Enterochromaffin Research Articles

Lactate dehydrogenase A is a diagnostic biomarker associated with immune infiltration, m6A modification and ferroptosis in endometrial cancer

BackgroundLactate dehydrogenase A (LDHA) has been confirmed as a tumor promoter in various cancers, but its role in endometrial cancer remains unclear.MethodsThe Cancer Genome Atlas (TCGA), quantitative real-time polymerase chain reaction and the Human Protein Atlas were utilized to analyzed the LDHA expression in EC. The LDHA levels of patients with different clinical features were compared based on the TCGA cohort. The Genome Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis of LDHA-related genes were conducted by R language. The influence of LDHA knockdown on cell proliferation, apoptosis, migration and invasion was detected by in vitro experiment. The relationship between LDHA expression and immune infiltration was explored by Tumor Immune Estimation Resource 2.0 and Gene Expression Profiling Interactive Analysis. The association of LDHA level with N6-methyladenosine (m6A) modification and ferroptosis was investigated based on the TCGA-UCEC and the GEO cohort.ResultsThe LDHA was overexpressed in EC tissues and EC cell lines, and had high predictive accuracy for the EC diagnosis. The LDHA level was associated with age, histological type, histologic grade, and radiation therapy. LDHA-related genes participated in multiple biological functions and signaling pathways. LDHA downregulation significantly promoted cell apoptosis and inhibited the proliferation, migration, and invasion of EC cells. LDHA expression was connected to multiple tumor-infiltrating lymphocytes (TILs), m6A-related genes, and ferroptosis-related genes.ConclusionLDHA has the potential to work as an EC biomarker associated with TILs, m6A modification, and ferroptosis in EC.

Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms.

Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.

The causal relationship between anti-CD20 antibodies and endometrial cancer: a Mendelian randomization study

PurposeTo determine the effects of anti-B cell surface marker CD20 antibody on the occurrence and progression of endometrial cancer to provide insights into clinical treatment in the future.MethodsWe performed a two-sample Mendelian randomization analysis (MR) to analyze the causal relationship between EC and immune cell markers. The genome-wide association study (GWAS) data of MS4A1 single nucleotide polymorphism encoding gene of CD20 were collected, and a drug target MR analysis was performed to detect the causal relationship between anti-CD20 antibody and the risk of EC. The risk of follicular lymphoma was used as a positive control, and EC was used as the outcome.ResultsEC exerted an effect on 28 immunophenotypes, predominantly on CD20. CD20 in immunoglobulin D+ CD38− B cells, memory B cells, and unsw memory B cells increased after EC onset. In addition, we detected one immunophenotype that exerted a dangerous effect on EC, i.e., CD3/TD CD4+ (mature stage of the T cell group). Simultaneously, CD20 could be used as both a risk factor and a protective factor for EC (P > 0.05). Anti-CD20 antibodies significantly reduced the risk of follicular lymphoma, including two GWAS pooled datasets. In addition, anti-CD20 antibodies exerted a protective effect on EC in two GWAS pooled datasets (P > 0.05).ConclusionOur study confirms the close relationship between CD20 and EC. Anti-CD20 antibodies may exert a protective effect on EC and reduce the risk of EC morbidity, providing a reference for future clinical diagnosis and treatment. However, further clinical verification of our results is warranted.

Synchronous bilateral typical pulmonary carcinoid tumours diagnosed by robotic navigation bronchoscopy: A unique case.

Pulmonary carcinoids are uncommon malignant neoplasms, believed to derive from specialized neuroendocrine cells known as Kulchitsky cells. We evaluated a 69-year-old female presenting symptoms consistent with carcinoid syndrome, such as intermittent flushing and diarrhoea, along with complaints of shortness of breath and cough. Imaging revealed bilateral lung nodules, confirmed by biopsy to be carcinoid tumours. The treatment of choice for carcinoid tumours is complete surgical resection. Nonetheless, individualized management plans are crafted based on the tumour's location and the patient's respiratory function as these present challenges to anatomical resection of tumours.

Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation.

Improving generation of insulin-producing islets from human pluripotent stem cells (hPSCs) would enhance their clinical relevance for treating diabetes. Here, we demonstrate that cytoskeletal state at the onset of differentiation is critical for definitive endoderm formation. Depolymerizing F-actin with latrunculin A (latA) during the first 24 hours of differentiation facilitates rapid exit from pluripotency and alters Activin/Nodal, BMP, JNK-JUN, and WNT pathway signaling dynamics during definitive endoderm formation. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers for other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved maturation, insulin secretion, and ability to reverse hyperglycemia. Furthermore, this latA treatment reduces enterochromaffin cells in the final cell population and corrects differentiations from hPSC lines that otherwise fail to consistently produce pancreatic islets, highlighting the importance of cytoskeletal signaling during differentiation onset.

Are pediatricians aware of the mysterious FPIES? Current diagnostic and treatment options. Case report

The prevalence of food allergies continues to grow steadily, and due to certain difficulties in diagnosing allergies not associated with immunoglobulin E, some conditions are little known. Such diagnosis-challenging diseases include food protein-induced enterocolitis syndrome (FPIES), a relatively low-prevalence disease most commonly occurring in early childhood but, in some cases, affecting adults as well. The pathogenesis of FPIES has not been reliably studied. FPIES is associated with elevated serum tryptase and release of pro-inflammatory cytokines, including interleukin-17. A characteristic symptom of FPIES is uncontrollable vomiting, which is probably triggered by the serotonin secreted by enterochromaffin cells, which activates the vagus nerve and the vomiting reflex, determining a good response of vomiting relief with ondansetron, a serotonin receptor antagonist. Changes in gut microbiota composition were also reported in FPIES. FPIES can lead to severe complications such as hypovolemic shock due to the rapid progression of symptoms and rapid dehydration, which often requires hospitalization of patients with acute FPIES. The provoking factors usually include products from the "big nine" allergens: cow's milk, eggs, gluten, soy, nuts, peanuts, fish, seafood, and sesame. FPIES can be acute or chronic; the manifestations slightly differ depending on the disease form. Laboratory diagnosis is difficult due to the lack of reliable biomarkers, and the diagnosis is established clinically and confirmed with an oral provocation test. The key treatment for FPIES is to eliminate the trigger protein from the diet, and depending on the severity of the disease, some patients may be allowed to consume a heat-treated allergen. The prognosis of FPIES is favorable: tolerance to the trigger product in most cases is developed within two years. Further studies are required to clarify the pathogenesis, prevalence, and treatment methods, with prospective follow-up of patients with a history of FPIES and the analysis of concurrent and subsequent diseases, including allergic conditions. The article presents two clinical cases of children diagnosed with FPIES.

Harnessing hybrid molecules for drug development

Harnessing hybrid molecules for drug development Stoyanka Nikolova, Professor from Paisii Hilendarski Plovdiv University, discusses the potential of harnessing hybrid molecules for drug development and their possible application in addressing the clinical challenge of irritable bowel syndrome. Irritable bowel syndrome (IBS) remains a clinical challenge. It’s the most common gastrointestinal disorder. IBS has no definitive treatment but could be controlled by non-pharmacologic management, eliminating some exacerbating factors such as certain drugs, stress conditions, and changes in dietary habits. Intestine peristaltic reflexes and sensory relays are significantly regulated by serotonin, predominantly found in intestine enterochromaffin cells.

FTX promotes esophageal cancer progression and desensitizes esophageal cancer cells to ionizing radiation by microRNA-99a/b-3p/WEE1/ERCC1 axis

Abstract Objectives This study was conducted to uncover the underlying cellular and molecular mechanisms of FTX dysregulation in EC. Methods The gene expression in tumor tissues was detected using western blot, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR). The dual-luciferase reporter and RNA FISH assays confirmed the interaction between miRNA and target genes. Mouse models for Xenograft and lung metastasis were used to assess EC cell tumorigenesis and metastasis. Results This study finds that up-regulated FTX in patients with esophageal cancer correlates with poor clinical outcomes. Silencing FTX inhibits esophageal cancer cell growth and migration in vitro and tumor metastasis in vivo. miR-99a/b-3p sensitizes esophageal cancer cells to ionizing radiation by WEE1 (Wee1-like protein kinase) and ERCC1 (excision repair cross-complementation group 1) in vitro. Conclusions FTX promotes the malignant biological phenotype of esophageal cancer cells. Mechanistically, FTX acts as a ceRNA to regulate the transcription of WEE1 and ERCC1 by sponging hsa-miR-99a/b-3p.

Lacticaseibacillus rhamnosus KY16 Improves Depression by Promoting Intestinal Secretion of 5-HTP and Altering the Gut Microbiota.

Increasing research suggests a connection between gut microbiota and depressive disorders. Targeted changes to the intestinal flora may contribute to alleviating anxiety and depression. This study aimed to identify probiotics that could attenuate stress-induced abnormal behavior and explore potential mechanisms. The administration of LR.KY16 significantly reduced stress-induced abnormal behaviors and physiological dysfunction. The mechanism may be via regulating the structure of the intestinal microbiota in mice, increasing the abundance of Akkermansia muciniphila, prompting enterochromaffin cells to secrete 5-HTP in the gut, which enters the brain through the bloodstream and promotes the synthesis of 5-HT in the brain, and then activates brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) through the 5-HT1A receptor. In addition, LR.KY16 also increased the expression of claudin-7, occludin, and zonula occludens-1 (ZO-1) in the colon, inhibited microglial M1 polarization, and inhibited systemic inflammation.

Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1-HMMR Signaling Axis.

Adipocyte is a predominant component of the omental adipose tissue that influences the tumor microenvironment and increases the risk of endometrial cancer progression (EC), however, little is known about the underlying mechanism. In this study, using a co-culture model, we found that the adipocyte-EC cell interaction promoted SIRT1 signaling in vitro and in vivo xenograft mice models. Furthermore, immunostaining of SIRT1 protein showed significantly higher expression of SIRT1 in endometrial cancer patients than in normal endometria. RNA sequencing analysis revealed HMMR (hyaluronan-mediated motility receptor), an oncogene, as a downstream effector of SIRT1 in adipocyte-associated EC. Transient knockdown and chromatin immunoprecipitation assays showed that SIRT1 inhibition impedes transcription of the HMMR gene via FOXM1, and reduced expression of HMMR in co-cultured EC cells blocks AURKA activation via TPX2, leading to cell cycle arrest. This is the first study to report the positive correlation between SIRT1 and HMMR in EC patient tumors and might be used as a potential biomarker in EC. Notably, SIRT1 regulates HMMR expression in a FOXM1-dependent manner, and interfering with SIRT1 may provide a promising strategy for the management of endometrial cancer.

Prediction of the drug intestinal absorption and drug-induced intestinal toxicity with the use of cultured human/animal crypt-derived intestinal stem cells

Prediction of intestinal drug absorption and drug-induced intestinal toxicity is critical for the development of orally-administered drugs. However, it is difficult to accurately predict these events because of large species differences and a lack of appropriate in vitro assay. Then, we proposed the use of human crypt-derived intestinal cells for the prediction of intestinal absorption and the risk of intestinal toxicity. 3D human intestinal spheroids were established from fresh surgical specimens of proximal jejunum and terminal ileum using the conditioned media containing Wnt3a, R-spondin 3, and noggin. To generate 2D monolayer, spheroids were enzymatically dissociated into single cells and plated onto Matrigel-precoated culture plates/inserts. We have confirmed the activities of typical drug-metabolizing enzymes and uptake/efflux transporters in human jejunal spheroid-derived differentiated cells. Intestinal availability (Fg) estimated from the apical-to-basal permeation clearance across the jejunal monolayer showed a good correlation with in vivo human Fg values for five CYP3A substrate drugs. As for the prediction of intestinal toxicity, we found that the degree of ATP decreases in intestinal spheroids incubated with different EGFR-TKIs varied greatly depending on the drugs and the rank order of the extent of ATP decrease corresponded with that of frequency of clinically-observed diarrhea. We also constructed enterochromaffin (EC) cell-rich spheroids and quantified serotonin release from EC cells upon exposure to drugs for the prediction of drug-induced nausea and vomiting. As a result, we found that the serotonin release was related to the high/low risk of nausea and vomiting of each ALK/ROS1 kinase inhibitors.

Pancreatic and Ileal Neuroendocrine Tumors: Metastatic Disease or a Novel MEN Syndrome?

Multiple endocrine neoplasms are a feature of multiple endocrine neoplasia (MEN) syndromes types 1, 2, 4, and 5. However, the ileum is not usually involved in these disorders. We report a series of patients with neuroendocrine tumors (NETs) involving both the pancreas and the ileum. We searched the laboratory information system and personal consultation records of the authors from 2019 to 2023 for patients who had neuroendocrine tumors (NETs) involving both the pancreas and ileum. In a series of 846 patients, we identified 4 patients with pancreatic and ileal NETs, 2 female and 2 male, ages 52 to 75. Two female patients had primary EC cell tumors of the ileum with metastasis to the pancreas that showed expression of CDX2 and serotonin similar to the ileal primary tumors. Two males had primary lesions in the 2 sites with different immunoprofiles; the ileal tumors expressed CDX2 and serotonin and were negative for ARX, whereas the pancreatic tumors expressed ARX, glucagon, and pancreatic polypeptide and were negative for CDX2 and serotonin. In both male patients, the nontumorous pancreas showed preneoplastic changes in the endocrine elements, suggesting germline predisposition to endocrine neoplasia. Testing for known genetic alterations underlying MEN syndromes has not identified a genetic alteration that can be implicated in the development of NETs in both pancreas and ileum. Our series indicates the rare occurrence of NETs in both the pancreas and ileum and emphasizes the importance of using the correct biomarkers to distinguish metastasis from primary neoplasms at the different sites. The rare occurrence of primary ileal and pancreatic NETs may represent a novel MEN syndrome with as yet unknown germline predisposition.

Scalable Bioreactor-based Suspension Approach to Generate Stem Cell-derived Islets From Healthy Donor-derived iPSCs.

Induced pluripotent stem cells (iPSCs) offer the potential to generate autologous iPSC-derived islets (iPSC islets), however, remain limited by scalability and product safety. Herein, we report stagewise characterization of cells generated following a bioreactor-based differentiation protocol. Cell characteristics were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction, patch clamping, functional assessment, and in vivo functional and immunohistochemistry evaluation. Protocol yield and costs are assessed to determine scalability. Differentiation was capable of generating 90.4% PDX1+/NKX6.1+ pancreatic progenitors and 100% C-peptide+/NKX6.1+ iPSC islet cells. However, 82.1%, 49.6%, and 0.9% of the cells expressed SOX9 (duct), SLC18A1 (enterochromaffin cells), and CDX2 (gut cells), respectively. Explanted grafts contained mature monohormonal islet-like cells, however, CK19+ ductal tissues persist. Using this protocol, semi-planar differentiation using 150 mm plates achieved 5.72 × 104 cells/cm2 (total 8.3 × 106 cells), whereas complete suspension differentiation within 100 mL Vertical-Wheel bioreactors significantly increased cell yield to 1.1 × 106 cells/mL (total 105.0 × 106 cells), reducing costs by 88.8%. This study offers a scalable suspension-based approach for iPSC islet differentiation within Vertical-Wheel bioreactors with thorough characterization of the ensuing product to enable future protocol comparison and evaluation of approaches for off-target cell elimination. Results suggest that bioreactor-based suspension differentiation protocols may facilitate scalability and clinical implementation of iPSC islet therapies.

GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation.

Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer-related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT-qPCR) was used to examine hub gene expression. ECA-109 and TE-12 cells were transfected using the pcDNA3.1 expression vector encoding GABRP. The cell counting kit-8 (CCK-8), cell scratch and Transwell assays were performed to assess the effect of GABRP on EC cell proliferation, migration and invasion. Epithelial-mesenchymal transition (EMT)-associated protein levels were measured by Western blotting. Subsequently, CFTR was knocked down to verify whether GABRP affected biological events in EC cells by targeting CFTR. Seven hub genes were identified, including GABRP, FLG, ENAH, KLF4, CD24, ABLIM3 and ABLIM1, which all could be used as diagnostic biomarkers for EC. The RT-qPCR results indicated that the expression levels of GABRP, FLG, KLF4, CD24, ABLIM3 and ABLIM1 were downregulated, whereas the expression level of ENAH was upregulated. Invitro functional assays demonstrated that GABRP overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, GABRP promoted the expression of CFTR, and CFTR knockdown significantly counteracted the influence of GABRP overexpression on biological events in EC cells. Overexpression of GABRP inhibited EC progression by increasing CFTR expression, which might be a new target for EC treatment.

ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma

BackgroundEndometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.MethodsThe research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.ResultsThe study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.ConclusionHOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.

Forces Bless You: Mechanosensitive Piezo Channels in Gastrointestinal Physiology and Pathology.

The gastrointestinal (GI) tract is an organ actively involved in mechanical processes, where it detects forces via a mechanosensation mechanism. Mechanosensation relies on specialized cells termed mechanoreceptors, which convert mechanical forces into electrochemical signals via mechanosensors. The mechanosensitive Piezo1 and Piezo2 are widely expressed in various mechanosensitive cells that respond to GI mechanical forces by altering transmembrane ionic currents, such as epithelial cells, enterochromaffin cells, and intrinsic and extrinsic enteric neurons. This review highlights recent research advances on mechanosensitive Piezo channels in GI physiology and pathology. Specifically, the latest insights on the role of Piezo channels in the intestinal barrier, GI motility, and intestinal mechanosensation are summarized. Additionally, an overview of Piezo channels in the pathogenesis of GI disorders, including irritable bowel syndrome, inflammatory bowel disease, and GI cancers, is provided. Overall, the presence of mechanosensitive Piezo channels offers a promising new perspective for the treatment of various GI disorders.

LncRNA TRPM2-AS promotes endometrial carcinoma progression and angiogenesis via targeting miR-497-5p/SPP1 axis

BackgroundAnti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear.MethodsWe screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS’s function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC.ResultsWe found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes.ConclusionThe depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS’s role in regulating angiogenesis and provides a novel target for EC treatment.

Morphometric features of the duodenal wall in piglets during different periods of postnatal and neonatal ontogenesis under the influence of the ‘Globigen Jump Start’ feed additive

The morphological parameters of the small intestinal mucosa, such as villi size and crypts, play a key role in the formation of the intestinal tube’s absorption surface. The number of goblet and enterochromaffin cells indicates the epithelium’s functional condition in terms of mucus secretion and production of catecholamines and hormones (serotonin, dopamine). That is why it is important to study and determine certain morphometric parameters of the duodenal wall in piglets during different periods of neonatal and postnatal development, especially during stress situations, namely weaning and transition to protein feeding. The article presents the resulting effect studies of ‘Globigen Jump Start’ feed additive on the histo-morphological parameters of the piglets’ duodenal mucosa on day 7, 14 and 28 of life. A positive effect on mitigating weaning stress was manifested by a decrease in the quantitative and linear indicators of histoarchitectonics of intestinal wall’s individual morphological components. A significant increase in goblet cells, especially in the experimental group, had a positive impact on the mucopolysaccharide synthesis. The piglets’ gastrointestinal tract physiology involves a complex interaction between the central nervous system, metasympathetic nervous system, APUD system, and endocrine system. Due to these systems, the information is transmitted according to the direct and reverse communication mechanisms in the regulation of the gastrointestinal tract function. An increase in the number of enterochromaffin cells and their nuclei diameter in the experimental group of piglets indicated an increased synthesis of catecholamines and hormones. It has an extremely positive effect on the immune and physiological status of piglets, thus emphasizing the crucial role of serotonin in neuronal metabolism and the formation of stress resistance. The increase in the thickness of the duodenal wall muscle layer, in our opinion, occured due to the active peristalsis, which was enhanced by the action of some catecholamines, which were synthesized in a slightly larger amount under the influence of nutrients making up the ‘Globigen Jump Start’ feed additive.

Mixed adenoma-neuroendocrine tumor of the stomach: analysis of nine cases with literature review.

Mixed adenoma-neuroendocrine tumor (MANET) comprises adenoma and well-differentiated neuroendocrine tumor (NET) components. Given the limited information on this due to its rarity, we aimed to clarify the clinicopathologic features and optimal management of gastric MANETs in a case series and literature review. Nine patients with gastric MANETs, including eight male and one female patient (mean age, 72years), were identified from the institutional pathology archive. Endoscopically, the tumors appeared as flat elevated lesions with sizes ranging from 0.8 to 4.4cm. One patient had familial adenomatous polyposis, and no patient had autoimmune gastritis. All MANETs developed in the gastric body mucosa exhibiting chronic metaplastic atrophic gastritis. The glandular components were intestinal-type low-grade adenoma, and focal high-grade dysplasia was also recognized in three cases. The NET component was in middle/deep lamina propria in six cases and confined to deep lamina propria in the remaining three cases. Minimal cytologic atypia was found in the NET component, with no recognizable mitosis and a Ki-67 labeling index of < 2%. The NET component mostly showed diffuse positivity for serotonin and CDX2, suggesting that it consists of enterochromaffin cells. Diffuse p53 immunostaining was observed only in the high-grade adenomatous component of one case. No recurrence was observed during the follow-up period of 2-94months. Correct distinction between the NET and poorly differentiated carcinoma components is crucial to prevent overtreatment of gastric MANETs. Considering its indolent nature, endoscopic resection is the primary recommendation for gastric MANETs as well as for pure adenomas.

Concept of Pittadharakala Sa Eva Majjadharakala - A Review

Sushruta has explained seven Kala, Pittdhara Kala is the seventh Kala which is Sthana of Agni and it is the part which is in between the Amashaya and Pakvashaya called as Grahani.[2] According to modern science it comprises of pyloric part of stomach and small intestine that means Pittadhara Kala can be co-related with mucus membrane of stomach, duodenum, jejunum and ileum. Majjakshaya symptoms are Asthisaushirya, Bhrama, Timirdarshana.[10] Asthisaushirya can be co-related with osteoporosis. Enterochromaffin cells are present in gut that produce serotonin in gut and then release it in blood. It reaches to the bone and binds with Htr1b receptor at the surface of osteoblast and decreases bone formation. So the study of this concept of Pittadhara Kala Sa Ev Majjadhara Kala will be more beneficial for treating the patients of osteoporosis.