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As endogenous courier vesicles, exosomes play crucial roles in macromolecule transmission and intercellular communication. Therefore, exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few years. However, few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral administration. Additionally, the mechanisms underlying their biomimetic properties as oral delivery vehicles remain unknown. Herein, insulin-loaded milk-derived exosomes (EXO@INS) were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic rats. Surprisingly, EXO@INS (50 and 30 IU/kg) elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected insulin. Further mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake, pH adaptation during gastrointestinal transit, nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus penetration. This study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.
Pubmed ID: 35847507 RIS Download
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The IARC TP53 Mutation Database compiles all TP53 gene variations identified in human populations and tumor samples. Data are compiled from the peer-reviewed literature and from generalist databases. The following datasets are available: # TP53 somatic mutations in sporadic cancers # TP53 germline mutation in familial cancers # Common TP53 polymorphisms identified in human populations # Functional and structural properties of P53 mutant proteins # TP53 gene status in human cell-lines # Mouse-models with engineered TP53 The database includes various annotations on the predicted or experimentally assessed functional impact of mutations, clinicopathologic characteristics of tumors and demographic and life-style information on patients. The database is meant to be a source of information on TP53 mutations for a broad range of scientists and clinicians who work in different research areas: # Basic research, to study the structural and functional aspects of the p53 protein # Molecular pathology of cancer, to understand the clinical significance of mutations identified in cancer patients # Molecular epidemiology of cancer, to analyze the links between specific exposures and mutation patterns and to make inferences about possible causes of cancer # Molecular genetics, to analyze genotype/phenotype relationships
View all literature mentionsCell line Caco-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
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