-
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were...
Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were collected from 25 UC patients and 25 healthy individuals at the General Hospital of Xizang Military Region. The expression levels of lncRNA H19 were detected, and the receiver operating characteristic (ROC) curve analysis was performed using serum samples. An in vitro inflammatory model was established in HT29 colorectal cells under lipopolysaccharide (LPS) stimulation, and the expression levels of lncRNA H19 were observed in HT29 cells through fluorescence quantitative PCR. HT29 cells with downregulated lncRNA H19 was constructed using lentivirus-mediated shRNA. The effect of lncRNA H19 on cell survival was analyzed through MTT assay. Cell apoptosis was detected by flow cytometry, and the protein expression levels of apoptosis and autophagy markers were analyzed through Western blot. After treatment with rapamycin, the survival of HT29 cells was observed by MTT assay. Results lncRNA H19 was highly expressed in the colonic mucosa and serum samples of UC patients with the ROC area being 0.786. Following LPS stimulation, the expression levels of lncRNA H19 was significantly increased in a time-dependent manner. Downregulation of lncRNA H19 can promote cell survival, inhibit cell apoptosis and increase autophagy level in HT29 cells. Treatment with rapamycin significantly increased the cell survival rate. Conclusion Knock-down of lncRNA H19 increases autophagy levels, inhibits LPS-induced apoptosis and promotes the survival of colon cells.
Topics: Humans; RNA, Long Noncoding; Apoptosis; Autophagy; Lipopolysaccharides; Colitis, Ulcerative; HT29 Cells; Male; Female; Middle Aged; Adult; Gene Knockdown Techniques
PubMed: 38952094
DOI: No ID Found -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal...
[Vitamin D3 alleviates the gastritis that associated with Helicobacter pylori infection in mice with hypercholesterolemia by enhancing the activity of vitamin D receptors in the liver tissue and blocking the signaling pathway of JAK/STAT3].
Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Methods High-cholesterol mouse model and Hp infected mouse model were established. Each was treated with VD3 via oral administration for 8 weeks. Real-time quantitative PCR was used to detect the expression of vitamin D receptor (VDR), insulin-induced gene 2 (Insig-2), and gastrin mRNA. Western blot analysis was used to examine the expression of JAK, STAT3, and cyclooxygenase-2 (COX2) proteins in gastric tissues. Biochemical analyses were performed to measure serum cholesterol levels, and ELISA was utilized to evaluate serum gastrin, interleukin 6 (IL-6), and IL-8 levels, along with histopathological examination of liver and gastric tissues using HE staining. Results After oral administration of VD3, the levels of VDR and Insig-2 in mouse liver tissue significantly increased in the high cholesterol group and the high cholesterol combined with Hp infection group. And the expression of serum gastrin decreased. The expression of JAK, STAT3 in gastric tissues reduced, as did the expression of COX2. Serum cholesterol levels decreased, with no significant changes in IL-6 levels, but a reduction in IL-8 levels. Compared to the control group, the high cholesterol combined with Hp infection group showed reduced hepatic ballooning degeneration and alleviated gastric tissue inflammation. In addition, inflammation in gastric tissue was also reduced in the cholesterol group and the Hp infection group. Conclusion VD3 alleviates gastritis by enhancing the activity of VDR in liver tissues, blocking the JAK/STAT3 signaling pathway, and inhibiting the expression of inflammatory factors.
Topics: Animals; Helicobacter Infections; STAT3 Transcription Factor; Cholecalciferol; Receptors, Calcitriol; Signal Transduction; Liver; Mice; Janus Kinases; Gastritis; Male; Helicobacter pylori; Hypercholesterolemia
PubMed: 38952091
DOI: No ID Found -
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi =... Jun 2024Objective To investigate the significance of nucleoporin 85 (NUP85) ex-pression in hepatocellular carcinoma (HCC) and analyze its relevance to immune response. Methods A...
Objective To investigate the significance of nucleoporin 85 (NUP85) ex-pression in hepatocellular carcinoma (HCC) and analyze its relevance to immune response. Methods A comprehensive analysis was conducted using various online databases to assess the mRNA and protein expression of NUP85 in HCC, as well as its mutation status and prognostic diagnostic value. The immune relevance of NUP85 was evaluated using single-cell sequencing data and resources from the Tumor Immune Estimation Resource (TIMER) and the Gene Expression Profiling Interactive Analysis 2021 (GEPIA2021) databases. The drug sensitivity of NUP85 was analyzed through the Genomic Landscape of Cancer (GSCA) and the Clinical Bioinformatics Home. Co-expressed genes of NUP85 in HCC were filtered using the Hepatocellular Carcinoma Comprehensive Molecular Database (HCCDB), and the correlation between NUP85 and its related genes was analyzed using the R language "limma" package. The gene ontology (GO) functions, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) of NUP85 and its related genes were performed using the R language "clusterProfiler" package. The Clinical Bioinformatics Home was utilized to construct heatmaps and prognostic risk scoring models for NUP85 and its related genes. Results NUP85 mRNA and protein expression were upregulated in HCC, showing high levels across dif-ferent stages and grades, which indicates a poor prognosis for patients. The mutation rate of NUP85 in HCC samples was 19%, significantly affecting the overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) of patients. NUP85 was highly expressed in various immune cells, including macrophages, B cells, and T cells, and was positively correlated with the infiltration levels of multiple immune cells. The expression of NUP85 was significantly correlated with multiple drugs, such as Milademetan (PD0325901), a structural analog of Vemurafenib (PLX4720), and Regorafenib (PD0325901). The GO functions of NUP85 and its co-expressed genes were mainly enriched in organelle fission, nuclear division, and chromosome segregation, while the KEGG pathways were primarily enriched in the cell cycle and kinesin proteins. These factors significantly and unfavorably affected the OS of HCC patients, and the areas under the ROC curve (AUC) for the 1-year, 3-year, and 5-year OS prognostic diagnosis of HCC patients were all greater than 0.7. Conclusion The high expression of NUP85 in HCC is correlated with a poor prognosis and is related to various immune cells and drugs, making it a potential biomarker for di-agnosis, treatment, and prognosis in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Nuclear Pore Complex Proteins; Prognosis; Gene Expression Regulation, Neoplastic; Male
PubMed: 38952090
DOI: No ID Found -
Virulence Dec 2024Vancomycin-resistant () infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling...
Vancomycin-resistant () infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing , but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.
Topics: Animals; Peritonitis; Mice; Disease Models, Animal; Enterococcus faecium; Gram-Positive Bacterial Infections; Host-Pathogen Interactions; Vancomycin-Resistant Enterococci; Sepsis; Cytokines; Mice, Inbred C57BL; Macrophages; Signal Transduction
PubMed: 38951957
DOI: 10.1080/21505594.2024.2367659 -
Microbiome Jun 2024Shotgun metagenomics for microbial community survey recovers enormous amount of information for microbial genomes that include their abundances, taxonomic, and...
BACKGROUND
Shotgun metagenomics for microbial community survey recovers enormous amount of information for microbial genomes that include their abundances, taxonomic, and phylogenetic information, as well as their genomic makeup, the latter of which then helps retrieve their function based on annotated gene products, mRNA, protein, and metabolites. Within the context of a specific hypothesis, additional modalities are often included, to give host-microbiome interaction. For example, in human-associated microbiome projects, it has become increasingly common to include host immunology through flow cytometry. Whilst there are plenty of software approaches available, some that utilize marker-based and assembly-based approaches, for downstream statistical analyses, there is still a dearth of statistical tools that help consolidate all such information in a single platform. By virtue of stringent computational requirements, the statistical workflow is often passive with limited visual exploration.
RESULTS
In this study, we have developed a Java-based statistical framework ( https://github.com/KociOrges/cviewer ) to explore shotgun metagenomics data, which integrates seamlessly with conventional pipelines and offers exploratory as well as hypothesis-driven analyses. The end product is a highly interactive toolkit with a multiple document interface, which makes it easier for a person without specialized knowledge to perform analysis of multiomics datasets and unravel biologically relevant patterns. We have designed algorithms based on frequently used numerical ecology and machine learning principles, with value-driven from integrated omics tools which not only find correlations amongst different datasets but also provide discrimination based on case-control relationships.
CONCLUSIONS
CViewer was used to analyse two distinct metagenomic datasets with varying complexities. These include a dietary intervention study to understand Crohn's disease changes during a dietary treatment to include remission, as well as a gut microbiome profile for an obesity dataset comparing subjects who suffer from obesity of different aetiologies and against controls who were lean. Complete analyses of both studies in CViewer then provide very powerful mechanistic insights that corroborate with the published literature and demonstrate its full potential. Video Abstract.
Topics: Metagenomics; Humans; Software; Microbiota; Gastrointestinal Microbiome; Computational Biology; Metagenome; Crohn Disease
PubMed: 38951915
DOI: 10.1186/s40168-024-01834-9 -
Journal of Nanobiotechnology Jul 2024Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to... (Review)
Review
Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.
Topics: Hydrogels; Liver Neoplasms; Carcinoma, Hepatocellular; Humans; Animals; Embolization, Therapeutic
PubMed: 38951911
DOI: 10.1186/s12951-024-02547-9 -
Journal of Biomedical Science Jun 2024Cholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and...
BACKGROUND
Cholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated.
METHODS
Extrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8 T cells were performed to study the immune-suppressive effect of phenotypic-altered neutrophils. Clinical samples collected from colorectal cancer patients with liver metastasis and cholestasis were applied to RNA-Seq.
RESULTS
Compared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-β-muricholic acid (Tβ-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8 T cells, indicating that the immunosuppressive phenotype of neutrophils was directly induced by BAs. Importantly, targeting BA anabolism with Obeticholic acid (OCA) under cholestasis effectively suppressed liver metastasis progression, enhanced the efficacy of immune checkpoint blockade, and prolonged survival of mice.
CONCLUSIONS
Our study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism.
Topics: Animals; Neutrophils; Mice; Liver Neoplasms; Colorectal Neoplasms; Cholestasis; Tumor Microenvironment; Male; Mice, Inbred C57BL; Humans; Disease Models, Animal
PubMed: 38951890
DOI: 10.1186/s12929-024-01052-3 -
Journal of Translational Medicine Jul 2024Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM...
BACKGROUND
Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM development, however, not only the role of vascular endothelial dysfunction in UM remains unknown, but also their analysis at the single-cell level has been lacking. A comprehensive analysis is essential to clarify the role of the endothelium in the development of UM.
METHODS
By using single-cell RNA transcriptomics data of 11 cases of primary and liver metastasis UM, we analyzed the endothelial cell status. In addition, we analyzed and validated ECs in the in vitro model and collected clinical specimens. Subsequently, we explored the impact of endothelial dysfunction on UM cell migration and explored the mechanisms responsible for the endothelial cell abnormalities and the reasons for their peripheral effects.
RESULTS
UM metastasis has a significantly higher percentage of vascular endothelial cells compared to in situ tumors, and endothelial cells in metastasis show significant senescence. Senescent endothelial cells in metastatic tumors showed significant Krüppel-like factor 4 (KLF4) upregulation, overexpression of KLF4 in normal endothelial cells induced senescence, and knockdown of KLF4 in senescent endothelium inhibited senescence, suggesting that KLF4 is a driver gene for endothelial senescence. KLF4-induced endothelial senescence drove tumor cell migration through a senescence-associated secretory phenotype (SASP), of which the most important component of the effector was CXCL12 (C-X-C motif chemokine ligand 12), and participated in the composition of the immunosuppressive microenvironment.
CONCLUSION
This study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.
Topics: Humans; Uveal Neoplasms; Melanoma; Liver Neoplasms; Endothelial Cells; Single-Cell Analysis; Kruppel-Like Factor 4; Cell Movement; Cellular Senescence; Kruppel-Like Transcription Factors; Cell Line, Tumor; Chemokine CXCL12; Gene Expression Regulation, Neoplastic; Female; Male
PubMed: 38951874
DOI: 10.1186/s12967-024-05430-1 -
European Journal of Medical Research Jul 2024Esophageal perforations are a complex clinical scenario that have been poorly studied. To date, there is no grading of esophageal perforations, the reason being that the...
OBJECTIVES
Esophageal perforations are a complex clinical scenario that have been poorly studied. To date, there is no grading of esophageal perforations, the reason being that the outcome is very heterogeneous, because the perforation is very heterogeneous. A grading of the severity of the perforation may guide treatment, and could ultimately affect morbidity and mortality.
METHODS
The observation period of the study was four years. All patients with a perforation of the esophagus aged 18 to 90 years were included. All anastomotic insufficiencies or fistulas after surgery of the esophagus were excluded. The cause of the injury and the time interval between the event and the start of therapy were analyzed. The severity of each perforation was classified based on the results of a diagnostic CT scan, gastroscopy as well as clinical and laboratory findings. Therapy and signs of infection were evaluated. Endpoints of the study were patient recovery or death. The study was conducted as a retrospective single-center study at a university hospital of Düsseldorf. The study has been approved by the review board. Patients gave their informed consent before data collection. All data were analyzed using SPSS 29 (IBM SPSS Statistics software).
RESULTS
Age, gender and cause of the esophageal perforation did not impact significantly on overall survival. The duration of injury > 24 h (p = 0.01), presence of mediastinitis (p = 0.01) and necrosis of the esophagus (p = 0.02) were associated with an unfavorable outcome. The correlation of the clinical grading of the severity of the perforation based on the endoscopic, radiological and clinical findings with the overall survival of patients was significant. Patients categorized into the four grades of severity (I-IV) had an overall survival of 100%, 100%, 70% and 50%, respectively.
CONCLUSION
The severity of esophageal perforations can be systematically rated grades I to IV based on the radiological, endoscopic and clinical findings at diagnosis. Due to the grading and its correlation to the overall survival, a comparison of patients, their treatment and outcome becomes possible. In future, the grade of a perforation may guide treatment, and therefore affect morbidity and mortality.
Topics: Humans; Esophageal Perforation; Male; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Adolescent; Retrospective Studies; Young Adult
PubMed: 38951825
DOI: 10.1186/s40001-024-01910-8 -
Journal of Translational Medicine Jul 2024The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients' clinical outcomes. However, the prognostic...
BACKGROUND
The spatial context of tumor-infiltrating immune cells (TIICs) is important in predicting colorectal cancer (CRC) patients' clinical outcomes. However, the prognostic value of the TIIC spatial distribution is unknown. Thus, we aimed to investigate the association between TIICs in situ and patient prognosis in a large CRC sample.
METHODS
We implemented multiplex immunohistochemistry staining technology in 190 CRC samples to quantify 14 TIIC subgroups in situ. To delineate the spatial relationship of TIICs to tumor cells, tissue slides were segmented into tumor cell and microenvironment compartments based on image recognition technology, and the distance between immune and tumor cells was calculated by implementing the computational pipeline phenoptr.
RESULTS
MPO neutrophils and CD68IDO1 tumor-associated macrophages (TAMs) were enriched in the epithelial compartment, and myeloid lineage cells were located nearest to tumor cells. Except for CD68CD163 TAMs, other cells were all positively associated with favorable prognosis. The prognostic predictive power of TIICs was highly related to their distance to tumor cells. Unsupervised clustering analysis divided colorectal cancer into three subtypes with distinct prognostic outcomes, and correlation analysis revealed the synergy among B cells, CD68IDO1TAMs, and T lineage cells in producing an effective immune response.
CONCLUSIONS
Our study suggests that the integration of spatial localization with TIIC abundance is important for comprehensive prognostic assessment.
Topics: Humans; Colorectal Neoplasms; Prognosis; Male; Female; Middle Aged; Tumor Microenvironment; Cluster Analysis; Aged; Lymphocytes, Tumor-Infiltrating; Immunohistochemistry; Macrophages; Spatial Analysis
PubMed: 38951801
DOI: 10.1186/s12967-024-05418-x