DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.

DNA is an organic molecule that is highly vulnerable to chemical alterations and breaks caused by both internal and external factors. Cells possess complex and advanced mechanisms, including DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which together minimize the potentially harmful effects of DNA damage. However, in cancer cells, the normal DNA damage tolerance and response processes are disrupted or deregulated.

Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma.

mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer.

Hyper-Branched Cationic Cyclodextrin Polymers for Improving Plasmid Transfection in 2D and 3D Spheroid Cells.

In this article, we used monolayer two dimensional (2D) and 3D multicellular spheroid models to improve our understanding of the gene delivery process of a new modified cationic hyper-branched cyclodextrin-based polymer (Ppoly)-loaded plasmid encoding Enhanced Green Fluorescent Protein (EGFP). A comparison between the cytotoxicity effect and transfection efficiency of the plasmid DNA (pDNA)-loaded Ppoly system in 2D and 3D spheroid cells determined that the transfection efficiency and cytotoxicity of Ppoly-pDNA nanocomplexes were lower in 3D spheroids than in 2D monolayer cells. Furthermore, histopathology visualization of Ppoly-pDNA complex cellular uptake in 3D spheroids demonstrated that Ppoly penetrated into the inner layers.

Hyper-Branched Cyclodextrin-Based Polymers as Anticoagulant Agents: In Vitro and In Vivo Studies.

This study tested the anticoagulant effect of cyclodextrin (CD) hyper-branched-based polymers (HBCD-Pols). These polymers were synthesized and tested for their coagulant characteristics in vitro and in vivo. Due to their polymeric structure and anionic nature, the polymers can chelate Ca, reducing the free quantity in blood.

Oral supplementation of solvent-free kynurenic acid/cyclodextrin nanosponges complexes increased its bioavailability.

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPβ-CD and βNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation.

Circulating salivary and serum miRNA-182, 320a, 375 and 503 expression levels in type 2 diabetes.

Aim: Early-stage diagnosis of diabetes through non-invasive and diagnostic biofluid-like saliva has become a very popular approach to facilitate future preventive interventions and improve patient care. Meanwhile, the alteration of small non-coding RNA in human fluids has been suggested as a probable precedent for the early stages of diabetes.

Methods: In the present study, we checked the expression of miR-320a, 182-5p, 503, and 375 by using quantitative PCR in both stimulated and unstimulated saliva and blood samples of 40 adult patients with type-2 diabetes compared to 40 healthy individuals.

Dextrin-Based Nanohydrogels for Rokitamycin Prolonged Topical Delivery.

Macrolides are widely used antibiotics with a broad spectrum of activity. The development of drug carriers to deliver this type of antibiotics has attracted much research. The present study aims at developing new swellable dextrin-based nanohydrogels for the topical delivery of rokitamycin, as model macrolide.

Nutraceutical Concepts and Dextrin-Based Delivery Systems.

Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, etc. The effect of nutraceuticals is similar to pharmaceuticals, even though the term nutraceutical has no regulatory definition.

Cyclodextrin-Based Nanosponges as Perse Antimicrobial Agents Increase the Activity of Natural Antimicrobial Peptide Nisin.

At present, antibiotic resistance is considered a real problem. Therefore, for decades scientists have been looking for novel strategies to treat bacterial infections. Nisin Z, an antimicrobial peptide (AMP), can be considered an option, but its usage is mainly limited by the poor stability and short duration of its antimicrobial activity.

Magnetic Composites of Dextrin-Based Carbonate Nanosponges and Iron Oxide Nanoparticles with Potential Application in Targeted Drug Delivery.

Magnetically driven nanosponges with potential application as targeted drug delivery systems were prepared via the addition of magnetite nanoparticles to the synthesis of cyclodextrin and maltodextrin polymers crosslinked with 1,1'-carbonyldiimidazole. The magnetic nanoparticles were obtained separately via a coprecipitation mechanism involving inorganic iron salts in an alkaline environment. Four composite nanosponges were prepared by varying the content of magnetic nanoparticles (5 wt% and 10 wt%) in the cyclodextrin- and maltodextrin-based polymer matrix.

Stabilization and Anticancer Enhancing Activity of the Peptide Nisin by Cyclodextrin-Based Nanosponges against Colon and Breast Cancer Cells.

The great variability of cancer types demands novel drugs with broad spectrum, this is the case of Nisin, a polycyclic antibacterial peptide that recently has been considered for prevention of cancer cells growth. As an accepted food additive, this drug would be very useful for intestinal cancers, but the peptide nature would make easier its degradation by digestion procedures. For that reason, the aim of present study to investigate the protective effect of two different β-cyclodextrin-based nanosponges (carbonyl diimidazole and pyromellitic dianhydride) and their anti-cancer enhancement effect of Nisin-Z encapsulated with against colon cancer cells (HT-29).

Salivary microRNA-126 and 135a: a potentially non-invasive diagnostic biomarkers of type- 2 diabetes.

Purpose: Emerging of miRNAs have illustrated the new mechanistic layer to regulate type 2 diabetes process and suggests a possible role of these RNAs in this defect. Thus, we designed this study to improve our understanding of salivary miRNA-126 and 135a expression utility as an easy of collection and non-invasive way in diabetic patients instead of blood sample.

Methods: This case-control study was done on TD (n = 40) and healthy individuals (n = 40).

Cyclodextrin Monomers and Polymers for Drug Activity Enhancement.

Cyclodextrins (CDs) and cyclodextrin (CD)-based polymers are well-known complexing agents. One of their distinctive features is to increase the quantity of a drug in a solution or improve its delivery. However, in certain instances, the activity of the solutions is increased not only due to the increase of the drug dose but also due to the drug complexation.

A physicochemical, thermodynamical, structural and computational evaluation of kynurenic acid/cyclodextrin complexes.

In this work, the interaction between Kynurenic acid (KYNA) and several natural and modified cyclodextrins (CDs) is carried out. Among all the CD tested, HPβ-CD showed the strongest complexation constant (K), with a value of 270.94 ± 29.

Effect of the Cross-Linking Density on the Swelling and Rheological Behavior of Ester-Bridged β-Cyclodextrin Nanosponges.

The cross-linking density influences the physicochemical properties of cyclodextrin-based nanosponges (CD-NSs). Although the effect of the cross-linker type and content on the NSs performance has been investigated, a detailed study of the cross-linking density has never been performed. In this contribution, nine ester-bridged NSs based on β-cyclodextrin (β-CD) and different quantities of pyromellitic dianhydride (PMDA), used as a cross-linking agent in stoichiometric proportions of 2, 3, 4, 5, 6, 7, 8, 9, and 10 moles of PMDA for each mole of CD, were synthesized and characterized in terms of swelling and rheological properties.

Circulating miR-135 May Serve as a Novel Co-biomarker of HbA1c in Type 2 Diabetes.

Hemoglobin A1c (HbA1c) is a reliable marker of insulin resistance in normal glucose tolerance patients; however, several physiological, environmental, and genetic factors may affect HbA1c and cause false results. Therefore, it is essential to use new biomarkers due to increasing diabetes predictive value. Recently, it has been indicated that microRNAs (miRNAs) are involved in the pathophysiology of diabetes, particularly, in insulin resistance pathways.

Evaluating the Role of Promoter Methylation in Patients Predisposed to Hypercoagulable States via Methylation Specific PCR.

Background: Hypercoagulable states (HS) can result from several different inherited and acquired disease conditions that cause abnormalities in the genes, proteins and cellular factors involved in the coagulation cascade. Novel insight into the molecular mechanisms involved in the coagulation pathways can provide a framework to develop improved therapeutics to treat patients with coagulation disorders. Therefore, investigating the genetic abnormalities present in patients with coagulation disorders can offer critical insight into disease pathogenesis.