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Background and Aims: Breast cancer is a leading cause of incidence and mortality in women globally. Identifying new molecular markers can aid in cancer diagnosis, targeted therapy, and treatment monitoring. This study aimed to measure the expression of the X-box binding protein 1 (XBP1) gene, an index of the unfolded protein response (UPR), and long noncoding RNAs (lncRNAs), including Nuclear Enriched Abundant Transcript 1 (NEAT1), Cancer Susceptibility Candidate 2 (CASC2), and Long Intergenic Nonprotein Coding RNA 299 (LINC00299), as possible regulators of the UPR pathway., Methods: Total RNA was extracted from 40 samples of breast tumor tissues and their respective controls. The expression level of lncRNAs CASC2, NEAT1, and LINC00299 was quantified using reverse transcription-polymerase chain reaction (RT-PCR). The ratio of the spliced form of XBP1 to its unspliced form (XBP1u) was determined by PCR and electrophoresis., Results: The results showed a 2.8-fold increase in the ratio of XBP1s/u in breast cancer tissues compared to adjacent nonmalignant samples ( p  < 0.05). Additionally, the level of lncRNAs NEAT1, CASC2, and LINC00299 in breast tumor tissues increased significantly by twofold, 1.5-fold, and 2.3-fold, respectively, compared to adjacent nonmalignant samples ( p  < 0.05)., Conclusions: Based on the association between the expression of lncRNAs CASC2, LINC00299, and NEAT1 and the XBP1s/u ratio, these lncRNAs could be potential regulators of the UPR pathway. Also, CASC2 and NEAT1 genes could be suggested as suitable biomarkers to distinguish cancerous tissue from noncancerous breast tissue due to their significant increase in expression in cancerous samples compared to adjacent noncancerous., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Selective photosensitized oxidation of amyloid protein aggregates is being investigated as a possible therapeutic strategy for treating Alzheimer's disease (AD). Photo-oxidation has been shown to degrade amyloid-β (Aβ) aggregates and ameliorate aggregate toxicity in vitro and reduce aggregate levels in the brains of AD animal models. To shed light on the mechanism by which photo-oxidation induces fibril destabilization, we carried out an all-atom molecular dynamics (MD) simulation to examine the effect of methionine (Met35) oxidation on the conformation and stability of a β-sheet-rich Aβ 9-40 protofibril. Analyses of up to 1 μs simulations showed that the oxidation of the Met35 residues, which resulted in the addition of hydrophilic oxygens in the fibril core, reduced the overall conformational stability of the protofibril. Specifically, Met35 disrupted the hydrophobic interface that stabilizes the stacking of the two hexamers that comprise the protofibril. The oxidized protofibril is more solvent exposed and exhibits more backbone flexibility. However, the protofibril retained the underlying U-shaped architecture of each peptide upon oxidation, and although some loss of β-sheets occurred, a significant portion remained. Our simulation results are thus consistent with our experimental observation that photo-oxidation of Aβ40 fibril resulted in the dis-agglomeration and fragmentation of Aβ fibrils but did not cause complete disruption of the fibrillar morphology or β-sheet structures. The partial destabilization of Aβ aggregates supports the further development of photosensitized platforms for the targeting and clearing of Aβ aggregates as a therapeutic strategy for treating AD., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimer's disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. We have shown that a novel class of oligo- p -phenylene ethynylenes (OPEs) exhibit selective binding and fluorescence turn-on in the presence of prefibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-β (Aβ) and α-synuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of Aβ fibrils and compared its efficacy to the well-known but nonselective photosensitizer methylene blue (MB). Our results show that, while MB photo-oxidized both monomeric and fibrillar conformers of Aβ40, OPE oxidized only Aβ40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed but retained the characteristic β-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPE's photosensitizing activity overcomes the limitation of off-target oxidation of traditional photosensitizers and represents an advancement of PDT as a viable strategy to treat neurodegenerative disorders.

The threat of antibiotic-resistant bacteria is an ever-increasing problem in public health. In this report, we examine the photochemical properties with a proof-of-principle biocidal assay for a novel series of regio-regular imidazolium derivative poly-(3-hexylthiophene)/sodium dodecyl sulfate (P3HT-Im/SDS) materials from ultrafast sub-ps dynamics to μs generation of reactive oxygen species (ROS) and 30 min biocidal reactivity with Escherichia coli ( E. coli ). This broad series encompassing pure P3HT-Im to cationic, neutral, and anionic P3HT-Im/SDS materials are all interrogated by a variety of techniques to characterize the physical material structure, electronic structure, and antimicrobial activity. Our results show that SDS complexation with P3HT-Im results in aggregate materials with reduced ROS generation and light-induced anti-microbial activity. However, our characterization reveals that the presence of non-aggregated or lightly SDS-covered polymer segments is still capable of ROS generation. Full encapsulation of the P3HT-Im polymer completely deactivates the light killing pathway. High SDS concentrations, near and above critical micelle concentration, further deactivate all anti-microbial activity (light and dark) even though the P3HT-Im regains its electronic properties to generate ROS.

Much recent effort has been directed toward the development of novel antimicrobial materials able to defeat new and antibiotic resistant pathogens. In this report, we study the efficacy of cationic poly(phenylene ethynylene), polythiophene, and oligo(phenylene ethynylene) electrolytes against laboratory strains of Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis . The focus of the study is to quantitatively evaluate the speed and extent of dark and light-activated antimicrobial activity. Using cell plating with serial dilutions, we determined that planktonic bacteria suspensions exposed to the antimicrobials (at 10 μg/mL) result in several log kills at 10 min both in the dark and under UV irradiation (360 nm) for all eight synthetic antimicrobials. However, there are significant differences in the ease of killing the different pathogens. In most trials, there is significantly greater killing under light-irradiation, indicating these materials may be used as versatile disinfectants.

Reduction-responsive biodegradable micelles were prepared by linking of poly(ethylene glycol) and poly(ε‑caprolactone) with disulfide bond (PEG-SS-PCL) for co-delivery of superparamagnetic iron oxide (SPIO) nanoparticles (NPs) and an anticancer agent, doxorubicin (DOX). This amphiphilic diblock copolymer shows redox-responsive properties, which is arising from disulfide bonds throughout the main chain. The ability of these copolymers for self-assembly with oleic acid modified SPIONs can help to organize nanomicelles in aqueous solution. Doxorubicin (DOX) was loaded in the magnetic nanomicelles with a loading of 32%. Coarse-Grained Molecular Dynamics (CG-MD) simulation approach was exploited to reassure the construction of self-assembled PEG-PCL micelles in presence of oleic acid and water solvent while the hydrophobic and hydrophilic ratios of each block copolymer were equally chosen and each oleic acid was connected to Fe 3 O 4 nanoparticles. Our results confirmed the stability, cytocompatibility, magnetic and redox-responsive properties for these self-assembled nanomicelles and revealed that the DOX-SPION-loaded reduction-sensitive nanomicelles could be used in drug targeting to the cancer cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Self-assembly of A 6 D amphiphilic peptides in explicit water is studied by using coarse-grained molecular dynamics simulations. It is observed that the self-assembly of randomly distributed A 6 D peptides leads to the formation of a network of nano-fibers. Two other simulations with cylindrical nano-fibers as the initial configuration show the dynamic stability of the self-assembled nano-fibers. As a striking feature, notable fluctuations occur along the axes of the nano-fibers. Depending on the number of peptides per unit length of the nano-fiber, flat-shaped bulges or spiral shapes along the nano-fiber axis are observed at the fluctuations. Analysis of the particle distribution around the nano-fiber indicates that the hydrophobic core and the hydrophilic shell of the nano-structure are preserved in both simulations. The size of the deformations and their correlation times are different in the two simulations. This study gives new insights into the dynamics of the self-assembled nano-structures of short amphiphilic peptides.