TMT-Based Quantitative Proteomic Profiling of Human Esophageal Cancer Cells Reveals the Potential Mechanism and Potential Therapeutic Targets Associated With Radioresistance.

PURPOSE: The recurrence of esophageal squamous cell carcinoma (ESCC) in radiation therapy treatment presents a complex challenge due to its resistance to radiation. However, the mechanism underlying the development of radioresistance in ESCC remains unclear. In this study, we aim to uncover the mechanisms underlying radioresistance in ESCC cells and identify potential targets for radiosensitization. METHODS: We established two radio-resistant cell lines, TE-1R and KYSE-150R, from the parental ESCC cell lines TE-1 and KYSE-150 through fractionated irradiation. A TMT-based quantitative proteomic profiling approach was applied to identify changes in protein expression patterns. Cell Counting Kit-8, colony formation, γH2AX foci immunofluorescence and comet assays were utilized to validate our findings. The downstream effectors of the DNA repair pathway were confirmed using an HR/NHEJ reporter assay and Western blot analysis. Furthermore, we evaluated the expression of potential targets in ESCC tissues through immunohistochemistry combined with mass spectrometry. RESULTS: Over 2,000 proteins were quantitatively identified in the ESCC cell lysates. A comparison with radio-sensitive cells revealed 61 up-regulated and 14 down-regulated proteins in the radio-resistant cells. Additionally, radiation treatment induced 24 up-regulated and 12 down-regulated proteins in the radio-sensitive ESCC cells. Among the differentially expressed proteins, S100 calcium binding protein A6 (S100A6), glutamine gamma-glutamyltransferase 2 (TGM2), glycogen phosphorylase, brain form (PYGB), and Thymosin Beta 10 (TMSB10) were selected for further validation studies as they were found to be over-expressed in the accumulated radio-resistant ESCC cells and radio-resistant cells. Importantly, high S100A6 expression showed a positive correlation with cancer recurrence in ESCC patients. Our results suggest that several key proteins, including S100A6, TGM2, and PYGB, play a role in the development of radioresistance in ESCC. CONCLUSIONS: Our results revealed that several proteins including Protein S100-A6 (S100A6), Protein-glutamine gamma-glutamyltransferase 2 (TGM2), Glycogen phosphorylase, brain form (PYGB) were involved in radio-resistance development. These proteins could potentially serve as biomarkers for ESCC radio-resistance and as therapeutic targets to treat radio-resistant ESCC cells.

Combination of comprehensive thermal care and detail-oriented nursing care in the operating room for managing gestational diabetes mellitus.

BACKGROUND: As the incidence of gestational diabetes mellitus (GDM) increases, its impact on cesarean sections has attracted widespread attention. Omni-directional, insulated care and detailed care are of great significance in this patient population, as they can effectively improve the quality of care in the operating room. AIM: To explore the effect of the integrated use of comprehensive thermal insulation. METHODS: Women with GDM who underwent cesarean sections at our hospital between April 2023 and February 2024 were included in this retrospective study. The participants were randomly allocated to two groups: The observation and control groups. An all-around thermal insulation nursing strategy, including preoperative, intraoperative, and postoperative temperature maintenance, was adopted. In addition, detailed nursing care measures, such as blood glucose monitoring, wound care, and psychological counseling, were implemented in the observation group. RESULTS: Comparative observation revealed that all-around thermal insulation care can effectively prevent the incidence of maternal hypothermia caused by surgery, reduce the risk of infection, and promote blood circulation. The implementation of detailed care improved maternal satisfaction and reduced the incidence of complications via the appropriate management of fluctuations in the blood glucose levels and optimization of the nursing process before and after surgery according to the patient's characteristics. CONCLUSION: The application of a combination of comprehensive thermal insulation and detailed nursing care improved the overall quality of perioperative care.

Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies.

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

Opportunistic use of chest low-dose computed tomography (LDCT) imaging for low bone mineral density and osteoporosis screening: cutoff thresholds for the attenuation values of the lower thoracic and upper lumbar vertebrae.

Background: Osteoporosis remains substantially underdiagnosed and undertreated worldwide. Chest low-dose computed tomography (LDCT) may provide a valuable and popular opportunity for osteoporosis screening. This study sought to evaluate the feasibility of the screening of low bone mineral density (BMD) and osteoporosis with mean attenuation values of the lower thoracic compared to upper lumbar vertebrae. The cutoff thresholds of the mean attenuation values in Hounsfield units (HU) were derived to facilitate implementation of opportunistic screening using chest LDCT. Methods: The participants aged 30 years or older who underwent chest LDCT and quantitative computed tomography (QCT) examinations from August 2018 to October 2020 in our hospital were consecutively included in this retrospective study. A region of interest (ROI) was placed in the trabecular bone of each vertebral body to measure the HU values. The correlations of mean HU values of lower thoracic (T11-T12) and upper lumbar (L1-L2) vertebrae with age and lumbar BMD obtained with QCT were performed using the Pearson correlation coefficient, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve was generated to determine the cutoff thresholds for distinguishing low BMD from normal and osteoporosis from non-osteoporosis. Results: A total of 1,112 participants were included in the final study cohort (743 men and 369 women, mean age 58.2±8.9 years; range, 32-88 years). The mean HU values of T11-T12 and L1-L2 were significantly different among 3 QCT-defined BMD categories of osteoporosis, osteopenia, and normal (P<0.001). The differences in HU values between T11-T12 and L1-L2 in each category of bone status were statistically significant (P<0.001). The mean HU values of T11-T12 (r=-0.453, P<0.001) and L1-L2 (r=-0.498, P<0.001) had negative correlations with age. Positive correlations were observed between the mean HU values of T11-T12 (r=0.872, P<0.001) and L1-L2 (r=0.899, P<0.001) with BMD. The optimal cutoff thresholds for distinguishing low BMD from normal were average T11-T12 ≤157 HU [AUC =0.941, 95% confidence interval (CI): 0.925-0.954, P<0.001] and L1-L2 ≤138 HU (AUC =0.950, 95% CI: 0.935-0.962, P<0.001), as well as distinguishing osteoporosis from non-osteoporosis were average T11-T12 ≤125 HU (AUC =0.960, 95% CI: 0.947-0.971, P<0.001) and L1-L2 ≤107 HU (AUC =0.961, 95% CI: 0.948-0.972, P<0.001). There was no significant difference between the AUC values of T11-T12 and L1-L2 for low BMD (P=0.07) and osteoporosis (P=0.92) screening. Conclusions: We have conducted a study on low BMD and osteoporosis screening using mean attenuation values of lower thoracic and upper lumbar vertebrae. Assessment of mean attenuation values of T11-T12 and L1-L2 can be used interchangeably for low BMD and osteoporosis screening using chest LDCT, and their cutoff thresholds were established.

Murine exosomal miR-30a aggravates cardiac function after acute myocardial infarction via regulating cell fate of cardiomyocytes and cardiac resident macrophages.

After acute myocardial infarction (AMI), intercellular communication is crucial for maintaining cardiac homeostasis and patient survival. Exosomes secreted by cardiomyocytes serve as carriers for transporting microRNA(miRNAs), participating in intercellular signaling and the regulation of cardiac function. This study aims to investigate the role of exosomal microRNA-30a(miR-30a) during AMI and its underlying mechanisms. AMI was induced by permanent ligation of the left anterior descending (LAD) artery in C57BL/6 mice. The expression of miR-30a in mice was respectively enhanced and inhibited by administering agomiR-30a and antagomiR-30a. Using HL-1 cardiomyocytes and RAW264.7 macrophages for in vitro experiments, HL-1 cardiomyocytes were cultured under hypoxic conditions to induce ischemic injury. Following isolation and injection of exosomals, a variety of validation methods were utilized to assess the expression of miR-30a, and investigate the effects of enriched exosomal miR-30a on the state of cardiomyocytes. After AMI, the level of exosomal miR-30a in the serum of mice significantly increased and was highly enriched in cardiac tissue. Cardiomyocytes treated with agomiR-30a and miR-30a-enriched exosomes exhibited inhibition of cell autophagy, increased cell apoptosis, mice showed an larger myocardial infarct area and poorer cardiac function. Exosomes released from hypoxic cardiomyocytes transferred miR-30a to cardiac resident macrophages, promoting the polarization into pro-inflammatory M1 macrophages. In conclusion, murine exosomal miR-30a exacerbates cardiac dysfunction post-AMI by disrupting the autophagy-apoptosis balance in cardiomyocytes and polarizing cardiac resident macrophages into pro-inflammatory M1 macrophages. Modulating the expression of miR-30a may reduce cardiac damage following AMI, and targeting exosomal miR-30a could be a potential therapeutic approach for AMI.

Bulk anda single-cell transcriptome profiling reveals the molecular characteristics of T cell-mediated tumor killing in pancreatic cancer.

Background: Despite the potential of immune checkpoint blockade (ICB) as a promising treatment for Pancreatic adenocarcinoma (PAAD), there is still a need to identify specific subgroups of PAAD patients who may benefit more from ICB. T cell-mediated tumor killing (TTK) is the primary concept behind ICB. We explored subtypes according to genes correlated with the sensitivity to TKK and unraveled their underlying associations for PAAD immunotherapies. Methods: Genes that control the responsiveness of T cell-induced tumor destruction (GSTTK) were examined in PAAD, focusing on their varying expression levels and association with survival results. Moreover, samples with PAAD were separated into two subsets using unsupervised clustering based on GSTTK. Variability was evident in the tumor immune microenvironment, genetic mutation, and response to immunotherapy among different groups. In the end, we developed TRGscore, an innovative scoring system, and investigated its clinical and predictive significance in determining sensitivity to immunotherapy. Results: Patients with PAAD were categorized into 2 clusters based on the expression of 52 GSTTKs, which showed varying levels and prognostic relevance, revealing unique TTK patterns. Survival outcome, immune cell infiltration, immunotherapy responses, and functional enrichment are also distinguished among the two clusters. Moreover, we found the CATSPER1 gene promotes the progression of PAAD through experiments. In addition, the TRGscore effectively predicted the responses to chemotherapeutics or immunotherapy in patients with PAAD and overall survival. Conclusions: TTK exerted a vital influence on the tumor immune environment in PAAD. A greater understanding of TIME characteristics was gained through the evaluation of the variations in TTK modes across different tumor types. It highlights variations in the performance of T cells in PAAD and provides direction for improved treatment approaches.

Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

Effects and mechanisms of prussian blue nanozymes with multiple enzyme activities on nasopharyngeal carcinoma cells.

Prussian blue nanozymes (PBNs) with multiple enzyme activities are prepared and their activities of antitumor in nasopharyngeal carcinoma cells (CEN2) are also explored in this research. On the one hand, it shows that PBNs can exert the catalase-like (CAT-like) activity to decompose hydrogen peroxide (H2O2) into non-toxic H2O in CEN2 cells. The O2 release of H2O2 catalysed by PBNs effectively alleviates the hypoxic environment of tumors, which inhibits the glycolysis of tumor and reduces the production of lactic acid. On the other hand, we also find that PBNs also has peroxidase-like (POD-like) enzymatic activity, which can catalyze the production of·OH from H2O2 in tumor cells and result in tumor cell apoptosis. This study lays a solid biomedical foundation for the development of safe and non-toxic nanozymes, as well as the expansion of their application in tumor treatment.

Self-assembled miR-134-5p inhibitor nanoparticles ameliorate experimental bronchopulmonary dysplasia (BPD) via suppressing ferroptosis.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants with increased levels of reactive oxygen species (ROS) and ferroptosis. Herein, we designed a peptide-based nanoparticle to deliver therapeutic molecules to pulmonary, thereby ameliorating BPD. The BPD-induced damages of lung tissues were detected by H&E and immunohistochemistry staining. Inflammatory cytokines, Fe2+, and ROS levels were quantified by the indicated kits, respectively. The targeting relationship was verified by luciferase reporter assay and pull-down assay. Subsequently, self-assembled miR-134-5p inhibitor nanoparticles with pulmonary epithelial cell-targeting were synthesized. The characteristics were detected by transmission electron microscopy, luminescence imaging, and dynamic light scattering. A significant ferroptosis was observed in the BPD mice. The protein level of GPX4 was decreased significantly compared to the control group. Constantly, miR-134-5p showed positive regulation on ferroptosis by targeting GPX4. The designed nanoparticles were mainly accumulated in the lung region. Besides, it ameliorated experimental bronchopulmonary dysplasia via suppressing ferroptosis, in vivo and in vitro. Our findings provided a miR-134-5p/GPX4 axis in regulating ferroptosis of BPD and prompted the potential of applying the peptide-based nanoparticle to BPD treatment.

A Meta-analysis of Randomised Controlled Trials Comparing Combination Therapy as Second-line Treatment With Monotherapy in Advanced Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation.

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR mutation; however, resistance is common. Combinatorial strategies have been explored to improve survival. This meta-analysis assesses the efficacy and safety of combination therapy versus monotherapy in patients with advanced NSCLC who failed first-line EGFR-tyrosine kinase inhibitor treatment. METHODS: We searched randomized controlled trials from PubMed, Web of Science, Google Scholar, Cochrane Library, and ClinicalTrial.gov. The efficacy and toxicity of combination treatment groups were assessed in terms of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: This meta-analysis included 6 randomized controlled trials covering 785 participants. The results showed that the combined regimen arm had no significant improvement of PFS (log hazard ratio = -0.228, 95% CI: -0.543 to 0.087, P = 0.157), ORR (odds ratio = 1.147 [95% CI: 0.577, 2.281], P = 0.695), DCR (odds ratio = 1.578 [95% CI: 0.428, 5.821], P = 0.493), and AEs, including fatigue and diarrhea (odds ratio = 0.833 [95% CI: 0.297, 2.333], P = 0.728 for fatigue and odds ratio = 2.268 [95% CI: 0.544, 9.448], P = 0.261 for diarrhea). CONCLUSIONS: Combination therapy may not provide a significant improvement in PFS, ORR, DCR, and incidence of AEs compared with monotherapy in patients with advanced NSCLC with EGFR mutations. Further research is needed to investigate the optimal sequencing of combination therapy in patients with NSCLC with different molecular targets to determine the most effective treatment strategy that can improve outcomes and quality of life for these patients.

Innate immune response restarts adaptive immune response in tumors.

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the anti-tumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy.

Retrolaminar migration as a complication of intraocular silicone oil injection detected on unenhanced CT.

AIM: To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine and prone. METHODS: For this retrospective study, 29 patients who had a history of SiO injection treatment and underwent unenhanced head computed tomography (CT) were included from January 2019 to October 2022. The patients were divided into migration-positive and negative groups. Clinical history and CT features were compared using Whitney U and Fisher's exact tests. The dynamic position of SiO was observed within the ventricular system in supine and prone. CT images were visually assessed for SiO migration along the retrolaminar involving pathways for vision (optic nerve, chiasm, and tract) and ventricular system. RESULTS: Intraocular SiO migration was found in 5 of the 29 patients (17.24%), with SiO at the optic nerve head (n=1), optic nerve (n=4), optic chiasm (n=1), optic tract (n=1), and within lateral ventricles (n=1). The time interval between SiO injection and CT examination of migration-positive cases was significantly higher than that of migration-negative patients (22.8±16.5mo vs 13.1±2.6mo, P<0.001). The hyperdense lesion located in the frontal horns of the right lateral ventricle migrated to the fourth ventricle when changing the position from supine to prone. CONCLUSION: Although SiO retrolaminar migration is unusual, the clinician and radiologist should be aware of migration routes. The supine combined with prone examination is the first-choice method to confirm the presence of SiO in the ventricular system.

A Novel lncRNA FUAT1/TNS4 Axis Confers Chemoresistance by Suppressing Reactive Oxygen Species-Mediated Apoptosis in Gastric Cancer.

Aims: Reactive oxygen species (ROS) play a vital role in conveying the cytotoxicity and resistance of most chemotherapy drugs. Therefore, gaining a comprehensive understanding of the intricate activities against oxidative stress in cancer cells may provide valuable insights into the discovery of common mechanisms underlying chemoresistance. Results: We identified a novel long noncoding RNA (lncRNA), designated fluorouracil-associated transcript-1 (FUAT1), as a key nongenetic player involved in ROS-mediated intrinsic chemoresistance by employing a unique screening strategy based on transcriptome sequencing (RNA-Seq) technology. To investigate the precise role of the FUAT1 regulatory axis in chemoresistance, we conducted a series of in vitro and in vivo assays including gain/loss-of-function and rescue experiments. Mechanistically, our findings revealed that FUAT1 upregulates Tensin 4 (TNS4) by sponging miR-140-5p, which allows gastric cancer cells to survive chemotherapy by inhibiting ROS-mediated apoptosis. Clinically, we observed that the FUAT1/TNS4 regulatory axis is negatively associated with overall survival and progression-free survival among gastric and colon cancer patients treated with 5-fluorouracil adjuvant chemotherapy. Innovation: We devised a novel screening strategy distinct from conventional approaches using drug-resistant strains. Through this approach, we identified the previously unrecognized lncRNA FUAT1/TNS4 axis that plays a critical role in ROS-mediated intrinsic chemoresistance. Conclusions: Our findings shed light on fundamental adaptive mechanisms employed by cancer cells to respond to chemotherapy and provide new insights into developing strategies aiming at overcoming chemoresistance.

Quantitation of macropinocytosis in glioblastoma based on high-content analysis.

BACKGROUND: Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods. METHODS: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test. RESULTS: The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment. CONCLUSIONS: HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within the article and its supplementary materials.

[Research Progress in Oral Diseases and Oral Microbiota of Organ Transplant Patients].

Organ transplantation is an effective treatment for end-stage organ diseases. However, organ transplant recipients are susceptible to a wide variety of oral diseases, including gingival enlargement, periodontitis, oral mucosal diseases, oral malignant tumors, and dental caries. Oral microbiota may have played an important role in the organ transplant patients' increased susceptibility to oral diseases and is associated with adverse events after organ transplantation, which is gradually gaining more attention among scholars. We, herein, reviewed the common oral diseases, including periodontal tissue diseases, oral mucosal diseases, oral malignant tumors, and dental caries in organ transplantation patients. Furthermore, we discussed the characteristic changes in the oral microbiota of organ transplantation patients and the influencing factors of these changes. In-depth study of oral microbiota of organ transplant patients provides a reference for the prevention and treatment of relevant diseases after organ transplantation and serves an important role in oral and systemic health management of organ transplant patients.

Prognostic value of lncRNAs related to fatty acid metabolism in lung adenocarcinoma and their correlation with tumor microenvironment based on bioinformatics analysis.

Background: As a key regulator of metabolic pathways, long non-coding RNA (lncRNA) has received much attention for its relationship with reprogrammed fatty acid metabolism (FAM). This study aimed to investigate the role of the FAM-related lncRNAs in the prognostic management of patients with lung adenocarcinoma (LUAD) using bioinformatics analysis techniques. Methods: We obtained LUAD-related transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) database. The lncRNA risk models associated with FMA were constructed by single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network (WGCNA), differential expression analysis, overlap analysis, and Cox regression analysis. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were utilized to assess the predictive validity of the risk model. Gene set variation analysis (GSVA) revealed molecular mechanisms associated with the risk model. ssGSEA and microenvironment cell populations-counter (MCP-counter) demonstrated the immune landscape of LUAD patients. The relationships between lncRNAs, miRNAs, and mRNAs were predicted by using LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using DAVID v6.8. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of the prognostic lncRNAs. Results: We identified 249 differentially expressed FMA-related lncRNAs in TCGA-LUAD, six of which were used to construct a risk model with appreciable predictive power. GSVA results suggested that the risk model may be involved in regulating fatty acid synthesis/metabolism, gene repair, and immune/inflammatory responses in the LUAD process. Immune landscape analysis demonstrated a lower abundance of immune cells in the high-risk group of patients associated with poor prognosis. Moreover, we predicted 279 competing endogenous RNA (ceRNA) mechanisms for 6 prognostic lncRNAs with 39 miRNAs and 201 mRNAs. Functional enrichment analysis indicated that the ceRNA network may be involved in the process of LUAD by participating in genomic transcription, influencing the cell cycle, and regulating tissue and organogenesis. In vitro experiments showed that prognostic lncRNA CTA-384D8.35, lncRNA RP5-1059L7.1, and lncRNA Z83851.4 were significantly upregulated in LUAD primary tumor tissues, while lncRNA RP11-401P9.4, lncRNA CTA-384D8.35, and lncRNA RP11-259K15.2 were expressed at higher levels in paraneoplastic tissues. Conclusion: In summary, the prognostic factors identified in this study can be used as potential biomarkers for clinical applications. ceRNA network construction provides a new vision for the study of LUAD pathogenesis.

Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.

Background: It is well known that hypoxia and ferroptosis are intimately connected with tumor development. The purpose of this investigation was to identify whether they have a prognostic signature. To this end, genes related to hypoxia and ferroptosis scores were investigated using bioinformatics analysis to stratify the risk of lung adenocarcinoma. Methods: Hypoxia and ferroptosis scores were estimated using The Cancer Genome Atlas (TCGA) database-derived cohort transcriptome profiles via the single sample gene set enrichment analysis (ssGSEA) algorithm. The candidate genes associated with hypoxia and ferroptosis scores were identified using weighted correlation network analysis (WGCNA) and differential expression analysis. The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature. The efficacy, accuracy, and clinical value of the prognostic model were evaluated using an independent validation cohort, Receiver Operator Characteristic (ROC) curve, and nomogram. The analysis of function and immune cell infiltration was also carried out. Results: Here, we appraised 152 candidate genes expressed not the same, which were related to hypoxia and ferroptosis for prognostic modeling in The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort, and these genes were further validated in the GSE31210 cohort. We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma. ROC and nomogram analyses showed that risk scores based on prognostic signatures provided desirable predictive accuracy and clinical utility. Moreover, gene set variance analysis showed differential enrichment of 33 hallmark gene sets between different risk groups. Additionally, our results indicated that a higher risk score will lead to more fibroblasts and activated CD4 T cells but fewer myeloid dendritic cells, endothelial cells, eosinophils, immature dendritic cells, and neutrophils. Conclusion: Our research found a 14-gene signature and established a nomogram that accurately predicted the prognosis in patients with lung adenocarcinoma. Clinical decision-making and therapeutic customization may benefit from these results, which may serve as a valuable reference in the future.

Characterization of chromatin regulators identified prognosis and heterogeneity in hepatocellular carcinoma.

Liver carcinogenesis is a multiprocess that involves complicated interactions between genetics, epigenetics, and transcriptomic alterations. Aberrant chromatin regulator (CR) expressions, which are vital regulatory epigenetics, have been found to be associated with multiple biological processes. Nevertheless, the impression of CRs on tumor microenvironment remodeling and hepatocellular carcinoma (HCC) prognosis remains obscure. Thus, this study aimed to systematically analyze CR-related patterns and their correlation with genomic features, metabolism, cuproptosis activity, and clinicopathological features of patients with HCC in The Cancer Genome Atlas, International Cancer Genome Consortium-LIRI-JP cohort, and GSE14520 that utilized unsupervised consensus clustering. Three CR-related patterns were recognized, and the CRs phenotype-related gene signature (CRsscore) was developed using the least absolute shrinkage and selection operator-Cox regression and multivariate Cox algorithms to represent the individual CR-related pattern. Additionally, the CRsscore was an independent prognostic index that served as a fine predictor for energy metabolism and cuproptosis activity in HCC. Accordingly, describing a wide landscape of CR characteristics may assist us to illustrate the sealed association between epigenetics, energy metabolism, and cuproptosis activity. This study may discern new tumor therapeutic targets and exploit personalized therapy for patients.

Consumption of Wheat Peptides Improves Functional Constipation: A Translational Study in Humans and Mice.

SCOPE: Wheat peptides (WP) are rich in glutamic acid, glutamine, and other bioactive compounds that may benefit gut function and health. This study aims to evaluate the effects of regular consumption of WP on constipation-induced complications and gut microbiota in humans and mice. METHODS AND RESULTS: A randomized trial of 49 functional constipation participants is conducted. The weekly amount of spontaneous bowel movements (SBM) increases by 2.09 per week after WP treatment, and by 0.40 per week among the placebo group (PL). Concomitantly, the secondary outcomes show significant improvements in the quality of life-related to constipation (PAC-QOL), constipation severity, and satisfaction with the intervention. In the animal study, WP effectively alleviates constipation symptoms and affects the secretion of intestinal mobility-related neurotransmitters and gastrointestinal hormones in loperamide-induced constipation mice. Additionally, WP regulates the gene and protein expression levels of water-electrolyte metabolism and intestinal mobility. Furthermore, WP treatment decreases the abundance of several gut microbiota positively correlated to constipation (Turicibacter, Bacteroides_f_Bacteroidaceae, and Streptococcus) in mice. CONCLUSION: WP ameliorates constipation in humans and mice, which could be partly explained by improving water-electrolyte metabolism, boosting intestinal motility, and reshaping gut microbiota.