Turkish Journal of Gastroenterology最新文献

Background/aims: This study aimed to evaluate the anticarcinogenic potential of Scleromitrion diffusum (Willd.) R. J. Wang (SD) extracts in vitro, along with exploring the underlying compatibility mechanisms.

Materials and methods: Scleromitrion diffusum (Willd.) R. J. Wang extract was prepared and gastric cancer (GC) cells were treated to detect the half maximal inhibitory concentration (IC50)/proliferation and migration/invasion by MTS method and transwell assay. The compatibility mechanisms of SD were analyzed by systems pharmacology strategy, combined with cellular experimental validation.

Results: Scleromitrion diffusum (Willd.) R. J. Wang extract showed inhibitory ability on the proliferation of the GC cell lines dose- and time-dependently. A total of 3 active ingredients are involved in anti-gastric cancer effects of SD, based on the top 50 pathways. The "herb-composition-target-pathway" network showed the multi-target and multi-pathway characteristics of SD. There were 52 related targets shared by SD and GC. The cellular experiments supported that SD significantly reduced ERBB2 and ERBB3 expression levels in GC cells. The overexpression of ERBB2 or ERBB3 partially offset the anti-tumor effects of SD.

Conclusion: Scleromitrion diffusum (Willd.) R. J. Wang inhibited gastric cancer growth and metastasis in vitro, which may be related to the inhibition of the ERBB2/ERBB3/PI3K/AKT pathway.

Background/aims: Mushroom intoxication poses a considerable public health risk due to its potential for severe toxicity and fatality. This study aims to investigate demographic trends, diagnostic locations, and mortality rates of patients with mushroom intoxication.

Materials and methods: This retrospective cohort study utilized data from the National Electronic Database of the Turkish Ministry of Health. The study focused on patients without chronic liver disease or prior liver transplantation presenting with mushroom intoxication between 2018 and 2023. Demographic information, diagnostic locations, and mortality rates were analyzed, considering a six-year period to ensure even seasonal distribution.

Results: Among 30459 individuals admitted with mushroom intoxication, 44.75% were male, with a mean age of 45.84 years. The Black Sea, Marmara, and Central Anatolia regions had the highest number of cases, with specific cities like Tokat, Bolu, Yozgat, and Kastamonu having the highest rates per 100,000 population in 2022. Mushroom intoxication predominantly occurred in May, June, October, and November. Hospitalization occurred in 8.9% of cases, with a 6.6% mortality rate within 90 days and 1.3% progressing to liver transplantation. Notably, mushroom intoxication cases increased by 130% in the first half of 2023, particularly in May and June, correlating with increased rainfall.

Conclusion: Mushroom intoxication is a serious public health issue, with morbidity and mortality influenced by climate factors. The study highlights a significant increase in cases in the first half of 2023, potentially linked to heightened rainfall and climate change.

Background/aims: Hepatocellular carcinoma (HCC) represents a primary liver malignancy with a multifaceted molecular landscape. The interplay between liquid-liquid phase separation (LLPS) and ferroptosis-a regulated form of cell death-has garnered interest in tumorigenesis. However, the precise role of LLPS and ferroptosis-related genes in HCC progression and prognosis remains obscure. Unraveling this connection could pave the way for innovative diagnosis and therapeutic strategies.

Materials and methods: The differentially expressed genes (DEGs) were identified based on 3 GEO datasets, followed by overlapping with LLPS-related and ferroptosis-related genes. Based on central hub genes, a diagnostic model was developed through LASSO regression and validated using KM survival analysis and real-time quantitative polymerase chain reaction (RT-qPCR). Then the effects of NRAS on the development of HCC and ferroptosis were also detected.

Results: We identified 24 DEGs overlapping among HCC-specific, LLPS, and ferroptosis-related genes. A diagnostic model, centered on 5 hub genes, was developed and validated. Lower expression of these genes corresponded with enhanced patient survival rates, and they were distinctly overexpressed in HCC cells. NRAS downregulation significantly inhibited HepG2 cell proliferation and migration (P < .01). Fe2+ content and ROS levels were both significantly increased in the si-NRAS group when compared to those in the si-NC group (P < .01), while opposite results were observed for the protein level of GPX4 and GSH content.

Conclusion: The diagnostic model with 5 hub genes (EZH2, HSPB1, NRAS, RPL8, and SUV39H1) emerges as a potential innovative tool for the diagnosis of HCC. NRAS promotes the carcinogenesis of HCC cells and inhibits ferroptosis.

The vital roles of circular RNAs (circRNAs) in human tumorigenesis have attracted more attention. Circ_0008035 is one of the most up-regulated circRNAs in gastric cancer (GC). Herein, we explored the associated mechanism of circ_0008035 in GC. EdU incorporation experiments were performed to monitor cell proliferation ability. Cell cycle progression, apoptosis, angiogenesis, migration, and invasion were analyzed using flow cytometry, Tube formation, and Transwell assays respectively. Protein expression was detected by Western blot. Dual-luciferase reporter experiments were applied to demonstrate the relationship between circ_0008035 or SMAD family member 2 (SMAD2) and microRNA-429 (miR-429). Mouse xenograft assays were conducted for evaluation of the role of circ_0008035 in vivo. Circ_0008035 content was elevated in GC tissues (P < .0001) and cell lines (P < .001), and its deficiency hindered GC cell proliferation (P < .01), HUVEC angiogenesis (P < .05), and GC cell metastasis (P < .01) and triggered apoptosis (P < .01). Circ_0008035 could sponge miR-429 to up-regulate SMAD2 expression (P < .0001). Circ_0008035 absence restrained tumor growth in vivo (P < .01). MiR429 was a mediator of circ_0008035 function, and miR-429 hindered GC cell malignant phenotypes by SMAD2. Circ_0008035 aggravates GC cell malignant progression partially by targeting the miR-429/SMAD2 axis. Considering the inhibitory effect of circ_0008035 deficiency on GC progression, targeting circ_0008035 may be a potential approach to prevent or treat GC.

Background/aims: The incidence of colorectal cancer (CRC) has been increasing in recent years worldwide. Aconitine is a diester diterpenoid alkaloid that exhibits an antitumor role in several cancers. Nevertheless, it remains unclear whether aconitine also has antitumor activity in CRC. This study aims to investigate the effects of aconitine on the malignant behaviors of CRC cells.

Materials and methods: 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay was utilized for cell viability assessment. Flow cytometry, western blotting, wound healing, and Transwell assays were implemented for examining the aconitine effect on CRC cell apoptosis, migration, and invasiveness. Animal experiments were performed to further elucidate aconitine's effect on CRC tumorigenesis.

Results: Aconitine time- and dose-dependently restrained CRC cell viability but was not cytotoxic to normal colorectal mucosa cells. Aconitine facilitated CRC cell apoptosis and hindered cell migration and invasiveness. Aconitine blocked tumor growth in xenograft mouse models.

Conclusion: Aconitine exerts an anti-CRC effect by promoting cell apoptosis and blocking cell migration and invasiveness.

Ferroptosis is a newly identified type of cell death which is strongly linked to the development of several diseases. Whereas, the role of ferroptosis in the improvement of ethanol-induced hepatocytes injury by selenium has not been confirmed. In this study, an in vitro cell damage model was established using half inhibition concentration of ethanol to induce NCTC clone 1469. Cell activity, lipid peroxidation, apoptosis and the expression of markers related to ferroptosis pathway was determined. A mouse model of alcoholic liver disease (ALD) was constructed and the effectiveness of selenium and ferrostatin-1 in treating ALD in vivo was assessed by serum liver function tests, tissue staining and immunohistochemistry for ferroptosis related proteins. Pretreatment with selenomethionine and ebselen significantly improved ethanol-induced reduction in hepatocyte viability, elevated GSH levels and SOD enzyme activity, reduced MDA and iron content, while improving ethanol-induced changes in apoptosis levels and ferroptosis markers GPX4, SLC7A11, and ACSL4, with the effect of Selenomethionine being more significant. In vivo results also indicated that intervention with selenium or ferroptosis inhibitors significantly improved ethanol-induced liver tissue damage, significantly reduced serum ALT and AST levels, upregulated GPX4 and SLC7A11, but reduced ACSL4 protein levels in liver tissue. The process of ethanol damage to hepatocytes is regulated by the ferroptosis pathway. Selenium may exert a beneficial role in ethanol-induced hepatocyte injury by antagonizing oxidative stress and regulating apoptosis and ferroptosis pathways.

Peptostreptococcus anaerobius plays an important role in the development of colorectal cancer, and previous studies by our group have demonstrated that Peptostreptococcus anaerobius promotes resistance to 5-Fu chemotherapy in animal models of colorectal cancer. In this study, the effects of Peptostreptococcus anaerobius on chemotherapy resistance in colorectal cancer and its possible mechanism of action were investigated from the clinical point of view. Patients were selected according to exclusion and inclusion criteria and divided into sensitive and chemotherapy groups (n = 20/group). Fecal samples were collected from the patients. The bacterial 16S rRNA genes in the samples were sequenced and the abundance and varieties in the fecal bacteria were compared between the 2 groups. Immunohistochemistry and Western blotting were used to assess interleukin 23 levels in tumor tissues. Significantly elevated abundance of Peptostreptococcus was observed in fecal samples from chemoresistant colorectal cancer patients compared to those from chemosensitive individuals. Immunohistochemistry and Western blotting results showed that chemoresistant patients had higher levels of interleukin 23 relative to chemosensitive patients and the levels were positively associated with Peptostreptococcus. Peptostreptococcus may mediate the development of chemoresistant colorectal cancer by promoting the upregulation of interleukin 23. Efforts to target Peptostreptococcus thus have the potential to alter the prognosis of colorectal cancer patients.