Applications of artificial intelligence in gastroscopy: a narrative review.

Gastroscopy, a critical tool for the diagnosis of upper gastrointestinal diseases, has recently incorporated artificial intelligence (AI) technology to alleviate the challenges involved in endoscopic diagnosis of some lesions, thereby enhancing diagnostic accuracy. This narrative review covers the current status of research concerning various applications of AI technology to gastroscopy, then discusses future research directions. By providing this review, we hope to promote the integration of gastroscopy and AI technology, with long-term clinical applications that can assist patients.

A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers.

BACKGROUND: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. METHODS: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. RESULTS: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). CONCLUSION: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.

Radiation-induced gastric injury during radiotherapy: molecular mechanisms and clinical treatment.

Radiotherapy (RT) has been the standard of care for treating a multitude of cancer types. Radiation-induced gastric injury (RIGI) is a common complication of RT for thoracic and abdominal tumors. It manifests acutely as radiation gastritis or gastric ulcers, and chronically as chronic atrophic gastritis or intestinal metaplasia. In recent years, studies have shown that intracellular signals such as oxidative stress response, p38/MAPK pathway and transforming growth factor-ß signaling pathway are involved in the progression of RIGI. This review also summarized the risk factors, diagnosis and treatment of this disease. However, the root of therapeutic challenges lies in the incomplete understanding of the mechanisms. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of RIGI.

MUC13 promotes the development of esophageal cancer by upregulating the expression of O-glycan process-related molecules.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by poor prognosis, aggressiveness, and poor survival. Mucin 13 (MUC13) is a member of the membrane-bound mucin and located on chromosome 3q21.2 and consists of α and ß subunits. It has been found that MUC13 is overexpressed in a variety of tumor cells and acts a vital role in the invasiveness and malignant progression of several types of tumors. However, the role and regulatory mechanism of MUC13 in the progression of esophageal cancer remain unclear. METHODS: The expression level of MUC13 was detected in 15 esophageal cancer tissues and 15 pairs of adjacent nontumor tissues by immunohistochemistry (IHC). In addition, the expression of MUC13 mRNA level in human esophageal cancer cell lines (EC9706 and ECA109 and TE-1) was measured by qRT-PCR. In vitro, after silencing MUC13 with lentiviral interference technology, CCK8 assay, clone formation assay, and flow cytometry were applied to investigate the proliferation activity, clone formation ability and anti-apoptosis ability of EC9706 and ECA109 cells. The tumor xenograft growth assay was used to confirm the influence of MUC13 knockdown on the growth of esophageal tumors in vivo. The qRT-PCR assay and western blot experiments were taken to study the mechanism of MUC13 regulating the proproliferation and antiapoptotic of esophageal cancer. RESULTS: The results showed that MUC13 was overexpressed in esophageal cancer tissues and cell lines (EC9706 and ECA109 and TE-1), especially in EC9706 and ECA109 cells, but low expressed in human esophageal epithelial cell line (HEEC). Next, silencing MUC13 inhibits proliferation, blocks cell cycle progression, and promotes cell apoptosis in vitro, and restrains the growth of esophageal cancer tissues in vivo. Finally, MUC13 affects the proproliferation and antiapoptotic by regulating the expression of GLANT14, MUC3A, MUC1, MUC12, and MUC4 that closely related to O-glycan process. CONCLUSIONS: This study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

A comparative analysis of small RNA sequencing data in tubers of purple potato and its red mutant reveals small RNA regulation in anthocyanin biosynthesis.

Anthocyanins are a group of natural pigments acting as stress protectants induced by biotic/abiotic stress in plants. Although the metabolic pathway of anthocyanin has been studied in potato, the roles of miRNAs on the metabolic pathway remain unclear. In this study, a purple tetraploid potato of SD92 and its red mutant of SD140 were selected to explore the regulation mechanism of miRNA in anthocyanin biosynthesis. A comparative analysis of small RNAs between SD92 and SD140 revealed that there were 179 differentially expressed miRNAs, including 65 up- and 114 down-regulated miRNAs. Furthermore, 31 differentially expressed miRNAs were predicted to potentially regulate 305 target genes. KEGG pathway enrichment analysis for these target genes showed that plant hormone signal transduction pathway and plant-pathogen interaction pathway were significantly enriched. The correlation analysis of miRNA sequencing data and transcriptome data showed that there were 140 negative regulatory miRNA-mRNA pairs. The miRNAs included miR171 family, miR172 family, miR530b_4 and novel_mir170. The mRNAs encoded transcription factors, hormone response factors and protein kinases. All these results indicated that miRNAs might regulate anthocyanin biosynthesis through transcription factors, hormone response factors and protein kinase.

Clinical-Pathological Characteristics of Adenosquamous Esophageal Carcinoma: A Propensity-Score-Matching Study.

There are few studies on esophageal adenosquamous carcinoma (ADSC). Our study intended to investigate the clinical and survival features of ADSC. We included esophageal cancer (EC) data from the Surveillance, Epidemiology, and End Results program database to explore clinical and survival traits. Propensity score matching (PSM), the multivariate Cox regression model, and survival curves were used in this study. A total of 137 patients with ADSC were included in our analysis. The proportion of ADSC within the EC cohort declined from 2004 to 2018. Besides, results indicated no significant difference in survival between ADSC and SCC groups (PSM-adjusted HR = 1.249, P = 0.127). However, the survival rate of the ADSC group was significantly worse than that of the ADC group (PSM-adjusted HR = 1.497, P = 0.007). For the ADSC group, combined treatment with surgery had a higher survival rate than other treatment methods (all P < 0.001). Surgical resection, radiotherapy, and chemotherapy were independent protective prognostic factors (all P < 0.05). The proportion of ADSC has been declining from 2004 to 2018. The prognosis of ADSC is not significantly different from that of SCC but is worse than that of ADC. Surgery, radiotherapy, and chemotherapy could improve the prognosis of patients. Comprehensive treatment with surgery as the main treatment is more beneficial for some patients.

A study on the diagnosis of the Helicobacter pylori coccoid form with artificial intelligence technology.

Background: Helicobacter pylori (H. pylori) is an important pathogenic microorganism that causes gastric cancer, peptic ulcers and dyspepsia, and infects more than half of the world's population. Eradicating H. pylori is the most effective means to prevent and treat these diseases. H. pylori coccoid form (HPCF) causes refractory H. pylori infection and should be given more attention in infection management. However, manual HPCF recognition on slides is time-consuming and labor-intensive and depends on experienced pathologists; thus, HPCF diagnosis is rarely performed and often overlooked. Therefore, simple HPCF diagnostic methods need to be developed. Materials and methods: We manually labeled 4,547 images from anonymized paraffin-embedded samples in the China Center for H. pylori Molecular Medicine (CCHpMM, Shanghai), followed by training and optimizing the Faster R-CNN and YOLO v5 models to identify HPCF. Mean average precision (mAP) was applied to evaluate and select the model. The artificial intelligence (AI) model interpretation results were compared with those of the pathologists with senior, intermediate, and junior experience levels, using the mean absolute error (MAE) of the coccoid rate as an evaluation metric. Results: For the HPCF detection task, the YOLO v5 model was superior to the Faster R-CNN model (0.688 vs. 0.568, mean average precision, mAP); the optimized YOLO v5 model had a better performance (0.803 mAP). The MAE of the optimized YOLO v5 model (3.25 MAE) was superior to that of junior pathologists (4.14 MAE, p < 0.05), no worse than intermediate pathologists (3.40 MAE, p > 0.05), and equivalent to a senior pathologist (3.07 MAE, p > 0.05). Conclusion: HPCF identification using AI has the advantage of high accuracy and efficiency with the potential to assist or replace pathologists in clinical practice for HPCF identification.

An R2R3-MYB transcription factor VyMYB24, isolated from wild grape Vitis yanshanesis J. X. Chen., regulates the plant development and confers the tolerance to drought.

In grapevines, the MYB transcription factors play an important regulatory role in the phenylpropanoid pathway including proanthocyanidin, anthocyanin, and flavonoid biosynthesis. However, the role of MYB in abiotic stresses is not clear. In this study, an R2R3-MYB transcription factor, VyMYB24, was isolated from a high drought-tolerant Chinese wild Vitis species V. yanshanesis. Our findings demonstrated that it was involved in plant development and drought tolerance. VyMYB24 is a nuclear protein and is significantly induced by drought stress. When over-expressed in tobacco, VyMYB24 caused plant dwarfing including plant height, leaf area, flower size, and seed weight. The GA1+3 content in transgenic plants was reduced significantly, and spraying exogenous gibberellin could recover the dwarf phenotype of VyMYB24 transgenic plants, suggesting that VyMYB24 might inhibit plant development by the regulation of gibberellin (GA) metabolism. Under drought stress, the VyMYB24 transgenic plants improved their tolerance to drought with a lower wilting rate, lower relative electrical conductivity, and stronger roots. Compared to wild-type tobacco plants, VyMYB24 transgenic plants accumulated less reactive oxygen, accompanied by increased antioxidant enzyme activity and upregulated gene expression levels of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) genes. In addition, transgenic plants accumulated more proline, and their related synthetic genes NtP5CR and NtP5CS genes were significantly upregulated when exposed to drought. Besides, abiotic stress-responsive genes, NtDREB, NtERD10C, NtERD10D, and NtLEA5, were upregulated significantly in VyMYB24 transgenic plants. These results indicate that VyMYB24 plays a positive regulatory role in response to drought stress and also regulates plant development, which provides new evidence to further explore the molecular mechanism of drought stress of the MYB gene family.

Feasibility and reproducibility of a plasma-based multiplex DNA methylation assay for early detection of gastric cancer.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer death and an important barrier to increasing life expectancy in China. Early detection of GC can significantly reduce its mortality rate. METHODS: A new plasma-based multiplex DNA methylation assay combining simultaneous detection of three biomarkers (KCNQ5, C9orf50 and CLIP4) and one control gene (ACTB) was developed. It was used to examine 12 paired tissue samples and a training cohort of 151 plasma samples. Its performance was subsequently confirmed in validation cohort 1 (n = 105) and validation cohort 2 (n = 139). RESULTS: Three methylation markers showed significantly higher methylation levels in GC tissues than in paired adjacent tissues. The assay showed a sensitivity of 67.9 % with a specificity of 86.6 % for GC detection in the training cohort, and the AUC was 0.786 (95 % CI: 0.701-0.855). The methylation levels in GC patients were significantly higher than those in benign gastric tumors and in control group. Meanwhile, the assay achieved a sensitivity of 65.5 % with a specificity of 90.0 % in the validation cohort 1, and the AUC was 0.805 (95 % CI: 0.716-0.876). In the validation cohort 2, its sensitivity and specificity were 73.7 % and 84.1 %, respectively, and the AUC was 0.851 (95 % CI: 0.776-0.909). CONCLUSION: The plasma-based multiplex DNA methylation assay was highly specific for GC early detection. It has the potential to become an alternative approach to improve diagnosis of GC in the clinics.

Radiotherapy-Induced Digestive Injury: Diagnosis, Treatment and Mechanisms.

Radiotherapy is one of the main therapeutic methods for treating cancer. The digestive system consists of the gastrointestinal tract and the accessory organs of digestion (the tongue, salivary glands, pancreas, liver and gallbladder). The digestive system is easily impaired during radiotherapy, especially in thoracic and abdominal radiotherapy. In this review, we introduce the physical classification, basic pathogenesis, clinical characteristics, predictive/diagnostic factors, and possible treatment targets of radiotherapy-induced digestive injury. Radiotherapy-induced digestive injury complies with the dose-volume effect and has a radiation-based organ correlation. Computed tomography (CT), MRI (magnetic resonance imaging), ultrasound (US) and endoscopy can help diagnose and evaluate the radiation-induced lesion level. The latest treatment approaches include improvement in radiotherapy (such as shielding, hydrogel spacers and dose distribution), stem cell transplantation and drug administration. Gut microbiota modulation may become a novel approach to relieving radiogenic gastrointestinal syndrome. Finally, we summarized the possible mechanisms involved in treatment, but they remain varied. Radionuclide-labeled targeting molecules (RLTMs) are promising for more precise radiotherapy. These advances contribute to our understanding of the assessment and treatment of radiation-induced digestive injury.

A retrospective study of the antibiotic-resistant phenotypes and genotypes of Helicobacter pylori strains in China.

Helicobacter pylori antibiotic resistance is a serious concern in China, where it severely influences treatment for H. pylori infection. To overcome this, it is essential to apply personalized therapies based on local or individual data on antibiotic-resistant phenotypes or genotypes. We conducted a large-scale multi-center study with a retrospective cross-sectional observational design to investigate the antibiotic-resistant phenotypes and genotypes of H. pylori in China. Strains were isolated from the gastric biopsy samples of H. pylori-infected patients from five different regions in China. The strains were tested for antibiotic-resistant phenotypes and genotypes, and the agreement between the two was assessed. In total, 4242 H. pylori strains were isolated and cultured, with an 84.43% success rate. The primary and secondary antibiotic resistance rates of H. pylori were 37.00% and 76.93% for clarithromycin, 34.21% and 61.58% for levofloxacin, 2.20% and 6.12% for amoxicillin, 1.61% and 3.11% for furazolidone, 1.18% and 3.31% for tetracycline, and 87.87% and 93.48% for metronidazole, respectively. The dual-resistance patterns for metronidazole/clarithromycin, metronidazole/levofloxacin, and clarithromycin/levofloxacin were 43.6%, 38.4%, and 26.1%, respectively. Clarithromycin- and levofloxacin-resistant H. pylori phenotypes and genotypes showed satisfactory agreement. Based on these findings, clarithromycin- and levofloxacin-resistant genotype testing could partially replace traditional antibiotic susceptibility testing in China. Continuous monitoring and personalized treatments based on individual and local H. pylori antibiotic-resistance data remain necessary.

VvXYLP02 confers gray mold resistance by amplifying jasmonate signaling pathway in Vitis vinifera.

Xylogen-like proteins (XYLPs) are essential for plant growth, development, and stress responses. However, little is known about the XYLP gene family in grape and its protective effects against gray mold a destructive disease caused by Botrytis cinerea. We identified and characterized six common XYLPs in the Vitis vinifera genome (VvXYLPs). VvXYLP expression pattern analyses with B. cinerea infection showed that VvXYLP02 was significantly up-regulated in the resistant genotype but down-regulated or only slightly up-regulated in the susceptible genotype. VvXYLP02 overexpression in Arabidopsis thaliana significantly increased resistance to B. cinerea, indicating that the candidate gene has functional importance. Furthermore, JA treatment significantly up-regulated VvXYLP02 expression in V. vinifera. JA-responsive genes were also up-regulated in VvXYLP02 overexpression lines in A. thaliana under B. cinerea inoculation. These findings suggest that VvXYLP02, which is induced by JA upon the pathogen infection, enhances JA dependent response to enforce plant resistance against gray mold disease.

Association of LDLR rs1433099 with the Risk of NAFLD and CVD in Chinese Han Population.

BACKGROUND AND AIMS: Recent genome-wide association studies have shown that low-density lipoprotein receptor (LDLR) rs1433099 polymorphism is associated with cardiovascular disease (CVD) risk in many countries. However, the association of LDLR rs1433099 with CVD in China has not been reported yet. There are no studies on LDLR rs1433099 and non-alcoholic fatty liver disease (NAFLD) as well. The purpose of this study was to investigate whether LDLR rs1433099 is related to CVD or NAFLD in the Chinese population. METHODS: LDLR rs1433099 polymorphism was genotyped in 507 individuals, including 140 healthy controls, 79 NAFLD patients, 185 CVD patients, and 103 patients with NAFLD combined with CVD. The expression of LDLR was tested by the sequence detection system, and clinical parameters were assessed by biochemical tests and physical examination. RESULTS: The genotype distribution of LDLR rs1433099 was not statistically different among the NAFLD group, the CVD group, the combined group, and the healthy control group (p>0.05). There was no significant correlation of LDLR rs1433099 genotypic distribution or allele frequency and the risk of NAFLD, CVD or NAFLD combined with CVD (p>0.05). In the CVD group, T allele carriers had higher alkaline phosphatase and gamma-glutamyl transpeptidase than non-carriers (p<0.05). CONCLUSIONS: Our study demonstrated that the LDLR rs1433099 polymorphism is not a risk factor of NAFLD. The LDLR rs1433099 polymorphism may increase the risk of CVD through a mechanism involving alkaline phosphatase and gamma-glutamyl transpeptidase.

Cloning and functional characterization of seed-specific LEC1A promoter from peanut (Arachis hypogaea L.).

LEAFY COTYLEDON1 (LEC1) is a HAP3 subunit of CCAAT-binding transcription factor, which controls several aspects of embryo and postembryo development, including embryo morphogenesis, storage reserve accumulation and skotomorphogenesis. Herein, using the method of chromosomal walking, a 2707bp upstream sequence from the ATG initiation codon site of AhLEC1A which is a homolog of Arabidopsis LEC1 was isolated in peanut. Its transcriptional start site confirmed by 5' RACE was located at 82 nt from 5' upstream of ATG. The bioinformatics analysis revealed that there existed many tissue-specific elements and light responsive motifs in its promoter. To identify the functional region of the AhLEC1A promoter, seven plant expression vectors expressing the GUS (ß-glucuronidase) gene, driven by 5' terminal series deleted fragments of AhLEC1A promoter, were constructed and transformed into Arabidopsis. Results of GUS histochemical staining showed that the regulatory region containing 82bp of 5' UTR and 2228bp promoter could facilitate GUS to express preferentially in the embryos at different development periods of Arabidopsis. Taken together, it was inferred that the expression of AhLEC1A during seed development of peanut might be controlled positively by several seed-specific regulatory elements, as well as negatively by some other regulatory elements inhibiting its expression in other organs. Moreover, the GUS expression pattern of transgenic seedlings in darkness and in light was relevant to the light-responsive elements scattered in AhLEC1A promoter segment, implying that these light-responsive elements harbored in the AhLEC1A promoter regulate skotomorphogenesis of peanut seeds, and AhLEC1A expression was inhibited after the germinated seedlings were transferred from darkness to light.

Transcriptome analysis reveals that exogenous ethylene activates immune and defense responses in a high late blight resistant potato genotype.

Ethylene (ET) is one of the many important signaling hormones that functions in regulating defense responses in plants. Gene expression profiling was conducted under exogenous ET application in the high late blight resistant potato genotype SD20 and the specific transcriptional responses to exogenous ET in SD20 were revealed. Analysis of differentially expressed genes (DEGs) generated a total of 1226 ET-specific DEGs, among which transcription factors, kinases, defense enzymes and disease resistance-related genes were significantly differentially expressed. GO enrichment and KEGG metabolic pathway analysis also revealed that numerous defense regulation-related genes and defense pathways were significantly enriched. These results were consistent with the interaction of SD20 and Phytophthora infestans in our previous study, indicating that exogenous ET stimulated the defense response and initiated a similar defense pathway compared to pathogen infection in SD20. Moreover, multiple signaling pathways including ET, salicylic acid, jasmonic acid, abscisic acid, auxin, cytokinin and gibberellin were involved in the response to exogenous ET, which indicates that many plant hormones work together to form a complex network to resist external stimuli in SD20. ET-induced gene expression profiling provides insights into the ET signaling transduction pathway and its potential mechanisms in disease defense systems in potato.

Comparison of defense responses of transgenic potato lines expressing three different Rpi genes to specific Phytophthora infestans races based on transcriptome profiling.

Potato late blight, one of the most devastating diseases in potato, is caused by the oomycete Phytophthora infestans. Over 20 resistance genes have been cloned including R1, R3a, and R3b. The distinctions between defense response mechanisms mediated by different resistance genes are still unclear. Here we performed transcriptome profiling in three transgenic lines, R1, R3a, and R3b, and wild-type Desiree under inoculation with two P. infestans isolates, 89148 (race 0) and CN152 (super race), using RNA-seq. Compared with wild type, specific differentially expressed genes (DEGs) were identified in the three transgenic lines. The highest number of DEGs occurred in transgenic R3b, with 779 DEGs in response to isolate 89148 and 864 DEGs in response to infection by CN152, followed by transgenic R1 lines with 408 DEGs for isolate 89148 and 267 DEGs for CN152. Based on gene ontology, the most common GO terms (15 for 89148 and 20 for CN152) were enriched in transgenic R3a and R3b lines. This indicates that the defense pathways mediated by R3a and R3b are more similar than those mediated by R1. Further separate GO analysis of up- or down-regulated DEGs showed that the down-regulated DEGs mainly functioned in mediating the resistance of potato to P. infestans 89148 by response to stress biological process and to CN152 by oxidation reduction biological process. KEGG pathways of DNA replication, plant-pathogen interaction and pentose and glucuronate interconversions are unique for transgenic R1, R3a, and R3b lines in incompatible interactions. Quantitative real-time PCR experimental validation confirmed the induced expression of DEGs in the late blight resistance signaling pathway. Our results will lay a solid foundation for further understanding the mechanisms of plant-pathogen interactions, and provide a theoretical reference for durable resistance in potato.

Transcriptional Differences in Peanut (Arachis hypogaea L.) Seeds at the Freshly Harvested, After-ripening and Newly Germinated Seed Stages: Insights into the Regulatory Networks of Seed Dormancy Release and Germination.

Seed dormancy and germination are the two important traits related to plant survival, reproduction and crop yield. To understand the regulatory mechanisms of these traits, it is crucial to clarify which genes or pathways participate in the regulation of these processes. However, little information is available on seed dormancy and germination in peanut. In this study, seeds of the variety Luhua No.14, which undergoes nondeep dormancy, were selected, and their transcriptional changes at three different developmental stages, the freshly harvested seed (FS), the after-ripening seed (DS) and the newly germinated seed (GS) stages, were investigated by comparative transcriptomic analysis. The results showed that genes with increased transcription in the DS vs FS comparison were overrepresented for oxidative phosphorylation, the glycolysis pathway and the tricarboxylic acid (TCA) cycle, suggesting that after a period of dry storage, the intermediates stored in the dry seeds were rapidly mobilized by glycolysis, the TCA cycle, the glyoxylate cycle, etc.; the electron transport chain accompanied by respiration was reactivated to provide ATP for the mobilization of other reserves and for seed germination. In the GS vs DS pairwise comparison, dozens of the upregulated genes were related to plant hormone biosynthesis and signal transduction, including the majority of components involved in the auxin signal pathway, brassinosteroid biosynthesis and signal transduction as well as some GA and ABA signal transduction genes. During seed germination, the expression of some EXPANSIN and XYLOGLUCAN ENDOTRANSGLYCOSYLASE genes was also significantly enhanced. To investigate the effects of different hormones during seed germination, the contents and differential distribution of ABA, GAs, BRs and IAA in the cotyledons, hypocotyls and radicles, and plumules of three seed sections at different developmental stages were also investigated. Combined with previous data in other species, it was suggested that the coordination of multiple hormone signal transduction nets plays a key role in radicle protrusion and seed germination.

mRNA and lncRNA Expression Profiling of Radiation-Induced Gastric Injury Reveals Potential Radiation-Responsive Transcription Factors.

Radiation-induced gastric injury is a serious concern that may limit the duration and the delivered dose of radiation. However, the genome-wide molecular changes in stomach upon ionizing radiation have not been reported. In this study, mouse stomach was irradiated with 6 or 12 Gy X-ray irradiation and we found that radiation resulted in the atrophy of gastric mucosa and abnormal morphology of chief and parietal cells. Radiation-induced gastric injury was accompanied by an increase in the serum levels of pepsinogen A and pepsinogen C but not gastrin-17. The expression profiles of messenger RNA (mRNA) and long noncoding RNA (lncRNA) in normal and irradiated gastric tissues were measured by microarray analysis. Results revealed 17 upregulated and 10 downregulated mRNAs were consistent in 6 and 12 Gy irradiated gastric tissues, including D site-binding protein (Dbp) and fibrinogen-like protein 1 (Fgl1). Thirteen upregulated and 96 downregulated lncRNAs were commonly changed in 6 and 12 Gy irradiated gastric tissues. The dysregulated mRNAs were implicated in multiple pathways and showed coexpression with lncRNAs. To identify motifs for transcription factors and coactivators in the proximal promoter regions of the dysregulated RNAs, the bioinformatic tool Biopython was used. A variety of common motifs that are associated with transcription factors were identified, including ZNF263, LMX1B, and Dlx1. Our findings illustrate the molecular changes during radiation-induced gastric injury and the potential transcription factors driving this alteration.

SIRT1 inhibits gastric cancer proliferation and metastasis via STAT3/MMP-13 signaling.

Gastric cancer prognoses are persistently poor due to cancer's penchant to metastasize. As a crucial regulator of signal transducer and activator of transcription (STAT3) signaling, sirtuin 1's (SIRT1) function in gastric cancer has not been well understood. Here, we report upregulated expression of SIRT1 in tissues isolated from gastric cancer patients. However, we show that the depletion of SIRT1-mediated enhanced cancer cell proliferation and metastasis, and resulted in the enrichment of phosphorylated STAT3, acetylated STAT3, and matrix metalloproteinase 13 (MMP-13) in both in vivo and in vitro experiments. Additionally, we demonstrate that small interfering RNAs targeting the production of STAT3, AG490, and CL-821983 in cancer cells depleted of SIRT1 reduce metastasis. Our findings indicate that MMP-13 expression is associated with lymph node metastasis and poor survival outcomes in gastric cancer patients. In vivo models also showed that depleted SIRT1 promoted gastric cancer growth via the STAT3/MMP-13 axis. In conclusion, SIRT1 depletion encourages gastric cancer progression through the activation of STAT3/MMP-13 signaling, suggesting that SIRT1 may function as a tumor suppressor. We postulate that the upregulation of SIRT1 in gastric cancer patients may be the result of a feedback mechanism that aims to oppose the damaging effects of STAT3 signaling. As such, SIRT1 activators could potentially serve as preventive and therapeutic treatments for metastatic gastric cancer.