent hazards of malignant changes that may be associated with chronic irritation of the stones to the gall bladder mucosa and because of histopathological types of ca. bladder that associated with gall stones are either tubular adenocarcinoma or undifferentiated carcinoma which have bad prognosis thus, after operation should send the gall bladder for histopathological examination to detect any malignant changes and deal with it as early as possible.

Background: Gallbladder cancer (GBC) is highly prevalent in Northern and Eastern India and often diagnosed late, leading to poor outcomes. Identifying precursor lesions is essential, as the metaplasia-dysplasia-carcinoma sequence plays a central role in gallbladder carcinogenesis. This study examines precancerous mucosal changes in cholelithiasis and evaluates their histopathological patterns and clinical relevance for early detection.Materials and methods: This cross-sectional study included 100 patients with ultrasonography-confirmed cholelithiasis who underwent cholecystectomy at Sir Sunderlal Hospital, Banaras Hindu University. Patients with hepatic or metabolic comorbidities were excluded. Clinical characteristics and hematological and biochemical parameters were recorded. Resected gallbladder specimens were examined for microanatomical and histological alterations. Statistical analysis was performed using IBM Corp. Released 2026. IBM SPSS Statistics for Windows, Version 26. Armonk, NY: IBM Corp., with p<0.05 considered significant.Results: A total of 100 patients with cholelithiasis were stratified into four clinical severity grades. Of these, 36 were male, and 64 were female. The mean age showed no significant variation across the groups (p = 0.480), indicating a uniform age distribution among the study population. Serum alkaline phosphatase levels showed a marked, statistically significant rise with increasing severity (p < 0.0001). Significant inter-group differences were also observed in hemoglobin, platelet count, bilirubin fractions, total protein, urea, and selected anthropometric parameters (p < 0.05). Histopathological evaluation revealed epithelial hyperplasia as the most common lesion (58%), followed by low-grade dysplasia (22%) and intestinal metaplasia (10%), while normal mucosa was seen in only 10% of cases (p < 0.001). These findings demonstrate a clear progression of microanatomical alterations consistent with the metaplasia-dysplasia-carcinoma sequence.Conclusion: Chronic cholelithiasis was associated with significant mucosal changes, mainly epithelial hyperplasia, intestinal metaplasia, and low-grade dysplasia, supporting the metaplasia-dysplasia-carcinoma sequence. Alkaline phosphatase levels rose progressively with disease severity, indicating ongoing tissue injury. These findings highlight the importance of routine histopathological examination for early detection of precursor lesions.

The etiologic and pathogenic spectrum of exposure keratopathy: Diagnostic and therapeutic implications.

To develop a treatment strategy based on the analysis of clinical manifestations and the results of morphofunctional diagnostics for patients with gastroesophageal reflux disease (GERD) aimed at preventing the development and progression of intestinal metaplasia (IM) of the esophageal epithelium. The study included 50 subjects diagnosed with GERD. After esophagogastroduodenoscopy with biopsy and subsequent morphological examination of the esophageal mucosa, two groups were formed: patients with GERD complicated by IM, also known as Barrett's esophagus (n = 19), patients with GERD without IM (n = 31). All participants underwent high-resolution esophageal manometry and 24-hour impedance pH monitoring. The study found that in patients with GERD complicated by IM, complaints of intense heartburn and difficulty swallowing occurred more often than in patients with GERD without IM. According to manometry, the resting pressure of the lower esophageal sphincter in patients with GERD and IM (15.1 [1.3; 36.4] mmHg) was lower than in patients with GERD without IM (20.3 [5.5; 42.1] mmHg). This difference was statistically significant (p = 0.002). In patients with GERD and IM, esophageal motility is less effective; this was translated in a decrease in the distal contractile integral of the esophagus to 276.5 [0.2; 567.7] mmHg × s × cm, while in patients with GERD without IM, it was much higher: 942.5 [47.3; 3759.7] mmHg × s × cm. Difficulties in swallowing were associated with a reduced effectiveness of esophageal motility. In patients with GERD complicated by IM, more acid gastroesophageal refluxes were observed compared to patients without IM (72.5 [53.5; 91.5] vs 54.2 [29.9; 78.3]; p = 0.036). They also have a greater percentage of time with pH < 4.0 in the esophagus (14.5 [9.7; 19.3] vs 10.3 [5.6; 14.9]; p = 0.028) and higher DeMeester index values (35.4 [1.9; 114.5] vs 15.1 [0.2; 47.7]; p = 0.004). GERD is a multifactorial disease with a primary impairment of the motor function of the upper gastrointestinal tract. The acidic reflux may affect the development of the intestinal type of epithelial metaplasia.

The mechanism underlying the role of trefoil factor family 3 (TFF3) in intestinal metaplasia remains unclear. This study reveals the molecular mechanism by which TFF3, in the process of gastric mucosal epithelial cell intestinal metaplasia (IM) induced by high salt, activates the JAK2/STAT3/CDX2 pathway, providing a potential target for the occurrence of IM. An in vitro model of high salt-induced intestinal metaplasia was established using bioinformatics to screen the GEO dataset for significantly differentially expressed genes related to intestinal metaplasia. The gastric epithelial cell line GES-1 was cultured in high-salt medium, and changes in cell function and the expression of TFF3, JAK2, STAT3, and CDX2 were examined following TFF3 knockdown or overexpression. Subsequent experiments disrupted the TFF3-JAK2/STAT3-CDX2 pathway to assess its effects on gene expression and cell function. The expression of TFF3 is upregulated during intestinal metaplasia, which promotes cell proliferation and migration. TFF3 regulates the expression of JAK2, STAT3, and CDX2 and activates the JAK2/STAT3 pathway to induce CDX2 expression in gastric epithelial cells, leading to intestinal metaplasia. Functional assays revealed that the TFF3-JAK2/STAT3-CDX2 pathway enhances both cell proliferation and migration. TFF3 induces intestinal metaplasia in gastric epithelial cells through the JAK2/STAT3-CDX2 pathway, providing new insights into the underlying mechanism and therapeutic strategies for intestinal metaplasia.

Chronic inflammatory rhinitis (CIR) is among the most common causes of chronic nasal signs in dogs. Despite research efforts, the etiology of CIR remains mostly undiscovered. The aim of our study was to describe the histological findings in nasal biopsies of control dogs without signs of nasal disease compared to dogs with CIR. The study groups were control dogs euthanized for reasons unrelated to this study (n = 20) and previously collected, archived nasal biopsies from dogs diagnosed with CIR (n = 20). A CIR diagnosis was based on clinical presentation, computed tomography, rhinoscopy, and histopathological findings indicative of CIR. Inflammatory cell counts and changes in the mucosal epithelium and associated lamina propria were evaluated from nasal biopsy specimens. The numbers of lymphocytes and plasma cells (P < .0001), neutrophils (P < .0001), and eosinophils (P = .0016) in the lamina propria, and mucosal intraepithelial leukocytes (P < .0001) were significantly higher in dogs with CIR compared to control dogs. A small population of leukocytes was also observed in control dogs, likely representing a physiological immune cell population. The type of inflammation in CIR is not purely lymphoplasmacytic, as both neutrophils and eosinophils were also detected in CIR dogs. The mucosal epithelium was thicker (P = .006), and visible goblet cells (P < .001) were decreased, in dogs with CIR, with a multifocal loss of cilia in some dogs, which may represent a form of respiratory epithelial metaplasia. Epithelial alterations likely play a role in the pathophysiology of CIR and contribute to the clinical signs.

Many aspects of laser rhinosurgery including the reaction of the nasal mucosa to the effects of a holmium laser, remain controversial to this day. This has allowed us to determine the purpose of our study as the examination of morphological changes in the mucous membrane in the region formed by rhinoantrostomy using both traditional and original (endoscopic laser rhinoantrostomy) techniques. Morphological analysis of 48 samples showed that the formation of the rhinoantrostome using the traditional method significantly more often leads to epithelial metaplasia, multilayered atrophic changes, decreased number of vessels in the mucosa, and a decrease in goblet- and ciliated cell numbers (p<0.001) compared to laser treatment. The revealed morphological changes may contribute to the development of stagnation and impaired drainage of nasal secretions from the maxillary sinus in the area formed by the rhinostome in the traditional way, and may provoke the development of postoperative nasal syndrome in the postoperative period. This indicates a significant advantage of using the laser method for rhinostomy.

Backgroundː Exposure to e-cigarettes in human bronchial epithelial cells was found to induce mucociliary airway dysfunction in vitro. Additionally, e-cigarettes were shown to reduce the viability of gingival epithelial cells and promote cell apoptosis or necrosis. Methodsː The experimental study (true experimental design) employed a control group and a treatment group, with simple randomization of 20 Wistar rats per group, resulting in a total of 40 Wistar rats in the study. Then histopathological examination was performed to assess tissue damage. Resultsː Research resultsshowed that 400 mg curcumin provided effective protection against nasal mucosal damage caused by e-cigarette smoke exposure, by reducing the severity of epithelial disarrangement, erosion, inflammation, and epithelial metaplasia. However, mild to moderate histopathological changes still occurred, so additional approaches are needed for more optimal protection Conclusionsː It can be concluded that there is a relationship between the effectiveness of oral curcumin administration on the nasal mucosa of Wistar rats after exposure to electronic cigarette smoke.

BackgroundSquamous metaplasia is commonly observed in eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP). However, its underlying mechanisms remain unclear. This study aimed to evaluate the role of glucose transporter 1 (GLUT1) in the development of squamous metaplasia in eCRSwNP.MethodsTissue proteomics was employed to identify disease-specific proteins in eCRSwNP. Immunofluorescence, western blotting, and RT-qPCR were used for validation. Human nasal epithelial cells were utilized to assess GLUT1 expression and its regulatory mechanisms. A chronic rhinosinusitis with nasal polyps (CRSwNP) mouse model was used to examine the effect of GLUT1 inhibition on squamous metaplasia and nasal inflammation.ResultsProteomic analysis revealed a disease-specific protein expression profile in eCRSwNP polyps. Cohort validation demonstrated that GLUT1 and keratin 13 (KRT13) expression levels were significantly higher in the eCRSwNP group, with expression primarily localized in the epithelial regions. GLUT1 expression was positively correlated with the incidence of squamous metaplasia as well as KRT13 and involucrin (IVL) expression. In vitro experiments confirmed that combined Interleukin (IL)-4/IL-13 treatment upregulated GLUT1, KRT13, and IVL expression in human nasal epithelial cells in a dose-dependent manner, whereas GLUT1 inhibition reduced KRT13 and IVL expression, possibly through suppression of the PI3K-AKT signaling pathway. Animal experiments demonstrated that GLUT1 inhibition alleviated squamous metaplasia and inflammation in the nasal mucosa of mice.ConclusionElevated GLUT1 expression plays a key role in driving squamous metaplasia in eCRSwNP. GLUT1 inhibition attenuates nasal epithelial squamous metaplasia and inflammation in CRSwNP.

Abstract In the airway, epithelial cells can transiently differentiate into goblet cells, but dysregulated immune responses to allergen lead to persistent goblet cell metaplasia and mucus hypersecretion in rhinosinusitis and severe asthma. The molecular mechanisms that govern goblet cell differentiation are incompletely understood, and no available therapy directly targets this process to alleviate mucus-related symptoms. Here, we show that the unfolded protein response (UPR) and its most deeply-conserved mediator, IRE1α, are activated as human basal cells differentiate into highly secretory goblet cells. Conditional knockout of IRE1α in the mouse lung epithelium demonstrates that IRE1α is cell autonomously required for efficient goblet cell metaplasia stimulated by Th2 inflammation in allergen-challenged mice. Likewise, IRE1α loss of function by genetic knockout or a highly selective kinase inhibitor of IRE1α (KIRA8) blocks goblet cell metaplasia airway epithelial cells cultured at air-liquid interface (ALI). To further delineate the molecular mechanism of IRE1α's regulation goblet cell metaplasia, we cultured cells at ALI with a kinase modulator (PAIR2) that blocks IRE1α's RIDD activity while preserving its XBP1 splicing activity. We find that IRE1α's XBP1 splicing activity regulates the fate of differentiating airway epithelial cells, in contrast to the alveolus, where IRE1α's RIDD activity controls plasticity. In cells from human donors, the kinase inhibitor KIRA8 blocks IL-13 induced goblet cell differentiation, suggesting that kinase inhibitors of IRE1α may have therapeutic potential for controlling symptoms of mucus hypersecretion in asthma patients. Ongoing work will further define the transcriptional targets of XBP1 in differentiating airway cells, and a possible role for IRE1α in suppressing ciliogenesis. Our data suggests that IRE1α may enhances goblet cell metaplasia by simultaneously promoting secretory maturation through XBP1 and possibly suppressing ciliary fate through RIDD. Grant Support AADCRC IOF Fund (NIAID)U19AI077439 (NIAID)K08HL157654 (NHLBI)F32HL145990 (NHLBI)T32HL007185 (NHLBI)

Abstract RATIONALE: Obesity and asthma frequently co-occur, with 60% of asthma patients being obese. This obese asthma (OA) subgroup has worse clinical outcomes, including poor asthma control and reduced corticosteroid responsiveness, likely driven by poorly understood non-T2 inflammatory mechanisms. Here, we examine airway biospecimens from obese asthma patients to explore airway inflammation and epithelial remodeling phenotypes. METHODS: Bulk RNA-sequencing was performed on nasal airway brushings from the Asthma Characterization Protocol (ACP). Bronchial brushings and biopsies from the Obesity and Metabolic Dysfunction in Asthma study were analyzed using bulk/scRNA-sequencing and immunofluorescent histology. Co-expression networks were obtained from the bulk data and then used to identify disease endotypes and investigate responses driven by obese asthma. Airway specimen single-cell data were analyzed using Seurat analysis pipeline. RESULTS: Network analysis of nasal RNA-seq data from obese (n=135) and lean (n=55) asthma patients identified T1 (interferon), T2 (IL-4, IL-13, IL-5), T17 (IL-17), and IL36G-driven inflammatory networks and endotyping based on network expression showed 26%, 25%, 21%, and 30% of obese asthmatics highly expressed these networks, respectively. Obese asthmatics were more likely to exhibit at least one of these endotypes (64%) than lean patients (47%, p=0.032). These inflammatory changes coincided with downregulation in the expression of genes involved in epithelial integrity, including CLD17, JAM3, and several cadherin/protocadherin and integrin genes. Examining lower airway effects, gene networks from bronchial brushings revealed a higher proportion of obese asthmatics expressing the T1 endotype compared to lean asthmatics and healthy controls (p=0.026). Pathway analysis of dysregulated genes in obsese versus lean asthma (FDR&amp;lt;0.05) indicated upregulation of interferon-driven gene expression, including ISG, IFIT, and OAS gene families, and dysregulation of metabolic pathways related to obesity (arginine/proline, glucose, sphingolipid metabolism). Bronchial biopsy scRNA-seq demonstrated elevated expression of squamous metaplasia markers, KRT13 and KRT6A, in club and basal cell populations among obese asthmatics (FDR&amp;lt;0.05). This matched epithelial remodeling and squamous metaplasia signatures indicated by upregulation of keratinization and mucin biosynthesis pathways (p&amp;lt;0.05) in the obese asthma bronchial brush RNA-seq data. Squamous epithelial remodeling was also visualized by SPRR3+ labeling and H&amp;E staining observed in 29% of obese asthmatics, which was entirely absent in biopsies from lean asthmatics. CONCLUSIONS: Obese asthmatics are more prone to airway inflammation of various forms, but most commonly involves interferon-driven, T1 inflammation. Moreover, systemic metabolic dysfunction in these patients extends to the airway epithelium. This pronounced inflammation in patients with obese asthma likely drives observed epithelial metaplastic and remodeling phenotypes.

Abstract Rationale: Airway diseases such as COPD are characterized by epithelial mucous metaplasia leading to airway obstruction. We recently identified that the autophagy protein degradation pathway was critical to the regulation of mucin granules in airway secretory cells of mice. This suggests that mucin granule degradation may significantly contribute to the regulation of secretory cell biology in health and disease. In this study, we explored the abundance and function of lysosomes in airway secretory cells in normal and COPD-derived airway epithelial cells. Methods: To explore the lysosome pathway in eliminating excess mucin granules, we utilized the Calu-3 cell line and normal and COPD-derived primary human airway epithelial cells (hAEC). Cells were treated with pharmacologic lysosomal inhibitors. Lysosome function was examined by immunoblotting and molecular probes that detect lysosomal acidification or acid hydrolase function. Mucin content was evaluated by immunoblotting, immunostaining, and transmission electron microscopy. Results: We examined lysosomal abundance using the lysosomal surface marker, LAMP1, in differentiated hAEC (ALI ≥21 day). LAMP1 immunostaining was primarily localized in secretory cells rather than ciliated cells. Interestingly, we found a significant decrease in LAMP1+ lysosomes in COPD-derived hAEC (Figure 1 A,B). This difference in lysosome abundance was confirmed in human segmental airway sections from end-stage COPD. Inhibition of lysosomal acidification (bafilomycin A1), lysosomal cathepsin enzyme activity (PepstatinA1-E64D), or autophagosome-lysosome fusion by MYH-1485 led to an accumulation of mucin granules in CALU-3 cultured cells (Figure 1 D-G). Inhibition of lysosome activity led to a detection of increased fusion events between mucin granules and LAMP1+ lysosomes as detected by super-resolution microscopy and by transmission electron microscopy. The importance of lysosome function was confirmed in hAECs treated with IL-13. Lysosomal inhibition with MYH-1485 led to a significant increase in MUC5AC levels during IL-13 induced mucous metaplasia (Figure 1 H,I). Conclusion: Lysosomes are an organelle found more abundantly in secretory cells and contribute to the regulation of cytoplasmic mucin granules. However, COPD airway cells have decreased LAMP1+ lysosomes, which may contribute to the pathogenesis of that disease.

1205: HIGH-FAT DIET PROMOTES GASTRIC EPITHELIAL REMODELING AND METAPLASIA IN A MURINE MODEL

Helicobacter pylori - causes pathologies such as gastritis, peptic ulcer disease, adenocarcinoma. Pseudopyloric mucosal metaplasia in the incisura region is significantly correlated with the development of precancerous changes - atrophy and intestinal metaplasia. Pseudopyloric metaplasia of the gastric mucosa develops as a result of persistence of H. pylori infection. Immunohistochemical and histological study of gastric mucosa biopsy specimens from patients with dyspeptic complaints was performed. Chronic non-atrophic gastritis was histologically detected in 21 patients. Of these, 17 (80.95%) were H. pylori-positive. Out of 55 patients with chronic atrophic gastritis, 38 (69.1%) were H. pylori-positive. Ki-67 IM was significantly increased during the development of atrophic gastritis: in the antral region to 50.6±8.3 (P&lt;0.05), in atrophy and pseudopyloric metaplasia in the incisura region to an average of 47.3±8.2 (P&lt;0.05) and in the gastric body region to an average of 46.9±7.4 (P&lt;0.05). In chronic atrophic gastritis, p53 expression was detected in the antral region in 22 (40.0%) patients, and in atrophy and pseudopyloric metaplasia in the incisura region in 18 (50.0%) and in the body in 4 (57.1%). All patients were H. pylori-positive. Intestinal metaplasia was found in 36 (65.5%) patients in the antral region, 34 (61.8%) patients in the incisura region and 24 (43.6%) patients in the body of the stomach This study showed that in chronic H. pylori-associated atrophic gastritis there is an acceleration of cell proliferation and impaired apoptosis, especially in areas of atrophy, as well as pseudopyloric and intestinal epithelial metaplasia, leading to an increased risk of gastric cancer.

Abstract This case is a unique co‐presentation of mixed uterine and ovarian teratoma in a middle‐aged female Labrador dog with chief complaint of purulent vaginal discharge. On ultrasonographic examination, a large anechoic mass with several echogenic flakes in uterine lumen and cystic cavitation of endometrial surface was identified without any metastasis on radiography. After 2‐week medicinal therapy, ovariohysterectomy of dog was done and pyometra with large greyish white globoid soft fibroid mass (8.5 × 9.5 cm) on anterior border of right uterine horn formed remarkable findings. The histopathological analysis revealed stratified squamous metaplasia of endometrial epithelium with strong epidermal reaction pattern, in addition to, indistinct areas of degenerated hair follicle(s) and melanin deposits, areas of irregular, aggressive neuro‐fibromatous stroma, amidst muscular stroma turned fibrous and adipose connective tissues component. The dog recovered uneventfully. Therefore, we report rare case of mixed uterine and ovarian teratoma along with cystic endometrial hyperplasia‒pyometra complex in dog.

Abstract This is an ex-smoker patient with a history of long-standing ulcerative colitis with persistent activity and refractory to several biological therapies. She has ongoing symptoms, such as bloody diarrhea, weight loss, and severe anemia that require regular intravenous iron transfusions. Despite attempts to control the disease with different medications, including Infliximab and Vedolizumab, the patient remains symptomatic and elevates markers of disease activity, such as fecal calprotectin. At follow-up, the patient presented with a chronic cough, which led to studies that revealed the presence of a hypermetabolic pulmonary nodule in the left lower lobe, suspected of primary pulmonary neoplasia, and an atypical pulmonary resection was performed. Diagnosis reveals possible respiratory granulomatous intestinal epithelial metaplasia due to histological findings in the lung, consistent with an uncommon extraintestinal manifestation in the context of uncontrolled ulcerative colitis. Finally, a change of therapeutic target with Ustekinumab was initiated due to the previous failure of anti-TNF and Vedolizumab treatments in the control of ulcerative colitis, with clinical improvement in the digestive and respiratory spheres.