Exosomes derived from ITGB1 modified Telocytes alleviates LPS-induced inflammation and oxidative stress through YAP1/ROS axis.

Aims: Previous studies have demonstrated a significant upregulation of Integrin Beta 1 (ITGB1) in Telocytes. This study aims to explore the roles and underlying mechanisms of ITGB1 in inflammation and oxidative stress following Lipo-polysaccharide (LPS) administration in Telocytes. Methods: We observed an increase in reactive oxygen species (ROS) production, accompanied by a reduction in ITGB1 levels post-LPS treatment. Results: Notably, inhibiting ROS synthesis markedly reduced LPS-induced ITGB1 expression. Additionally, ectopic ITGB1 expression mitigated LPS-induced inflammation and oxidative stress, evident through decreased levels of pro-inflammatory markers such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1ß, IL-6, and Monocyte Chemoattractant Protein (MCP)-1. Depletion of endothelial Yes-Associated Protein 1 (YAP1) notably diminished the levels of inflammatory markers and ROS production. Furthermore, exosomes secreted by ITGB1-modified Telocytes promoted Human Umbilical Vein Endothelial Cells (HUVECs) proliferation and inhibited apoptosis. In vivo experiments revealed that exosomes from ITGB1-modified Telocytes modulated functional and structural changes, as well as inflammatory responses in Acute Lung Injury (ALI). Conclusion: These findings highlight the critical role of the YAP1/ROS axis in LPS-induced Telocyte injuries, underlining the therapeutic potential of targeting ITGB1 for mitigating inflammation and oxidative stress in these cells.

Function and prognostic value of N6-methyladenosine-modified RNAs in lung adenocarcinoma.

BACKGROUND: Aberrant regulation of N6-methyladenosine (m6A) modification is reportedly vital for cancer progression, including lung adenocarcinoma (LUAD). However, current studies mainly focus on the function and mechanism of m6A-modified regulators, such as m6A writers (METTL3 and METTL14), erasers (ALKBH5 and FTO), and readers (YTHDF1 and YTHDF2). The landscape, function, and prognostic value of RNAs by m6A-modified have not been fully clarified until now. METHODS: The present study identified 57 RNAs with significantly different m6A-methylation levels in LUAD tissues using epitranscriptomic microarray analysis. RESULTS: Among the 57 RNAs, 28 and 29 were hypermethylated and hypomethylated, respectively. The m6A-methylation level increased in mRNA and long non-coding RNA (lncRNA) but decreased in small non-coding RNA. After pathway enrichment analyses, RNA metabolism-associated pathways such as nucleotide metabolism were enriched in total and m6A-hypermethylated mRNAs. Furthermore, lncRNA networks were built using miRNet tools, revealing that the immune system was closed to m6A-modified lncRNAs. To evaluate the prognostic value of mRNAs with hypermethylated or hypomethylated, we calculated the risk scores, and constructed signatures to predict the survival time of patients with LUAD using multicox regression analysis. In addition, hypermethylated-mRNA and hypomethylated-mRNA signatures were established. The survival plotter showed that these two signatures effectively predicted the survival time of patients with LUAD. CONCLUSIONS: The results of the present study support the evidence for understanding the expression, function, and potential prognostic values of m6A-modified RNAs, possibly promoting effective therapies for patients with LUAD.

Signature and Molecular Mechanism of Mitochondrial Energy Metabolism Pathway-Related Genes in Lung Adenocarcinoma.

Objective: The mitochondrial energy metabolic pathway (MEMP) is the primary energy metabolism of tumor cells, and its disruption may promote cancer emergence, spreading, and immune escape. However, there is a lack of studies to determine the relationship between relevant functional mechanisms and lung adenocarcinoma (LUAD) prognosis. Methods: Gene set enrichment analysis (GSEA) was employed to determine MEMP pathway-related genes. Then, a prognostic model was created using the MEMP key genes that were found by LASSO-Cox regression analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided the training and validation sets. Furthermore, the infiltration of immune cells was examined by ssGSEA. Finally, a screening of candidate therapeutic compounds for LUAD patients was performed using DrugBank, Protein Data Bank (PDB), and AutoDock Vina databases. Results: First, 266 MEMP pathway-related genes that exhibited aberrant activity in tumors were identified. Then, 19 MEMP key genes were used to build a prognostic model, which can successfully predict the survival rates of LUAD patients after 1, 3, and 5 years, respectively. The Kaplan-Meier curve showed that patients in the high-risk group had considerably lower survival outcomes than those in the low-risk group. Furthermore, it was discovered that the high-risk group had the majority of activated T cells, while the low-risk group tended to have more other activated immune cells. The majority of immunological checkpoints expressed themselves more strongly in the high-risk group as well. Finally, 11 prospective medication small molecules were obtained from the projected potential therapeutic drugs, with DB0980 being regarded as the most promising of them for the treatment of LUAD. Conclusion: This current study developed reliable prognostic signature, called MEMP score, which provides new guidance for prognostic assessment, immunotherapy, and drug development in LUAD. Thereby, DB0980 appears to be the most likely approach for the treatment of LUAD.

Influence of salinity on the heterogeneous catalytic ozonation process: Implications to treatment of high salinity wastewater.

The heterogeneous catalytic ozonation process is a promising treatment option for high salinity reverse osmosis concentrate (ROC) however the influence of salts on the catalyst performance is not well understood. In this work, we investigate the effect of salts on the performance of the catalytic ozonation process for treatment of synthetic ROC using a commercially available Fe-loaded Al2O3 catalyst. Our results show that the presence of salts influences the rate and extent of degradation of organic compounds present in the synthetic ROC when subjected to the heterogeneous catalytic ozonation process. Scavenging of aqueous O3 by chloride ions and/or transformation of organics (particularly humics) to more hydrophobic form as a result of charge shielding between adjacent functional groups and/or intramolecular binding by cations inhibits the bulk oxidation of organics to a measurable extent. While the scavenging of aqueous hydroxyl radicals at the salt concentrations investigated here was minimal, the accumulation of chloride ions in the electric double layer near the catalyst surface, particularly when pH< pHpzc, results in more significant scavenging of surface associated hydroxyl radicals. Overall, the presence of salts (particularly chloride ions) has a significant influence on the performance of both conventional and catalytic ozonation processes with some scope to mitigate this effect through appropriate choice of catalyst.

Histopathologic characteristics and immunotypes of perivascular epithelioid cell tumors (PEComa).

OBJECTIVES: In order to provide further evidence for the origin and differentiation of PEComa, the clinicopathologic and immunophenotype findings were analyzed in 26 cases with literature review. METHODS: Immunohistochemistry and special staining were used. RESULTS: Multinucleated giant cells and polymorphism were scattered visibly in 53.8% and 76.9% of the cases and spotty necrosis and hemorrhage were observed in 38% of the cases. Capsular micro-invasion was detected in 46% cases accompanied by hemorrhage and/or necrosis in the tumors with diameters larger than 5 cm. It was also found that 100% of cases diffusely expressed SMA, Melan-A, and vimentin except one negative for HMB-45. The tumor cells partly expressed CD56, CD99, desmin, and S-100 and were negative for CK-pan, TFE3, CD117, CD44, and CD34. Clinical follow-up found that 22 out of 23 patients were alive, with no recurrence or progression, ranging from 42 to 82 months. However, one patient died from leukemia. CONCLUSIONS: In this study, the histopathologic features with the co-expressions of SMA and melanin, were the diagnostic basis of PEComas. The interspersed expressions of desmin and S-100 were helpful for the differential diagnosis of leiomyoma and neuroma. The expressions of S-100, CD56, and CD99 supported the origins of the pluripotent cells from the neural crests. Tumors larger than 5 cm in diameter with micro-hemorrhaging/necrosis and micro-capsular invasions should be considered either uncertain or of malignant potential. The spontaneous rupturing of blood vessels may be related to the amyloidosis and desmin negative expression, and broken elastic fibers.