Advancements in exosome isolation technologies are pivotal for transforming personalized medicine and enhancing clinical diagnostics. Exosomes, small extracellular vesicles with diameters ranging between 30 and 150 nm, are secreted into bodily fluids by a variety of cells and play essential roles in intercellular communication. These vesicles facilitate the transfer of nucleic acids, lipids, and proteins, affecting a wide range of biological and pathological processes. Given their importance in disease diagnostics, therapy, and as biomarkers, there has been a surge in developing methods to isolate them from fluids such as urine, saliva, blood, and cerebrospinal fluid. While traditional isolation techniques like ultracentrifugation and polymer-based precipitation have been foundational, recent technological advances have introduced more precise methods like microfluidics and immunoaffinity capture. These newer methods enable high-throughput and specific exosome isolation by targeting surface markers, thus enhancing purity. However, challenges such as balancing purity with yield and the lack of standardized protocols across different laboratories persist, impacting the consistency of findings. By integrating advanced isolation techniques and discussing their implications in diagnostics and therapy, this review aims to catalyze further research and adoption of exosome-based technologies in medicine, marking a significant stride towards tailored healthcare solutions.
Chitosan is a natural anionic polysaccharide with a changeable architecture and an abundance of functional groups; in addition, it can be converted into various shapes and sizes, making it appropriate for a variety of applications. This article examined and summarized current developments in chitosan-based materials, with a focus on the modification of chitosan, and presented an abundance of information about the fabrication and use of chitosan-derived products in periodontal regeneration. Numerous preparation and modification techniques for enhancing chitosan performance, as well as the uses of chitosan and its metabolites, were reviewed critically and discussed in depth in this study. Chitosan-based products may be formed into different shapes and sizes, considering fibers, nanostructures, gels, membranes, and hydrogels. Various drug-loaded chitosan devices were discussed regarding periodontal regeneration.
ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm–multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69–0.87, F = 403.46–292.11, etc., internal validation parameters; Q2LOO = 0.69–0.86, Q2LMO = 0.69–0.86, CCCcv = 0.82–0.93, etc., or external validation parameters Q2F1 = 0.64–0.82, Q2F2 = 0.63–0.82, Q2F3 = 0.65–0.81, R2ext = 0.65–0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.
The Semliki Forest Virus (SFV) is an RNA virus with a positive-strand that belongs to the Togaviridae family’s Alphavirus genus. An epidemic was observed among French troops stationed in the Central African Republic, most likely caused by the SFV virus. The two transmembrane proteins El and E2 and the peripheral protein E3 make up the viral spike protein. The virus binds to the host cell and is internalized via endocytosis; endosome acidification causes the E1/E2 heterodimer to dissociate and the E1 subunits to trimerize. Lupenone was evaluated against the E1 spike protein of SFV in this study based on state-of-the-art cheminformatics approaches, including molecular docking, molecular dynamics simulation, and binding free energy calculation. The molecular docking study envisaged major interactions of Lupenone with binding cavity residues involved non-bonded van der Waal’s and Pi-alkyl interactions. Molecular dynamic simulation of a time scale 200 ns corroborated interaction pattern with molecular docking studies between Lupenone and E1 spike protein. Nevertheless, Lupenone intearcation with the E1 spike protein conforming into a stable complex substantiated by free energy landscape (FEL), PCA analysis. Free energy decomposition of the binding cavity resdiues of E1 spike protein also ensured the efficient non-bonded van der Waal’s interaction contributing most energy to interact with the Lupenone. Therefore, Lupenone interacted strongly at the active site conforming into higher structural stability throughout the dynamic evolution of the complex. Thus, this study perhaps comprehend the efficiency of Lupenone as lead molecule against SFV E1 spike protein for future therapeutic purpose.
Cancer stem cells (CSCs) are self-renewing and slow-multiplying micro subpopulations in tumour microenvironments. CSCs contribute to cancer's resistance to radiation (including radiation) and other treatments. CSCs control the heterogeneity of the tumour. It alters the tumour's microenvironment cellular singling and promotes epithelial-to-mesenchymal transition (EMT). Current research decodes the role of extracellular vesicles (EVs) and CSCs interlink in radiation resistance. Exosome is a subpopulation of EVs and originated from plasma membrane. It is secreted by several active cells. It involed in cellular communication and messenger of healthly and multiple pathological complications. Exosomal biological active cargos (DNA, RNA, protein, lipid and glycan), are capable to transform recipient cells' nature. The molecular signatures of CSCs and CSC-derived exosomes are potential source of cancer theranostics development. This review discusse cancer stem cells, radiation-mediated CSCs development, EMT associated with CSCs, the role of exosomes in radioresistance development, the current state of radiation therapy and the use of CSCs and CSCs-derived exosomes biomolecules as a clinical screening biomarker for cancer. This review gives new researchers a reason to keep an eye on the next phase of scientific research into cancer theranostics that will help mankind.
19 January 2023 in Naunyn-Schmiedeberg's Archives of Pharmacology