Transgelin promotes ferroptosis to inhibit the malignant progression of esophageal squamous cell carcinoma.

The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co­expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit­8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca­109 and KYSE­150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription­quantitative PCR, co­immunoprecipitation and fluorescence co­localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl­CoA synthetase long­chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca­109 and KYSE­150 cells in vitro compared with the control group; in vivo, TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca­109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis­associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.

Nonpoint Source Pollution (NPSP) Induces Structural and Functional Variation in the Fungal Community of Sediments in the Jialing River, China.

Nonpoint source pollution (NPSP) from human production and life activities causes severe destruction in river basin environments. In this study, three types of sediment samples (A, NPSP tributary samples; B, non-NPSP mainstream samples; C, NPSP mainstream samples) were collected at the estuary of the NPSP tributaries of the Jialing River. High-throughput sequencing of the fungal-specific internal transcribed spacer (ITS) gene region was used to identify fungal taxa. The impact of NPSP on the aquatic environment of the Jialing River was revealed by analysing the community structure, community diversity, and functions of sediment fungi. The results showed that the dominant phylum of sediment fungi was Rozellomycota, followed by Ascomycota and Basidiomycota (relative abundance > 5%). NPSP caused a significant increase in the relative abundances of Exosporium, Phialosimplex, Candida, Inocybe, Tausonia, and Slooffia, and caused a significant decrease in the relative abundances of Cercospora, Cladosporium, Dokmaia, Setophaeosphaeria, Paraphoma, Neosetophoma, Periconia, Plectosphaerella, Claviceps, Botrytis, and Papiliotrema. These fungal communities therefore have a certain indicator role. In addition, NPSP caused significant changes in the physicochemical properties of Jialing River sediments, such as pH and available nitrogen (AN), which significantly increased the species richness of fungi and caused significant changes in the fungal community ß-diversity (P < 0.05). pH, total phosphorus (TP), and AN were the main environmental factors affecting fungal communities in sediments of Jialing River. The functions of sediment fungi mainly involved three types of nutrient metabolism (symbiotrophic, pathotrophic, and saprotrophic) and 75 metabolic circulation pathways. NPSP significantly improved the pentose phosphate pathway, pentose phosphate pathway, and fatty acid beta-oxidation V metabolic circulation pathway functions (P < 0.05) and inhibited the chitin degradation to ethanol, super pathway of heme biosynthesis from glycine, and adenine and adenosine salvage III metabolic circulation pathway functions (P < 0.05). Hence, NPSP causes changes in the community structure and functions of sediment fungi in Jialing River and has adversely affected for the stability of the Jialing River Basin ecosystem.

Role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.

BACKGROUND AND AIM: Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors. METHODS: A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2). RESULT: Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%, p < .001). Complete endoscopic resection was performed in all the patients. No complications occurred in any of the patients. No esophageal stenosis, recurrence, or metastases was found in all patients during the follow-up period. CONCLUSION: The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.

Corrigendum: Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial-Mesenchymal Transition.

[This corrects the article DOI: 10.3389/fonc.2021.709486.].

Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota.

Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.

Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial-Mesenchymal Transition.

OBJECTIVE: This article investigates the role of Transgelin (TAGLN) in the epithelial-mesenchymal transition (EMT) of esophageal squamous cell carcinomas (ESCC) and its possible mechanism of inhibiting the invasion of these cancers. METHODS: Tissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between Transgelin expression level and prognosis of patients with ESCC. Transgelin siRNA was used to knock down Transgelin expression. The expression of Transgelin in Eca-109 and KYSE-150 cells was overexpressed by Transgelin-overexpressing plasmid. The effects of Transgelin overexpression and knockdown on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, and CCK-8 cell activity assay. RT-PCR and Western blot were used to detect the effect of Transgelin overexpression or knockdown on the mRNA and protein expressions of E-cadherin and Vimentin. TCGA data were used to analyze Transgelin co-expressed genes and further study the GO and KEGG enrichment analysis results under the influence of Transgelin. RESULTS: The expression of Transgelin was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The targeted Transgelin siRNA and Transgelin-overexpressing plasmid can effectively regulate the expression of Transgelin mRNA and protein in Eca-109 and KYSE-150 cells. After overexpression of Transgelin, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells were significantly decreased compared with those of the control group (P < 0.05). However, Transgelin knockdown could promote the proliferation, migration, and invasion of ESCC cells. The overexpression of Transgelin inhibits EMT in ESCC. With the increase of Transgelin expression in Eca-109 and KYSE-150 cells, the expression of E-cadherin increased, while the expression of Vimentin decreased, and the difference was statistically significant (P < 0.05). CONCLUSION: Transgelin can inhibit the malignant progression of ESCC by inhibiting the occurrence of EMT.

Gastrointestinal bleeding caused by jejunal angiosarcoma: A case report.

BACKGROUND: Angiosarcoma is a rare disease with a poor prognosis. Its occurrence in the small intestine is low, and gastrointestinal bleeding caused by small intestinal angiosarcoma is unusual. CASE SUMMARY: Here, we report the case of a 57-year-old man who presented with hematochezia for 1 mo. The patient had a medical history of chronic viral hepatitis B for 15 years. The causes of gastrointestinal bleeding were initially diagnosed as esophagogastric variceal bleeding or portal hypertensive gastropathy before endoscopy. However, after a complicated diagnostic and therapeutic process, including gastroendoscopy, colonoscopy, contrast-enhanced computed tomographic (CT), positron emission computed tomography/CT, capsule endoscopy, and pathological and immunohistochemical examinations, small intestinal angiosarcoma was diagnosed. Arrest of bleeding was achieved after surgical treatment. Furthermore, the patient had lung cancer with bone and adrenal metastases. At the follow-up 10 mo after the operation, the patient was alive. CONCLUSION: Gastroenterologists should maintain strong vigilance to small intestinal angiosarcoma, which is necessary for the early identification of this infrequent but fatal disease.

Cartilage Oligomeric Matrix Protein promotes epithelial-mesenchymal transition by interacting with Transgelin in Colorectal Cancer.

Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown. Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice. Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum, was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer. Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.

Large population-based study using the SEER database: is endoscopic resection appropriate for early gastric cancer patients in the United States?

AIM: To investigate whether endoscopic treatment is applicable to American patients and explores the predictors of lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Patients with EGC confined to either mucosa (T1a, n = 1799) and submucosa (T1b, n = 1689) were identified from the Surveillance, Epidemiology, and End Result database. Multivariate logistic regression, Kaplan-Meier method, and univariate/multivariate Cox regression were used to assess the correlation between invasion depth and LNM or prognosis. A nomogram for predicting LNM was constructed and internally validated. RESULTS: EGC limited to T1a exhibited a 2.4% incidence of LNM, which increased to 11.1% when the depth invaded T1b.LNM was present at 1.4%, 5.2%, and 5.0% for sizes ≤2, 2-5, and >5cm of low-grade T1a EGC, respectively, (p = .019) and at 4.8%, 12.4%, and 28.6% of T1b EGC, respectively (p < .001).The multivariate logistic model revealed that older age, T1b invasion, larger tumor size, and high-grade lesions were associated with a higher risk of LNM. Moreover, the T1a EGC patients had better cancer-specific survival (OS) and overall survival(CSS) compared with the T1b EGC patients (5-year OS: 77.2% versus 67.4%, p < .001; 5-year CSS: 90.6% versus 81.4%, p < .001). The discrimination of the prediction model was 0.745. CONCLUSIONS: Endoscopic treatment may only be suitable for patients in the US population who have low-grade T1a lesions of less than 2 cm in size. Patients with T1a lesions of greater than 2 cm in size, lesions with high-grade, and all T1b lesions may benefit from radical surgical resection with lymphadenectomy.

Reliability of Endoscopic Ultrasound Using Miniprobes and Grayscale Histogram Analysis in Diagnosing Upper Gastrointestinal Subepithelial Lesions.

BACKGROUND: To assess the role of endoscopic ultrasound (EUS) in the diagnosis of upper gastrointestinal subepithelial lesions (SELs) and to investigate EUS combined with a grayscale histogram analysis for the differentiation of leiomyomas and gastrointestinal stromal tumors (GISTs). METHODS: A retrospective study of 709 patients with upper gastrointestinal SELs was conducted by EUS before endoscopic resection. The EUS findings of SELs and pathological results after endoscopic resection were compared. The EUS images of SELs, particularly, leiomyoma and GIST, were further analyzed via a grayscale histogram to differentiate between the two tumors. RESULTS: Of the 709 patients, 47 cases were pathologically undetermined. The diagnostic consistency of EUS with endoscopic resection was 88.2% (584/662), including 185 muscularis mucosa, 61 submucosa, and 338 muscularis propria, respectively. The diagnostic consistency of EUS with pathology was 80.1% (530/662). The gray value of GISTs was significantly higher than that of leiomyomas (58.9 ± 8.3 vs. 39.5 ± 5.9, t = 57.0, P < 0.0001). The standard deviation of leiomyomas was significantly lower than that of GISTs (20.6 ± 7.0 vs. 39.8 ± 9.3, t = 23.7, P < 0.0001). The grayscale histogram analysis of GISTs showed higher echo ultrasound, and the echo of leiomyoma was more uniform. CONCLUSION: EUS is the preferred procedure for the evaluation of upper gastrointestinal SELs. EUS combined with a grayscale histogram analysis is an effective method for the differentiation of leiomyomas and GISTs.

Abnormal serum carbohydrate antigen 19-9 levels in a patient with splenic retiform haemangioendothelioma concomitant with hepatic amyloidosis: A case report.

BACKGROUND: Carbohydrate antigen 19-9 (CA 19-9) is a glycoprotein that is used as a reliable tool for monitoring pancreatic cancer. Serum CA 19-9 levels are increased in patients suffering from liver, lung, and other non-malignant diseases. Haemangioendothelioma is a vascular neoplasm with a borderline biological behaviour. However, no case of haemangioendothelioma has yet been reported to be associated with CA 19-9. CASE SUMMARY: A 54-year-old Chinese man was referred to our hospital for discontinuous fatigue and unintentional weight loss for over one year. Laboratory investigations revealed an elevated serum CA 19-9 concentration of 39 IU/mL (reference interval, 0-37 IU/mL) over one year before admission. Afterwards, coagulopathy appeared, and the patient's serum CA 19-9 concentration increased continuously. At the time of admission, abdominal pain and haemorrhagic shock burst occurred, and emergency medical operation was performed. Laboratory investigations conducted upon admission showed a serum CA19-9 concentration of 392.56 IU/mL. Surgical resection of the spleen was undertaken, and pathological examination showed retiform haemangioendothelioma. The patient developed jaundice ten days after surgical excision of the spleen. Pathological examination of needle biopsy samples of the liver yielded a diagnosis of hepatic amyloidosis. CONCLUSION: We describe a rare case of splenic retiform haemangioenthelioma concomitant with hepatic amyloidosis. Physicians should note abnormal serum CA 19-9 levels with early symptoms of fatigue and unintentional weight loss.

Immunoglobulin G4-Related Disease Manifesting as Isolated, Typical, and Nontypical Gastroesophageal Lesion: A Research of Literature Review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune inflammatory and fibrotic condition. The disease is characterized by tissue infiltration with dense lymphoplasmacytes and IgG4-positive plasma cells. SUMMARY: The aim of this study was to provide gastroenterologists with novel insights into evaluating the gastroesophageal involvement with IgG4-RD or mimickers of this condition and to give special attention to clinicopathological features. A literature review was performed using the PubMed database. A total of 39 studies presenting cases in the form of isolated, typical, and nontypical gastroesophageal involvement with IgG4-RD published between 2010 and 2018 were included. These studies were thoroughly reviewed for symptoms, lesion location, lesion type, lesion size, immune-histopathology, associated diseases, treatment, and follow-up. Of the 39 studies reviewed, 9 were esophageal IgG4-RD lesions, isolated esophageal IgG4-RD 66.66% (6/9), a typical form of esophageal IgG4-RD 11.11% (1/9), and nontypical form esophageal IgG4-RD 22.22% (2/9). The 30 gastric IgG4-RD that include isolated gastric IgG4-RD 46.66% (14/30), typical gastric IgG4-RD 40% (12/30), and nontypical gastric IgG4-RD 13.33% (4/30). The majority of lesions were inflammatory tumors, ulceration, nodular lesions, chronic gastritis, and malignant lesions. Key Messages: IgG4-RD may be manifested by isolated, typical and nontypical forms of gastroesophageal lesions and should be taken into consideration in the differential diagnosis. Corticosteroids may be the sole diagnostic treatment for this condition.

Efficacy and safety of endoscopic submucosal dissection for gastrointestinal neuroendocrine tumors: a 10-year data analysis of Northern China.

Objective: Endoscopy is the main method to treat gastrointestinal neuroendocrine tumors (GI-NETs), but the specific indications are still controversial. We aim to investigate the clinical outcomes of GI-NETs patients who experienced endoscopic submucosal dissection (ESD). Methods: We retrospectively reviewed the clinical features and prognosis of 65 GI-NETs patients who underwent ESD between 2008 and 2018. Results: A total of 65 patients diagnosed with GI-NETs pathologically, bearing 75 lesions, were found by endoscopy incidentally for other symptoms. The locations of these lesions were stomach (n = 24), duodenal bulb (n = 4) and rectum (n = 47). The diameter of 75 tumors were as follows: size ≤ 1 cm (78.7%), 1 cm < size ≤ 2 cm (17.3%), 2 cm < size ≤ 3.5 cm (4.0%). Endoscopic ultrasonography (EUS) suggested that 72 lesions were confined to submucosa and 3 lesions invaded into muscularis propria. The rates of en bloc resection and complete resection were all 100% and the rates of intraoperative bleeding and perforation were 2.7% and 1.3%, respectively. None of the 65 patients had lymph nodes and distant metastasis during the period of study. Conclusion: For GI-NETs without lymph nodes and distant metastases, the lesion confined to submucosa with the diameter ≤1 cm is absolute indication of ESD. For rectal neuroendocrine tumors limited in submucosa with the diameter between 1 and 2 cm, and Type 1 gastric neuroendocrine tumors predicted to be T2, ESD should be prioritized to preserve gastrointestinal volume and function at initial treatment.

Treatment recommendations for small gastric gastrointestinal stromal tumors: positive endoscopic resection.

Objectives: To evaluate the safety and efficacy of endoscopic resection and discuss the treatment strategy of small gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. Material and methods: The data of 713 patients, who underwent endoscopic submucosal dissection (ESD) for gastric submucosal tumors (SMTs), were retrospectively analyzed. We investigated the clinicopathological features and analyzed the risk potential of small gastric GISTs, and documented therapeutic and follow-up outcomes. We also compared the follow-up results between operated patients and 58 patients who were suspected of small gastric GISTs and underwent regular surveillance under endoscopic ultrasound (EUS) in the same period. Results: GISTs were the most common gastric SMTs (289 cases, 40.5%), of which small GISTs were found in 250 cases. The mitotic index was less than 5 in all cases. However, 122 out of 250 cases (48.8%) had adverse factors under EUS, which were related to tumor size (p < .01). ESD was successfully performed in all patients, and no serious complication or perioperative death occurred. The follow-up period for 42.07 ± 22.49 months revealed improvement of symptoms in 80.2% patients and showed no recurrence or metastasis. Of the 58 patients selected for EUS surveillance, 48 (82.8%) presented with gastrointestinal symptoms and 41 out of 48 (85.4%) were not relieved during follow-up and 16 (27.6%) with severe psychological problems. Conclusions: ESD is a safe and effective treatment for small GISTs, which helps to confirm the diagnosis, improve symptoms and reduce the psychological pressure. Thus, we recommend endoscopic resection is a good option for small gastric GISTs once diagnosed.

Etiological aspects of intragastric bezoars and its associations to the gastric function implications: A case report and a literature review.

RATIONALE: Intragastric bezoar is a stony mass found trapped in the stomach, though it can occur in other locations of the gastro-intestinal tract. The etiology of intragastric bezoar is multifactorial, includes certain risk factors and predisposing factors such as coexisting medical disorders, anatomic abnormalities, and gastric motility disorders, which contribute to the development of intragastric bezoar. PATIENT CONCERNS: In this report, we present a rare case of intragastric bezoar with epigastric pain after prolonged consumption of jujubes. To our knowledge, this is the first case of intragastric bezoar to be reported after jujubes ingestion. DIAGNOSES: An upper gastrointestinal (GI) endoscopy performed which revealed an 8 × 5-cm intragastric diospyrobezoar with an adjacent necrotic pressure ulcer of size 0.8 × 0.5-cm without signs of bleeding. INTERVENTIONS: For therapeutic intervention, Coca-Cola ingestion and lithotripsy were applied. OUTCOMES: The therapeutic course was uneventful. There was no recurrence during 1-year follow-up. LESSONS: In our literature, jujube emerged as a new player. A bezoar composed of unripened fruit content in the stomach, could be the cause of chronic abdominal pain, dyspepsia, gastric reflux or heartburn. Moreover, this study provides a detailed overview of recently published literature regarding intragastric manifestations of bezoar, etiological factors, diagnostic and therapeutic approaches.

Laterally spreading tumour of the distal stomach: a case report.

BACKGROUND: Laterally spreading tumours (LSTs) are superficial neoplasms that usually extend laterally along the intra-luminal wall of the gastrointestinal tract. Recently, the incidence of LSTs in the colorectal mucosa has greatly increased. However, LSTs in the stomach are exceedingly rare and have never been previously reported. CASE PRESENTATION: Here, we report a 69-year-old male with epigastric pain and a gastric LST 6 cm in diameter located in the distal stomach and grossly extended into the duodenal bulb. The stomach lesion was initially diagnosed as high-grade intraepithelial neoplasia, while the duodenal lesion was diagnosed as a tubulovillous adenoma. A therapeutic strategy of endoscopic submucosal dissection and distal gastrectomy was applied. The surgeries and postoperative course were uneventful, and the patient remained asymptomatic 1 year after surgery. CONCLUSIONS: This is a clinically significant case, as it provides detailed information regarding laterally spreading early gastric cancer and emphasizes the diagnostic and therapeutic approaches for early gastric cancerous lesions.