Defining the biological functions and clinical significance of AKR1C3 in gastric carcinogenesis through multiomics functional analysis and immune infiltration analysis.

Background: Human aldo-keto reductase family 1 member C3 (AKR1C3) is an important molecule that participates in multiple physiological metabolic processes. However, its expression, biological functions and clinical significance in gastric carcinogenesis are unclear. Methods: We collected data from several public data portals and clinical samples and systematically analyzed the clinical significance of tissue and plasma AKR1C3 expression. Then, we filtered prognostic risk factors and established novel prognosis-related nomogram models for predicting overall survival time and postoperative recurrence risk. The application value of the nomogram models was further assessed using clinical samples. Moreover, we explored the potential biological functions of AKR1C3 in gastric carcinogenesis and metastasis through multiomics functional analysis and immune infiltration analysis. Results: AKR1C3 levels were reduced in cancer tissue but increased significantly in the plasma of GC patients; AKR1C3 expression in either sample type was closely associated with multiple clinicopathological characteristics. By combining clinicopathological factors and AKR1C3 levels, two novel nomogram models were developed to predict overall survival time and postoperative recurrence risk. Multiomics functional analysis revealed that when its expression is dysregulated, AKR1C3 can widely participate in gene expression regulation through multiple regulatory modes at the gene, RNA and protein levels and exert various crucial biological effects in carcinogenesis and metastasis. Moreover, AKR1C3 expression was correlated with the infiltration of several immune cell types, and AKR1C3 was predicted to interact with several clinical drugs. Conclusion: Dysregulated AKR1C3 expression is related to gastric carcinogenesis and immunotherapy response and is a promising biomarker and effective biotherapy target in GC.

Machine learning to establish three sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Nevertheless, GC still lacks effective diagnosed and monitoring method and treating targets. This study used multi omics data to explore novel biomarkers and immune therapy targets around sphingolipids metabolism genes (SMGs). METHOD: LASSO regression analysis was performed to filter prognostic and differently expression SMGs among TCGA and GTEx data. Risk score model and Kaplan-Meier were built to validate the prognostic SMG signature and prognostic nomogram was further constructed. The biological functions of SMG signature were annotated via multi omics. The heterogeneity landscape of immune microenvironment in GC was explored. qRT-PCR was performed to validate the expression level of SMG signature. Competing endogenous RNA regulatory network was established to explore the molecular regulatory mechanisms. RESULT: 3-SMGs prognostic signature (GLA, LAMC1, TRAF2) and related nomogram were constructed combing several clinical characterizes. The expression difference and diagnostic value were validated by PCR data. Multi omics data reveals 3-SMG signature affects cell cycle and death via several signaling pathways to regulate GC progression. Overexpression of 3-SMG signature influenced various immune cell infiltration in GC microenvironment. RBP-SMGs-miRNA-mRNAs/lncRNAs regulatory network was built to annotate regulatory system. CONCLUSION: Upregulated 3-SMGs signature are excellent predictive diagnosed and prognostic biomarkers, providing a new perspective for future GC immunotherapy.

Analysis of Helicobacter pylori resistance in patients with different gastric diseases.

Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.

Clinical Significance of Disulfidptosis-related Genes and Functional Analysis in Gastric Cancer.

Background: Worldwide, gastric cancer (GC) remains intractable due to its poor prognosis and high morbidity and mortality. Disulfidptosis is a novel kind of cell death mediated by abnormal accumulation of intracellular disulphides. The correlation between disulfidptosis and GC is still unknown. Therefore, it is necessary to elucidate the pathogenesis and mechanism of disulfidptosis and GC for clinical diagnosis and intervention. Methods: RNA-sequencing data from several public data portals and clinical samples were collected. We compared the expression levels of four key genes of disulfidptosis, including SLC7A11, SLC3A2, RPN1, and NCKAP1, in GC and selected prognostic genes to build a novel GC prognosis-related nomogram model. The biological functions and immune landscape of the identified prognostic genes were explored. Results: Overexpressed NCKAP1 and SLC7A11 were prognostic disulfidptosis-related genes in GC. We combined these genes and several clinicopathological factors to build a prognostic nomogram model for GC. Meanwhile, the ROC curves showed that NCKAP1 and SLC7A11 were promising biomarkers for GC screening. The biological and cellular functions were focused on actin activities, GTPase and immunoreaction. The tumour immune microenvironment and immune therapy targets were identified. Competing endogenous RNA network was built to explore the downstream regulatory mechanisms. Finally, the elevated NCKAP1 and SLC7A11 expression in GC was validated via qRT-PCR in a cell line and tissue line. Conclusion: In conclusion, NCKAP1 and SLC7A11 are promising prognostic and diagnostic biomarkers for GC that correlate with the activities of actin, energy metabolism of GTPase, immune infiltration and immunotherapy.

Clinical significance and potential application of cuproptosis-related genes in gastric cancer.

BACKGROUND: Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis. AIM: To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy. METHODS: We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics. RESULTS: Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map. CONCLUSION: In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.

Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis.

BACKGROUND: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. OBJECTIVE: Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools. METHODS: We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR. RESULTS: We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes. CONCLUSIONS: In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis.

Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice.

Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis-related gene mutations, rRNA coding gene mutations, and cell wall synthesis-related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.

Identification of novel prognostic biomarkers in the TF-enhancer-target regulatory network in hepatocellular carcinoma and immune infiltration analysis.

Background: Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism of HCC for clinical intervention. Methods: We collected data from several public data portals and systematically analysed the association between transcription factors (TFs), eRNA-associated enhancers and downstream targets. We next filtered the prognostic genes and established a novel prognosis-related nomogram model. Moreover, we explored the potential mechanisms of the identified prognostic genes. The expression level was validated by several ways. Results: We first constructed a significant TF-enhancer-target regulatory network and identified DAPK1 as a coregulatory differentially expressed prognosis-related gene. We combined common clinicopathological factors and built a prognostic nomogram model for HCC. We found that our regulatory network was correlated with the processes of synthesizing various substances. Moreover, we explored the role of DAPK1 in HCC and found that it was associated with immune cell infiltration and DNA methylation. Several immunostimulators and targeting drugs could be promising immune therapy targets. The tumor immune microenvironment was analyzed. Finally, the lower DAPK1 expression in HCC was validated via the GEO database, UALCAN cohort, and qRT-PCR. Conclusion: In conclusion, we established a significant TF-enhancer-target regulatory network and identified downregulated DAPK1 as an important prognostic and diagnostic gene in HCC. Its potential biological functions and mechanisms were annotated using bioinformatics tools.

Preoperative and postoperative clinical signatures of postgastrectomy venous thromboembolism in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: This study aimed to identify preoperative and postoperative risk factors of venous thromboembolism (VTE) after gastrectomy in gastric cancer (GC) patients. METHODS: 757 GC patients underwent gastrectomy at our institution and 246 patients with elevated postoperative D-dimer levels who received Doppler ultrasonography of lower/upper extremity veins were enrolled. Clinicopathological factors data were collected, and the differences in clinicopathological factors between postoperative VTE (+) and VTE (-) groups were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of postgastrectomy VTE. RESULTS: Of 246 patients with elevated postgastrectomy D-dimer concentrations, 74 patients showed thrombosis in lower/upper extremity veins. Among preoperative factors, age, WBC level, D-dimer concentration, and blood glucose level were significantly higher in the postoperative VTE (+) group. Among the postoperative factors, hemoglobin level was significantly lower in the postoperative VTE (+) group. Among the pathological factors, tumor stage, depth of invasion and TNM classification indicated higher malignancy in the postoperative VTE (+) group. Univariate logistic regression analysis indicated age, preoperative blood glucose level, postoperative hemoglobin level, tumor stage, depth of invasion, and TNM classification as the independent risk factors for postgastrectomy VTE, whereas multivariate logistic regression analysis revealed age and tumor stage as independent risk factors for postgastrectomy VTE. CONCLUSION: Our study revealed that age, preoperative blood glucose level, postoperative anemia, and tumor malignancy were independent risk factors for GC patients exhibiting postgastrectomy VTE. Therefore, the perioperative monitoring, assessment and management of risk factors are important in achieving better outcomes after gastrectomy.

The Effect of Cryopreservation on the Survival of Nocardia farcinica and Yersinia pestis vaccine strains.

Pathogenic microorganisms are valuable biological resources, closely related to biosecurity, human health, environmental protection, and renewable energy. It is very important to properly preserve the microbial resources by methods to maintain the purity, viability, and integrity, and to avoid prolonged degradation. The present work aims to explore the cryopreservation technology of Nocardia farcinica (Gram-positive bacteria) and Yersinia pestis vaccine strains (Gram-negative bacteria). The effects of cryoprotectants (CPAs), freezing temperature, and freeze-thaw cycles on the two bacteria in the cryopreservation process were studied. The results showed that the addition of CPAs (glycerol, propylene glycol, sucrose, glucose, l-carnitine, l-proline, and skim milk) significantly enhanced the survival rates of the N. farcinica and Y. pestis vaccine strains. However, high concentrations of CPAs can produce biochemical toxicity in the two pathogens. The utilization of composite CPAs not only reduced the toxicity but also improved the survival rates of samples during cryopreservation. The optimal composite CPA for N. farcinica is 0.292 M sucrose, 0.62 M l-carnitine, and 2.82 M glycerol. The optimal composite CPA for Y. pestis is 0.62 M l-carnitine, 8.46 M glycerin, and 0.292 M sucrose. The results showed that the quality of the strains stored at -80°C and -196°C was better. For the case of freeze-thaw cycles, the two pathogens have different degrees of reduction, and the survival rate of Y. pestis decreased more than that of N. farcinica. The uniform distribution of bacteria in CPAs can form uniform nucleation sites in the solution system, which is beneficial to the cryopreservation of strains, as can be seen from the experimental results from a differential scanning calorimeter. This study may provide a reference for better preservation of precious natural biological resources of pathogenic microorganisms.

Research Progress of Machine Learning and Deep Learning in Intelligent Diagnosis of the Coronary Atherosclerotic Heart Disease.

The coronary atherosclerotic heart disease is a common cardiovascular disease with high morbidity, disability, and societal burden. Early, precise, and comprehensive diagnosis of the coronary atherosclerotic heart disease is of great significance. The rise of artificial intelligence technologies, represented by machine learning and deep learning, provides new methods to address the above issues. In recent years, artificial intelligence has achieved an extraordinary progress in multiple aspects of coronary atherosclerotic heart disease diagnosis, including the construction of intelligent diagnostic models based on artificial intelligence algorithms, applications of artificial intelligence algorithms in coronary angiography, coronary CT angiography, intravascular imaging, cardiac magnetic resonance, and functional parameters. This paper presents a comprehensive review of the technical background and current state of research on the application of artificial intelligence in the diagnosis of the coronary atherosclerotic heart disease and analyzes recent challenges and perspectives in this field.

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application.

BACKGROUND: Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. METHODS: Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan-Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. RESULTS: Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease-free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease-free survival time. The nomograms showed good accuracy of predicting survival time. CONCLUSION: Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced-stage patients.

High expression of the ferroptosis-associated MGST1 gene in relation to poor outcome and maladjusted immune cell infiltration in uterine corpus endometrial carcinoma.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) tightly correlates with dysregulated iron homeostasis. MGST1 (microsomal glutathione S-transferase 1) involves in the regulation of oxidative stress and plays a key role in inhibiting iron-mediated cell death in cancer cells. Hence, we aimed to illuminate the characteristics of MGST1 expression and prognosis in UCEC using bioinformatics prediction to provide novel perspectives for theoretical supplementation and ferroptosis-based immunotherapy. METHODS: We retrieved MGST1 expression data via several public data portals. The relationships between MGST1 expression and clinicopathologic characteristics as well as survival time were evaluated via multivariate methods and Kaplan-Meier survival curves. The MGST1-interacting protein-protein interaction was also established by the STRING website. The TIMER and GEPIA databases were used to illustrate the association between MGST1 expression and infiltrated immune cells. We used the MethSurv website and the UALCAN website to determine the relationship between MGST1 expression and DNA methylation. RESULTS: MGST1 overexpression in UCEC compared with normal tissues correlates with different histological types, a lack of hormone therapy and poor survival time. MGST1 interacts with several ferroptosis-related proteins. Overexpression of MGST1 was accompanied by lower levels of NK cell and CD8+ T cell infiltration, higher myeloid-derived suppressor cell infiltration and different immunocytes with corresponding markers. Hypermethylation and low promoter methylation cooperate to regulate MGST1 expression. CONCLUSION: Elevated MGST1 expression is related to tumour development and poor prognosis, as well as dysregulated infiltration of immune cells in UCEC, which can be a potential prognostic indicator and ferroptosis-based immunotherapy target.

Hsa_circ_0001020 Serves as a Potential Biomarker for Gastric Cancer Screening and Prognosis.

Circular RNAs (circRNAs) are an intriguing class of RNAs with covalently closed-loop structures. With characteristics of high stability and disease-specific expression, circRNAs are emerging as ideal targets for cancer therapy. However, the screening utility and clinical value of circRNAs in gastric cancer (GC) remain largely elusive. We detected levels of hsa_circ_0001020 in cell lines and tissue and plasma samples and investigated its clinicopathological correlations. Kaplan-Meier survival curves and regression analyses were used to analyze its prognostic value. Receiver operating characteristic curves and biomarker combinations were examined to verify its screening value. Bioinformatics analysis was also performed to predict potential biological functions. Our tests found that hsa_circ_0001020 was significantly upregulated in GC cell lines, GC tissue samples, and even in plasma. High hsa_circ_0001020 expression levels in GC tissues were significantly associated with distal metastasis and blood carbohydrate antigen 19-9 (CA19-9). GC patients with high hsa_circ_0001020 had a lower overall survival and disease-free survival time than the low levels. Regression analysis suggested that the level of hsa_circ_0001020 expression was an independent prognostic factor for survival time. As a biomarker for GC, hsa_circ_0001020 showed a superior AUC, sensitivity, and specificity than carcinoembryonic antigen and CA19-9, and was suitable for combination with clinical tumor biomarkers. Bioinformatics analysis provided valuable clues for the possible oncogenic pathways of GC, such as the FoxO and p53 signaling pathways. In conclusion, our study found that hsa_circ_0001020 in GC could be a reliable biomarker to screen for GC and predict prognosis.

[Preparation and application of decellularized extracellular matrix bioink: a review].

Decellularized extracellular matrix (dECM), which contains many proteins and growth factors, can provide three-dimensional scaffolds for cells and regulate cell regeneration. 3D bioprinting can print the combination of dECM and autologous cells layer by layer to construct the tissue structure of carrier cells. In this paper, the preparation methods of tissue and organ dECM bioink from different sources, including decellularization, crosslinking, and the application of dECM bioink in bioprinting are reviewed, with future applications prospected.

Fabrication of a dual-layer cell-laden tubular scaffold for nerve regeneration and bile duct reconstruction.

Tubular scaffolds serve as a controllable extracellular environment to guide the repair and regeneration of tissues. But it is still a challenge to achieve both excellent mechanical properties and cell compatibility of artificial scaffolds for long-term structural and biological stability. In this study, a four-step solution casting method was developed to fabricate dual-layer cell-laden tubular scaffolds for nerve and bile duct regeneration. The dual-layer tubular scaffold consisted of a bone marrow mesenchymal stem cells (BMSCs)-laden hydrogel inner layer and an outer layer of gelatin methacrylate (GelMA)/polyethylene glycol diacrylate. While the inner layer had a good biocompatibility, the outer layer had desired mechanical properties. The interfacial toughness, Young's modulus, maximum tensile strain, and compressive modulus of dual-layer tubular scaffolds were 65 J m-2, 122.37 ± 23.21 kPa, 100.87 ± 40.10%, and 39.14 ± 18.56 N m-1, respectively. More importantly, the fabrication procedure was very cell-friendly, since the BMSC viability encapsulated in the inner layer of 10% (w/v) GelMA reached 94.68 ± 0.43% after 5 d of culture. Then, a preliminary evaluation of the potential application of dual-layer tubular scaffolds as nerve conduits and biliary scaffolds was performed, and demonstrated that the cell-laden dual-layer tubular scaffolds proposed in this work are expected to extend the application of tubular scaffolds in tissue engineering.

Biological roles and potential clinical values of circular RNAs in gastrointestinal malignancies.

Circular RNAs (circRNAs), a class of endogenous RNA molecules, are produced by alternative splicing of precursor RNA and are covalently linked at the 5' and 3' ends. Recent studies have revealed that dysregulated circRNAs are closely related to the occurrence and progression of gastrointestinal malignancies. Accumulating evidence indicates that circRNAs, including circPVT1, circLARP4, circ-SFMBT2, cir-ITCH, circRNA_100782, circ_100395, circ-DONSON, hsa_circ_0001368, circNRIP1, circFAT1(e2), circCCDC66, circSMARCA5, circ-ZNF652, and circ_0030235 play important roles in the proliferation, differentiation, invasion, and metastasis of cancer cells through a variety of mechanisms, such as acting as microRNA sponges, interacting with RNA-binding proteins, regulating gene transcription and alternative splicing, and being translated into proteins. With the characteristics of high abundance, high stability, extensive functions, and certain tissue-, time- and disease-specific expressions, circRNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.

Signet ring cell carcinoma hidden beneath large pedunculated colorectal polyp: A case report.

BACKGROUND: Large pedunculated colorectal polyps are not frequent among colonic polyps. We present a clinical case of a large pedunculated colorectal polyp with signet ring cell cancer infiltrating the submucosa and lymph node invasion in a patient who ultimately underwent additional surgery. Clinicians should attach importance to pedunculated colorectal polyps and choose the most appropriate therapy. CASE SUMMARY: A 52-year-old female farmer underwent routine screening colonoscopy and denied constipation, diarrhea, hematochezia, or other gastrointestinal symptoms. Her past medical history and general biochemical examination results were unremarkable. During the colonoscopy, a 25-mm pedunculated polyp in the sigmoid colon was identified. The superficial epithelium was macroscopically congestive, rough, and granular, showing characteristic features of adenoma. We first ligated the root of the pedunculated polyp using nylon loops as well as a titanium clip. Histopathological examination revealed high-grade intraepithelial neoplasia of the tumor surface and a negative margin with signet ring cell adenocarcinoma infiltrating the submucosal layer. The deepest infiltration was approximately 0.9 cm from the tumor surface and 0.55 cm from the stratum basale. We performed radical resection of the left colon with lymph node dissection after two weeks. The lesion was completely resected, and pathological assessment revealed signet ring cell adenocarcinoma infiltrating the submucosal layer as well as lymph node invasion (stage PT1N1M0 and grade IIIA in pathological grading, NRAS-, BRAF V600E-, KRAS-). CONCLUSION: This case highlights the importance of paying attention to the malignancy of large pedunculated polyps. Polyps or adenomas removed via endoscopy must be evaluated histologically. Even if adenomas may be fragile, endoscopy doctors should still remove polyps as completely as possible and choose perpendicular sections through the stalk and base to fix by formaldehyde solution.

HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.

Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.

MicroRNA-Mediated Regulation of HMGB1 in Human Hepatocellular Carcinoma.

High-mobility group box 1 (HMGB1) is a potential therapeutic target and novel biomarker in a variety of malignant tumors, including hepatocellular carcinoma (HCC). More recently, a number of microRNAs (miRNAs) are identified as a class of regulators for broad control of HMGB1-mediated biological actions in eukaryotic cells. In this review article we will describe representative miRNAs involved in regulating the HMGB1 signaling pathways in HCC cell lines and/or animal models. We also propose the possible mechanisms underlying the miRNA/HMGB1 axis and discuss the future clinical significance of miRNAs targeting HMGB1 molecule for HCC therapy.