Surface Epithelium Research Articles

Risk Factors and Outcomes of Management in Fistulizing Crohn's Disease

Abstract Background Crohn's disease (CD) patients often encounter perianal fistula formation, which can cause significant morbidity. Chronic transmural bowel inflammation in CD can lead to sinus tracts evolving into fistulas—abnormal connections between epithelial surfaces. Roughly 35-40% of patients develop fistulas, primarily perianal (54%), with internal fistulas posing diagnostic and therapeutic challenges. Fistulizing CD manifests severe symptoms, affecting quality of life and necessitating frequent hospitalizations and surgeries. Aim of the Work The aim of the work was to develop risk prediction and identify outcomes of management in fistulizing Crohn's disease. Patients and Methods This case-control study encompassed 90 Egyptian CD patients, divided into two groups: those with fistulas (external or internal) and those without. Patients were recruited from the Ain Shams outpatient clinic and Gastroenterology and Hepatology department. Clinical, radiological (CT or MR enterography), and colonoscopic assessments were performed. Risk factors, clinical characteristics, and treatment outcomes were examined. Results In the study, males were more prevalent in the fistula group; however, the difference wasn't statistically significant. Similarly, age and smoking differences were not statistically significant between the study groups. Entero-Entero fistulas were the most common, with Remicade and surgery being the predominant management strategy. NSAID intake significantly correlated with the fistula group. CDAI scores were higher in the fistula group but improved significantly with treatment in both groups. While colonoscopy findings varied minimally before and after treatment, cecum lesions showed significant increase post-treatment in the fistula group. No significant differences existed in outcomes according to management strategy within the fistula group. Conclusion In conclusion, this study underscores the heightened risk of NSAID intake in fistulizing Crohn's disease, emphasizes the effectiveness of CDAI scores in assessing disease activity and monitoring treatment outcomes, and highlights the importance of personalized management strategies for fistula patients. The significant increase in cecum lesions after treatment within the fistula group suggests the need for focused attention to this aspect. However, the study's limited scope on Egyptian CD patients calls for careful consideration when applying these findings to broader populations.

Functional and radiological sinonasal outcomes of CFTR modulators for sinus disease in cystic fibrosis: A meta-analysis.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease. English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements. Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD=12.80, [95% confidence interval, CI: 10.46‒15.13], p<0.001, n=222), with no heterogeneity detected (I2=0%, p=0.820). There was also a significant improvement in Lund‒Mackay scores (SMD=1.25, [95% CI: 0.58‒1.91], p<0.001, n=88), with heterogeneity detected (I2=67%, p=0.030). CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.

Oral delivery of solid lipid nanoparticles surface decorated with hyaluronic acid and bovine serum albumin: A novel approach to treat colon cancer through active targeting

The present study aims to prepare and evaluate solid lipid nanoparticles (SLNs) loaded with irinotecan (IRN) drug and daidzein (DZN) isoflavonoid and surface coated with ligand materials such as hyaluronic acid (HA) and bovine serum albumin (BSA) with additional coating of chitosan for active targeting to receptors present on colon surface epithelium for oral targeted delivery. The optimized batch was evaluated for particle size, zeta potential exhibiting nanometric size with good entrapment efficiency. Nanoparticles were found to be spherical. FTIR and DSC revealed that all the excipients and formulation were compatabile to each other and showed better encapsulation exhibiting amorphous and crystallinity forms. In vitro drug release of SLNs confirmed that initially a burst release, followed by sustained release pattern was exhibited. Cell lines studied performed on HT-29 cells showed demonstrated that conjugated SLNs inhibited cytotoxicity at 75 μg/ml, indicating that cells were taken up through a receptor-mediated endocytosis process. Cell cycle analysis showed that cell arrest was done at 67.8 % (G0/G1 phase) and inhibited apoptosis by 56 %. Further during In vivo studies, RT-PCR study revealed downregulation of Carcinoembryonic antigen (CEA), a non-specific serum biomarker overexpressed in tumor cells and upregulation of pro-inflammatory cytokine TNF-α. Histopathological study revealed that conjugated (HA-BSA) coated with chitosan SLNs restored normal mucosa and colon architecture, depicting all mucosal layers. Hence, these conjugated SLNs may serve as a novel combination for the treatment of colon cancer.

Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies

Extremely well-differentiated gastric-type adenocarcinoma (EWDGA) is a rare type of gastric cancer composed of deceptively bland-looking malignant cells resembling normal foveolar or pyloric epithelium. The histological features of this tumor have not been recognized by many pathologists, and inter-observer variation studies are lacking. Here, we report seven EWDGAs and inter-observer variation of six preoperative biopsies was evaluated by 11 pathologists in a single institute. Based on the pathological diagnosis of the endoscopic biopsy slides, the average rate of definite malignancy diagnosis was 15.2 %, and the overall diagnostic concordance rate was 34.9 % among 11 pathologists. Microscopically, the surface epithelium was preserved and only a few atypical tumor glands were scattered in most endoscopic biopsies. Structural atypia was minimal, and the tumor glands were barely distinguishable from normal glands. Although nuclear atypia was minimal, enlarged nuclei, relatively large glands with irregular shapes, and abundant cytoplasmic mucin were observed in gastric pinch biopsies. In preoperative biopsies, no cases showed p53 overexpression, and Ki-67 labeling index ranged from 3 % to 35 % and was higher compared to non-neoplastic glands in 3 cases. After gastrectomy, four (57.1 %) patients had advanced gastric cancer and three (42.9 %) had lymph node metastasis. Genomic profiling of the four patients revealed mutations of TP53, BRAF, KRAS, STK11, and MDM2/CCND1 amplification. Immunohistochemistry for p53 was not helpful while Ki-67 may be helpful when staining pattern is distinct from the non-neoplastic mucosa. In conclusion, it is challenging to diagnose EWDGA using biopsy specimens. Recognizing and addressing this rare entity will increase diagnostic accuracy to ensure the early diagnosis of cancer.

Dysbiosis and fecal microbiota transplant: Contemplating progress in health, neurodegeneration and longevity.

The gut-brain axis plays an important role in mental health. The intestinal epithelial surface is colonized by billions of commensal and transitory bacteria, known as the Gut Microbiota (GM). However, potential pathogens continuously stimulate intestinal immunity when they find the place. The last two decades have witnessed several studies revealing intestinal bacteria as a key factor in the health-disease balance of the gut, as well as disease-emergent in other parts of the body. Various neurological processes, such as cognition, learning, and memory, could be affected by dysbiosis in GM. Additionally, the aging process and longevity are related to systemic inflammation caused by dysbiosis. Commensal GM affects brain development, behavior, and healthy aging suggesting that building changes in GM might be a potential therapeutic method. The innovation in GM dysbiosis is intervention by Fecal Microbiota Transplantation (FMT), which has been confirmed as a therapy for recurrent Clostridium difficile infections and is promising for other clinical disorders, such as Parkinson's disease, Multiple Sclerosis (MS), Alzheimer's disease, anddepression. Additionally, FMT may be possible to promote healthy aging, and extend longevity. This review aims to connect dysbiosis, neurological disorders, and aging and the potential of FMT as a therapeutic strategy to treat these disorders, and to enhance the quality of life in the elderly.

Human Mesofluidic Intestinal Model for Studying Transport of Drug Carriers and Bacteria Through a Live Mucosal Barrier.

The intestinal mucosal barrier forms a critical interface between lumen contents such as bacteria, drugs, and drug carriers and the underlying tissue. Current in vitro intestinal models, while recapitulating certain aspects of this barrier, generally present challenges with respect to imaging transport across mucus and uptake into enterocytes. A human mesofluidic small intestinal chip was designed to enable facile visualization of a mucosal interface created by growing primary human intestinal cells on a vertical hydrogel wall separating channels representing the intestinal lumen and circulatory flow. Type I collagen, fortified via cross-linking to prevent deformation and leaking during culture, was identified as a suitable gel wall material for supporting primary organoid-derived human duodenal epithelial cell attachment and monolayer formation. Addition of DAPT and PGE2 to culture medium paired with air-liquid interface culture increased the thickness of the mucus layer on epithelium grown within the device for 5 days from approximately 5 mm to 50 μm, making the model suitable for revealing intriguing features of interactions between luminal contents and the mucus barrier using live cell imaging. Time-lapse imaging of nanoparticle diffusion within mucus revealed a zone adjacent to the epithelium largely devoid of nanoparticles up to 4.5 hr after introduction to the lumen channel, as well as pockets of dimly lectin-stained mucus within which particles freely diffused, and apparent clumping of particles by mucus components. Multiple particle tracking conducted on the intact mucus layer in the chip revealed significant size-dependent differences in measured diffusion coefficients. E. coli introduced to the lumen channel were freely mobile within the mucus layer and appeared to intermittently contact the epithelial surface over 30 minute periods of culture. Mucus shedding into the lumen and turnover of mucus components within cells were visualized. Taken together, this system represents a powerful tool for visualization of interactions between luminal contents and an intact live mucosal barrier.

Pathogenetic role of changes in the colon mucous barrier in patients with ulcerative colitis and the possibility of correction

The aim of this study was to evaluate the changes in the colon mucosal barrier in patients with ulcerative colitis (UC) and to analyze the efficacy of using Zafacol IQ in the complex therapy of these patients. Materials and methods. A prospective, multicenter, randomized, comparative study was conducted in parallel groups to investigate the efficacy and safety of the Zafacol IQ administration in the complex therapy of patients with UC. 64 patients with left‑sided UC of medium‑severe course in the acute stage were observed. There were 34 men and 30 women among the patients; the average age was (46.6±5.8) years. The diagnosis of UC was established clinically and confirmed endoscopically and histologically. The study included patients suffering from UC for at least 1 year. All patients underwent endoscopic examination of the large intestine with biopsy before treatment and after 6 weeks of therapy. The biopsy was stained with hematoxylin and eosin; the PAS reaction was performed. To determine the content of mucins in colonic mucus and the state of tight junctions, an immunohistochemical study was conducted with mucins (MUC‑2, MUC‑4) and proteins of the tight junction family Claud‑1 and Claud‑7. Before and after therapy, the status of the main bacterial enterotypes (Bacteroidetes, Firmicutes, Actinobacteria), as well as the level of regulatory, butyrate‑producing bacteria (Faecalibacterium prausnitzii, Akkermansia muciniphila) were studied in all patients using the polymerase chain reaction qRT‑PCR method. Results. Before therapy, against the background of the development of clinical symptoms, UC patients had a violation of the integrity of the epithelium with the formation of erosive‑ulcerative defects and changes in the colon mucous membrane with the development of inflammatory cell infiltration and disorders of mucus formation and increased epithelial permeability. Before treatment, changes in the colon microbial landscape were detected in UC patients, with a significant decrease in Bacteroidetes and Firmicutes against the background of an increase in representatives of Actinobacteria and other, mostly opportunistic flora. In addition, a reduction in the regulatory butyrate‑producing bacteria (Akkermansia muciniphila and Faecalibacterium prausnitzii) was fixed in patients with UC. The use of Zafacol IQ in patients contributed to a lower level of clinical activity of the disease, increased the frequency of achieving endoscopic remission of UC after complex treatment, led to a decrease in active neutrophils in the cellular infiltrate, improved mucus formation with tendencies to normalize its quality characteristics, an increase in glycoproteins and glycosaminoglycans, as well as MUC2 in colonic mucus, contributed to a decrease in epithelial permeability and an increase in the expression of Claud­­1 and Claud­­7 in goblet cells with an increase in Bacteroidetes, Firmicutes and Faecalibacterium prausnitzii. Conclusions. The use of Zafacol IQ in the complex therapy of UC patients was effective and safe. This drug in combination with mesalazine contributed to positive clinical dynamics and a lower level of clinical activity of the disease, increased the frequency of endoscopic remission of UC. Pronounced positive morphological dynamics were observed: an improvement in mucus formation, an increase in the intensity of the PAS reaction, an increase in MUC2 in the colonic mucus, a decrease in epithelial permeability, and an increase in the expression of Claud‑1 and Claud‑7 in both goblet cells and in the surface epithelium. Complex therapy with the appointment of ­Zafacol IQ contributed to the normalization of the intestinal microbiome in UC patients — an increase in Bacteroidetes, Firmicutes and Faecalibacterium prausnitzii with a tendency to decrease Actinobacteria.

Ciliary Function, Antigen Stasis and Asthma.

The prevalence of asthma exceeds 3% of the population. Asthma is observed to be more common in children following severe viral lower respiratory illnesses that affect ciliary function, but mechanisms linking ciliary function to asthma pathogenesis have been obscure. Recent data regarding primary ciliary dyskinesia (PCD) may help us to understand the association. Here, I will review what is known about the relationship between ciliary function and asthma. PCD is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33-mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Moreover, variants in genes that affect the function of cilia can be associated with poor lung function, even in the absence of PCD, and with increased asthma severity. The role of antigen stasis on the surface of dysfunctional airway cilia in the pathophysiology of asthma is a novel area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma.

A lymphocyte chemoaffinity axis for lung, non-intestinal mucosae and CNS.

Tissue-selective chemoattractants direct lymphocytes to epithelial surfaces to establish local immune environments, regulate immune responses to food antigens and commensal organisms, and protect from pathogens. Homeostatic chemoattractants for small intestines, colon and skin are known1,2, but chemotropic mechanisms selective for respiratory tract and other non-intestinal mucosal tissues remain poorly understood. Here we leveraged diverse omics datasets to identify GPR25 as a lymphocyte receptor for CXCL17, a chemoattractant cytokine whose expression by epithelial cells of airways, upper gastrointestinal and squamous mucosae unifies the non-intestinal mucosal tissues and distinguishes them from intestinal mucosae. Single-cell transcriptomic analyses show that GPR25 is induced on innate lymphocytes before emigration to the periphery, and is imprinted in secondary lymphoid tissues on activated B and T cells responding to immune challenge. GPR25 characterizes B and T tissue resident memory cells and regulatory T lymphocytes in non-intestinal mucosal tissues and lungs in humans and mediates lymphocyte homing to barrier epithelia of the airways, oral cavity, stomach, and biliary and genitourinary tracts in mouse models. GPR25 is also expressed by T cells in cerebrospinal fluid and CXCL17 by neurons, suggesting a role in central nervous system (CNS) immune regulation. We reveal widespread imprinting of GPR25 on regulatory T cells, suggesting a mechanistic link to population genetics evidence that GPR25 is protective in autoimmunity3,4. Our results define a GPR25-CXCL17 chemoaffinity axis with the potential to integrate immunity and tolerance at non-intestinal mucosae and the CNS.

Immune checkpoint inhibitor-induced gastrointestinal injury: prevalence of cytomegalovirus, adenovirus and Epstein-Barr virus

AimsWidespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The...

Peri-Ampullary Tumour; An Unusual Cause of Upper Gastrointestinal Bleeding

Periampullary tumors are cancers that arise in the region of the around the ampulla of Vater, where the bile duct and pancreatic duct converge and empty into the small intestine. This region is very critical for digestive enzyme and bile secretions. This may be associated with slow disease progression, age related changes delayed onset of symptoms and lack of screening and diagnostic facilities. These tumours can be challenging to diagnose and manage due to their proximity to several vital structures. Upper gastrointestinal bleeding may be a rare clinical presentation following tumoral ulceration, erosion into blood vessels or nearby structures or secondary complications like pancreatitis or portal hypertension. Identifying the anatomical origin of these malignancies is usually a herculean task. This will require prompt oesophagogastroduodenoscopy and imaging to determine the source and appropriate management. This is especially true given the region's transitional character, closeness to various structures, and overlapping features among them. We present periampullary tumour an unusual cause of upper gastrointestinal bleeding in a resource limited setting. A52 year old Nigerian male was admitted at the Usmanu Danfodiyo University Teaching Hospital, Sokoto for evaluation following a 3 months history of progressive weight loss, generalized body weakness and a burning and occasionally colicky, persistent, non-radiating epigastric pain, loss of appetite, easy fatiguability, occasional dizziness and recurrent non-projectile post-prandial non-billous vomiting. Though he had no hematemesis, he had history of passage of malaena. The patient was fully conscious on admission, pale, wasted with a markedly tender epigstric region. He was tachycardic with a minimal elevation in blood pressure level of 138/94mmHg. He had an international normalized ratio (INR) of 1.0. Oesophagogastroduodenoscopy was performed which showed a polypoid fungating mass at the1st extending to the 2nd part of the duodenum. A Computerized Tomogram scan of the abdomen showed a diffuse circumferential duodenal wall thickening of 1st and 2nd parts (more in 2nd part) with reduction in luminal calibre of duodenum and mildly dilated pancreatic, common bile, common hepatic ducts. Multiple biopsies were taken for histology which showed moderately differentiated aadenocarcinoma. Surface epithelium composed of columnar epithelial cells which can be seen in the top right of the image below with an invasive tumour, seen infiltrating the lamina propria in the lower left. He went on to have an exploratory laparotomy with triple bypass involving a side to side gastrojejunal anastomosis and cholecystojejunostomy and entero-enterotomy folowing which he went on to receive chemotherapy. As of the time of this write up the patient has recuperated well following his treatment.

The Pseudomonas aeruginosa sphBC genes are important for growth in the presence of sphingosine by promoting sphingosine metabolism.

Sphingoid bases, including sphingosine, are important components of the antimicrobial barrier at epithelial surfaces where they can cause growth inhibition and killing of susceptible bacteria. Pseudomonas aeruginosa is a common opportunistic pathogen that is less susceptible to sphingosine than many Gram-negative bacteria. Here, we determined that deletion of the sphBCD operon reduced growth in the presence of sphingosine. Using deletion mutants, complementation, and growth assays in P. aeruginosa PAO1, we determined that the sphC and sphB genes, encoding a periplasmic oxidase and periplasmic cytochrome c, respectively, were important for growth on sphingosine, while sphD was dispensable under these conditions. Deletion of sphBCD in P. aeruginosa PA14, P. protegens Pf-5, and P. fluorescens Pf01 also showed reduced growth in the presence of sphingosine. The P. aeruginosa sphBC genes were also important for growth in the presence of two other sphingoid bases, phytosphingosine and sphinganine. In wild-type P. aeruginosa, sphingosine is metabolized to an unknown non-inhibitory product, as sphingosine concentrations drop in the culture. However, in the absence of sphBC, sphingosine accumulates, pointing to SphC and SphB as having a role in sphingosine metabolism. Finally, metabolism of sphingosine by wild-type P. aeruginosa protected susceptible cells from full growth inhibition by sphingosine, pointing to a role for sphingosine metabolism as a public good. This work shows that metabolism of sphingosine by P. aeruginosa presents a novel pathway by which bacteria can alter host-derived sphingolipids, but it remains an open question whether SphB and SphC act directly on sphingosine.

Acute Toxicity of Zinc Sulphate (ZNSO4) on the Estuarine Blood Clam Anadara granosa (Linnaeus, 1758)

Zinc is an essential trace element for taking role in electron transfer in many enzymatic reactions. However, its prolonged and excessive intake may lead to toxic effect. Aquatic organisms take up zinc in proportion to the dissolved concentration of the metal in water. Generally, uptake occurs throughout epithelial surfaces related to absorption and excretion of ions such as the gill membranes. Heavy metals can accumulate in the tissues of aquatic organisms and cause a range of hazardous effects to all organisms through bio-magnifications. There are a number of studies carried out on the toxicity of Zinc sulphate. The aim of this study was to investigate the acute toxicity effects of Zinc sulphate on the clam Anadara granosa. Clam samples were exposed to different concentrations (3, 6, 9, 12, and 15.00 mg/L) of Zinc sulphate for 96h and their cumulative mortality was calculated in 12 hours intervals. Results were analyzed by SPSS 20 to obtain number of cumulative mortality and lethal concentrations. The blood clam Anadara granosa LC50 and LC90 for zinc sulphate at 96 hours were 4.63 and 9.28mg/L in the current study. Mortality rate was increased with the increase in metal concentrations and time.

Gilthead seabream mucus glycosylation is complex, differs between epithelial sites and carries unusual poly N-acetylhexosamine motifs

Gilthead seabream (Sparus aurata) is a marine finfish of economic importance in aquaculture. Despite its adaptability to varying culture conditions, gilthead seabream culture can be affected by viral, bacterial or parasitic diseases. The main route of entry of pathogens is through mucosal surfaces. Teleost external and internal surfaces are covered by mucus, mainly comprised of highly glycosylated proteins called mucins. The mucin glycans regulate pathogen growth, adhesion, virulence and inter and intra species communication. Here, we characterized the gilthead seabream mucus glycosylation, compared it to previously described species and investigated associations with microbiota. 214 glycans were identified. The majority of the glycans were found at more than one epithelial surface, but 27, 22 and 89 O-glycan structures were unique to skin, gill and intestinal sample groups, respectively. Six O-glycan core types were observed. The majority of the seabream skin and gill O-glycans were neutral with unusual poly HexNAc motifs. In contrast, seabream intestinal O-glycans were highly acidic and not of the ‘poly HexNAc’ type observed in skin and gill. Furthermore, gilthead seabream gill mucosa had less oligomannose and more complex N-glycans compared to skin and intestine. The concentration and diversity of bacteria was similar in skin, gill and intestine, but the bacterial species differed between epithelia and co-varied with glycan epitopes. The presence of a complex mucus glycosylation with plenty of glycan epitopes for bacterial foraging, suggest that the skin mucosal defense in seabream includes an abundant resident microbiota. This large library of structures provides a platform for further studies, for example aiming to identifying glycans to use for diagnostic purposes, to study host-microbe interactions or disease intervention therapies.

Collagenous and lymphocytic gastritis in pediatric patients. A single-center experience observing an increase in diagnosis in recent years

Background Collagenous gastritis (CG) and Lymphocytic gastritis (LG) are rare types of gastritis. Thick sub-epithelial collagen bands characterize CG. Numerous lymphocytes in the surface and foveolar epithelium characterize LG. We aimed to characterize these disorders in our pediatric unit. Methods A retrospective review of children diagnosed with CG and LG between 2000 and 2023. Baseline data; demographics, anthropometric, symptoms, laboratory data, macroscopic and histopathologic findings. Follow-up data; treatment, improvement of symptoms and laboratory parameters. Results We identified 31 children, 11 (35.5%) had CG and 20 (64.5%) LG, mean age 9.07 ± 5.04 years. Seven (22.6%) children were diagnosed between 2000 and 2016 and 24 (77.4%) between 2017 and 2023. Baseline characteristics included gastrointestinal symptoms in 16 (51.6%), iron deficiency anemia in 22 (71%), with a mean hemoglobin level of 8.8 ± 2.5 gr/dl. Gastric endoscopic findings were normal in 12 (38.7%), demonstrated nodularity in 14 (45.2%) and an inflamed mucosa without nodularity in 5 (16.1%). Helicobacter pylori was positive in 3 (9.7%) children, celiac disease was diagnosed in 7 (22.6%). Treatment included iron supplementation in 24 (77.4%), proton pump inhibitors in 16 (51.6%) and a gluten free diet in seven. Mean follow-up was 2.9 ± 2.2 years. Hemoglobin levels normalized in 21/22; however, 9 (29%) patients required repeat iron supplementation. Eight patients had a repeat endoscopy (6 CG and 2 LG) without changes in their gastric histopathology. Conclusions CG and LG are not rare in pediatric patients. Physicians and pathologist should be aware of these types of gastritis.

Planarian Mucus: A Novel Source of Pleiotropic Cytotoxic and Cytostatic Agents against Cancer Cells.

Biological evolution has generated a vast array of natural compounds produced by organisms across all domains. Among these, secondary metabolites, selected to enhance an organism's competitiveness in its natural environment, make them a reservoir for discovering new compounds with cytotoxic activity, potentially useful as novel anticancer agents. Slime secretions, the first barrier between epithelial surfaces and the surrounding environment, frequently contain cytotoxic molecules to limit the growth of parasitic organisms. Planarians, freshwater Triclads, continuously secrete a viscous mucus with multiple physiological functions. The chemical composition of planarian mucus has been only partially elucidated, and there are no studies reporting its cytotoxic or cytostatic effects. In this study, we developed a protocol for collecting mucus from Dugesia japonica specimens and we demonstrated that it inhibits the growth of cancer cells by activating cytostatic and ROS-dependent cytotoxic mechanisms inducing lipid droplet accumulation and mitochondrial membrane reorganization. Although further research is needed to identify the specific chemicals responsible for the anticancer activity of planarian mucus, this work opens up numerous research avenues aimed at better understanding the mechanisms of action of this product for potential therapeutic applications.

Identification of prevention marker associated with DNA replication in ovarian cancer: Expression of MCM2 protein and bioinformatics analysis

Ovarian cancer is one of the types of gynecological cancers that is considered to be particularly dangerous. Ovarian cancer treatment has come a long way in recent years, but the disease is still quite likely to spread to other parts of the body. In this line of research, our goal is to pinpoint the shifts in gene expression profiles that are responsible for the avoidance of ovarian cancer. The dataset GSE54388 which was deposited in the Gene Expression Omnibus (GEO) database was processed in order to find differentially expressed genes (DEGs) that were present between human ovarian surface epithelium samples and tumor epithelial component samples. The weighted gene correlation network analysis, also known as WGCNA, was performed on the modules that were associated with the ovarian cancer group. The Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the Gene Set Enrichment Analysis (GSEA) were used to compile a summary of the DEGs that were found in the Venn analysis of the Royalbule module. This analysis found 186 genes that overlapped in the royal blue module. Using the cytohubba plug-in that is included in the Cytoscape software, the Protein-protein Interaction (PPI) network was created and then searched to identify hub genes. Based on these findings, it seems that 10 genes have a role as hub genes in the prevention of ovarian cancer.

Human Ovarian Surface Epithelium Organoids as a Platform to Study Tissue Regeneration.

The ovarian surface epithelium (OSE), the outermost layer of the ovary, undergoes rupture during each ovulation and plays a crucial role in ovarian wound healing while restoring ovarian integrity. Additionally, the OSE may serve as the source of epithelial ovarian cancers. Although the OSE regenerative properties have been well studied in mice, understanding the precise mechanism of tissue repair in the human ovary remains hampered by limited access to human ovaries and suitable in vitro culture protocols. Tissue-specific organoids, miniaturized in vitro models replicating both structural and functional aspects of the original organ, offer new opportunities for studying organ physiology, disease modeling, and drug testing. Here, we describe a method to isolate primary human OSE (hOSE) from whole ovaries and establish hOSE organoids. We include a morphological and cellular characterization showing heterogeneity between donors. Additionally, we demonstrate the capacity of this culture method to evaluate hormonal effects on OSE-organoid growth over a 2-week period. This method may enable the discovery of factors contributing to OSE regeneration and facilitate patient-specific drug screenings for malignant OSE.

Integrated genomic/epigenomic analysis stratifies subtypes of clear cell ovarian carcinoma, highlighting their cellular origin

The cellular origin of clear cell ovarian carcinoma (CCOC), a major histological subtype of ovarian carcinoma remains elusive. Here, we explored the candidate cellular origin and identify molecular subtypes using integrated genomic/epigenomic analysis. We performed whole exome-sequencing, microarray, and DNA methylation array in 78 CCOC samples according to the original diagnosis. The findings revealed that ARID1A and/or PIK3CA mutations were mutually exclusive with DNA repair related genes, including TP53, BRCA1, and ATM. Clustering of CCOC and other ovarian carcinomas (n = 270) with normal tissues from the fallopian tube, ovarian surface epithelium, endometrial epithelium, and pelvic peritoneum mesothelium (PPM) in a methylation array showed that major CCOC subtypes (with ARID1A and/or PIK3CA mutations) were associated with the PPM-lile cluster (n = 64). This cluster was sub-divided into three clusters: (1) mismatch repair (MMR) deficient with tumor mutational burden-high (n = 2), (2) alteration of ARID1A (n = 51), and (3) ARID1A wild-type (n = 11). The remaining samples (n = 14) were subdivided into (4) ovarian surface epithelium-like (n = 11) and (5) fallopian tube-like (considered as high-grade serous histotype; n = 3). Among these, subtypes (1–3) and others (4 and 5) were found to be associated with immunoreactive signatures and epithelial-mesenchymal transition, respectively. These results contribute to the stratification of CCOC into biological subtypes.

Hydroquinone impairs trophoblast migration and invasion via AHR-twist-IFITM1 axis

IntroductionEmbryo implantation is a tightly regulated process, critical for a successful pregnancy. After attachment of the blastocyst to the surface epithelium of the endometrium trophoblast migrate from the trophectoderm and invade into the stromal component of endometrium. Alterations on either process will lead to implantation failure or miscarriage. Volatile organic compounds (VOCs) such as benzene induce pregnancy complications, including preterm birth and miscarriages. The mechanism of this effect is unknown. The objective of this study was to elucidate the impact of benzene metabolite, Hydroquinone, on trophoblast function. We tested the hypothesis that Hydroquinone activates the Aryl hydrocarbon receptor (AhR) pathway modulating trophoblast migration and invasion. MethodsFirst-trimester trophoblast cells (Sw.71) were treated with hydroquinone (6 and 25 μM). Trophoblast migration and invasion was evaluated using a 3D invasion/migration model. Gene expression was quantified by q-PCR and Western blot analysis. ResultsHydroquinone impairs trophoblast migration and invasion. This loss is associated with the activation of the AhR pathway which reduced the expression of Twist1and IFITM1. IFITM1 overexpression can rescue impaired trophoblast migration. DiscussionOur study highlights that hydroquinone treatment induces the activation of the AhR pathway in trophoblast cells, which impairs trophoblast invasion and migration. We postulate that activation of the AhR pathway in trophoblast suppress Twist1 and a subsequent IFITM1. Thus, the AhR-Twist1-IFITM1 axis represent a critical pathway involved in the regulation of trophoblast migration and it is sensitive to benzene exposure. These findings provide crucial insights into the molecular mechanisms underlying pregnancy complications induced by air pollution.