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      Functionalized Carbon Nanotubes for Delivery of Ferulic Acid and Diosgenin Anticancer Natural Agents

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          Abstract

          It was investigated whether loading multi-wall carbon nanotubes (CNTs) with two natural anticancer agents: ferulic acid (FUA) and diosgenin (DGN), may enhance the anticancer effect of these drugs. The CNTs were functionalized with carboxylic acid (CNTCOOH) or amine (CNTNH 2), loaded with the above pro-drugs, as well as both combined and coated with chitosan or chitosan–stearic acid. Following physicochemical characterization, the drug-loading properties and kinetics of the drug’s release were investigated. Their effects on normal human skin fibroblasts and MCF-7 breast carcinoma cells, HepG2 hepatocellular carcinoma cells, and A549 non-small-cell lung cancer cells were evaluated in vitro. Their actions at the molecular level were evaluated by assessing the expression of lncRNAs (HULC, HOTAIR, CCAT-2, H19, and HOTTIP), microRNAs (mir-21, mir-92, mir-145, and mir-181a), and proteins (TGF-β and E-cadherin) in HepG2 cells. The release of both pro-drugs depended on the glutathione concentration, coating, and functionalization. Release occurred in two stages: a no-burst/zero-order release followed by a sustained release best fitted to Korsmeyer–Peppas kinetics. The combined nanoformulation cancer inhibition effect on HepG2 cancer cells was more pronounced than for A549 and MCF7 cells. The combined nanoformulations had an additive impact followed by a synergistic effect, with antagonism demonstrated at high concentrations. The nanoformulation coated with chitosan and stearic acid was particularly successful in targeting HepG2 cells and inducing apoptosis. The CNT functionalized with carboxylic acid (CNTCOOH), loaded with both FUA and DGN, and coated with chitosan–stearic acid inhibited the expression of lncRNAs and modulated both microRNAs and proteins. Thus, nanoformulations composed of functionalized CNTs dual-loaded with FUA and DGN and coated with chitosan–stearic acid are a promising drug delivery system that enhances the activity of natural pro-drugs.

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          Functional Classification and Experimental Dissection of Long Noncoding RNAs

          Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.
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            Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery.

            We show that large surface areas exist for supramolecular chemistry on single-walled carbon nanotubes (SWNTs) prefunctionalized noncovalently or covalently by common surfactant or acid-oxidation routes. Water-soluble SWNTs with poly(ethylene glycol) (PEG) functionalization via these routes allow for surprisingly high degrees of pi-stacking of aromatic molecules, including a cancer drug (doxorubicin) with ultrahigh loading capacity, a widely used fluorescence molecule (fluorescein), and combinations of molecules. Binding of molecules to nanotubes and their release can be controlled by varying the pH. The strength of pi-stacking of aromatic molecules is dependent on nanotube diameter, leading to a method for controlling the release rate of molecules from SWNTs by using nanotube materials with suitable diameter. This work introduces the concept of "functionalization partitioning" of SWNTs, i.e., imparting multiple chemical species, such as PEG, drugs, and fluorescent tags, with different functionalities onto the surface of the same nanotube. Such chemical partitioning should open up new opportunities in chemical, biological, and medical applications of novel nanomaterials.
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              DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts

              microRNAs (miRNAs) are short non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of coding gene expression. Long non-coding RNAs (lncRNAs) have been recently reported to interact with miRNAs. The sponge-like function of lncRNAs introduces an extra layer of complexity in the miRNA interactome. DIANA-LncBase v1 provided a database of experimentally supported and in silico predicted miRNA Recognition Elements (MREs) on lncRNAs. The second version of LncBase (www.microrna.gr/LncBase) presents an extensive collection of miRNA:lncRNA interactions. The significantly enhanced database includes more than 70 000 low and high-throughput, (in)direct miRNA:lncRNA experimentally supported interactions, derived from manually curated publications and the analysis of 153 AGO CLIP-Seq libraries. The new experimental module presents a 14-fold increase compared to the previous release. LncBase v2 hosts in silico predicted miRNA targets on lncRNAs, identified with the DIANA-microT algorithm. The relevant module provides millions of predicted miRNA binding sites, accompanied with detailed metadata and MRE conservation metrics. LncBase v2 caters information regarding cell type specific miRNA:lncRNA regulation and enables users to easily identify interactions in 66 different cell types, spanning 36 tissues for human and mouse. Database entries are also supported by accurate lncRNA expression information, derived from the analysis of more than 6 billion RNA-Seq reads.
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                Author and article information

                Journal
                ACS Appl Bio Mater
                ACS Appl Bio Mater
                mt
                aabmcb
                ACS Applied Bio Materials
                American Chemical Society
                2576-6422
                22 January 2024
                19 February 2024
                : 7
                : 2
                : 791-811
                Affiliations
                []Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC) , 33 El-Behouth Street, Dokki, Giza 12622, Egypt
                []Supplementary General Sciences, Future University , End of 90th Street, Fifth Settlement, New Cairo 11835, Egypt
                [§ ]Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC) , 33 El-Behouth Street, Dokki, Giza 12622, Egypt
                []Institute of High Pressure Physics, Polish Academy of Sciences , Sokolowska 29/37, 01-142 Warsaw, Poland
                []Analytical Chemistry Department, Faculty of Pharmacy, October 6 University , Giza 12585, Egypt
                [# ]Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University , Cairo 11511, Egypt
                []Faculty of Materials Engineering, Warsaw University of Technology , Wołoska 41, 02-507 Warsaw, Poland
                []NANOMATPL Ltd. , 14/38 Wyszogrodzka Street, Warsaw 03-337, Poland
                []Faculty of Chemical and Process Engineering, Warsaw University of Technology , 1 Warynskiego Street, 00-645 Warsaw, Poland
                Author notes
                [* ]Email: ke.abouaitah@ 123456nrc.sci.eg . Phone: +20233371635. Fax: +20233371010.
                [* ]Email: w.lojkowski@ 123456labnano.pl . Phone: +48-22-888-0429 or +48-22-632-4302. Fax: +48-22-632-4218.
                Author information
                https://orcid.org/0000-0001-8521-0688
                Article
                10.1021/acsabm.3c00700
                10880110
                38253026
                49d73b9d-4acf-49ed-b8dd-50ae4817219f
                © 2024 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 25 August 2023
                : 03 January 2024
                : 22 December 2023
                Funding
                Funded by: Institute of High-Pressure Physics, Polska Akademia Nauk, doi NA;
                Award ID: NA
                Categories
                Article
                Custom metadata
                mt3c00700
                mt3c00700

                carbon nanotubes,codelivery system,diosgenin and ferulic acid,kinetic release,cancer cells,long noncoding rnas/micrornas/tgf-β and e-cadherin protein

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