Intracellular silver accumulation in Chlamydomonas reinhardtii upon exposure to carbonate coated silver nanoparticles and silver nitrate

The intracellular silver accumulation ({Ag}(in)) upon exposure to carbonate coated silver nanoparticles (AgNP, 0.5-10 μM, average diameter 29 nm) and silver nitrate (20-500 nM) was examined in the wild type and in the cell wall free mutant of the green alga Chlamydomonas reinhardtii at pH 7.5. The {Ag}(in) was measured over time up to 1 h after a wash procedure to remove silver ions (Ag(+)) and AgNP from the algal cell surface. The {Ag}(in) increased with increasing exposure time and with increasing AgNP and AgNO(3) concentrations in the exposure media, reaching steady-state concentrations between 10(-5) and 10(-3) mol L(cell)(-1). According to estimated kinetic parameters, high Ag(+) bioconcentration factors were calculated (>10(3) L L(cell)(-1)). Higher accumulation rate constants were assessed in the cell wall free mutant, indicating a protective role of the cell wall in limiting Ag(+) uptake. The bioavailability of AgNP was calculated to be low in both strains relative to Ag(+), suggesting that AgNP internalization across the cell membrane was limited.     

Internal quality and antioxidants content of cold-stored red sweet peppers as affected by polyethylene bag packaging and hot water treatment

Physical (weight, firmness) and compositional (sugars, organic acids, ascorbic acid, phenolic compounds and carotenoids) changes of red sweet peppers (Capsicum annuum L.) were monitored during 21 days of cold storage (at 7.5 °C); fruits were stored without packaging, packaged in low density polyethylene bags, or after hot water dipping (53 °C for 4 min) and packaging. Packaging prevented water loss, and preserved the firmness of the fresh product. Sugars (fructose and glucose) content was practically constant throughout the whole storage time, for all treatments. A moderate accumulation of citric acid was observed during storage, but no marked effects of packaging and hot water dipping on citric and malic acid content. Ascorbic acid content slightly increased in unpackaged and packaged fruits, but not in treated+packaged peppers. Hydroxycinnamics total content seemed not to be affected by cold storage, packaging or hot water treatment, whereas glycosylated flavonoids showed somewhat lowered levels during storage, particularly in the case of unpackaged and packaged+treated fruits. Regarding carotenoids content, the effect of the considered storage conditions seemed to be much smaller than that due to ripening stage. Provitamin A content showed an increasing trend in unpackaged and packaged fruits; packaged+treated peppers were characterised by a lower retention of provitamin A and a higher level of capsanthin and cucurbitaxanthin A with respect to not treated fruits. On the whole, packaging and hot water treatment did not produce noticeable adverse effects on the majority of the examined compositional quality parameters.     

Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic–pituitary–thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.     

Advances in the Structural Strategies of the Self-Assembly of Photoresponsive Supramolecular Systems

Photosensitive supramolecular systems have garnered attention due to their potential to catalyze highly specific tasks through structural changes triggered by a light stimulus. The tunability of their chemical structure and charge transfer properties provides opportunities for designing and developing smart materials for multidisciplinary applications. This review focuses on the approaches reported in the literature for tailoring properties of the photosensitive supramolecular systems, including MOFs, MOPs, and HOFs. We discuss relevant aspects regarding their chemical structure, action mechanisms, design principles, applications, and future perspectives.     

Release of Soybean Isoflavones by Using a β-Glucosidase from Alicyclobacillus herbarius

β-Glucosidases are used in the food industry to hydrolyse glycosidic bonds in complex sugars, with enzymes sourced from extremophiles better able to tolerate the process conditions. In this work, a novel β-glycosidase from the acidophilic organism Alicyclobacillus herbarius was cloned and heterologously expressed in Escherichia coli BL21(DE3). AheGH1 was stable over a broad range of pH values (5–11) and temperatures (4–55 °C). The enzyme exhibited excellent tolerance to fructose and good tolerance to glucose, retaining 65 % activity in the presence of 10 % (w/v) glucose. It also tolerated organic solvents, some of which appeared to have a stimulating effect, in particular ethanol with a 1.7-fold increase in activity at 10 % (v/v). The enzyme was then applied for the cleavage of isoflavone from isoflavone glucosides in an ethanolic extract of soy flour, to produce soy isoflavones, which constitute a valuable food supplement, full conversion was achieved within 15 min at 30 °C.     

Overcoming Biological Barriers in Neuroblastoma Therapy: The Vascular Targeting Approach with Liposomal Drug Nanocarriers

Neuroblastoma is a rare pediatric cancer characterized by a wide clinical behavior and adverse outcome despite aggressive therapies. New approaches based on targeted drug delivery may improve efficacy and decrease toxicity of cancer therapy. Furthermore, nanotechnology offers additional potential developments for cancer imaging, diagnosis, and treatment. Following these lines, in the past years, innovative therapies based on the use of liposomes loaded with anticancer agents and functionalized with peptides capable of recognizing neuroblastoma cells and/or tumor‐associated endothelial cells have been developed. Studies performed in experimental orthotopic models of human neuroblastoma have shown that targeted nanocarriers can be exploited for not only decreasing the systemic toxicity of the encapsulated anticancer drugs, but also increasing their tumor homing properties, enhancing tumor vascular permeability and perfusion (and, consequently, drug penetration), inducing tumor apoptosis, inhibiting angiogenesis, and reducing tumor glucose consumption. Furthermore, peptide‐tagged liposomal formulations are proved to be more efficacious in inhibiting tumor growth and metastatic spreading of neuroblastoma than nontargeted liposomes. These findings, herein reviewed, pave the way for the design of novel targeted liposomal nanocarriers useful for multitargeting treatment of neuroblastoma.     

Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.     

Discovery of a Class of Potent and Selective Non-competitive Sentrin-Specific Protease 1 Inhibitors

Sentrin-specific proteases (SENPs) are responsible for the maturation of small ubiquitin-like modifiers (SUMOs) and the deconjugation of SUMOs from their substrate proteins. Studies on prostate cancer revealed an overexpression of SENP1, which promotes prostate cancer progression as well as metastasis. Therefore, SENP1 has been identified as a novel drug target against prostate cancer. Herein, we report the discovery and biological evaluation of potent and selective SENP1 inhibitors. A structure-activity relationship (SAR) of the newly identified pyridone scaffold revealed allosteric inhibitors with very attractive in vitro ADMET properties regarding plasma binding and plasma stability for this challenging target. This study also emphasizes the importance of biochemical mode of inhibition studies for de novo designed inhibitors.     

Atomic‐Resolution Structure of a Class C β‐Lactamase and Its Complex with Avibactam

β‐Lactamases (BLs) are important antibiotic‐resistance determinants that significantly compromise the efficacy of valuable β‐lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non‐β‐lactam BL inhibitor introduced into clinical practice. Ceftazidime–avibactam represents one of the few last‐resort antibiotics available for the treatment of infections caused by near‐pandrug‐resistant bacteria. TRU‐1 is a chromosomally encoded AmpC‐type BL of Aeromonas enteropelogenes, related to the FOX‐type BLs and constitutes a good model for class C BLs. TRU‐1 crystals provided ultrahigh‐resolution diffraction data for the native enzyme and for its complex with avibactam. A comparison of the native and avibactam‐bound structures revealed new details in the conformations of residues relevant for substrate and/or inhibitor binding. Furthermore, a comparison of the TRU‐1 and Pseudomonas aeruginosa AmpC avibactam‐bound structures revealed two inhibitor conformations that were likely to correspond to two different states occurring during inhibitor carbamylation/recyclization.