Exosomes: a significant medium for regulating drug resistance through cargo delivery.

Exosomes are small lipid nanovesicles with a diameter of 30-150 nm. They are present in all body fluids and are actively secreted by the majority of cells through the process of exocytosis. Exosomes play an essential role in intercellular communication and act as significant molecular carriers in regulating various physiological and pathological processes, such as the emergence of drug resistance in tumors. Tumor-associated exosomes transfer drug resistance to other tumor cells by releasing substances such as multidrug resistance proteins and miRNAs through exosomes. These substances change the cell phenotype, making it resistant to drugs. Tumor-associated exosomes also play a role in impacting drug resistance in other cells, like immune cells and stromal cells. Exosomes alter the behavior and function of these cells to help tumor cells evade immune surveillance and form a tumor niche. In addition, exosomes also export substances such as tumoricidal drugs and neutralizing antibody drugs to help tumor cells resist drug therapy. In this review, we summarize the mechanisms of exosomes in promoting drug resistance by delivering cargo in the context of the tumor microenvironment (TME).

Low Complement Factor H-Related 3 (CFHR3) Expression Indicates Poor Prognosis and Immune Regulation in Cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is a cancerous tumor that leads to a high rate of morbidity and death. Complement factor H-related 3 (CFHR3) is a gene belonging to the CFHR gene family. In this study, we investigated the usefulness of CFHR3 in the diagnostic stage and CCA prognosis prediction. In the interim, we looked at its coexpressed genes and their roles. The correlation between CFHR3 and immunological infiltration was also investigated. Methods: The expression of the genes data and the clinical information were obtained from the databases of The Cancer Genome Atlas (TCGA) together with the Gene Expression Omnibus (GEO). The crucial gene was found to be the overlapping gene in the two databases. The area under the curve (AUC) and the Kaplan-Meier survival curve were used to describe the usefulness of the predictive prognosis of CCA patients. Univariate regression analysis and multivariate survival analysis were performed to find the independent prognosis factors. The PPI network was constructed based on the STRING database, and the coexpression approach was utilized in predicting the coexpression genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed to identify the related functions. Additionally, the probable mechanism of the important gene was examined using gene set enrichment analysis (GSEA). The correlation between CFHR3 and immune infiltration was discovered using TIMER. The LncACTdb 3.0 database was used to analyze the location of CFHR3 in the cell. The cBioPortal database was used to find the mutation in CFHR3. Results: TCGA datasets and GEO datasets revealed an elevated expression level of CFHR3 in normal tissues as well as a lower expression level in cholangiocarcinoma tissues in the present research. The low expression level of CFHR3 was related to an unfavorable prognosis. Using CFHR3 expression in diagnosis and predicting the patient prognosis (AUC = 1.000) is valuable. Using the CFHR3 gene and a time-lapse prediction, we could estimate survival rates over 1, 2, and 3 years. The AUC values were more than 0.6(AUC = 0.808; 0.760; 0.711). Functional enrichment analysis revealed a substantial correlation between this signature and complement and coagulation cascades. The same outcomes from GSEA were achieved. We found the key gene widely exists in the nucleus, exosomes, and cytoplasm of normal cells using the LncACTdb 3.0 database. In immune regulation analysis, we identified that the expression level of CFHR3 had a positive correlation with infiltrating levels of B cells, neutrophils, and macrophages, but correlated negatively with cholangiocarcinoma cells, CD8+ T cells, and monocytes.

Exploring the role of mast cells in the progression of liver disease.

In addition to being associated with allergic diseases, parasites, bacteria, and venoms, a growing body of research indicates that mast cells and their mediators can regulate liver disease progression. When mast cells are activated, they degranulate and release many mediators, such as histamine, tryptase, chymase, transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α(TNF-α), interleukins cytokines, and other substances that mediate the progression of liver disease. This article reviews the role of mast cells and their secretory mediators in developing hepatitis, cirrhosis and hepatocellular carcinoma (HCC) and their essential role in immunotherapy. Targeting MC infiltration may be a novel therapeutic option for improving liver disease progression.

[RAPD analysis and construction of specific DNA probes between Pinellia ternata and Typhonium flagelliforme].

OBJECTIVE: To establish a molecular marking method to identify Pinellia ternata and Typhonium flagelliforme. METHODS: Twenty-two random oligonucleotide primers were used in RAPD analysis on the genomic DNA of two types of Pinellia ternata in Sichuan and two types of Typhonium flagelliforme in Guangxi. The special fragments were sequenced, marked as probes and then conducted Southern blot. RESULTS: A great deal of special bands was found between Pinellia ternata and Typhonium flagelliforme. A Pinellia ternata specific molecule was screened. CONCLUSION: RAPD analysis and specific DNA probes show potential value in the identification of Pinellia ternata and Typhonium flagelliforme.

Down-regulation of Bcl-XL by RNA interference suppresses cell growth and induces apoptosis in human esophageal cancer cells.

AIM: To determine the inhibitory effect of the vector-generated small interfering RNAs (siRNAs) on the expression of the Bcl-X(L) gene in established human esophageal cancer cells, and to investigate the effect of the Bcl-X(L) siRNAs on cell growth and apoptosis in esophageal cancer cells. METHODS: Three siRNA-expressing vectors targeting different sites of the Bcl-X(L) gene were constructed from pTZ-U6+1 vector. Cultured esophageal cancer cells were transfected with the siRNA-expressing vector (or the control vector) using lipofectamine 2000. Bcl-X(L) gene expression was determined with semiquantitative RT-PCR assay and Western blotting. Among the three siRNA-expressing vectors, the most highly functional vector and its effect on cell growth and apoptosis in esophageal cancer cells was further analyzed. RESULTS: Of the three siRNA-expressing vectors, siRNA-expressing vector No.1 was the most potent one which suppressed Bcl-X(L) mRNA production to 32.5% of that in the untreated esophageal cancer cells. Western blotting analysis showed that siRNA-expressing vector No.1 markedly down-regulated the expression of Bcl-X(L) in human esophageal cancer cells. Treatment of esophageal cancer cells with siRNA-expressing vector No.1 resulted in inhibition of cell growth and induction of apoptosis. CONCLUSION: Down-regulation of Bcl-X(L) by vector-generated small interfering RNAs can suppress cell growth and induce apoptosis in human esophageal cancer cells.

Overexpression of S-adenosylhomocysteine hydrolase and down-regulation of prohibitin and c-Myc binding protein in the human esophageal squamous cell line HEEC exposed to N-nitrosomethylbenzylamine.

Numerous studies have shown that N-nitrosamines and their precursors are probable etiological factors for esophageal cancer. Certain N-nitrosamines have been shown to induce esophageal cancer in animal models. However, the molecular mechanisms by which N-nitrosamines promote esophageal carcinogenesis remain poorly understood. In this study, we compared the protein expression profiles of the human esophageal squamous cell line HEEC before and after treatment with various concentrations of N-nitrosomethylbenzylamine (NMBA). There were no marked changes in protein expression in HEEC cells exposed to 2 or 10 µg/ml NMBA. Twenty-eight differentially expressed protein spots were identified in HEEC cells exposed to 50 µg/ml NMBA. Two tumor suppressor proteins, prohibitin and c-Myc binding protein, were found to be down-regulated in NMBA-treated HEEC cells. S-adenosylhomocysteine hydrolase, a regulator of biological methylation, was found to be up-regulated in NMBA-treated HEEC cells. These findings may contribute to the further study of the molecular mechanism by which N-nitrosamines promote esophageal carcinogenesis.