Purpose:To elucidate how Salidroside-loaded, oligopeptide-modified tumor exosomes (Salidroside@T-exo) rewire the PI3K/AKT/mTOR axis to remodel the immune microenvironment (IME) and reverse acquired PD-1 resistance in breast cancer. Materials and Methods:CSC-exosomes were surface-engineered with TMTP1 peptide and electroporated with Salidroside. PD-1-resistant MA782/5s-8101-R cells and an orthotopic mouse model were used. Multi-omics, flow cytometry, ELISA, immunofluorescence, in vivo imaging, and molecular assays examined immune and signaling outcomes. Results:Salidroside@T-exo restored T-cell IFN-γ and GZMB secretion, suppressed CD8+ T-cell apoptosis, and inhibited p-PI3K/p-AKT/p-mTOR in T cells. CSC migration, invasion, and stemness (OCT4, NANOG, SOX2) were markedly reduced. Tumor growth, Ki-67 index, and CSC frequency dropped while TUNEL-positive cells rose. Conclusion:Salidroside@T-exo reverses PD-1 blockade resistance by simultaneously inhibiting PI3K/AKT/mTOR signaling in T cells and eradicating breast CSCs, offering a clinically translatable strategy for refractory breast cancer immunotherapy.

Gaseous carbonyl compounds serve as crucial precursors and intermediates in atmospheric photochemical reactions, significantly contributing to ambient ozone formation. To determine whether the impact of carbonyl compounds on regional ozone pollution is driven by their abundance or by specific secondary chemical processes, simultaneous field observations and observation-based modeling of ambient carbonyls were conducted at nine sites within the Chengdu Plain Urban Agglomeration (CPUA), China, during 4–18 August 2019, when three episodes of regional heavy ozone pollution occurred across eight cities within CPUA. Throughout the study, the total mixing ratios of 15 carbonyls ranged from 10.7 ± 4.2 to 35.2 ± 13.4 ppbv. The spatial distribution reveals that regions with higher concentrations of carbonyl compounds, such as around Chengdu, are also areas with more severe ozone pollution. Both the abundance and the chemical reactivity of carbonyl compounds, especially formaldehyde and acetaldehyde, play crucial roles in ozone formation in the CPUA. On ozone pollution days, carbonyl concentrations significantly increased by 22.8 % to 66.2 %. While the abundance of carbonyls is an important factor, their significant role in heavy ozone pollution within the CPUA is primarily driven by secondary chemical processes, particularly those involving alkenes and biogenic volatile organic compounds (BVOCs). Sites with higher average ozone concentrations during observations were mainly in the VOC-limited regime, while others were in the transitional regime. Additionally, the mutual transport of carbonyl compounds between cities in the CPUA suggests that regional collaboration is essential to address ozone pollution effectively. These findings offer valuable insights for developing effective strategies to control regional ozone pollution.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy driven by glycolysis and immune evasion, with limited therapeutic options. This study develops RGD-modified glucose oxidase-loaded liposomes (RGD-Lipo@GOx) to target TNBC by modulating the MIF/NR3C2 axis, aiming to inhibit glycolysis and remodel the immune microenvironment. RGD-Lipo@GOx exhibited high encapsulation efficiency and tumor specificity. Bioinformatics analyses confirmed upregulated MIF and downregulated NR3C2 in TNBC. In vitro, RGD-Lipo@GOx suppressed glycolysis, migration, and invasion in MDA-MB-231 and BT-549 cells, upregulating NR3C2 and inhibiting MIF and PI3K/AKT signaling. In vivo, a TNBC xenograft model demonstrated enhanced tumor targeting, significant growth inhibition, and reduced glycolysis without systemic toxicity. These results highlight RGD-Lipo@GOx's potential as a nanotherapeutic platform that disrupts TNBC's metabolic and immune evasion mechanisms. Its high efficacy and safety suggest potential for clinical translation, particularly in combination with immunotherapies, and applicability to other glycolysis-driven cancers, advancing nanomedicine for precision oncology.

Obesity is a major global health issue. This study aimed to elucidate its molecular mechanisms by analysing the expression of lncRNAs, miRNAs, and mRNAs in visceral adipose tissue. Through integrated transcriptome sequencing and bioinformatics analysis of obese and normal groups, we observed 118, 92 and 227 differentially expressed lncRNAs, miRNAs and mRNAs, respectively. Functional enrichment analysis revealed these genes were primarily involved in immune response and inflammation-related pathways. A competing endogenous RNA (ceRNA) network was constructed, identifying key interactions among five target genes, including SDC4. Validation confirmed SDC4 was significantly upregulated in obese subjects, and this expression level positively correlated with body mass index and triglyceride. These findings suggest that SDC4 offers the possibility of being a therapeutic target for obesity.

Breast cancer (BC) represents a major contributor to cancer-associated deaths among women, underscoring the need for novel therapeutic approaches. This study explores the role of miR-155-5p as an oncogenic driver in BC progression through a multi-omics approach. Elevated miR-155-5p expression was observed in serum exosomes and tumor tissues, with its upregulation correlating with advanced pathological stages, lymph node metastasis, and unfavorable clinical outcomes. Functional experiments demonstrated that miR-155-5p enhances cellular proliferation, motility, and invasive capacity while inhibiting apoptosis in BC. Mechanistically, miR-155-5p exerts its effects by directly suppressing Nedd4 Family Interacting Protein 1 (NDFIP1), thereby initiating activation of the NF-κB axis. This activation was characterized by increased nuclear translocation of NF-κB p65 and enhanced secretion of inflammatory cytokines, including IL-6 and TNF-α. In vivo, knockdown of miR-155-5p effectively suppressed tumor growth and metastasis, with these effects reversed by silencing NDFIP1. These results highlight the miR-155-5p/NDFIP1/NF-κB axis as a critical pathway in BC progression, providing new insights into its molecular mechanisms. miR-155-5p emerges as a promising diagnostic marker and therapeutic candidate, suggesting the feasibility of miRNA-based interventions in BC treatment. This study highlights the pivotal role of integrative omics technologies in uncovering cancer-related regulatory networks.

BACKGROUND:Esophagogastric anastomotic leakage is a common complication after esophageal cancer surgery. Therefore, how to treat and predict is the focus of clinicians' research. AIMS:To analyze the risk factors of cervical and intrathoracic anastomotic leakage after radical resection of esophageal cancer and establish a prediction model to provide a basis for early clinical prevention and treatment. METHODS:We retrospectively analyzed the clinical data of 776 esophageal squamous cell carcinoma patients who underwent Sweet (n=115), Ivor-Lewis (n=278), and McKeown (left neck anastomosis) (n=383) esophagectomy at Yancheng First People's Hospital from August 2019 to December 2021. Univariate and logistic regression models were used to analyze the independent risk factors of anastomotic leakage after esophageal cancer surgery, and a nomogram prediction model was established. RESULTS:Of the 776 patients, 95 experienced postoperative anastomotic leakage, with an incidence of 12.2%. There were 63 cases of cervical anastomotic leakage and 32 cases of intrathoracic anastomotic leakage. The multivariate logistic regression analysis showed that BMI, high blood pressure, chronic bronchitis, peptic ulcer, operation way, anastomotic location, and postoperative albumin were independent risk factors for postoperative anastomotic leakage of esophageal cancer (p < 0.05). Our nomogram prediction model yielded a high predictive value, with an area under the receiver operating characteristic curve of 0.765 (95% CI 0.716-0.814). CONCLUSION:The occurrence of anastomotic leakage after esophageal cancer surgery is related to various factors, including BMI, hypertension, chronic bronchitis, peptic ulcer, operation way, anastomotic way, postoperative albumin, and anastomotic location. The clinical prediction model can promote the early detection, diagnosis, intervention, and treatment of anastomotic leakage and shorten the hospitalization time of patients.

Breast cancer is a heterogeneous disease with a high incidence, but its proteomes have not yet been thoroughly characterized. To construct a comprehensive dynamic network of breast cancer-related proteins, we integrated the whole-cell proteome (WCP), phospho-proteome, malonyl-proteome of breast cancer tumor tissues and adjacent healthy tissues. We identified 2,417 differentially expressed proteins (DEPs), 646 differentially phosphorylated proteins (DPPs), and 107 differentially malonylated proteins (DMPs). Functional enrichment analysis revealed that these differentially expressed proteins are involved in extracellular matrix (ECM) interactions and immune-related pathways. Protein‒protein interaction (PPI) analysis revealed posttranslational modification (PTM) crosstalk between proteins involved in phosphorylation and malonylation. The acetyltransferase EP300 and deacetylase HDAC1 are involved in the DPP network, whereas the phosphatase PKM is a hub protein in the DMP network. Kinase-substrate enrichment analysis (KSEA) revealed the activation of the kinases CSNK1D, ROCK1, ROCK2, and CDK2. Overall, this study provides a foundation for understanding the functions of phosphorylation and malonylation in breast cancer. It systematically reveals critical features of breast cancer, providing a resource for exploring PTM crosstalk within and across proteins involved in the disease.

The regulatory potential of long noncoding RNA (lncRNA) FBXL19-AS1 has been highlighted in various cancers, but its effect on triple-negative breast cancer (TNBC) remains unclear. Here, we aimed to elucidate the role of FBXL19-AS1 in TNBC and its underlying mechanism. RT-qPCR was employed to detect the expressions of FBXL19-AS1 and miR-378a-3p in tissues and cells. Immunohistochemical staining and western blot were utilized to detect the expression levels of proteins. Cell activities were detected using flow cytometry, CCK-8, and transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were deployed to investigate interactions of different molecules. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathways were used to analyze the downstream pathway. In vivo xenograft model was conducted to detect the effect of FBXL19-AS1 on tumor growth. FBXL19-AS1 was overexpressed in TNBC tissues and cell lines compared with counterparts. FBXL19-AS1 knockdown suppressed TNBC cell activities, whereas its overexpression exhibited the opposite effect. Mechanistically, FBXL19-AS1 was found to interact with miR-378a-3p. Further analysis revealed that miR-378a-3p exerted tumor-suppressive effects in TNBC cells. Additionally, miR-378a-3p targeted and downregulated the expression of ubiquitin aldehyde binding 2 (OTUB2), a deubiquitinase associated with TNBC progression. In vivo experiments substantiated the inhibitory effects of FBXL19-AS1 knockdown on TNBC tumorigenesis, and a miR-378a-3p inhibitor partially rescued these effects. The downstream pathway of the miR-378a-3p/OTUB2 axis was explored, revealing connections with proteins involved in modifying other proteins, removing ubiquitin molecules, and influencing signaling pathways, including the Hippo signaling pathway. Western blot analysis confirmed changes in YAP and TAZ expression levels, indicating a potential regulatory network. In summary, FBXL19-AS1 promotes exacerbation in TNBC by suppressing miR-378a-3p, leading to increased OTUB2 expression. The downstream mechanism may be related to the Hippo signaling pathway. These findings propose potential therapeutic targets for TNBC treatment.

Abstract. Gaseous carbonyl compounds serve as crucial precursors and intermediates in atmospheric photochemical reactions, significantly contributing to ambient ozone formation. To investigate the impact of gaseous carbonyls on regional ozone pollution, simultaneous field observations and observation-based modelling of ambient carbonyls were conducted at nine sites within the Chengdu Plain Urban Agglomeration (CPUA), China during August 4–18, 2019, when three episodes of regional heavy ozone pollution occurred across eight cities within CPUA. Throughout the study, the total mixing ratios of 15 carbonyls ranged from 10.70 to 35.18 ppbv, in which formaldehyde (48.1 %), acetone (19.9 %), and acetaldehyde (17.5 %) were most abundant within the CPUA. Ambient levels of carbonyls and ozone showed some positive correlations in space (especially pronounced around Chengdu in both northern and southern directions) and in diurnal variations with higher concentrations of carbonyls during ozone pollution episodes. Photochemical reactivity analysis emphasized the significant contributions of carbonyls, especially formaldehyde and acetaldehyde, to ozone formation. The ozone formation sensitivity for sites experiencing severe ozone pollution were classified as VOCs-limited regime, while others were categorized as transitional regime. Local primary emissions, mutual air transportation among cities within the CPUA and photochemical secondary processes were recognized to contribute significantly to the production or the contamination of carbonyls in ambient air, with alkenes and alkanes being important secondary precursors of carbonyls. This study highlights the pivotal role of carbonyls in heavy ozone pollution within the CPUA, China, providing valuable scientific insights to guide the development of effective countermeasures for regional ozone pollution control in the future.

For patients diagnosed with advanced gastric or gastroesophageal cancer (AGC) that is not amenable to surgical intervention, the standard of care for first-line treatment consists of fluoropyrimidine and platinum-based chemotherapy. The incorporation of novel agents into these standard first-line regimens could potentially improve patient prognosis; options for such augmentations include both immune-based and targeted therapy combinations. To provide a comparative analysis of these different first-line combination treatments, a network meta-analysis was conducted. Outcome measures comprised overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3-4 treatment-related adverse events (TRAEs). Data were drawn from 22 randomized controlled trials, encompassing 10,787 patients and 17 distinct treatment regimens. Our findings suggest that FGFR2b-targeted therapy, specifically when used in combination with chemotherapy (bemarituzumab_chemo), exhibited the greatest efficacy. This was followed by immunotherapy-based combination regimens (CPS ≥5, Sintilimab_chemo). Further, targeted combination therapy featuring CLAUDIN 18.2 (zolbetuximab_chemo) appeared beneficial based on individual patient characteristics. In the case of HER2-positive patients, the trastuzumab_chemo regimen is recommended, as most existing studies have excluded this subpopulation. These results have significant implications for both clinical decision-making and patient care in the realm of advanced gastric or gastroesophageal cancer treatment.

Background This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta (R)) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative.Methods Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32.Results Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade >= 3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups.Conclusions QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer.Trial registration Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

YT521-B homology (YTH) domain family (YTHDF) proteins serve as readers that directly recognise m6A modifications. In this study, we aim to probe the role of YTHDF1 in environmental carcinogen-induced malignant transformation of gastric cells and gastric cancer (GC) carcinogenesis. We established a long-term low-dose MNU-induced malignant transformation model in gastric epithelial cells. In vivo and in vitro experiments were conducted to validate the malignant phenotype and characterise the roles of YTHDF1 and its downstream genes in malignant transformation cells. Additionally, we explored downstream m6A modification targets of YTHDF1 using RNA-sequencing, RNA immunoprecipitation, and proteomics analyses, and conducted validation experiments in cell experiments and clinical samples. Long-term low-dose exposure of MNU converted normal Gges-1 cells into malignant cells. YTHDF1 mRNA and protein expression are increased in MNU-induced malignant cells (p<0.001). Meanwhile, YTHDF1 knockdown inhibits the malignant potential of MNU-treated cells (p<0.01). YTHDF1 knockdown specifically suppresses HSPH1 protein, but not RNA levels. RIP-qPCR validates HSPH1 is the target of YTHDF1 (p<0.01). HSPH1 knockdown impairs the malignant potential of MNU-induced transformed cells. The increased expression of the key regulatory factor YTHDF1 in MNU-induced gastric carcinogenesis affects malignant transformation and tumorigenesis by regulating the translation of downstream HSPH1. These findings provide new potential targets for preventing and treating environmental chemical-induced gastric carcinogenesis.

Background: Bariatric surgery has been reported to improve degeneration, inflammation, and fibrosis in nonalcoholic fatty liver disease, but the effects of bariatric surgery on the associated clinical outcomes is not known.Objectives: This work aimed to assess the impacts of bariatric surgery on adverse liver outcomes in people with obesity.Setting: An electronic search was performed on EMBASE, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL).Methods: The primary outcome was the incidence of adverse liver outcomes following bariatric surgery. Liver cancer, cirrhosis, liver transplantation, liver failure, and liver-related mortality were defined as adverse hepatic outcomes.Results: We analyzed data from 18 studies comprising 16,800,287 post bariatric surgical patients and 10,595,752 control patients. We found that bariatric surgery reduced the risk of adverse liver outcomes in people with obesity (hazard ratio [HR] = .33, 95% confidence interval [CI] = .31-.34; I2 = 98.1%). The subgroup analysis showed that bariatric surgery reduced the risk of nonalcoholic cirrhosis (HR = .07, 95% CI = .06-.08; I2 = 99.3%) and liver cancer (HR = .37, 95% CI = .35- .39; I2 = 97.8%), although bariatric surgery may also increase the risk of postoperative alcoholic cirrhosis (HR = 1.32, 95% CI = 1.35-1.59).Conclusions: This systematic review and meta-analysis revealed that bariatric surgery lowered the incidence of adverse hepatic outcomes. However, bariatric surgery may also increase the risk of alcoholic cirrhosis after surgery. Future randomized controlled trials are required to further investigate the effects of bariatric surgery on liver of people with obesity. (Surg Obes Relat Dis 2023;19:717-726.) & COPY; 2023 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.

Background: The high rate of weight regain after laparoscopic sleeve gastrectomy is a great chal-lenge. The systemic immune-inflammation index (SII; calculated by neutrophils, lymphocytes, and platelets) and prognostic nutritional index (PNI; calculated by albumin and lymphocytes) are widely used as prognostic factors in various diseases.Objectives: The objective of this study was to investigate independent the independent risk factors associated with weight regain in patients after laparoscopic sleeve gastrectomy.Setting: A single-center retrospective study.Methods: Weight regain was defined as the percentage of increase in body weight >10% in comparison with the nadir weight postoperatively. Eligible patients admitted to the bariatric center of our hospital were consecutively enrolled and grouped according to the occurrence of weight regain within 5 postoperative years. Univariate and multivariate logistic regression analyses were performed to assess potential risk fac-tors. A nomogram model containing the risk factors was then constructed and evaluated by R.Results: A total of 217 patients were enrolled, and 87 (40.1%) patients experienced weight regain. Univariate and logistic regression analyses indicated that depression (odds ratio [OR]: 2.51, 95% con-fidence interval [CI]: 1.20-5.22, P = .015), psychological counseling (OR: 2.27, 95% CI: 1.20-4.33, P =.017), preoperative C-reactive protein (OR: 2.20, 95% CI: 1.18-4.13, P =.012), and combination of SII-PNI scores (OR: .45, 95% CI: .31-.67, P , .001) were 4 independent risk factors for postop-erative weight regain in laparoscopic sleeve gastrectomy patients. The area under the curve of the constructed nomogram model for predicting weight regain was .706.Conclusions: This study concluded that the combination of the SII-PNI was an independent risk fac-tor for weight regain and that the nomogram model based on the combination of the SII-PNI had a good predictive value. (Surg Obes Relat Dis 2023;19:50-58.) (c) 2023 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Globally, due to the rapid development of bacterial resistance, bacterial infections lead to significant mortality and morbidity which require efficient strategies to eradicate these infections. Herein, we prepared a dual-responsive synergistic drug delivery nanoparticle carrier (NPS@Bai/Cip), which responds to sub-acid bacterial microenvironments and targets phosphatase or phospholipase at infection sites. Nanoparticles surfaces were positively (10.0 mV) charged under acidic conditions, leading to good bacterial adhesion and enhanced drug accumulation. NPS@Bai/Cip showed good antibacterial and anti-biofilm activity against drug-resistant Pseudomonas aeruginosa. NPS@Bai/Cip could inhibit the biofilm formation via affecting the swimming, swarming, and twitching motilities of P. aeruginosa. NPS@Bai/Cip was used to treat drug-resistance P. aeruginosa-induced infection in rats by improving wound healing and reducing inflammatory responses. Thus, NPS@Bai/Cip functioned as an antibacterial and antibiofilm agent with good potential for treating bacteria-induced infections.

Adipogenesis and fat accumulation are closely associated with the development of obesity. Sleeve gastrectomy (SG) is an effective treatment for obesity and associated metabolic disorders. Leptin is downregulated after SG and Src homology phosphatase 2 (Shp2) has an important role in leptin signaling. The role of Shp2 in SG and the mechanisms of fat reduction following SG were further investigated in the current study. Sham and SG operations were performed on obese type-2 diabetes model Sprague-Dawley rats. Primary pre-adipocytes were isolated from the inguinal white adipose tissue (ingWAT) of the rats. Shp2 expression in ingWAT pre-adipocytes was silenced using small interfering RNA transfection. Shp2 function was inhibited using the specific inhibitor, SHP099. In addition, Shp2 was overexpressed using lentivirus. Gene and protein expression analysis was performed after adipocyte differentiation. Furthermore, Shp2-overexpressing ingWAT pre-adipocytes treated with the β-catenin inhibitor, PNU-74654, were also used for gene and protein expression analysis. Adipogenic markers, including triglycerides, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (Cebpα), adiponectin, fatty acid-binding protein 4 and leptin, were examined. Compared with the sham, triglyceride, leptin, PPARγ and Cebpα levels were significantly reduced in the ingWAT from the SG group. Shp2 expression levels were reduced following leptin treatment. Moreover, genetic analysis demonstrated depot-specific adipogenesis following Shp2 silencing or inhibition in ingWAT pre-adipocytes. Conversely, Shp2 overexpression decreased the expression of adipogenic markers by enhancing β-catenin expression. PNU-74654 treatment abolished the downregulation of adipogenic markers caused by Shp2 overexpression. SG decreased leptin levels in ingWAT, which in turn upregulated Shp2, and Shp2 suppressed fat accumulation and adipogenic differentiation by activating the Wnt/β-catenin signaling pathway. Overall, this may represent a potential mechanism of fat reduction in SG, and Shp2 may serve as a potential therapeutic target for the treatment of obesity and type-2 diabetes.

This study aimed to at explore exploring the biological functions of dysregulated circRNA in Crohn’s disease (CD) pathogenesis, with the overarching goal of and providing potential novel therapeutic targets. CircRNA microarray and quantitative real time-polymerase chain reaction (qRT-PCR) analyses were performed to investigate and verify the candidate dysregulated circRNA. The Next, clinical, in vivo, and in vitro studies were performed to investigate explore the biological function and mechanisms of the candidate circRNA in CD. The therapeutic effect of poly (lactic-co-glycolic acid)-microspheres (PLGA MSs)-carried oe-circGMCL1 in experimental colitis models of IL-10 knock-out mice was assessed. CircGMCL1 was identified as the candidate circRNA by microarray and qRT-PCR analyses. Results showed that circGMCL1 expression was negatively correlated with CD-associated inflammatory indices, suggesting that it is a CD-associated circRNA. Microarray and bioinformatics analyses identified miR-124-3p and Annexin 7 (ANXA7) as its downstream mechanisms. The in vitro studies revealed that circGMCL1 mediates its effects on autophagy and NLRP3 inflammasome-mediated pyroptosis in epithelial cells through the ceRNA network. Moreover, the in vivo studies identified the therapeutic effect of PLGA MSs-carried oe-circGMCL1 in experimental colitis models. This study suggests that circGMCL1 protects intestinal barrier function against Crohn’s colitis through alleviating NLRP3 inflammasome-mediated epithelial pyroptosis by promoting autophagy through regulating ANXA7 via sponging miR-124-3p. Therefore, circGMCL1 can serve as a potential biological therapeutic target for Crohn’s colitis.

Background Increasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network. Methods Microarray datasets GSE83521 and GSE93541 were obtained from the Gene Expression Omnibus (GEO). Then, we used computational biology to identify circRNAs that were differentially expressed in both GC tissue and plasma compared to normal controls; then, we detected the expression of the selected circRNAs in gastric cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We also identified circRNA-related candidate miRNAs and their target genes with online tools. Combining the predicted miRNAs and target mRNAs, a competing endogenous RNA regulatory network was established. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted by using String and Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained three differentially co-expressed circRNAs (DECs). A circRNA-miRNA-mRNA network was constructed based on 3 circRNAs, 43 miRNAs and 119 mRNAs. Results GO and KEGG analysis showed that the regulation of apoptotic signaling pathway and PI3K-Akt signaling pathway were highest degrees of enrichment respectively. We established a protein-protein interaction (PPI) network consisting of 165 nodes and 170 edges and identified hub genes by using MCODE plugin in Cytoscape. Furthermore, a core circRNA-miRNA-mRNA network was constructed based on hub genes. Hsa_circ_0001013 was finally determined to play an important role in the pathogenesis of GC according to the core circRNA-miRNA-mRNA network. Conclusions We propose a new circRNA-miRNA-mRNA network that is associated with the pathogenesis of GC. The network may become a new molecular biomarker and could be used to develop potential therapeutic strategies for gastric cancer.

Long noncoding RNA (LncRNA) dysregulation has been shown to exhibit a regulatory effect in various cancers. However, the effect of LINC01287 on breast cancer (BC) has not been illustrated. The aim of this research was to explore the expression and function of LncRNA LINC01287 in BC. LINC01287 expression in clinical tissues and BC cell lines was detected. The luciferase reporter assay was performed to verify the correlation between LINC01287, microRNA 98 (miR-98), and the insulin-like growth factor 1 receptor (IGF1R). The CCK-8 assay was performed to examine cell viability. Cell invasion and migration capacity was determined by transwell and wound healing assays. The protein level of IGF1R, phosphorylated mitogen-activated protein kinase 1 and 2 (p-MEK1/2), and phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) was analyzed by western blotting. LINC01287 expression markedly increased in BC cell lines. Subsequent studies identified LINC01287 as a downstream target of miR-98. In addition, LINC01287 knockdown and miR-98 overexpression significantly stagnated progression of BC cells. LINC01287 knockdown also downregulated IGF1R levels. Moreover, LINC01287 knockdown notably downregulated the phosphorylation of MEK1/2 and ERK1/2. The in vivo assay verified that LINC01287 can regulate tumorigenesis of BC. Our findings showed that LINC01287 was overexpressed in BC cells and tissues. LINC01287 promoted the malignant characteristics of BC cells and acted as an oncogene. Its regulatory effect may be associated with the miR-98/IGF1R/MEK/ERK signaling pathway. Therefore, LINC01287 has potential for use as a biomarker or therapeutic target for the treatment of BC.