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International Journal of Biological... Jun 2024Nanocellulose (NC) is a promising biopolymer for various biomedical applications owing to its biocompatibility and low toxicity. However, it faces challenges in tissue...
Nanocellulose (NC) is a promising biopolymer for various biomedical applications owing to its biocompatibility and low toxicity. However, it faces challenges in tissue engineering (TE) applications due to the inconsistency of the microenvironment within the NC-based scaffolds with target tissues, including anisotropy microstructure and biomechanics. To address this challenge, a facile swelling-induced nanofiber alignment and a novel in situ biomineralization reinforcement strategies were developed for the preparation of NC-based scaffolds with tunable anisotropic structure and mechanical strength for guiding the differentiation of bone marrow-derived mesenchymal stem cells for potential TE application. The bacterial cellulose (BC) and cellulose nanofibrils (CNFs) based scaffolds with tunable swelling anisotropic index in the range of 10-100 could be prepared by controlling the swelling medium. The in situ biomineralization efficiently reinforced the scaffolds with 2-4 times and 10-20 times modulus increasement for BC and CNFs, respectively. The scaffolds with higher mechanical strength were superior in supporting cell growth and proliferation, suggesting the potential application in TE application. This work demonstrated the feasibility of the proposed strategy in the preparation of scaffolds with mechanical anisotropy to induce cells-directed differentiation for TE applications.
PubMed: 38944070
DOI: 10.1016/j.ijbiomac.2024.133515 -
Ecotoxicology and Environmental Safety Jun 2024Gastric cancer is a leading cause of cancer-related deaths influenced by both genetic and environmental factors. Triphenyl phosphate (TPP) is a prevalent flame...
BACKGROUND
Gastric cancer is a leading cause of cancer-related deaths influenced by both genetic and environmental factors. Triphenyl phosphate (TPP) is a prevalent flame retardant, but its health implications remain to be thoroughly understood.
OBJECTIVE
To explore the link between TPP exposure and gastric cancer by examining gene expression patterns and developing a predictive model.
METHODS
Gene expression data were sourced from The Cancer Genome Atlas (TCGA) and the Comparative Toxicogenomics Database (CTD). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were employed for analysis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to obtain phosphate flame retardant-related scores. A predictive model was constructed through differential analysis, univariate COX regression, and LASSO regression. Molecular docking was performed to assess protein interactions with TPP.
RESULTS
ssGSEA identified scores related to phosphate flame retardants in gastric cancer, which had a strong association with immune-related traits. Several genes associated with TPP were identified and used to develop a prognostic model that has clinical significance. Molecular docking showed a high binding affinity of TPP with MTTP, a gene related to lipid metabolism. Pathway analysis indicated that TPP exposure contributes to gastric cancer through lipid metabolic processes.
CONCLUSION
The study establishes a potential correlation between TPP exposure and gastric cancer onset, pinpointing key genes and pathways involved. This underscores the significance of environmental factors in gastric cancer research and presents a potential diagnostic tool for clinical application.
PubMed: 38944011
DOI: 10.1016/j.ecoenv.2024.116618 -
Ecotoxicology and Environmental Safety Jun 2024Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts...
Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3β and elevate the levels of β-catenin, thereby activating the Wnt/β-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/β-catenin signaling pathway.
PubMed: 38944010
DOI: 10.1016/j.ecoenv.2024.116602 -
International Immunopharmacology Jun 2024Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved...
BACKGROUND AND AIMS
Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear.
METHODS
The expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter.
RESULTS
EMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells.
CONCLUSIONS
EMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.
PubMed: 38943975
DOI: 10.1016/j.intimp.2024.112553 -
International Immunopharmacology Jun 2024Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs)...
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.
PubMed: 38943969
DOI: 10.1016/j.intimp.2024.112547 -
Translational Oncology Jun 2024Tumor derived Extracellular vesicles (EVs) in circulating system may contain tumor-specific markers, and EV detection in body fluids could become an important tool for...
Tumor derived Extracellular vesicles (EVs) in circulating system may contain tumor-specific markers, and EV detection in body fluids could become an important tool for early tumor diagnosis, prognosis assessment. Meningiomas are the most common benign intracranial tumors, few studies have revealed specific protein markers for meningiomas from patients' body fluids. In this study, using proximity labeling technology and non-tumor patient plasma as a control, we detected protein levels of EVs in plasma samples from meningioma patients before and after surgery. Through bioinformatics analysis, we discovered that the levels of EV count and protein count in meningioma patients were significantly higher than those in healthy controls, and were significantly decreased postoperatively. Among EV proteins in meningioma patients, the levels of MUC1, SIGLEC11, E-Cadherin, KIT, and TASCTD2 were found not only significantly elevated than those in healthy controls, but also significantly decreased after tumor resection. Moreover, using publicly available GEO databases, we verified that the mRNA level of MUC1, SIGLEC11, and CDH1 in meningiomas were significantly higher in comparison with normal dura mater tissues. Additionally, by analyzing human meningioma specimens collected in this study, we validated the protein levels of MUC1 and SIGLEC11 were significantly increased in WHO grade 2 meningiomas and were positively correlated with tumor proliferation levels. This study indicates that meningiomas secret EV proteins into circulating system, which may serve as specific markers for diagnosis, malignancy predicting and tumor recurrent assessment.
PubMed: 38943923
DOI: 10.1016/j.tranon.2024.102046 -
Biochimica Et Biophysica Acta.... Jun 2024Toll-like receptor 9 (Tlr9) is a pathogen recognition receptor detecting unmethylated DNA derivatives of pathogens and damaged host cells. It is therefore an important...
BACKGROUND & AIMS
Toll-like receptor 9 (Tlr9) is a pathogen recognition receptor detecting unmethylated DNA derivatives of pathogens and damaged host cells. It is therefore an important modulator of innate immunity. Here we investigated the role of Tlr9 in fibrogenesis and progression of hepatocellular carcinoma in chronic liver disease.
MATERIALS AND METHODS
We treated mice with a constitutive deletion of Tlr9 (Tlr9) with DEN/CCl for 24 weeks. As a second model, we used hepatocyte-specific Nemo knockout (Nemo) mice and generated double knockout (NemoTlr9) animals.
RESULTS
We show that Tlr9 is in the liver primarily expressed in Kupffer cells, suggesting a key role of Tlr9 in intercellular communication during hepatic injury. Tlr9 deletion resulted in reduced liver fibrosis as well as tumor burden. We observed down-regulation of hepatic stellate cell activation and consequently decreased collagen production in both models. Tlr9 deletion was associated with decreased apoptosis and compensatory proliferation of hepatocytes, modulating the initiation and progression of hepatocarcinogenesis. These findings were accompanied by a decrease in interferon-β and an increase in chemokines having an anti-tumoral effect.
CONCLUSIONS
Our data define Tlr9 as an important receptor involved in fibrogenesis, but also in the initiation and progression of hepatocellular carcinoma during chronic liver diseases.
PubMed: 38943920
DOI: 10.1016/j.bbadis.2024.167321 -
European Journal of Cancer (Oxford,... Jun 2024Circulating tumor DNA (ctDNA) has emerged as a promising tool for early cancer detection and minimal residual disease monitoring. However, the biology underlying ctDNA...
BACKGROUND
Circulating tumor DNA (ctDNA) has emerged as a promising tool for early cancer detection and minimal residual disease monitoring. However, the biology underlying ctDNA release and its variation across cancer types and histologies remains poorly understood. This study investigated the biology behind ctDNA shedding in colorectal cancer.
METHODS
The study included a local cohort of 747 stage I-III colorectal cancer patients. All patients had ctDNA measurement prior to treatment and extensive clinical data. Primary tumor RNA sequencing and whole exome sequencing was performed in 95 and 652 patients respectively. Additionally, the study evaluated 89 non-small cell lung cancer patients from the TRACERx cohort, comprising primary tumor RNA sequencing and ctDNA measurement.
RESULTS
We found tumor size and proliferative capacity to be key factors associated with ctDNA shedding in colorectal cancer. Furthermore, we found that the secretory and CMS3 colorectal cancer subtypes exhibited lower ctDNA shedding, while microsatellite instability (MSI) tumors had higher levels of ctDNA. Mutational analysis did not reveal any genes or pathways associated with ctDNA shedding in colorectal cancer. A comparison of transcriptomic profiles across multiple cancer types demonstrated that colorectal cancer and lung squamous cell carcinoma tumors shared a high-proliferative ctDNA shedding phenotype, while lung adenocarcinoma tumors displayed a distinct low-proliferative subgroup. Additionally, proliferation levels correlated with ctDNA detection sensitivity across multiple cancer types.
CONCLUSION
These findings suggest that tumor size and proliferative capacity are drivers of ctDNA release in colorectal cancer and provide insights into the biology of ctDNA shedding on a pan-cancer level.
PubMed: 38943900
DOI: 10.1016/j.ejca.2024.114186 -
Theriogenology Jun 2024This study examined how the vitrification of pig blastocysts using either the superfine open pulled straw (SOPS) or Cryotop method affects the expression profile of...
This study examined how the vitrification of pig blastocysts using either the superfine open pulled straw (SOPS) or Cryotop method affects the expression profile of embryonic microRNA (miRNA) transcriptomes, as well as its relation to changes in the expression of target genes (TGs). Surgically collected pig blastocysts were vitrified using either the SOPS method (n = 60; 4-6 embryos/device) or the Cryotop system (n = 60; 20 embryos/device). Embryos were cultured in vitro for 24 h after warming. Fresh blastocysts (n = 60) cultured for 24 h served as controls. After in vitro culture, five pools of eight viable blastocysts from each group were prepared for miRNA expression analysis based on a microarray approach. Then, biological interpretation of miRNAs profiles and integrative analysis of miRNA and mRNA transcriptome data were performed. Survival after 24 h of in vitro culture was similar (>96 %) for both the vitrification systems and the control group (100 %). Compared with the controls, the SOPS-vitrified blastocysts had 94 (one upregulated and 93 downregulated) differentially expressed (DE) miRNAs, and the Cryotop-vitrified blastocysts had 174 DE miRNAs (one upregulated and 173 downregulated). One DE miRNA (miR-503) in the SOPS group and three DE miRNAs (miR-7139-3p, miR-214 and miR-885-3p) in the Cryotop group were annotated for Sus scrofa. The integrative analysis showed that 27 and 61 DE TGs were regulated by the DE miRNAs in blastocysts vitrified with the SOPS and Cryotop systems, respectively. The TGs enriched one pathway (the TGF-β signaling pathway) for the SOPS system and four pathways (HIF-1, Notch, ascorbate and aldarate metabolism and glycosphingolipid biosynthesis-ganglio series) for the Cryotop system. In summary, vitrification via the SOPS and Cryotop systems dysregulates miRNAs, with slight differences between methods. The altered miRNAs identified in this study were related mainly to cell proliferation, apoptosis, and the response to cell stress. Further studies are needed to clarify the consequences of dysregulation of miRNAs involved in the TGF-β (SOPS-vitrified blastocyst) and Notch (Cryotop-vitrified blastocyst) signaling pathways, particularly if they can affect embryonic development.
PubMed: 38943899
DOI: 10.1016/j.theriogenology.2024.06.001 -
Journal of Hazardous Materials Jun 2024The rapid proliferation of the halophilic pathogen Vibrio parahaemolyticus poses a severe health hazard to halobios and significantly impedes intensive mariculture. This...
The rapid proliferation of the halophilic pathogen Vibrio parahaemolyticus poses a severe health hazard to halobios and significantly impedes intensive mariculture. This study aimed to evaluate the potential application of gliding arc discharge plasma (GADP) to control the infection of Vibrio parahaemolyticus in mariculture. This study investigated the inactivation ability of GADP against Vibrio parahaemolyticus in artificial seawater (ASW), changes in the water quality of GADP-treated ASW, and possible inactivation mechanisms of GADP against Vibrio parahaemolyticus in ASW. The results indicate that GADP effectively inactivated Vibrio parahaemolyticus in ASW. As the volume of ASW increased, the time required for GADP sterilization also increased. However, the complete sterilization of 5000 mL of ASW containing Vibrio parahaemolyticus of approximately 1.0 × 10 CFU/mL was achieved within 20 min. Water quality tests of the GADP-treated ASW demonstrated that there were no significant changes in salinity or temperature when Vibrio parahaemolyticus (1.0 ×10 CFU/mL) was completely inactivated. In contrast to the acidification observed in plasma-activated water (PAW) in most studies, the pH of ASW did not decrease after treatment with GADP. The HO concentration in the GADP-treated ASW decreased after post-treatment. The NOconcentration in the GADP-treated ASW remained unchanged after post-treatment. Further analysis revealed that GADP induced oxidative stress in Vibrio parahaemolyticus, which increased cell membrane permeability and intracellular ROS levels of Vibrio parahaemolyticus. This study provides a viable solution for infection with the halophilic pathogen Vibrio parahaemolyticus and demonstrates the potential of GADP in mariculture.
PubMed: 38943886
DOI: 10.1016/j.jhazmat.2024.135015