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Polymeric Gene Delivery Carriers for Pulmonary Diseases
Published in Severian Dumitriu, Valentin Popa, Polymeric Biomaterials, 2020
Xiang Gao, Regis R. Vollmer, Song Li
Hyaluronic acid (HA), a natural anionic mucopolysaccharide, can be deposited onto the cationic surface of DNA/PEI complexes to recharge the surface potential and reduce nonspecific interactions with proteins. HA can also be used as a ligand to target-specific cell receptors. Furthermore, HA-coating enhanced the transcriptional activity of the plasmid/PEI complexes, probably through loosening the tight binding between DNA and PEI, which facilitated the approach of transcription factors. Amphoteric HA derivative having spermine side chains (Spn-HA) with a structure similar to HMG protein showed higher transcription-enhancing activity than HA. Plasmid/PEI/Spn-HA ternary complexes exhibited 29-fold higher transgene expression than naked plasmid/PEI complexes in CHO cells (Ito et al., 2006).
MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma
Published in Archives of Environmental & Occupational Health, 2020
Elena Sturchio, Maria Grazia Berardinelli, Priscilla Boccia, Miriam Zanellato, Silvia Gioiosa
To date, the available tissue and serological biomarkers for the diagnosis of MM [megakaryocyte potentiating factor (MPF), Osteopontin (OPN), Fibulin-3, high mobility group B1 (HMGB1)15] are characterized by a low sensitivity and specificity. For these reasons, they cannot be considered reliable tools for the identification of subjects exposed to asbestos and other carcinogenic fibers, and for MM detection and diagnosis at earlier stages of growth.1 Currently, serum mesothelin, so called Soluble Mesothelin-Related Peptides (SMRPs) is the only diagnostic biomarker officially approved by the Food and Drug Administration, characterized by good specificity but low sensitivity, especially for non-epithelioid mesothelioma and it has been approved only for monitoring tumor recurrence after therapy.15–17
Investigating orthodontic tooth movement: challenges and future directions
Published in Journal of the Royal Society of New Zealand, 2020
Fiona A. Firth, Rachel Farrar, Mauro Farella
Numerous studies have been performed by New Zealand researchers in which cultured PDL cells or osteoblasts have been mechanically loaded (Wescott et al. 2007; Pinkerton et al. 2008; Saminathan et al. 2012; Itskovich 2016; Firth 2017). Interestingly, a transient increase in apoptosis and expression of two apoptosis-related caspases (enzymes involved in programmed cell death and inflammation) has been detected in mechanically strained PDL cells in a two-dimensional (2D) culture, however the mechanism for this has not been identified (Wescott et al. 2007; Pinkerton et al. 2008; Saminathan et al. 2012). In response to the application of cyclic tensile force to PDL cells, the upregulation of certain osteogenic-specific genes (e.g. bone morphogenetic protein 2 [BMP2], BMP6 and sex-determining region Y-related high mobility group box9 [SOX9]), and downregulation of others (BMP4 and epidermal growth factor [EGF]) was also an important finding (Wescott et al. 2007). Between days one and seven following the commencement of force application, BMPs have been shown to induce expression of runt-related transcription factor 2 (Runx-2) and also bind to osteoblast cell surface receptors, triggering upregulation of osteoblast function (Masella and Meister 2006; Vansant et al. 2018). These findings confirm the complexity of the sequence of events occurring during the week immediately following the initial force application. They also support the proposal that there may be a genetic component to the variation in individual responses to these forces.
Epigenetic modifications associated with pathophysiological effects of lead exposure
Published in Journal of Environmental Science and Health, Part C, 2019
Madiha Khalid, Mohammad Abdollahi
Perinatal Pb exposure in adult mice showed a nonlinear dose-response and decreased methylated regions in IAPs 110, 236, and 506.9 These results were similar to those of other studies reporting a nonmonotonic response in IAP DNA methylation in mouse brains after Pb exposure.63,68 The methylated IAPs have been found to match three binding motifs, namely TEA domain transcription factor 4 (TEAD4), high mobility group AT-hook 2 (HMGA2), and Far upstream element binding protein 1 (FUBP1). TEAD4 is linked to narcolepsy and cancer,87–89 HMGA2 is linked to altered metabolism, obesity, and T2DM,90 and FUBP1 is associated with gliomas,91 suggesting an epigenetic link of Pb exposure early in life and risks of poor health outcomes later in life. Also, upregulated HMGB1 (P < 0.05) expression in rat was observed due to 100 μM Pb exposure.92 Another study reported dysbiosis, increased hepatic TG, cholesterol level and metabolic disorder due to 0.1 mg/L Pb exposure in mice.93 Despite these results, the impacts of either prenatal or postnatal Pb exposure on metabolism were inconclusive, requiring further investigation.