Exosomes are described as nanoscale extracellular vesicles (EVs) secreted by multiple cell types and extensively distributed in various biological fluids. They contain multifarious bioactive molecules and transfer them to adjoining or distal cells through systemic circulation, participating in intracellular and intercellular communication, and modulating host−tumor cell interactions. Recent research has indicated that exosomes obtained from different biological fluids and their contents (proteins, nucleic acids, glycoconjugates, and lipids) can serve as biomarkers for cancer diagnosis, prognosis, and therapeutic response. Furthermore, the discovery of exosomes as therapeutic delivery vehicles has drawn much attention in antineoplastic drug delivery. They can be utilized for therapeutic delivery of proteins, genetic drugs, and chemotherapeutic drugs. Herein, this review summarizes the biogenesis, structure, and components of exosomes, focusing primarily on their two possible applications as diagnostic biomarkers and therapeutic delivery vehicles for cancers.
bAntimicrobial peptides with amphipathic -hairpin-like structures have potent antimicrobial properties and low cytotoxicity. The effect of VR or RV motifs on -hairpin-like antimicrobial peptides has not been investigated. In this study, a series of -hairpin-like peptides, Ac-C(VR) n D PG (RV) n C-NH 2 (n ؍ 1, 2, 3, 4, or 5), were synthesized, and the effect of chain length on antimicrobial activity was evaluated. The antimicrobial activity of the peptides initially increased and then decreased with chain length. Longer peptides stimulated the toxicity to mammalian cells. VR3, a 16-mer peptide with seven amino acids in the strand, displayed the highest therapeutic index and represents the optimal chain length. VR3 reduced bacterial counts in the mouse peritoneum and increased the survival rate of mice at 7 days after Salmonella enterica serovar Typhimurium infection in vivo. The circular dichroism (CD) spectra demonstrated that the secondary structure of the peptides was a -hairpin or -sheet in the presence of an aqueous and membrane-mimicking environment. VR3 had the same degree of penetration into the outer and inner membranes as melittin. Experiments simulating the membrane environment showed that Trp-containing VRW3 (a VR3 analog) tends to interact preferentially with negatively charged vesicles in comparison to zwitterionic vesicles, which supports the biological activity data. Additionally, VR3 resulted in greater membrane damage than melittin as determined using a flow cytometry-based membrane integrity assay. Collectively, the data for synthetic lipid vesicles and whole bacteria demonstrated that the VR3 peptide killed bacteria via targeting the cell membrane. This assay could be an effective pathway to screen novel candidates for antibiotic development.
A series of mononuclear ruthenium arene complexes with thiosemicarbazone (TSC) ligands (A-type, 1-8) and their corresponding di-nuclear analogues (B-type, 9-16) were synthesized and characterized by NMR, elemental analysis and HR-ESI-mass spectrometry. The molecular structures of 1, 2, 6, 9-11 and 13-16 were determined using single-crystal X-ray diffraction analysis. The Gibbs free energy of the two examples of the two types of complexes (1 and 9) and the bonding order in their single-crystals were studied using density functional theory (DFT) calculations. The compounds were further evaluated for their in vitro antiproliferative activities against CNE-2 human nasopharyngeal carcinoma, KB human oral epithelial carcinoma, SGC-7901 human gastric carcinoma, HepG2 human liver carcinoma, HeLa human cervical carcinoma and HEK-293T noncancerous cell lines. Furthermore, the interactions between the compounds and DNA were studied by electrophoretic mobility spectrometry studies.
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