Comprehensive assessment of the anti-obesity effects of highland barley total, insoluble, and soluble dietary fiber through multi-omics analysis.

The impact of different forms of dietary fiber (total, insoluble or soluble) derived from the same source on health remains incompletely understood. In this study, the effects of total, insoluble, and soluble dietary fiber extracted from highland barley (HDF, HIDF, and HSDF) on combating obesity were evaluated and compared. A high-fat diet (HFD) was used to induce obesity in a murine model, followed by gavage administration of HDF, HIDF, or HSDF, and a comprehensive multi-omics approach was utilized to assess and compare the effects of these dietary fibers on obesity-related parameters. The results showed that all three dietary fibers significantly reduced body weight, modified blood lipid profiles, and ameliorated tissue damage in HFD-fed mice. Additionally, 16S rRNA sequencing analysis of mice feces showed that three types of dietary fiber exerted varying degrees of impact on the composition and abundance of gut microbiota while simultaneously promoting the biosynthesis of short-chain fatty acids. Specifically, HDF supplementation remarkably enhanced the abundance of Coprococcus, while HIDF and HSDF supplementation elevated the levels of Akkermansia and Allobaculum, respectively. Transcriptomic and proteomic results suggested the PPAR signaling pathway as a central regulatory mechanism influenced by these fibers. HDF and HIDF were particularly effective in modulating biological processes related to triglyceride and fatty acid metabolism, identifying Abcc3 and Dapk1 as potential targets. Conversely, HSDF primarily affected processes related to membrane lipids, ceramides, and phospholipids metabolism, with Pck1 identified as a potential target. Collectively, HDF, HIDF, and HSDF demonstrated distinct mechanisms in exerting exceptional anti-obesity properties. These insights may inform the development of personalized dietary interventions for obesity.

Pan-cancer analysis of the disulfidptosis-related gene RPN1 and its potential biological function and prognostic significance in gliomas.

Background: Numerous studies have shown a strong correlation between disulfidptosis and various cancers. However, the expression and function of RPN1, a crucial gene in disulfidptosis, remain unclear in the context of cancer. Methods: Gene expression and clinical information on lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. RPN1 expression was analyzed using the Timer2.0 and the Human Protein Atlas (HPA) databases. Prognostic significance was assessed using Cox regression analysis and Kaplan-Meier curves. Genetic mutations and methylation levels were examined using the cBioPortal and UALCAN platforms, respectively. The relationship between RPN1 and tumor mutation burden (TMB) and microsatellite instability (MSI) across different cancer types was analyzed using the Spearman correlation coefficient. The relationship between RPN1 and immune cell infiltration was analyzed using the Timer2.0 database, whereas variations in drug sensitivity were explored using the CellMiner database. Receiver operating characteristic curves validated RPN1's diagnostic potential in glioma, and its correlation with immune checkpoint inhibitors (ICIs) was assessed using Spearman's correlation coefficient. Single-sample gene set enrichment analysis elucidated a link between RPN1 and immune cells and pathways. In addition, a nomogram based on RPN1 was developed to predict patient prognosis. The functional impact of RPN1 on glioma cells was confirmed using scratch and Transwell assays. Result: RPN1 was aberrantly expressed in various cancers and affected patient prognosis. The main mutation type of RPN1 in the cancer was amplified. RPN1 exhibited a positive correlation with myeloid-derived suppressor cells, neutrophils, and macrophages, and a negative correlation with CD8+ T cells and hematopoietic stem cells. RPN1 expression was associated with TMB and MSI in various cancers. The expression of RPN1 affected drug sensitivity in cancer cells. RPN1 was positively correlated with multiple ICIs in gliomas. RPN1 also affected immune cell infiltration into the tumor microenvironment. RPN1 was an independent prognostic factor for gliomas, and the nomogram demonstrated excellent predictive performance. Interference with RPN1 expression reduces the migratory and invasive ability of glioma cells. Conclusion: RPN1 exerts multifaceted effects on different stages of cancer, including immune infiltration, prognosis, and treatment outcomes. RPN1 expression affects the prognosis and immune microenvironment infiltration in patients with glioma, making RPN1 a potential target for the treatment of glioma.

Pan-cancer Analysis of the Disulfidptosis-related Gene NCKAP1 and Its Prognostic Value for Lung Adenocarcinoma.

BACKGROUND: The nck-associated protein 1 (NCKAP1) of the disulfidptosis-related gene is essential in programmed cell death. However, a comprehensive analysis of the biological significance of NCKAP1 in pan-cancer is lacking. METHODS: Gene expression matrices and clinical expression information of cancers were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEX) databases. A comprehensive analysis of NCKAP1 expression, biological function, gene mutation, immune cell infiltration, DNA methylation, and drug sensitivity profiles in pan-cancer was performed using the Timer2.0, HPA, GEPIA, STRING, cBioPortal, UALCAN and CellMiner databases. The prognostic value of NCKAP1 was investigated based on COX regression analysis and the Kaplan-Meier(K-M) curves. A nomogram was established to verify the clinical value of NCKAP1 for LUAD. The correlation between NCKAP1 and immune cells and signaling pathways were investigated by single-sample gene set enrichment analysis(ssGSEA). Validation was performed using PCR, Western Blot (WB), and Transwell assays. RESULT: Significant differences in expression levels, mutation levels, and methylation levels of NCKAP1 between tumor and normal samples. NCKAP1 affects the prognosis of various cancers. NCKAP1 is strongly associated with microsatellite instability (MSI) and tumor mutational burden (TMB). The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicate that NCKAP1 is strongly associated with cell death and tumor immunity. The expression of NCKAP1 affects the sensitivity to various drugs. Moreover, NCKAP1 is an independent predictor of prognosis in LUAD patients. The results of ssGSEA showed that elevated NCKAP1 expression was positively correlated with multiple immune-related signaling pathways. PCR analysis showed that the expression of NCKAP1 was increased in LUAD cells. Transwell invasion assay showed that overexpression of NCKAP1 resulted in enhanced invasion of LUAD cells. CONCLUSIONS: We comprehensively analyzed the relationship between NCKAP1 and pan-cancer and its potential clinical value. NCKAP1 could be a potential immune marker for various cancers (especially LUAD), providing new insights and insights for cancer therapy.

Comprehensive analysis to identify a novel diagnostic marker of lung adenocarcinoma and its immune infiltration landscape.

Background: Lung cancer continues to be a problem faced by all of humanity. It is the cancer with the highest morbidity and mortality in the world, and the most common histological type of lung cancer is lung adenocarcinoma (LUAD), accounting for about 40% of lung malignant tumors. This study was conducted to discuss and explore the immune-related biomarkers and pathways during the development and progression of LUAD and their relationship with immunocyte infiltration. Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database and the Cancer Genome Atlas Program (TCGA) database. Through the analysis of differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator(LASSO), selecting the module with the highest correlation with LUAD progression, and then the HUB gene was further determined. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were then used to study the function of these genes. Single-sample GSEA (ssGSEA) analysis was used to investigate the penetration of 28 immunocytes and their relationship with HUB genes. Finally, the receiver operating characteristic curve (ROC) was used to evaluate these HUB genes accurately to diagnose LUAD. In addition, additional cohorts were used for external validation. Based on the TCGA database, the effect of the HUB genes on the prognosis of LUAD patients was assessed using the Kaplan-Meier curve. The mRNA levels of some HUB genes in cancer cells and normal cells were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: The turquoise module with the highest correlation with LUAD was identified among the seven modules obtained with WGCNA. Three hundred fifty-four differential genes were chosen. After LASSO analysis, 12 HUB genes were chosen as candidate biomarkers for LUAD expression. According to the immune infiltration results, CD4 + T cells, B cells, and NK cells were high in LUAD sample tissue. The ROC curve showed that all 12 HUB genes had a high diagnostic value. Finally, the functional enrichment analysis suggested that the HUB gene is mainly related to inflammatory and immune responses. According to the RT-qPCR study, we found that the expression of DPYSL2, OCIAD2, and FABP4 in A549 was higher than BEAS-2B. The expression content of DPYSL2 was lower in H1299 than in BEAS-2B. However, the expression difference of FABP4 and OCIAD2 genes in H1299 lung cancer cells was insignificant, but both showed a trend of increase. Conclusions: The mechanism of LUAD pathogenesis and progression is closely linked to T cells, B cells, and monocytes. 12 HUB genes(ADAMTS8, CD36, DPYSL2, FABP4, FGFR4, HBA2, OCIAD2, PARP1, PLEKHH2, STX11, TCF21, TNNC1) may participate in the progression of LUAD via immune-related signaling pathways.

Prognostic value of preoperative chemotherapy for thymic epithelial tumors: A propensity-matched analysis based on the SEER database.

Background: The aim of this study was to assess the impact of preoperative chemotherapy on long-term survival (≥1 month) in patients with thymic epithelial tumors (TETs) and conditions suitable for chemotherapy using data from surveillance, epidemiology, and end-result databases. Methods: This retrospective study controlled for confounding factors by propensity score matching (PSM), analyzed overall survival (OS) and cancer-specific survival (CSS) by Kaplan-Meier methods, and analyzed factors affecting the prognosis of patients undergoing surgery for thymic epithelial tumors by univariate and multifactorial Cox regression. Results: A total of 2,451 patients who underwent surgery for TETs were identified from the Surveillance, Epidemiology, and End Results database. Preoperative chemotherapy significantly improved OS and CSS in patients with stage III/IV TETs compared to patients without preoperative chemotherapy. Subgroup analysis showed that patients younger than 60 years of age with TETs, patients with thymic carcinoma, and patients with TETs with multiple cancers were more likely to benefit from preoperative chemotherapy. Conclusion: This study found that preoperative chemotherapy is a viable option for advanced thymoma with favorable overall and cancer-specific survival rates, but patient history and physical condition should be fully considered in conjunction with diagnostic imaging findings to assess patient tolerance to chemotherapy.

Circ-EIF3I facilitates proliferation, migration, and invasion of lung cancer via regulating the activity of Wnt/ß-catenin pathway through the miR-1253/NOVA2 axis.

Many studies have shown that circular RNA (circRNA) is an important regulator mediating the malignant progression of cancer. However, the role and mechanism of circ-EIF3I in lung cancer (LC) development are still unclear. A total 36 paired LC tumor tissues and adjacent normal tissues were enrolled. The expression of circ-EIF3I, microRNA (miR)-1253, and neuro-oncological ventral antigen 2 (NOVA2) was measured by quantitative real-time PCR. The proliferation, apoptosis, migration, and invasion of LC cells were determined by MTT assay, colony formation assay, flow cytometry, and transwell assay. Dual-luciferase reporter assay was performed to verify the interaction between miR-1253 and circ-EIF3I or NOVA2. The protein levels of NOVA2 and Wnt/ß-catenin pathway-related markers were detected by western blot analysis. Xenograft tumor was constructed to explore the function of circ-EIF3I on LC tumor growth. Circ-EIF3I was upregulated in LC tumor tissues and cells. Silenced circ-EIF3I could suppress the proliferation, migration, invasion, and enhance the apoptosis of LC cells in vitro, as well as reduce LC tumor growth in vivo. Circ-EIF3I could sponge miR-1253, and miR-1253 inhibitor overturned the regulation of circ-EIF3I knockdown on LC cell progression. NOVA2 was confirmed to be a target of miR-1253, which could reverse the inhibitory effects of miR-1253 on LC cell progression. Further experiments showed that circ-EIF3I regulated NOVA2 expression by sponging miR-1253. In addition, circ-EIF3I silencing could inhibit the activity of Wnt/ß-catenin pathway via regulating the miR-1253/NOVA2 axis. Circ-EIF3I might function as an oncogene in LC, which promoted LC progression by the miR-1253/NOVA2/Wnt/ß-catenin network.

Survival outcomes in esophageal cancer patients with a prior cancer.

ABSTRACT: To achieve a deeper understanding of patients who developed esophageal cancer (EC) as a second primary malignancy, which may help guide in clinical practice for these patients in the future.In the primary cohort, EC patients with a prior malignancy were identified from the surveillance, epidemiology, and end result 18 database. The 5 most common types of prior cancers were picked out based on the frequency of occurrence. In addition, Kaplan-Meier and log-rank tests were performed to investigate the survival impacts of prior cancers on EC patients. Besides, a competing-risk model was constructed to explore the relationship between EC-treatment and EC-specific mortality. In the secondary cohort, patients with stage I-III (N0M0) EC from 2004 to 2014 were enrolled. After propensity score matching, univariate and multivariate Cox analyses were developed to determine the prognostic factors for EC patients.A total of 1199 EC patients with a prior cancer were identified in the primary cohort. The 5 most common sites of prior cancers were prostate, female breast, bladder, lung and bronchus, and larynx. Kaplan-Meier analyses revealed that EC patients with prior prostate cancer and bladder cancer had the best overall survival (OS), while those with prior cancers of larynx and lung and bronchus had the worst OS. Fine and Gray competing risks analysis indicated that the administration of surgery was closely associated with better EC-specific survival (P < .001). In the secondary cohort, multivariate Cox analyses found that age at diagnosis, race, tumor grade, tumor extent, nodal status and metastasis stage, histology, and the administration of surgery were prognostic factors for OS and cancer-specific survival in EC patients. Besides, the existence of a prior cancer was an independent prognostic factor for cancer-specific survival.EC remains to be the most important cause of death in EC patients with a prior cancer. EC related treatment should be actively adopted in patients with a prior cancer, as they were more likely to die from EC than the prior cancer. EC patients with a prior cancer had comparable OS than those without.