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In addition, we found that functional disruption of sfxn1 causes hypochromic anemia that is distinct from SA. These findings reveal that sfxn1 is genetically conserved and essential for the maturation of erythrocyte via facilitating the production of hemoglobin, which may provide a possible guidance for the future clinical treatment of sfxn1 mutation associated hematological disorders.Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and transcriptional modulators with crucial functions in hepatic and whole-body energy homeostasis. Besides their well-documented roles in lipid and glucose metabolism, emerging evidence also implicate PPARs in the control of other processes such as inflammatory responses. Recent technological advances, such as single-cell RNA sequencing, have allowed to unravel an unexpected complexity in the regulation of PPAR expression, activity and downstream signaling. Here we provide an overview of the latest advances in the study of PPARs in liver physiology, with a specific focus on formerly neglected aspects of PPAR regulation, such as tissular zonation, cellular heterogeneity, circadian rhythms, sexual dimorphism and species-specific features.Dysregulation of transcription factors is one of the common problems in the pathogenesis of human cancer. Among them, SOX9 is one of the critical transcription factors involved in various diseases, including cancer. The expression of SOX9 is regulated by microRNAs (miRNAs), methylation, phosphorylation, and acetylation. Interestingly, SOX9 acts as a proto-oncogene or tumor suppressor gene, relying upon kinds of cancer. Recent studies have reported the critical role of SOX9 in the regulation of the tumor microenvironment (TME). Additionally, activation of SOX9 signaling or SOX9 regulated signaling pathways play a crucial role in cancer development and progression. Accumulating evidence also suggests that SOX9 acquires stem cell features to induce epithelial-mesenchymal transition (EMT). Moreover, SOX9 has been broadly studied in the field of cancer stem cell (CSC) and EMT in the last decades. However, the link between SOX9 and cancer drug resistance has only recently been discovered. Furthermore, its differential expression could be a potential biomarker for tumor prognosis and progression. This review outlined the various biological implications of SOX9 in cancer progression and cancer drug resistance and elucidated its signaling network, which could be a potential target for designing novel anticancer drugs.Lack of selectivity together with severe side effects in conventional cancer treatment have afforded the development of new strategies based on gene therapy. Nowadays, gene therapy is employed through both viral and non-viral vectors. NVL-655 order In spite of the high transfection activity of viral vectors, some drawbacks have pointed out to non-viral vectors as a safer alternative. To overcome low efficiency as well as other issues associated with the use of non-viral vectors, complexes formed by lipids and polymers with DNA, named lipoplexes and polyplexes respectively, have been modified in order to improve its features. Suitability of cancer gene therapy also requires the capacity to distinguish between normal and tumoral cells. This requirement has been solved by the addition of specific ligands that enable receptor binding and subsequent endocytosis. In this article we review the most recent approaches in structure modification of non-viral vectors through different methods comprising conjugation, addition of helper lipids or changes in design and synthesis as well as the strategy based on exploiting receptors that are usually overexpressed in malignancies. Such improvements confer specificity, efficient gene delivery, condensation, protection of DNA and low levels of toxicity avoiding off-target effects which turn into a potential tool to treat cancer.Skin regeneration is one of the most important issues in tissue engineering. Research on more effective biomaterials that will enhance regeneration while enabling requirements of a healing skin site is an important challenge in skin tissue engineering. In this study, heparin was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) which were then incorporated into Sericin/Gelatin (Ser/Gel) nanofibers during the electrospinning process in order to develop a combined system that has controlled release approach, besides the ability to help the regeneration of skin tissue by the involvement of biopolymers; gelatin, and sericin. The loading capacity and heparin encapsulation efficiency in the nanoparticles were determined as 30.04 mg/g of polymer and 60%, respectively. Cumulative release of heparin from NPs for 1 week was faster than from NPs loaded gelatin scaffolds and from dual protein (Ser/Gel) scaffolds with ratios 1/7 and 1/2 (approximately 85%, 65%, 55%, and 40%, respectively). Sericin addition slowed down the degradation properties of the scaffold. The scaffold having a Ser/Gel ratio (1/2) was found as the most promising candidate because of its proper fiber morphology, high water retention, and low degradation degree.Due to the increasing inability of antibiotics to treat multidrug-resistant (MDR) bacteria, metal and metal oxide nanoparticles have been gaining interest as antimicrobial agents. Among those, silver nanoparticles have been used extensively as broad-spectrum antimicrobial agents. Here, we describe a newly-developed, 10-min (120 °C at 5 bar pressure) microwave-assisted synthesis of silver nanoparticles made from the wood biopolymer lignin as a reducing and capping agent. The resulting lignin-capped silver nanoparticles (AgLNPs) had an average particle diameter of 13.4 ± 2.8 nm. Antimicrobial susceptibility assays against a variety of MDR clinical Gram-positive and Gram-negative pathogens revealed a minimal inhibitory concentration (MIC) of AgLNPs ≤5 µg/mL. AgLNPs (10 µg/mL) showed ≤20% cytotoxicity towards monocytic THP-1 cells and were well tolerated when administered subcutaneously in mice at high concentrations (5 mg at a concentration of 100 mg/mL) with no obvious toxicity. AgLNPs showed efficacy in an in vivo infection (abscess) mouse model against MDR Pseudomonas aeruginosa LESB58 and methicillin-resistant Staphylococcus aureus USA300.
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